Endocrine System – Etiology, Pathogenesis Of Endocrinopathies

Table of Contents


In pathology of endocrine system, The etiology of diseases of the endocrine glands is very diverse. Organic lesions caused by trauma, hemorrhage, intoxication or infection are of the greatest clinical importance.

Endocrinopathies are acquired and hereditary.

Violations sometimes relate to all functions of the endocrine gland (total), and sometimes – only their parts (partial endocrinopathies).

Depending on the level of dysregulation and biosynthesis of the hormone, primary, secondary and tertiary forms of pathology are distinguished.

Different types of damage lead to hyperfunction, hypofunction or dysfunction of the endocrine glands.


1. Dysregulatory – associated with primary disorders of nervous, humoral and other types of regulation.

2. Dissecretory – associated with damage to the endocrine glands themselves.

3. Dysmetabolic – associated with a violation of the destruction or transformation of the hormone (usually with liver pathology).

4. Dissecretory – associated with a violation of hormone secretion.

5. Dissensitive – associated with impaired sensitivity (receptor defect) of effector formations.

Additionally, endocrinopathies are distinguished, caused by a change in the degree of strength of the bond between the hormone and the protein that transports it, as well as in the disorder of interhormonal relationships.


Pituitary dysfunction:

  • congenital and acquired;
  • primary and secondary;
  • violations of the anterior lobe, posterior lobe and the entire pituitary gland.
  • Dysfunctions of the entire gland (panhypopituitarism) and partial dysfunction.
  • dysfunction is expressed by an increase (hyperfunction) or a decrease (hypofunction) in the activity of the gland.

Diseases caused by partial or complete shutdown of the pituitary gland (hypopituitary syndrome) include:

  • Simmonds disease (hypothalamic-pituitary insufficiency);
  • Sheehan’s disease (postpartum hypopituitarism);
  • pituitary dwarfism (pituitary dwarfism);
  • hypothalamic-pituitary obesity;
  • adiposogenital dystrophy (Pekhkrants-Babinsky-Fröhlich syndrome);
  • diabetes insipidus.

Diseases caused by hyperfunction of the pituitary gland develop more often in the presence of hormonally active tumors (adenomas):

  • hyperhydropexy cider;
  • acromegaly;
  • gigantism.



In pathology of endocrine system, This concept includes hypothalamic-pituitary insufficiency, postpartum hypopituitarism and pituitary cachexia.

Hormonal insufficiency of the hypothalamic-adenohypophyseal system develops on the basis of infectious, toxic, vascular (for example, with systemic collagenoses), traumatic, tumor and allergic (autoimmune) lesions of the anterior pituitary gland and or hypothalamus.

A similar clinical syndrome also occurs as a result of radiation and surgical hypophysectomy. Any infection and intoxication can lead to dysfunction of the hypothalamic-adenohypophyseal system. Tuberculosis, malaria, syphilis often cause destructive processes in the hypothalamus and pituitary gland.

The disease is often preceded by influenza, encephalitis, typhus, dysentery, purulent processes in various organs and tissues with thromboembolic complications and pituitary necrosis, craniocerebral trauma, accompanied by intracerebral hemorrhages in the hypothalamus or pituitary gland with the formation of cysts as a result of hematoma resorption. The development of hypopituitarism may be based on fungal lesions, hemochromatosis, sarcoidosis, primary and metastatic tumors.

Frequent causes of the disease in women are abortion and especially childbirth, complicated by eclampsia in the last months of pregnancy, sepsis, thromboembolism, massive blood loss, leading to impaired blood circulation in the pituitary gland, angiospasm, hypoxia and necrosis. Hypothalamic-pituitary insufficiency in women with severe toxicosis in the second half of pregnancy is in some cases associated with the development of autoimmune processes. Evidence of this is the detection of antibodies to the extract of the anterior pituitary gland.

Ischemic changes in it, although rare, also occur in men after gastrointestinal, nosebleeds and as a result of systematic long-term donation.

Regardless of the nature of the damaging factor and the nature of the destructive process, which ultimately leads to atrophy and sclerosis of the pituitary gland, the pathogenetic basis of the disease in all clinical variants of hypothalamic-pituitary insufficiency is a decrease or complete suppression of the production of adenohypophyseal tropic hormones. Resultat – secondary hypofunction of the adrenal glands, thyroid and genital

out glands – In rare cases of simultaneous involvement of the posterior lobe or the pituitary stalk in the pathological process, it is possible to reduce the content of vasopressin with the development of diabetes insipidus. It should be borne in mind: a simultaneous decrease in ACTH and corticosteroids, antagonistic to vasopressin in relation to water metabolism, can level and alleviate clinical manifestations. Depending on the location, extent and intensity of the destructive process, it is possible that a uniform, complete (panhypopituitarism) or partial (when the production of one or several hormones persists) cessation or drop in the level of hormone formation in the pituitary gland. Isolated hypofunction of one of the tropic hormones occurs very rarely, in particular in the syndrome of “empty Turkish saddle”.

Lack of pituitary tropic hormones leads to a sharp decrease in the functions of the peripheral endocrine glands. A decrease in the production of somatotropin is accompanied by depletion, splanchnomikria. Loss of gonadotropic function of the pituitary gland leads to ovarian failure, amenorrhea, atrophy of the uterus, vagina, mammary glands. Deficiency of thyrotropin is the cause of the development of the pituitary myxedema. The consequence of a sharp decrease in the production of corticotropin is the development of chronic insufficiency of the adrenal cortex up to adissonic crises. It is in this sequence that pituitary insufficiency progresses: first, the loss of gonadotropic, somatotropic functions follows, then thyro- and corticotropic functions. Polymorphism of clinical symptoms of Simmonds disease – from erased forms of partial hypopituitarism (pituitary myxedema, hypocorticism) to an expanded clinic of total (panhypopituitarism) – due to the combination and degree of insufficiency of certain tropic hormones of the pituitary gland. The adenohypophysis has large functional reserves. Explicit signs of insufficiency are revealed only when 75-90% of the glandular tissue is destroyed.

In the pathology of the endocrine system, In cases of predominant involvement in the process of the hypothalamus, dystrophic and destructive processes in the pituitary gland may not be. A feature of the course of such forms of the disease is the prevalence of vegetative disorders. The inevitable inadequate production of releasing hormones leads to subsequent functional insufficiency of the pituitary gland and a deficiency of tropic hormones with clinical symptoms of partial hypopituitarism.

Postpartum hypopituitarism – Sheehan’s syndrome – is characterized by insufficiency of the function of the adenohypophysis and partly of the thyroid, adrenal and gonads. The most common cause of the disease is necrosis of the adenohypophysis due to complications of childbirth – profuse bleeding, postpartum sepsis. Profuse bleeding, collapse disrupt the portal circulation, followed by necrosis of the glandular tissue of the pituitary gland. Septic embolism of the adenohypophysis vessels also leads to a similar outcome.

