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Table of contents

1. Diseases of the thyroid gland. Diffuse toxic goiter
2. Diseases of the thyroid gland. Complications of diffuse toxic goiter (Thyrotoxic crisis. Endocrine ophthalmopathy. Pretibial myxedema)
3. Diseases of the thyroid gland. Hypothyroidism (Hypothyroidism. Congenital hypothyroidism)
4. Diseases of the thyroid gland. Thyroiditis (Acute purulent thyroiditis. Acute non-purulent thyroiditis. Subacute thyroiditis. Autoimmune (lymphocytic) thyroiditis. Postpartum thyroiditis. Chronic fibrous invasive Riedel thyroiditis. Chronic specific thyroiditis)
5. Diabetes
6. Treatment of diabetes mellitus (Insulin therapy. Tableted sugar-reducing drugs)
7. Complications of diabetes. Ketoacidosis
8. Hyperosmolar coma
9. lactic acidosis and hyperlactacidemic coma
10. Hypoglycemia and hypoglycemic coma
11. Late Complications of Diabetes Mellitus (Diabetic Nephropathy, Diabetic Retinopathy, Diabetic Neuropathy, Diabetic Foot Syndrome)
12. Syndrome Itsenko-Cushing
13. Diabetes insipidus
14. Pathology of phosphorus-calcium metabolism, parathyroid glands and bone metabolism. Hyperparathyroidism (Primary hyperparathyroidism. Secondary and tertiary hyperparathyroidism)
15. Hypoparathyroidism
16. Peudohypoparathyroidism and pseudopseudohypoparathyroidism
17. Osteoporosis
18. Hypothalamo-pituitary diseases. Craniopharyngioma (Craniopharyngioma. Other hypothalamic-pituitary diseases)
19. Acromegaly and Gigantism
20. Panhypopituitarism
21. Somatotropic insufficiency

Diffuse toxic goiter is an organ-specific autoimmune disease characterized by a persistent pathological increase in the production of thyroid hormones, as a rule, by a diffusely enlarged thyroid gland, followed by a violation of the functional state of various organs and systems, primarily the cardiovascular system, the central nervous system. The disease affects women 5 to 10 times more often than men.

The main role in the development of diffuse toxic goiter is assigned to a genetic predisposition, i.e., the presence of certain histocompatibility genes in the genetic material. The factors provoking the onset of the disease are stress, infections, insolation, etc.

The presence of a hereditary nature of diffuse toxic goiter is confirmed by the fact that 15% of patients have relatives with the same pathology. In 50% of the patient's relatives, antithyroid antibodies are determined in the blood.

The development of the disease is possible if there is a genetic predisposition and exposure to provoking factors that contribute to the implementation of the information contained in the histocompatibility genes.

Quite often, it is noted that diffuse toxic goiter develops in parallel with other diseases of an autoimmune nature.

It is believed that as a result of a violation of the proper functioning of the immune system in the body, a mutation of T-lymphocytes occurs and they begin to act on the tissue of the thyroid gland, perceiving its antigens as foreign.

Mutated T-lymphocytes can independently damage the thyroid gland.

However, they have a direct toxic effect. In addition, T-lymphocytes can pathologically affect the tissue of the thyroid gland indirectly, with the help of B-lymphocytes. B-lymphocytes in this case begin the production of antithyroid antibodies.

In the case of binding of thyroid cells (thyrocytes) to thyroid-stimulating hormone receptors, antithyroid antibodies have a stimulating effect on the gland. As a result of the fact that these antibodies are capable of such an effect, they are called thyroid-stimulating immunoglobulins. In addition to such a mechanism for the development of diffuse toxic goiter, the function of T-suppressors is also impaired under the influence of a disruption in the normal functioning of the immune system. In the absence of pathology, T-suppressors control the process of the body's immune response.

Since with diffuse toxic goiter there is an increase in the production of thyroid hormones, thyrotoxicosis develops, the degree of which affects the severity of the clinical manifestations of the disease.

An increase in the amount of thyroid hormones in the blood leads to their pathological effect on many organs and systems of the body. First of all, the cardiovascular system suffers.

The development of a "thyrotoxic" heart is characteristic, in which its dystrophy occurs. Clinically, this pathology is manifested by constant sinus tachycardia, the appearance of extrasystoles, arrhythmia develops, which can be paroxysmal or constant, pulse pressure rises, in most cases systolic arterial hypertension is noted. In addition to the cardiovascular system, the central nervous system is also affected. The symptoms of her defeat are as follows: tearfulness, irritability, emotional lability, movements become fussy, there is a tremor of the fingers of outstretched hands - a symptom of Marie, as well as a tremor of the whole body.

There is a development of catabolic syndrome, which is clinically manifested by a decrease in body weight of a progressive nature, body temperature rises to subfebrile numbers. Appetite is usually increased, sweating, muscle weakness are noted.

In addition, there is the development of osteopenia (decrease in bone mineralization). Quite often, patients complain of increased fragility of nails and hair loss. The function of the digestive system is disturbed, which is manifested by stool disorders, abdominal pain without a clear localization. As the disease progresses, characteristic eye symptoms appear.

Graefe's symptom - when looking up, the upper eyelid lags behind the iris.

Kocher's symptom - when looking down, the upper eyelid also lags behind the iris.

Symptom of Mobius - the patient cannot fix his gaze on a closely located object.

Geoffroy's symptom - when looking up, the patient wrinkles his forehead.

Symptom of Stelwag - rare blinking.

Dalrymple's symptom - the palpebral fissure is expanded, a white strip of sclera is noted between the iris and the upper eyelid.

Rosenbach's symptom - a small tremor of closed eyes. The main link in the pathogenesis of all the above symptoms is that the vegetative innervation of the eyes is disturbed.

With a pronounced diffuse toxic goiter, an increase in the size of the thyroid gland is noted, which can be determined either by palpation in the case of a slight increase in it, or by examining the neck area, which is possible with a sufficiently strong increase in its size.

There are two classifications of degrees of enlargement of the thyroid gland. The classification according to Nikolaev (1955) includes V degrees of gland enlargement:

0 degree - the thyroid gland is not palpable at all.

I degree - an enlarged isthmus of the thyroid gland is palpated.

II degree - an increase in the thyroid gland is noted during palpation and during the act of swallowing.

III degree - there is an increase in the size of the neck.

IV degree - the goiter is greatly enlarged and changes the shape of the neck.

V degree - goiter is very large.

There is a WHO classification (1994), according to which there are III degrees of enlargement of the gland:

0 degree - no goiter.

I degree - the goiter is not visible during examination, but is palpated. At the same time, the size of its shares is not more than the size of the distal phalanx of the thumb;

II degree - goiter is visible during examination.

In addition to these symptoms, the function of other endocrine glands of the body is also disturbed. Women have menstrual irregularities.

Men have gynecomastia. Fibrocystic mastopathy may also develop. Adrenal function is also impaired, which is manifested by relative adrenal insufficiency.

Diffuse toxic goiter in some cases is observed in newborns. This is possible if the disease is observed in their mothers. There are two forms of damage to newborns.

In the first form, the symptoms of the disease are observed in children at birth: low body weight, tachycardia, muscle hypotension, fever. The development of this form of diffuse toxic goiter is explained by the transfer of antibodies from mother to child through the placenta.

The second form of diffuse toxic goiter in a newborn appears at the age of 3-6 months. In this case, the course of the disease is usually very severe and in 20% of cases ends in the death of the child. If the child survives, then in most cases he has brain damage.

To confirm the diagnosis of diffuse toxic goiter, it is necessary to conduct a blood test for thyroid hormones. At the same time, there is a decrease in the amount of thyroid-stimulating hormone and a simultaneous increase in the amount of thyroxine (T₄) and triiodothyronine (T₃). An ultrasound of the thyroid gland is performed to determine the presence of a diffuse process and determine its size.

If the total volume of the thyroid gland exceeds 45 cm³, it is necessary to carry out surgical treatment of this disease. According to indications, a scintigraphy of the thyroid gland is performed.

When making a diagnosis, it is necessary to take into account the size of the goiter, its severity, and the presence of concomitant diseases. There are three degrees of severity of diffuse toxic goiter: mild, moderate and severe.

The diagnosis of mild severity is made in the presence of the following symptoms: heart rate - 80 - 120 beats per minute, pronounced weight loss of the patient, hand tremor is weak, a slight decrease in performance.

The average severity is characterized by the following criteria: the number of heartbeats - 100-120 beats per minute, pulse pressure is increased, weight loss of more than 10 kg, decreased performance.

Severe degree of thyrotoxicosis: heart rate - more than 120 beats per minute, atrial fibrillation is noted, mental disorders are expressed, dystrophy of internal organs is detected, body weight is sharply reduced (more than 10 kg), disability.

There is another classification of the severity of diffuse toxic goiter, due to which the diagnosis is less difficult. According to this classification, subclinical, manifest and complicated types of the course of the disease are distinguished.

The subclinical course is characterized by blurred clinical symptoms. The diagnosis of this course is made on the basis of laboratory methods for examining blood for hormones. At the same time, the normal content of thyroxine and triiodothyronine is determined, the level of thyroid-stimulating hormone is reduced.

With a manifest type of diffuse toxic goiter, a vivid clinical picture is noted.

In blood tests, a decrease in thyroid-stimulating hormone is determined up to its complete absence, the level of thyroid hormones is increased.

A complicated variant of the course is characterized by the addition of a heart rhythm disturbance in the form of atrial fibrillation to the clinical symptoms, symptoms of heart failure, relative adrenal insufficiency are noted, dystrophic changes appear in the internal organs, the patient's mental state is sharply impaired, and there is a pronounced lack of body weight.

Differential diagnosis is carried out with a number of diseases in which thyrotoxicosis also develops. Such diseases can be toxic adenoma and functional autonomy of the thyroid gland, multinodular toxic goiter, as well as transient gestational thyrotoxicosis.

There are medical and surgical types of treatment of diffuse toxic goiter. Drug therapy includes the use of antithyroid drugs, treatment with radioactive iodine. In the case of surgical treatment, it is necessary to carry out preoperative preparation, which consists in the appointment of thyreostatics.

Thyrostatic drugs include Mercazolil, Thiamazole, Carbimazole. Thyrostatic drugs, in particular mercasolil and propylthiouracil, block the synthesis of thyroid hormones, and also affect the cellular link of immunity.

The difference in the action of propylthiouracil is the ability to convert the process of intrathyroid hormone genesis towards the formation of triiodothyronine, which has less biological activity compared to thyroxine.

Initially, high doses of the drug are used (20-40 mg / day). In the future, they switch to a maintenance dose (5-15 mg / day).

Thyrostatics are usually prescribed together with β-blockers, such as anaprilin (80-120 mg / day) and atenolol (50-100 mg / day). The purpose of prescribing this group of drugs is to relieve tachycardia and autonomic symptoms. In addition, β-blockers, as well as thyreostatics, promote the conversion of thyroxine to triiodothyronine.

After 3-4 weeks of drug therapy, the level of thyroid hormones in the blood reaches normal values, i.e., a state of euthyroidism is formed.

After reaching this state, the dosage of thyreostatics is reduced gradually. At the same time appoint the drug L-thyroxine.

Its dosage is 50-75 mcg / day. This drug is prescribed to maintain a state of euthyroidism. Therapy with these drugs in a maintenance dose continues for 1,5 - 2 years. Then drug therapy stops completely, and the patient is under the supervision of an endocrinologist, since there is a possibility of developing a relapse of thyrotoxicosis.

Therapy with thyreostatics can give its own complications, the most dangerous of which is agranulocytosis. To prevent this complication, it is necessary to carry out treatment under control: take blood tests, especially in the first 3 months from the start of thyreostatic therapy.

During this period, the blood condition is monitored every 7-10 days, and subsequently every 3-4 weeks. In case of a decrease in the number of leukocytes to the numbers 3 x 10⁹/l and below, you must immediately stop taking thyreostatic drugs.

Usually, the state of agranulocytosis develops abruptly, which is clinically manifested by a high increase in body temperature, the appearance of dyspeptic disorders, and a sore throat may join. In case of development of relative adrenal insufficiency resort to the appointment of glucocorticoids.

Another treatment for the condition of thyrotoxicosis is the use of radioactive iodine 131_J. Apply local irradiation of the area of ​​the thyroid gland, in which radioactive iodine enters its tissue.

There it decomposes with the formation of β-particles, which are able to penetrate into the thickness of the gland by only 2 mm. There is an absolute contraindication for radioactive iodine therapy. Such a contraindication is pregnancy and lactation. If this type of treatment was received by a woman of reproductive age, then after its termination, she should use contraceptive methods for 1 year. Men of reproductive age must use contraceptive methods for 120 days.

In the case of the development of diffuse toxic goiter during pregnancy, the dosage of thyreostatics is reduced, since large dosages can have a pathological effect on the fetus. Propylthiouracil is usually prescribed, which in smaller quantities than Mercazolil penetrates the placental barrier and has practically no pathological effect on the fetus. L-thyroxine in the treatment of diffuse toxic goiter during pregnancy is not prescribed, since its use requires an increase in the dosage of thyreostatic drugs, which will have an adverse effect on the fetus. Surgical treatment of diffuse toxic goiter during pregnancy is possible only according to strict indications in the II or III trimester. In some cases, surgical treatment is necessary.

Indications for it are frequent recurrences of thyrotoxicosis against the background of ongoing drug therapy, intolerance to drugs of the thyreostatic group, the presence of a node in the thyroid tissue, as well as the retrosternal location of the goiter.

There are also contraindications to surgical treatment. These are: myocardial infarction within the last 2 months, stroke, malignant neoplasms localized outside the thyroid gland. During the operation, a resection of the thyroid gland is performed, which is usually subtotal. In most cases, the weight of the remaining thyroid stump is about 5 g.

Lecture number 2. Diseases of the thyroid gland. Complications of diffuse toxic goiter

Complications of the course of diffuse toxic goiter can be thyrotoxic crisis, endocrine ophthalmopathy and pretibial myxedema.

1. Thyrotoxic crisis

Thyrotoxic crisis is a very serious condition that complicates diffuse toxic goiter and can be quite a serious threat to the patient's life. The pathogenesis of the development of thyrotoxic crisis is still not fully understood, but there are a number of hypotheses. According to one of them, it is believed that with the development of this complication, an increase in the number of free forms of thyroxine and triiodothyronine occurs due to a violation of the process of their binding. According to another hypothesis, the development of a thyrotoxic crisis is associated with an increase in the body's sensitivity to catecholamines. The provoking factor in this case is an infectious disease, the stressful state of the body and others, characteristic clinical symptoms develop.

The patient's condition deteriorates sharply, which is associated with an increase in the manifestations of all the symptoms characteristic of the state of thyrotoxicosis. The development of a thyrotoxic crisis is necessarily combined with the appearance of relative adrenal insufficiency.

In most cases, symptoms of liver failure and pulmonary edema are added. Thyrotoxic crisis usually develops suddenly. The patient becomes excessively mobile, his excitation is noted.

On examination, the patient's forced position is observed, which is characteristic of a thyrotoxic crisis: the legs are bent at the knees and spread apart ("frog posture"). Hypotension of the muscles is characteristic, which is clinically manifested by a speech disorder. The body temperature rises, while the skin feels hot and moist. There is an increase in the number of heartbeats up to 130 beats per minute. The heart rhythm may be disturbed. Urgent remedial action is needed. The following groups of drugs are used as treatment: thyreostatics, β-blockers, glucocorticoids. It is also necessary to carry out measures to detoxify the body. Initially, intravenous administration of hydrocortisone at a dose of 50-100 mg every 4 hours is necessary.

Quite large doses of thyreostatics are prescribed, for example, the dose of propylthiouracil is 1200-1500 mg per day.

To prevent the entry into the bloodstream of those hormones that have already been synthesized and are currently in the thyroid gland, inorganic iodine is used, which can be administered either orally or intravenously. Detoxification therapy involves intravenous administration of a liquid in a volume of about 3 liters per day, usually consisting of isotonic sodium chloride solution and 5% glucose solution.

Of the drugs of the group of β-blockers, propranolol is usually used, the dosage of which depends on the route of administration. In the case of the oral route of administration of the drug, its dose is 20-40 mg, with intravenous administration, the dosage is less and is 1-2 mg. The drug is administered every 6 hours.

2. Endocrine ophthalmopathy

This complication is a lesion of periorbital tissues of autoimmune origin. With this disease, there is a dystrophic change in various structures of the eye, for example, oculomotor muscles.

The pathogenesis of the development of this complication lies in the fact that antibodies to thyroid-stimulating hormone formed in the body under the influence of autoimmune processes contribute to the development of inflammatory changes in the retrobulbar tissue.

At the same time, these changes capture fibroblasts, the activity of which increases, which in turn leads to an increase in the volume of retrobulbar tissue.

The above changes lead to the development of exophthalmos and degeneration of the oculomotor muscles. The disease proceeds in stage III.

Stage I is characterized by the appearance of swelling of the eyelids, patients complain of pain in the eyes, lacrimation.

Stage II is characterized by the addition of a complaint of double vision when looking at objects (diplopia). During the examination, gaze paresis is noted when looking up, as well as restriction of eye aversion to the side.

Stage III is the most severe and is characterized by incomplete closure of the palpebral fissure, as well as pronounced dystrophic changes in the eyeballs, such as atrophy of the optic nerve and the appearance of ulcerative defects on the cornea.

Clinical symptoms of endocrine ophthalmopathy develop gradually. At first, changes are observed only from one eye. With the progression of the pathology, the second eye is affected. Patients begin to be disturbed by a feeling of pressure, localized behind the eyeballs. As the process progresses, the feeling intensifies. Increased sensitivity to light joins, pain in the eyes. Over time, exophthalmos develops, which usually leads to incomplete closure of the eyelids. With an increase in the volume of periorbital fiber, a violation of the venous outflow from the eyes occurs, which is manifested by the appearance of edema around the eyeball. Also, the progression of the process leads to compression of the optic nerve, which is clinically manifested by impaired color perception, narrowing of the visual fields and edema of the optic nerve, which is detected when examined by an ophthalmologist.

To diagnose endocrine ophthalmopathy and determine its activity, a urine test is performed to determine glycosaminoglycans in its composition. The amount of these substances in the urine is increased when the process is active, and when it subsides, their number decreases. Instrumental diagnostic methods are ultrasound, computed tomography and magnetic resonance imaging. The method of positional tonometry is also used. Using this method, the length of the retrobulbar space is determined, as well as the state of the oculomotor muscles (their thickness and density). Treatment of endocrine ophthalmopathy includes the mandatory treatment of diffuse toxic goiter, or rather, the state of thyrotoxicosis. It is necessary to achieve a stable state of euthyroidism. In the case of the development of the second stage of endocrine ophthalmopathy, it is necessary to prescribe glucocorticoid preparations at a dose of 50-100 mg / day. The drug is taken at this dosage for 2 weeks.

Then the dosage is halved and gradually brought to 5 mg / day. Therapy with a maintenance dose of the drug continues for 2 to 3 months. In case of ineffectiveness of glucocorticoid therapy, treatment with X-rays is resorted to.

With the threat of developing loss of vision, surgical treatment is performed, in which, in order to reduce exophthalmos, the bottom and lateral wall of the orbit are removed.

3. Pretibial myxedema

This complication of diffuse toxic goiter develops in extremely rare cases. The pathogenesis of this pathology is identical to the pathogenesis of the development of endocrine ophthalmopathy.

Clinically, pretibial myxedema is manifested by hyperemia of the skin of the anterior surface of the lower leg. In this area, edema and tissue thickening are formed.

In most cases, this symptomatology is accompanied by itching in the anterior surface of the lower leg. Therapy of this type of complication consists in the appointment of glucocorticoid preparations locally.

Lecture number 3. Diseases of the thyroid gland. Hypothyroidism

1. Hypothyroidism

Hypothyroidism is a clinical syndrome caused by a prolonged, persistent deficiency of thyroid hormones in the body or a decrease in their biological effect at the tissue level.

Perhaps the development of congenital hypothyroidism. Predisposing factors for this are thyroid aplasia or dysplasia, congenital thyroid-stimulating hormone deficiency, endemic goiter, and peripheral thyroid hormone resistance syndrome.

Most often the disease is primary. There are a number of reasons contributing to its development. Such reasons may be autoimmune damage to the thyroid gland, resection of the thyroid gland, treatment with radioactive iodine. In extremely rare cases, hypothyroidism can occur as an outcome of various forms of thyroiditis (subacute, fibrosing, specific), with excessive use of thyreostatic drugs in the treatment of diffuse toxic goiter. Sometimes the cause of primary hypothyroidism cannot be determined. In this case, the diagnosis of idiopathic hypothyroidism is made.

The causes of secondary hypothyroidism are insufficiency of the function of the pituitary gland with its tumors, removal, irradiation, deficiency of thyroid-stimulating hormone. Hypothalamic hypothyroidism develops as a result of impaired synthesis and secretion of thyroliberin. Peripheral type of hypothyroidism (tissue) develops with tissue resistance to thyroid hormones. In hypothyroidism, there is a decrease in the amount of synthesized thyroid hormones. This leads to pathological changes in many organs and systems of the body due to a violation of the formation of a number of enzymes. With this disease, the synthesis of glycosaminoglycans is disrupted, which is manifested by infiltration of the skin, subcutaneous adipose tissue, mucous membranes, and muscles, including the heart muscle. In addition, water-salt metabolism is also disturbed.

There are several classifications of hypothyroidism. Classification by pathogenesis:

1) primary (thyroid);

2) secondary (pituitary);

3) tertiary (hypothalamic);

4) tissue (transport, peripheral). Classification by severity:

1) latent (subclinical): an elevated level of thyroid-stimulating hormone with a normal content of thyroxine;

2) manifest: hypersecretion of thyroid-stimulating hormone with a reduced level of thyroxine, divided into compensated and decompensated;

3) severe course (complicated): severe complications such as cretinism, heart failure, effusion in the serous cavities, secondary pituitary adenoma.

The clinical picture of hypothyroidism can be different. The usual complaints of patients when contacting a hospital are weight gain, dry skin, thickening, speech becomes fuzzy. Since hypothyroidism affects almost all organs and systems of the body, patients may be disturbed by pain in the right hypochondrium that appears after exercise. Often there are violations of the stool in the form of constipation. There may be pain in the chest, as well as shortness of breath when walking. In most cases, women have irregular menstruation. Patients note a decrease in intelligence and memory of a progressive nature. Hypothyroidism is accompanied by the development of a number of syndromes.

Hypothermic metabolic syndrome is characterized by a pronounced increase in body weight and a decrease in temperature. Hypothyroid dermopathy is manifested by the appearance of myxedematous edema, swelling around the eyes is noted, the face becomes puffy, the size of the lips and tongue increases.

When examining the oral cavity, the presence of imprints of teeth along the edges of the tongue is noted. The skin acquires an icteric coloration, which is explained by hypercarotinemia. There is swelling of the nasal mucosa, auditory tube, middle ear organs and vocal cords. Clinically, this is manifested by difficulty in nasal breathing, decreased hearing acuity and hoarseness. Examination reveals polyserositis. The central and peripheral nervous system is affected, patients complain of lethargy, drowsiness, memory loss, the appearance of muscle pain and paresthesia. The examination determines a decrease in heart rate, a decrease in tendon reflexes and symptoms of polyneuropathy. The syndrome of damage to the cardiovascular system is characteristic, during the examination there is bradycardia, heart failure, as well as changes on the ECG in the form of a negative T wave and its low voltage. In addition, there is a decrease in blood pressure. The digestive system is affected, which is manifested by an increase in the size of the liver, a violation of the stool, a decrease in appetite, nausea, and vomiting.

An objective examination determines dyskinesia of the biliary tract, colon, as well as atrophic changes in the gastric mucosa. The development of an anemic syndrome is characteristic. Anemia may be normochromic, normocytic, iron-deficient, or B₁₂- deficient. Patients note an increase in hair fragility, hair loss and slow growth. These symptoms constitute the syndrome of ectodermal disorders. The syndrome of an empty Turkish saddle is also characteristic.

The mechanism of development of this syndrome is that as a result of a decrease in the level of thyroid hormones in the case of primary hypothyroidism, a long-term persistent increase in the function of the adenohypophysis occurs. This leads to an increase in its size. During therapy with thyroid hormones, a decrease in the size of the adenohypophysis is noted, which is the cause of this syndrome. Due to hypothyroidism, there is a decrease in the chemosensitivity of the respiratory center, which is the cause of the development of apnea syndrome. Usually this syndrome manifests itself in a dream. The appearance of a syndrome of hyperprolactinimichesky hypogonadism is also noted, which is characteristic of primary hypothyroidism.

Clinically, the syndrome is manifested by menstrual dysfunction and secondary polycystic ovaries. Diagnosis of hypothyroidism in most cases is difficult due to the predominant lesion of any organ system.

Secondary hypothyroidism is characterized by its course. They lie in the fact that not an increase in body weight can be observed, but, on the contrary, its decrease, up to exhaustion, can be noted.

The syndrome of hypothyroid dermopathy does not have such vivid clinical symptoms. Myxedematous edema is usually absent. For secondary hypothyroidism, the development of heart failure, polyserositis, an increase in the size of the liver and the appearance of B₁₂- deficiency anemia.

A complication of the course of hypothyroidism is myxedema coma, which occurs in extremely rare cases. Usually, the development of this complication is observed in elderly patients if hypothyroidism has not been diagnosed for a long time, as well as in the presence of severe concomitant diseases. The appearance of myxedematous (hypothyroid) coma can be triggered by cooling the body, exposure to drugs for anesthesia, as well as during treatment with neuroleptics and barbiturates.

The pathogenesis of myxedematous coma is associated with the fact that with a long course of hypothyroidism, there is a violation of tissue respiration, as well as suppression of the function of the adrenal cortex. Since antidiuretic hormone is an antagonist of thyroid hormones, in the event of a deficiency of the latter, the level of antidiuretic hormone increases.

The following clinical picture is characteristic: a decrease in body temperature, respiratory failure, hypercapnia, a decrease in heart rate and blood pressure, heart failure develops, acute urinary retention and dynamic intestinal obstruction. All this leads to the development of a stuporous state, and subsequently coma. Mortality in this complication is very high and reaches 80%.

To make a diagnosis, it is necessary to conduct a blood test for thyroid hormones. Indicators of hormone levels depend on the severity of hypothyroidism and the level of damage. In the case of primary hypothyroidism, there is an increase in the level of thyroid-stimulating hormone and a simultaneous decrease in the amount of thyroxine. In primary hypothyroidism, antithyroid antibodies are usually detected, which is explained by the rather frequent development of this disease as a result of an autoimmune lesion of the thyroid gland. Secondary hypothyroidism is characterized by a decrease in the level of thyroid-stimulating hormone and thyroxine.

In some cases, it is necessary to make a differential diagnosis of primary and secondary hypothyroidism. To do this, use a test with thyroliberin, which is administered intravenously in an amount of 200 mg. After 30 minutes, the amount of thyroid-stimulating hormone in the blood is determined. If there is an increase in thyroid-stimulating hormone up to 25 mIU / l or more, a diagnosis of primary hypothyroidism is made. If hypothyroidism is secondary, then the level of thyroid-stimulating hormone in the blood does not change.

In the case when the cause of hypothyroidism is isolated pituitary insufficiency, it is necessary to conduct a differential diagnosis with other autoimmune diseases, in which there is insufficiency of the pituitary-dependent endocrine glands.

Some diseases, such as heart failure, myocardial infarction, renal and hepatic failure, and others, are accompanied by dysfunction of the 5-deiodinase enzyme. This leads to a decrease in the amount of triiodothyronine, with a simultaneous normal level of thyroxine and thyroid-stimulating hormone. If a low level of triiodothyronine is detected, a differential diagnosis with the above diseases is necessary.

Replacement therapy is required. For this purpose, L-thyroxine is prescribed. Therapy with this drug begins with the appointment of small doses, about 12,5 mcg / day. L-thyroxine is taken 30 minutes before meals in the morning. Then, over a period of time, there is a gradual increase in the dose of the drug until a constant maintenance is reached.

In the case of an elderly patient, an increase in dosage is carried out within 2-3 months, with a young age - within 3-4 weeks. If the course of hypothyroidism is accompanied by pathology from the cardiovascular system, then the dosage increases over 4-6 months. The calculation of the full maintenance dose of the drug is carried out strictly individually and is 1,6 μg / kg of body weight per day. If there is any concomitant disease, then the dosage is determined at the rate of 0,9 mcg / kg of body weight per day.

The therapeutic effect of the use of L-thyroxine is controlled by the level of thyroid-stimulating hormone in the blood. Normalization of the level of thyroid-stimulating hormone should occur no later than 4 months after the start of treatment. If this does not happen, then it is possible to increase the dose by 25 mcg. In the case of normalization of the level of thyroid-stimulating hormone, it is necessary to conduct a control study for several years.

Secondary hypothyroidism is treated according to the same principles as primary. The effectiveness of the treatment of secondary hypothyroidism is assessed by the level of thyroxine in the blood. A necessary condition for the treatment of secondary hypothyroidism is the compensation of secondary hypocorticism.

Treatment of hypothyroidism begins already with its subclinical course. This is due to the fact that at this stage a number of morphological changes are already taking place in the body, for example, atherosclerotic changes. The use of triiodothyronine preparations, as well as preparations consisting of this hormone and thyroxine, is not recommended.

The appointment of these drugs increases the risk of developing pathology from the cardiovascular system, which is associated with the formation of a state of drug-induced thyrotoxicosis when using triiodothyronine preparations.

