"We eat in order to live." Food is one of the sources of potential energy from the sun, which is converted into driving energy inside the body. vitality. This is why eating behavior plays an important role in our lives. Two interconnected integrative systems—nervous and endocrine—are involved in its provision and regulation. They also “monitor” future fate the food we absorb - for its correct transformation and timely delivery to the final destination - every cell of the body. “Excesses” are sent in reserve - to the fat depot, ready to be mobilized from there at the first request (lack of food and/or high energy expenditure). Excessively overloaded “reservoirs” indicate that there has been a failure in certain behavioral and/or metabolic mechanisms.

The nervous and endocrine systems “speak” different languages, but work together. There is a small organ in our body that perfectly “understands” both and serves as the main intermediary in their work. This is the hypothalamus. On the one hand, it is connected with key centers of nervous regulation - the cerebral cortex, amygdala, hippocampus, cerebellum, brainstem, and spinal cord. On the other hand, it regulates the functioning of the pituitary gland, the central “control panel” of the endocrine system. Control over the intake, processing and “targeted use” of food is also essential without the participation of the hypothalamus. Moreover, both from the “nervous” (feelings of hunger and satiety) and from the humoral (regulation of lipid, carbohydrate metabolism, etc.) mechanisms. It is not without reason that the hypothalamus is involved in disturbances of energy metabolism of any type.

Obesity is always a consequence of the dominance of energy “income” over “expense”. There are many reasons for this disharmony. But no matter which of them the disorders “start” with, over time a pathological cause-and-effect tangle is formed, covering a variety of regulatory mechanisms.

Hypothalamic obesity is a diagnosis when organic and/or functional lesions of the hypothalamus act as the primary trigger. As a result, there is an increase in the mechanisms of appetite stimulation (for example, an increase in the production of neuropeptide Y) and a suppression of the “feedback” system that inhibits it (for example, a decrease in the sensitivity of cells to the “controller” of energy metabolism - the hormone leptin). In addition, a shift in equilibrium also occurs due to a decrease in energy expenditure. Thus, the pathological basis for gaining excess weight is a simultaneous violation of both the flow of energy (food) into the body and its consumption.

The functioning of the hypothalamus can be disrupted by:

• congenital anomalies;
• tumors of the hypothalamus itself and organs associated with it anatomically and/or functionally (for example, hypothalamic hamartoma, craniopharyngioma, meningioma, etc.);
• head injuries and surgical interventions (including due to a persistent increase in intracranial pressure);
• infectious diseases of the central nervous system (for example, encephalitis, meningitis);
• systemic pathologies (for example, sarcoidosis, histiocytosis);
• congenital or acquired anatomical defects (for example, aneurysm).

Signs of hypothalamic obesity

A characteristic feature of this type of obesity is a very rapid rate of weight gain, usually accompanied by a pronounced increase in appetite.

Hypothalamic obesity (HO) is also manifested by multiple changes in most organs and systems. This is explained by the direct and/or indirect participation of the hypothalamus in their work.

GO is accompanied by:

• changes in eating behavior;
• lethargy, drowsiness;
• imbalance of hormones of the reproductive system and disorders of its functioning (infertility, menstrual disorders, decreased potency);
• symptoms of malfunctions of the autonomic nervous system (impaired sweating, increased blood pressure, headache, etc.)
• endocrine disorders (hypothyroidism, type 2 diabetes);
• changes on the skin;
• visual impairment, etc.

Endocrine obesity

Both the creation (lipogenesis) and consumption (lipolysis) of fat reserves are regulated by hormones - active executors of the “will” of the endocrine system. In addition, the secretions of the endocrine glands regulate the course of most energy-consuming processes in the body. Therefore, dysfunction of the endocrine glands (both hyper- and hypofunction) is one of the causes of excess fat accumulation. For example:

1. Lack of thyroid hormones leads to both decreased intensity metabolic processes, and to slow down the breakdown of fats.
2. Excessive formation of secretions (glucocorticoids) of the adrenal cortex enhances the synthesis of fatty acids and their storage in fat depots in the form of triglycerides.
3. Excess insulin (due to pancreatic tumors; long-term stress and eating disorders; pathologies of the pituitary gland, adrenal glands, reproductive system; liver diseases, etc.) also leads to increased formation and storage of fats. And... is a direct consequence of obesity.
4. Disturbance in the formation of the above-mentioned adipose tissue hormone, leptin, which not only regulates eating behavior through direct effects on the hypothalamus, but also increases the body’s energy costs through stimulation of the sympathetic nervous system. In addition, leptin reduces insulin production.
5. Diseases of the pituitary gland disrupt fat metabolism both directly and indirectly, changing the functioning of the subordinate endocrine glands (genital, thyroid, adrenal glands).