Pituitary dwarfism (dwarfism, nanosomy, microsomia) in the absolute sense means a disease, the main manifestation of which is a sharp delay in growth (the growth of men – up to 130 cm, women – up to 120 cm), associated with a disorder of the secretion of growth hormone of the anterior lobe of the pituitary gland. In a broader sense, nanism is a violation of growth and physical development, caused not only by an absolute deficiency of growth hormone due to pathologies of the pituitary gland itself, but also with a disorder of the hypothalamic regulation of its functions, defects in the biosynthesis of growth hormone, a violation of tissue sensitivity to this hormone. Slow down or stop

growth – either an independent disease or a symptom of another pathology. In most of those suffering from this pathology, the changes are not limited only to the disorder of GH secretion and sensitivity to it, but also affect other tropic hormones of the pituitary gland, causing various combinations of endocrine and metabolic disorders.

Most forms of pituitary dwarfism are genetic diseases. The most common is panhypopituitary dwarfism, inherited mainly in a recessive manner. Presumably, there are 2 types of transmission of this form of pathology (autosomal and through the X chromosome). With her, a defect in the secretion of STH is most often combined with that of gonadotropins and thyroid-stimulating hormone.

A large group of patients with nanism (primary cerebral, cerebral-pituitary) is made up of persons with various types of organic pathology of the central nervous system, arising in utero or in early childhood. The anatomical substrate that causes it is underdevelopment or absence of the pituitary gland, its dystrophy in the pathology of the Turkish saddle formation, cystic degeneration of the pituitary gland, its atrophy due to compression by a tumor (craniopharyngioma, chromophobic adenoma, meningioma, glioma). Dwarfism due sometimes traumatic injuries of the hypothalamic-pituitary region (intrauterine, generic, postnatal), often occurs in multiple pregnancy and childbirth in breech, sheath previa or transverse position rotated leg (born as a 1 / 3sick with nanism). Infectious and toxic influences are important (intrauterine viral infections, tuberculosis, syphilis, malaria, toxoplasmosis; diseases in early childhood, sepsis of newborns, meningo- and arachnoencephalitis, etc.), which can damage the pituitary gland itself, the hypothalamic centers regulating its function, normal functional communication in the central nervous system.

In the pathology of the endocrine system, General Etiology And Pathogenesis Of Endocrinopathies. Pathogenetic Classification Of Endocrinopathies


In the pathology of the endocrine system, Hypothalamic-pituitary obesity is observed in a third of patients with pathological obesity and is associated with damage to the hypothalamus.

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

The disease is caused by a defect in the nuclei of the hypothalamus, which regulate appetite. It has been shown experimentally 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, 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 growth hormone involved in lipogenesis decreases in the blood. The weakening of the gonadotropic function of the pituitary gland entails hypofunction of the gonads with the clinic of hypogonadism.

In addition to endocrine disorders, metabolic disorders (persistent hyperlipidemia, changes in electrolyte metabolism) are characteristic of most obese patients. Consequently, with obesity, a number of endocrine-metabolic disorders develop, characteristic of such metabolic diseases as diabetes mellitus and atherosclerosis. In special studies, it was determined: in obese patients, poor results of the glucose tolerance test occur 7-10 times more often than in people with normal body weight. That is why obesity is now considered a risk factor for diabetes and atherosclerosis.

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



In the pathology of the endocrine system, Adiposogenital dystrophy is one of the forms of hypothalamic obesity. It is characterized by a combination of obesity with hypogenitalism. Children of preschool age and adolescents in puberty are ill. 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 found earlier in boys.

The reasons are inflammatory or neoplastic processes in the hypothalamus that underlie other forms of hypothalamic obesity. Of acute pathologies, a viral infection (influenza, scarlet fever, etc.) is more often noted, and of chronic ones – tuberculosis. You should also remember about possible intrauterine infections (encephalitis), birth trauma, 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 have hypoplasia and atrophy of the gonads, underdevelopment of secondary sexual characteristics. Possible hypofunction of the thyroid gland and insufficiency of the adrenal cortex. Overfeeding and severe obesity in childhood often leads to a secondary violation of the hypothalamic regulation of the endocrine glands and hypogonadism.



In the pathology of the endocrine system, Diabetes insipidus is a disease characterized by diabetes, increased plasma osmolarity, stimulating thirst, and compensatory fluid intake.

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, a negative clearance of “free” water is provided on a scale necessary for homeostasis, and urine concentration is completed.

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

In the pathology of the endocrine system, 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 lobe of the 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 onset of diabetes insipidus decreases significantly. The disease can occur after craniocerebral (accidental or surgical), mental trauma, electric shock, hypothermia, during pregnancy, soon 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, bronchi metastasizes to the pituitary gland. A number of hemoblastoses are also known – leukemia, erythromyelosis, lymphogranulomatosis, in which the infiltration of pathological elements of the blood of the hypothalamus or pituitary gland causes diabetes insipidus. The latter accompanies generalized xanthomatosis, it is one of the symptoms of endocrine diseases (Symmonds, Sheehan, gigantism,

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

In the pathology of the endocrine system, The combination of diabetes mellitus and diabetes insipidus is also more common among its familial forms. Currently, a number of patients with idiopathic diabetes insipidus are assumed to have an autoimmune nature of the disease with damage to the nuclei of the hypothalamus (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, lithium poisoning) or by a functional enzymatic defect in the canal cells or decreased cAMP production sensitivity to its effect).

Hypothalamic-pituitary forms of diabetes insipidus with insufficient vasopressin secretion can be associated with damage to any part of the hypothalamic-pituitary system. The pairedness of the hypothalamic neurosecretory nuclei and the fact that clinical manifestation requires the defeat of at least 80% of the cells secreting vasopressin, provide great opportunities for internal compensation. There is, albeit small, the likelihood of diabetes insipidus with lesions in the pituitary funnel, where neurosecretory pathways from the nuclei of the hypothalamus are connected. Deficiency of vasopressin reduces fluid reabsorption in the distal renal nephron and promotes the release of a large amount of hypoosmolar (non-concentrated) urine. Primary arising polyuria entails general dehydration with loss of intracellular and intravascular fluid with hyperosmolarity (above 290 mosm / l) plasma and thirst, indicating a violation of water homeostasis. It has now been established that vasopressin causes not only antidiuresis, but also antinatriuresis. With hormone deficiency, especially during a period of dehydration, when aldosterone is also stimulated, sodium is retained in the body, causing hypernatremia and hypertonic (hyperosmolar) dehydration.



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

The reasons are often not established. Mental and physical trauma, infections with damage to the hypothalamus are important. A certain role is assigned to autoimmune and genetic factors.

In the pathology of the endocrine system, Due to the defeat of the hypothalamus, namely the supraoptic and paraventricular nuclei, an increased incretion of vasopressin, the main regulator of osmotic pressure, occurs. Vasopressin reduces urine output and promotes fluid retention in the body. Other endocrine changes in the regulation of water metabolism, in particular, the overproduction of aldosterone, are also “to blame” for the progression of the disease.



