Pathology of the Endocrine system - 2

The endocrine system is a set of anatomically, histologically and cytologically

differentiated structures that produce hormones.
Hormones are synthesized in anatomically autonomous structures (endocrine
glands), as well as endocrine cells of other organs and tissues.
• Endocrine glands: adenohypophysis, pineal gland, thyroid gland, parathyroid
glands, adrenal glands.
• Endocrine cells of organs and tissues: hypothalamus, pancreas, testis, ovary,
thymus, lungs, gastrointestinal tract, kidneys, heart.
By the distance from the hormone-producing cell to the target cell, endocrine
(distant), paracrine (at a short distance) and autocrine (hormone-producing cell is
its target) regulation variants are distinguished.

Etiology and pathogenesis of endocrine disorders

There are centrogenic, primary glandular and postglandular variants of the initial
links in the pathogenesis of endocrine disorders.

Centrogenic initial link

It is caused by a violation of the mechanisms of neurohumoral regulation of the
endocrine glands by the neurons of the cerebral cortex or the hypothalamic-
pituitary system.
• At the level of the cerebral cortex, this is due to:
♦ Development defects and organic brain damage (more often as a result of
hemorrhage, tumor growth, trauma).
♦ By the action of toxins (eg ethanol, drugs, microbial endo- and exotoxins).
♦ Disorders of higher nervous activity (as a rule, neuroses, prolonged stress,
psychosis).
• At the level of the hypothalamus and pituitary gland is most often caused by:
♦ Gene defects (mutations in the genes of liberins, statins, adeno- and
neurohypophyseal hormones, as well as their synthesis enzymes).
♦ Direct injury (eg, tumor growth or decay, hemorrhage, trauma).
♦ Exposure to toxic substances (eg ethanol, tetanus toxin).
Disorders of the functions of the cerebral cortex and hypothalamic-pituitary system
lead to disorders in the formation of hypothalamic neurohormones (liberins,
statins, ADH), as well as hormones of the adenohypophysis. The latter, in turn,
causes disturbances in the functions of the corresponding glands and endocrine
cells, regulated by the tropic hormones of the adenohypophysis.

Primary glandular disorders

Primary glandular disorders are caused by disorders in the synthesis or incretion of
hormones by the endocrine glands or individual endocrine cells. This is observed
when:
♦ changes in the mass of endocrine cells and the level of hormone production;
♦ fluctuations in the activity or content of hormone biosynthesis enzymes;
♦ deficiency of substrates for hormone synthesis;
♦ decrease in the synthesis of hormones with prolonged hyperfunction of the
gland;
♦ violation of the deposition or release of hormones by cells.

Postglandular endocrinopathies
Postglandular endocrinopathies are caused by various disorders of hormone
transport, its reception and postreceptor changes in target cells.
• The transport mechanism is an excessive decrease or increase in the binding of
hormones to their transport proteins (eg, insulin, cortisol, iodine-containing thyroid
hormones).
• The "counter-hormonal" mechanism includes several options that lead to a
decrease or elimination of the effects of hormones. Of greatest clinical significance
are:
♦ Transport proteins. Unrelated hormones are rapidly inactivated in the blood.
♦ Antibodies. Found antibodies to all protein hormones (for example, insulin,
adenocorticotropic hormone, somatopropin).
♦ Enzymes. An increase in the activity of insulinase, glutathione reductase or
glutathione transferase leads to the destruction of insulin; monoamine oxidase or
catechol-o-methyltransferase - adrenaline.
♦ Change in the conformation of hormone molecules. It is observed in conditions
of pronounced acidosis in cells and interstitial fluid, as well as in the interaction of
hormones with toxins, heavy metal salts, free radicals.
♦ Hormone antagonists. Thus, an excess of catecholamines, cortisol, glucagon,
growth hormone, thyroid hormones in the blood counteracts the realization of the
effects of insulin and vice versa.
• The receptor (reactive) mechanism is associated with a violation of the
interaction of the hormone with its receptor. There are several varieties of this
mechanism:
♦ Changes in the number of hormone receptors (their increase or decrease), as well
as deviations from the normal ratio of high and low affinity receptors.
♦ Formation of anti-receptor antibodies (for example, to insulin receptors or TTH).
♦ Blockade of receptors by non-hormonal ligands similar to hormone molecules
(eg insulin, thyroid hormones).
♦ Cross-hormone effect (for example, growth hormone can activate prolactin
receptors, resulting in galactorrhea).
• The metabolic mechanism is a violation of hormone metabolism. For example,
disorders of degradation in hepatocytes of insulin and steroid hormones; excessive
deiodination of thyroxine.

Pathophysiology of the hypothalamo-hypophysical system

Pathology of the adenohypophysis

Varieties of typical forms of disorders of the adenohypophysis are differentiated
taking into account the following criteria:
♦ the level of production or effects of hormones: hypofunction (hypopituitarism)
and hyperfunction (hyperpituitarism);
♦ “scale” of lesions of the adenohypophysis: partial and total;
♦ time of occurrence in ontogenesis: early and late;
♦ origin: primary (pituitary), secondary (hypothalamic);
♦ manifestations: diseases, syndromes, pathological conditions.

