Diagnosis and treatment of iatrogenic hypercortisolism. Itsenko-Cushing's syndrome (hypercorticism): symptoms, causes and treatment of the disease Hypercorticism symptoms treatment
Symptoms and course of hypercortisolism
| System | Complaints | Objective signs of complaints (analysis of complaints / examination / tests) |
|---|---|---|
| General signs/symptoms | General weakness/fatigue is chronic and paroxysmal. Weight gain. tendency to relapse infectious diseases (20-50%) | Overweight |
| Characteristic facial change | - | Round/full/moon face (90-100%). Blush cheeks / cheekbones (90-100%). Red face/ruddy face (plethora) (90-100%). Eruptions on the face (0-20%). Periorbital edema/swollen eyelids. Edema face. Sclera injection |
| Skin, skin appendages and subcutaneous fat | Redness of the skin. Tendency to bruise | Skin erythema. Skin darkening/hyperpigmentation. Hirsutism, hypertrichosis (70-90%). Thinning skin, thin as parchment, easily vulnerable skin. Bruises, hemorrhages (50-70%). Purple/pink striae (70-80%). Acne-like rashes (0-20%) |
| Centripetal fat accumulation (90-100%): supraclavicular fat deposition; "bovine" ("menopausal") hump above the VII cervical vertebra (50-70%); abdominal obesity/"beer belly"; increased belly/thigh ratio | ||
| Edema on the legs (20-50%). Baldness (0-20%) | ||
| Musculoskeletal system | Loss of muscle mass. Muscle weakness (50-70%). Difficulty climbing stairs | Thin limbs. Amyotrophy. Weakness of the proximal muscles. Weakness of the thigh muscles. Osteopenia/osteoporosis (50-70%) |
| Respiratory system | - | - |
| The cardiovascular system | heartbeat | Tachycardia. Increased blood pressure (70-90%). Diastolic arterial hypertension. Hypokalemic alkalosis (20-50%) |
| Digestive system | Thirst/polydipsia (if diabetes develops). Decreased/loss of taste sensation | - |
| urinary system | Acute back pain (renal colic) | Pasternatsky's symptom is positive. Nephrolithiasis (20-50%) |
| Reproductive and endocrine systems | Decreased libido, anorgasmia in men and women (90-100%). Erectile dysfunction (70-80%) | Bilateral swelling of the mammary glands. Galactorrhea/lactorrhea/prolonged lactation |
| Violation of menstrual function (70-90%): amenorrhea primary/secondary; irregular periods/vaginal bleeding; oligomenorrhea/hypomenorrhea | ||
| Diabetes | ||
| Nervous system, sense organs | Acute/chronic back pain (20-50%). Decreased sensitivity to odors/anosmia. Headache (20-50%) | - |
| mental status | Insomnia. Excitability. Emotional instability / tantrums / short temper (50-70%). Vulnerability / incontinence. Aggressiveness | Change of character, gradual. Problems with appropriate behavior. psychotic behavior. Strange behavior. destructive behavior. Delirium with excitement. Violation of judgment. Depression (50-70%) |
The clinical picture varies depending on the hypersecretion of which hormone or which combination of them is associated with the development of the disease. Anatomical changes in the adrenal cortex in hypercortisolism can be different. Most often they consist in cortical perplasia, its adenomatous growth, and sometimes hypercorticism is associated with the growth of a malignant tumor.
There are the following clinical forms hypercortisolism.
1. Congenital virilizing hyperplasia of the adrenal cortex(adrenogenital syndrome). It occurs more often in women; due to synthesis in the adrenal cortex a large number steroid hormones that have the biological action of male sex hormones. The disease is congenital.
Etiology unknown. It is assumed that in the cells of the adrenal cortex, the enzyme systems that ensure the normal synthesis of hormones are disturbed.
clinical picture. It is determined mainly by the androgenic and metabolic action of male sex hormones, which enter the body in excess. In some patients, this is accompanied by symptoms of insufficiency or excess of other adrenal hormones - glucocorticoids, mineralocorticoids. Depending on the characteristics of hormonal disorders, clinical forms of the disease are distinguished. The most common is a purely virilous form, less often a hypertensive form, in which, in addition to signs of virilization, there are symptoms associated with excessive intake of mineralocorticoids from the adrenal cortex. In addition, in some patients, virilization is combined with individual symptoms of insufficient production of glucocorticoids (salt loss syndrome) or with increased intake of etiocholanone from the adrenal glands, accompanied by periodic fever.