In the case of the development of hypothyroid coma, it is necessary to prescribe thyroid hormones, as well as glucocorticoids. Treatment with thyroxine begins with a dose of 250 mcg administered intravenously every 6 hours for the first few days. Then the dosage is reduced to the usual numbers. In addition, triiodothyronine is administered using a gastric tube, which is necessary due to the delayed action of thyroxine. The drug is administered every 12 hours. The initial dose is 100 mcg, and then reduced to 25-50 mcg. Of the preparations of glucocorticoids, prednisone is used, administered intravenously, and hydrocortisone, administered intramuscularly. The dose of prednisolone is 10-15 mg and the drug is administered every 2-3 hours. Hydrocortisone is administered 3-4 times a day at a dose of 50 mg. With a decrease in the clinical manifestations of hypothyroid coma, the dosage of these drugs is gradually reduced.

2. Congenital hypothyroidism

The main factor in the development of congenital hypothyroidism is the insufficiency of thyroid hormones, which can be partial or complete. The most common cause of this disease is thyroid dysgenesis, as well as iodine deficiency. In this case, primary congenital hypothyroidism develops. More rare causes of congenital primary hypothyroidism is a violation of the formation of thyroid hormones. The causes of this pathology may be violations of hormone genesis at various levels: a defect in thyroid-stimulating hormone receptors, a violation of iodine transport, a violation of the function of the pyroxidase system, and a violation of the synthesis of thyroglobulin. Quite often, congenital hypothyroidism of this genesis is inherited in an autosomal recessive manner. Characteristic of this disease is an increase in the size of the thyroid gland. Congenital hypothyroidism can be secondary, which happens with the pathology of the pituitary gland, as well as tertiary - with damage to the hypothalamus. Secondary and tertiary congenital hypothyroidism occurs in very rare cases. Another form of the disease is also possible, in which tissue resistance to thyroid hormones is noted. With this form of congenital hypothyroidism, the level of thyroid-stimulating hormone and thyroid hormones is not changed compared to the norm. If during pregnancy a woman took thyreostatics, then the development of transient hypothyroidism of the newborn is possible. This form of the disease can also occur with the transplacental transfer of antithyroid antibodies from mother to child.

In the early postnatal period, it is rarely possible to identify clinical manifestations of the disease. Characteristic signs of congenital hypothyroidism are usually post-term pregnancy, a large fetus (weight more than 4000 g), with full-term pregnancy there may be signs of immaturity of the fetus. Late discharge of meconium, as well as the umbilical residue, the umbilical wound heals for a long time, physiological jaundice lasts a longer time. When examining a newborn, swelling is noted in the face, lips and eyelids, the size of the tongue is increased. In the supraclavicular fossae, as well as on the back surfaces of the feet and hands, edema is observed in the form of dense pads. At the age of 3-4 months, the following manifestations of primary congenital hypothyroidism are noted: appetite is reduced, the child gains weight poorly, stool disorders in the form of constipation, flatulence, the skin is pale, dry, its peeling is noted, the hair is dry and brittle, with palpation of the hand and feet are cold, muscle hypotonia is noted. At the age of 5-6 months, there are signs of a delay in physical and psychomotor development.

On the 4th - 5th day of life, a blood test of all newborns is performed to determine the level of thyroid-stimulating hormone and thyroxine. Conducting a study at an earlier date is unacceptable, this is due to the fact that during this period quite often the results are false positive. If the child was born prematurely, then a blood test for hormones is carried out on the 7th - 14th day of life. The normal level of thyroid-stimulating hormone in the blood of a newborn is considered to be less than 20 mIU / l. If the level of thyroid-stimulating hormone is higher than this figure, then a second study is necessary. The diagnosis of "suspected congenital hypothyroidism" is made when the level of thyroid-stimulating hormone is more than 50 mIU / l. In the case of an increase in the content of thyroid-stimulating hormone over 100 mIU/l, there is every reason to make a diagnosis of congenital hypothyroidism.

If at the first examination the level of thyroid-stimulating hormone in the blood of a newborn was more than 20, but less than 50 mIU/l, and at the second examination it slightly exceeded 20 mIU/l, it is necessary to prescribe replacement therapy with L-thyroxine. If at the first examination the level of thyroid-stimulating hormone is more than 50 mIU / l, then it is necessary to prescribe replacement therapy immediately. In the absence of confirmation of the presence of congenital hypothyroidism during a second blood examination, replacement therapy is canceled. For differential diagnosis of true congenital hypothyroidism with transient, 2 weeks and 1 month after the start of replacement therapy, a control laboratory blood test is performed.

When the diagnosis of true congenital hypothyroidism is confirmed, continuous replacement therapy is carried out up to 1 year of life. After that, L-thyroxine is canceled for 2 weeks and a second blood test for thyroid-stimulating hormone and thyroxine is performed. If the indicators of the level of these hormones in the blood against the background of the withdrawal of L-thyroxine are within the normal range, then the treatment is canceled.

If replacement therapy was started in the first month of a child's life, then mental development does not suffer. The dosage of L-thyroxine is based on 8 - 12 mcg / kg of body weight per day.

Lecture No. 4. Diseases of the thyroid gland. Thyroiditis

There are several types of thyroiditis: acute purulent, acute non-purulent, subacute, autoimmune, postpartum, chronic fibrous invasive Riedel thyroiditis, chronic specific forms.

1. Acute purulent thyroiditis

Etiological factors in the development of acute purulent thyroiditis can be staphylococci, streptococci, pneumococci and Escherichia coli. Also, the cause of this disease can be an infectious lesion of a bacterial nature. In the case of a weakened organism, hematogenous or lymphogenous transfer of infectious agents from foci of chronic infection can occur. The characteristic complaints of patients with acute purulent thyroiditis are pain and difficulty during the act of swallowing, as well as an unpleasant feeling in the neck. With the progression of the process in the area of ​​​​the thyroid gland, swelling and hyperemia are observed. On palpation of this area, sharp pain is noted.

Closely located lymph nodes, such as cervical and subclavian, are involved in the pathological process. The pain may radiate to the ear over time. There is an increase in body temperature up to 38,5 ° C and above. The duration of the disease ranges from 4 weeks to 4 months. In the case of late diagnosis of the disease, as well as the lack of treatment or its incorrect tactics, various complications of acute purulent thyroiditis can develop, such as purulent mediastinitis, sepsis, abscess, neck phlegmon, aspiration pneumonia.

When examining blood, there is an increase in ESR, neutrophilic leukocytosis. With ultrasound of the thyroid gland, the presence of a hypoechoic area in its thickness is determined. In advanced cases, during a test puncture of the thyroid gland, a purulent discharge is determined. The main method of treatment of this pathology is surgical. In the postoperative period, active antibiotic therapy is carried out. If an abscess develops, drainage should be performed.

2. Acute non-purulent thyroiditis

The correct diagnosis for this disease occurs in extremely rare cases, since in most cases the patient's condition is regarded as ARVI or an exacerbation of chronic tonsillitis. The usual complaints of patients with acute non-purulent thyroiditis are an increase in body temperature, as well as a sore throat that appears when swallowing. Also, a common complaint is the appearance of a feeling of pressure in the thyroid gland and pain on palpation of this area. The causes of the development of acute non-purulent thyroiditis can be various injuries of the thyroid gland, hemorrhages in its tissue. This causes aseptic inflammation in the thyroid gland. Treatment consists in the appointment of non-steroidal anti-inflammatory drugs and analgesics. The duration of the disease does not exceed a few days. The prognosis is always favorable.

3. Subacute thyroiditis

The disease is about 5 times more common in women than in men. In most cases, the disease occurs at the age of 30-60 years in the autumn-winter period. As a rule, subacute thyroiditis develops against the background of influenza, mumps, measles, and upper respiratory tract diseases, that is, it has a viral etiology. In addition, there is a genetic predisposition to this disease. The viral agent, getting into the bloodstream, penetrates into the tissue of the thyroid gland. There it is introduced into its cells - thyrocytes, leading to the release of the contents of the follicles of the gland into the bloodstream. Symptoms of subacute thyroiditis usually begin to appear 5 to 6 weeks after any viral infection. Patients in typical cases complain of sudden onset pain in the thyroid gland, aggravated by swallowing and making any movements of the neck. In this case, there may be irradiation of pain in the lower jaw and ears. The pain can be of varying intensity, and can also change. Patients may note the "volatile" nature of the pain, that is, its constant transition from one area of ​​\uXNUMXb\uXNUMXbthe neck to another. In addition, an objective examination shows tachycardia, weight loss, which is progressive. These general symptoms are explained both by the presence of an infectious agent in the body and the occurrence of a state of thyrotoxicosis as a result of damage to the thyroid gland follicles and the release of their contents into the bloodstream.

On palpation of the thyroid gland, one can note its soreness. The thyroid gland is usually enlarged, its consistency becomes dense. Depending on the volume of the affected tissue of the gland, pain on palpation can be both local and diffuse. In blood tests, there is an increase in ESR, a small leukocytosis, an increase in the level of thyroglobulin and thyroid hormones. Subacute thyroiditis occurs in several stages: such as initial, or thyrotoxic, hypothyroid, normalization of thyroid status.

There are a number of criteria for making a diagnosis of subacute thyroiditis. One of them is an increase in ESR with a simultaneous slight leukocytosis, which in some cases may be absent altogether. In addition, there is a decrease in the absorption of radioactive iodine by the thyroid gland tissue with a simultaneous increase in the level of serum thyroglobulin and thyroid hormones. To confirm the diagnosis, a Crile test is performed, which consists in giving the patient 20-40 mg of prednisolone. If after 24-72 hours there is a decrease in pain in the neck, a decrease in body temperature and a decrease in ESR in the general blood test, then the test is positive and speaks in favor of subacute thyroiditis.

Otherwise, the test is negative. Tactics of treatment depends on the severity of the course of the disease. In the case of a mild course, only non-steroidal anti-inflammatory drugs, such as aspirin, can be prescribed. It is prescribed at a dosage of 0,5 g 4 times a day strictly every 6 hours for 3 months. In most cases, patients go to the doctor in an already more severe stage of the disease. This requires the appointment of glucocorticoids, such as prednisolone. Initially, the drug is prescribed at a dose of 30-40 mg. After 1-3 weeks, depending on the results obtained from the treatment, the dosage of the drug is gradually reduced by 5 mg per week. The duration of the drug is also 3 months. The combined use of aspirin and prednisolone is not advisable. The prognosis for subacute thyroiditis in the vast majority of cases is positive.

4. Autoimmune (lymphocytic) thyroiditis

In most cases, the disease affects women. Autoimmune thyroiditis is a disease with a hereditary predisposition. The cause of the development of pathology is the presence of a genetic defect that leads to a violation of the body's immune response. In this case, T-lymphocytes are formed, which have a destructive effect on the cells of the thyroid gland. Quite often, autoimmune thyroiditis is combined with other diseases of an autoimmune nature, such as type I diabetes mellitus, pernicious anemia, chronic autoimmune hepatitis, autoimmune primary hypocorticism, vitiligo, rheumatoid arthritis, etc. antithyroid antibodies in the blood.

With the development of autoimmune thyroiditis, the thyroid gland undergoes a number of morphological changes. In almost 100% of cases, the process ends with the formation of a state of hypothyroidism.

At the onset of the disease, as a rule, thyrotoxicosis is noted, which may be the result of damage to thyrocytes during autoimmune processes and the entry into the bloodstream of a large amount of already synthesized thyroid hormones. Another reason for the development of thyrotoxicosis may be the circulation in the blood of a large number of antibodies that enhance the synthesis of thyroid hormones. Ultimately, most patients develop a state of hypothyroidism, which is regarded as irreversible. But still, in some cases, spontaneous restoration of thyroid function is possible. Methods for diagnosing autoimmune thyroiditis include ultrasound of the thyroid gland, laboratory blood tests, and needle biopsy. In the study of blood, the presence of antibodies to thyroglobulin is determined. In some cases, quite rarely, antibodies to thyroid-stimulating hormone can be observed. In healthy people, there may be an increase in the level of antibodies to thyroglobulin in the blood, which does not lead to the development of autoimmune thyroiditis. A sufficiently high increase in the level of antibodies speaks in favor of an already developed autoimmune thyroiditis or may indicate a high risk of developing this pathology. With ultrasound of the thyroid gland, a diffuse decrease in its echogenicity is noted, which may also indicate in favor of diffuse toxic goiter. The indication for a puncture biopsy of the thyroid gland is usually the presence of a nodular formation in its tissue.

In this case, the study is carried out in order to exclude the presence of a tumor formation in the gland tissue. The diagnosis of autoimmune thyroiditis is established only in the presence of several signs characteristic of it. The development of a state of hypothyroidism usually leads to the activation of the sympathoadrenal system of a compensatory nature. In this regard, patients note a sudden feeling of fear, palpitations, trembling in the hands, sweating. Against the background of primary hypothyroidism, a state of hyperprolactinemia develops, which leads to polycystic ovaries. Treatment of autoimmune thyroiditis can be either conservative or surgical. Usually treated with conservative methods. In the case of the first phase of the disease - thyrotoxic - symptomatic agents are prescribed, for example, α-blockers, as well as thyreostatics. After reaching the state of euthyroidism, treatment is carried out with the help of hormonal drugs. Thyroxine is prescribed at a dose of 75 - 100 mcg / day. There are a number of indications for the appointment of surgical treatment of autoimmune thyroiditis. These include the presence of concomitant neoplastic changes in the tissue of the thyroid gland, as well as the large size of the goiter, leading to compression of adjacent anatomical structures.

5. Postpartum thyroiditis

The development of this disease has no connection with the presence of a hereditary predisposition and the amount of iodine consumed by a woman. Postpartum thyroiditis affects 3-5% of women in the postpartum period. The development of thyrotoxicosis, in this case of a transient nature, is associated with damage to the thyroid gland follicles as a result of the inflammatory process.

Usually, postpartum thyroiditis appears 1-3 months after childbirth. At the same time, transient thyrotoxicosis develops, which usually does not have a pronounced clinical picture.

Then a state of hypothyroidism develops, usually lasting 6 to 8 months. After this period of time, spontaneous remission occurs. An objective examination shows a diffuse enlargement of the thyroid gland, which is painless on palpation.

In a laboratory blood test, the appearance of antibodies to thyroglobulin or microsomal antigen is noted. The diagnosis of postpartum thyroiditis is established in cases where the disease is associated with childbirth, diffuse enlargement of the thyroid gland, the presence of transient thyrotoxicosis, manifested by low absorption of radioactive iodine by the thyroid tissue and a simultaneous increase in the level of thyroxine and triiodothyronine in the blood.

In addition, a high titer of antibodies to the microsomal antigen should be noted in the blood. Ultrasound of the thyroid gland shows diffuse changes of a hypoechoic nature. With the development of a state of hypothyroidism, thyroxin preparations are prescribed. The duration of therapy does not exceed 6 months.

6. Chronic fibrous invasive Riedel thyroiditis

The disease occurs in extremely rare cases. Its etiology is still unclear. This pathology is characterized by fibrous replacement of normal thyroid tissue.

At the same time, changes in the surrounding tissues of an invasive nature can also be noted. The usual complaints of patients are those symptoms that occur when squeezing the surrounding anatomical structures.

For a correct diagnosis, a needle biopsy is necessary. Treatment of pathology is surgical. The volume of the operation can be different - from the intersection of the isthmus of the thyroid gland to its extirpation. In the event of a state of hypothyroidism, hormonal preparations are prescribed - L-thyroxine. In some cases, in the postoperative period resort to the appointment of glucocorticoids.

7. Chronic specific thyroiditis

The development of this type of thyroiditis can complicate the course of such diseases as tuberculosis, lymphogranulomatosis, amyloidosis, sarcoidosis, actinomycosis.

Diagnosis is based on the data of the puncture biopsy and the presence of symptoms of the underlying disease. Treatment of this condition requires initial treatment of the underlying disease.

Lecture number 5. Diabetes mellitus

Diabetes mellitus is a systemic disease of a heterogeneous nature that develops as a result of an absolute (type I) or relative (type II) insulin deficiency, which initially leads to a violation of carbohydrate metabolism, and then to a violation of all types of metabolism and damage to all functional systems of this organism.

In diabetes mellitus, macro- and microangiopathy develops, i.e., vessels of small and large caliber are affected. Thus, in diabetes mellitus, vascular damage is generalized.

As a result, the blood supply to the organs and tissues of the body is disrupted, which leads to a violation of their function, which in advanced cases can be a danger to the life of the patient.

The 1999 WHO classification is currently recognized, according to which the following types of diabetes mellitus are distinguished:

1) diabetes mellitus type I:

a) autoimmune;

b) idiopathic;

2) diabetes mellitus type II;

3) other specific types of diabetes;

4) gestational diabetes mellitus.

Type I diabetes mellitus (insulin-dependent) is characterized by a destructive lesion of pancreatic β-cells, which leads to the development of absolute insulin deficiency.

Type II diabetes mellitus is characterized by relative insulin deficiency and tissue resistance to the effects of insulin.

In addition, in type II diabetes mellitus, a predominant defect in insulin secretion may be observed, and tissue resistance to it may or may not be present. Other types of diabetes can occur as a result of various pathological processes in the body. This may be a defect in the function of β-cells of a genetic nature, a genetic defect in the effect of insulin on tissues, various diseases of the exocrine part of the pancreas, various endocrinopathies, diabetes under the influence of drugs or other chemicals, exposure to infectious agents, unusual forms of diabetes mellitus can also occur, such as usually immune-mediated.

Also, in rare cases, there are various genetic syndromes occurring in combination with diabetes mellitus. Gestational diabetes mellitus occurs exclusively during pregnancy.

The following genetic defects in the function of pancreatic β-cells are distinguished: MODY-1, MODY-2, MODY-3, MODY-4, mitochondrial DNA mutation and other genetic defects in insulin action (type A insulin resistance, leprechaunism, Rabson-Mendenhall syndrome, lipoatrophic diabetes, etc.).

Pancreatitis, pancreatic injury, pankeatectomy, neoplasia, cystic fibrosis, hemochromatosis, and fibrocalculous pancreatopathy are diseases of the exocrine pancreas that can provoke the development of diabetes mellitus.

Diabetogenic endocrinopathies include acromegaly, Cushing's syndrome, glucagonoma, pheochromocytoma, thyrotoxicosis, somatostatinoma, aldosteroma, etc.

The development of diabetes mellitus can be provoked by a number of medicinal and other chemicals, such as vacor, pentamidine, nicotinic acid, glucocorticoids, thyroid hormones, diazoxide, α-adrenoreceptor agonists, thiazides, dilantin, α-interferon, etc.

Diabetes mellitus can be caused by infections such as congenital rubella, cytomegalovirus, and some others.

The following genetic syndromes are sometimes combined with diabetes mellitus: Down's syndrome, Klinefelter's syndrome, Turner's syndrome, Wolfram's syndrome, Friedreich's ataxia, Huntington's chorea, Lawrence-Moon-Biedl syndrome, myotonic dystrophy, porphyria, Prader-Willi syndrome and some other syndromes.

All symptoms of diabetes mellitus can be divided into two groups: symptoms of hyperglycemia and symptoms specific to type I or type II diabetes.

The symptoms of hyperglycemia are as follows: thirst, polyuria, pruritus and increased susceptibility to various infections.

In the event that all of the above symptoms occur as a result of inadequate hypoglycemic therapy, they are considered as symptoms of decompensation of diabetes mellitus.

Specific complaints for type I diabetes mellitus are a significant decrease in body weight, weakness, which can be pronounced, decreased performance, and increased drowsiness is noted by patients.

In some cases, the onset of the disease is characterized by an increase in appetite. As the disease progresses, there is a decrease in appetite up to anorexia against the background of ketoacidosis. The state of ketoacidosis is characterized by the appearance of the smell of acetone from the mouth, nausea, vomiting are noted, abdominal pain is characteristic, dehydration of the body occurs, which usually ends in the development of a coma, i.e. ketoacidotic coma.

The occurrence of such symptoms in type XNUMX diabetes occurs as a result of an absolute deficiency of insulin in the patient's body. Type II diabetes mellitus is more mild. Symptoms of hyperglycemia are usually mild, and in some cases they are completely absent.

Usually, the diagnosis of diabetes mellitus is an incidental finding during routine examination of the population. Efficiency in type II diabetes mellitus remains unchanged, appetite is not disturbed, and may even be increased.

In most cases of type II diabetes, patients are overweight. This form of diabetes mellitus is characterized by the presence of a hereditary predisposition and manifests itself in typical cases after 40 years.

The diagnosis of diabetes mellitus II can sometimes be made not by an endocrinologist, but by a completely different doctor, such as a gynecologist, urologist, dermatologist or optometrist.

Suspicious for the presence of type II diabetes mellitus are the following pathological conditions of the body: chronic pustular processes on the skin, lipoid necrobiosis, candidiasis of the skin and mucous membranes, furunculosis, chronic urinary tract infections, chronic conjunctivitis, cataracts, vaginal itching, amenorrhea and inflammatory diseases of the genital organs of nonspecific character in women.

Type I diabetes mellitus is characterized by acute development. In some cases, the first sign of type XNUMX diabetes may be impaired consciousness up to a coma, which usually occurs against the background of any infectious diseases. Diabetes mellitus is characterized by the presence of complications that can be acute and chronic.

An acute complication of type I diabetes mellitus is ketoacidotic coma. For type II diabetes mellitus, a more characteristic complication is hyperosmolar coma, which develops extremely rarely.

As a result of inadequate therapy with hypoglycemic drugs, a state of hypoglycemia, or hypoglycemic coma, may develop, which is typical for both types of diabetes mellitus. Chronic or late complications of diabetes mellitus develop several years after the onset of the disease and are typical for types I and II.

Such complications are macroangiopathy, nephropathy, retinopathy, neuropathy, diabetic foot syndrome. The development of these complications is associated with a long-term state of hyperglycemia in any type of diabetes mellitus.

In the case of determining the amount of glucose after a meal, the glucose content fluctuates between values ​​of 5,6-6,7, then a glucose tolerance test must be performed to confirm the diagnosis. Before the test, the patient should not eat for 12 hours.

For this, the test is carried out in the morning on an empty stomach. Within 3 days before the test, the patient must adhere to a diet and or a stress test, its content increases in capillary blood by about 1,1 mmol / l compared to venous blood. Blood plasma contains 0,84 mmol/l more glucose than whole blood. If the glucose content is indicated without any additional information, then it refers to capillary whole blood.

In the event that the patient has any signs of the presence of diabetes mellitus, it is only necessary to note the blood glucose content of more than 10 mmol / l at any time to make a diagnosis.

The diagnosis of diabetes mellitus is considered reliable if the fasting blood glucose is equal to or greater than 6,7 mmol / l twice. If corresponds to the optimal content of carbohydrates. At the same time, the patient cancels the intake of drugs such as thiazide diuretics, various contraceptives and glucocorticoids.

The glucose tolerance test itself consists in the fact that the patient in the morning on an empty stomach drinks 75 g of glucose diluted in 250-300 ml of water for 5 minutes. Two hours later, the blood glucose content was determined. The following are considered normal values: fasting blood glucose ‹ 2 mmol / l, after 6,7 hours - ‹ 2 mmol / l. If the patient has diabetes mellitus, then the fasting glucose content is 7,8 mmol / l, and 6,7 hours after the load - 2 mmol / l.

In the case of impaired glucose tolerance, the amount of glucose on an empty stomach is 6,6 mmol / l, and after 2 hours it is in the range of 7,8 - 11,1 mmol / l. If the patient has various forms of malabsorption in the intestine, the glucose tolerance test may turn out to be false positive, that is, the blood glucose will be within the normal range.

When taking blood to determine the glucose content, the first drop is not used for this. This is due to the fact that those products that are used for disinfection contain alcohol, which increases glucose levels. An elevated glucose level can be determined in cases where the patient has inflammatory diseases, after stressful conditions, various injuries, after surgical interventions on the stomach, when the normal passage of food through the intestines changes, and in other conditions.

According to WHO, the diagnosis of diabetes mellitus is considered reliable if one of the following three conditions is present:

1) the presence of symptoms of diabetes mellitus, such as polyuria, polydipsia, progressive weight loss, combined with a blood glucose level equal to or greater than 11,1 mmol / l when determined at any time;

2) fasting blood glucose - 6,1 mmol/l or more;

3) the content of glucose in capillary blood 2 hours after the stress test - 11,1 mmol/l or more.

To differentiate the type of diabetes mellitus, the determination of the C-peptide content is used. Its amount indirectly indicates the ability of pancreatic b-cells to secrete insulin.

These cells synthesize proinsulin, which consists of A-, B- and C-chains. In them, the C-peptide is cleaved from proinsulin and active insulin is formed. C-peptide and active insulin enter the bloodstream in equal amounts. 50% of insulin binds in the liver.

In the peripheral circulation, insulin has a half-life of about 4 minutes. C-peptide does not bind in the liver. It has a half-life of about 30 minutes. C-peptide does not bind to peripheral receptors.

If, in the study on an empty stomach, the content of C-peptide is ‹ 0,4 nmol / l, then this indicates a high degree of type I diabetes mellitus in a patient. More informative is the test using stimulation (for example, the test with glucagon is widely used). Initially, the content of C-peptide on an empty stomach is determined.

Then 1 ml of glucagon is injected intravenously. Six minutes later, the C-peptide content is also determined.

Sufficient secretory activity of pancreatic β-cells is characterized by the content of C-peptide on an empty stomach of more than 0,6 nmol/l, and after stimulation more than 1,1 nmol/l. If the content of C-peptide after stimulation is 0,6 nmol/l or less, then the patient needs endogenous insulin. In the case of a test against the background of decompensation of metabolic processes in diabetes mellitus, it is not informative.

When decompensated, a state of hyperglycemia is observed, which, in turn, leads to damage to the β-cells of the gland and obtaining false results of the test with glucagon. Long-term use of insulin preparations in the treatment of diabetes mellitus does not in any way affect the results of the tests.

Laboratory methods are also used to determine the quality of compensation in diabetes mellitus. For this purpose, the glucose content is determined both on an empty stomach and after a meal, the glucose content in the urine, the amount of total (see Table 1) cholesterol. Of greatest importance in this matter is the content of glycated hemoglobin in the blood (HbA₁) (table according to I. I. Dedov). Assessment of the quality of therapy for diabetes mellitus is carried out strictly individually.

As a result of the long course of the disease, there is an increased risk of developing late complications of diabetes mellitus.

Thus, in those people who have recently been diagnosed with type XNUMX diabetes, it is necessary to achieve normal blood glucose levels for a long time.

In patients with already long-term diabetes mellitus, achieving a normal level of glycemia is not advisable.

Type I diabetes mellitus is an autoimmune disease that can develop as a result of exposure to a viral infection on the body, as well as under the influence of a number of other environmental factors that act against the background of a given individual's genetic predisposition to diabetes mellitus.

Under the influence of pathological factors on the pancreatic tissue, the structure of surface antigens of β-cells changes, which leads to the development of an autoimmune process.

Under its influence, the pancreatic islets of the gland are infiltrated by immunocompetent cells, i.e., insulitis develops. This, in turn, leads to the destruction of damaged β-cells. A decrease in glucose tolerance is observed when approximately 75% of pancreatic β-cells die.

If, against this background, any stressful situation develops, for example, surgery or the introduction of an infectious agent into the body, the first symptoms of diabetes appear.

If 80-90% of β-cells are affected, then type I diabetes mellitus manifests itself clinically without the influence of additional factors.

The antigenic properties of pancreatic β-cells can change under the influence of a number of factors, which may be viral infections, the influence of genetic factors, environmental factors, and also the nature of nutrition.

The leading role in the development of diabetes belongs to the influence of infectious agents, as evidenced by the fairly frequent detection in the blood of patients of antibodies to viruses such as rubella virus, cytomegalovirus, mumps virus, Coxsackie virus, encephalomyelitis virus and a number of others. The titer of these antibodies is usually quite high. In the event that a woman has had rubella during pregnancy, in about 25% of cases her child will develop type I diabetes during her life.

There is also evidence of the existence of a genetic predisposition to the development of type I diabetes mellitus, but its role has not yet been fully elucidated. The development of this disease is more likely in the presence of HLA DR haplotypes.₃, D.R.₄ and D.Q.

If the father has type I diabetes, the probability of developing the same pathology in the child does not exceed 5%, if the mother has the disease, the probability does not exceed 2,5%.

In the case of type I diabetes in both parents, the probability of developing a pathology in a child increases and is about 20%. The hereditary nature of the disease is observed only in 5-10% of children with diabetes mellitus.

The risk of developing type I diabetes in siblings depends on the degree of identity of their HLA ... In the event that siblings have identical HLA, then the probability of developing the disease is about 18%. If the HLA of the sibs are not identical, then the likelihood of developing diabetes is low.

Clinically, type 40 diabetes mellitus appears before the age of 14 years, and most often at XNUMX years of age. The clinical picture in each case will be individual. In diabetes, there is a decrease in the amount of secreted insulin, which leads to the development of hyperglycemia. This increases the osmolarity, which causes the appearance of osmotic diuresis.

In addition, the thirst center located in the brain is stimulated, which explains the increased thirst in this pathology.

With a decrease in the amount of glucose in the blood, glycogenolysis in the liver increases. This mechanism is aimed at covering the energy costs of the body. Activation of glycogenolysis occurs due to the influence of contrainsular hormones, such as: glucagon, cortisol, catecholamines, growth hormone. Type I diabetes mellitus is characterized by low levels of insulin in the blood or its complete absence.