An imbalance in fat metabolism can also be a consequence of dysfunction of the gonads.

Signs of endocrine obesity

The main symptom is excess fat deposits. Their character is determined by the type of endocrine pathology. Other symptoms are:

• signs of pathologies that cause lipid metabolism disorders;
• a consequence of obesity itself.

• increased blood pressure and heart rhythm disturbances are consequences of increased stress on the cardiovascular system;
• difficulty breathing (shortness of breath);
• fluid retention;
• lethargy, decreased performance, sleep disturbance;
• increased sweating;
• consequences of physical inactivity and increased load on the musculoskeletal system (joint pain, spinal problems);
• work disorders digestive system(constipation, heartburn), etc.

Treatment of hypothalamic obesity

Principles:

• decreased intake of energy sources into the body and increased energy expenditure (diet and physical activity);
• drug correction of metabolic disorders (for example, the use of substances that reduce the formation of insulin and/or increase the rate of metabolic processes);
• surgical interventions aimed at reducing food consumption and/or its absorption - the so-called. bariatric surgery.

Treatment of endocrine obesity

First of all, it is necessary to eliminate the root cause of obesity - specific hormonal dysfunction. For example, using hormone replacement therapy. Otherwise, the principles of treatment are similar to those given above.

A huge role is played by the patient’s motivation to get rid of the disease and awareness of it. psychological reasons. Therefore, psychotherapeutic assistance is not excluded.

Traditional medicine methods (instead of or together with classical ones) can also be used in the treatment of people suffering from obesity. Acupuncture, classical and resonant homeopathy, osteopathy, qigong therapy and herbal medicine have a holistic effect on a person, helping his body find and implement the optimal way to overcome the disease.

The hypothalamus is the main center for regulating appetite and body weight. Damage to the ventromedial region of the hypothalamus, paraventricular and dorsomedial nuclei is manifested by hyperphagia and obesity. Damage to the lateral part of the hypothalamus, on the contrary, causes a decrease in appetite. Also, a key role in energy metabolism (including the regulation of appetite and body weight) belongs to the arcuate (arcuate) nucleus of the hypothalamus (the arcuate nucleus, which is in close contact with the capillaries at the base of the hypothalamus, is sensitive to the content in the bloodstream nutrients and hormones, and thus receives information about the energy reserves in peripheral tissues)

It is now considered proven that, regardless of the form of obesity (primary or secondary), the key link in the pathogenesis is a disruption of the hormonal connection between adipose tissue, which produces the hormone leptin, and the hypothalamus. The hypothalamus plays a major role in the regulation energy balance in organism. Damage to its ventromedial region or paraventricular nuclei is accompanied by: 1 - increased appetite, 2 - decreased energy expenditure and 3 - increased body weight (BW).

note! The diagnosis of “hypothalamic obesity” (HO) is established if there is a connection between the development of obesity and damage to the hypothalamus. Genetic defects of the melanocortin system and pharmacotherapy (antipsychotic drugs) can also lead to HO. According to modern concepts, mutations in melanocortin receptor type 4 (MC3/4-R) are the most common cause of monogenic obesity in humans. Only isolated cases of idiopathic hypothalamic dysfunction in children accompanied by obesity have been described.

A distinctive feature of HO is hyperphagia. However, obesity can develop without the presence of hyperphagia. The degree of weight gain during HO may vary. Typically, with HO, due to damage to the hypothalamus, body weight begins to suddenly, quickly and inevitably increase. G. Bray et al. (1984) suggested that it is the change in the rate of body weight gain after damage to the hypothalamus, and not its absolute value, that is the defining feature indicating the hypothalamic mechanism for the development of obesity.