The clinical picture depends on the age at which the violation of hormonal production by the adrenal cortex occurs. If the increased production of androgens occurs in the prenatal period, girls are born with various developmental disorders of the external genital organs, to some extent resembling the structure of the male genital organs, while the internal genital organs are differentiated correctly. If hormonal disorders occur after birth, both girls and boys experience accelerated growth, good muscle development, great physical strength and sexual development disorders: in girls, early appearance of male-type sexual hair growth, clitoral hypertrophy, underdevelopment of the uterus, lack of menstruation; in boys, early development of the penis, early appearance of sexual hair growth, delayed development of the testicles. In adult women, the disease is manifested by male-type hair growth on the face and body, underdevelopment of the mammary glands and uterus, clitoral hypertrophy, menstrual irregularities (amenorrhea, hypooligomenorrhea), and infertility. The hypertensive form of the disease is characterized by a combination of virilization and persistent hypertension. The combination of virilization with salt wasting syndrome in adults is rare.
Diagnosis based on the characteristic clinical picture of the disease. Of great diagnostic importance is the increased urinary excretion of 17-ketosteroids, which can reach 100 mg per day1. Examination of the excretion of 17-ketosteroids makes it possible to distinguish the disease from the often occurring virilous hypertrichosis of hereditary or national origin.
The differential diagnosis from virilizing ovarian tumors is based on the results of a gynecological examination and the absence of a significant increase in 17-ketosteroid excretion in ovarian tumors. The Li-for test with a decrease in the excretion of 17-ketosteroids under the influence of taking prednisolone or dexamethasone helps to distinguish virilizing hyperplasia of the adrenal cortex from an androgen-producing tumor. In a tumor, the excretion of 17-ketosteroids does not decrease or decreases only slightly. The test is based on the suppression of adrenocorticotropic function of the pituitary gland by corticosteroid drugs. Before the test, the daily excretion of 17-ketosteroids in the urine is determined twice, then for 3 days daily at intervals of 6 hours, dexamethasone or prednisolone (5 mg each) is given. On the 3rd day, urinary excretion of 17-ketosteroids is determined. With virilizing hyperplasia of the adrenal cortex, it decreases by at least 50%; in patients with a tumor of the adrenal cortex, a significant decrease does not occur. In doubtful cases, a special X-ray examination is indicated to exclude an adrenal tumor.
Treatment. Assign glucocorticoid drugs (prednisolone or other corticosteroids in equivalent doses, which are set individually under the control of the study of excretion of 17-ketosteroids) in order to inhibit the production of ACTH by the pituitary gland. This leads to the normalization of the function of the adrenal cortex: the release of excess androgens ceases, the excretion of 17-ketosteroids decreases to normal, a normal ovarian-menstrual cycle is established, and male-type hair growth is limited.
Treatment is carried out for a long time. In cases of resistance to conservative treatment, surgery (subtotal resection of the adrenal glands) is possible, followed by hormone replacement therapy (prednisolone, deoxycorticosterone acetate in individually set doses).
2. Androgen-producing tumors of the adrenal cortex. Tumors that produce androgens - androsteromas - are benign and malignant.
According to the clinical picture, the disease is close to severe virilizing hyperplasia of the adrenal cortex, but, as a rule, proceeds with more pronounced symptoms, especially rapidly progressing in a malignant tumor. Meet at different ages.
Diagnosis. The basis for it is the characteristic clinical picture in individuals who did not have virilization symptoms before, as well as a particularly high urinary excretion of 17-ketosteroids, exceeding 1000 mg per day in some patients. The test with the appointment of prednisolone, with the introduction of ACTH is characterized by the absence of a decrease in the excretion of 17-ketosteroids, which makes it possible to distinguish the disease from congenital adrenal hyperplasia.
X-ray examination with the introduction of gas either directly into the near-renal tissue, or retroperitoneally by means of a presacral puncture, can detect a tumor.
Malignant tumors are characterized by a severe course and prognosis due to early metastasis to the bones, lungs, liver and decay of tumor tissue.
Treatment surgical (removal of the adrenal gland affected by the tumor). In the postoperative period, with the appearance of signs of hypocorticism (due to atrophy of the unaffected adrenal gland) - replacement therapy.