HYPOPITUITARISM

Hypopituitarism is a deficiency in the content or effects of one or more hormones

of the adenohypophysis.
Causes of hypopituitarism: destruction, ischemia, hemorrhages, inflammation,
malformations, genetic defects in the cells of the adenohypophysis.
Types of hypopituitarism
• Partial hypopituitarism. There are no "pure" partial forms of adenohypophyseal
insufficiency. As a rule, in each patient only signs of deficiency of one of the
hormones of the adenohypophysis dominate.
♦ Pituitary dwarfism (pituitary dwarfism, microsomia, nanosomy). It develops with
a deficiency of STH or somatoliberin.
♦ Pituitary hypogonadism (pituitary eunuchoidism) develops with defects in FSH,
lutropin and their receptors.
♦ Pituitary (neuroendocrine) obesity.
♦ Disorders of sexual differentiation.
• Panhypopituitarism. The concept of "total hypopituitarism" is used when 75-90%
of the parenchyma of the adenohypophysis is damaged. Examples of this
pathology: postpartum hypopituitarism (Shean's syndrome) and pituitary cachexia
(Simmonds disease).

Pathogenesis and manifestations

The mechanisms of development and manifestation of hypopituitarism are very
variable, depending on the scale and degree of damage to the pituitary gland, the
underlying pathology and many other factors. There are three main groups of
signs: polyhormonal insufficiency, neurosomatic disorders and mental disorders.
• Signs of polyhormonal deficiency. They are the result of a deficiency of certain
adenohypophyseal hormones.
♦ STH: progressive loss of body weight, changes in the skin and its derivatives
(dryness, wrinkling of the skin, brittle hair and nails), dystrophic and degenerative
changes in bone tissue (decalcification, osteoporosis).
♦ TTH: development of hypothyroidism (which is manifested by a decrease in
intelligence and physical activity, dystrophic changes in organs).
♦ Gonadotropins: signs of eunuchoidism and infantilism.
♦ ACTH: the development of hypocorticism, manifested by a deficiency of gluco-
and mineralocorticoids, as well as sex hormones.
• Neurosomatic disorders.
♦ Caused by damage to the nuclei of the hypothalamus: hypothermia (rarely - low-
grade fever), autonomic disorders (transient hypoglycemia, polyuria, hypotensive
reactions, collapses, tetanic convulsions, etc.).
♦ Caused by an increase in intracranial pressure (with intracranial growth of a
neoplasm or hemorrhage): limitation of visual fields, decreased visual acuity,
headaches.
• Mental disorders. Most often they are characterized by apathy, depression, a
decrease in the emotional level of assessing events, hallucinations, and paranoid
psychosis.

HYPERPITUITARISM
Hyperpituitarism is an excess of the content or effects of one or more hormones of
the adenohypophysis.
Causes . In most cases, hyperpituitarism is the result of an adenoma of the anterior
pituitary gland (less often malignant tumors, hypothalamic pathology,
accompanied by overproduction of liberins or hypoproduction of statins).
Types of hyperpituitarism
Hyperpituitarism is characterized, as a rule, by partial pathology.
• Pituitary gigantism (macrosomia) - an excessive increase in height, body size and
internal organs. According to the time of occurrence in ontogenesis, it is an early
form of endocrinopathy.
♦ Initial links of pathogenesis: centrogenic (lead to overproduction of
somatoliberin or growth hormone or a decrease in the production of somatostatin),
primary glandular (due to the pathology of acidophilic cells of the
adenohypophysis), postglandular (most often due to increased sensitivity of
receptors to GH).
♦ Manifestations and their mechanisms: an increase in height (usually above 200
cm in men and 190 cm in women), a discrepancy between the size and mass of
internal organs and the size of the body (more often the organs are also enlarged -
splanchnomegaly), disproportionate muscle development (the degree of muscle
development usually lags behind body size), hyperglycemia, hypogenitalism,
mental disorders (emotional instability, irritability, sleep disturbance, decreased
mental performance).
• Acromegaly - a disproportionate increase in the size of individual parts of the
body (more often the hands, feet, internal organs), combined with significant
disorders of the organism. According to the time of occurrence in ontogenesis - a
late form of endocrinopathy (after the completion of ossification of the epiphyseal
cartilage).
♦ Initial links of pathogenesis: the same as in pituitary gigantism.
♦ Manifestations and their mechanisms: metabolic disorders (persistent
hyperglycemia and often diabetes; increased blood levels of cholesterol, lecithin,
ketone bodies, drugs), sexual disorders (decreased libido; impotence in men;
dysmenorrhea and galactorrhea in women).
• Hyperprolactinemia.
• Syndrome of the pituitary premature sexual development.
It is characterized by the appearance of some or all of the secondary sexual
characteristics, in some cases - the onset of puberty (in girls up to 8, in boys up to
9 years of age). It develops as a result of premature secretion of gonadoliberins or
hypersecretion of gonadotropins.
Pathology of the neurohypophysis
Diseases of the neurohypophysis lead to imbalances in water balance as a result of
ADH endocrinopathies (insufficiency or redundancy of ADH effects). These
include central forms of diabetes insipidus (lack of ADH effects) and syndrome of
inappropriate ADH secretion (redundancy of ADH effects).

INSUFFICIENT DIABETES
Central forms of diabetes insipidus (diabetes insipidus) develop as a result of a
lack of antidiuretic hormone (ADH) effects.
• Pathogenesis. Initial links of pathogenesis:
♦ centrogenic (neurogenic);
♦ hypothalamic-pituitary: impairment of ADH synthesis, inhibition of ADH
transport to the neurohypophysis, disorders of the accumulation and release of
ADH into the blood;
♦ postglandular: hyposensitization of ADH receptors in the kidneys, increased
inactivation of ADH in tissues.
• The main manifestations of diabetes insipidus and their mechanisms.
♦ Polyuria. Daily urine output is usually 3-15 liters, sometimes up to 20-30 liters.
At the same time, urine has a very low osmolality.
♦ Hyperosmolality of blood plasma (more than 290 mOsm / kg) of intracellular
and other biological fluids.
♦ Hypernatremia. It is a consequence of the activation of the production, release
and effects of aldosterone.
♦ Polydipsia. Caused by pathological thirst.