The reasons leading to damage to the hypothalamus, and, accordingly, to the development of HO are:

[1 ] true tumors: ( ! most common reason development of HO in children and adolescents), glioma, meningioma, germinoma, pituitary macroadenoma, teratoma, chordoma, metastases;

read also the article “Space formations of the hypothalamic region and disturbances of the central regulation of homeostasis” Dzeranova L.K., Pigarova E.A., Petrova D.V., Federal State Budgetary Institution “Endocrinological Research Center” of the Ministry of Health of Russia, Moscow; article published in the journal “Obesity and Metabolism” No. 3, 2014 [read]

[2 ] malformations and hamartomas: hypothalamic hamartoma;
[3 ] infectious lesions: tuberculosis, arachnoiditis, encephalitis;
[4 ] consequences of treatment: surgical intervention, radiation therapy, as well as installation of subthalamic implants (for deep brain stimulation in Parkinson's disease);
[5 ] other anomalies: aneurysm, histiocytosis X, sarcoidosis.

The main clinical signs of HO are hyperphagia with pronounced eating disorders and hypothalamic dysfunction of various types: most often - hypogonadotropic hypogonadism, and with anatomical damage to the hypothalamus, in addition - drowsiness, growth hormone deficiency, secondary hypocortisolism, central hypothyroidism and diabetes insipidus. Fat deposition is observed mainly on the abdomen (in the form of an apron), buttocks, and thighs. Skin changes during HO are manifested by trophic disorders such as cyanotic or small pink stretch marks (on the thighs, abdomen, shoulders, armpits), hyperpigmentation (neck, elbows, friction points). Various signs of autonomic dysfunction are observed: increased arterial and intracranial pressure, sweating disorders, autonomic, adrenergic (diencephalic) crises. Other symptoms associated with HO include headache, visual impairment, in women - various menstrual cycle disorders, infertility, hirsutism, in men - decreased potency.

SISTERS WITH HYPOTHALAMIC TYPE OF OBESITY (after D.R. Klein, 1956)

Considering the complexity of HO syndrome, its treatment requires simultaneous impact on various parts of its pathogenesis. However, GO therapy is palliative, in addition, non-drug treatment (diet and physical exercise), although necessary, is ineffective. Studies on the use of various pharmacotherapy for HO are relatively few and include the use of sympathomimetics, somatostatin analogues (to suppress insulin secretion), and sibutramine. In addition, one study involving three patients with postoperative HO demonstrated the beneficial effect of supraphysiological doses of triiodothyronine, which resulted in weight loss in the absence of signs of thyrotoxicosis. In general, according to the studies conducted, pharmacotherapy with GO gives moderately positive results; however, to clarify the effectiveness of the use of various medicines with GO, longer and larger-scale trials are required. An attractive treatment option for HO is bariatric surgery. A number of studies have shown that various types of bariatric interventions in patients with HO lead not only to a decrease or stabilization of body weight, but also, to one degree or another, contribute to the normalization of metabolic disorders that occur in this category of patients.

With this approach, it is necessary to put pituitary obesity in the first place: it is more often called dystrophia adiposo-genitalis. The clinical picture consists of the following signs: 1) obesity, 2) hypoplasia of the reproductive apparatus and 3) a number of neurological disorders.

I will analyze these symptoms in more detail (Fig. 158, 159).

There are two types of obesity. Sometimes fat accumulations are observed only in favorite places - on the chest, abdomen and buttocks, and other parts of the body do not present major deviations from the norm. Sometimes it covers much more areas, but still, in the end, not the whole body. So, for example, even with severe obesity, the back of the head for some reason is not covered in much fat. In the extremities, there is also an unevenness of obesity: in the arms below the elbow and in the legs below the knees it is comparatively less than in the central sections (Fig. 160, 161).

Along with obesity, growth disorder is also often observed.

Rice. 158. Dystrophia adiposo-gemtahs (Iv Gosp.ter class SAGU, collection of Dr. I. A Kassirsky.)