3. Itsenko-Cushing's syndrome. It is associated with increased production of hormones, mainly glucocorticoids, by the adrenal cortex due to hyperplasia, a benign or malignant tumor (corticosteroma). Rare, more common in women of childbearing age.
clinical picture. Full, round, red face, excessive development of fiber on the body with disproportionately thin limbs; hypertrichosis (in women - according to the male type); purple striae distensae cutis in the pelvic and shoulder girdle, inner thighs and shoulders; hypertension with high systolic and diastolic pressure, tachycardia; in women - hypotrophy of the uterus and mammary glands, clitoral hypertrophy, amenorrhea, in men - sexual weakness, usually polyglobulia (erythrocytosis), hypercholesterolemia, hyperglycemia, glucosuria, osteoporosis.
Treatment of the disease is slow for benign, small and slightly progressive adenomas. With adenocarcinoma, the syndrome develops rapidly, the disease is especially difficult, complicated by disorders caused by tumor metastases, most often to the liver, lungs, and bones.
Diagnosis. Differential diagnosis between Itsenko-Cushing's syndrome, associated with primary changes in the adrenal cortex, and the disease of the same name of pituitary origin can be difficult. Diagnosis is facilitated by x-ray studies (pneumoretroperitoneum, sighting x-ray of the Turkish saddle). The diagnosis of a tumor of the adrenal cortex is confirmed by a sharply increased content of 17-ketosteroids in daily urine, reaching in severe cases, with large and malignant adenomas, several hundred and even 1000 mg per day, as well as an increased content of 17-hydroxycorticosteroids.
Treatment. Timely removal of a tumor of the adrenal cortex in the absence of metastases leads to regression or mitigation of all symptoms of the disease. However, recurrence is possible after surgery. The prognosis for an inoperable tumor is hopeless. Death can occur from cerebral hemorrhage, from associated septic processes, pneumonia, tumor metastases during internal organs(liver, lungs).
In view of the atrophy of the second, unaffected, adrenal gland, to prevent the development of acute adrenal insufficiency after surgery, 5 days before surgery and in the first days after it, ACTH-zinc phosphate is used 20 units 1 time per day intramuscularly, the day before surgery is prescribed, in addition , hydrocortisone. With a sharp drop in blood pressure after surgery, intramuscular administration of deoxycorticosterone acetate is indicated.
In cases where the operation is not possible, symptomatic treatment is prescribed according to indications: antihypertensive and cardiac drugs, insulin, a diabetic diet with salt restriction and an increased content of potassium salts (fruits, vegetables, potatoes), potassium chloride.
4. Primary aldosteronism(Conn's syndrome). It is caused by a tumor of the adrenal cortex (aldosteroma), which produces the mineral-corticoid hormone - aldosterone. A rare disease that occurs in middle age, more often in women.
clinical picture. The sick are worried headache, attacks of general weakness, thirst, frequent urination. There are paresthesias, epileptiform convulsions, hypertension with especially high diastolic pressure. The content of potassium in the blood is sharply reduced, and therefore characteristic ECG changes are observed (see Hypokalemia), the sodium content is increased, the specific gravity of the urine is low.
Diagnosis is based on the presence of hypertension, attacks of muscle weakness, paresthesia, seizures, polydipsia, polyuria, hypokalemia and the above ECG changes, as well as increased aldosterone in the urine (the norm is from 1.5 to 5 mcg per day) and the absence of renin in the blood. In differential diagnosis, it is necessary to keep in mind secondary aldosteronism, which can be observed with nephritis, cirrhosis of the liver and some other diseases accompanied by edema, as well as with hypertension. Radiographic indications of a tumor of the adrenal gland are of great diagnostic value.
Treatment surgical. A temporary effect is given by taking aldactone or veroshpiron, potassium chloride. Limit the intake of table salt.
Pathogenesis of symptoms and signs
On the skin with hyperglucocorticism in 50-70% of patients, wide atrophic (located below the surface of unaffected skin) striae, pink or purple, appear. Usually they are localized on the abdomen, less often - on the chest, shoulders, hips. A bright permanent blush on the face (plethora) is associated with atrophy of the epidermis and underlying connective tissue. Bruises easily, wounds do not heal well. All these symptoms are due to the inhibitory effect advanced level glucocorticoids on fibroblasts, loss of collagen and connective tissue.
If hypercortisolism is caused by hypersecretion of ACTH, then hyperpigmentation of the skin develops, since ACTH has a melanocyte-stimulating effect.