In this case, there is no normal synthesis of glycogen and its deposition in the liver. In response to the release of contra-insular hormones, there is no increase in the processes of glycogenolysis adequate to the energy costs of the body, and an increase in the level of glycemia does not occur. In response to the action of contrainsular hormones, the process of gluconeogenesis is activated, which can lead to a severe impairment of the patient's condition up to the formation of ketoacidotic coma.

Insulin normally leads to an increase in the synthesis of protein and fat in the body, i.e., it has an anabolic effect. In the case of a decrease in the content of insulin in the blood, a violation of the course of these processes occurs, which leads to a decrease in the body weight of patients, the appearance of progressive muscle weakness and a decrease in working capacity up to its complete loss.

The absence of insulin in the body leads to the activation of proteolysis and the inclusion of gluconeogenesis due to the appearance of free amino acids in the bloodstream. There is a decrease in muscle mass. The process of oxygen supply to the tissues of the body is disrupted, i.e., hypoxia develops, which is due to the fact that about 20% of hemoglobin is glycosylated.

Decompensation of metabolic processes and the development of ketoacidotic coma can occur against the background of various infections or injuries. An increase in blood glucose levels in this case causes an increase in diuresis and dehydration of the body. With a lack of insulin in the bloodstream, lipolysis is activated, which, in turn, leads to an increase in the amount of free fatty acids in the blood.

Since diabetes mellitus in the liver disrupts the processes of fat synthesis, free fatty acids are included in the process of ketogenesis. At the same time, such metabolic products as acetone and acetoacetic acid appear in the blood. They are ketone bodies and lead to the development of ketosis and then ketoacidosis. If the body continues to lose fluid, i.e., is subject to progressive dehydration, ketoacidotic coma occurs. Ketone bodies that appear in the bloodstream cause irritation of the peritoneum and the appearance of symptoms of an acute abdomen, i.e., pseudoperitonitis develops. In addition, nausea and vomiting may occur, which makes it difficult to diagnose. To make a correct diagnosis, it is necessary to conduct a study of the patient's blood and urine for the presence of ketone bodies and glucose.

Type 0,3 diabetes may present in children with pyelonephritis or a urinary tract infection. After the start of treatment of diabetes mellitus with insulin preparations for a rather long period of time, the doses of the drug may remain small and even be less than 10 U / kg. This period of time when the dosage remains minimal is referred to as the remission phase. In the case of the development of a state of ketoacidosis, the secretion of insulin by the existing β-cells of the pancreas is reduced by 15-XNUMX%. The use of insulin preparations during this period leads to the restoration of the function of the remaining cells.

At their expense, the body is provided with insulin at a minimum level. In the event that the patient follows the diet prescribed to him, doses his physical activity, the remission phase can continue for a rather long period.

If the residual secretion of insulin remains in the body and is about 1 U / h, then it can compensate for the necessary basal level of the hormone in the blood. Residual secretion of insulin in the body lasts longer if insulin therapy is carried out from the very beginning of the disease.

When even small amounts of glucose appear in the urine, and the fasting blood glucose is 5,5-6,5 mmol / l, 1 hour after a meal - more than 8 mmol / l when treated with insulin preparations at a dose of 0,3 -0,4 U/kg, the remission phase is considered completed.

Diabetes mellitus type II is, in its pathogenesis, a group of metabolic disorders of a heterogeneous nature. This disease is characterized by a variety of clinical manifestations. Type II diabetes mellitus is divided into two groups: diabetes mellitus II a and diabetes mellitus II b. Diabetes mellitus II a proceeds without obesity. Often, under its mask, diabetes mellitus of a latent autoimmune nature proceeds. Diabetes mellitus II b is characterized by the presence of obesity. In patients with diabetes mellitus IIa, achieving a normal level of glucose in the blood presents certain difficulties, which is observed even with the use of tablet sugar-lowering drugs at the maximum dose. After about 1-3 years after the start of therapy with tableted sugar-lowering drugs, the effect of their use disappears completely.

In this case, resort to the appointment of insulin preparations. In diabetes mellitus type IIa, diabetic polyneuropathy develops in more frequent cases, which progresses more rapidly than in diabetes mellitus type IIb. Type II diabetes mellitus is characterized by a hereditary predisposition. The probability of developing diabetes of this type in a child in the presence of the same disease in one of the parents is approximately 40%. The presence of obesity in humans contributes to the development of impaired glucose tolerance and type II diabetes mellitus. Obesity of the first degree increases the risk of developing type II diabetes by 3 times.

If there is moderate obesity, then the likelihood of diabetes increases by 5 times. With obesity of the III degree, the probability of manifestation of type II diabetes mellitus increases by more than 10 times. The pathogenesis of type II diabetes mellitus includes several stages. The first stage is characterized by the presence in a person of an innate tendency to obesity and an increased content of glucose in the blood. The second stage includes hypodynamia, an increase in the amount of food consumed, combined with a violation of insulin secretion by pancreatic β-cells, which leads to the development of body tissue resistance to the effects of insulin on them. In the third stage of the pathogenesis of type II diabetes mellitus, impaired glucose tolerance develops, which leads to metabolic syndrome. The fourth stage is characterized by the presence of type II diabetes mellitus in combination with hyperinsulinism. At the fifth stage of pathogenesis, the function of β-cells is depleted, which, in turn, leads to the appearance in this patient of the need for exogenous insulin. Leading in the development of type II diabetes mellitus is the presence of tissue insulin resistance. It is formed as a result of a decrease in the functional ability of pancreatic β-cells. Several mechanisms have been identified for dysfunction of insulin-producing cells.

1. In the absence of pathology, insulin is secreted by β-cells with a certain frequency, which is usually 10-20 minutes. In this case, the level of insulin in the blood is subject to fluctuations.

In the presence of interruptions in insulin secretion, the sensitivity of receptors to this hormone is restored. Type II diabetes mellitus can occur with an increase in the content of insulin in the bloodstream, while the absence of the periodicity of its secretion. At the same time, fluctuations in its content in the blood, characteristic of a normal organism, are absent.

2. With an increase in blood glucose levels after a meal, there may not be an increase in insulin release. At the same time, secreted insulin is not able to be ejected from β-cell vesicles. Its synthesis in vesicles continues in response to an increase in blood glucose, despite its excess. The glucose content in this pathology does not reach normal values ​​(see Table 2).

3. Type II diabetes mellitus is characterized by the fact that the amount of glucagon in the body increases with an increase in blood glucose. Under the influence of insulin secretion, the production of glucagon does not stop.

4. Premature emptying of β-cells of the gland may occur, when active insulin has not yet been formed. The proinsulin released into the bloodstream does not have activity against hyperglycemia. Proinsulin can have an atherogenic effect.

With an increase in the amount of insulin in the blood (hyperinsulinemia), excess glucose constantly enters the cell. This leads to a decrease in the sensitivity of insulin receptors, and then to their blockade. At the same time, the number of insulin receptors gradually decreases, and there is also a suppression of post-receptor mechanisms, due to which insulin can exert its effects indirectly. Against the background of hyperinsulinemia, glucose and fats that enter the body as a result of food intake are deposited in excess by adipose tissue. This leads to an increase in insulin resistance of body tissues. In addition, with hyperinsulinemia, the breakdown of fats is suppressed, which, in turn, contributes to the progression of obesity. An increase in blood glucose has an adverse effect on the functional ability of β-cells of the gland, leading to a decrease in their secretory activity.

Since the increased content of glucose in the blood is observed constantly, for a long time, insulin is produced by the cells in the maximum amount, which, in the end, leads to their depletion and the cessation of insulin production. For treatment, exogenous administration of insulin is used; in the norm, 75% of the consumed glucose is utilized in the muscles, deposited in the form of a glycogen reserve.

As a result of the resistance of muscle tissue to the action of insulin, the process of formation of glycogen from glucose in it decreases. Tissue resistance to the hormone occurs as a result of mutation of genes that encode special proteins that transport glucose into the cell.

In addition, with an increase in the level of free fatty acids, the formation of these proteins decreases, which leads to a violation of the sensitivity of β-cells to glucose. This leads to impaired insulin secretion.

metabolic syndrome. This syndrome precedes the development of type II diabetes mellitus. A distinctive feature of the syndrome from diabetes mellitus is the absence of stable hyperglycemia, which is associated with an increase in insulin production, which ensures the overcoming of tissue resistance to the hormone.

To prevent the development of diabetes, it is necessary to adhere to a diet (Table 2) and reduce body weight. If these recommendations are followed, the risk of diabetes mellitus is reduced by 30-50%.

Metabolic syndrome leads to the development of not only type II diabetes mellitus, but also to atherosclerosis and essential hypertension. The syndrome is accompanied by tissue resistance to insulin, hyperinsulinemia, an increase in the content of C-peptide in the blood, and a violation of glucose tolerance.

In the blood, the amount of triglycerides and ANP is increased, the amount of HDL is reduced. In most cases, patients develop abdominal obesity, women have hyperandrogenism, and arterial hypertension often develops.

Type II diabetes is often diagnosed incidentally during a routine blood test. Patients may first seek medical care when there are already late complications of diabetes.

Exclusion or confirmation of the diagnosis of diabetes mellitus is necessary if the patient has frequent urinary tract infections or ultrasound diagnoses fatty liver. Almost all patients with type II diabetes are obese to some degree. Efficiency quite often does not decrease, but, on the contrary, may even be increased.

The tissues of the body may not experience an energy deficit, which is associated with an increase in insulin secretion. In type II diabetes mellitus, minimal insulin production is maintained, which explains the uncharacteristic development of the state of ketoacidosis and ketoacidotic coma.

Diabetes mellitus of this type is characterized by the development of hyperosmolar coma. Its pathogenesis is associated with the fact that the patient develops polyuria, as a result of which the body loses fluid and hyperosmolarity develops.

A prolonged and persistent increase in the amount of glucose in the blood leads to visual impairment, which can become irreversible with an advanced form of the disease.

Lecture number 6. Treatment of diabetes

To achieve a positive therapeutic effect in diabetes mellitus, it is necessary to compensate for insulin deficiency in the body, correct hormonal and metabolic disorders, and also prevent and treat existing late complications of diabetes mellitus. To achieve these effects, the following principles of therapy must be observed: diet, individually selected physical activity, the use of drugs that lower blood glucose levels, as well as patient education.

The diet for type I and type II diabetes is different. In type II diabetes, the goal of diet therapy is to reduce body weight. In type I diabetes, the diet is a forced restriction of the quantity and quality of food intake, which is associated with the inability to accurately mimic the physiological secretion of insulin. Diet in this case is necessary to maintain the optimal level of compensation of metabolic processes.

In type I diabetes, it is necessary to teach the patient to self-calculate the dose of exogenously administered insulin, depending on the food he takes. If the patient's body weight is within the normal range, then the energy value of the food taken should correspond to the energy requirement - an isocaloric diet.

If the patient has an excess of body weight, then the diet should be hypocaloric. During the period of decompensation of metabolic processes, a pronounced decrease in body weight often occurs. In such cases, a hypercaloric diet is required.

This diet includes an increase in the amount of carbohydrates to 50-60% of its total energy value. Carbohydrates have the following effects: reduce the resistance of adipose tissue to the action of insulin, increase the rate of glucose utilization by cells. To reduce the atherogenicity of the diet, the amount of fat is reduced to 20-30%. The amount of proteins is reduced to 10-15%, which leads to a slowdown in the development of microangiopathy. Carbohydrates, which are easily digestible, are strictly limited. These carbohydrates are sucrose and glucose. For a gradual increase in blood glucose levels, the diet should be dominated by carbohydrates containing a long carbon chain.

Sweeteners are often used. They are divided into two groups: natural (caloric) and artificial (non-caloric). The first group includes fructose, xylitol, sorbitol. The use of fructose leads to an increase in the level of glycemia 3 times less than when using the same amount of glucose.

Xylitol and sorbitol do not affect glycemic levels in any way. The second group of sweeteners includes saccharin, acesulfame, cyclamate, L-aspartame, sucralose. In the presence of phenylketonuria in a patient with diabetes, the use of L-aspartame is contraindicated.

In the presence of renal failure, the use of cyclamate is limited. In case of heart failure, the use of acesulfame is limited. Dietary fiber, which is part of vegetables, fruits and grains, has a hypoglycemic effect due to the fact that it accelerates the movement of food through the intestines. Also, when eating these products, the absorption of cholesterol and fatty acids decreases.

The amount of dietary fiber should be at least 40 g per day. If the diet is followed by persons suffering from type II diabetes, there is a decrease in body weight, which leads to compensation of metabolic processes as a result of restoring the sensitivity of cellular receptors to insulin. If the patient has type II b diabetes mellitus, the diet should be hypocaloric with a gradual decrease in the energy value of food. Typically, calorie content is reduced by 500 kcal / day, which leads to a decrease in body weight by 1-2 kg per month.

If type II diabetes mellitus is combined with obesity, then the calorie content of food is reduced by 15-17 kcal/kg of body weight. If the patient suffers from type I diabetes, then it is necessary to calculate the number of bread units. These calculations are necessary to determine the dose of insulin preparations, which are administered before each meal. One bread unit corresponds in energy value to 10-12 g of carbohydrates. Special tables have been compiled for counting grain units. Bread units do not fully reflect the energy value of food, since their calculation does not take into account the amount of proteins and fats.

1. Insulin therapy

Insulin is a pancreatic hormone that performs a regulatory function. Pancreatic cells produce proinsulin, which is inactive. As a result of the action of enzymes, the C-peptide is cleaved from proinsulin. The result is active insulin. It enters the bloodstream and travels through the portal vein system to the liver. In the liver, half of the incoming insulin binds to receptors. The rest of the hormone enters the general bloodstream, and then to the muscles and fatty tissue.

The main share of the hormone, about 80%, is metabolized in the liver and kidneys. The rest is metabolized in muscle and adipose tissue. The secretion of insulin by the pancreas is divided into basal and food.

The basal secretion of the hormone is approximately 1 U / h, which ensures the optimal content of glucose in the blood between meals. Dietary secretion of insulin occurs after a meal, which results in an increase in blood glucose levels.

The amount of insulin produced is approximately 1-1,5 units per 10-15 g of carbohydrates. Insulin secretion also fluctuates throughout the day. Its largest amount is produced in the early morning hours, the smallest in the evening.

For the treatment of diabetes mellitus, the best drug is human insulin, obtained by a semi-synthetic or biosynthetic method. The semi-synthetic method consists in replacing alanine with threonine in porcine insulin. The biosynthetic method consists in inserting a portion of the human genome that is responsible for the formation of insulin into the genome of an intestinal bacterium or yeast culture. As a result of this manipulation, microorganisms begin to synthesize human insulin.

Insulin preparations are divided into preparations of short and prolonged action. Short-acting drugs are rapidly absorbed, which provides a large concentration of insulin in the blood. Short-acting insulins have several routes of administration: subcutaneous, intramuscular, intravenous.

Long-acting insulins are divided into two groups: medium-acting and long-acting.

Intermediate-acting drugs are slowly absorbed, which provides the onset of their action approximately 1-1,5 hours after administration.

Long-acting preparations consist of large crystals, which ensures even slower absorption. The drugs of this group begin to act 4-5 hours after administration. The duration of their action is 28-36 hours.

The maximum effect is reached 8-14 hours after administration. Despite such a long-term effect of drugs in this group, one injection per day is usually not enough. This is due to the impossibility of providing these drugs with sufficient basal insulin in the blood during the day.

There are a number of indications for the appointment of insulin therapy. These include type I diabetes mellitus, pancreatectomy, the inability to achieve compensation of metabolic processes by diet in diabetes during pregnancy, as well as a number of conditions that occur during the course of type II diabetes mellitus.

Such conditions include hyperosmolar or lactic acid coma, precomatous state, progressive weight loss, ketoacidosis, a decrease in the content of C-peptide in the blood of less than 0,2 nmol / l during a test with glucagon, fasting blood glucose more than 15 mmol/l, the impossibility of achieving compensation of metabolic processes against the background of prescribing tableted hypoglycemic drugs at the maximum daily dose, the onset and rapid progression of late complications of diabetes mellitus, various surgical interventions.

Therapy with insulin preparations is the closest to the physiological secretion of insulin during the day. There are several principles of insulin therapy.

The first principle is that basal secretion of insulin during the day is provided by twice the introduction of insulin preparations in the morning and in the evening. The total dose of these two injections of insulin should not exceed half of the total daily dose of the drug.

The second principle of insulin therapy says that the replacement of food secretion of insulin occurs due to the introduction of short-acting drugs before each meal. The dosage of drugs is calculated from the estimated amount of carbohydrates that the patient plans to take. In addition, the existing level of glucose in the blood before meals is taken into account. This level of glycemia is determined by the patient independently using an individual glucometer. Such insulin therapy, which includes both long-acting and short-acting drugs, is called basal-bolus.

Since the patient must calculate the amount of insulin administered each time, taking into account the existing level of glycemia and the number of bread units that he intends to take at the moment, the third provision speaks of the need for patient education. It is also necessary to carry out strict medical quality control of insulin therapy.

There are traditional and intensive insulin therapy. When conducting traditional insulin therapy, the patient is, as it were, dependent on food intake. In the event that food intake does not occur, the patient may develop a state of hypoglycemia. Intensive insulin therapy has both its advantages and disadvantages.

The advantages of intensive insulin therapy are more effective compensation of metabolic processes and glycemia levels; independent calculation of the dosage of the drug by patients, taking into account the existing level of glycemia; change by the patient at his own discretion of the daily routine, the quality and quantity of foods that he would like to eat, as well as an independent dosage of physical activity; the achievement of intensive insulin therapy the most effective prevention of late complications of diabetes mellitus, the risk of which is reduced by about 50-80%.

Disadvantages of intensive insulin therapy include the following: the patient must monitor blood glucose several times a day, sometimes up to 5-6 times a day; there is a need for patient education, which requires certain costs on the part of the medical staff and on the part of the patient himself; conditions of mild hypoglycemia develop even with accurately administered intensive insulin therapy.

Patients with type II diabetes in most cases do not need to prescribe insulin preparations. However, in some cases, the patient needs to take endogenous insulin. Such patients are divided into two groups.

The first group includes young patients (28-40 years old) who are not obese. In such patients, compensation of metabolic processes in diabetes mellitus was achieved for a long time by prescribing tableted sugar-reducing drugs.

The second group includes patients with type II diabetes mellitus who have been using sulfonylurea drugs for treatment for a long time, against which they developed resistance to this group of drugs. In this case, the developed resistance is secondary. Resistance develops in approximately 11% of patients with type II diabetes mellitus 3 years after the appointment of sulfonylurea drugs.

The reason for the development of resistance may be the development of a complete deficiency of insulin in the body with the progression of the disease or the progression of insulin resistance already present in the body against the background of a chronic violation of the diet and taking the maximum possible doses of the drug. Prescribing insulin preparations to such patients presents rather great difficulties, which is associated with the presence of insulin resistance in body tissues.

Before prescribing endogenous insulin, it is necessary to fully exhaust the possibilities of therapy with a diet and tablet sugar-lowering drugs.

There are several tactics of insulin therapy. Sometimes insulin therapy is temporary and can last from several weeks to several months. This tactic is used in the absence of true insulin deficiency. With such therapy, it is possible to restore the sensitivity of insulin-producing cells, as well as body tissues to sulfonylurea drugs. Cancellation of the introduction of exogenous insulin should occur gradually. In the interim, treatment in combination with tableted sugar-reducing drugs is possible.

Another treatment tactic is to prescribe insulin in combination with oral antidiabetic drugs from the very beginning of therapy. In this case, intermediate-acting insulin is used. Its injections are carried out at night; thus, the onset of action of the drug falls on the early morning hours.

Sulfonylureas are used throughout the day to achieve normal blood glucose levels. Initially, the dose of the drug is small, which is necessary to prevent the state of hypoglycemia.

The dose of insulin at the first injection is no more than 6-8 IU every 2-3 days, the dosage is increased by 2 IU. The increase in dosage occurs until the level of fasting glycemia in the early morning hours drops to 6-6,8 mmol / l.

If combination therapy is ineffective or signs of decompensation of metabolic processes appear, then it is necessary to transfer the patient to insulin therapy.

The dosage of insulin is made taking into account the following data: blood glucose, time of day, the number of bread units that the patient intends to consume, as well as the intensity of physical activity before and after eating. The time interval between insulin administration and food intake is selected individually.

In most cases, this interval is from 15 to 30 minutes. One of the goals of insulin therapy is to normalize fasting glucose levels. The evening dose of insulin is administered at about 22-23 hours, since its action occurs after 8-9 hours.

When calculating the evening dose of insulin, it is necessary to take into account the possibility of developing a state of hypoglycemia in the morning. Sometimes, when an increased level of glycemia is detected in the morning, patients begin to increase the amount of insulin administered in the evening, which leads to an even greater increase in the level of glycemia in the morning on an empty stomach.

The increase in blood glucose in the morning is explained by the following processes. With the introduction of a large amount of insulin in the evening, by about 2-3 am, a state of hypoglycemia develops.

This can be manifested by sleep disorders with the appearance of nightmares, any actions of the patient that are unconscious can be noted, in the morning, patients note the appearance of a headache and a state of weakness. The development of a state of hypoglycemia at night causes a compensatory release into the bloodstream of glucagon, which is a hormone with an action opposite to insulin. This leads to the development of hyperglycemia in the morning and is called the Somoji phenomenon. Closer to the morning, the action of insulin decreases and may stop altogether, which also causes an increase in blood glucose levels. This phenomenon is called the "morning dawn" phenomenon.

In this case, it is necessary to exclude the Somogyi phenomenon, for which it is necessary to carry out glycemic control at about 3 am. After eliminating the Somogyi phenomenon, it is necessary to postpone the evening administration of insulin to a later time, and then carry out a gradual increase in the dose under constant control of the level of glycemia at 3 am. After the patient reaches normalization of the level of glycemia in the morning, they begin to control the amount of glucose in the blood after a meal, which is necessary to assess the adequacy of the administered dose of insulin before breakfast.

The content of glucose in the blood is determined after 1-1,5 hours after a meal. Reception of 1 bread unit causes an increase in the level of glycemia by 1,6-2,2 mmol / l. A decrease in glucose levels by the same value occurs with the introduction of 1 IU of insulin. This suggests that the number of units of insulin administered before meals is equal to the number of bread units that the patient plans to consume. In case of hyperglycemia, the dose of insulin should be increased before meals. If there is a state of hypoglycemia, the dose of insulin is reduced.

In the case of traditional insulin therapy, the calculation of bread units is practically irrelevant. For constant self-monitoring of the level of glycemia, patients should have an individual glucometer. In the case of a glucose content of more than 13 mmol / l and the presence of glucose in the urine, it is necessary to analyze for the presence of acetonuria.

To determine the quality of compensation of metabolic processes in diabetes mellitus, the level of glycated hemoglobin in the blood is determined. Glucose enters erythrocytes independently of insulin, thus, the degree of hemoglobin glycosylation is directly proportional to the amount of glucose during the 110 days of the existence of erythrocytes, if hyperglycemia is constant, then about 20% of hemoglobin is glycosylated. In addition to hemoglobin, many other proteins undergo glycosylation.

This fact is of great importance in the pathogenesis of late complications of diabetes mellitus. The content of glycosylated hemoglobin is examined every 3 months. Despite the fact that during the period of remission of diabetes mellitus secretion of insulin is maintained in a small volume, insulin therapy continues.

During this period, it is possible to refuse the introduction of insulin of an average duration of action, since the residual secretion of insulin is similar in its values ​​to basal.

In this case, only short-acting insulin is administered before each meal. Its dosage is calculated from the estimated number of grain units. Patients use subcutaneous insulin. Intramuscular and intravenous administration is used in emergency situations.

The onset of effect after administration of short-acting insulin depends on the injection site. The fastest action is observed when injected under the skin of the abdomen. The effect is observed after 15-30 minutes, reaching its maximum after 45-60 minutes. The slowest action is observed when injected under the skin of the thigh. The onset of the effect is noted after 1-1,5 hours, while only 75% of the total injected insulin is absorbed. An intermediate position is occupied by injections into the shoulder area.

It is recommended to inject short-acting insulin under the skin of the abdomen, and intermediate-acting insulin under the skin of the shoulder or thigh. The rate of insulin absorption increases with warming of the injection site.

The place of injection of the drug should constantly change. The distances between injections should be at least 12 cm. Insulin administration using syringe pens is now widespread.

Insulin therapy is accompanied by a number of complications. The most common state of hypoglycemia and hypoglycemic coma. The latter is the most dangerous complication of insulin therapy. In addition, allergic reactions can be observed, which can be both local and general. Local allergic reactions are noticeable on examination and are located at the injection site.

May present with itching, redness, or induration. General allergic reactions are manifested by urticaria, Quincke's edema or anaphylactic shock, the latter are extremely rare.

2. Tableted antidiabetic drugs

These drugs are used to treat type II diabetes. There are also contraindications for their use, such as acute complications of diabetes mellitus, severe damage to the liver and kidneys with impaired function, pregnancy, childbirth, lactation, blood diseases, acute inflammatory diseases, vascular complications of diabetes mellitus in the organic stage, surgical interventions, weight loss progressive bodies.

Tableted sugar-lowering drugs are divided based on their impact on the pathogenesis of diabetes mellitus.

Such links are impaired insulin secretion, insulin resistance of tissues, increased production of glucose in the liver, and glucose toxicity. Based on this, 3 groups of drugs are distinguished:

1) drugs that increase the secretion of insulin. They stimulate the synthesis and release of insulin by pancreatic β-cells.

These drugs include sulfonylurea and nonsulfonylurea drugs (glinides);

2) drugs that reduce tissue resistance to insulin. They reduce the formation of glucose in the liver, and also enhance the utilization of glucose by tissues. This group includes biguanides and trisuazolindiones;

3) drugs that inhibit the absorption of carbohydrates in the gastrointestinal tract. This group includes α-glucosidase inhibitors.

Sulfonylureas. These include glibenclamide, gliclazide, glimeperide, glipizide, gliquidone. The drugs of this group act on the β-cells of the pancreas.

On the membrane of these cells there are specific receptors to which sulfonylurea drugs bind, which causes the closure of potassium channels.

Simultaneously, depolarization of the cell membrane occurs, which causes the opening of calcium channels. Calcium begins to enter the cell, which causes its degranulation and the release of insulin into the bloodstream.

In the absence of pathology, insulin secretion occurs biphasically. With adequate therapy with sulfonylurea drugs, the sensitivity of b-cells to an increase in glucose levels increases.

In this case, the production of insulin will approach physiological. In the case of prescribing excessively large doses of drugs in the absence of indications, as well as chronic dietary disorders, lead to constant hyperstimulation of β-cells, which, in turn, causes an increase in tissue resistance to insulin, the development of hyperinsulinemia and hyperglycemia. Hyperglycemia may become permanent.

The resulting constant hyperstimulation of β-cells when taking large doses of sulfonylurea drugs causes the depletion of these cells, which leads to the vital need for insulin injections.

The appointment of sulfonylurea drugs is necessary if the patient has type II diabetes mellitus in combination with normal body weight, the presence of high values ​​of fasting glycemia, as well as a decrease in the amount of C-peptide in the blood.

If a patient has acetonuria, progressive weight loss, minimal C-peptide in the blood, and no increase after a meal or after a glucagon test, the β-cells are considered to be depleted.

In this case, resort to the appointment of insulin therapy. Weight loss while taking sulfonylurea drugs can lead to an increase in the sensitivity of body tissues to insulin and the development of a state of hypoglycemia.

Sulfonylureas are divided into drugs of the first and second generations. First-generation drugs are practically not used at present.

Mostly second-generation drugs are used, which cause fewer side effects. Side effects from taking sulfonylurea drugs are very diverse.

A state of hypoglycemia may occur, which occurs when an insufficient amount of food is taken, the patient has renal failure, cumulation of the drug, when taking long-acting drugs, and also against the background of a general decrease in body weight.

Possible side effects from the blood, such as: leukopenia, agranulocytosis, thrombocytopenia. These complications occur in very rare cases. Possible allergic reactions. In the form of a rare variant of allergy, the development of cholestatic jaundice can be noted.

Glibenclomid. This drug is used most often. The effect appears 40 minutes after its administration, reaching its maximum after 2 hours. The effect lasts for 10-12 hours.

The drug is completely metabolized in the liver and 50% is excreted in the urine, the other 50% is excreted in the bile. Treatment begins with the appointment of 2,5 mg of glibenclomid 30 minutes before meals. If the effect is absent for several days, then the dose of the drug is gradually increased.

If there is no effect after a single dose of 5 mg of glibenclomide, it is necessary to take the drug at a dose of 2,5 mg 30 minutes before dinner. If the dosage of the drug is more than 15 mg, then a further increase in the dose does not lead to an increase in the effect.

Gliclazide. Begins to act 30 minutes after ingestion. The peak of efficiency is observed after 2-3 hours. The duration of action is 12 hours.

The drug is completely metabolized in the liver. Excreted with the help of the kidneys. At the beginning of treatment, the daily dose is 40-80 mg.

The maximum possible dose is 320 mg. The daily dose of the drug is divided into 2 doses. Gliclazide has hypoglycemic properties, and also has a positive effect on microcirculation, homeostasis and improves the rheological properties of blood.

Glipizide begins to act after 10-30 minutes, the peak of efficiency is observed after 1,5 hours. The effect lasts 8-10 hours. The drug is completely metabolized by the liver, excreted through the kidneys.

The likelihood of developing a state of hypoglycemia is minimal. The initial dose of the drug is 2,5-5 mg, and the maximum daily dose should not exceed 20 mg. The daily dose is divided into 2-4 doses.