Syndrome of inadequate secretion of ADH

The syndrome of inadequate secretion of ADH develops as a result of excess ADH
effects and is characterized by oliguria and edema.
• Pathogenesis. Initial pathogenetic links: centrogenic and primary glandular.
♦ Centrogenic. It is characterized by neurogenic cortical-subcortical stimulation of
the formation of ADH in the hypothalamus and its transport to the
neurohypophysis.
♦ Primary glandular. It is a consequence of excessive production and
neurosecretion of ADH by hypothalamic neurons, ectopic synthesis of ADH (for
example, small cell lung carcinomas), or a combination of both.
• Manifestations: oliguria, weight gain, hyponatremia, increased sodium ions in
urine, neuropsychiatric disorders.

ADRENAL PATHOLOGY
The adrenal glands - paired endocrine glands - consist of a cortex (mesodermal
origin) and cerebral (neuroectodermal origin). Functionally, these are two glands:
the cortex (the cortex accounts for about 80% of the mass of the gland) and the
brain part. The adrenal cortex synthesizes corticosteroids (mineral and
glucocorticoids, as well as dehydroepiandrosterone), the chromaffin cells of the
brain part - catechol amines.

Typical forms of adrenal pathology are divided into two large groups:
hyperfunctional and hypofunctional states.
• Hyperfunctional partial states: hypercortisolism (hyperaldosteronism, Itsenko-
Cushing's syndrome and disease, corticogenital syndrome), overproduction of
catecholamines by the medulla.
• Hypofunctional states: (adrenal insufficiency).

HYPERALDOSTERONISM
Hyperaldosteronism is the general name for syndromes resulting from
hypersecretion or disorders of aldosterone metabolism and characterized by the
presence of edema, ascites, hypokalemia and renovascular arterial hypertension.
Hyperaldosteronism syndrome can be primary or secondary. In some cases,
pseudohyperaldosteronism develops.

Primary hyperaldosteronism
• Causes: aldosterone-producing adenoma of the glomerular cortex of one of the
adrenal glands; primary hyperplasia of the glomerular zone of the adrenal cortex.
• Consequences and manifestations. In these conditions, Conn's syndrome
develops (due to hyperaldosteronemia): headaches, polyuria, weakness, decreased
renin activity, hypokalemia, alkalosis, hypervolemia and arterial hypertension.
Secondary hyperaldosteronism
• Causes: conditions that cause a decrease in the volume of circulating blood or
blood pressure (heart failure, nephrotic syndrome, liver cirrhosis, polyuria).
• Effects. Renal hypoperfusion causes the activation of the renin-angiotensin
system. Excessive formation of angiotensin leads to overproduction of aldosterone
by both adrenal glands.
• Manifestations: increased blood plasma renin activity, increased blood
angiotensin, hyperaldosteronemia and Conn's syndrome.

HYPERCORTISOLISM
• Causes and types of hypercortisolism.
♦ Itsenko-Cushing's syndrome. It is characterized by a high level of cortisol in the
blood with a low content of adrenocorticotropic hormone (ACTH) in it. It is
caused by hyperproduction of glucocorticoids in the fascicular zone of the adrenal
cortex.
♦ Itsenko-Cushing's disease. It is characterized by high blood levels of both ACTH
and glucocorticoids. Caused by overproduction of ACTH in the adenohypophysis.
♦ Syndromes of ectopic (heterotopic) ACTH hypersecretion.
♦ Iatrogenic Itsenko-Cushing's syndrome. It develops with prolonged
administration of glucocorticoid preparations into the body for therapeutic
purposes. In this case, as a rule, hypotrophy of the cortex of both adrenal glands is
observed.
• Main manifestations: arterial hypertension, excessive fat deposition (mainly in
the face, shoulders, trunk), muscle weakness, osteoporosis, hyperglycemia and
diabetes mellitus, "stretch bands", decreased anti-infective resistance.

ADRENOGENITAL SYNDROME
Adrenogenital syndrome is a pathological condition caused by hypersecretion of
androgens in the adrenal cortex and manifested by signs of virilization. Almost all
cases of adrenogenital syndrome are congenital.
The syndrome is caused by a deficiency in one of the enzymes necessary for the
synthesis of cortisol. Cortisol deficiency stimulates the production of corticoliberin
and ACTH, which leads to hyperplasia of the adrenal cortex and excessive
production of those ACTH-dependent steroids, the synthesis of which is not
impaired with this enzyme deficiency.
Types of adrenogenital syndrome: congenital and acquired.
• Congenital adrenogenital syndrome (95% of all cases). Clinical options: viril
form (uncomplicated virilism), salt-wasting form (with hypotensive syndrome) and
hypertensive form.
• Acquired adrenogenital syndrome.
♦ Reason: androsteroma is a benign tumor from the adenocytes of the reticular
adrenal cortex. Such tumors synthesize excess amounts of androgens.
♦ Manifestations of acquired adrenogenital syndrome may differ from congenital
forms by normal or slightly increased blood levels of ACTH.
Manifestations: virilization of the external genital organs of girls, macrosomia,
hirsutism, masculinization, early false puberty in boys.