Often there is a fungal infection of the skin, nails (onychomycosis).
Increased deposition and redistribution of subcutaneous adipose tissue is one of the most characteristic and early symptom complexes of hyperglucocorticism. Fat is deposited mainly centripetally - on the trunk, abdomen, face ("moon-shaped face"), neck, above the VII cervical vertebra ("buffalo mound") and in the supraclavicular fossae - with relatively thin limbs (due to the loss of not only fat, but also muscle tissues). Obesity, despite the lipolytic effect of glucocorticoids, is due in part to an increase in appetite against the background of hyperglucocorticism and hyperinsulinemia.
Muscle weakness develops in 60% of patients with hyperglucocorticism, predominantly in the proximal muscles, which is most pronounced on lower limbs. Muscle mass decreases due to stimulation of protein catabolism.
Osteoporosis can be detected in more than half of patients, and clinically in the initial stage of the disease it is manifested by back pain. In severe cases, pathological fractures of the ribs and compression fractures of the vertebral bodies develop (in 20% of patients). The mechanism of development of osteoporosis in hyperglucocorticism is due to the fact that glucocorticoids inhibit calcium absorption, stimulate PTH secretion, increase urinary calcium excretion, which leads to a negative calcium balance, and normocalcemia is maintained only due to reduced osteogenesis and calcium resorption from bones. The formation of kidney stones in 15% of patients with hyperglucocorticism is associated with hypercalciuria.
Hyperglucocorticism may be accompanied by an increase in blood pressure, since glucocorticoids increase cardiac output and tone peripheral vessels(by regulating the expression of adrenergic receptors, they enhance the action of catecholamines), and also affect the formation of renin in the liver (angiotensin I precursor).
With long-term treatment with glucocorticoids and with their high doses, the risk of peptic ulcer formation increases, but in patients with endogenous hyperglucocorticism and against the background of short courses of glucocorticoid treatment, it is low.
From the side of the central nervous system, an excess of glucocorticoids first causes euphoria, but with chronic hyperglucocorticism, various mental disorders develop in the form of increased emotional vulnerability, excitability, insomnia and depression, as well as increased appetite, decreased memory, concentration and libido. Rarely, psychosis and mania occur.
In patients with glaucoma, hyperglucocorticism causes an increase intraocular pressure. During treatment with glucocorticoids, cataracts may develop.
With steroid diabetes signs of a hyperglycemic syndrome join the symptoms described above. Although hyperglucocorticism does not lead to clinically pronounced hypothyroidism, an excess of glucocorticoids suppresses the synthesis and secretion of TSH and impairs the conversion of T4 to T3, which is accompanied by a decrease in the concentration of T3 in the blood.
Hyperglucocorticism is accompanied by suppression of the secretion of gonadotropins and a decrease in gonadal function, which in women is manifested by suppression of ovulation and amenorrhea.
The introduction of glucocorticoids increases the number of segmented lymphocytes in the blood and reduces the number of lymphocytes, monocytes and eosinophils. By suppressing the migration of inflammatory cells to the site of injury, glucocorticoids, on the one hand, exhibit their anti-inflammatory effect, and on the other hand, they reduce resistance to infectious diseases in patients with hyperglucocorticism. In increased quantities, glucocorticoids also inhibit humoral immunity.
Diagnosis of hypercortisolism
None of the laboratory diagnostic tests for hypercortisolism can be considered absolutely reliable, so it is often recommended to repeat and combine them. The diagnosis of hypercortisolism is established on the basis of increased excretion of free cortisol in the urine or dysregulation of the hypothalamic-pituitary-adrenal system:
- daily excretion of free cortisol is increased;
- daily excretion of 17-hydroxycorticosterone is increased;
- there is no daily biorhythm of cortisol secretion;
- the content of cortisol at 23-24 h is increased.
Outpatient research
- Free cortisol in daily urine. The proportion of false negative results in this test reaches 5-10%, so the study is recommended to be carried out 2-3 times. False-positive results also provoke the use of fenofibrate, carbamazepine, and digoxin, and false-negative results are possible with reduced glomerular filtration (<30 мл/мин).
- Overnight dexamethasone test. False-negative results (i.e., no reduction in cortisol) occur in 2% of healthy individuals and increase to 20% in obese patients and among hospitalized patients.
If both of the above tests do not confirm hypercortisodism, its presence in the patient is unlikely.