Gliquidone. This drug can be prescribed in the presence of kidney disease, as it is 95% excreted through the intestines.

The effect develops 40 minutes after taking the drug, reaching its peak after 2 hours. The duration of action is 6-8 hours. The minimum dose of the drug is 30 mg, the maximum is 180 mg. The drug is taken 2-3 times a day, depending on the dose.

Glimepiride stimulates β-cells, increasing insulin secretion, and also reduces tissue resistance to the hormone. The drug can be taken 1 time per day. The initial dose is usually 1 mg, the maximum daily dose is 8 mg.

Nonsulfonylurea secretagogues (glinides) are a new group of tableted sugar-lowering drugs.

These drugs stimulate the secretion of insulin by the pancreas.

There are a number of indications for the use of these drugs: newly diagnosed type II diabetes mellitus in combination with signs of insufficient secretion of endogenous insulin; the presence of postprandial hyperglycemia; elderly and senile age; intolerance to other tableted sugar-lowering drugs. The best results of therapy with glinides are observed while maintaining a small secretion of insulin.

In some cases, prolonged-release insulin may be used. Repaglinide and nateglinide are widely distributed. Side effects are similar to side effects when using sulfonylurea drugs.

Biguanides. Of this group of drugs, metformin is the most widely used. There are several mechanisms of hypoglycemic action of drugs. Metformin reduces the intensity of gluconeogenesis in the liver, leading to a decrease in the formation of glucose.

Under its influence, the sensitivity of tissues to insulin increases. In addition, the drug has a mildly pronounced anorexigenic effect. In addition, the absorption of carbohydrates in the intestine slows down. When using the drug, there is a decrease in LDL, as well as total cholesterol in the blood plasma.

The drug reduces the concentration of fibrinogen in the blood and accelerates thrombolysis, that is, it has a fibrinolytic effect. Basically, metformin is prescribed for type II diabetes mellitus with obesity or hyperlipidemia. A single dose of the drug is 500 - 1000 mg, daily - 2,5-3 g.

The frequency of administration depends on the dose and is 1-3 times a day. At night, under the influence of the drug, the formation of glucose in the liver decreases.

Thus, it is most advisable to start treatment with taking the drug once a day in the evening in order to prevent the development of hyperglycemia in the morning.

The drug can be used as monotherapy with a diet or in combination with insulin or sulfonylurea drugs.

Combined treatment is prescribed if monotherapy does not bring the desired effect. The most dangerous complication of the use of biguanides is lactic acidosis.

An increase in the level of lactates in the blood is associated with an increase in its formation in the muscles, and also with the fact that lactate is the main substrate of gluconeogenesis, which is suppressed during therapy with drugs of this group.

In the case of an x-ray examination using iodine-containing substances, before general anesthesia, as well as in the perioperative period, it is necessary to temporarily cancel metformin.

In some cases, a number of side effects are noted, such as flatulence, nausea, diarrhea, epigastric discomfort, decreased appetite, and a metallic taste in the mouth.

Dyspeptic disorders occur as a result of a slowdown in the absorption of glucose in the intestine, which leads to an increase in fermentation processes.

Sometimes allergic reactions develop. The state of hypoglycemia develops in extremely rare cases, which is associated with the absence of an increase in insulin secretion under the influence of metformin.

There are a number of contraindications to the use of metformin. These include the state of hypoxia, acidosis, dysfunction of the liver, kidneys, lungs, heart failure, old age.

Treatment with metformin requires monitoring of hemoglobin levels once every 1 months, serum creatinine and transaminase levels once a year. If possible, the level of lactate in the blood is monitored once every 6 months.

An emergency blood test for lactate is performed when muscle pain occurs. The normal level of lactate is 1,3-3 mmol/L.

Thiazolidinediones, or sensitizers. This is a new group of tableted sugar-lowering drugs. These drugs eliminate tissue resistance to insulin, which is the main cause of type II diabetes.

In addition, sensitizers have a hypolipidemic effect.

They reduce the amount of triglycerides and at the same time increase the content of HDL, which have anti-atherogenic properties.

Thus, along with the treatment of diabetes, prevention of the cardiovascular system is carried out. The two most widely used drugs in this group are rosiglitazone and pioglitazone.

The use of these drugs does not cause the development of a state of hypoglycemia, since they do not cause an increase in insulin secretion by the pancreas.

Treatment with glitazones requires monitoring of serum transaminases once a year.

The following side effects may develop: liver dysfunction, edema, weight gain.

There are a number of indications for prescribing drugs in this group: newly diagnosed type II diabetes mellitus with signs of tissue resistance to insulin, if diet therapy is ineffective; lack of effect from taking sulfonylureas and biguanides; intolerance to other tableted sugar-lowering drugs.

Contraindications: an increase in the number of transaminases in the blood serum by more than 2 times, heart failure III, IV degrees. Perhaps the combined use of drugs in this group with sulfonylurea drugs, metformin or insulin.

a-glucosidase inhibitors. The drug glucobay (acarbose) is mainly used. Absorption of di- and oligosaccharides does not occur in the intestine. Initially, they are broken down into monosaccharides that can be absorbed in the intestines.

Cleavage occurs under the influence of α-glycosides. Glucobay blocks α-glucosidases, which leads to a decrease in the absorption of carbohydrates in the intestine.

The blockage of digestive enzymes is reversible. Under the influence of glucobay, postprandial (after eating) hyperglycemia decreases. The decrease occurs on average by 2,2 mmol / l.

Glucobay has a positive therapeutic effect only if the patient's diet contains only complex carbohydrates. If simple sugars are taken in food, then treatment with glucobay is ineffective.

Treatment with the drug begins with a small dose, which is 50 mg 3 times a day before meals. Gradually, the dose is increased to 100 mg 3 times a day.

The effect is achieved if the tablets are not chewed and taken immediately before meals or during meals. The state of hypoglycemia is not characteristic of glucobay monotherapy.

The following side effects may develop: flatulence, diarrhea, allergic reactions. Dyspeptic disorders occur as a result of the fact that undigested carbohydrates enter the large intestine, where they are processed by the bacterial flora, which is accompanied by significant gas formation.

Contraindications: intestinal diseases with malabsorption, acute and chronic hepatitis, diverticula, ulcers, stenosis and fissures of the gastrointestinal tract, acarbose intolerance.

It is not recommended to use the drug during pregnancy, lactation, as well as for persons under 18 years of age.

Lecture No. 7. Complications of diabetes. Ketoacidosis

Acute complications of diabetes mellitus pose a serious threat to the life of patients. Acute complications include hyperglycemic and hypoglycemic coma.

The most common state of hypoglycemia develops, which occurs with a rapid decrease in blood glucose. Hyperglycemic coma is divided into ketoacidotic, hyperosmolar and hyperlactacidemic (lactic acid).

Diabetic ketoacidosis is an acute decompensation of metabolic processes as a result of progressive insulin deficiency, manifested by a sharp increase in the content of glucose and ketone bodies in the blood, as well as the development of metabolic acidosis.

Metabolic disorders in the development of ketoacidosis proceed in several stages.

The first stage - decompensation of metabolic processes - is manifested by the presence of clinical symptoms of hyperglycemia and glucosuria. There is an increase in blood glucose and its appearance in the urine.

The second stage is ketoacidosis. There is a progression of metabolic disorders, symptoms of intoxication are observed, which is manifested by depression of consciousness in the form of stupor or confusion, as well as other characteristic clinical manifestations. Laboratory examination revealed hyperglycemia, a sharply positive reaction to acetone in the urine.

The third stage is precoma. There is a more pronounced oppression of consciousness up to stupor.

The fourth stage is coma. There is a profound violation of all types of metabolism, consciousness is completely absent. This condition poses a threat to the life of the patient.

Quite often, acute metabolic disorders in diabetes mellitus, which are accompanied by a high level of glycemia, ketonuria, acidosis, and impairment of consciousness of any degree, are combined by the term "diabetic ketosis". This pathological condition is most characteristic of type I diabetes mellitus.

In most cases, the state of ketoacidosis develops as a result of a change in the treatment regimen in the form of a long skip or complete unauthorized withdrawal of drugs.

For the most part, patients do this if they have no appetite, fever, nausea, vomiting.

Quite often it turns out that the break in taking sugar-lowering tablets was several months or even years. The second place among the causes of ketoacidosis is occupied by acute inflammatory diseases, exacerbation of chronic and infectious diseases. There may be a combination of both causes.

Errors in insulin therapy, such as insufficient dosage or administration of an unsuitable drug, also cause the development of ketoacidosis. Myocardial infarction and stroke can be both a cause and a consequence of ketoacidosis.

The development of ketoacidosis is possible during pregnancy, when there is an increase in the need for insulin and the appearance of relative tissue resistance to it. Ketoacidosis occurs during stressful conditions such as shock, sepsis, trauma, and surgery.

The main role in the pathogenesis of ketoacidosis belongs to a sharp deficiency of insulin. As a result, there is a decrease in the supply of glucose to the cells, and, as a result, a state of hyperglycemia develops. In violation of the utilization of glucose by cells in tissues, energy hunger develops.

This causes an increase in the release of hormones such as glucagon, cortisol, adrenaline, ACTH and growth hormone into the bloodstream. These hormones have an action opposite to insulin, i.e. they cause an increase in the processes of gluconeogenesis, glycogenolysis, proteolysis and lipolysis. As a result of stimulation of gluconeogenesis, the synthesis of glucose in the liver increases, which enters the bloodstream, increasing the existing hyperglycemia. Hyperglycemia leads to an increase in plasma osmolarity, as a result of which fluid from the cells passes into the vascular bed. As a result, cellular dehydration develops, the amount of electrolytes in the cell decreases sharply, first of all, the amount of potassium decreases.

When the renal permeability threshold for glucose is exceeded, it enters the urine, i.e., glucosuria develops. Since glucose is an osmotically active substance, water and electrolytes enter the urine with it.

As a result, dehydration of the body develops, severe electrolyte disorders, blood clotting is noted, leading to thrombosis.

As a result of severe dehydration and hypovolemia, the intensity of renal and cerebral blood flow decreases, which leads to tissue hypoxia.

The decrease in renal blood flow causes the appearance of oligonuria or anuria, which leads to a rapid increase in blood glucose. Tissue hypoxia causes activation of anaerobic glycolysis and an increase in the content of lactate, which cannot be utilized as a result of lactate dehydrogenase deficiency against the background of insulin deficiency. This leads to lactic acidosis.

An increased content of contra-insular hormones leads to the activation of lipolysis in adipose tissue. As a result, the content of free fatty acids in the blood increases, which in excess enter the liver.

Free fatty acids in this case are the main source of energy, which causes the appearance of a large number of ketone bodies in the blood as a result of their oxidation.

The number of ketone bodies in the blood increases rapidly, which is associated not only with an increase in their production, but also with the fact that their excretion in the urine decreases. Ketone bodies dissociate with the formation of hydrogen ions in large quantities, which leads to the development of metabolic acidosis.

Clinically, it will be manifested by Kussmaul breathing, as well as the development of abdominal syndrome. Also, with diabetic ketoacidosis, hypokalemia develops, which leads to dysfunction of the heart, disorders of the gastrointestinal tract, as well as other disorders leading to cerebral edema. First of all, with metabolic disorders, the central nervous system suffers, which is manifested by a progressive impairment of consciousness.

The development of ketoacidotic coma is the last stage of the ketoacidotic cycle. It is preceded by three stages: ketosis, ketoacidosis, precoma. Each stage, as it approaches a coma, is characterized by an aggravation of metabolic disorders, which enhances clinical manifestations and leads to greater depression of consciousness.

Ketoacidotic coma in most cases develops over several days. The stages of ketosis are characterized by the following clinical symptoms: dryness of the mucous membranes and skin of a progressive nature, the appearance of thirst, polyuria, an increase in weakness, a decrease in appetite and body weight. Patients complain of headache and increased drowsiness.

In the exhaled air, there is a slight smell of acetone. The criterion for the diagnosis of ketosis is the detection of ketonuria. With the progression of metabolic disorders, the stage of ketoacidosis develops.

Clinically, it is manifested by the appearance of symptoms of general dehydration in the form of dry mucous membranes, tongue, skin, muscle tone and skin turgor are reduced, there is a tendency to arterial hypotension, tachycardia, oliguria and signs of blood clotting are observed, such as an increase in hematocrit, leukocytosis and erythremia.

In most cases, as a result of intoxication of the body, nausea and vomiting appear. With the progression of ketoacidosis, vomiting becomes more frequent, aggravating dehydration of the body. The vomit is usually blood-brown in color. The rhythm of breathing is disturbed, Kussmaul breathing appears.

The smell of acetone from the patient is more clearly defined. There is a paretic expansion of capillaries, which causes the appearance of a diabetic blush.

Quite often, patients are concerned about pain in the abdomen without a clear localization, there is tension in the muscles of the anterior abdominal wall. These symptoms appear as a result of irritation of the peritoneum and solar plexus with ketone bodies, small hemorrhages in the peritoneum, and intestinal paresis.

The precoma stage is distinguished by the progression of impaired consciousness, symptoms of dehydration and intoxication. In the absence of treatment, the progression of damage to the central nervous system occurs, which ends with the development of coma.

Coma is characterized by a complete lack of consciousness. There is a sharp smell of acetone, Kussmaul's breath, the face is pale, there is a blush on the cheeks.

Signs of dehydration are characteristic: dryness of mucous membranes, tongue, skin. Tissue turgor is reduced, as well as muscle tone and eyeballs. Arterial pressure is reduced, the pulse is frequent, weak filling. Reflexes and all kinds of sensitivity are reduced or absent, depending on the depth of the coma. There is an enlargement of the liver. There are 4 forms of ketoacidotic coma.

1. Cardiovascular form. Leading in the clinical picture is a severe collapse in combination with a pronounced decrease in pressure, both arterial and venous. Often this form of coma is complicated by thrombosis of the coronary vessels, vessels of the lungs, lower extremities and other organs.

2. Gastrointestinal form. Characterized by repeated vomiting, abdominal pain of uncertain localization, muscle tension of the anterior abdominal wall. During the examination, there are signs of peritoneal irritation, in the blood - neutrophilic leukocytosis.

3. Renal form. There are symptoms of acute renal failure (proteinuria, cylindruria, hyperazotemia).

4. Encephalopathic form. It is typical for the elderly, especially in the presence of atherosclerosis of the cerebral vessels. It is manifested by cerebral symptoms, as well as focal symptoms, such as hemiparesis, asymmetry of reflexes and the appearance of pyramidal symptoms.

Diagnosis is based on a blood test to determine the level of glycemia and gas composition. Ketoacidosis is characterized by metabolic acidosis. In this case, the pH can be reduced to 6,8.

On palpation, there is a reduced turgor of tissues and eyeballs, the skin and mucous membranes are dry. During the examination, there is a decrease in blood pressure, a drop in body temperature, as well as reduced muscle tone and tendon reflexes.

In case of depression of the respiratory center and the development of pulmonary edema, intubation is necessary. It is necessary to carry out rehydration therapy. During the first hour, 1 liter of isotonic saline is injected. During the second and third hours, 500 ml of the solution is injected. In the future, the rate of fluid administration is 300 ml/h. When the glucose content in the blood decreases and is less than 14 mmol / l, they begin to pour in a 10% glucose solution.

The total volume of fluid administered should be 15% of body weight or more. At the same time, electrolyte disturbances are corrected. This is achieved by infusion of solutions containing potassium. If the potassium content in the blood serum is less than 3 mmol / l, an infusion of a 4% potassium chloride solution at a dose of 3 g / h is necessary.

If the potassium content is 3-4 mmol / l, then potassium chloride is also introduced, but its dose is 2 g / h, and with potassiumemia 4-5 mmol / l - 1,5 g / h. It is necessary to carry out insulin therapy, while adhering to the following rules: insulin is administered intravenously or deeply intramuscularly, short-acting drugs are used.

In the first hour, with intravenous jet administration, the dose is 10 units, with intramuscular injection - 16 units. Thereafter, 6 units of insulin are administered every hour.

When the blood glucose level is 12-14 mmol / l, the amount of insulin decreases to 3 units per hour. If the potassium content in the blood is less than 4 mmol / l, then it is administered additionally, and insulin administration is suspended.

In the absence of a decrease in the amount of glucose one hour after the start of therapy, even by 10%, 10-20 IU of short-acting insulin are reintroduced. If the blood pH is less than 7,1, resort to intravenous sodium bicarbonate.

To obtain information about the quality and quantity of urine excreted, bladder catheterization is performed. Since coma is accompanied by paresis of the stomach, there is a possibility of developing aspiration. In order to prevent it, a gastric tube is inserted. To achieve a positive therapeutic effect, it is necessary to find out the immediate cause of ketoacidotic coma and take measures to eliminate it.

The most dangerous complication is cerebral edema. In 90% of cases, this complication leads to death. With cerebral edema, swelling of neurons and neuroglia occurs with a simultaneous decrease in the amount of extracellular fluid.

This is the so-called cellular or cytotoxic variant of cerebral edema. It is believed that the pathogenesis of this complication is due to the fact that the formation of sorbitol and fructose increases in brain neurons. This occurs as a result of activation of the sorbitol pathway of glucose metabolism.

In addition, cerebral edema is associated with the occurrence of cerebral hypoxia. Under its influence, the activity of sodium-potassium ATP-ase in neurons decreases. This leads to the accumulation of sodium and water ions in these cells.

Yet a more common cause of cerebral edema in the treatment of ketoacidosis is considered to be an excessively rapid decrease in plasma osmolarity with the introduction of large amounts of fluid and insulin. To correct the acid-base state in ketoacidosis, intravenous sodium bicarbonate is used, which leads to an imbalance between the pH of the cerebrospinal fluid and peripheral blood. This imbalance leads to facilitating the flow of water into the neurons of the brain from the intercellular space.

In most cases, the complication develops 6 hours after the start of treatment for ketoacidotic coma. If the patient's consciousness remains preserved, then the development of cerebral edema is manifested by a deterioration in well-being, dizziness, headache, nausea, vomiting, visual impairment, fever, eyeball tension and instability of hemodynamic parameters.

If the patient is unconscious, then the basis for suspecting the development of cerebral edema will be the absence of positive dynamics while improving blood glycemia. If during the examination there is no reaction of the pupils to light, edema of the optic nerve and ophthalmoplegia are determined, then the diagnosis of cerebral edema is considered confirmed. In some cases, it may be necessary to perform computed tomography and ultrasound encephalography. Complications are treated with osmotic diuretics. For this purpose, intravenous drip administration of mannitol is carried out. The dose of the drug is administered at the rate of 1-2 g / kg. In addition, lasix is ​​injected intravenously in a dose of 80-120 mg and hypertonic sodium chloride solution in a volume of 10 ml.

The use of glucocorticoid preparations in each case is decided individually. To reduce intracranial pressure, it is necessary to take measures to achieve hypothermia of the brain, as well as active ventilation of the lungs.

Other complications of the treatment of ketoacidotic coma, which occur in more rare cases, are pulmonary edema, acute cardiovascular failure, DIC, metabolic alkalosis, and asphyxia. To prevent the development of all these complications, it is necessary to constantly monitor hemostasis, hemodynamics, control the acid-base state of the blood, its osmolarity, as well as the appearance of neurological symptoms.

Lecture number 8. Hyperosmolar coma

A condition in which there is an increased content of highly osmotic compounds in the blood, such as sodium and glucose, is called hyperosmolarity. As a result of weak diffusion of these substances into cells, a rather pronounced difference in oncotic pressure appears between the extra- and intracellular fluid.

As a result, intracellular dehydration first develops, which subsequently leads to general dehydration of the body. Intracellular dehydration is primarily subject to brain cells. The greatest risk of developing a state of hyperosmolarity occurs in type II diabetes mellitus, more often in the elderly. In type 50 diabetes, hyperosmolar coma develops extremely rarely. Hyperosmolar coma is accompanied by a high level of glycemia, which can be XNUMX mmol / l or more. With hyperosmolar coma, the phenomenon of ketoacidosis is absent. Hyperosmolar coma is a more severe complication of diabetes than ketoacidotic coma.

The development of hyperosmolar coma provokes dehydration and insulin deficiency. Dehydration, in turn, is provoked by such conditions as vomiting, diarrhea, acute pancreatitis or cholecystitis, blood loss, long-term use of diuretic drugs, impaired renal function of a concentration nature, etc. A variety of injuries, surgical interventions, and long-term use of steroid drugs.

Initially, there is an increase in the concentration of glucose in the blood. There are several causes of hyperglycemia: severe dehydration, increased production of glucose in the liver, as well as a large amount of glucose entering the blood exogenously. The concentration of glucose in the blood is constantly increasing.

This fact is due to two reasons. The first reason is a violation of kidney function, in which the amount of glucose excreted in the urine decreases.

The second reason is that excess glucose suppresses insulin secretion, as a result of which it is not utilized by cells. The progressive increase in glucose concentration is toxic to pancreatic β-cells. As a result, they completely stop producing insulin, exacerbating the existing hyperglycemia. The response to dehydration is a compensatory increase in aldosterone production. This leads to hypernatremia, which, like hyperglycemia, exacerbates the state of hyperosmolarity.

The initial stages of hyperosmolar coma are characterized by the appearance of osmotic diuresis. This, together with the hyperosmolarity of the blood plasma, causes the rapid development of hypovolemia, dehydration of the body, a decrease in the intensity of blood flow in the internal organs and an increase in vascular collapse.

General dehydration of the body is accompanied by dehydration of brain neurons, severe microcirculation disorders, which is the main cause of impaired consciousness and the appearance of other neurological symptoms. Dehydration leads to an increase in blood viscosity. This, in turn, causes an excess amount of tissue thromboplastin to enter the bloodstream, ultimately leading to the development of DIC.

The development of symptoms of hyperosmolar coma occurs slowly - a few days or weeks. Initially, there is an increase in signs of decompensation of diabetes mellitus, such as thirst, weight loss and polyuria. At the same time, muscle twitches appear, which constantly increase and turn into convulsions of a local or generalized nature. Impairment of consciousness can be observed already in the first days of the disease. First, these disorders are manifested by a decrease in orientation in the surrounding space. Constantly progressing, disturbances of consciousness can go into a state of coma, which is preceded by the appearance of hallucinations and delirium.

Hyperosmolar coma is characterized by the fact that its neurological symptoms are polymorphic and are manifested by convulsions, paresis and paralysis, speech disorders, the appearance of nystagmus, and pathological meningeal symptoms. Usually, the combination of these symptoms is considered as an acute violation of cerebral circulation.

On examination, symptoms of severe dehydration are revealed: dryness of the skin and visible mucous membranes, skin turgor, muscle tone and tone of the eyeballs are reduced, pointed facial features are noted. Breathing becomes shallow, frequent.

The smell of acetone in the exhaled air is absent. There is a decrease in blood pressure, frequent pulse. Quite often, body temperature rises to high numbers. Usually the final stage is the development of hypovolemic shock, which is caused by pronounced circulatory disorders.

When examining blood, there is an increase in the amount of glucose up to 50 mmol / l and above, hypernatremia, hyperchloremia, hyperazotemia, polyglobulia, erythrocytosis, leukocytosis and an increase in hematocrit. A characteristic distinguishing feature is an increase in plasma osmolarity, which is normally 285-295 mosmol / l.

Compared with ketoacidotic coma, hyperosmolar therapy has its own characteristics. In this case, therapy is aimed at eliminating dehydration in the body, combating hypovolemic shock, as well as normalizing indicators of the acid-base state. In the case of the development of hyperosmolar coma, patients are hospitalized in the intensive care unit. At the prehospital stage of treatment, gastric lavage and the introduction of a urinary catheter are performed. A necessary measure is the establishment of oxygen therapy. In the intensive care unit, the following laboratory tests are carried out: determination of the level of glycemia, the level of potassium, sodium, urea, lactate, ketone bodies, serum creatinine, indicators of the acid-base state and effective plasma osmolarity.

Rehydration therapy for hyperosmolar coma is carried out in a larger volume than for ketoacidotic coma. The amount of intravenously administered fluid reaches 6-10 liters per day. In the first hour of this type of therapy, intravenous administration of 1-1,5 liters of liquid is carried out, in the second and third hours 0,5-1 liters are injected, in the next hours - 300-500 ml.

The choice of solution for intravenous administration depends on the sodium content in the blood. If the level of sodium in the blood serum is more than 165 mEq / l, then the introduction of saline solutions is contraindicated. In this case, rehydration therapy begins with the introduction of a 2% glucose solution.

If the sodium level is 145-165 meq / l, then rehydration therapy is carried out with a 0,45% (hypotonic) sodium chloride solution. Already during rehydration, there is a pronounced decrease in the level of glycemia due to a decrease in its concentration in the blood.

With this type of coma, there is a high sensitivity to insulin, so its intravenous administration is carried out in minimal doses, which are about 2 IU of short-acting insulin per hour.

In the case of a decrease in the level of glycemia by more than 5,5 mmol / l, and plasma osmolarity by more than 10 mosmol / l per hour, pulmonary and cerebral edema may develop. In the case of a decrease in the level of sodium after 4-5 hours from the start of rehydration therapy, while maintaining a pronounced level of hyperglycemia, it is necessary to conduct hourly intravenous insulin at a dose of 6-8 IU. Upon reaching the level of glycemia below 13,5 mmol / l, the dose of insulin is halved and averages 3-5 U / h.

Indications for switching to subcutaneous insulin administration are maintaining glycemia at a level of 11-13 mmol / l, the absence of acidosis of any etiology, and the elimination of body dehydration. The dose of insulin in this case is the same and is administered at intervals of 2-3 hours, depending on the level of glycemia. Recovery of potassium deficiency in the blood can begin immediately after its detection or after 2 hours from the start of infusion therapy.

Potassium deficiency begins to be restored immediately after its detection in the event that kidney function is preserved. The amount of intravenously administered potassium depends on its level in the blood. If the amount of potassium is less than 3 mmol / l, then every hour 3 g of potassium chloride is injected intravenously, with a potassium content of 3-4 mmol / l - 2 g of potassium chloride, 4-5 mmol / l - 1 g of potassium chloride. Upon reaching the level of potassium 5 mmol / l or more, the introduction of a solution of potassium chloride is stopped.

In addition to these measures, it is necessary to fight the collapse, to carry out antibiotic therapy. In order to prevent thrombosis, heparin is administered intravenously at a dose of 5000 IU 2 times a day under the obligatory control of the hemostasis system.

Lecture No. 9. Lactic acidosis and hyperlactacidemic coma

Lactic acidosis is a condition of metabolic acidosis that results from elevated levels of lactic acid in the blood. Lactic acidosis is not a specific complication of diabetes mellitus. This condition has a polyetiological nature. The development of lactic acidosis can be triggered by various diseases and conditions that are accompanied by tissue hypoxia, as well as an increase in the intensity of formation and a decrease in lactate utilization. In cases accompanied by tissue hypoxia, type A lactic acidosis develops. This can be with cardiogenic, endotoxic, hypovolemic shock, anemia, carbon monoxide poisoning, epilepsy or pheochromocytoma. In pathological conditions characterized by an increase in the formation and a decrease in the utilization of lactate, type B lactic acidosis develops.₁. This is typical for renal or hepatic insufficiency, oncological diseases and hemoblastoses, severe infections, decompensated diabetes mellitus. Lactic acidosis type B₂ develops with the use of biguanides, poisoning with methanol or ethylene glycol, cyanides, with excessive parenteral administration of fructose. It is also possible to develop lactic acidosis type B.₃, which occurs with hereditary metabolic disorders, for example, with a deficiency of glucose-6-phosphate dehydrogenase or methylmalonic acidemia.

Lactate is a metabolic product that is directly involved in carbohydrate metabolism. Lactate, together with pyruvate, is a substrate for glucose synthesis during neoglucogenesis. The formation of lactate increases with the development of hypoxia, when aerobic glycolysis is inhibited and anaerobic glycolysis is activated. The end product of anaerobic glycolysis is lactic acid. In this case, lactate is synthesized in the body faster than it turns into pyruvate, and is utilized in the process of neoglucogenesis. Normally, the ratio of lactate to pyruvate is expressed as 10:1.

The more frequent development of lactic acidosis in diabetes mellitus is explained by the fact that its often occurring decompensation contributes to a state of chronic hypoxia as a result of an increase in the level of glycated hemoglobin, which has an increased affinity for oxygen.

In addition, quite often patients with type II diabetes mellitus, especially the elderly, have several concomitant diseases. The most common such diseases are pathologies of the cardiovascular system, which are characterized by a state of chronic hypoxia. The state of severe hypoxia usually accompanies such acute complications of diabetes mellitus as ketoacidotic and hyperosmolar coma. In these cases, the resulting lactic acidosis exacerbates the already serious condition of patients. In addition, their life prognosis becomes more unfavorable. As a result of insulin deficiency in diabetes mellitus, the level of muscle pyruvate dehydrogenase decreases, which leads to an increase in lactate synthesis and the creation of prerequisites for the development of type B lactic acidosis.

The most common cause of lactic acidosis in diabetes mellitus is the intake of hypoglycemic drugs from the biguanide group, such as phenformin and buformin. These drugs have the ability to activate anaerobic glycolysis in the small intestine and muscles, which, in turn, leads to an increase in lactate production and inhibition of gluconeogenesis in the liver. Currently, these drugs are not available. Metformin is a modern drug of the biguanide group. This drug does not cause such a pronounced accumulation of lactate due to other structural and pharmacokinetic features. By its nature, lactic acidosis in most cases has a mixed origin, that is, it is type A + type B. Several factors are simultaneously involved in the pathogenesis of mixed lactic acidosis. At the same time, comorbidity, which is accompanied by hypoxia, as well as decompensation of diabetes mellitus, plays a more significant role. Against the background of these changes, anaerobic glycolysis is activated in the body, which is accompanied by the formation of excess lactate. An important additional factor in the pathogenesis of lactic acidosis is the addition of pathology from the kidneys, which leads to a deterioration in the excretion of lactate from the body.