HYPERCATECHOLAMINEMIA
• Hypercatecholaminemia is observed in tumors from chromaffin cells -
pheochromocytomas, developing both isolated and in some forms of familial
polyendocrine adenomatosis.
• Manifestations of hypercatecholaminemia: arterial hypertension, acute
hypotensive reactions with fainting, hypertensive crises, cardiac arrhythmias,
hyperglycemia, increased concentration of catecholamine metabolites in the urine,
hyperlipidemia, increased sweating, retinopathies, weight loss, tremors and others.

ADRENAL INSUFFICIENCY
Hypofunctional conditions of the adrenal glands are referred to as "adrenal
insufficiency". Among the many conditions associated with adrenal insufficiency,
Addison's disease, adrenal crisis, Waterhouse-Friderichsen syndrome,
adrenoleukodystrophy (co-leukodystrophy and Addison's disease), autoimmune
polyglandular syndrome and hypoaldosteronism.

Addison's disease
Addison's disease is a chronic primary insufficiency of the adrenal cortex. It
occurs with bilateral damage to the adrenal glands, leading to their failure, i.e.
decrease (or cessation) of the secretion of glucocorticoids and mineralocorticoids.
• Causes: immune autoaggression (in 80% of cases), tuberculosis. As a syndrome,
chronic adrenal insufficiency is present in many inherited diseases.
• Views. Distinguish between primary, secondary and iatrogenic forms of
Addison's disease.
♦ The primary form (glandular, adrenal) Addison's disease is caused by damage to
the adrenal glands. The death of cortical cells is accompanied by a deficiency of
corticosteroids.
♦ The secondary form (centrogenic, hypothalamic-pituitary) is caused by damage
to the hypothalamus or pituitary gland. Deficiency of corticoliberin or ACTH leads
to hypofunction of the adrenal cortex.
♦ The iatrogenic form of Addison's disease is a consequence of the cessation of the
introduction of corticosteroids into the body after their prolonged use for
therapeutic purposes. The resulting condition is referred to as "corticosteroid
withdrawal syndrome" or iatrogenic adrenal insufficiency. It is caused by
prolonged suppression of the function of the hypothalamic-pituitary-adrenal
system and atrophy of the adrenal cortex.
• Manifestations and their mechanisms
♦ Muscle weakness, fatigue. Mechanisms: imbalance of ions in biological fluids
and muscles (decrease in [Na +], excess [K +]; impaired translocation of Ca2 +
across biological membranes), hypoglycemia, dystrophic changes in myocytes.
♦ Arterial hypotension.
♦ Polyuria. Mechanism: decreased reabsorption of fluid in the renal tubules due to
hypoaldosteronism.
♦ Hypohydration of the body, hypovolemia and hemoconcentration. Due to
polyuria.
♦ Violation of cavity and membrane digestion and absorption. Mechanisms:
insufficient secretion of digestive juices, increased osmolality of intestinal contents
(due to the excretion of excess Na + into the intestinal lumen) and "osmotic"
diarrhea.
♦ Hypoglycemia. Reason: deficiency of glucocorticoids, which leads to inhibition
of gluconeogenesis.
♦ Hyperpigmentation of the skin and mucous membranes in primary adrenal
insufficiency. Mechanism: an increase (in conditions of cortisol deficiency) in the
secretion of both ACTH and melanocyte-stimulating hormone by the
adenohypophysis.
♦ Reduction of body hair, especially in the armpit and pubis. Cause: Insufficiency
of adrenal androgens.

Adrenal crisis
Acute adrenal insufficiency includes a hypoadrenal (adrenal) crisis and an Addison
crisis, a complication of Addison's disease.
• Causes:
♦ Destruction of both adrenal glands in the event of injury.
♦ Bilateral hemorrhage into the medulla and tissue of the adrenal cortex (for
example, in childbirth, with an overdose of heparin, acute or fulminant sepsis). In
the latter case, they speak of Waterhouse-Friederiksen syndrome.
♦ Removal of the adrenal gland affected by the hormone-producing tumor.
Insufficiency develops as a result of hypo or atrophy of the cortex of the second
adrenal gland.
• Manifestations of acute insufficiency of the adrenal cortex: acute hypotension,
hypohydration of the body, insufficiency of systemic circulation, collapse, fainting.
Hypoaldosteronism is a partial adrenal insufficiency. Manifestations of
hypoaldosteronism: hyponatremia, hyperkalemia, arterial hypotension,
bradycardia, muscle weakness, fatigue.

HYROID DISEASE
The thyroid gland secretes the peptide hormone calcitonin and iodine-containing
hormones (triiodothyronine - T3 and thyroxine - T4). Calcitonin (thyrocalcitonin)
is produced by light cells of the thyroid gland. The functional antagonist of
calcitonin, parathyrocrine (parathyroid hormone, PTH), is synthesized in the main
cells of the parathyroid glands.
Iodine-containing hormones produce follicular epithelial cells. Numerous diseases
of the thyroid gland, hathose characterized by changes in the level or effects of
iodine-containing hormones are assigned to two groups: hyperthyroid states
(hyperthyroidism) and hypothyroid states (hypothyroidism).