Possible concomitant conditions, diseases and complications
- Cushing's disease.
- Nelson syndrome/ACTH-secreting pituitary tumor.
- Multiple endocrine tumors, type 1 syndrome.
- Secondary hyperaldosteronism.
- Hyperandrogenism in women.
- Decreased secretion of gonadotropins (in women).
- Gynecomastia.
- Primary hyperparathyroidism.
- growth retardation in adolescents.
- Obesity.
- Black acanthosis.
- Hyperpigmentation.
- Simple acne.
- Skin candidiasis.
- Fungal infections of the skin.
- Furunculosis.
- Pyoderma.
- Skin infections.
- Reticular livedo.
- Edema.
- Secondary steroid nonspecific myopathy.
- Osteoporosis / osteopenia.
- Syndrome of male osteoporosis.
- Aseptic / avascular necrosis of the bone in the joints.
- Compression pathological fractures of the vertebral-intravenous-vertebral collapse.
- Kyphoscoliosis.
- Fractures are generalized, repeated pathological.
- Pulmonary embolism.
- Pulmonary tuberculosis.
- Secondary systolic arterial hypertension.
- Hypervolemia.
- Thrombophlebitis of the veins of the hands / deep veins.
- Kidney stones (nephrolithiasis).
- Hypokalemic nephropathy.
- Fluid retention.
- Peptic ulcer disease.
- Posterior cataract.
- secondary glaucoma.
- Cataract.
- Depression.
- Hypertensive/metabolic encephalopathy.
- Psychosis.
- Pseudotumor of the brain.
- ovarian dysfunction.
- anovulatory cycles.
- Infertility (sterility in men).
- Impotence / erectile dysfunction.
- Leukocytosis.
- Lymphocytopenia.
- Polycythemia.
- Hypertriglyceridemia.
- Hypokalemia.
- Hypernatremia.
- Hyponatremia.
- Hypercalciuria.
- Hypocalcemia.
- Alkalosis is hypokalemic, metabolic.
- Hypophosphatemia.
- Hypomagnesemia.
- Hyperuricemia.
- Hypouricemia.
- Generalized bacterial infection.
- Suppression of cellular immunity.
Diseases and conditions from which hypercortisolism is differentiated
- adrenogenital syndrome.
- Chronic alcoholism.
- Obesity.
- Simple acne.
- Fibromyalgia.
- Osteomalacia.
Treatment of hypercortisolism
Treatment depends on the etiology of hypercortisolism. Surgical treatment:
- hypersecretion of ACTH by the pituitary gland;
- ectopic ACTH syndrome;
- glucosteroma. Conservative treatment:
- iatrogenic hypercortisolism;
- inoperable tumor (constant use of metyrapone, aminoglutethimide, mitotanar, ketoconazole or mifepristone to eliminate the symptoms of hypercortisolism).
Total hypercortisolism. Etiology and pathogenesis of hypercorticism. Since the adrenal cortex is a hormone-forming complex of mineralocorticoids, glucocorticoids, androgens, and since steroid hormones partially overlap the biological effects of each other, the pathology of hypercorticism is very mosaic. ACTH serves as a functional regulator for all zones (for the beam zone, its role is undivided), and therefore total hypercortisolism syndrome includes unconditional hyperproduction of glucocorticoids, often with more or less pronounced symptoms of hyperaldosteronism and hyperandrogenism.
According to the etiology and pathogenesis of development total hypercortisolism distinguish the following options:
I. Primary adrenal hypercortisolism as a result of primary hyperplasia of the gland (ACTH-independent) - Itsenko-Cushing's syndrome;
II. Secondary hypercortisolism with excessive hypothalamic-pituitary stimulation of the gland (ACTH-dependent) - Itsenko-Cushing's disease;
III. Secondary hypercortisolism with excessive ectopic production of ACTH outside the hypothalamic-pituitary region;
IV. Iatrogenic hypercortisolism with exogenous administration of corticosteroids.
I. In a quarter of cases, hypercortisolism is associated with a primary tumor lesion of the cortical substance of the gland. This pathology is called ACTH-independent Itsenko-Cushing's syndrome. Most often, this tumor grows from the cells of the zona fasciculata - glucosteroma (with an excess of glucocorticoids). A type of glucosteroma is glucoandrosteroma with excess synthesis in addition to androgens. In this case, the picture of Itsenko-Cushing's syndrome is combined with hyperandrogenism: in boys in the form of premature puberty, in women - virilism.