Rice. 159. The same case.

two opposing types: pituitary dwarfism or pituitary gigantism. In the first case, we are talking about those dwarfs that I have already described to you. You remember that they are generally distinguished by a certain tendency towards being overweight. But sometimes this fullness reaches such proportions that it can be put in the foreground and talk about pituitary obesity, complicated by pituitary dwarfism. You can do the opposite - consider the case as pituitary dwarfism complicated by obesity. This will be a purely terminological disagreement, because, as you will see later, pathogenetically both parts of the clinical picture come from the same source - a disorder of the functions of the cerebral appendage (Fig. 162).

Sometimes, on the contrary, obesity is combined with a tendency towards big

Rice. 160. Dystrophia adiposo-genitalis.

Rice. 161. The same case.

growth. True, gigantism in the exact sense of the word does not exist - it is simply a question of relatively high growth - up to general character the build quite clearly bears the features that I noted when I described pituitary gigantism. Therefore, here too, with a certain right, one can put either obesity or gigantism in the foreground, and consider the second half of the clinical picture to be a complication. And again, such a disagreement will be purely verbal, since ultimately all symptoms of the disease. They have the same origin (Fig. 163).

Of course, a certain percentage of cases occur without any growth disorders.

Hypoplasia of the genital organs is especially pronounced in cases where the disease began to develop very early - before the onset of puberty. But even if it began late, a certain evolution of the genital organs can still be noticed. A functional disorders in both cases there is always a weakening of libidinis and potentiae in men, cessation of menstruation in women. Secondary sexual characteristics are either weakly expressed from the very beginning, or in cases with late onset they gradually disappear. The last group of symptoms is neurological in nature. These are general and nested brain symptoms - the same as with acromegaly: headaches, drowsiness, decreased vision, changes in its field, congestive nipple, palsies of individual cranial nerves, polyuria, etc. This group of symptoms, if there is one at all , refers to the stages of the disease, relatively late.

Rice. 162. Constitutional obesity. (From the State Ter. Class of SAGU; collection of Dr. I. A. Kassirsky.)

Rice. 163. Dystrophia adiposo-genitalis with symptoms of eunuchoidism. (From the collection of Dr. A.F. Korovnikov.)

the course of the disease is a slow increase at first, then a long period of stationary state and finally a new progression until death. the pathological anatomy of suffering is the same as acromegaly: we are talking about tumors either of the appendage itself, or infundibuli, or neighboring areas of the base of the brain. Sometimes there is no tumor, but there is edema of the brain. pathogenesis in the most general outline comes down to a disorder of the functions of the brain appendage. But which part of him is to blame for this is not yet entirely clear. At one time, everything was reduced to hypofunction of the posterior lobe; Now they also add the participation of the interstitial lobe (pars intermedia).

Regarding therapy, we can only repeat everything that was said about acromegaly.

Hypothalamic-pituitary obesity is observed in a third of patients with morbid obesity and is associated with damage to the hypothalamus.

Among the causes of the disease are: viral or bacterial chronic infections, intoxication, skull trauma, brain tumors, hemorrhages, as well as genetic predisposition.

The disease is caused by a defect in the hypothalamic nuclei that regulate appetite. It has been experimentally shown that damage to the ventromedial nuclei of the hypothalamus is accompanied by increased appetite and obesity. Primary damage to the hypothalamus also increases appetite, resulting in excess fat deposition and increased formation of fat from carbohydrates.

Other endocrine glands are also involved in the progression of the disease. Obese patients are characterized by hyperinsulinism, increased blood levels and accelerated urinary excretion of corticosteroids. The level of somatotropin involved in lipogenesis decreases in the blood. Weakening of the gonadotropic function of the pituitary gland entails hypofunction of the gonads with a clinical picture of hypogonadism.

In addition to endocrine ones, most obese patients are also characterized by metabolic disorders (persistent hyperlipidemia, changes in electrolyte metabolism). Consequently, with obesity, a number of endocrine metabolic disorders develop, characteristic of such metabolic diseases as diabetes mellitus and atherosclerosis. Special studies have determined that in obese patients, poor results of the glucose tolerance test are 7-10 times more common than in people with normal body weight. This is why obesity is now considered a risk factor for the development of diabetes mellitus and atherosclerosis.

The consequence of impaired hypothalamic regulation and the listed hormonal disorders is a shift in the balance between lipogenesis and lipolysis towards the predominance of lipogenesis processes.