In the pathology of the endocrine system, 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 originating from acidophilic or main cells of the pituitary gland). In clinical practice, there are cases of the development of Itsenko-Cushing’s disease with encephalitis, arachnoencephalitis, traumatic damage to the 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 in menopause. The development of the disease may be preceded by a craniocerebral or mental trauma, however, 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 an increase in the tone of the serotonergic system, the mechanism of regulation of the functions of the hypothalamic-pituitary-adrenal system and the circadian rhythm of CRH-ACTH-cortisol secretion are disrupted; the principle of “feedback” ceases to work 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 by the pituitary gland and the release of cortisol, corticosterone, aldosterone, androgens of the adrenal cortex. Chronic long-term cortisolemia causes a symptom complex of hypercortisolism (Itsenko-Cushing’s disease). Disorders of the hypothalamic-pituitary-adrenal relationship in the disease are combined with a change in the secretion of other tropic hormones of the pituitary gland. The secretion of growth hormone significantly decreases, the level of gonadotropins and TSH decreases, and prolactin increases. The action 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. Violation of protein metabolism

dit to an increase in the excretion of nitrogen in the urine, a decrease in the level of albumin. A characteristic symptom of the disease is muscle weakness, which is explained by dystrophic changes in the 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 content of potassium in plasma, erythrocytes, 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 a violation of the central mechanisms of regulation of vascular tone. Hypersecretion of glucocorticoids with pronounced mineralocorticoid activity, in particular corticosterone and aldosterone, is also important. Disruption of the function of the renin-angiotensin-aldosterone system leads to the development of persistent hypertension.

The loss of potassium by 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 glucocorticoid potentiation of the effect of catecholamines and biogenic amines, in particular serotonin.

In the pathology of the endocrine system, In the pathogenesis of osteoporosis in Itsenko-Cushing’s disease, the catabolic effect of glucocorticoids on bone tissue is of great importance. The mass of the bone tissue itself, as well as the content of organic matter and its components (collagen, mucopolysaccharides) in it, decreases, and the activity of alkaline phosphatase decreases. Due to the conservation of mass and the violation of the structure of the protein matrix, the ability of bone tissue to fix calcium decreases. A significant role in the occurrence of osteoporosis belongs to a decrease in the absorption of calcium in the gastrointestinal tract, which is associated with inhibition of the processes of calciferol hydroxylation. 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. 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 steroidal diabetes mellitus, relative insulin deficiency, insulin resistance and an increase in the level of counterinsular hormones are of great importance.


In the pathology of the endocrine system, Acromegaly is a disease caused by excess production of growth hormone. It is manifested by increased growth of the skeleton, organs and tissues. This disease of the adenohypophysis occurs equally often among men and women, predominantly of mature age (30-50 years). With an increase in the production of growth hormone in children, when the growth zones are not yet closed, a 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 the gradual development, pathology can be latent for a long time, so it is often difficult to establish its cause. Cases of the onset of the disease after trauma, infection, after pregnancy and in the climacteric period are described. The infectious process in the hypothalamus plays a particularly important role. Whether these factors are the causes of the disease or only provoking factors is not always clear. In recent years, great importance has been attached to heredity, which is confirmed by the presence of a familial form of acromegaly.

The pathogenesis is based on the increased production of somatotropin by acidophilic cells of the adenohypophysis against the background of pituitary adenoma. The typical and most frequent localization of the adenoma is in the area of ​​the sella turcica, but this tumor can develop from the embryonic rudiments of the pituitary gland and is located on the back of the pharynx or in the sphenoid bone. Much less often, the 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 an intense growth of the bones of the skeleton, an increase in the volume of muscles and internal organs (splachnomegaly).

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

As the tumor grows, the hyperfunction of the adenohypophysis is replaced by hypofunction, which leads to insufficiency 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 are described, the cause is malignant pituitary adenoma. Growing intensively, the tumor early metastases to the bones of the skull, chest, and spinal column.

Gigantism is characterized by the accelerated proportional growth of adolescents, i.e. persons with incomplete 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 mainly among boys in the prepubertal and pubertal period.

The main cause of gigantism, as in acromegaly, is an acidophilic adenoma of the pituitary gland, which secretes an excess of growth hormone. Other causes include infection, trauma, hemorrhage, leading to hyperplasia of acidophilic, less often chromatophilic cells.

Increased production of somatotropin leads to intensive epiphyseal bone growth. Since in adolescence the ossification of the epiphyseal cartilage is not over, there is an excessive growth of bones in length. The stimulating effect of growth hormone extends to soft tissues, as well as to internal organs (splanchnomegaly).



In the pathology of the endocrine system, Increased corticosteroid production is often associated with hormone-active tumors. There are the following types.

1. Aldosteroma – a tumor producing aldosterone, causes the development of primary aldosteronism.

2. Glucosteroma – produces mainly glucocorticoids, forms the clinic of Itsenko-Cushing’s syndrome.

3. Androsteroma – produces mainly androgens, leads to virilization in women.

4. Corticoestroma – secretes estrogens, causing feminization in men.

5. Mixed tumors – glucoandrosteroma, etc.

In the pathology of the endocrine system, Glucosteroma is characterized by a disorder of varying severity of all types of metabolic processes. One of the early signs of the disease is a violation of fat metabolism, mainly in the form of redistribution of fats – climacteric hump, relative emaciation of the limbs. Increased blood pressure, thirst, and the appearance of purple stretch marks on the abdomen are also characteristic. Often, a disorder of carbohydrate metabolism is detected with the possible development of diabetes mellitus. Hypokalemia and osteoporosis are also noted.

In the pathology of the endocrine system, Androsteroma is a virilizing tumor that occurs mainly in women and is characterized by excess production of androgens. Clinically, the disease is manifested by varying degrees of virilization. Typical are a decrease in the subcutaneous fat layer, an increase in muscle mass, increased hair growth on the face and extremities, atrophy of the mammary glands, cessation of menstruation, virilization of the clitoris.

In the pathology of the endocrine system, Corticoestroma is a relatively rare estrogen-producing tumor. Clinically manifested in males by bilateral gynecomastia, feminization of the physique, and often testicular hypotrophy. Patients also have pronounced signs of increased production of gluco- and mineralocorticoids – obesity, moderate arterial hypertension.

In the pathology of the endocrine system, Aldosteroma (primary aldosteronism, Conn’s syndrome) is based on hypersecretion of aldosterone. Clinical manifestations consist of severe electrolyte disturbances, renal dysfunctions and arterial hypertension. Along with general and muscle weakness, thirst and increased urination are noted. Changes in potassium and magnesium levels increase neuromuscular irritability and cause recurrent seizures. Hypokalemia is typical, less often hypernatremia with an increase in intracellular sodium is observed.

Congenital adrenal cortex dysfunction (congenital adrenogenital syndrome) (PATHOLOGY OF ENDOCRINE SYSTEM)

In the pathology of the endocrine system, A genetically determined disease associated with a deficiency of enzyme systems that provide the synthesis of glucocorticoids. The increased release of ACTH leads to an increase in the secretion of mainly androgens.

Hereditary deficiency of the enzyme 20,22 – desmolase disrupts the synthesis of steroids from cholesterol into active steroids (aldosterone, cortisol and androgens are not formed). Salt wasting syndrome, glucocorticoid insufficiency, and pseudohermaphroditism develop in males.

Deficiency of 3-ol-dehydrogenase leads to disruption of the synthesis of cortisol and aldosterone in the early stages of their formation. Patients develop a clinical picture of salt loss syndrome, and manifestations of incomplete masculinization of the external genitals are also noted.