Another cause of ACTH-independent Itsenko-Cushing's syndrome is primary bilateral non-tumor hyperplasia of the adrenal cortex . It occurs in adolescents and young adults. The leading link in the pathogenesis is recognized as an autoimmune stimulating mechanism similar to Basedow's disease. Experimentally obtained steroidogenic and mitozogenic (growth) immunoglobulins to the cells of the adrenal cortex. In some cases, primary bilateral non-tumor hyperplasia is considered as a hereditary autosomal dominant variant of the syndrome - Carney's symptom complex. A fairly rare cause of primary hypercortisolism is bilateral hyperplasia of the adrenal cortex. The mechanism of this disorder is thought to be an ACTH-like stimulatory action of a gastro-inhibitory peptide synthesized by the gastrointestinal glands.
II. In the vast majority of cases, the cause of hypercortisolism is a tumor of the anterior pituitary gland - basophilic adenoma, or chromophobic tumors that secrete excess ACTH - adrenocorticotropinomas . Such a pathology in Russia is called Itsenko-Cushing's disease. Its pathogenesis is associated with a mutation of the G protein of the pituitary cells, which has an affinity for corticoliberin, as a result of which adrenocorticotrophs acquire excessive activity for this hypothalamic releasing factor.
"Antediluvian" methods of treating Itsenko-Cushing's disease by resection or extirpation of the adrenal gland with unrecognized pituitary adenomas led to the rapid growth of the same adrenocorticotropinomas due to stimulation of tumor cells of the adenohypophysis with hypothalamic corticoliberin against the background of hypocorticism, and Itsenko-Cushing's disease was replaced by Nelson's syndrome [volumetric tumor growth in the skull without signs of hypercorticism (if the adrenal glands were resected)].
III. A relatively rare cause of secondary hypercortisolism is ectopic tumors from cells of the diffuse endocrine system (apudomas) that secrete ACTH, less often corticoliberins. This pathology occurs with bronchogenic lung cancer, digestive tract carcinomas, medullary thyroid cancer, tumors of the islets of Langerhans, thymomas. This form of hypercortisolism is sometimes combined with hypersecretion by tumor cells and other biologically active substances - vasopressin, oxytocin, gastrin, etc. In fact, the described pathology is the content of the paraneoplastic syndrome of tumor growth. The level of ACTH in ectopic secretion exceeds it in Itsenko-Cushing's disease.
IV. Iatrogenic hypercortisolism occurs with long-term treatment with medium or short-term therapy with ultra-high doses of glucocorticoids.
Pathogenesis manifestations of total hypercorticism is determined by an excess of hormones of the adrenal cortex as a result of hyperplasia of adrenocorticocytes.
Glucocorticoids are hormones of the universal metabolic cycle. ACTH is an absolute stimulator of their secretion, so the picture of hypercorticism is determined by the effects of both corticosteroids and ACTH itself (for example, one of the results of ACTH action may be skin hyperpigmentation), as well as proopiomelanocortin and its derivatives. The combination with the features of hyperaldosteronism is explained both by the stimulation of ACTH and by the mineralocorticoid effect of large doses of glucocorticoids. Recall that mineralocorticoids are the most important regulators of potassium-sodium and water balance, and androgens are regulators of sexual functions, stress and anabolism processes.
Itsenko-Cushing's disease. A decrease in dopamine activity and an increase in the tone of the serotonergic system of the central nervous system increase the production of corticoliberin, ACTH, and then cortisol (secondary cortisolism) due to a violation of the "feedback" mechanisms. Hypercortisolism does not have an inhibitory effect on the central nervous structures. The disease is characterized not only and not so much by an increase in ACTH secretion as by stimulation of the production of adrenal hormones - cortisol, corticosterone, aldosterone, androgens.
Violations of the hypothalamic-pituitary relationships are combined with changes in the secretion of other tropic hormones of the pituitary gland - the production of growth hormone is inhibited, the content of gonadotropins and thyrotropic hormone decreases, but the secretion of prolactin increases.
The clinic of Itsenko-Cushing's disease is determined by a disorder of all types of metabolism regulated by steroid hormones of the adrenal glands.