ADIPOSOGENITAL DYSTROPHY (PECHKRANZ-BABINSKI-FROHLICH SYNDROME)

Adiposogenital dystrophy- one of the forms of hypothalamic obesity. Characterized by a combination of obesity and hypogenitalism. Children get sick preschool age and adolescents in puberty. If the disease develops in adults due to trauma, inflammation or tumor and is accompanied by obesity and secondary genital atrophy, we should talk about hypothalamic syndrome. The incidence of the disease is the same in boys and girls, but genital hypoplasia is detected earlier in boys.

The causes are inflammatory or tumor processes in the hypothalamus, which underlie other forms of hypothalamic obesity. Among acute pathologies, viral infections (influenza, scarlet fever, etc.) are most often noted, and among chronic ones, tuberculosis. You should also remember about possible intrauterine infections (encephalitis), birth injuries, and toxoplasmosis.

In addition to the ventromedial nuclei that regulate appetite, adiposogenital dystrophy affects the mediobasal parts of the hypothalamus, which are responsible for the secretion of gonadotropins. Therefore, along with obesity, patients experience hypoplasia and atrophy of the gonads, and underdevelopment of secondary sexual characteristics. Hypofunction of the thyroid gland and adrenal insufficiency are possible. Overfeeding and severe obesity in childhood often leads to a secondary disruption of the hypothalamic regulation of the endocrine glands and hypogonadism.

DIABETES INSIPIDUS

Diabetes insipidus- a disease characterized by diabetes, increased plasma osmolarity, inducing thirst, and compensatory consumption large quantity liquids.

The disease is associated with a deficiency of vasopressin, which controls the reabsorption of water in the distal tubules of the nephron, where, under physiological conditions, negative clearance of “free” water is ensured on the scale necessary for homeostasis, and urine concentration is completed.

There are a number of etiological classifications of diabetes insipidus. More often than others, they use a division into central (neurogenic, hypothalamic) diabetes insipidus with insufficient production of vasopressin (complete or partial) and peripheral. The central forms include true idiopathic (familial or acquired) diabetes insipidus. In peripheral diabetes insipidus, normal production of vasopressin is maintained, but sensitivity to the hormone of renal tubular receptors is reduced or absent (nephrogenic vasopressin-resistant diabetes insipidus) or vasopressin is intensely inactivated in the liver, kidneys, and placenta.

The development of central forms of diabetes insipidus is based on inflammatory, degenerative, traumatic, tumor and other lesions of the hypothalamic-pituitary system (anterior nuclei of the hypothalamus, supraopticohypophyseal tract, posterior pituitary gland). The specific causes of the disease are very diverse. True diabetes insipidus is preceded by a number of acute and chronic diseases: influenza, meningoencephalitis, tonsillitis, scarlet fever, whooping cough, all types of typhus, septic conditions, tuberculosis, syphilis, malaria, brucellosis, rheumatism. Influenza, with its neurotropic effects, is more common than other infections. As the overall incidence of tuberculosis, syphilis and other chronic infections decreases, their causal role in the occurrence of diabetes insipidus decreases significantly. The disease can occur after traumatic brain injury (accidental or surgical), mental trauma, electric shock, hypothermia, during pregnancy, shortly after childbirth, abortion; in children - after birth trauma. Symptomatic diabetes insipidus is caused by primary and metastatic tumors of the hypothalamus and pituitary gland, adenoma, teratoma, glioma and (especially often) craniopharyngioma, sarcoidosis. Cancer of the breast, thyroid gland, and bronchi most often metastasizes to the pituitary gland. A number of hemoblastoses are also known - leukemia, erythromyelosis, lymphogranulomatosis, in which infiltration of pathological elements in the blood of the hypothalamus or pituitary gland causes diabetes insipidus. The latter accompanies generalized xanthomatosis and is one of the symptoms of endocrine diseases (Simmonds syndrome, Sheehan syndrome, gigantism, adiposogenital dystrophy).

However, in a significant number of patients (60-70%), the origin of the disease remains unknown - “idiopathic” diabetes insipidus. Among the idiopathic forms, genetic ones should be distinguished, sometimes observed in three, five and even seven subsequent generations. The mode of inheritance is either autosomal dominant or recessive.