Deficiency of 17 – hydroxylase causes a breakdown in the synthesis of androgens, estrogens and cortisol, which leads to sexual underdevelopment. Hypertension and hypokalemic alkalosis are associated with increased secretion of corticosterone and 11-deoxycorticosterone.

Moderate 21-hydroxylase deficiency is clinically manifested by “viril” syndrome. The production of aldosterone and cortisol is not impaired. The increased production of androgens leads to masculinization in women and macrogenitosomia in men.

With a complete block of 21-hydroxylase, along with virilization, salt loss syndrome develops – the loss of sodium and chloride in the urine. In severe cases, there is acute adrenal insufficiency; often exsicosis due to diarrhea and vomiting.

Deficiency of 11 – hydroxylase leads to an increase in the amount of 11-deoxycorticosterone, which has a high mineralocorticoid activity, which causes sodium and chloride retention; along with virilization, hypertension is formed.

With a deficiency of 18-oxidase (only aldosterone synthesis is disturbed), a salt-wasting syndrome is formed.


In the pathology of the endocrine system, Severe condition of the body, clinically manifested by vascular collapse, severe adynamia, impaired consciousness in conditions of a sudden decrease or cessation of corticosteroid secretion. More often, acute adrenal insufficiency develops in patients with primary or secondary adrenal lesions. Decompensation of metabolic processes in patients with chronic

adrenal insufficiency resulting from acute infections, injuries, operations, heavy physical exertion leads to the development of an acute form of the disease (addison crisis).

In the pathology of the endocrine system, Acute failure occurs without a previous pathology of the adrenal glands. The disease caused by thrombosis or embolism of the veins of the adrenal glands is called Waterhouse-Friederiksen syndrome. Hemorrhagic adrenal infarction with this syndrome occurs against the background of infections – meningococcal, pneumococcal or streptococcal with the development of bacteremia, less often with the defeat of the poliomyelitis virus.

In newborns, the most common cause of adrenal apoplexy is birth trauma, less often infectious and toxic factors.

Acute hemorrhages in the adrenal glands are described in stress, sepsis, burns, in AIDS patients.

The pathogenesis of acute adrenal insufficiency is based on the decompensation of all types of metabolism and adaptation processes.

Due to the lack of synthesis of gluco- and mineralocorticoids, sodium and chloride are lost in the urine with the subsequent development of dehydration. The volume of circulating blood decreases, possibly the development of shock. Disorder of potassium metabolism is characterized by a sharp increase in blood, intercellular fluid and in cells. An excess of potassium in the heart muscle leads to a decrease in its function. Indomitable vomiting, frequent loose stools are manifestations of severe electrolyte imbalance.

Carbohydrate metabolism is also severely disturbed: the content of glycogen in the liver and skeletal muscles decreases, and insulin sensitivity increases. The development of hypoglycemia can lead to hypoglycemic coma.

With a lack of glucocorticoids, protein metabolism is also upset with a decrease in the level of urea – the end product of nitrogen metabolism.


In the pathology of the endocrine system, The primary form associated with damage to the adrenal cortex is distinguished, and the secondary form is associated with impaired ACTH secretion by the pituitary gland.

Common causes of primary damage to the adrenal glands include autoimmune processes, tuberculosis, syphilis, fungal infections, and more rare – vascular tumors, metastases, vein and arterial thrombosis. Recently, there has been an increase in autoimmune lesions of the adrenal glands. The involvement of organ-specific immunoglobulins M, impaired immunoregulation in the form of a deficiency of T-suppressors, or a disorder of the interaction of T-suppressors and T-helpers was revealed.

A decrease in the production of adrenal cortex hormones leads to disruption of all types of metabolism in the body. Deficiency of glucocorticoids contributes to a decrease in glycogen stores in the liver and muscles, followed by the development of a hypoglycemic state (weakness, muscle weakness). Protein synthesis in the liver is also inhibited, and water retention in the body increases. Due to a decrease in the volume of muscle tissue, body weight also decreases.

Hyperpigmentation of the skin and mucous membranes (manifestation of primary adrenal insufficiency) is typical. Hypotension often develops.


In the pathology of the endocrine system, Hyperfunction of the adrenal medulla is observed mainly in hormone-active tumors (pheochromocytoma). About 10% of neoplasms from chromaffin tissue are associated with the familial form of the disease with inheritance in an autosomal dominant manner. The pathogenesis is determined by the excess production of catecholamines. Hypertension often develops. Disorders of carbohydrate and protein metabolism are also essential. Since chromaffin cells belong to the APUD system, the diversity of the clinic is also associated with their ability to produce other amines and peptides (serotonin, vasointestinal peptide, ACTH-like factor).


In the pathology of the endocrine system, Stress (tension) is a non-specific reaction of the body that occurs under the influence of any strong stimuli (stressors). Under stress, the same type of changes in the body is noted –

in the adrenal glands, thymus, lymph nodes, blood composition and metabolism and occurs at the level of nerve, endocrine-humoral, systemic, organ, cellular and subcellular components.

A special place in stress is given to catecholamines (adaptive-trophic action of the sympathoadrenal system). They mediate early stress responses by providing an easily available energy source, glucose. Characteristic features of the activation of adrenergic formations: rapid response and equally rapid inactivation of their mediators; a catecholamine chemical signal is received throughout the body. The sympathetic nervous system and the adrenal medulla do not always respond in parallel, i.e. each type of stress has its own characteristics. The sympathetic nervous system plays an important role in the response to cooling, exercise. The adrenal medulla is more important in responding to mental stress, hypoxia, hypoglycemia. During fasting, activation of the medulla is noted,

G. Selye (1936) – the creator of the doctrine of the general syndrome of adaptation

tion – attached the main importance to the activation of the hypothalamic-pituitary-adrenal system. Stress causes an increase in glucocorticoid levels, and they increase the body’s resistance to adverse effects. The adaptive role of glucocorticoids is realized through the following mechanisms:

1) mobilization of the body’s energy and structural resources (the content of glucose, fatty acids, amino acids, nucleotides increases in the blood);

2) directed transport of mobilized resources from inactive systems to a functional system that carries out an adaptive response;

3) direct or indirect influence of “stress” hormones on the activity of lipases, phospholipases, the intensity of lipid peroxidation; is on the main processes, renewal of the lipid layer of biomembranes;

4) activation of the adenylate cyclase system of cell membranes and an increase in the concentration of the main natural activator in the cell – calcium;

5) anabolic phase of stress, manifested by generalized activation of protein synthesis and the formation of a systemic structural trace and long-term adaptation

The transition of an adaptive stress response to a damaging one is determined by the duration or excessive exposure to the stressor (the transition from eustress to distress, according to G. Selye).

Adaptation syndrome consists of three successive stages: stages of anxiety, resistance and exhaustion.

The anxiety reaction consists in the rapid mobilization of the body’s defenses and, in turn, consists of the shock and counter-shock phases. In the shock phase, muscle and arterial hypotension, hypothermia, hypoglycemia, blood clotting, eosinopenia and increased capillary permeability are noted. Activation of catabolic processes leads to involution of the thymic-lymphatic apparatus, negative nitrogen balance, ulcerative lesions of the gastric and duodenal mucosa.