Violation protein metabolism in general, it proceeds under the sign of protein catabolism mainly in muscles and mesenchymal elements (myocytes, skin cells, connective tissue, bones, lymphoid organs), and anabolic processes even predominate in the liver and central nervous system. For this reason, myasthenia gravis (muscle weakness), muscle wasting develops. Violation of protein synthesis is reflected in the protein composition of the connective tissue, glycosaminoglycans, protein content in blood plasma (especially albumin), immunoglobulins (antibodies). Increased deamination of amino acids leads to hyperazoturia. Collagenogenesis is inhibited, which leads to thinning and stretching of the skin in areas of fat accumulation (a symptom of tissue paper), which contribute to the formation of characteristic striae (stretch bands) of purple-violet color due to vasopathies, erythrocytosis and hypertension. In young patients, the growth and metabolism of vitamin D are disturbed. Wound healing is inhibited.
Fat metabolism . by the most X A typical manifestation of hypercortisolism is central obesity: against the background of hypotrophy of the extremities, fat is deposited in the abdomen, face, neck, and in the interscapular space. The most likely causes of obesity are polyphagia, hyperinsulinism, uneven distribution of insulin and glucocorticoid receptors in various lipocytes, stimulation of leptin production by corticosteroids, direct lipogenetic effects of ACTH and glucocorticoids. An excess of glucocorticoid receptors is observed in central lipocytes, and insulinism enhances lipogenesis in them, increases the intake of glucose and fatty acids.
An excess of glucocorticoids has a lipolytic effect, causing predominantly type II hyperlipoproteinemia (due to low and very low density lipoproteins, cholesterol, triglycerides), which, according to the mechanism of development, can be attributed to production and retention forms. The development of hyperlipoproteinemia is associated with increased synthesis of triglycerides in the liver, lipolysis, and blocking of apo-B receptors in many consumer cells.
carbohydrate metabolism . Glucocorticoids have a contra-insular effect - they inhibit the work of glucose transporters (glutes-4) into insulin-dependent tissues (lipocytes, myocytes, cells of the immune system) in favor of insulin-independent organs - the central nervous system, heart, diaphragm, and others. In the liver, gluconeogenesis, glucogenesis, glycogenesis are enhanced. In some patients with insufficient reserves of pancreas β-cells, secondary non-insulin-dependent diabetes mellitus is formed, which is complicated by ketoacidosis due to the high ketogenicity of glucocorticoids (which, by the way, is characteristic of insulin-dependent diabetes mellitus). In other patients, in the case of hyperfunction of β-cells of the islets of Langerhans, hyperinsulinism develops, which stabilizes the situation, and obvious steroid diabetes does not occur.
Water-salt metabolism and acid-base balance . They are characterized by sodium retention and the loss of hydrogen and potassium ions, due to which the content of K + in the cells of excitable tissues (neurons, cardiomyocytes, myocytes), as well as in blood plasma and erythrocytes, is significantly reduced. Hypokalemic alkalosis develops. Increased volumes of extracellular fluid and blood (hypervolemia, plethora). The absorption of calcium in the intestine is inhibited, and its excretion in the kidneys is enhanced. Nephrocalcinosis and nephrolithiasis develop, secondary pyelonephritis joins. The result can be kidney failure. A decrease in calcium in the body leads to the development of secondary hyperparathyroidism. Parathyroid hormone activates the transition of bone stem cells into osteoclasts and inhibits the transformation of the latter into osteoblasts. Cortisol also inhibits the transition of osteoclasts to osteoblasts. An increase in osteoclasts and an increase in their activity cause bone resorption. The latter loses its ability to fix calcium, resulting in osteoporosis.
The cardiovascular system . Chronic hypercortisolism causes symptomatic hypertension, the development of which is associated with the following mechanisms:
1) an increase in blood volume (hypervolemia, plethora),
2) increased sensitivity of adrenoreceptors of resistive vessels to pressor factors due to an increase in the sodium content and a decrease in potassium in the myocytes of resistive vessels (that is, due to an increase in their vasomotor tone),
3) edema of smooth muscles of arterioles and venules,
4) activation of the renin-angiotensin system due to stimulation of liver synthesis of α 2 -globulin (angiotensinogen) and endothelin I by glucocorticoids,
5) the inhibitory effect of corticosteroids on the release of atrial natriuretic peptide.