Lactic acidosis is initially manifested by increased fatigue, increasing weakness, drowsiness, nausea, and vomiting. These symptoms resemble decompensated diabetes mellitus. The main symptom that can cause suspicion of lactic acidosis is the appearance of muscle pain, which is caused by the accumulation of lactic acid in them. Severe metabolic acidosis in diabetic patients can develop in just a few hours. Usually, its signs are Kussmaul breathing, peripheral vasodilation, a sharp decrease in blood pressure, heart rhythm disturbances, confusion, stupor or coma. The cause of death in lactic acidosis is, as a rule, acute cardiovascular failure or paralysis of the respiratory center.

A biochemical blood test shows a high content of lactic acid, the presence of signs of decompensated metabolic acidosis. In the study of indicators of the acid-base state, an increase in the anion gap is noted.

Normally, the level of lactate in the venous blood is 0,5-2,2 mmol / l, in the arterial - 0,5-1,6 mmol / l. If the level of lactate in the blood serum is above 5,0 mmol / l, then this indicates lactic acidosis. If the lactate level is 2,2-5,0 mmol / l, and the pH of the arterial blood is less than 7,25, then this also speaks in favor of lactic acidosis. The differential diagnosis is primarily with diabetic ketoacidosis.

Treatment should primarily be aimed at combating shock, hypoxia, acidosis, and electrolyte disturbances. It is necessary to correct carbohydrate disorders, as well as treat concomitant diseases that could cause the development of lactic acidosis. The most effective method for removing excess lactic acid from the body is hemodialysis. It uses a lactate-free buffer. To eliminate excess CO₂, which is formed in the body as a result of acidosis, artificial hyperventilation of the lungs is carried out. For this purpose, the patient must be intubated.

With a decrease in pCO₂ up to 25-30 mm Hg. Art. there is a restoration of intracellular pH in hepatocytes and cardiomyocytes, which improves metabolism and helps to reduce the level of lactate in the blood. To reduce the formation of lactate, it is necessary to increase the activity of enzymes such as pyruvate dehydrogenase and glycogen synthetase. This is achieved by intravenous infusion of glucose in the amount of 5 - 12,5 g / h in combination with short-acting insulin, the dose of which is 2-4 - 6 units hourly. In addition to these measures, it is necessary to prescribe vaso- and cardiotonic drugs, taking into account hemodynamic parameters. 7,0% sodium bicarbonate is used at pH ‹ 100. This drug is administered once very slowly intravenously in a volume of XNUMX ml.

Lecture No. 10. Hypoglycemia and hypoglycemic coma

Hypoglycemia most often complicates the course of diabetes mellitus in patients receiving treatment with insulin or oral hypoglycemic agents. Hypoglycemia is a clinical syndrome caused by an abnormally low level of glucose in the blood plasma. Hypoglycemia can be mild when the patient manages it on their own with a sufficient amount of carbohydrates. In the case of severe hypoglycemia, loss of consciousness is noted, which requires intravenous administration of glucose or glucagon. In most cases, the state of hypoglycemia is observed in patients who undergo intensive insulin therapy. Especially often, the state of hypoglycemia develops in elderly patients suffering from type II diabetes mellitus and receiving antidiabetic drugs of the glibenclamide group, which have a long half-life and a cumulative effect. Quite often, hypoglycemia in such patients is recurrent. An extreme manifestation of a hypoglycemic state is a hypoglycemic coma. It is defined as an acute, life-threatening condition caused by a rapid and pronounced decrease in blood glucose levels, which, in turn, causes the development of energy starvation of body cells, edema of the brain substance, and in advanced cases, decortication and even decerebration. Typically, hypoglycemia in diabetes mellitus occurs with a rapid decrease in glucose levels to the lower limit of normal - 3,3 mmol / l. Symptoms of hypoglycemia can develop already at a glycemia of 4-6 mmol / l.

In such cases, there is a pronounced drop in the level of glycemia in the blood for a short period of time. In addition, in the case of constant and prolonged hyperglycemia in diabetes mellitus, passive diffusion of glucose into tissues is simulated. Since cell membranes are adapted to hyperglycemia in diabetes mellitus, when the level of glycemia in the blood decreases, passive diffusion of glucose in the tissue stops, which leads to energy starvation of brain cells.

The main reason for the development of hypoglycemia is an excess of insulin in the body in relation to the amount of carbohydrates supplied with food or from endogenous sources (glucose production by the liver), as well as accelerated utilization of carbohydrates during intensive muscular work. The development of hypoglycemia is provoked by the following factors: excessive physical activity, alcohol consumption, dietary disturbance in the form of an incorrect diet or insufficient carbohydrate content in it, as well as an overdose of insulin or hypoglycemic tablets. The development of hypoglycemia contributes to the first trimester of pregnancy, childbirth, chronic hepatitis and hepatosis in diabetes mellitus, nephropathy with renal failure, insufficiency of the adrenal cortex and thyroid gland, as well as taking certain medications, such as salicylates.

A decrease in blood glucose levels primarily affects the state of the central nervous system, since it is the only substrate for brain metabolism. When the level of glucose in the blood drops below the physiological level, its entry into the brain cells decreases, which leads to their energy starvation. This condition is called neuroglycopenia. It manifests itself at different stages with various neurological disorders, which ultimately lead to loss of consciousness and the development of hypoglycemic coma. Separate structures of the central nervous system have different sensitivity to energy hunger. Initially, during hypoglycemia, gray matter cells located in the cerebral cortex are affected, since they have the greatest intensity of metabolic processes. This fact explains the appearance of symptoms of neuroglycopenia in all more or less pronounced hypoglycemic conditions. The centers of the medulla oblongata, such as: respiratory and vasomotor, have the least sensitivity to hypoglycemia. This explains the fact that respiration, vascular tone and cardiac activity persist for a long time even in cases where prolonged hypoglycemia leads to irreversible decortication. To maintain the level of glucose in the blood while reducing its entry into the brain cells, the processes of glycogenolysis, gluconeogenesis, proteolysis, lipolysis are activated in the body, and the process of glucose utilization by peripheral tissues is also inhibited. These mechanisms are carried out under the control of counter-insulin hormones, which include glucagon, catecholamines, glucocorticoids, growth hormone, adrenocorticotropic hormone. The concentration of these hormones increases sharply against the background of hypoglycemia, which leads to stimulation of the autonomic nervous system and the appearance of a set of autonomic symptoms. In addition, the development of hypoglycemia is accompanied by a compensatory increase in cerebral blood flow by 2-3 times, which ensures a higher level of oxygen supply. All compensatory mechanisms that are activated during the development of a state of hypoglycemia can maintain the viability of the brain for a relatively short period of time. If the duration of hypoglycemic coma is less than 30 minutes, then with adequate treatment and a rapid return of consciousness, complications and consequences, as a rule, are not observed. Prolonged hypoglycemia poses a danger to the life of the patient. As a result of prolonged energy starvation, edema of the substance of the brain develops, small-point hemorrhages appear in the brain tissues. Ultimately, these pathological changes are the cause of violations in the cells of the cerebral cortex of a structural nature, and subsequently - to their death.

Hypoglycemic coma is characterized by a sudden development against the background of a satisfactory condition. The development of coma is preceded by a state of mild hypoglycemia, which is stopped by taking a sufficient amount of carbohydrates. The period of hypoglycemia is accompanied by the appearance of precursors of hypoglycemic coma. They are manifested by a number of autonomic symptoms, such as excessive sweating, hunger, restlessness, anxiety, palpitations, mydriasis, and increased blood pressure. In the case of the development of a state of hypoglycemia during sleep, patients are disturbed by nightmares. Quite often, the appearance of autonomic symptoms is preceded by symptoms of neuroglycopenia. Such symptoms can be inappropriate behavior, disorientation in space, aggressiveness, mood changes, amnesia, dizziness and headache, as well as visual disturbances in the form of diplopia, the appearance of "fog" and flickering "flies".

If untreated, neuroglycopenia worsens, which is clinically manifested by the development of psychomotor agitation, muscle hypertonicity, tonic or clonic convulsions. This state lasts a short period of time and is replaced by a coma. Hypoglycemic coma is characterized by the following clinical signs: profuse sweating, increased muscle tone, the appearance of convulsive syndrome.

The brightness of the clinical picture depends on the speed of the decrease in blood glucose levels: the faster this happens, the brighter the clinical manifestations. Harbingers of hypoglycemic coma do not appear in all cases. If diabetes mellitus proceeds for a sufficiently long time and is accompanied by the development of autonomic neuropathy, as well as frequent hypoglycemic coma, then patients do not feel the precursors of the onset of this pathological condition. If the hypoglycemic coma proceeds for a long time, then there are signs of cerebral edema.

Such signs are usually hemiplegia, stiff neck and other pathological symptoms of a neurological nature. Also, the appearance of shallow breathing, a decrease in blood pressure, reflexes are reduced or completely drop out, bradycardia is detected. Death occurs as a result of decortication and decerebration. A sign of the onset of these conditions is the lack of pupillary reaction to light.

When examining blood, there is a decrease in glucose levels to 3 mmol / l and below. The reaction to acetone in the urine may be positive, which is associated with previous decompensation of diabetes mellitus. For differential diagnosis with acute cerebrovascular accident, inflammatory diseases of the brain, traumatic brain injury and other pathological conditions, echoencephaloscopy, computed tomography and spinal puncture are necessary.

Treatment must be immediate. Lack of treatment within 2 hours from the onset of the development of hypoglycemic coma significantly worsens the prognosis. Initially, it is necessary to carry out an intravenous jet injection of a 40% glucose solution in a volume of 20-60 ml. Usually the amount of glucose administered is determined by the recovery of the patient's consciousness. If consciousness is not restored, then the volume of injected glucose can be increased to 100 ml, before the arrival of the ambulance medical team, it is necessary to inject 1 ml of glucagon intramuscularly. This measure is ineffective in the case of alcoholic hypoglycemia, as well as in the case of hypoglycemia as a result of an overdose of insulin. The lack of effect from the introduction of glucagon in the first case is explained by the fact that the production of glucose in the liver is blocked by ethanol. In the second case, glycogen stores in the liver are depleted due to an overdose of insulin. If, after the introduction of a glucose solution, the patient's consciousness quickly returned to normal, then hospitalization can not be carried out. In other cases, it is necessary to urgently hospitalize the patient in the endocrinological or therapeutic department. Therapeutic measures begin at the prehospital stage and consist of intravenous drip infusion of a 10% glucose solution. In a hospital, a 40% solution is administered intravenously in a volume of 150-200 ml. If this event does not bring effect, then there is a possibility of developing cerebral edema. If this condition is confirmed, anti-edematous therapy is necessary. At the same time, with the help of slow intravenous administration of a 10% glucose solution, it is necessary to maintain its level in the blood within 11-13 mmol / l. At the same time, other causes that could lead to loss of consciousness are excluded. Anti-edematous therapy consists in the introduction of a 15% solution of mannitol, the dose of which is based on 1-2 g/kg of body weight. After the introduction of mannitol, lasix is ​​injected in an amount of 80–120 mg and an isotonic solution of sodium chloride in a volume of 10 ml, in addition to these drugs, intravenous administration of 10 ml of a 25% solution of magnesium sulfate can be used. It is recommended to use a 20% solution of piracetam, which is administered intravenously in a volume of 10-20 ml. Normalization of the patient's consciousness can occur only after a few days. During this period, constant monitoring by a neuropathologist, intravenous drip of a 10% glucose solution and monitoring of its level in the blood are necessary. When the glucose content becomes stable and is 13-14 mmol / l, they switch to subcutaneous administration of short-acting insulin. The drug is administered at a dose of 2-6 IU every 4 hours.

It is necessary to organize diabetes schools, where the patient is told about the symptoms of hypoglycemia, its causes and methods of relief. In the case of upcoming physical exertion, the patient should increase the amount of carbohydrates by 1-2 bread units; the intake of such an amount of carbohydrate is made before and after physical exertion. If physical activity is planned for more than 2 hours, then the amount of insulin administered on this day should be reduced by 25-50%. The amount of strong alcoholic beverages should be limited to 50-75 g. Also, to prevent the development of hypoglycemia, it is important to follow a diet. In order to prevent hypoglycemia from developing at night, it is necessary to include foods containing protein in dinner. In order to stop mild hypoglycemia, the patient can eat sugar or drink a sweet carbonated drink.

Lecture No. 11. Late complications of diabetes

Late complications of diabetes include diabetic angiopathy. Diabetic angiopathy is a generalized vascular lesion that extends both to small vessels and to vessels of medium and large caliber.

With the defeat of small vessels, such as arterioles, venules and capillaries, microangiopathy develops. With the defeat of vessels of medium and large caliber, macroangiopathy develops. Microangiopathies lead to the development of diabetic nephropathy and retinopathy. When macroangiopathy affects the vessels of the heart, brain and main vessels of the lower extremities. The main role in the development of diabetic angiopathy belongs to hyperglycemia. Glycosylation products are dangerous. Their action is to change the structure and metabolism of body proteins, primarily cell membrane proteins. This leads to thickening and increased permeability of the latter. Also, glycosylation products increase the production of cytokines, which, in turn, activate cell proliferation and hyperplasia, increase thrombus formation due to increased platelet aggregation. In diabetic angiopathy, superoxidanion is formed. This substance inactivates nitric oxide, leading to dysfunction of the vascular endothelium. These changes cause a decrease in the ability of the endothelium to cause vasodilation, an increase in the permeability of the vascular wall and a violation of the rheological properties of the blood, which causes the development of hemostasis and thrombosis.

1. Diabetic nephropathy

Diabetic nephropathy is a specific lesion of the kidneys in diabetes mellitus, which is accompanied by morphological changes in the capillaries and arterioles of the renal glomeruli, leading to their occlusion, sclerotic changes, a progressive decrease in the filtration function of the kidneys and the development of chronic renal failure.

The initial signs of diabetic nephropathy are detected after 5 to 10 years from the onset of diabetes. This complication is the leading cause of death in type XNUMX diabetes.

There are a number of mechanisms in the development of diabetic nephropathy. Under the influence of constant hyperglycemia, the afferent arteriole of the glomerulus undergoes dilatation. Damage to the renal vessels causes a thickening of the basement membrane, impaired renal perfusion and, as a result, an increase in blood pressure. Since dilatation of the afferent arteriole occurs and the tone of the efferent arteriole increases, intraglomerular pressure increases, which progresses under the influence of an increase in the volume of primary urine. An increase in pressure inside the glomeruli leads to a change in the vessels and parenchyma of the kidney. The permeability of the renal filter is impaired, which is manifested by microalbuminuria, and then by proteinuria. The progression of the process leads to the development of glomerulosclerosis, which is manifested by chronic renal failure.

Diabetic nephropathy is characterized by several stages: microalbuminuria, proteinuria, chronic renal failure. The stage of microalbuminuria and proteinuria is not diagnosed during a routine examination.

The stage of microalbuminuria is characterized by an increase in the excretion of albumin in the urine from 30 to 300 mg per day. In the general analysis of urine, the protein is not detected. A characteristic clinical picture does not develop at this stage. In some cases, there may be a slight increase in blood pressure.

The stage of proteinuria is characterized by an increase in urinary protein excretion of more than 300 mg per day. At first, only albumins are found in the urine, i.e. proteinuria is selective. With the progression of the disease, the selectivity of proteinuria decreases, which is manifested by urinary excretion of coarse proteins - globulins. If proteinuria is more than 3,5 g per day, this indicates the development of nephrotic syndrome. Clinically, it is manifested by edema localized on the face. An increase in blood pressure develops in 65-80% of patients, with an increase in both systolic and diastolic pressure. Arterial hypertension in diabetic nephropathy is characterized by stability and lack of sensitivity to antihypertensive drugs. Nephrotic syndrome leads to the development of dysproteinemia, and with progression to hypoproteinemia.

From the time when persistent proteinuria is established, there is a decrease in the glomerular filtration rate of less than 80 ml / min, a decrease in the concentration ability of the kidneys, which leads to hypoisostenuria, and then to an increase in the level of creatinine and urea in the blood. This is the stage of chronic renal failure. At this stage, all the symptoms characteristic of chronic renal failure are added to proteinuria. This stage has a progressive course, the pace of which can be different.

The stage of chronic renal failure is characterized by a decrease in the body's need for exogenous insulin. This fact is explained by a decrease in the activity of insulinase, as well as a decrease in the binding of insulin to plasma proteins as a result of hypoproteinemia. Clinically, this stage is manifested by an increased tendency to hypoglycemic states. To prevent them, it is necessary to reduce the dose of insulin administered and at the same time increase the carbohydrate content in food. Arterial hypertension is the most powerful factor in the progression of chronic renal failure. In most cases, various inflammatory processes of the urinary system occur at this stage, such as ascending pyelonephritis, etc.

The first two stages of diabetic nephropathy are diagnosed in case of detection of microalbuminuria in two or more urine tests, while albuminuria is 30-300 mg / day. These figures characterize the stage of microalbuminuria. The stage of proteinuria is diagnosed if the amount of albumin is more than 300 mg per day. In diabetic nephropathy, there is an increase in the glomerular filtration rate, which is determined using the Rehberg test.

In this case, the glomerular filtration rate is more than 140 ml per minute. The stage of chronic renal failure is characterized by massive proteinuria of more than 3,5 g per day, hypoalbuminemia, hypercholesterolemia.

To achieve a positive effect, it is necessary to start treatment at the first stage of diabetic nephropathy. The goal of therapy at this stage is to normalize blood pressure levels. The drugs of choice are ACE inhibitors.

The drugs of this group normalize blood pressure indicators, as well as reduce intraglomerular pressure and permeability of the glomerular basement membranes. The drugs used are enalapril, perindopril, lisinopril, etc. Monotherapy is usually performed. In the case of a normal level of blood pressure, drugs of this group are also prescribed, but in a small dose. Also at the first stage, sulodexide, a drug from the group of glycosaminoglycans, is prescribed to restore damaged glomerular basement membranes.

Therapy at the stage of proteinuria should include the appointment of insulin in patients with type II diabetes mellitus, the appointment of a diet with a reduced amount of salt in case of arterial hypertension. Arterial hypertension is also treated with ACE inhibitors. Usually monotherapy with these drugs is carried out. The blood pressure level to be reached is 130/85 mm Hg. Art. If monotherapy with ACE inhibitors is ineffective, additional therapy with calcium antagonists, such as verapamil or diltiazem, is carried out.

In addition, α-blockers (atenolol), diuretics (furosemide), angiotensin receptor antagonists (losartan) can be prescribed.

Therapy for the development of chronic renal failure is determined by its stage. Distinguish conservative stage and terminal. The conservative stage is characterized by a glomerular filtration rate of 30-60 ml/min. The main thing in this stage is diet. In the case of arterial hypertension, the amount of table salt is limited to 3 g per day, the amount of carbohydrates must be increased in order to cover energy costs. Of the medications at this stage, insulin and ACE inhibitors are mandatory. To correct lipid metabolism disorders, simvastatin is used, calcium-phosphorus metabolism disorders - calcium carbonate or calcium acetate, acid-base state, namely acidosis - sodium bicarbonate. If necessary, drugs are used to treat anemia, as well as sorbents. In the case of the end stage of chronic renal failure, which is characterized by a decrease in the glomerular filtration rate of less than 15 ml / min, treatment is carried out in specialized nephrological hospitals. Treatment options include chronic hemodialysis or peritoneal dialysis. If there is a need and opportunity, a kidney transplant is performed.

2. Diabetic retinopathy

Diabetic retinopathy is a lesion of capillaries, arterioles and venules of the retina, which is manifested by the development of microaneurysms, hemorrhages, and the presence of exudative changes. As well as the proliferation of newly formed vessels. There are three stages of diabetic retinopathy: nonproliferative, preproliferative, proliferative.

In diabetes mellitus, vasoconstriction is noted, which is accompanied by the development of hypoperfusion. There are degenerative changes in blood vessels with the formation of microaneurysms. With the progression of hypoxia, vascular proliferation is noted, as a result of which fatty degeneration of the retina develops and deposits of calcium salts in it. Deposition of lipids in the retina leads to the formation of dense exudates. The appearance of proliferating vessels is accompanied by the formation of shunts, the functioning of which causes the expansion of retinal veins, which aggravates its hypoperfusion. The so-called stealing phenomenon develops. This leads to the progression of retinal ischemia, resulting in the formation of infiltrates and scars. With a far advanced process, retinal detachment may occur. Aneurysm ruptures, hemorrhagic infarctions, and massive vascular invasion lead to vitreous hemorrhages. If proliferation of the vessels of the iris develops, this leads to secondary glaucoma.

The clinical picture depends on the stage of diabetic retinopathy. The non-proliferative stage is characterized by the appearance of microaneurysms, punctate hemorrhages, and solid exudative foci in the retina. There is retinal edema. Retinal hemorrhages are located in the center of the fundus or along large veins and are represented by small dots, strokes or dark spots of a rounded shape. Exudates are usually localized in the central part of the fundus and have a yellow or white color.

The preproliferative stage is characterized by the appearance of pronounced fluctuations in the caliber of retinal vessels, their doubling, tortuosity and looping. The presence of a large number of exudates, both hard and soft, is noted. Characteristic is the appearance of a large number of hemorrhages in the retina, while some of its parts are deprived of blood supply due to thrombosis of small vessels. The proliferative stage is characterized by the formation of new retinal vessels that are thin and fragile. This leads to the frequent occurrence of repeated hemorrhages in the retina. With the progression of this stage, the germination of newly formed vessels into the vitreous body is noted.

These changes lead to hemophthalmos and the formation of vitreoretinal bands, which leads to retinal detachment and the development of blindness. New vessels that form in the iris are quite often the cause of secondary glaucoma.

To confirm the diagnosis of diabetic retinopathy, it is necessary to conduct a number of studies, both objective and instrumental. Research methods include external examination of the eyes, determination of visual acuity and visual fields, slit lamp studies of the cornea, iris and anterior chamber angle of the eye in order to determine the level of intraocular pressure. In case of clouding of the vitreous body and the lens, an ultrasound of the eye is performed. If necessary, fluorescein angiography and fundus photography are performed.

The main principle in the treatment of this complication is to achieve compensation of metabolic processes in diabetes mellitus. To prevent blindness, laser photocoagulation of the retina is performed. This technique can be used at any stage of diabetic retinopathy, but the greatest effect is achieved when used in the early stages. The purpose of this technique is to stop the functioning of newly formed retinal vessels. If diabetic retinopathy has already reached the proliferative stage, then the method of transconjunctival cryocoagulation can be used. If diabetic retinopathy is complicated by hemophthalmos, then at any stage it is possible to perform vitrectomy - removal of the vitreous body and vitreoretinal bands.

3. Diabetic neuropathy

Diabetic neuropathy implies damage to the central and peripheral nervous system in diabetes mellitus.

There is the following classification (PK Thomas, JDWard, DA Greene).

1. Sensorimotor neuropathy:

1) symmetrical;

2) focal (mononeuropathy) or polyfocal (cranial, proximal motor, limb and trunk mononeuropathy).

2. Autonomic (vegetative) neuropathy:

1) cardiovascular (orthostatic hypotension, cardiac denervation syndrome);

2) gastrointestinal (atony of the stomach), biliary dyskinesia, diabetic enteropathy);

3) urogenital (with dysfunction of the bladder, with impaired sexual function);

4) violation of the patient's ability to recognize hypoglycemia;

5) pupil dysfunction;

6) dysfunction of the sweat glands (distal anhidrosis, hyperhidrosis when eating).

The key link in the pathogenesis of this complication is chronic hyperglycemia. There are three theories of the development of diabetic neuropathy.

Polyolmyoinositol theory. According to her, as a result of hyperglycemia inside the nerve, there is a significant increase in the concentration of glucose. Since glucose in excess is not completely metabolized, this contributes to the formation of sorbitol. This substance is osmotically active. As a result of an increase in the concentration of sorbitol inside the nerve, the activity of sodium-potassium ATP-ase decreases. This fact causes swelling of axons, as well as other structures of the neuron of a progressive nature.

Theory of endoneural microangiopathy. It consists in the fact that as a result of microangiopathy of the vessels of the nerves, axonal hypoxia develops, which, in turn, leads to metabolic disorders and the occurrence of microhemorrhages.

The manifestation of diabetic neuropathy depends on its type according to the classification.

With sensory neuropathy, there is initially a violation of vibration sensitivity. Identification of this violation is carried out using a graduated tuning fork, which is installed on the head of the first tarsal bone. Diagnosis is based on the patient's feeling of vibration of the tuning fork. The most common symptom of the distal form of this complication of diabetes mellitus is the appearance of a feeling of numbness and paresthesia in the lower extremities. The usual complaints are sensations of chilliness in the legs, which are warm on palpation. Restless legs syndrome is characteristic of sensorimotor neuropathy. This syndrome is a combination of hypersensitivity with the appearance of paresthesia at night. Leg pain often occurs at night.

As the pathology progresses, these sensations appear in the arms, as well as in the chest and abdomen. With a long course of the disease, the death of small pain nerve fibers occurs, which is manifested by a spontaneous cessation of pain in the limbs. Sensorimotor neuropathy may be accompanied by hypesthesia, the manifestations of which are loss of sensitivity in the "stocking and gloves" type. In the event of a violation of proprioceptive sensitivity, the development of sensory ataxia is noted, which consists in difficulty in movement and impaired coordination of movement. Since there is a violation of pain sensitivity, patients often do not notice small injuries to the feet, which subsequently become easily infected. In the case of mononeuropathy, in most cases, the facial, abducens, and sciatic nerves are affected.

Cardiovascular form. With autonomic neuropathy, the vagus nerve is the first to be affected, which leads to an increase in the sympathetic effect on the heart. These changes explain the development of resting tachycardia. The progression of the process leads to damage to the sympathetic nervous system, which is manifested by some decrease in tachycardia. All these changes in the innervation of the heart muscle lead to a violation of its adaptation to physical stress.

The gastrointestinal form of diabetic neuropathy develops as a result of insufficient cholinergic regulation of the function of the gastrointestinal tract. Clinically, this form is manifested by atony of the esophagus, the development of reflux esophagitis, paresis of the stomach is noted, in which both slowing down and accelerating its emptying can occur. As a result of impaired intestinal motility, there is an alternation of diarrhea and constipation. In addition, there is a violation of the exocrine function of the pancreas. Quite often, salivation develops, as well as biliary dyskinesia, in which the tendency to form stones increases.

The urogenital form is a consequence of the spread of the pathological process to the sacral plexus. In this case, the regulation of the function of the urogenital tract is disturbed. Clinically, this form of diabetic neuropathy can be manifested by atony of the ureters of the bladder, reflux or stasis of urine, and an increased tendency to infection of the urinary system. In 50% of men, the appearance of erectile dysfunction, retrograde ejaculation is noted, and there is also a violation of the painful innervation of the testicles. In women, there may be a violation of the hydration of the vagina.

Impaired ability to recognize hypoglycemia. Normally, with hypoglycemia, there is an emergency release of glucagon into the bloodstream. Its initial release occurs as a result of parasympathetic stimulation of the pancreatic islets. Subsequently, the release of glucagon is carried out due to the mechanisms of humoral regulation. With the development of diabetic neuropathy, glucagon release occurs due to the first mechanism. There is also a loss of symptoms that are harbingers of hypoglycemia. All these violations lead to the fact that the patient loses the ability to recognize the approaching hypoglycemia.

Diabetic neuropathy is accompanied by impaired pupillary function, which is manifested by Argyle-Robertson syndrome or impaired adaptation of vision in the dark.

Violation of the function of the sweat glands develops as a result of a violation of the innervation of the skin of a trophic nature. Since the function of the sweat glands falls out, the skin becomes dry - anhidrosis occurs.

Treatment of this complication is carried out in three stages. The first stage is to achieve compensation of metabolic processes in diabetes mellitus. For this purpose, intensive insulin therapy is carried out. The second stage of treatment is to stimulate the regeneration of damaged nerve fibers. For this purpose, lipoic acid preparations and B vitamins are used.

Under the influence of lipoic acid preparations, the energy balance in the nerve formations is restored, and their further damage is also prevented. Initially, the drug is administered intravenously at a dose of 300-600 mg / day. The duration of such therapy is 2-4 weeks. After this time, they switch to the tablet form of the drug at a dose of 600 mg / day for 3-6 months. The third stage is to carry out symptomatic therapy, which depends on the form of diabetic neuropathy.

4. Diabetic foot syndrome

Diabetic foot syndrome is a pathological condition of the foot in diabetes mellitus, which occurs against the background of damage to peripheral nerves, skin and soft tissues, bones and joints and is manifested by acute and chronic ulcers, osteoarticular lesions and purulent-necrotic processes.