Hyperthyroidism
Hyperthyroidism is a condition characterized by an excess of the effects of
iodine-containing hormones in the body.
The term "thyrotoxicosis" is usually used to denote severe hyperthyroidism and
hyperthyroidism caused by an excess of exogenous thyroid hormones (for
example, as a result of an incorrectly calculated dose of medications or by
mistake).
Causes and types of hyperthyroidism
Various factors cause damage at different levels of regulation of the hypothalamic-
pituitary-thyroid system. In this regard, primary, secondary and tertiary
hyperthyroidism are distinguished.
• In primary hyperthyroidism, various factors affect the thyroid itself or ectopic
thyroid tissue. The most common causes: diffuse or nodular toxic goiter, toxic
adenoma of the thyroid gland, the introduction of iodine preparations into the body
- the phenomenon of "iodine-Basedow".
• Secondary hyperthyroidism is caused by overproduction of TSH. The most
significant cause is a secreting pituitary adenoma.
• Tertiary hyperthyroidism is caused by exposure to neurons in the hypothalamus.
The most common cause is neurosis.

Manifestations of hyperthyroidism and their mechanisms

The most typical manifestations of hyperthyroidism
• Nervous system: increased nervous and mental excitability, emotional imbalance,
nervousness, feelings of unmotivated anxiety and fear, impaired concentration and
consistency of thoughts, increased neuromuscular excitability.
• Cardiovascular system: syndrome "thyrotoxic heart" (hyperfunction and
hypertrophy of the myocardium, tachycardia and arrhythmias, heart failure,
cardiosclerosis), increased systolic blood pressure (often - systolic arterial
hypertension), decreased diastolic blood pressure, increased blood flow.
• Digestive system: changes in appetite (increase in young and decrease up to
anorexia in elderly patients), disturbance of gastric and intestinal digestion,
increased gastrointestinal motility and diarrhea.
• Ophthalmic symptoms are pathognomonic for hyperthyroidism. The
pathogenesis of ophthalmopathy is based on immune autoaggression reactions.
Manifestations:
♦ Exophthalmos - forward displacement of the eyeball. Causes: edema and
lymphocytic infiltration of retro-orbital tissue, fibrosis and degeneration of the
oculomotor muscles (these changes, in addition to exophthalmos, cause diplopia -
double vision of objects when looking at them, as well as limitation of the mobility
of the eyeball).
♦ Dryness, erosion and ulceration of the cornea of the eye. Reasons: violation of
eyelid closure due to their edema and exophthalmos, as well as disorders of the
formation and outflow of tear fluid.
♦ Blindness. Causes: compression of the optic nerve by edematous tissue and
degenerative changes in it, keratitis.
♦ "Eye symptoms": Dahlrymplya, Graefe, Shtelvag and others.
• Metabolism: increased basal metabolism; increased proteolysis, lipolysis,
glycogenolysis; negative nitrogen balance, mobilization of fat from the depot,
activation of cholesterol metabolism, inhibition of glucogenesis.
• The musculoskeletal system. Thyrotoxic myopathy and osteoporosis develop.
• The skin is warm, moist, especially on the palms. This is largely due to an
increase in basal metabolic rate.
• Thyroid hormones and thyriotropic hormone (TТH).
♦ The total and free fractions of tridthyronine (T3) or thyroxine (T4) are increased.
♦ TТH: its content is significantly reduced (with primary hyperthyroidism) or
increased (with secondary and tertiary hyperthyroidism).

Thyrotoxic crisis
Thyrotoxic crisis is the most severe complication of thyrotoxicosis, fraught with
death. It is characterized by a progressive ("explosive") aggravation of the course
of hyperthyroidism.
• The most common causes: trauma, surgery (even minor), stress, infectious and
non-infectious acute or exacerbation of chronic diseases, intoxication.
• The main links of pathogenesis.
♦ A sharp significant increase in the content of thyroid hormones in the blood.
♦ Increasing acute adrenal insufficiency (as a result of stress accompanying the
thyrotoxic crisis).
♦ Excessive activation of the sympathoadrenal system. It leads to
hypercatecholaminemia and the realization of the cytotoxic effects of
catecholamines.
• Manifestations: neuropsychiatric disorders (agitation, delirium, loss of
consciousness), increased neuromuscular excitability, progressive renal failure, an
increase in body temperature, circulatory disorders, breathing disorders. The
outcome of a thyrotoxic crisis depends on the timeliness of its diagnosis and the
effectiveness of treatment. Lethality with it reaches 60%.
Hypothyroidism
Hypothyroidism is a condition caused by insufficient secretion or effects of
thyroid hormones.
CAUSES AND TYPES OF HYPOTHYROSIS
Depending on the level of the lesion, there are primary, secondary and tertiary
hypothyroidism, as well as postglandular hypothyroidism.
• Primary hypothyroidism (90% of hypothyroidism cases) develops when the
thyroid gland is damaged and is accompanied by an increase in TSH levels.
• Secondary hypothyroidism develops when the pituitary gland is damaged with
insufficient TSH and subsequent hypothyroidism.
• Tertiary hypothyroidism is caused by damage to the hypothalamus and
insufficient release of thyroliberin, which leads to a decrease in the secretion of
TSH and thyroid hormones.

MAIN CLINICAL FORMS OF HYPOTHYROIDISIS

The main clinical forms of hypothyroidism are chronic autoimmune thyroiditis
(Hashimoto's disease), cretinism, myxedema, and hypothyroid (myxedema) coma.