The combination of diabetes mellitus and diabetes insipidus is also more common among its familial forms. Currently, in a number of patients with idiopathic diabetes insipidus, it is assumed that the disease has an autoimmune nature with damage to the hypothalamic nuclei (similar to the destruction of other endocrine organs in autoimmune syndromes). Nephrogenic diabetes insipidus is more common in children and is caused either by anatomical inferiority of the renal nephron (congenital malformations, cystic-degenerative and infectious-dystrophic processes, amyloidosis, sarcoidosis, methoxyfluorane poisoning, lithium) or a functional enzymatic defect (impaired cAMP production in renal tubular cells or decreased sensitivity to its effect).

Hypothalamic-pituitary forms of diabetes insipidus with insufficiency of vasopressin secretion can be associated with damage to any part of the hypothalamic-pituitary system. The pairing of the neurosecretory nuclei of the hypothalamus and the fact that for clinical manifestation it is necessary to damage at least 80% of the cells secreting vasopressin, provide great opportunities for internal compensation. There is, albeit a small, probability of diabetes insipidus with lesions in the area of ​​the pituitary infundibulum, where the neurosecretory pathways coming from the nuclei of the hypothalamus connect. Vasopressin deficiency reduces fluid reabsorption in the distal renal nephron and promotes the excretion of large amounts of hypoosmolar (unconcentrated) urine. Primary polyuria entails general dehydration with loss of intracellular and intravascular fluid with hyperosmolarity (above 290 mOsm/l) of plasma and thirst, indicating a violation of water homeostasis. It has now been established that vasopressin causes not only antidiuresis, but also antinatriuresis. In case of hormone deficiency, especially during periods of dehydration, when aldosterone is also stimulated, sodium is retained in the body, causing hypernatremia and hypertonic (hyperosmolar) dehydration.

HYPERHYDROPEXIC SYNDROME (ANTIDIABETES INSIPIDUS, PARCHON'S SYNDROME)

Hyperhydropyrexic syndrome refers to rare diseases of the hypothalamic-pituitary region. It is based on hyperproduction of vasopressin. More common in women.

The reasons are often not identified. Mental and physical trauma, infections with damage to the hypothalamus are important. Autoimmune and genetic factors play a certain role.

Due to damage to the hypothalamus, namely the supraoptic and paraventricular nuclei, there is an increased incretion of vasopressin, the main regulator of osmotic pressure. Vasopressin reduces diuresis and promotes fluid retention in the body. Other endocrine changes in the regulation of water metabolism, in particular, hyperproduction of aldosterone, are also to blame for the progression of the disease.

ITZENKO-CUSHING'S DISEASE

Itsenko-Cushing's disease- one of the most severe neuroendocrine diseases, which is based on a violation of the regulatory mechanisms that control the hypothalamic-pituitary-adrenal system. The pathological process is associated with damage to the hypothalamic-pituitary system (basophilic adenoma arising from acidophilic or chief cells of the pituitary gland). In clinical practice, there are cases of the development of Itsenko-Cushing's disease with encephalitis, arachnoencephalitis, traumatic injury skull and other organic diseases of the central nervous system, with bronchogenic cancer, cancer of the thymus, thyroid and pancreas, uterus and ovaries, after childbirth or during menopause. The development of the disease may be preceded by a traumatic brain or mental injury, but in half of the patients the cause cannot be determined. There are references to genetic factors.

The pathogenetic basis of Itsenko-Cushing's disease is changes in the mechanism of control of ACTH secretion. Due to a decrease in dopamine activity, which is responsible for the inhibitory effect on the secretion of CRH and ACTH and the increase in the tone of the serotonergic system, the mechanism of regulation of the functions of the hypothalamic-pituitary-adrenal system and the daily rhythm of CRH-ACTH-cortisol secretion are disrupted; the principle of “feedback” ceases to operate with a simultaneous increase in the level of ACTH and cortisol; the reaction to stress disappears - an increase in cortisol under the influence of insulin glycemia.