The counter-shock phase is characterized by an increase in blood pressure, muscle tone, and blood glucose levels.

In the stage of resistance with hypertrophy of the adrenal cortex, activation of gluconeogenesis and anabolic processes is revealed.

With prolonged or excessive exposure to a stressor, adaptation is impaired, atrophy of the adrenal cortex, a drop in blood pressure, and increased breakdown of proteins develop.

Lack of adaptation or its complications are, according to G. Selye, the cause of the development of adaptation diseases (rheumatism, bronchial asthma, heart disease, blood vessels, kidneys).

When adapting to repeated or prolonged exposure to stressors, the degree of activation of adrenergic centers, releasing factors, ACTH release and an increase in the concentration of catecholamines and corticosteroids decreases, but their more pronounced activation is noted with the introduction of exogenous ACTH. This is one of the mechanisms of “patience” and prevention of stress damage. To a greater extent, such mechanisms are mediated through stress-limiting systems (GABAergic, dopaminergic and serotonergic systems of the brain) and the anticorticoid defense system (increased binding of transcortin).

It is also important that the stage of resistance with a relatively weak stressor is characterized by an increase in resistance not only to this factor, but also to a number of others. Regular exposure to mild to moderate irritants (subject to personality) – exercise, cold showers, and many others –

increases the ability of stress-implementing systems for adaptive responses.



In the pathology of the endocrine system, Diffuse toxic goiter (Graves ‘disease, Graves’ disease), according to modern concepts, is a genetically determined, autoimmune disease. The role of the hereditary factor is confirmed by the presence of familial cases of the disease, the detection of thyroid antibodies in the blood of relatives, the high frequency of other autoimmune diseases, and the coincidence of specific HLA antigens (B8, DR3).

The pathogenesis of the disease is due to a hereditary defect, apparently, of T-lymphocyte suppressors, which leads to the accumulation of “forbidden” clones of T-lymphocyte helpers. In this regard, the formation of autoantibodies to thyroid antigens is stimulated. The peculiarity of such antibodies is their stimulating effect on the cells of the thyroid follicles, which leads to the development of hyperfunction and hypertrophy of the thyroid gland. Immunoglobulins that stimulate the thyroid gland are combined into a common group –

TSI. The most studied long-acting thyroid stimulator is

LATS. With thyrotoxicosis, it is secreted in about 90% of cases, although it is not a strictly specific symptom, since it is also detected in patients with subacute thyroiditis, Hashimoto’s thyroiditis.

The level of TSH is often reduced due to the suppression of its pituitary production by high concentrations of thyroid hormones. In rare cases, there are patients with TSH-produced pituitary adenoma, while the TSH content is significantly increased and there is no TSH response to TRH.

Under the influence of mental trauma, an increase in the secretion of catecholamines occurs, followed by parahypophyseal activation of the thyroid gland. Suppression of the thymus often develops, which leads to an increase in the frequency of autoimmune diseases.

Since an excess of thyroid hormones affects various organs and systems, the clinical picture of thyrotoxicosis is complex and diverse. In addition to the cardinal symptoms – goiter, exophthalmos (bulging eyes), tremor and tachycardia – patients have increased nervous excitability, temperature fluctuations (usually subfebrile condition), and increased reflexes. Patients are excessively active, but they often have weakness, attacks of muscle weakness.

Exophthalmos is possible both with thyrotoxicosis and with hypothyroidism and Hashimoto’s thyroiditis. Thyrotoxic exophthalmos is caused by an excess of thyroid hormones, hypersensitivity to catecholamines and impaired autonomic innervation. Ophthalmopathy is an autoimmune disease associated with the formation of exophthalmic antibodies, edema of periorbital tissues.

Disorders of the cardiovascular system in diffuse toxic goiter are caused, on the one hand, by a pathologically increased sensitivity to catecholamines, on the other –

the direct effect of excess thyroid hormones on the myocardium. The cumulative effect of these factors, mediated through the peripheral circulation, leads to hemodynamic disorders, hypoxia and severe metabolic-dystrophic damage with the development of thyrotoxic cardiomyopathy. Clinically, this is manifested by arrhythmias (tachycardia, extrasystole, atrial fibrillation and flutter) and heart failure.

In the pathology of the endocrine system, A thyrotoxic crisis is a severe, often life-threatening complication of diffuse toxic goiter associated with an exacerbation of all its symptoms. A provoking role can be played by stressful situations, physical overstrain, infections, and surgical interventions. In the pathogenesis of a crisis, the sudden entry into the blood of large amounts of thyroid hormones, increased adrenal insufficiency, activation of the higher parts of the nervous system, the sympathoadrenal system are of primary importance.


In the pathology of the endocrine system, In most cases (up to 95%), the disease is caused by a pathological process in the thyroid gland itself, which reduces the production of thyroid hormones (primary hypothyroidism). Violation of the regulatory and stimulating effect of hypothalamic releasing factor (thyreoliberin) or pituitary TSH leads to tertiary and secondary hypothyroidism, respectively. It is also possible that peripheral hypothyroidism is associated either with a disorder of the metabolism of thyroid hormones in the periphery (the formation of T4 not T3, but only reverse T3), or with a decrease in the sensitivity of the nuclear receptors of organs and tissues to thyroid hormones.

Primary hypothyroidism most often occurs on the basis of chronic autoimmune thyroiditis. Thyroid tissue, having passed the stage of lymphoid infiltration, gradually atrophies and is replaced by fibrous tissue. Other causes of primary hypothyroidism include the following.

1. Complications of therapeutic measures (resection of the gland, treatment with radioactive iodine, radiation therapy, the use of thyreostatic drugs – mercazolil, lithium, long-term intake of sulfa and hormonal drugs);

2. Tumors, acute and chronic infections leading to destructive changes (thyroiditis, abscess, tuberculosis, actinomycosis);

3. Aplasia and hypoplasia of the thyroid gland due to defects in intrauterine development.

Secondary and tertiary hypothyroidism develops with inflammatory, destructive or traumatic lesions of the pituitary gland and / or hypothalamus (tumor, hemorrhage, necrosis, surgical or radiation hypophysectomy) with insufficient release of TRH and TSH and a subsequent decrease in the production of thyroid hormones. More often, secondary hypothyroidism occurs as part of the general pituitary pathology and is combined with hypogonadism, hypocorticism, and excess growth hormone.

In the pathology of the endocrine system, The pathogenesis of hypothyroidism is determined by a decrease in the level of thyroid hormones with a wide range of effects on physiological and metabolic processes in the body. All types of metabolism, oxygen utilization by tissues are suppressed, oxidative processes are inhibited, enzymatic activity, gas exchange and basal metabolism are weakened. Slowing down the synthesis and catabolism of proteins and their excretion from the body cause a significant accumulation of protein breakdown products in organs and tissues. Acid glycosaminoglycans (mainly derivatives of glucuronic acid) are excessively deposited in the heart, lungs, kidneys and, above all, in the skin. Their excess changes the colloidal structure of the connective tissue, they increase its hydrophilicity and bind sodium, which forms myxedema against the background of obstructed lymphatic drainage.