Cretinism and myxedema

Cretinism develops with mild or moderate hypothyroidism. Distinguish between
sporadic (congenital) and endemic cretinism (endemic goiter).
Myxedema is a severe form of hypothyroidism that usually develops in adults and
adolescents. A characteristic feature of myxedema is mucous edema of the skin
and subcutaneous tissue, in which there is no fossa when pressed.
• Causes of cretinism:
♦ Congenital cretinism is caused by malformations of the thyroid gland, as well as
mutations in the genes of thyroliberin, TSH, T3 and T4.
♦ Causes of endemic goiter: iodine deficiency or excess of thyrostatic substances
in water and food, lack of a number of microelements in the body (cobalt,
molybdenum, zinc and copper).
• Pathogenesis of cretinism. The initial and main pathogenetic link in both types of
cretinism is T3 and T4 deficiency.
• Manifestations of cretinism. They are largely similar in sporadic and endemic
variants.
♦ Goiter.
♦ Lagging physical development both during the newborn period and at
subsequent stages of life.
♦ Disorders of mental development (more or less pronounced impairment of the
intellect, up to idiocy).
Hypothyroidism manifestations and their mechanisms
The signs below are common to all types of hypothyroidism. However, their
combination and severity in specific patients may be different.
• Nervous system: hypothyroid encephalopathy (decreased intelligence,
hyporeflexia, lethargy, drowsiness, frequent depression), paresthesia, cerebellar
ataxia, decreased tone of the sympathoadrenal system.
• CVS: cardiomegaly, heart failure, bradycardia, microcirculation disorders,
decreased blood flow rate, cardialgia.
• Gastrointestinal tract: decreased appetite, often nausea, indigestion due to
hypoacid gastritis, frequent constipation, sometimes - intestinal obstruction.
• Kidneys and urinary tract: decreased excretory function of the kidneys due to
their hypoperfusion with blood; infection of the urinary tract (due to hypotension
and hypokinesia of their muscles).
• Metabolism: hyperlipoproteinemia, hypoglycemia, inhibition of proteosynthesis,
decreased basal metabolism.
• Musculoskeletal system: the development of myopathies (manifested by
myalgias, decreased muscle strength, increased fatigue), joint lesions
(characterized by arthralgias, arthrosis).
• Growth of the organism. In children, growth retardation is revealed.
• Skin, its derivatives, subcutaneous tissue, mucous membranes, serous cavities:
development of myxedema. Reasons: a significant increase in the hydrophilicity of
the connective tissue, fluid retention in the body, binding of a large amount of fluid
by the tissue colloid (containing an excess of glycosaminoglycans and Na +) with
the formation of mucin - a mucus-like compound. Manifestations:
♦ Puffiness (swelling) of the face, coarsening of its features, hypomimicity (mask-
like), edema of periorbital tissue.
♦ Brittle hair, hair loss, fragility of nails.
♦ Swelling of the vocal cords. The tongue is enlarged, teeth imprints are visible on
its lateral surfaces. The result is a deep, harsh voice; fuzzy, difficult speech.
♦ Aseptic polyserositis. It is manifested by the accumulation of excess serous fluid
in the cavities of the pericardium, peritoneum, pleura, etc.

Hypothyroid coma
Hypothyroid (myxedema) coma is an extremely severe, often fatal manifestation of
hypothyroidism (mortality in it reaches 75%). It is the final stage of any type of
hypothyroidism if it is not properly treated or not.
• Causes: hypothermia, circulatory failure of any genesis, acute infections,
intoxication, stress, bleeding, hypoglycemia, hypoxia.

• Manifestations: severe bradycardia, arterial hypotension, collapse, respiratory

failure, increasing hypoxia, renal failure, hypothermia, depression and loss of
consciousness.

IMPAIRMENT OF THE FUNCTIONS OF THE PARTHYGROID GLANDS

The parathyroid glands are located on the back of the thyroid gland under its
capsule. The function of the glands is the synthesis and secretion of
parathyreocrine (PTH). PTH, together with calcitonin and catacalcin, as well as
vitamin D, regulates calcium and phosphate metabolism. Various diseases caused
by changes in the level or effects of PTH can be considered as being referred to as
hyperparathyroid (hyperparathyroidism) or hypoparathyroid (hypoparathyroidism)
conditions.