The development of Itsenko-Cushing's disease is based on both an increase in the secretion of ACTH from the pituitary gland and the release of cortisol, corticosterone, aldosterone, and androgens from the adrenal cortex. Chronic long-term cortisolemia causes the symptom complex of hypercortisolism (Itsenko-Cushing's disease). Disturbances in the hypothalamic-pituitary-adrenal relationship during the disease are combined with changes in the secretion of other pituitary tropic hormones. The secretion of growth hormone decreases significantly, the level of gonadotropins and TSH decreases, and prolactin increases. The effect of excess of the main corticosteroid - cortisol -

is that with the breakdown of enzyme systems, the processes of dissimilation and deamination of amino acids are accelerated. The result of these processes is an increase in the rate of protein breakdown and a slowdown in their synthesis. Disorders of protein metabolism lead to

leads to an increase in nitrogen excretion in the urine and a decrease in albumin levels. A characteristic symptom of the disease is muscle weakness, which is explained by dystrophic changes in muscles

and hypokalemia. Hypokalemic alkalosis is associated with the effect of glucocorticoids on electrolyte metabolism. Hormones promote sodium retention in the body, which leads to the excretion of potassium salts. The potassium content in plasma, red blood cells, skeletal muscles and heart muscle is significantly reduced.

The pathogenesis of arterial hypertension in Itsenko-Cushing's disease is complex and insufficiently studied. An undoubted role is played by disruption of the central mechanisms of regulation of vascular tone. Important There is also hypersecretion of glucocorticoids with pronounced mineralocorticoid activity, in particular corticosterone and aldosterone. Dysfunction of the renin-angiotensin-aldosterone system leads to the development of persistent hypertension.

The loss of potassium from muscle cells causes a change in vascular reactivity and an increase in vascular tone. A certain role in the pathogenesis of hypertension is also played by the potentiation by glucocorticoids of the effect of catecholamines and biogenic amines, in particular serotonin.

In the pathogenesis of osteoporosis in Itsenko-Cushing's disease, the catabolic effect of glucocorticoids on bone tissue is of great importance. Weight itself bone tissue, as well as the content of organic matter and its components (collagen, mucopolysaccharides) decreases, and the activity of alkaline phosphatase decreases. Due to the preservation of mass and disruption of the structure of the protein matrix, the ability of bone tissue to fix calcium is reduced. A significant role in the occurrence of osteoporosis belongs to a decrease in calcium absorption in the gastrointestinal tract, which is associated with inhibition of the processes of hydroxylation of calciferol. The destruction of protein components in the blood and secondary demineralization cause osteoporosis. Excretion of large amounts of calcium by the kidneys causes nephrocalcinosis, the formation of kidney stones, secondary pyelonephritis and renal failure. A disorder of carbohydrate metabolism in Itsenko-Cushing's disease is accompanied by an increase in the functions of alpha, beta and delta cells of the pancreas. In the pathogenesis of steroid diabetes mellitus, relative insulin deficiency, insulin resistance and increased levels of contrainsular hormones are of great importance.

ACROMEGALY AND GIGANTISM

Acromegaly - a disease caused by excess production of somatotropin. Manifested by increased growth of the skeleton, organs and tissues. This disease of the adenohypophysis occurs equally often among men and women, predominantly mature age(30-50 years old). With an increase in the production of somatotropin in children, when the growth zones are not yet closed, proportional growth of the skeleton, organs and tissues occurs (gigantism). Acromegaly and gigantism are considered as diseases of the same nature, as age-related variants of the same process.

Due to its gradual development, the pathology may long time occurs hidden, so it is often difficult to establish its cause. Cases of the disease occurring after injury, infection, after pregnancy and during menopause have been described. The infectious process in the hypothalamus plays a particularly significant role. Whether the listed factors are the causes of the disease or just provoking factors is not always clear. In recent years, great importance has been attached to heredity, which is confirmed by the presence family form acromegaly.

The pathogenesis is based on increased production of somatotropin by acidophilic cells of the adenohypophysis against the background of pituitary adenoma. The typical and most common localization of adenoma is in the area of ​​the sella turcica, but this tumor can develop from the embryonic rudiments of the pituitary gland and be located on the back of the pharynx or in the sphenoid bone. Much less often, excessive formation of somatotropin is caused not by adenomatosis, but by diffuse hyperplasia of acidophilic cells. Hyperfunction of the adenohypophysis is sometimes associated with a primary lesion of the hypothalamus. The main metabolic effect of somatotropin is to enhance protein synthesis. With its hypersecretion, an increase in anabolic processes is observed, manifested by intensive growth of skeletal bones, an increase in the volume of muscles and internal organs (splachnomegaly).