Deficiency of thyroid hormones delays the development of brain tissue and inhibits higher nervous activity, especially in childhood. In adults, hypothyroid encephalopathy develops, characterized by a decrease in mental activity and intelligence, a weakening of conditioned and unconditioned reflex activity.

The activity of the adrenal cortex is limited, the peripheral metabolism of corticosteroids and sex hormones is disrupted. A compensatory increase in the content of catecholamines in the absence of the required level of thyroid hormones is not realized due to a decrease in the sensitivity of β-adrenergic receptors. According to the feedback mechanism, the secretion of TSH and often prolactin is increased. TSH stimulates compensatory hyperplasia of thyroid tissue, the formation of cysts, adenomas.

A complication of the disease is a hypothyroid coma, accompanied by suppression of DC, a progressive decrease in cardiac output, increasing brain hypoxia and hypothermia. An important link in pathogenesis is hypocorticism. With prolonged hypothermia (30 ° C), the functions of all internal organs, especially the adrenal glands, are weakened.


In the pathology of the endocrine system, The most common autoimmune chronic thyroiditis is Hashimoto’s goiter. The disease is of hereditary origin and is associated with the DR5, DR3, B8 loci. A genetic defect in immunocompetent cells causes a breakdown in natural tolerance and infiltration of the thyroid gland by macrophages, lymphocytes and plasma cells. This is, apparently, about the primary defect of T-suppressors. The formation of antibodies, immune complexes causes the release of biologically active substances; the end result is destructive changes in thyrocytes and the development of hypothyroidism. Excessive production of TSH enhances the growth of the preserved epithelium (with subsequent infiltration by lymphoid cells), which, against the background of an increase in hypothyroidism symptoms, increases the size of the thyroid gland; a goiter is formed.


In the pathology of the endocrine system, A disease occurring in geographic areas with an iodine deficiency in the environment and characterized by an enlarged thyroid gland. An area is considered endemic if more than 10% of the population has clinical signs of goiter.

In addition to iodine deficiency, in the development of endemic goiter, the intake of goitrogenic substances (thiocyanates and thiooxizolidones contained in vegetables), iodine in an inaccessible form for absorption, genetic disorders of intrathyroid metabolism of iodine and hormone biosynthesis, and autoimmune mechanisms are also essential. The role of deficiency of microelements (cobalt, copper, zinc, molybdenum), bacterial and worm pollution of the environment is also shown. Familial goiter and high concordance in monozygotic twins suggest the presence of genetic factors.

In response to iodine deficiency, the following compensatory mechanisms are activated: an increase in the thyroid clearance of inorganic iodine, thyroid hyperplasia, an increase in T3 synthesis, an increase in the conversion of T4 to T3 in peripheral tissues.

The clinical picture of endemic goiter is the symptoms of hypothyroidism. In severe cases, deaf-dumbness and cretinism are often noted, associated with deep pathology in the intrauterine period of development.


Parathyroid gland pathophysiology (PATHOLOGY OF ENDOCRINE SYSTEM)

In the pathology of the endocrine system, Along with thyrocalcitonin and the active form of vitamin D 3 (1,25-dioxycholecalciferol), parathyroid hormone (PTH) provides calcium and phosphorus homeostasis. The main targets of PTH are the kidneys and bones of the skeleton, but its effect on calcium absorption in the intestine, carbohydrate tolerance, serum lipid levels, and its role in the development of impotence and pruritus are known.

The main effect of PTH in bones is to enhance the processes of resorption, which affects both mineral and organic components. PTH promotes the growth and activation of osteoclasts, which is accompanied by increased osteolysis and increased bone resorption. This dissolves crystals of hydroxyapatite with the release of calcium and phosphorus into the blood (the main mechanism for increasing the level of calcium in the blood).

The most important effect of PTH on the kidney is a decrease in phosphorus resorption with an increase in phosphaturia. PTH reduces calcium clearance, tubular reabsorption of sodium and its bicarbonate, increases the formation of vitamin D 3 in the kidneys , which in turn increases calcium reabsorption in the small intestine, stimulating the activity of calcium-binding protein in its wall.

In the pathology of the endocrine system, Hyperparathyroidism (HPT) – fibrocystic osteodystrophy, Recklinghausen’s disease, caused by pathological hyperproduction of PTH. There are primary, secondary and tertiary HPT. In primary HPT, overproduction of PTH is caused by the development of an adenoma (parathyroid adenoma), less often – diffuse hyperplasia or cancer.

Secondary HPT is associated with the hyperfunction of the parathyroid glands in conditions of prolonged hyperphosphatemia and 1.25 (OH) 2 D 3 deficiency in chronic renal insufficiency, and stichronic hypocalcemia in diseases of the gastrointestinal tract.

Tertiary HPT is associated with the development of adenoma of the parathyroid glands and its autonomous functioning under conditions of prolonged secondary HPT (according to the principle of “hyperfunction – hyperplasia tumor”).

With HPT, bone resorption occurs with a neoplasm of a young, still slightly mineralized bone, which contains less calcium. Due to the lack of calcium, the bones become soft, under the influence of load they easily bend, break (pathological fractures).

Excessive excretion of calcium by the kidneys leads to polyuria and hypostenuria; kidney stones are often formed. Impregnation of the renal parenchyma with calcium salts (nephrocalcinosis) can subsequently lead to renal failure.

In the pathology of the endocrine system, Hypoparathyroidism is an insufficiency of the parathyroid glands, caused by changes in the secretion of PTH, accompanied by a violation of calcium-phosphorus metabolism. Etiological variants of hypoparathyroidism: postoperative, radiation, vascular, caused by infectious injury, congenital underdevelopment, as well as autoimmune genesis.

In the pathogenesis of the disease, the main role is played by the absolute or relative deficiency of PTH with hyperphosphatemia and hypocalcemia. There is a violation of absorption in the intestine of calcium, a decrease in its mobilization from the bones and reabsorption in the kidneys. Lack of PTH leads to hypocalcemia, independently or indirectly, due to a decrease in the synthesis of vitamin D 3 in the kidneys . The electrolyte balance is disturbed with a change in the Ca – P and Na – K ratio.

There is a breakdown in the permeability of cell membranes, the polarization processes in the synapse area change. As a result, neuromuscular excitability and general autonomic reactivity increase; the result is convulsions. In the genesis of tetany, impairment of magnesium metabolism (hypomagnesemia) is important. It promotes the penetration of sodium ions into the cell and the release of potassium from it, which also increases neuromuscular excitability. The development of alkalosis gives a similar effect.



In the pathology of the endocrine system, Diabetes mellitus is a collective, differentiated group of clinical syndromes based on absolute or relative insulin deficiency. It is characterized by a violation of the metabolism of the main energy substrates – carbohydrates, proteins, fats, and is also accompanied by primary or secondary changes in the secretion of many hormones – not only insulin, but also glucagon, catecholamines, STH, cortisol –

or at least sensitivity to them.

Diabetes mellitus is, apparently, a combined polyendocrine form of pathology. It is accompanied by the accelerated development of atherosclerosis, increases the risk of coronary artery disease by 4 times or more, serves as the main cause of blindness and occupies

3rd place among the main causes of death.