Hyperparathyroidism
Hyperparathyroidism is characterized by an increase in serum PTH or an increase
in the effects of PTH. Distinguish between primary (glandular), secondary
(hypercalcemic) and tertiary hyperparathyroidism, as well as
pseudohyperparathyroidism. Primary hyperparathyroidism is caused by the
pathology of the parathyroid glands themselves. Causes: autonomously functioning
adenoma, primary glandular hyperplasia, parathyroid carcinoma. Secondary
hyperparathyroidism is caused by prolonged hypocalcemia, usually associated with
hyperphosphatemia. This leads to hyperfunction and hyperplasia of the parathyroid
glands. Causes:
♦ Kidney disease leading to hypocalcemia (the most common cause): chronic renal
failure, tubulopathy, and renal rickets.
♦ Intestinal pathology: malabsorption syndrome, steatorrhea.
♦ Pathology of bone tissue: osteomalacia, deforming osteodystrophy (Paget's
disease).
♦ Hypovitaminosis D.
Tertiary hyperparathyroidism is caused by long-term secondary
hyperparathyroidism. The latter leads to the development of adenomas (or
adenomas), which acquire the property of autonomous functioning and
hyperproduction of PTH. Under these conditions, the inverse relationship between
the level of Ca2 + in the blood and the secretion of PTH is destroyed.
Pseudohyperparathyroidism is the overproduction of PTH by ectopic tumors. It is
observed in familial polyendocrine adenomatosis and paraneoplastic syndromes.
Hypoparathyroidism
Hypoparathyroid states are characterized by a decrease in blood levels or the
severity of the effects of PTH in the body.
Causes and types of hypoparathyroidism
Distinguish between glandular and extraglandular hypoparathyroidism
(pseudohypoparathyroidism).
• Primary (glandular) hypoparathyroidism is caused by the absence, damage or
removal of the parathyroid glands.
• Extraglandular (peripheral) hypoparathyroidism is also called
pseudohypoparathyroidism. An example is Albright's disease, an inherited disease
characterized by resistance of target organs to PTH.
Manifestations of hypoparathyroidism
• Hypocalcemia, usually associated with hyperphosphatemia. Reasons: impaired
absorption of Ca2 + in the intestine, inhibition of Ca2 + mobilization from bones, a
decrease in Ca2 + reabsorption in the kidney tubules.
• Increased neuromuscular excitability: tetanus and convulsions.
♦ Tetanus - a state of prolonged muscle tension, usually the flexors of the limbs, in
severe cases, the muscles of the face.
♦ Convulsions - involuntary contraction of muscle groups followed by relaxation
(clonic seizures), or continuing for a long time (tonic seizures). They are
accompanied by severe pain.
• Disorders of the functions of organs, tissues and their physiological systems.
♦ Neuropsychic disorders: increased nervous irritability (manifested by positive
symptoms of Khvostek and Trousseau), mental disorders (insomnia, depression,
bouts of melancholy, the development of neurotic states).
♦ Circulatory disorders: disturbance of central, organ-tissue and micro-
hemocirculation due to changes in cardiac output, fluctuations in the tone of
arterioles.
♦ Respiratory disorders: alveolar hypoventilation, sometimes asphyxia (with
laryngospasm, bronchospasm).
♦ Disorders of the digestive function: swallowing disorders, pylorospasm,
vomiting, abdominal pain, constipation, followed by diarrhea.
♦ Violation of urination. Observed with spasm of the muscles of the bladder.
♦ Cataract. It is caused by calcification of the lens with prolonged course of
hypoparathyroidism.

IMPAIRMENT OF ENDOCRINE FUNCTION GENITAL GLAND

Typical forms of pathology caused by disorders of the endocrine function of the
gonads are divided into three groups:
♦ violations of sexual differentiation;
♦ Disorders of sexual development in girls and sexual function in women;
♦ violations of sexual development in boys and sexual function in men.

Disorders of sexual development and sexual function in genetically female

persons
Puberty (puberty) in girls begins between the ages of 8 and 13 and occurs within 3-
4 years. The most significant signs of puberty include the growth and development
of mammary glands (thelarche), pubic and axillary hair growth, the onset of
menstruation (menarche), and the formation of a regular menstrual-ovarian cycle,
determined by changes in the endocrine status.
• The development of the mammary glands (may be asymmetrical), as a rule,
precedes the formation of pubic hair.
• Menarche (beginning of menstrual function). Menstruation begins at an average
age of 12.5 years, and usually lasts 4-5 days. During the first two years, your
menstrual cycle may be irregular. 20% of girls do not ovulate until the age of 17-
18.
The most common forms of puberty and sexual function disorders include
premature puberty, delayed puberty, endocrine hypo- and ovarian hyperfunction.

PREMATURAL MATURITY
Puberty is considered premature if any of the secondary sexual characteristics
appears in girls before 7.5 years of age. Distinguish between central (true),
peripheral (false) and partial (incomplete) premature puberty.

True premature puberty

Almost 90% of all cases of premature puberty are true (gonadotropin-dependent)
puberty. It occurs much more often in girls than in boys. This version of puberty is
called true because the body's puberty occurs, albeit prematurely, but according to
the usual (as in normal) scheme: activation of the hypothalamus and synthesis of
gonadoliberins, secretion of gonadotropic hormones, synthesis of sex hormones,
the formation of secondary female sexual characteristics.
• Causes:
♦ Premature activation of the synthesis of gonadoliberin. It is observed when the
diencephalic region is damaged.
♦ Hyperproduction of gonadotropins by the adenohypophysis. It usually occurs
with pituitary adenomas.
• Manifestations:
♦ Isosexuality of development of the body (ie, compliance with the genetic and
gonadal female sex).
♦ Complexity ("harmony") of development (including acceleration of body
growth, thelarche, pubic and axillary hair growth, the formation of other
characteristic secondary sexual characteristics).
♦ Completeness of development (characterized by menarche and premature onset
of ovulation).

Premature pseudopubertal
False premature sexual development is characterized by the acceleration of body
growth, as with true premature sexual development. However, pseudopubertal is
always incomplete (no ovulation and menarche).
• Cause: autonomous excess synthesis of estrogen in the ovaries or adrenal glands.
It is caused, as a rule, by a hormonally active tumor of the ovary.
• Manifestations: bivalence of sexual development (the possibility of isosexual or
heterosexual development), violation of harmony and incompleteness of sexual
development of the body.
♦ Isosexual (coinciding with the genetic and gonadal female sex) occurs when
excess estrogen is synthesized.

♦ Heterosexual development (does not match genetic and gonadal sex). Girls
develop secondary male sexual characteristics.

Partial premature sexual development

Incomplete premature sexual development is characterized by the early appearance
of any one or individual secondary sexual characteristics in the absence of others.
• Causes:
♦ Premature onset of ovarian estrogen synthesis, usually in excess (causing
premature thelarche).
♦ Excessive formation of androgens in the adrenal cortex (leading to premature
pubic and axillary hair growth).
♦ Increased sensitivity of target cells to estrogens (eg, breast cells).
• The most common manifestations:
♦ Telarhe (usually before the age of 2-4 years, less often after 6 years).
♦ Premature growth of pubic and axillary hair.