There are three forms of diabetic foot syndrome: neuropathic, ischemic and mixed (neuroischemic). 60-70% of cases of diabetic foot syndrome are neuropathic.

neuropathic form. Initially, with the development of diabetic neuropathy, the distal nerves are affected, and the longest nerves are affected. As a result of damage to the autonomic fibers that make up these nerves, a deficiency of trophic impulses to muscles, tendons, ligaments, bones and skin develops, which leads to their hypotrophy. The consequence of malnutrition is the deformation of the affected foot. In this case, the load on the foot is redistributed, which is accompanied by an excessive increase in it in certain areas. Such areas may be the heads of the metatarsal bones, which will be manifested by thickening of the skin and the formation of hyperkeratosis in these areas. Due to the fact that these areas of the foot experience constant pressure, the soft tissues of these areas undergo inflammatory autolysis. All these mechanisms eventually lead to the formation of an ulcer. Since there is a violation of the function of the sweat glands, the skin becomes dry and cracks easily appear on it. As a result of a violation of the pain type of sensitivity, the patient may not notice this. In the future, infection of the affected areas occurs, which leads to the appearance of ulcers. Their formation is facilitated by the immunodeficiency that occurs during decompensation of diabetes mellitus. Pathogenic microorganisms that in most cases infect small wounds are staphylococci, streptococci and bacteria of the intestinal group. The development of the neuropathic form of the diabetic foot is accompanied by a violation of the vascular tone of the lower extremities and the opening of arteriovenous shunts. This occurs as a result of an imbalance between the innervation of the adrenergic and cholinergic vessels. As a result of the expansion of the vessels of the foot, its swelling and fever develop.

Due to the opening of the shunts, tissue hypoperfusion and the phenomenon of steal develop. Under the influence of foot edema, increased compression of arterial vessels and ischemia of the distal parts of the foot (blue finger symptom) can occur.

The clinic is characterized by three types of lesions. These include neuropathic ulcers, osteoarthropathy, and neuropathic edema. Ulcers are most often located in the area of ​​the sole, as well as in the spaces between the toes. Neuropathic osteoarthropathy develops as a result of osteoporosis, osteolysis and hyperostosis, i.e. under the influence of dystrophic processes in the osteoarticular apparatus of the foot. Neuropathy can cause spontaneous bone fractures. In some cases, these fractures are painless. In this case, on palpation of the foot, its swelling and hyperemia are noted. Destruction in the bone-ligamentous apparatus can proceed for quite a long time. This is usually accompanied by the formation of a pronounced bone deformity, which is called the Charcot joint. Neuropathic edema develops as a result of impaired regulation of tone in the small vessels of the foot and the opening of shunts.

Treatment includes several measures: achievement of compensation for diabetes mellitus, antibiotic therapy, wound treatment, rest and unloading of the foot, removal of the area of ​​hyperkeratosis and wearing specially selected shoes.

Compensation of metabolic processes in diabetes mellitus is achieved by large doses of insulin. Such therapy for type II diabetes mellitus is temporary.

Therapy with bacterial preparations is carried out according to the general principle. In most cases, infection of foot defects is carried out by gram-positive and gram-negative cocci, E. coli, clostridia and anaerobic microorganisms. As a rule, a broad-spectrum antibiotic or a combination of several drugs is prescribed. This is due to the fact that usually the pathogenic flora is mixed.

The duration of this type of therapy can be up to several months, which is determined by the depth and prevalence of the pathological process. If antibiotic therapy is carried out for a long time, then it is necessary to repeat the microbiological study, the purpose of which is to detect emerging strains resistant to this drug. With a neuropathic or mixed diabetic foot, it is necessary to unload it until recovery.

With this technique, ulcers can heal within a few weeks. If patients have fractures or a Charcot joint, then the unloading of the limb should be carried out until the bones are completely fused.

In addition to these methods, it is mandatory to carry out local treatment of the wound, which includes the treatment of the edges of the ulcer, the removal of necrotic tissues within healthy ones, and the provision of asepsis of the wound surface. A dioxidine solution of 0,25 - 0,5% or 1% is widely used. You can also use a solution of chlorhexidine. If there is plaque on the wound surface, consisting of fibrin, then proteolytics are used.

The ischemic form of the diabetic foot syndrome develops when the main blood flow in the limb is disturbed, which occurs with the development of atherosclerotic lesions of the arteries.

The skin on the affected foot takes on a pale or cyanotic hue. In more rare cases, as a result of the expansion of superficial capillaries, the skin acquires a pinkish-red tint. These vessels dilate during ischemia.

In the ischemic form of the diabetic foot, the skin becomes cold to the touch. Ulcers form on the tips of the toes and on the marginal surface of the heel. On palpation of the artery of the foot, as well as in the popliteal and femoral arteries, the pulse becomes weakened or may be absent altogether, which is noted with stenosis of the vessel, which exceeds 90% of its lumen. Auscultation of large arteries in some cases determines the systolic murmur. In many cases, this form of diabetes mellitus complication is characterized by the appearance of pain symptoms.

Instrumental research methods are used to determine the state of arterial blood flow in the vessels of the lower extremities. Using the Doppler method, the ankle-brachial index is measured. This indicator is measured by the ratio of the systolic pressure of the artery of the foot and the brachial artery.

Normally, this ratio is 1,0 or more. In the case of atherosclerotic lesions of the arteries of the lower extremities, this indicator decreases to 0,8. If the indicator is equal to 0,5 or less, then this indicates a high probability of developing necrosis.

In addition to dopplerography, if necessary, angiography of the vessels of the lower extremities, computed tomography, magnetic resonance imaging, and ultrasound scanning of these vessels are performed.

Just as in the neuropathic form, it is necessary to achieve compensation for diabetes mellitus. Damage to the lower limb in this form of diabetic foot can be of varying severity.

The severity of the process is usually determined by three factors, including the severity of arterial stenosis, the degree of development of collateral blood flow in the limb, and the state of the blood coagulation system.

The usual method of treatment, which is preferred in the ischemic form of the diabetic foot, is revascularization surgery. These operations include: the formation of bypass anastomoses and thromboendarterectomy.

Minimally invasive surgical interventions can also be used, these include laser angioplasty, percutaneous transluminal angioplasty, and the combination of local fibrinolysis with percutaneous transluminal angioplasty and aspiration thrombectomy. In the event that there are no necrotic and ulcerative lesions, walking is recommended, which takes 1-2 hours a day, which contributes to the development of collateral blood flow in the limb (ergotherapy). For the prevention of thrombosis, the use of aspirin at a dose of 100 mg per day and anticoagulants is recommended. If blood clots are already present, fibrinolytics are used. In the case when the purulent-necrotic process in any variant of the diabetic foot is quite extensive, the issue of amputation of the lower limb is decided.

The main method of preventing the development of diabetic foot syndrome is the adequate treatment of diabetes mellitus and maintaining the compensation of metabolic processes at an optimal level. At each visit to the doctor, it is necessary to examine the lower extremities of the patient.

Such inspections should be carried out at least once every 1 months. It is also important to educate patients with diabetes, including the rules for foot care. It is necessary to keep the feet clean and dry, conduct warm foot baths, apply creams to prevent the appearance of cracks in the skin.

Lecture No. 12. Itsenko-Cushing's syndrome

Itsenko-Cushing's syndrome is a syndrome that is caused by endogenous hyperproduction or prolonged exogenous administration of corticosteroids.

There are two types of classification.

First type.

1. Itsenko-Cushing's disease.

2. Itsenko-Cushing's syndrome:

1) tumor:

a) adrenal gland;

b) ectopic;

c) gonads;

2) bilateral ACTH-independent nodular hyperplasia of the adrenal cortex;

3) taking glucocorticoids or ACTH preparations for therapeutic purposes.

Second type.

1. ACTH-dependent Cushing's syndrome:

1) pituitary corticotropinoma;

2) ectopic ACTH syndrome, or syndrome of ectopic production of ACTH, as well as corticoliberin by tumors;

3) exogenous administration of ACTH.

2. ACTH-independent Cushing's syndrome:

1) exogenous administration of glucocorticoids;

2) adenoma of the adrenal cortex;

3) nodular bilateral hyperplasia of the adrenal cortex.

In most cases, 90% of the cause of Cushing's syndrome is a pituitary adenoma. Another cause of the syndrome is an ectopic ACTH-producing tumor.

During the formation of a tumor that produces corticotropin, the normal secretion of ACTH is disrupted. This is accompanied by an increase in the sensitivity threshold of the pituitary gland to glucocorticoids. In some cases, an increase in cortisol production does not cause a decrease in ACTH production, i.e., the negative feedback mechanism is disrupted. An increase in the level of steroid hormones in the blood leads to multiple organ and polysystem damage.

In 90% of cases, the appearance of obesity of the cushingoid type is observed. In this case, the deposition of fat is noted mainly on the abdomen, chest, neck and face. Quite often, obesity is accompanied by atrophy of the muscles of the upper and lower extremities. The deposition of adipose tissue in certain parts of the body is explained by its unequal sensitivity to glucocorticoids.

Muscle atrophy develops as a result of the catabolic action of these hormones. The skin integuments acquire a marble hue, become thinned, dry, peeling and the appearance of a specific sheep smell are noted. Stretch marks of a purple-red or purple color appear on the skin. Stretch marks are predominantly located on the abdomen, inner thighs, in the area of ​​​​the mammary glands and shoulders. The occurrence of stretch marks is due to the breakdown of collagen in the skin and obesity. Skin hyperpigmentation may appear. A characteristic complication of Cushing's syndrome is the development of osteoporosis. Its cause is the leaching of calcium from bone tissue under the influence of glucocorticoids. Changes in osteoporosis are most clearly seen in the thoracic and lumbar spine.

Due to the fact that osteoporosis is combined with atrophy of the back muscles, changes in the spine are manifested by the formation of scoliosis and kyphoscoliosis. With the development of the disease in childhood, the child lags behind in growth, as the development of epiphyseal cartilages is inhibited.

With an excess of corticosteroids, alkalosis, arterial hypertension, myocardial dystrophy, cardiac arrhythmia, and heart failure often develop. Also, under the influence of a large amount of corticosteroids in the blood, the following symptoms are noted: drowsiness, polyphagia, polydipsia, impaired thermoregulation, depression or aggressiveness.

With a long course of the disease, steroid diabetes mellitus develops, the functioning of the immune system is disrupted. Since there is an increase in the formation of sex hormones, women have excessive male-type hair growth, as well as defeminization.

To confirm the diagnosis of Cushing's syndrome, a blood test is performed for the level of ACTH, as well as a large dexomethasone test, and the determination of the daily excretion of free cortisol in the urine. Instrumental diagnostic methods include X-ray examination of the bones of the skull and spine.

With Itsenko-Cushing's syndrome, radiographs show signs of osteoporosis. If there are signs of osteoporosis of the back of the Turkish saddle, then this indicates a pituitary microadenoma. Ultrasound of the adrenal glands, computed tomography and magnetic resonance imaging are also used.

If the cause of the syndrome is a pituitary adenoma, then the treatment is selective transsphenoidal adenomectomy.

From drug therapy, the appointment of inhibitors of steroidogenesis, such as lysodren, mamomit, nizoral, is widely used. In the absence of a positive effect from all types of therapy, a bilateral adrenalectomy is performed. If the cause of the syndrome is corticosteroma, then the affected adrenal gland is surgically removed, then replacement therapy is temporarily carried out until the function of the preserved adrenal gland is restored. If Cushing's syndrome is associated with ectopic ACTH synthesis, then surgical removal of the hormone-producing tumor is performed. Symptomatic therapy is also carried out, which consists in the use of antihypertensive drugs, sugar-lowering drugs, drugs for the treatment of osteoporosis, as well as potassium preparations.

Lecture number 13. Diabetes insipidus

Diabetes insipidus is a clinical syndrome resulting from a violation of the concentration function of the kidneys, which is associated with a deficiency of antidiuretic hormone or with a violation of the sensitivity of the renal tubules to its actions.

There is the following classification.

1. Central (hypothalamic-pituitary) diabetes insipidus:

1) idiopathic;

2) symptomatic.

2. Renal diabetes insipidus.

The etiology of central diabetes insipidus is unknown, i.e. it is idiopathic diabetes insipidus. In most cases, central diabetes insipidus is symptomatic, that is, it develops with any disease.

Such diseases can be influenza, tonsillitis, scarlet fever, whooping cough, tuberculosis, syphilis, rheumatism. Also, diabetes insipidus can be the result of a traumatic brain injury, electrical injury, hemorrhage in the pituitary gland or hypothalamus.

Also, the disease can be a symptom of a tumor of the hypothalamus or pituitary gland. As a result of antidiuretic hormone deficiency, the concentration function of the kidneys is impaired, which is manifested by the release of a large amount of low-density urine.

As a result of stimulation of the thirst center in the brain, polydipsia develops. It leads to an overload of the gastrointestinal tract, which is manifested by irritable bowel syndrome, biliary dyskinesia and prolapse of the stomach.

Renal diabetes insipidus may be the result of an anatomical inferiority of the renal nephron or a defect in enzymes that prevents the effect of vasopressin on the permeability of the renal tubular membrane to water.

The clinic depends on the degree of antidiuretic hormone deficiency. The amount of fluid that the patient absorbs during the day can vary from 3 to 40 liters or more.

The first sign of diabetes insipidus in children is nocturia, where the urine is discolored.

The disease can begin both acutely and gradually, there is a decrease in appetite, body weight, skin and mucous membranes become dry, sweating and salivation is reduced.

There are violations of the gastrointestinal tract, which is manifested by constipation, the development of colitis and chronic gastritis.

Examination reveals prolapse and enlargement of the stomach, enlargement of the bladder, ureters and renal pelvis.

With a decrease in the sensitivity of the center of thirst, dehydration develops. This condition is manifested by weakness, tachycardia, hypotension, headache, nausea and vomiting, and a violation of the rheological properties of the blood.

As a result of dehydration in the blood, the level of sodium, red blood cells, hemoglobin and residual nitrogen increases. With the progression of the pathological process, convulsions and psychomotor agitation appear.

In the case of diabetes insipidus, as a result of a pathological process, neurological symptoms develop in the brain, which depend on the localization of the pathological focus.

Characteristic of diabetes insipidus is the low density of urine, which is detected in the general analysis. The density of urine is less than 1,005.

Hypoosmolarity of urine is also noted, which is less than 300 mosm / l. When analyzing blood, plasma hyperosmolarity is more than 290 mosm / l.

Treatment involves the administration of antidiuretin by the intranasal route. The drug is administered 1-3 drops 1-3 times a day.

Treatment should be carried out under constant monitoring of diuresis and relative density of urine. If the patient has rhinitis, then antidiuretin is used sublingually.

If diabetes insipidus is nephrogenic, treatment includes the use of thiazide diuretics, non-steroidal anti-inflammatory drugs, and lithium.

Lecture No. 14. Pathology of phosphorus-calcium metabolism, parathyroid glands and bone metabolism. hyperparathyroidism

Classification of diseases caused by impaired secretion of parathyroid hormone.

I. Primary hyperparathyroidism.

1. Pathogenetic forms:

1) hyperfunctioning adenoma (adenomas);

2) hyperplasia of the parathyroid glands;

3) multiple endocrine neoplasia type I with hyperparathyroidism (Wermer's syndrome);

4) multiple endocrine neoplasia type II with hyperparathyroidism (Cipple's syndrome).

2. Clinical forms:

1) bone;

2) osteoporotic;

3) fibrocystic osteitis;

4) "pagetoid";

5) visceropathic;

6) with a primary lesion of the kidneys;

7) with a predominant lesion of the gastrointestinal tract;

8) with a predominant lesion of the neuropsychic sphere;

9) mixed form.

II. Secondary hyperparathyroidism.

1. Renal pathology: chronic renal failure, tubulopathy (Albright-Fanconi type), renal rickets.

2. Intestinal pathology (malabsorption syndrome).

3. Bone pathology (cyanotic osteomalacia, puerperal, idiopathic, Paget's disease).

4. Insufficiency of vitamin D diseases of the kidneys, liver, hereditary fermentopathy (calcium- and phosphopenic inherited forms of osteomalacia).

5. Malignant diseases (multiple myeloma).

III. Tertiary hyperparathyroidism.

IV. Pseudohyperparathyroidism.

V. Hormonally inactive cystic and tumor formations of the parathyroid glands.

VI. Hypoparathyroidism.

1. Congenital underdevelopment or absence of the parathyroid glands.

2. Idiopathic (autoimmune).

3. Postoperative.

4. Radiation damage.

5. Damage to the parathyroid glands during hemorrhage, heart attack.

6. Infectious damage.

VII. Pseudohypoparathyroidism.

Type I - insensitivity of target organs to parathyroid hormone, dependent on adenylate cyclase.

Type II - insensitivity of target organs to parathyroid hormone, independent of adenylate cyclase, possibly of autoimmune origin.

VIII. Pseudopseudohypoparathyroidism.

Hyperparathyroidism is a disease caused by hypersecretion of parathyroid hormone. According to the pathogenetic principle, hyperparathyroidism is divided into primary, secondary and tertiary.

An independent disease is primary hyperparathyroidism. Secondary and tertiary hyperparathyroidism - syndromes that complicate the course of other diseases (renal failure, malabsorption).

Primary hyperparathyroidism is a primary disease of the parathyroid glands, manifested by excessive production of parathyroid hormone with the development of hypercalcemia syndrome. Secondary hyperparathyroidism is a compensatory hyperfunction and hyperplasia of the parathyroid glands, which develops with prolonged hypocalcemia and hyperphosphatemia of various origins.

In tertiary hyperparathyroidism, the development of autonomous hyperproduction of parathyroid hormone by hyperplastic parathyroid glands or the formation of parathyroid adenoma occurs with long-term secondary hyperparathyroidism.

1. Primary hyperparathyroidism:

1) solitary adenoma (80%), multiple adenomas (5%);

2) hyperplasia of the parathyroid glands (15%);

3) carcinoma of the parathyroid glands (‹ 5%);

4) primary hyperparathyroidism within the syndromes of multiple endocrine neoplasia types I and II.

2. Secondary hyperparathyroidism:

1) renal secondary hyperparathyroidism;

2) secondary hyperparathyroidism with normal renal function:

a) malabsorption syndrome with calcium malabsorption;

b) pathology of the liver (rarely) - cirrhosis (impaired conversion of cholecalciferol), cholestasis (impaired resorption of cholecalciferol));

3) vitamin D deficiency (insufficient solar exposure).

3. Tertiary hyperparathyroidism.

1. Primary hyperparathyroidism

Primary hyperparathyroidism occurs with a frequency of about 25 new cases per 100 population per year. About 000% of cases of hypercalcemia syndrome are associated with primary hyperparathyroidism. After diabetes mellitus and thyrotoxicosis, primary hyperparathyroidism is the third most common endocrine disease. The peak incidence occurs at 35-40 years, while primary hyperparathyroidism is 50 times more common among women (available in 2% of women in the postmenopausal period). Hypercalcemia is recorded in adults in 3-0,5% of cases, more often in women over 1,1 years of age.

The most common cause of hyperparathyroidism is a solitary adenoma of the parathyroid gland (parathyroma), much less often - multiple adenomas (5%), even less often (‹ 5%) - parathyroid cancer. Primary hyperplasia of all parathyroid glands occurs in approximately 15% of patients.

Of fundamental clinical importance is the fact that primary hyperparathyroidism occurs in both variants of multiple endocrine neoplasia syndromes. Thus, when primary hyperparathyroidism is detected, a screening examination is necessary to identify other components (pheochromocytoma, medullary thyroid cancer, islet cell tumors).

Hyperproduction of parathyroid hormone leads to excessive excretion of phosphate through the kidneys. A decrease in the plasma level of the latter stimulates the synthesis of calcitriol, which promotes the absorption of excess Ca₂₊ in the intestine. In the advanced stages of the process, hypercalcemia is enhanced by the activation of osteoclasts by an excess of parathyroid hormone. An excess of parathyroid hormone leads to an acceleration of bone metabolism, acceleration of bone resorption and bone formation, but the formation of new bone lags behind its resorption, which leads to generalized osteoporosis and osteodystrophy, calcium leaching from bone depots and hypercalcemia, as well as hypercalciuria, which damages the renal tubular epithelium and the formation of kidney stones. Nephrocalcinosis, in turn, leads to decreased kidney function. In the occurrence of ulcerative lesions of the stomach and duodenum, hypercalcemia with arteriolosclerosis and vascular calcification play an important role. Hypercalcemia, along with an increase in blood pressure, creates the preconditions for the formation of left ventricular hypertrophy, the function of which is also worsened by valvular, coronary and myocardial calcifications typical of hyperparathyroidism.

Pathological and anatomical examination in the case of severe, advanced primary hyperparathyroidism, the bones are soft; flat bones can be easily cut with a knife, diffuse osteoporosis is detected, which is often combined with the formation of cysts. The deposition of calcifications in the kidneys, muscles, myocardium, walls of large arteries is revealed.

The clinical manifestations of hyperparathyroidism are varied. Currently, in more than 50% of cases, the diagnosis of primary hyperparathyroidism is established by incidental detection of hypercalcemia. Symptoms of primary hyperparathyroidism consist of renal, bone, neuromuscular and gastrointestinal syndromes. In accordance with this, bone, visceropathic, neuropsychic and mixed forms of hyperparathyroidism are distinguished. A severe complication of primary hyperparathyroidism is hypercalcemic crisis.

Renal symptoms are clinically expressed in 40-50% of cases. Thirst and polyuria with a decrease in the specific gravity of urine are among the earliest symptoms of hyperpatireosis and may be mistakenly regarded by doctors as manifestations of diabetes insipidus.

ADH-refractory insipidary syndrome (polyuria, polydipsia, hypoisosthenuria) is caused by impaired renal water reabsorption due to insensitivity of the renal tubules to ADH due to massive hypercalciuria. Nephrolithiasis, often accompanied by pyelonephritis, occurs in 25% of patients with hyperparathyroidism. Significantly less common, but severe nephrocalcinosis, leading to progressive renal failure. Primary hyperparathyroidism occurs in approximately 2-5% of all patients with urolithiasis.

Bone changes are detected in 50% of cases, while the osteoporotic variant, fibrocystic osteitis, is isolated. Diffuse osteopenia is most often detected radiographically: when examining the hands in 40% of cases, the spine - in 20%. In severe primary hyperparathyroidism, pathognomonic subperiosteal resorption and acroosteolysis of the terminal phalanges of the hands and feet can be detected. In severe cases, skeletal deformity, gait disturbance ("duck"), pathological bone fractures develop.

Cysts, giant cell tumors, and epulides are now extremely rare. Epulides are cystic formations, often mistaken for a malignant tumor, which is the reason for unreasonable operations. Joint damage often develops in the form of chondrocalcinosis.

Gastrointestinal symptoms are also detected in half of the patients. Most often it is anorexia, nausea, constipation, flatulence, weight loss. In 10% of cases, peptic ulcers of the stomach and (or) duodenum develop, in 10% - pancreatitis, rarely pancreatic calculosis. In 2 times more often than in the population, cholelithiasis occurs.

The clinical picture of the initial period of primary hyperparathyroidism is diverse and non-specific, which makes it difficult to make a diagnosis. Patients are concerned about general and muscle weakness, lethargy, adynamia, and increased fatigue. Depending on the form, early manifestations can be predominantly gastroenterological (acute epigastric pain, loss of appetite, nausea, sometimes a clinical picture of an acute abdomen develops, pancreatitis, pancreocalcinosis may develop); urological (polyuria, nephrolithiasis). The most pronounced symptoms occur when the skeletal system is affected: loosening and loss of teeth due to osteoporosis of the jaws, bone pain when walking, deformities of the chest bones, multiple pathological fractures.

Cardiovascular manifestations of hyperparathyroidism include arterial hypertension and arrhythmias. Left ventricular hypertrophy, detected even in the group of individuals with minimal manifestations of hyperparathyroidism, is one of the factors of increased mortality in this disease.

Psychoneurological disorders can be the only manifestations of the disease for a long time; their spectrum ranges from depression to dementia. Destruction of the spine and resulting radicular disorders lead to symptoms of tension, paralysis of the muscles of the pelvic girdle, lower extremities, paresthesia. Mental arousal is typical of a hyperparathyroid (hypercalcemic) crisis.

Hypercalcemic crisis is now rare - less than 5% of patients with primary hyperparathyroidism. The crisis develops at a plasma calcium level of about 4 mmol / l and is provoked by prolonged bed rest, the appointment of thiazide diuretics, calcium and vitamin D preparations. The appointment of the latter is based on an erroneous medical hypothesis about the presence of osteoporosis without specifying its specific genesis.

Clinically, the hypercalcemic crisis is characterized by the addition of manifestations of damage to the central nervous system (drowsiness, stupor, coma, psychosis) to the symptoms of hyperparathyroidism, following the growing symptoms of damage to the gastrointestinal tract (anorexia, nausea, vomiting, constipation, epigastric pain, thirst). Rapidly developing severe weakness, dehydration, anuria, coma, which is difficult to differentiate from a coma of another origin. The most severe neurological complication is myopathy involving not only the proximal parts of the body, but also the intercostal muscles and the diaphragm, requiring the transfer of the patient to mechanical ventilation. Fever up to 38-39 °C is typical.

Diagnosis of primary hyperparathyroidism is based on data from clinical, laboratory and instrumental studies. In a laboratory study, hypercalcemia is determined in 90% of cases of primary hyperparathyroidism. In most cases, it is combined with hypophosphatemia. In addition, hypercalciuria and hyperphosphaturia, an increase in plasma alkaline phosphatase and urinary excretion of hydroxyproline and cAMP are determined. Primary hyperparathyroidism is characterized not only by increased bone resorption, but also by increased bone formation, namely, a high level of bone metabolism, which corresponds to a high content of osteocalcin, which is a marker of osteoblastic function.

The diagnosis of primary hyperparathyroidism is confirmed by a high level of intact parathyroid hormone in plasma, which can be detected in 90% of cases of primary hyperparathyroidism.

The radiological marker of primary hyperparathyroidism is the detection of osteoporosis, which is characterized by a sharp thinning of the cortical layer of bones, the appearance of deformities, cysts, swellings, and protrusions. The phenomena of subperiosteal resorption are characteristic: subperiosteal resorption of the bone, especially noticeable in the hands. X-ray changes can be divided into 3 types:

1) osteoporotic (generalized osteoporosis);

2) classic, in which cysts, deformities, subperiosteal resorption, fibrocystic osteitis are detected against the background of osteoporosis;

3) pagetoid, in which the compact layer is not thinned, but, on the contrary, unevenly thickened, and a "cotton pattern" is revealed in the bones of the skull.

X-ray and ultrasound examinations can reveal nephrocalcinosis and nephrolithiasis. The classic ECG signs of hypercalcemia are shortening of the Q-T interval, S-T depression, atrioventricular block. Echocardiography reveals left ventricular hypertrophy, calcifications in the myocardium.

When diagnosing primary hyperparathyroidism, ultrasound is quite informative. Invasive studies are carried out only when the diagnosis of primary hyperparathyroidism is established for the purpose of topical diagnosis when non-invasive methods are not informative and include non-selective arteriography with contrast agents and vein catheterization with selective determination of parathyroid hormone.

In differential diagnosis, conditions accompanied by hypercalcemia, as well as other metabolic osteopathies, are excluded.

Malignant tumors are the most common (60%) cause of hypercalcemia syndrome. As a rule, we are talking about lung cancer, breast cancer, multiple myeloma. Hypercalcemia may be of osteolytic origin in widespread bone metastasis and may be paraneoplastic due to tumor production of a peptide related to parathyroid hormone, the level of which is elevated in 90% of cases of tumor hypercalcemia. With multiple myeloma, it is not determined. In the latter case, an increase in ESR, Bence-Jones protein in the urine, and also the absence of an increase in the level of parathyroid hormone are found.

Paget's disease (osteitis deformans) must be differentiated from the "pagetoid" form of hyperparathyroidism, which makes it possible to achieve normal levels of calcium, phosphorus and parathyroid hormone in Paget's disease.

Erased forms of primary hyperparathyroidism must be differentiated from benign familial hypocalciuric hypercalcemia resulting from a mutation in the gene encoding the formation of calcium-sensitive receptors. In the latter case, the level of parathyroid hormone is normal, there are no changes in the structure of the bones and somatic signs of hyperparathyroidism.

In recent years, subclinical (mild) forms of primary hyperparathyroidism have been increasingly recorded, the only manifestation of which is such low-specific symptoms as depression, weakness, sleep and memory disorders. Subclinical primary hyperparathyroidism is more common, mainly in the elderly, and is extremely difficult for timely diagnosis.

With parathyroidism, surgical treatment is indicated. By itself, the operation to remove a parathyroma is relatively short, and 90% of the time of the operation is spent on searching for a tumor. With an obvious clinical picture (visceropathic, bone form), confirmed by convincing laboratory data (hypercalcemia, high levels of intact parathyroid hormone), surgery is recommended even in the absence of convincing data from topical diagnostics.

The operation is absolutely indicated for saving the life of a patient with clinically obvious hyperparathyroidism and with primary hyperparathyroidism in young or somatically healthy patients. In case of accidentally detected asymptomatic primary hyperparathyroidism in patients over the age of 50 years, the intervention is carried out:

1) in the presence of progression of osteoporosis;

2) when the level of ionized calcium is more than 3 mmol / l (12 mg / dl), severe calciuria (more than 10 mmol / day or 400 mg / day) or in the presence of episodes of severe hypercalcemia;

3) in the presence of visceral complications of primary hyperparathyroidism (fibrous periostitis, nephrocalcinosis);

4) with a creatinine clearance less than 30% of the age norm.

If a decision is made not to perform surgery, patients should receive sufficient fluids, avoid physical inactivity and dehydration. They are contraindicated thiazide diuretics and cardiac glycosides. It is necessary to control the level of blood pressure, it is advisable for postmenopausal patients to prescribe estrogen treatment. Every 6 months it is necessary to examine the content of calcium, plasma creatinine, creatinine clearance, the level of calcium excretion. Ultrasound of the abdominal organs and bone densitometry are indicated annually.