  1. Spontaneous diabetes mellitus:
    • type I, or insulin-dependent diabetes;
    • type II, or non-insulin dependent diabetes.
  2. Secondary diabetes:
    1. with diseases of the gland (pancreatic diabetes – pancreatotomy, insufficiency of the gland function, hemochromatosis);
    2. hormonal disorders: excessive secretion of counter-insular hormones (acromegaly, Cushing’s syndrome, pheo-chromocytoma);
    3. medicinal – potassium-excreting diuretics, counterinsulyar hormones, psychotropic drugs, diphenylgens dantoin;
    4. associated with complex genetic syndromes (ataxia-telangiectasia, Lawrence-Moon-Biedl syndrome, myoto-dystrophy, Friedreich’s ataxia).
  3. Impaired glucose tolerance (previously called chemical, asymptomatic, latent and subclinical diabetes): normal fasting blood glucose, and 2 hours after taking glucose – more than 1400 mg / ml, but below 2000 mg / ml.
  4. Diabetes of pregnancy: impaired glucose tolerance that began during pregnancy.

The proposed classification does not exhaust all possible forms of diabetes mellitus. In particular, new syndromes have been found: diabetes associated with malnutrition; due to the formation of antibodies to insulin receptors; caused by genetic defects in the structure of insulin, familial hyperproinsulinemia, etc.

To date, it has not been possible to find a single etiological factor that causes spontaneous diabetes. More and more evidence is accumulating that diabetes mellitus is a heterogeneous group of disorders with different etiologies. Most often, the role of genetic factors, autoimmune processes and environmental factors (viral infections, nutritional errors) is revealed in the origin of diabetes mellitus.

The familial nature of diabetes has long been established. The incidence of the disease in relatives is 4-10 times higher. Concordance in monozygotes for diabetes is 45-96%, in dizygotes – 3-37%. Inheritance type

It is difficult to establish, therefore, they usually talk about a hereditary predisposition, which is associated with type I diabetes with the HLA – D locus in the short arm of chromosome 6, as well as with HLA antigens – B8, BW 15, DW 3, DW.

The presence of one of these haploids increases the risk of type I diabetes by 2-6 times. Apparently, genetic factors play a role in the development of all forms of spontaneous diabetes; each case has its own characteristics of inheritance, although lack of data complicates genetic analysis and identification of “prediabetes”. Violation of the genes of the short arm of the 6th chromosome creates the prerequisites for autoimmune destruction of islet B-cells, caused by the action of environmental factors. In patients with type I diabetes, antibodies to islet cell proteins are often found, which indicates an autoimmune component of pathogenesis.

For quite a long time, diabetes mellitus has been modeled in animals using chemical agents that have a destructive effect on islet B-cells (alloxan, dithizone, streptozotocin antibiotic). The pathology in such cases is very similar to type I diabetes in humans. B cells can also be selectively damaged by β-tropic viruses (Coxsackie-B, cytomegalovirus, measles virus, Epstein-Barr virus, mumps).

It should be concluded that the development of diabetes in each individual case is an integrated response to the combined action of many factors in various combinations – genetic predisposition, chemical and infectious factors, autoimmune processes, nutritional disorders, physical activity, mental stress situations, etc.

In type II diabetes, obesity is the main acquired factor involved in the development of the disease, which affects up to 80% of patients.

Obese people have an increased prevalence of diabetes. Its appearance depends more on how long a person has put on weight than on the degree of obesity. The mechanism of development of diabetes mellitus is associated with insulin resistance. Obesity is accompanied by hyperinsulinemia, both on an empty stomach and after a meal. Hyperinsulinemia is a consequence, not a cause of obesity, as evidenced by the fact that weight loss leads to a decrease in insulin levels, while an increase in it is accompanied by hyperinsulinemia. The factors that determine the magnitude of hyperinsulinemia in obesity include: the degree of obesity, the calorie content of food, the content of carbohydrates in it, and the degree of physical activity.

There is a direct correlation between body weight and the level of increased insulin in the blood (of course, with obesity, and not with an increase in muscle mass). Reducing the carbohydrate content of food and its calorie content leads to the normalization of insulin levels long before reaching normal body weight. Exercise promotes a decrease in insulin regardless of weight loss, since glucose uptake by working muscles does not depend on an increase in insulin secretion. Physical activity, as it were, turns skeletal muscles into insulin-independent tissues.

Hyperinsulinemia in obesity is apparently based on hyperaminoacidemia, which stimulates β-islet cells.

The regulation of insulin receptors (occupancy rate) is determined by the surrounding insulin concentration. Under conditions of hyperinsulinemia (obesity), the number of receptors decreases, while under conditions of hypoinsulinemia (fasting), it increases. It is the decrease in the number of insulin receptors in obesity that explains the development of insulin resistance.

In genetically predisposed individuals with a limited ability to secrete insulin, obesity creates demands for the hormone that exceed the capacity of β-cells. The influence on the development of diabetes and disturbances in the mechanisms of appetite regulation is also assumed.

Diabetes can form a second time due to destructive processes or surgery on the pancreas (pancreatic diabetes); as a result of hypersecretion of insulin antagonist hormones; in conditions of decreased glucose tolerance in non-endocrine disorders (uremia, liver cirrhosis). Presumably, in each case, genetic predisposition also plays a role. In this regard, in particular, the likelihood increases that a given degree of destruction of the pancreas or the degree of hypersecretion of counterinsular hormones will lead to hyperglycemia.

In pancreatophobic diabetes, there is a greater tendency to hypoglycemia, a lower incidence of ketosis and a lower need for insulin than in spontaneous diabetes.

To a large extent, these features are determined by glucagon deficiency, while in spontaneous diabetes, hyperglucanemia occurs.

Pancreatic diabetes mellitus is subdivided into fibrocalculous and protein deficient. With fibrocalculous dia-

Beta, calcifications and fibrosis of the gland are found in the pancreatic ducts without inflammatory processes. There is a low secretion of insulin and glucagon, disorder syndrome

suction. In the pathogenesis of this type of diabetes, it is important to

excess consumption of foodstuffs containing cyanides (sorghum, cassava, millet, beans), against the background of a deficiency of protein compounds.

Protein-deficient diabetes is defined by a diet low in protein and saturated fat.

Pancreatogenic diabetes is caused by an excessive intake of iron – with frequent blood transfusions, the use of alcohol stored in iron containers.

Prolonged hypersecretion of insulin antagonist hormones (STH, glucocorticoids) or hormones that block its secretion (catecholamines) is often accompanied by impaired glucose tolerance. The general features in these forms of diabetes are as follows.

1. Reversibility of hyperglycemia in the correction of the primary condition.

2. Absence in most cases of ketosis, which indicates the presence of endogenous insulin.

The following forms of secondary diabetes mellitus are distinguished, depending on the hypersecretion of counterinsular hormones.


In the pathology of the endocrine system, STH interferes with insulin-mediated transmembrane transfer and absorption of glucose, stimulates lipolysis. Patients with acromegaly have fasting hyperinsulinemia and an increased insulin response to food intake. Insulin resistance is determined, apparently, by a decrease in the binding of insulin to receptors.


In the pathology of the endocrine system, With severe hypercortisolism, hyperinsulinemia and insulin resistance often develop, and glucose tolerance also decreases. In addition to stimulating gluconeogenesis, glucocorticoids interfere with insulin-mediated glucose uptake.