DELAYED MATURITY
Delayed puberty is considered to be the absence of secondary sexual
characteristics in girls by the age of 14, as well as the absence of menstruation by
the age of 16 in the presence of secondary sexual characteristics.
Distinguish between primary and secondary forms of hypogonadism.
• Primary hypogonadism (ovarian, hypergonadotropic). It is a consequence of
inherited, congenital or acquired ovarian failure.
• Secondary hypogonadism (hypogonadotropic, extra-ovarian). It is caused by a
deficiency of gonadotropic hormones (FSH, LH) of a transient (transient) or
permanent (chronic) nature. The most common reasons are:
♦ Prolonged states of stress.
♦ Chronic wasting diseases (for example, malabsorption syndrome, chronic
myeloid leukemia, osteomyelitis, tuberculosis).
♦ Endocrinopathies (eg, diabetes mellitus, Itsenko-Cushing's syndrome,
hypothyroid conditions).
♦ Pathology of the hypothalamus (eg malformations).
♦ Pathology of the pituitary gland (for example, with encephalitis, trauma,
hemorrhage or neoplasm in the Turkish saddle).

Impairment of endocrine function ovary

Ovarian hypofunction
• Causes and types. Endocrine ovarian failure is divided into primary and
secondary.
♦ Primary ovarian failure (primary hypogonadism) - conditions caused by ovarian
pathology. There is an insufficient production of sex hormones by them, as well as
a compensatory increased level of FSH in the blood.
♦ Secondary insufficiency (secondary, or extra-ovarian hypogonadism). It is the
result of a deficiency of either the gonadoliberins of the hypothalamus or the
gonadotropic hormones of the adenohypophysis.
• Manifestations. Primary and secondary endocrine ovarian failure is characterized
by similar symptoms. The main ones include: menstrual irregularities, amenorrhea,
infertility.
♦ Menstrual irregularities. Manifested by dysfunctional uterine bleeding.
♦ Amenorrhea - the absence of menstruation for more than 6 months in women
with their earlier periodic onset (secondary amenorrhea), as well as the absence of
menarche in girls over 16 years of age (primary amenorrhea).
♦ Infertility - the absence of pregnancy during one year of regular sexual activity
without using methods of contraception. Infertility is registered in 10-15% of
married couples.

Ovarian hyperfunction
Endocrine ovarian hyperactivity is characterized by hyperandrogenism or
hyperestrogenism.
• Hyperandrogenism is a condition characterized by increased production or effects
of androgen action. It is detected in varying degrees of severity in 10-15% of
women. Manifestations: increased blood levels of androstenedione and
testosterone, changes in the LH / FSH ratio in the blood (usually more than 3),
hirsutism, amenorrhea, infertility, obesity.
• Hyperestrogenism. It is characterized by excess production or effects of estrogen
in the body. Manifestations: increased blood and urine levels of estrogen,
decreased levels of gonadotropic hormones, premature isosexual puberty,
menstrual irregularities (usually in the form of menorrhagias).

Disorders of sexual development and sexual function in genetically males

Puberty in boys begins at the age of 9.5 to 13.5 years and lasts about 3 years.
Testicular enlargement is usually the first sign of puberty. Also signs of puberty are
acne, pubertal gynecomastia, pubic and axillary hair and a number of others.
Endocrinogenic disorders of sexual development and sexual function in males are
manifested in the following typical forms: premature sexual development, delayed
sexual development, testicular hypofunction.

Premature sexual development

Premature puberty is a condition characterized by the appearance of all or some of
the secondary sexual characteristics in boys up to 9 years of age. This is often
combined with emotional and behavioral disorders, as well as impaired social
adaptation.
• Causes and types. Distinguish between true and false premature development of
boys.
♦ True (primary) premature development of boys is the result of hyperfunction of
the hypothalamic-pituitary system and is characterized by complete premature
sexual development (including activation of spermatogenesis in the testes). Cause:
premature activation of gonadoliberin secretion by hypothalamic neurons.
♦ False (secondary) premature development in boys occurs as a result of
autonomous hyperproduction of androgens. It is characterized by incomplete
premature sexual development (the appearance of signs of virilization without
activation of spermatogenesis). The most common causes: androgen-producing
testicular tumors, hyperplasia of Leydig cells and their synthesis of excess
testosterone, androgen hypersecretion by the adrenal cortex.

• Manifestations of premature puberty.

♦ Signs of virilization (appearance of pubic and axillary hair, coarsening of the
voice, enlargement of the testicles and penis).
♦ Low growth (due to premature termination of epiphyseal bone growth).

Delayed puberty and hypogonadism

The absence of signs of puberty in boys by the age of 14 is considered delayed
puberty.
• Causes of delayed puberty in boys and hypogonadism in men:
♦ Deficiency of gonadoliberins of the hypothalamus or gonadotropins of the
adenohypophysis.
♦ Decreased production of testosterone by the testes (as a result of trauma, growth
of neoplasms, developmental disorders, orchitis, etc.).
♦ Reduced sensitivity of target tissues to the action of testosterone.
• Manifestations of delayed puberty:
♦ Eunuchoidism (underdeveloped testicles and penis, absence or poorly expressed
secondary sexual characteristics, effeminate (girlish) voice, obesity, skeletal
imbalance).
♦ Decreased blood testosterone levels.
• Manifestations of male hypogonadism:
♦ Sexual development in men is not impaired. In this regard, the physique and
timbre of their voice are in the normal range.
♦ Decreased sex drive.
♦ Impotence.
♦ Infertility.