At the onset of the disease, excessive production of other tropic hormones of the pituitary gland is likely: thyro-, gonado-, and corticotropin, prolactin, which is associated with an increase in the function of the peripheral endocrine glands: gonads, thyroid and adrenal glands.

As the tumor grows, the hyperfunction of the adenohypophysis is replaced by hypofunction, which leads to failure of the peripheral endocrine glands.

With a tumor of significant size (3-5 cm in diameter), symptoms of increased intracranial pressure appear.

Cases of rapid progression of the disease have been described, the cause being a malignant pituitary adenoma. Intensively increasing, the tumor early metastasizes to the bones of the skull, chest, and spinal column.

Gigantism is characterized by accelerated proportional growth of adolescents, i.e. persons with unfinished physiological growth. With gigantism, growth exceeds the upper limits of the norm corresponding to a given sex and age. Height is considered pathological: 2 m for men and 1.9 m for women. The disease occurs predominantly among prepubertal and pubertal boys.

The main cause of gigantism, as with acromegaly, is an acidophilic pituitary adenoma that secretes excess somatotropin. Other causes include infection, trauma, hemorrhage, leading to hyperplasia of acidophilic and, less commonly, chromatophilic cells.

Increased production of somatotropin leads to intensive epiphyseal bone growth. Since ossification of the epiphyseal cartilages is not complete during adolescence, excessive growth of bones in length occurs. The stimulating effect of somatotropin also extends to soft fabrics, as well as on internal organs(splanchnomegaly).

Hypothalamic obesity (hypothalamic-pituitary) is characterized by excessive accumulation of fat both in places of physiological deposits and by its dysplastic redistribution mainly in the area of ​​the mammary glands, thighs, and abdomen. Unlike nutritional or hereditary obesity, hypothalamic obesity is based on damage to the diencephalic region. If the frequency of all forms of obesity ranges from 30 to 50%, then one third of this number is due to hypothalamic obesity.

Among the causes of hypothalamic obesity, viral or chronic infection is indicated. The influence of focal infection in the form of recurrent tonsillitis, sinusitis (frontal sinusitis, sinusitis), odontogenic infection, as well as intoxication and skull trauma, brain tumors, and hemorrhage cannot be excluded. As with other forms of obesity, the nutritional factor is a mandatory component, because without excess nutrition there is no obesity. Genetic predisposition also occurs.

The development of hypothalamic obesity is associated with damage to the ventromedial and venrolateral nuclei of the posterior hypothalamus, which regulate appetite. It has been experimentally established that damage to the ventromedial nuclei leads to excitation of the ventrolateral ones - the “appetite center”. This is accompanied by a sharp increase in appetite and the development of obesity. The influence of impaired hypothalamic regulation occurs in two ways:

1. through the autonomic nervous system and
2. pituitary tropic hormones.

The first of them is realized by the predominance of the tone of the parasympathetic part of the autonomic nervous system, which leads to stimulation of the biosynthesis and release of insulin.

In the same direction, β-endorphin produced in the adenohypophysis acts on insulin secretion. In turn, hyperinsulinemia worsens obesity.

The effect on the pituitary gland is accompanied by inhibition of the production of fat-mobilizing tropic hormones: ACTH, STH, TSH and also by reducing the activity of thyroxine, adrenaline and glucagon. Violation of hypothalamic regulation and the listed hormonal changes cause a change in the balance between lipogenesis and lipolysis towards the predominance of lipogenesis processes. A consequence of inhibition of the gonadotropic function of the pituitary gland is hypofunction of the gonads. With the development of obesity during puberty, this can lead to hypogonadism.

Along with hormonal changes, obese patients are characterized by metabolic disorders: pathological tolerance to carbohydrates, persistent hyperlipidemia, changes in electrolyte metabolism. Apparently, changes in the ratio of potassium and sodium electrolytes underlie fluid retention due to an increase in extracellular fluid, which cannot but contribute to an increase in body weight.

A.Efimov, N.Skrobonskaya, A.Cheban

"What is hypothalamic obesity" - article from the section