In the pathology of the endocrine system, Excess catecholamines can interfere with the secretion and / or action of insulin. In tumors with hypersecretion of predominantly norepinephrine, insulin secretion is inhibited. Hypersecretion of predominantly adrenaline leads to both a blockade of glucose uptake and hypoinsulinemia.

There are also known rare forms of pathology with the possible development of secondary diabetes mellitus in connection with a glucagon-secreting tumor, as well as with multiple endocrine insufficiency. Bronze (with hemochromatosis) and thymogenic secondary diabetes mellitus are described.

The clinical signs of diabetes mellitus are divided into three groups:

1) directly related to an increase in blood glucose levels – hyperglycemic; against the background of hyperglycemia, glucosuria, polyuria, polydipsia and polyphagia develop;

2) due to distant manifestations (microangio-pathia);

3) associated with the acceleration of the development of general pathological processes or an increased predisposition to them (atherosclerosis, skin and urinary infections).

Severe manifestations of diabetes mellitus, regardless of type, are diabetic microangiopathy and neuropathy. In their pathogenesis, metabolic disorders are important, especially hyperglycemia. Glycosylation of proteins, disturbance of cellular functions in non-insulin dependent tissues, changes in rheological properties of blood and hemodynamics are decisive.

Glucose, using a non-enzymatic process, reacts with the N-terminal

the amino group of the Hb A chain to form ketoamine –

Hb A 1C and Hb A ABC ; similarly with blood proteins, cell membranes, low density lipoproteins, proteins of peripheral nerves, collagen, elastin, lens. The formation of glycosylated forms of proteins leads to dysfunction, activation of the formation of antibodies. Increased stimulation of the polyol pathway of glucose metabolism in non-insulin dependent tissues leads to the accumulation of sorbitol and even fructose (utilization without the participation of insulin). The formation of an excess of intracellular sorbitol occurs in the cells of the nervous system, pericytes of the retina, lens, pancreas, kidneys, and vascular walls containing aldose reductase. An increase in the level of sorbitol causes an increase in osmotic pressure, cellular edema, and contributes to the disruption of microcirculation.

These are the features of the pathogenesis of diabetic angiopathies (nephropathies, retinopathies and neuropathies).

A formidable complication of diabetes mellitus (mortality rate reaches 50%) is diabetic coma.

• The most clinically important is hyperosmolar coma. Often, the latter is accompanied by the phenomena of ketoacidosis, when ketogenesis sharply increases against the background of lipolysis activation and deficiency of oxaloacetic acid and NADPH H2.

Hyperketonemia results in ketonuria with sodium loss and dehydration, as well as ketoacidosis. These are the features of the development of ketoacidotic coma in diabetes mellitus.

Atherosclerosis is formed in patients with diabetes mellitus prematurely, due to which a person ages prematurely and

She dies out of life. In the pathogenesis of atherosclerosis, changes in platelets, STH and lipoproteins are important.


Endothelial damage under conditions of increasing hypoxia is accompanied by an increase in the permeability of the vascular wall. Platelet adhesion to the damaged area is accompanied by local release of mitogen, which stimulates proliferation

and migration of smooth muscle cells. They are like macrophages

gum, capture lipids, including cholesterol. Lipids accumulate under the endothelium, which leads to narrowing and even complete closure of the vessel. Diabetes dramatically accelerates this process:

– under the influence of excess STH, the proliferation of smooth muscle cells increases;

– increased synthesis of thromboxanes promotes platelet adhesion and mitogen release;

– in diabetes, there is an increase in the level of low-density lipoproteins and a decrease in the content of high-density lipoproteins.

Diabetes mellitus is associated with many cases of stroke, myocardial infarction, and most amputations for gangrene of the toes.





In the pathology of the endocrine system, Full functioning is possible only with adequate interaction of all levels of regulation: the central nervous system, hypothalamus, pituitary gland, ovaries, as well as with sufficient activity of other endocrine glands.

Primary hypofunction includes:

  • ovarian dysgenesis (cider of depleted ovaries – early menopause);
  • resistant ovary syndrome;
  • various lesions of the ovaries (chemotherapy, radiation, inflammatory diseases, tumors, castration).

Primary hypofunction is characterized by genetic defects detected by the influence of various exogenous factors and is manifested by atresia of the follicular apparatus, low levels of estrogen and progestin production.

Secondary ovarian hypofunction is possible with:

  • functional disorders of the hypothalamic-pituitary system (stress, anorexia nervosa, hyperprolactinemia, etc.);
  • isolated hypogonadotropic ovarian hypofunction;
  • organic lesions of the hypothalamic-pituitary system;

topics (tumors, infectious and inflammatory lesions, circulatory disorders, trauma, radiation, intoxication, genetic defects).

In the pathology of the endocrine system, Ovarian hypofunction is a concept that unites a large number of diseases of different etiology and pathogenesis, which have similar symptoms: amenorrhea, infertility, hypoestrogenism, ovarian and uterine hypoplasia.


In the pathology of the endocrine system, Hypofunction of the male gonads (hypogonadism, testicular insufficiency) is a pathological condition with a decrease in the level of androgens, characterized by underdevelopment of the genitals and secondary sexual characteristics, as well as, as a rule, infertility.

Primary hypogonadism.

1. Congenital:

  • anorchism,
  • Klinefelter syndrome,
  • XX syndrome in men,
  • Shereshevsky-Turner syndrome in men,
  • del Castillo syndrome (Sertoli – cellular).
  • incomplete masculinization syndrome.

2. Acquired:

  • infectious and inflammatory lesion of the testicles (orchitis, epididymitis, vesiculitis),
  • caused by the impact of damaging external factors (cooling, overheating, intoxication),
  • tumors, trauma.


Secondary hypogonadism.

1. Congenital:

  • Callman syndrome,
  • isolated deficiency of luteinizing hormone (LH),
  • pituitary dwarfism,
  • craniopharyngioma,
  • Maddock syndrome.

2. Acquired:

  • infectious and inflammatory lesions of the hypothalamic-hypophisar area,
  • adiposogenital dystrophy,
  • tumors of the hypothalamus and pituitary gland,
  • loss of tropic functions as a result of traumatic or surgical damage to the hypothalamus and pituitary gland,
  • hyperprolactinemic syndrome.

Embryonic forms of androgen deficiency are manifested by anorchism with the subsequent development of hermaphroditism.

Pre-pubertal forms of hypogonadism, like embryonic ones, are characterized by a weak severity of secondary sexual characteristics and the formation of a “eunuchoid” syndrome.

In the pathology of the endocrine system, Acquired primary hypogonadism is more often associated with infectious and inflammatory diseases of the testicles and (or) their appendages, as well as with trauma, cooling or overheating.

Secondary hypogonadism most often occurs due to primary insufficiency of the hypothalamic-pituitary system against the background of its defeat in tumors, vascular disorders, inflammatory processes.

Congenital LH and FSH deficiency leads to the development of Kallman’s syndrome, and the combined violation of the gonadotropic and adrenocorticotropic functions of the pituitary gland leads to the development of Maddock’s syndrome.