With hyperplasia of the parathyroid glands, total parathyroidectomy is indicated with transplantation of the removed glands into the tissue of the forearm. After the elimination of hyperparathyroidism, osteoporosis is treated for a long time.

Treatment of hypercalcemic crisis with established hyperparathyroidism is carried out simultaneously with preparation for surgery. The first stage of treatment is rehydration with the introduction of about 2 - 4 liters of isotonic sodium chloride solution (injection rate of about 1 l / h), after which they begin to administer intravenous bisphosphonates (pamidronate or etidronate) for 4 - 24 hours. Loop diuretics (furosemide) should not be given as the first step in treatment, as this exacerbates extracellular fluid loss. Furosemide is administered intravenously after at least 30 minutes of rehydration with careful monitoring of electrolyte levels. Calcitonin is one of the safest drugs. In a crisis, it is recommended to administer it intramuscularly at 4-8 IU / kg every 6-12 hours. If the level of inorganic phosphorus in serum is less than 1 mmol / l (the norm for adults is 1-1,5 mmol / l), preparations containing phosphorus salts are used. If a hypercalcemic crisis develops with osteolytic metastases of malignant tumors, the cytostatic mithramycin is prescribed. With a hypercalcemic crisis that has developed as a result of an overdose of vitamin D preparations, glucocorticoids are prescribed. If the crisis has developed against the background of renal failure, hemodialysis with a calcium-free buffer is indicated.

2. Secondary and tertiary hyperparathyroidism

As follows from the classification, the main causes of secondary hyperparathyroidism are kidney failure and diseases of the digestive system. In accordance with this, renal and intestinal secondary hyperparathyroidism are distinguished.

Due to the widespread use of hemodialysis and the increase in life expectancy in patients with chronic renal failure (CRF), secondary hyperparathyroidism has become much more common.

By the time patients are transferred to hemodialysis, histological changes of varying degrees in the bone tissue are present in 90% of patients. The development of secondary hyperparathyroidism in chronic renal failure is primarily associated with impaired formation of active vitamin D in the kidneys.₃. A progressive increase in the plasma level of inorganic phosphorus begins already with a decrease in the glomerular filtration rate to 60 ml / min or less. Hypocalcemia stimulates the secretion of parathyroid hormone by the parathyroid glands. Renal osteopathy is a combination of osteomalacia and increased bone resorption as a result of overproduction of parathyroid hormone.

At the heart of the pathogenesis of the intestinal form of AIV is the malabsorption of calcium and vitamin D, which leads to hyperstimulation of the parathyroid glands. In patients after gastrectomy osteopathy occurs in approximately 30% of cases. Patients after Billroth-II surgery and total gastrectomy have a greater risk of developing osteomalacia than after Billroth-I surgery.

In liver diseases, the development of secondary hyperparathyroidism is associated with a violation of the conversion of cholecalciferol. Most often occurs in primary biliary cirrhosis. The pathogenesis of tertiary hyperparathyroidism may be associated with the gradual formation of autonomy of hyperfunctioning parathyroid glands with a violation of the feedback mechanism between calcium levels and excessive production of parathyroid hormone.

The clinical picture of secondary and tertiary hyperparathyroidism is usually dominated by the symptoms of the underlying disease, most often CRF. Specific symptoms are bone pain, weakness in the proximal muscles, arthralgia. Spontaneous fractures and skeletal deformities may occur. The formation of extraosseous calcifications has various clinical manifestations. With calcification of the arteries, ischemic changes can develop. Periarticular calcifications may be seen on the arms and legs. Calcification of the conjunctiva and cornea in combination with recurrent conjunctivitis is referred to as red eye syndrome.

Laboratory studies reveal hyperphosphatemia, normal or slightly reduced plasma calcium levels, and high levels of alkaline phosphatase. The most sensitive marker of secondary hyperparathyroidism, in particular, incipient renal osteopathy, is an increase in the level of intact parathyroid hormone in blood plasma.

Typical radiological signs of secondary hyperparathyroidism are subperiosteal and subchondral resorption of the bones of the hand (acroosteolysis), as well as the elbow and hip joints.

In chronic renal failure, prevention of osteopathy is indicated with an increase in plasma inorganic phosphorus levels of more than 1,5 mmol / l. In this case, calcium-containing drugs that bind phosphates (calcium gluconate, lactate, citrate), as well as aluminum phosphate-binding drugs are prescribed. In addition, prescribe drugs (rocaltrol) under the control of urinary calcium excretion, which should not exceed 300 mg per day. In tertiary hyperparathyroidism, when an autonomous adenoma is formed, surgical treatment is indicated in some cases.

Lecture number 15. Hypoparathyroidism

Hypoparathyroidism is a disease associated with parathyroid hormone deficiency as a result of prolapse or insufficient function of the parathyroid glands, manifested by hypocalcemia syndrome. Hypoparathyroidism of various origins occurs in 0,2-0,3% of the population.

There is the following classification.

1. Postoperative hypoparathyroidism.

2. Idiopathic (autoimmune) hypoparathyroidism:

1) isolated;

2) within the autoimmune polyglandular syndrome 1-10 types.

3. Hypoparathyroidism as a result of damage to the parathyroid glands as a result of irradiation, exposure to infectious factors, with amyloidosis, hemorrhages in a hormonally inactive tumor of the gland.

4. Aplasia of the parathyroid glands and thymus.

The most common form is postoperative hypoparathyroidism. At the same time, it develops not so much as a result of the complete removal of the glands, but due to a violation of their blood supply due to the occurrence of fiber fibrosis in the area of ​​surgical intervention.

In qualified surgeons operating on the thyroid gland, the incidence of postoperative hypoparathyroidism should not exceed 2%, and in repeated operations - 5-10%.

Sporadic forms of idiopathic hypoparathyroidism occur, as a rule, in young people. A rare disease in which hypoparathyroidism occurs is Di George syndrome. In this syndrome, parathyroid agenesis is combined with thymus aplasia and congenital heart defects. A rare cause of hypoparathyroidism is the destruction of the parathyroid glands by tumor infiltration in the neck, as well as in hemochromatosis and amyloidosis.

Neonatal transient hypoparathyroidism occurs in premature babies, which is associated with underdevelopment of the parathyroid glands. Functional forms of hypoparathyroidism occur with long-term hypomagnesemia. The latter develops with magnesium malabsorption (with malabsorption syndrome, chronic alcoholism), long-term treatment with diuretics.

The lack of parathyroid hormone leads to an increase in the level of phosphorus in the blood due to a decrease in the phosphaturic action of parathyroid hormone on the kidneys, as well as to hypocalcemia due to a decrease in calcium absorption in the intestine, a decrease in its mobilization from the bones and insufficient reabsorption in the renal tubules.

Thus, a distinctive feature of hypocalcemia in hypoparathyroidism is its combination with hyperphosphatemia. In other diseases that occur with hypocalcemia (deficiency or resistance to vitamin D), secondary hyperparathyroidism develops and, thus, hypophosphatemia.

Hypocalcemia and hyperphosphatemia lead to a universal violation of the permeability of cell membranes and thus to an increase in neuromuscular excitability and convulsive readiness, autonomic lability, and the deposition of calcium salts in the internal organs and walls of large vessels.

The main clinical manifestations of hypoparathyroidism are due to hypocalcemia and hyperphosphatemia, which lead to an increase in neuromuscular excitability and general autonomic reactivity, increased convulsive activity.

There are latent and manifest forms of hypoparathyroidism.

Latent hypoparathyroidism occurs without visible external symptoms and is clinically manifested only under the action of provoking factors or is detected during a special study.

The classic symptoms of hypoparathyroidism are tetanic spasms of skeletal muscles in combination with paresthesias and various autonomic disorders, as well as trophic disorders.

Convulsive contractions of the skeletal muscles (hypocalcemic tetany) in the idiopathic form occur in 75% of cases, and in the postoperative form - in 40%. Paresthesias and fibrillar twitches turn into painful tonic convulsions that occur with preserved consciousness, symmetrically involving the limb flexors, facial muscles ("obstetrician's hand", "horse foot", "fish mouth"), less often back extensors (opisthotonus).

Symptoms of Khvostek (contraction of mimic muscles when tapping at the exit site (n. facialis) and Trousseau (appearance of the "obstetrician's hand" 2-3 minutes after compression of the shoulder with a tonometer cuff) are classic and common, but not specific symptoms of hypoparathyroidism. Spasms of smooth muscles are manifested by laryngo- and bronchospasm, dysphagia, vomiting, diarrhea, constipation.From the vegetative manifestations, hypoparathyroidism is characterized by fever, chills, palpitations, pain in the region of the heart.

Epileptic seizures can be equivalents of tetanic convulsions. In this regard, patients are often mistakenly diagnosed with epilepsy.

There are no specific ECG changes with hypocalcemia; as a rule, the lengthening of the intervals Q - T is determined.

In patients with hypoparathyroidism, an ophthalmological examination may reveal cataracts, and magnetic resonance imaging of the head may show calcification of the basal ganglia. By itself, calcification of the basal ganglia (Fara's disease) is an incidental finding on computed tomography and magnetic resonance imaging in elderly patients.

Calcification of the basal ganglia often clinically manifests as extrapyramidal symptoms with choreoathetosis or parkinsonism.

Other trophic disorders often found in hypoparathyroidism are hair and nail growth disorders, defects in tooth enamel, dry skin, and osteosclerosis.

Laboratory diagnosis is based on the detection of hypocalcemia and hyperphosphatemia, which, with normal levels of creatinine and albumin, make the diagnosis of hypoparathyroidism very likely. In addition, with hypoparathyroidism, hypomagnesemia, hypercalciuria, decreased urinary excretion of phosphorus and cAMP, and a decrease in the plasma level of intact parathyroid hormone are detected. In response to the introduction of parathyroid hormone to a patient with hypoparathyroidism, urinary phosphate excretion increases tenfold (Ellsworth-Howard test).

Hypoparathyroidism is differentiated from other diseases that occur with a convulsive syndrome, as well as from a large group of conditions and diseases accompanied by hypocalcemia.

In all full-term newborns with the development of hypocalcemia, it is necessary to examine the level of calcium in the blood plasma of the mother to exclude subclinical hyperparathyroidism in her. In this case, hypercalcemia in the mother can lead to suppression of the function of the parathyroid glands in the fetus.

In patients undergoing thyroid surgery, it is necessary to differentiate between persistent and transient hypoparathyroidism.

The cause of transient hypoparathyroidism, the duration of which, as a rule, does not exceed 4 weeks, is probably reversible disturbances in the blood supply to the parathyroid glands, as well as the release of excess calcitonin into the blood.

Both with persistent and transient postoperative hypoparathyroidism, hypocalcemia develops in combination with convulsive syndrome already on the first or second day after surgery.

If postoperative hypocalcemia in combination with the lack of an adequate rise in the level of parathyroid hormone persists for more than 4-12 weeks, we can talk about the development of persistent postoperative hypoparathyroidism.

Until this time, patients are advised to prescribe monotherapy with calcium preparations, and only if persistent hypoparathyroidism is confirmed, add vitamin D preparations.

Severe hypocalcemia can develop with acute and extensive breakdown of large cell masses. Typical clinical situations in which this is observed are acute pancreatic necrosis, tumor disintegration with successful cytostatic therapy of malignant tumors, severe rhabdomyolysis after trauma, severe convulsive seizures, and intoxication.

In this case, in addition to severe hypocalcemia, hypophosphatemia, a high level of intracellular enzymes (lactate dehydrogenase, creatinine kinase) and uric acid are determined, and pronounced acidosis is noted.

Many of the symptoms of hypoparathyroidism can occur with what is called hyperventilatory tetany. In this regard, in the initial diagnosis of idiopathic hypoparathyroidism, it is advisable to investigate the gas composition of the blood.

Treatment of hypoparathyroidism is divided into relief of tetanic hypocalcemic crisis and maintenance therapy.

To stop the tetanic crisis, intravenous administration of 10-20 ml of a 10% solution of calcium gluconate is used, 10 ml of which contains 90 mg of elemental calcium. Calcium gluconate is recommended to be administered slowly, at a rate of no more than 2 ml / min.

With an increase in the level of calcium in the blood plasma to 2 mmol / l or more, the symptoms usually stop. With extreme caution, calcium preparations are administered to patients receiving cardiac glycosides; in this case, intravenous administration is not recommended.

For chronic maintenance therapy of hypoparathyroidism, calcium and vitamin D preparations are used. First, an attempt should be made to prescribe monotherapy with calcium preparations.

In many patients, in this way, it is possible to achieve satisfactory compensation of the disease, while there are no problems with possible complications of vitamin D therapy.

Of the preparations of calcium salts, it is possible to prescribe gluconate, citrate, lactate, chloride and carbonate. When determining the dose of the drug, the content of elemental calcium in a particular salt is of fundamental importance. Thus, 1 g of elemental calcium is contained in 2,5 g of calcium carbonate, 5 g of calcium citrate, 4 g of calcium chloride and 11 g of calcium gluconate.

The usual maintenance dose is 1,0-1,5 g of elemental calcium per day. If it is impossible to compensate for the disease with calcium preparations, vitamin D preparations are additionally prescribed.

The control parameters in the treatment of hypoparathyroidism are the level of calcium in the blood plasma and the level of its excretion in the urine.

Lecture No. 16. Peudohypoparathyroidism and pseudopseudohypoparathyroidism

Pseudohypoparathyroidism (Albright's congenital osteodystrophy) is a rare hereditary syndrome characterized by tissue resistance to parathyroid hormone, hypocalcemia, increased parathyroid function, short stature, and skeletal anomalies (shortening of the metacarpal and metatarsal bones).

Pseudohypoparathyroidism is the first endocrine disease, on the example of which the possibility of the existence of the phenomenon of violation of tissue sensitivity to the hormone (endogenous and exogenously administered) with an unchanged mechanism of its secretion and a normal plasma level has been proved.

Pathogenetically allocate pseudohyperparathyroidism I (Ia, Ib, Ic) and II types. The type of inheritance of pseudohypoparathyroidism has not yet been elucidated. Individuals with Albright osteodystrophy have a deletion of the terminal portion of the long arm of chromosome II. The female to male ratio is 2:1.

In pseudohypoparathyroidism type Ia, a 50% decrease in the activity of the Gs-subunit of the adenylate cyclase-receptor parathyroid hormone complexes was found. This defect is characteristic not only for renal parathyroid hormone receptors, but also for receptors of other hormones, which explains the combination of type I pseudohypoparathyroidism with resistance to other protein hormones (nephrogenic diabetes insipidus, hypoglycemic syndrome).

Type Ia pseudohypoparathyroidism is characterized by phenotypic features, referred to as Albright's osteodystrophy: a moon-shaped face, short stature, obesity, shortening of the IV and V metatarsal and metacarpal bones, heterotopic subcutaneous calcifications and exostoses. Mental retardation is often noted.

In pseudohypoparathyroidism type Ib, normal activity of the Gs subunit is determined. The development of pseudohypoparathyroidism is associated with a defect in the parathyroid hormone receptor itself. In pseudohypoparathyroidism type Ic, the activity of the Gs subunit is also normal, and the defect is most likely localized at the level of the catalytic subunit of adenylate cyclase.

In type II pseudohypoparathyroidism, the complex of parathyroid hormone receptors - adenylate cyclase functions normally, but there is a violation of the cAMP-dependent cellular response to the administration of parathyroid hormone. With exogenous administration of parathyroid hormone, an adequate increase in urinary excretion of cAMP is found, but there is no increase in phosphate excretion.

Pseudopseudohypoparathyroidism is a phenocopy of pseudohypoparathyroidism without its biochemical markers. Patients have typical changes in the phenotype (Albright osteodystrophy), characteristic of pseudohypoparathyroidism Ia, despite a normal level of calcium in the blood and a normal cAMP response to the administration of parathyroid hormone (PG).

The diagnosis of pseudohypoparathyroidism is based on the identification of a positive family history and the detection of malformations characteristic of type 1a pseudohypoparathyroidism in combination with biochemical signs of hypoparathyroidism (hypocalcemia, hyperphosphatemia). In all types of pseudohypoparathyroidism, except for Ia and Ic, there are no characteristic phenotypic changes (Albright's osteodystrophy).

In most cases, patients with pseudohypoparathyroidism have an elevated level of intact parathyroid hormone, which makes it possible to differentiate pseudohypoparathyroidism from hypoparathyroidism. A test with parathyroid hormone and the determination of cAMP and phosphate excretion helps to differentiate the types of pseudohypoparathyroidism.

Treatment of all types of pseudohypoparathyroidism involves the appointment of vitamin D supplements in combination with calcium supplements.

Lecture number 17. Osteoporosis

Osteoporosis is a systemic skeletal disease characterized by a decrease in bone mass per unit volume and a disorder in the microarchitectonics of bone tissue, leading to an increase in bone fragility and a high risk of fractures.

This definition is currently generally accepted, although from a clinical standpoint it is obvious that osteoporosis in most cases is secondary to a particular disease and, strictly speaking, is a syndrome.

Along with the term "osteoporosis", when assessing skeletal diseases, the term "osteopenia" is used, which has a double meaning. Since it is used to refer to the concept of "decrease in bone mineral density."

According to WHO data, osteoporosis as a cause of disability and death of patients from bone fractures ranks 4th among non-communicable diseases, second only to diseases of the cardiovascular system, oncological pathology and diabetes mellitus. This is due to the wide prevalence of osteoporosis, its multifactorial nature, late diagnosis and untimely initiation of treatment.

Osteoporosis is one of the most well-known metabolic diseases of the skeleton, the density of which increases with age. Every third woman after the onset of menopause and more than half of all persons aged 75-80 years have osteoporosis, the consequences of which are fractures of the vertebral bodies and tubular bones, which determines a significant increase in morbidity, disability and mortality among the elderly. About 20% of patients with hip fractures die within 6 months after the fracture, and of the remaining 50% become disabled. The incidence of hip fractures is one indicator of the prevalence of osteoporosis.

Most forms of osteoporosis should be considered symptomatic in a variety of diseases. Thus, the ICD-10 distinguishes between osteoporosis with abnormal bone fractures and without abnormal fractures.

According to morphological features, trabecular, cortical and mixed osteoporosis is distinguished, according to metabolic activity - osteoporosis with increased bone metabolism, with a low degree of bone tissue metabolism and with normal indicators of bone metabolism. The rate of bone loss can depend on many factors. With any pathophysiological mechanism, the bone mass will decrease, reaching a certain threshold value, after which the stage of fractures begins.

In osteoporosis with high bone turnover, high bone resorption is not compensated by normal or increased bone formation, and in osteoporosis with low bone turnover, the rate of bone resorption is normal or reduced, and the rate of bone formation is slow. Both forms can be detected as different stages of the osteoporotic process in one patient.

In the pathogenesis of postmenopausal osteoporosis, the triggering factor is estrogen deficiency, which sharply accelerates bone loss. The presence of estrogen receptors on osteoblasts has been proven, and estrogen deficiency contributes to the production by osteoblasts of a factor that stimulates both differentiation and activity of osteoclasts, which leads to increased bone resorption. The lack of estrogen contributes to a decrease in the release of calcitonin and an increased sensitivity of the bone to the resorptive effect of parathyroid hormone, as well as a secondary vitamin D deficiency and a decrease in calcium absorption in the intestine.

In the pathogenesis of senile osteoporosis, along with a deficiency of sex steroids and calcitonin, a negative calcium balance due to vitamin D deficiency and reduced absorption of calcium in the intestine are of great importance, which results in the formation of recurrent hyperparathyroidism and increased bone resorption. Violation of vitamin D metabolism is explained both by a decrease in insolation due to a decrease in outdoor exposure, and by a violation of the formation of active forms due to a deficiency of sex hormones. Excessive or insufficient secretion of more hormones at any age leads to osteoporosis. Examples of a sharp predominance of bone tissue resorption are the bone form of primary hyperparathyroidism and the pathology of bone metabolism in severe recurrent thyrotoxicosis.

An excess of glucocorticoids in Cushing's syndrome inhibits bone formation, while calcium absorption in the intestine decreases and its excretion by the kidneys increases, which creates a negative calcium balance, leads to secondary hyperparathyroidism and increased bone resorption.

The mechanism of development of osteoporosis in hypogonadism in women in the reproductive period is similar to that in postmenopausal women. A decrease in androgenic function in men leads to reduced bone formation and the formation of osteoporosis with low bone turnover.

Characteristic fractures for osteoporosis can be fractures of the proximal femur, vertebral bodies, and distal forearm bones, although fractures of any location can be observed. Vertebral fractures are one of the classic signs of osteoporosis, and their consequences in the form of back pain, dysfunction, and spinal deformities determine the level of disability and the public health significance of this issue.

The prevalence of these fractures in Russia was 11,8%. In almost 50% of cases, osteoporosis is asymptomatic or oligosymptomatic and is detected only in the presence of bone fractures. Postmenopausal, steroid and hypogonadal osteoporosis is characterized by predominant loss of trabecular bone tissue and, accordingly, fractures of the vertebral bodies, ribs and fractures of the radius in a typical location (type I osteoporosis).

The predominant lesion of the cortical bone tissue is inherent in senile osteoporosis, hyperparathyroidism and thyrotoxicosis (type II osteoporosis), while fractures of tubular bones and the femoral neck are more common; but frequent (especially in older age groups) and fractures of the vertebral bodies. Typical complaints of back pain, aggravated after physical exertion, with a long stay in one position. These pains disappear after lying down. The severity of the pain syndrome can be different not only in different patients, but also in the same patient at different stages of the disease.

During the examination, attention should be paid to the transformation of the patient's posture, deformity of the chest, decrease in height, the formation of skin folds on the lateral surface of the chest, and gait disturbances.

Diagnosis of osteoporosis involves the following tasks:

1) detection of osteopenia and bone fractures;

2) assessment of the level of metabolism in bone tissue (study of biochemical or morphological markers of bone resorption and bone formation, as well as indicators of calcium metabolism);

3) finding out the causes of osteopenia and differential diagnosis with other forms of metabolic osteopathy. Primary osteoporosis is primarily differentiated from osteomalacia, the bone form of primary hyperparathyroidism, the osteoporotic form of Paget's disease, myeloma, and bone metastases. The diagnosis of primary osteoporosis is made after the exclusion of the listed diseases.

The main objectives of the treatment of osteoporosis:

1) slowing down or stopping the loss of bone mass (ideally, its growth);

2) prevention of new bone fractures;

3) normalization of bone remodeling;

4) reduction of pain syndrome, expansion of motor activity;

5) improving the patient's quality of life.

Normalization of bone remodeling (suppression of increased bone resorption or stimulation of bone formation) is the mainstay of treatment. Treatment of the underlying disease in secondary osteoporosis or the abolition of drugs that adversely affect bone metabolism are often difficult to practice. Symptomatic therapy is an essential part of the treatment.

Drugs for the treatment of osteoporosis are conventionally divided into 3 groups:

1) predominantly reducing bone resorption (estrogens, calcitonins, bisphosphonates);

2) predominantly enhancing bone formation (fluorides, anabolic steroids, androgens, fragments of synthetic parathyroid hormone, growth hormone);

3) affecting both processes of bone remodeling (active metabolites of vitamin D, ossein hydroxyapatite complex, ipriflavon (osteochin)).

The choice of a specific drug is determined both by the form of osteoporosis and by the prevailing clinical symptoms. In addition, indications and contraindications for a particular type of therapy are taken into account.

In postmenopausal osteoporosis, as well as in osteoporosis of another genesis, postmenopausal women, in the absence of contraindications, are prescribed estrogen replacement therapy (proginova, cycloproginova, klimen, climonorm, livial, kliogest, etc.).

Treatment with calcitonin (miacalcic) is indicated for postmenopausal, steroid, senile and idiopathic osteoporosis, especially with severe pain. The duration of intermittent treatment with calcitonin can be 2-5 years. It is desirable to combine treatment with calcium preparations, as well as vitamin D.

Bisphosphonates (xydifon, alendronate) are indicated in the treatment of postmenopausal and senile osteoporosis in individuals without severe disorders of the gastrointestinal tract.

The indication for the use of fluorides (sodium fluoride, ossin, coreberon) is osteoporosis with a low level of bone metabolism. To prevent the development of osteomalacia (demineralization), calcium and vitamin D preparations are added during treatment with fluorides. When using fluorides, the frequency of side effects is relatively high (20-30%) in the form of dyspeptic phenomena, glossitis and gingivitis, arthralgia. The slow development of the therapeutic effect of fluorides requires patience from the patient and the doctor.

Anabolic steroids have no independent value in the treatment of osteoporosis, although they are often included in complex treatment regimens.

The active metabolites of vitamin D have been used at a dose of 0,5-1,0 mcg per day for several years. As monotherapy, they are indicated for senile, steroid and postmenopausal osteoporosis; are the drugs of choice for osteomalacia (1-3 mcg / day), renal osteodystrophy, rehabilitation after parathyrectomy. Active metabolites are also used in combination therapy with estrogens, calcitonin, bisphosphonates, ipriflavon, fluorides.

Side effects occur in 2-3% of cases and manifest as dyspeptic disorders, weakness, drowsiness, dry mouth. To prevent hypercalcemia, it is desirable to carry out treatment in individually selected doses with control of the level of calcium and creatinine in the blood once every 1 months.

Ipriflavon (osteochin) - a derivative of flavonoids synthesized in ferns and flowering plants, enhances bone formation, reduces the incidence of new bone fractures and has a moderate analgesic effect for 12 months of use.

Calcium salts have no independent value in the treatment of osteoporosis, but must be used in combination with other agents as the basis of pathogenetic therapy, as well as for the primary prevention of osteoporosis.

Symptomatic therapy involves analgesia, the appointment of corsets, physical therapy. Back pain reduces the patient's motor activity and quality of life.

To reduce pain, along with pathogenetic agents, analgesics, non-steroidal anti-inflammatory drugs, and muscle relaxants are used.

Corsets are absolutely indicated in the presence of compression fractures of the vertebral bodies and in severe osteoporosis. Semi-rigid corsets and semi-corsets are most often recommended. The possibility of muscle atrophy when wearing corsets is small and is not confirmed in the works of recent years. With a pronounced pain syndrome, only breathing exercises are recommended, with a decrease in pain - isometric exercises.

In the future, exercises are prescribed for the muscles of the abdomen, back, lower and upper limbs. Then they add exercises carried out in a standing position, dosed walking, swimming. Massage is prescribed no earlier than 4-6 months after the start of drug therapy.

Primary prevention of osteoporosis includes control of sufficient calcium intake in childhood, during pregnancy and lactation, sufficient sun exposure of the elderly, an active lifestyle and physical education with moderate physical activity, avoiding alcohol and smoking abuse, avoiding various unbalanced diets and starvation.

Lecture No. 18. Hypothalamo-pituitary diseases. Craniopharyngioma

Hypothalamic-pituitary diseases can be subdivided into diseases with a proven lesion of the hypothalamus proper, diseases with presumed hypothalamic origin, with hypothalamic-pituitary origin, and pituitary lesions proper.

1. Craniopharyngioma

Craniopharyngioma is a hypothalamic tumor originating from the remnants of Rathke's pouch (epithelial protrusion of the posterior pharyngeal wall of the embryo, which is the rudiment of the adenohypophysis), leading to pituitary disorders.

Tumor development is associated with impaired embryonic differentiation of Rathke's pouch cells. The tumor can be localized in the hypothalamus, third ventricle, sella turcica and often has a cystic structure. Craniopharyngioma is a rare disease, but the most common suprasellar tumor in children (5 - 10% of brain tumors in children).

Craniopharyngiomas are hormonally inactive tumors, the clinical manifestations of which are based on mechanical compression of the surrounding structures of the brain.

In most cases, craniopharyngioma manifests itself in childhood and adolescence. As a rule, there is a combination of symptoms of intracranial hypertension (headache, nausea, vomiting), chiasmatic syndrome (bitemporal hemianopsia, papilledema, decreased visual acuity) and endocrine-metabolic syndrome (delayed sexual and physical development, hypopituitarism). The development of cerebral edema or panhypopituitary coma is an indication for emergency hospitalization.

When hormonal research is determined by the deficiency of tropic hormones of the pituitary gland, hyperprolactinemia is possible. X-ray in 80% of cases, calcifications are detected in the tumor. The method of imaging diagnostics of craniopharyngioma is an MRI study.

Craniopharyngiomas must be differentiated from other diseases that occur with delayed sexual and physical development and hypopituitarism, as well as other tumors of the pituitary gland and brain.

Surgical treatment is indicated: removal of the tumor, possibly in combination with proton therapy and stereotactic injection of radioisotopes into the tumor. With incomplete removal, craniopharyngioma has a tendency to relapse. Restoration of childbearing function after removal of craniopharyngioma with the help of modern methods of treatment is fundamentally possible. The prognosis for life with craniopharyngioma is quite serious, since surgical treatment does not eliminate metabolic and endocrine disorders, the patient's ability to work always remains limited. With developed hypopituitarism, replacement therapy is carried out for life.

2. Other hypothalamic-pituitary diseases

Among the tumors of the hypothalamic region, in addition to craniopharyngioma, there are gliomas, hemangiomas, dysgerminomas, hamartomas, ganglioneurinomas, ependymomas, medulloblastomas, lipomas, neuroblastomas, lymphomas, plasmacytomas, colloid and dermoid cysts, sarcomas.

Depending on the localization of the lesion, neurological symptoms of varying severity, impaired pituitary functions, and behavioral changes are noted. In rare cases, especially in childhood, hypothalamic lesions can lead not only to a decrease, but also to activation of adenohypophyseal functions (for example, the appearance of hyperprolactinemia due to the “removal” of the inhibitory effect of dopamine on prolactin secretion or premature puberty due to loss of normal refractoriness to influence of gonadotropins).

The clinical manifestations of these lesions will depend on the age at which the tumor manifested, its location and size. The most striking clinical manifestations are hypogonadism or premature puberty (more than 50% of cases), diabetes insipidus (up to 30% of cases), mental disorders (one third of all cases), in about a third of patients - obesity or hyperphagia, in 20% of patients as the main Symptoms include somnolescence, anorexia, exhaustion, impaired thermoregulation, and, finally, sphincter activity is impaired in 10%. Approaches to the diagnosis and treatment of these tumors are similar to those for craniopharyngioma.

Tumor processes in the hypothalamic-pituitary region often have to be differentiated from systemic and genetic lesions.

Involvement in the pathological process of the hypothalamus is possible with a disseminated specific or nonspecific infectious process, as well as with the dissemination of systemic diseases.

As a rule, a clear clinical picture of hypopituitarism with a loss of one or another function or with the development of hyperprolactinemia is formulated more likely in a chronic disseminated process, while in acute bacterial damage, general systemic signs (intoxication, disorders of the central nervous system) come first, and hypothalamic disorders are more often manifested by the syndrome of inadequate production of vasopressin.

The likelihood of developing a particular lesion depends largely on age. In newborns, the hypothalamus may suffer from perinatal hemorrhage or bacterial meningitis, histiocytosis may develop at the age of several months, tuberculous meningitis may develop in older children, there may be leukemic infiltrates, as well as encephalitis. From the age of 10, the likelihood of developing sarcoidosis increases. These lesions are also possible in adulthood.

Many diseases of the hypothalamus, as well as any other pathological processes in the suprasellar region, can lead to compression of the pituitary stalk with the development of isolated pituitary syndrome. Damage to the pituitary stalk is accompanied by a characteristic change in the secretion of pituitary hormones. Diabetes insipidus develops in 80% of patients, and the most important factor in its development is the height of the damage to the pedicle: the closer the level of damage to the hypothalamus, the more likely it is to develop diabetes insipidus.

With isolated pituitary syndrome, the secretion of all tropic pituitary hormones stops with the development of secondary hypogonadism, hypothyroidism, hypocorticism, and growth hormone deficiency. The pathognomonic phenomenon for isolated pituitary syndrome is hyperprolactinemia.

Treatment of patients with this syndrome includes removal of the detected tumor, replacement therapy for diabetes insipidus and panhypopituitarism.

Lecture number 19. Acromegaly and gigantism

Acromegaly and gigantism are neuroendocrine syndromes resulting from excessive production or increased biological activity of growth hormone.

These two diseases should be considered as age-related variations of the same pathological process, the specific clinical manifestations of which are determined by the degree of completion of osteogenesis.

In children and adolescents with incomplete growth, chronic overproduction of growth hormone is manifested by gigantism, characterized by excessive, exceeding physiological boundaries, relatively proportional epiphyseal and periosteal bone growth, an increase in soft tissues and organs.

In adults, since further growth is impossible after ossification of the epiphyseal cartilages, acromegaly develops. With this pathology, accelerated growth of the body is noted, but not in length, but in width due to soft tissues, which is manifested by disproportionate periosteal growth of the bones of the skeleton, an increase in the mass of internal organs and a characteristic metabolic disorder.

Based on the classical scheme of hypothalamic-pituitary regulation of somatotropic function, a number of possible mechanisms can be identified that contribute to its hyperfunction and characteristic clinical manifestations:

1) the initial dysregulation at the level of the hypothalamus or the overlying parts of the central nervous system, which is realized in the excessive formation of somatoliberin or insufficient secretion of somatostatin;

2) the primary occurrence of a tumor process in the pituitary gland with impaired hypothalamic control and autonomous hypersecretion of growth hormone or its active forms;

3) an increase in the formation and activity of somatomedins, which directly affect the growth of the osteoarticular apparatus. The most common cause of acromegaly and gigantism is the autonomous production of growth hormone by a pituitary adenoma.

In most cases, acromegaly reveals a macroadenoma. By their origin, somatotropinomas (tumors from somatotrophs of the adenohypophysis) are monoclonal tumors that develop as a result of somatic mutation of somatotrophs.

In acromegaly, pituitary adenomas that secrete growth hormone are detected in 99% of cases. Immunohistochemically, in addition to pure somatotropic adenomas (about 45%), mixed prolactosomotropinomas (about 30%) are isolated. The remaining 25% of adenomas also produce other adenohypophyseal hormones (TSH, LH, FSH).

Ectopic production of growth hormone with the development of acromegaly is rare in lung, breast, pancreatic, and ovarian cancers.

Changes in organs in acromegaly are reduced to their true hypertrophy and hyperplasia (splanchnomegaly), which is associated with the predominant growth of mesenchymal tissues. The parenchyma and stroma of all internal organs (lungs, heart, liver, pancreas, intestines, spleen) are enlarged. With the progression of the disease due to the proliferation of connective tissue in all organs, sclerotic changes occur, accompanied by the progressive development of their insufficiency. In parallel, there is an increase in the risk of benign and malignant neoplasms in all tissues and organs, including endocrine ones.

In most cases, acromegaly develops between the ages of 30 and 50, it is more common in women, since both pregnancy itself and its non-physiological interruption are factors that activate somatotropic function. The vast majority of cases of gigantism and acromegaly are sporadic. Acromegaly occurs with a frequency of 3-4 cases per 1 million population.

Clinically, acromegaly is manifested by an increase in hands, feet, changes in appearance, disorders of carbohydrate metabolism, menstrual cycle and other symptoms.

Intracranial hypertension syndrome: an increase in intracranial pressure or compression of the sella turcica diaphragm by a growing tumor causes the development of headaches in acromegaly. In the latter case, the headaches are the most persistent, driving the patient into a frenzy.

Syndromes associated with the action of excess growth hormone on organs and tissues are manifested by a progressive pathological increase in linear growth and body size, hands, feet, nose, lower jaw, which is why patients are often forced to change shoes and gloves. A change in appearance, manifested by coarsening of facial features, is associated with an increase in the superciliary arches, zygomatic bones, and lower jaw. There is hypertrophy of the soft tissues of the face (nose, lips, ears).

An increase in the lower jaw leads to a change in bite due to the divergence of the interdental spaces. The tongue is enlarged (macroglossia), and teeth marks are visible on it.

An increase in the number and increase in the functional activity of the sweat glands lead to significant sweating. Activation and hypertrophy of the sebaceous glands, thickening of the skin leads to its characteristic appearance (it becomes dense, thickened, with deep folds, more pronounced on the scalp). In the area of ​​skin folds and places of increased friction, hyperpigmentation is noted. Often revealed hypertrichosis.

The effect of growth hormone on muscles and internal organs at the initial stages of the disease is hardly noticeable, and sometimes, especially among athletes and people of physical labor, it is perceived positively, since working capacity and physical activity increase, but as the disease progresses, muscle fibers degenerate (due to the proliferation of connective tissue and the relative lag in the growth of blood vessels from the increase in mass), causing increasing weakness, a progressive decrease in performance.

Due to impaired blood supply and sclerosis of hypertrophied internal organs, pulmonary and heart failure develops, which is the cause of death of patients.

Sleep apnea syndrome develops in 80% of patients with acromegaly. This is due to the proliferation of soft tissues of the upper respiratory tract and damage to the respiratory centers. Uncompensated long-term hyperproduction of growth hormone leads to the development of concentric myocardial hypertrophy, which is replaced by hypertrophic myocardial dystrophy, and in advanced cases of the disease it turns into dilated, which leads to progressive heart failure.

The syndrome of reproductive disorders, associated with concomitant hyperproduction of prolactin or with prolacto-like effects of growth hormone, is manifested by menstrual disorders up to amenorrhea, as well as often galactorrhea in women, impotence in men.

The syndrome of endocrine disorders associated with the influence of growth hormone on various types of metabolism, as well as with a change in the activity of other endocrine glands, is manifested by a violation of glucose tolerance and obvious diabetes mellitus, a change in phosphorus-calcium metabolism, a violation of fat metabolism, an increase in the thyroid gland is detected. As the tumor growth progresses, a clinical picture of hypothalamic-pituitary insufficiency develops, including the formation of secondary hypothyroidism, hypocorticism, and hypogonadism.

Syndrome of dysfunction of cranial nerves: chiasmal syndrome (bitemporal hemianopsia, narrowing of the visual fields); changes in the fundus include edema and atrophy of the optic disc; compression of the hypothalamus and impaired liquorodynamics lead to the appearance of drowsiness, sometimes to polyuria, there may be temperature rises, epileptiform syndrome, anosmia, ptosis, doubling, decreased sensitivity of the skin of the face, hearing loss.

The laboratory diagnosis of acromegaly is based on the study of the level of growth hormone. In many patients, it is sharply increased, and in this case, with a detailed clinical picture, the diagnosis can be considered established. However, in a number of patients, the level of growth hormone is only slightly elevated or corresponds to normal (0,5-5,0 ng/ml). In this regard, a number of functional trials have been proposed. The glucose tolerance test involves the study of the plasma level of growth hormone initially, as well as in blood samples every 30 minutes for 2,5 to 3 hours after the administration of 75 g of glucose. Normally, with a load of glucose, the level of growth hormone decreases. In the active phase of acromegaly, the level of growth hormone does not decrease below 2 ng / ml, or a paradoxical increase in the level of growth hormone is detected. In 60% of cases with acromegaly, 30-60 minutes after the administration of thyroliberin (500 μg intravenously), a pathological increase in the level of growth hormone is determined (by 50-100% of the initial level or more). Normally, there is no reaction to thyroliberin.

With clinically manifest and hormonally confirmed acromegaly, topical diagnosis of pituitary adenoma, as a rule, does not present any difficulties. With macroadenoma, characteristic changes are revealed on the craniogram; the method of choice for visualization of the adenoma is an MRI study.

The goal of the treatment of acromegaly is the elimination of autonomic hyperproduction of growth hormone, the normalization of the level of IGF-1 in the blood and the absence of an increase in the plasma level of growth hormone in the glucose tolerance test (75 g glucose) above 1 ng / ml. These criteria correspond to the remission of the disease. This goal is achieved by removal of the pituitary tumor or reduction of the tumor mass.

The method of choice in the treatment of patients with acromegaly is transsphenoidal removal of the pituitary adenoma. With microadenomas, in 85% of cases, the level of growth hormone after surgery returns to normal. In the case of small encapsulated adenomas, surgical treatment, as a rule, leads to a stable remission of the disease. With macroadenomas, complete recovery after the first operation is achieved in 30% of cases. Tumors with extrasellar growth have the worst prognosis. With the help of proton therapy on the pituitary gland in most patients, it is possible to achieve a decrease in the level of growth hormone 1 year after the course of treatment. Nevertheless, 10 years after proton therapy, in 70% of patients, the spontaneous level of growth hormone on average does not exceed 10 ng/ml.

For drug therapy that can only be considered temporary or palliative, dopaminomimetics and somatostatin analogues are currently used.

When treated with dopaminomimetics (bromocriptium, parlodel), 54% of patients experience a decrease in growth hormone levels below 10 ng / ml, and only 20% - below 5 ng / ml. A decrease in tumor size is observed in no more than 20% of patients. Treatment with long-acting somatostatin analogues (octreotide, sandostatin) is much more effective. In 90% of patients, a decrease in the level of GH is determined, in 53% of patients the level of GH decreases below 5 ng / ml. There is evidence of a higher percentage of radical adenomectomy if the operation was preceded by treatment with octreotide.

Lecture No. 20. Panhypopituitarism

Hypothalamic-pituitary insufficiency (panhypopituitarism) is a clinical syndrome that develops as a result of destruction of the adenohypophysis, followed by a persistent decrease in the production of tropic hormones and impaired activity of the peripheral endocrine glands.

One of the forms of hypothalamic-pituitary insufficiency is Simmonds disease, which refers to postpartum septic-embolic necrosis of hypertension, leading to severe cachexia and involution of organs and tissues. Sheehan's disease is the most common and more benign current variant of postpartum panhypopituitarism.

Etiology. The most common cause of hypopituitarism is circulatory disorders in the hypothalamic-pituitary region (hemorrhage, ischemia) that develop after childbirth, complicated by massive (more than 1 l) blood loss, thromboembolism, sepsis.

Hypertrophy of the anterior pituitary gland during pregnancy, which is replaced by its involution after childbirth, contributes to the fact that all of these complications lead to circulatory disorders in the pituitary gland, angiospasms, hypoxia and necrosis.

Repeated and frequent pregnancies and childbirth as factors of functional stress of the pituitary gland predispose to the development of hypopituitarism. Ischemic changes in the pituitary gland, although rare, can occur in men after gastrointestinal, nosebleeds. In recent years, hypothalamic-pituitary insufficiency in women with severe toxicosis in the second half of pregnancy in some cases is associated with the development of an autoimmune process in the pituitary gland - lymphocytic hypophysitis.

More rare causes of panhypopituitarism are tumors of the hypothalamic-pituitary region, tumor metastases in the hypothalamic-pituitary region, trauma (severe head injury with detachment of the pituitary stalk, radiation and surgical interventions on the pituitary gland), granulomatous processes (sarcoidosis, eosinophilic granuloma, syphilis).

The pathogenesis of panhypopituitarism is based on the deficiency of tropic hormones and growth hormone. Depending on the location, extent and intensity of the destructive process, the loss or decrease in hormone formation in the pituitary gland can be uniform and complete (panhypopituitarism) or partial, in which the production of one or more hormones is preserved.

Although necrotic processes in the pituitary gland were noted in 1,1-8,8% of all autopsies, partial hormonal deficiency develops when 60-70% of the anterior lobe is affected, and panhypopituitarism occurs when 90% or more are affected. Which leads to the development of secondary hypofunction of the adrenal glands, as well as the thyroid and gonads.

More rarely, with simultaneous involvement in the pathological process of the posterior lobe or pituitary stalk, a decrease in the level of vasopressin with the development of diabetes insipidus is possible.

A decrease in the production of growth hormone with its universal effect on protein synthesis leads to progressive atrophy of smooth and skeletal muscles and internal organs (splanchnomycria). Pronounced weight loss occurs in approximately 25% of patients. Loss of prolactin production leads to agalactia. With partial hypopituitarism, gonadotropic and somatotropic functions most often suffer, and the production of ACTH and TSH is much less frequently disturbed.

Manifestations of panhypopituitarism are determined by the rate of development and volume (preservation of separate triple functions) of destruction of the adenohypophysis.

The disease occurs much more often (65%) in young and middle-aged women (20-40 years old), but cases of the disease are known both in the elderly and at an earlier age. The development of Shien's syndrome in a 12-year-old girl after juvenile uterine bleeding is described. In most cases, the disease develops slowly over several years.

More often, somatotropic and gonadotropic activity are the first to decrease, then thyrotropic and adrenocorticotropic functions. Sometimes the clinical picture is dominated by an increasing loss of body weight, averaging 2-6 kg per month, in severe cases reaching 25-30 kg. Depletion is usually uniform, muscles atrophy, internal organs decrease in volume.

Changes in the skin are characteristic: thinning and dryness give the skin the appearance of tissue paper, wrinkling, peeling are noted in combination with a pale icteric, waxy color. Hair in the armpits and on the pubis disappears. The general appearance of patients is rather peculiar. Sometimes, against the background of general pallor, areas of dirty earthy pigmentation appear on the face and in the natural folds of the skin, acrocyanosis. As a result of a decrease in melanin synthesis, the nipples and skin in the perineum are depigmented.

Sweating and secretion of the sebaceous glands are weakened. Fragility and hair loss, their early graying, decalcification of bones develop, the lower jaw atrophies, teeth are destroyed and fall out. The phenomena of insanity and senile involution are rapidly growing.

Characterized by the sharpest general weakness, apathy, adynamia up to complete immobility, hypothermia, orthostatic collapse and coma, which, without specific therapy, lead to the death of the patient.

A decrease in the production of thyroid-stimulating hormone leads to the rapid or gradual development of hypothyroidism. Chilliness, drowsiness, lethargy, adynamia occur, mental and physical activity decreases. The number of heartbeats decreases, heart sounds become muffled, blood pressure decreases. Atony of the gastrointestinal tract and constipation develop.

Fluid retention, characteristic of hypothyroidism, manifests itself in different ways in patients with hypopituitarism. With severe depletion, there is usually no edema, and in patients with a predominance of symptoms of hypogonadism and hypothyroidism in the absence of ACTH deficiency, there is usually no large loss of body weight.

One of the leading places in the clinical symptoms is occupied by disorders of the sexual sphere, caused by a decrease or complete loss of the gonadotropic regulation of the sex glands. Sexual dysfunction often precedes the appearance of all other symptoms. Sexual desire is lost, potency decreases. The external and internal genital organs gradually atrophy. There are no signs of estrogenic activity in vaginal swabs. In women, menstruation stops, the mammary glands decrease in volume. With the development of the disease after childbirth, agalactia and amenorrhea are characteristic (menstruation does not resume). In rare cases of a protracted and erased course of the disease, the menstrual cycle, although disturbed, persists and even pregnancy is possible. In men, secondary sexual characteristics disappear (pubic, axillary hair, mustache, beard), testicles, prostate gland, seminal vesicles, penis atrophy. As a result of tubular and interstitial insufficiency of the testicles, oligoazoospermia occurs and testosterone levels decrease.

Acute pituitary insufficiency (pituitary coma) is a combination of acute adrenal insufficiency and hypothyroid coma.

In typical cases, the diagnosis of panhypopituitarism is not difficult. The appearance after a complicated birth or in connection with another cause of a complex of symptoms of insufficiency of the adrenal cortex, thyroid and gonads testifies in favor of hypothalamic-pituitary insufficiency. In severe forms (with Simmonds' disease), weight loss, atrophy of muscles, skin, subcutaneous tissue, hair loss, hypothermia, hypotension, osteoporosis, apathy, mental insanity dominate.

In Shien's disease, the clinical picture develops gradually, in some cases reaching a manifest stage many years after childbirth, manifesting itself as a loss of not all, but individual adenohypophyseal functions.

In a typical case, the "7 A" syndrome is detected (amenorrhea, agalactia, loss of axillary hair growth, depigmentation of the areola, pallor and hypotrophy of the skin, apathy, adynamia).

In patients with indolent disease, the diagnosis is made late, although the absence of lactation after delivery complicated by hemorrhage, prolonged disability and menstrual dysfunction should be suggestive of hypopituitarism.

Frequent laboratory findings in hypopituitarism are hypochromic and normochromic anemia, especially with severe hypothyroidism, sometimes leukopenia with eosinophilia and lymphocytosis. The blood glucose level is low, the glycemic curve with glucose loading is flattened. The content of cholesterol in the blood is increased.

When hormonal research is determined by a combination of low levels of hormones of peripheral endocrine glands (T₄, testosterone, estradiol, daily urinary excretion of free cortisol) with reduced or low levels of tropic hormones and growth hormone.

To clarify the reserves of pituitary hormones, stimulating tests with releasing hormones (thyroliberin, gonadotropin-releasing hormone) are indicated. With secondary (unlike primary) hypocorticism (Addison's disease), there is no loss of mineralocorticoid secretion, since the secretion of the latter is regulated mainly independently of the influences of ACTH. However, with a long-term deficiency of ACTH, which, in addition to secretory, has a trophic effect on the adrenal cortex, in addition to the fascicular and reticular zones, the glomerular zone of the adrenal cortex may also undergo atrophy, which will correspond to a decrease in the plasma level of aldosterone and an increase in renin activity in blood plasma. For the diagnosis of secondary hypocorticism, a test with ACTH is used in combination with determining the level of ACTH in plasma, as well as tests with metyrapone and with insulin hypoglycemia.

In panhypopituitarism, treatment should be aimed at compensating for hormonal deficiency and, if possible, at eliminating the cause of the disease. A tumor or cyst that causes destructive processes in the pituitary gland or hypothalamus is subject to radical treatment (surgical, radiation).

Hormone replacement therapy begins with compensation for secondary hypocorticism with corticosteroid preparations. The appointment of thyroid hormones before compensation of hypocorticism can lead to the development of acute adrenal insufficiency. Insufficiency of the gonads is compensated with the help of estrogens and progestins in women, androgenic drugs in men.

After preliminary treatment with sex hormones and reduction of atrophic processes in the genital organs, if it is desirable to restore fertility, gonadotropins are prescribed.

Thyroid insufficiency is eliminated by preparations of thyroid hormones. Treatment begins with L-thyroxine at a daily dose of 12,5 - 25 mcg, followed by an increase. In connection with the violation of somatotropic function, patients with hypothalamic-pituitary insufficiency are shown the appointment of growth hormone. Treatment for hypopituitary coma is similar to that for acute adrenal insufficiency.

Lecture number 21. Somatotropic insufficiency

Somatotropic insufficiency (lack of growth hormone) occurs in a large number of diseases and syndromes. According to etiology, congenital and acquired, as well as organic and idiopathic growth hormone deficiency are distinguished.

In the most common form, somatotropic insufficiency is manifested by the syndrome of dwarfism. Nanism is a clinical syndrome characterized by a sharp lag in growth and physical development, associated with an absolute or relative deficiency of growth hormone.

In most patients, there is a pathology of regulation and secretion of other pituitary hormones, as a rule, there are violations of the secretion of FSH, LH, TSH, which is accompanied by various combinations of endocrine and metabolic disorders (panhypopituitary nanism).

People of dwarf growth include men with a height below 130 cm, and women - below 120 cm. The smallest described growth of a dwarf was 38 cm.

Most forms of somatotropic insufficiency are genetic, while there is more often a primary pathology of a hypothalamic nature, and anterior pituitary hormone deficiency is a secondary phenomenon.

Genetic forms of dwarfism with an isolated defect in growth hormone due to a deletion of the growth hormone gene and with biological inactivity of growth hormone due to a mutation of this gene have been identified. Nanism due to peripheral tissue insensitivity to growth hormone is associated with a deficiency of somatomedins or a defect in growth hormone receptors.

The causes of pituitary dwarfism can be underdevelopment or aplasia of the pituitary gland, its dystopia, cystic degeneration, atrophy or tumor compression (craniopharyngioma, chromophobe adenoma, meningioma, glioma), trauma to the central nervous system of the intrauterine, birth or postnatal period.

Tumors of the adenohypophysis, hypothalamus, intrasellar cysts, and cranio-pharyngiomas lead to growth hormone deficiency.

In this case, compression of the pituitary tissue occurs with wrinkling, degeneration and involution of glandular cells, including somatotrophs with a decrease in the level of growth hormone secretion.

Infectious and toxic damage to the central nervous system in early childhood is important. Intrauterine lesions of the fetus can lead to "dwarfism from birth", the so-called cerebral primordial dwarfism.

This term combines a group of diseases, which includes Silver's nanism with hemi-asymmetry of the body and a high level of gonadotropins, Russell's congenital nanism.

Severe chronic somatic diseases are often accompanied by severe short stature, such as glomerulonephritis, in which azotemia directly affects the liver cells, reducing the synthesis of somatomedins; cirrhosis of the liver.

Changes in the internal organs during dwarfism are reduced to thinning of the bones, delayed differentiation and ossification of the skeleton.

Internal organs are hypoplastic, muscles and subcutaneous fatty tissue are poorly developed. With isolated deficiency of growth hormone, morphological changes in the pituitary gland are rarely detected.

For a long period of time, absolute or relative deficiency of growth hormone was regarded as a problem exclusively in pediatric endocrinology, and the main goal of substitution therapy was to achieve socially acceptable growth.

Growth hormone deficiency, which first appeared in adulthood, occurs with a frequency of 1: 10. The most common causes of it are pituitary adenomas or other tumors of the sellar region, the consequences of therapeutic measures for these neoplasms (surgeries, radiation therapy).

The main signs of nanism are a sharp lag in growth and physical development. Prenatal growth retardation is typical for children with intrauterine growth retardation with genetic syndromes, chromosomal pathology, hereditary growth hormone deficiency due to deletion of the growth hormone gene.

Children with classical somatotropic insufficiency are born with normal weight and body length and begin to lag behind in development from 2 to 4 years of age. To explain this phenomenon, it is assumed that up to 2-4 years of age, prolactin can give children an effect similar to growth hormone.

A number of works refute these ideas, indicating that some growth retardation is noted already after birth.

For children with an organic genesis of growth hormone deficiency (with craniopharyngioma, traumatic brain injury), later periods of manifestation of growth deficiency are characteristic, after 5-6 years of age.

With idiopathic growth hormone deficiency, a high frequency of perinatal pathology is revealed: asphyxia, respiratory distress syndrome, hypoglycemic conditions.

In a family history of children with constitutional growth retardation and puberty, from which it is necessary to differentiate somatotropic insufficiency, in most cases it is possible to identify similar cases of short stature in one of the parents.

With idiopathic pituitary dwarfism, against the background of growth retardation, normal proportions of the child's body are noted.

In untreated adults, childish body proportions are noted. Facial features are small ("doll face"), the bridge of the nose sinks. The skin is pale, with a yellowish tint, dry, sometimes there is cyanosis, marbling of the skin.

In untreated patients, "old appearance", thinning and wrinkling of the skin (geroderm) appear early, which is associated with a lack of anabolic action of growth hormone and a slow change in cell generations.

The distribution of subcutaneous adipose tissue ranges from malnourished to obese. Secondary hair growth is often absent. The muscular system is poorly developed. Boys usually have a micropenis.

Sexual development is delayed and occurs at the time when the bone age of the child reaches the pubertal level. A significant proportion of children with growth hormone deficiency have concomitant gonadotropin deficiency.

The main methods of clinical diagnosis of growth retardation are anthropometry and comparison of its results with percentile tables.

On the basis of dynamic observation, growth curves are constructed. In children with growth hormone deficiency, the growth rate does not exceed 4 cm per year. To exclude various skeletal dysplasias (achondroplasia, hypochondroplasia), it is advisable to assess the proportions of the body.

When evaluating the radiograph of the hands and wrist joints, the so-called bone age is determined, while the pituitary dwarfism is characterized by a significant delay in ossification. In addition, in some patients, destruction of the most injured areas of the skeleton under static load - the femoral heads - with the development of aseptic osteochondrosis is noted.

When x-raying the skull with pituitary dwarfism, as a rule, unchanged dimensions of the Turkish saddle are revealed, but it often retains the childlike shape of a "standing oval", has a wide ("juvenile") back.

An MRI study of the brain is indicated for any suspicion of intracranial pathology. For the diagnosis of pituitary dwarfism, the leading one is the study of somatotropic function.

A single determination of the level of growth hormone in the blood for the diagnosis of somatotropic insufficiency does not matter due to the episodic nature of growth hormone secretion and the possibility of obtaining low, and in some cases, zero basal values ​​of growth hormone even in healthy children. For a screening study, the determination of urinary excretion of growth hormone is acceptable.

In clinical practice, stimulation tests with insulin, clonidine, arginine, and a number of others are most widely used.

Growth hormone deficiency in adults is accompanied by a violation of all types of metabolism and extensive clinical symptoms. There is an increase in the content of triglycerides, total cholesterol and low density lipoproteins, a decrease in lipolysis.

Obesity develops mainly in the visceral type. Violation of protein synthesis leads to a decrease in the mass and strength of skeletal muscles, myocardial dystrophy with a decrease in cardiac output fraction is noted. There is a violation of glucose tolerance, insulin resistance. Hypoglycemic conditions are not uncommon. One of the most striking manifestations of the disease are changes in the psyche. There is a tendency to depression, anxiety, increased fatigue, poor general health, impaired emotional reactions, a tendency to social isolation.

A decrease in blood fibrinolytic activity, lipid spectrum disorders leading to the development of atherosclerosis, as well as changes in the structure and function of the heart muscle are the causes of a twofold increase in the mortality rate from cardiovascular diseases among patients with panhypopituitarism receiving replacement therapy that does not involve the appointment of growth hormone.

Against the background of somatotropin deficiency, a decrease in bone mass develops due to the acceleration of bone resorption, which leads to an increase in the frequency of fractures. One of the most valuable studies in the diagnosis of somatotropic insufficiency is the determination of the level of IGF-1 and IGF-2, as well as somatomedin-binding protein.

These studies underlie the diagnosis of dwarfism and other conditions related to the group of peripheral resistance to the action of growth hormone. The most informative and simple study is the determination of the plasma level of IGF-1. With its decrease, stimulating tests with insulin, clonidine, arginine, somatoliberin are carried out.

The pathogenetic therapy of pituitary dwarfism is based on replacement therapy with growth hormone preparations. The drug of choice is genetically engineered human growth hormone. The recommended standard dose of growth hormone in the treatment of classical growth hormone deficiency is 0,07 - 0,1 U / kg of body weight per injection daily subcutaneously at 20:00-22:00 h.

A promising direction in the treatment of peripheral resistance to growth hormone is treatment with recombinant IGF-1.

If growth hormone deficiency has developed as part of panhypopituitarism, in addition, replacement therapy for hypothyroidism, hypocorticism, hypogonadism, and diabetes insipidus is prescribed.

For the treatment of somatotropic insufficiency in adults, the recommended doses of genetically engineered human growth hormone range from 0,125 U/kg (initial dose) to 0,25 U/kg (maximum dose).

The optimal maintenance dose is selected individually based on the study of the dynamics of IGF-1. The question of the total duration of growth hormone therapy currently remains open.

Authors: Drozdov A.A., Drozdova M.V.

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