IN immune system secondary immunodeficiency, phagocytic insufficiency are formed, manifested by a decrease in resistance to infectious diseases. Skin bacterial and fungal infections develop. For this reason, and due to an excess of androgens, acne (acne vulgaris) and pustular-papular perioral dermatitis appear.
sexual functions. One of the early and permanent manifestations of Itsenko-Cushing's disease is a violation of sexual function, which is caused by a decrease in the gonadotropic function of the pituitary gland and an increase in the secretion of androgens by the adrenal cortex. In men, the production of androgens by the sex glands is inhibited (due to the suppression of the secretion of GnRH and luteinizing hormone by the feedback control mechanism), libido decreases and impotence develops. Excess androgens in the hormonal set of hypercortisolism in women form hirsutism (excessive hair growth), masculinization (acquisition of a male body type), changes in sexual behavior, dysmenorrhea, amenorrhea, spontaneous abortions, premature birth, secondary infertility, virilization.
Nervous system. Acute excess of glucocorticoids induces euphoria, psychosis, hallucinations and mania, and chronic - depression.
Changes in the blood . Glucocorticoids stimulate erythro- and leukopoiesis, trigger apoptosis of lymphocytes and eosinophils, resulting in the development of erythrocytosis, neutrophilia, lymphopenia, eosinopenia, change the state of the blood coagulation and anti-coagulation systems (development of thrombohemorrhagic syndromes).
Partial hypercortisolism. It is due to the pronounced the predominance of the secretion of one group of corticosteroids over the others and is represented by the following types:
1) hyperaldosteronism (primary and secondary);
2) adrenogenital syndrome (hyperandrogenism).
At the same time, there are practically no pure partial forms.
Primary hyperaldosteronism(Conn's syndrome).
I. The cause is tumors of the glomerular zone (aldosteroma) or with ectopic localization (ovary, intestine, thyroid gland). An excess of mineralocorticoids does not inhibit the production of ACTH, unlike glucosters, so atrophy of the healthy part of the adrenal glands does not occur.
II. Benign hereditary glucocorticoid-suppressed aldosteroma.
III. Bilateral hyperplasia of the glomerular zone of the adrenal cortex of unknown etiology. As in the case of micronodular cortical hyperplasia, the role of stimulatory antibodies is discussed in etiology.
IV. When eating licorice root (licorice) and using its preparations, the conversion of cortisol into cortisone is disrupted (the presence of hyperrizinic acid in plant materials inhibits the enzyme 11-β-hydroxylase). In this case, the syndrome of pseudohyperaldosteronism is reproduced. A similar enzyme defect is the cause of the hypertensive form of hereditary adrenal hyperplasia.
V. Lidl's syndrome - pseudohyperaldosteronism due to primary receptor hypersensitivity to aldosterone with its normal content in the blood.
VI. Iatrogenic administration of aldosterone.
In all forms of primary hyperaldosteronism, renin production, in contrast to secondary ones, is low. Hypervolemia through the receptor mechanism inhibits the synthesis of renin.
Secondary hyperaldosteronism. It develops due to the activation of the renin-angiotensin-aldosterone system and proceeds with a high level of renin in the blood plasma. The causes of secondary excessive secretion of aldosterone are:
1) Ischemia of the kidneys caused by damage to the renal arteries;
2) Hypovolemia;
3) Hyponatremia and excessive loss of sodium;
4) Primary non-tumor hyperplasia of cells of the juxtaglomerular apparatus of the kidney ( Bartter's syndrome, excess prostaglandins E 2);
5) Reninomas (tumors of cells of the juxtaglomerular apparatus of the kidney);
6) Pregnancy - estrogens stimulate the synthesis of renin and angiotensinogen.
Pathomorphology. In secondary hyperaldosteronism, there is no tumor and nodular hyperplasia, but hypersecretion and diffuse hypertrophy-hyperplasia are observed.
Manifestations of hyperaldosteronism consist of typical symptoms:
1) electrolyte-water disorders- hypernatremia and water retention (hypervolemia), hypokalemia and loss of hydrogen ions.
2) hypertension. It is accompanied by orthostatic fluctuations (due to potassium excretion, baroreceptors lose sensitivity to changes in systolic and diastolic blood pressure).
3) no edema - the production of atrial natriuretic peptides (atriopeptides) is increased compensatory. This mechanism removes some of the sodium and water and inhibits the formation of edema. Losses of potassium are also accompanied by polyuria, mainly at night.
4) severe hypokalemia generates muscle weakness, a violation of the flow of glucose with a current of potassium into the cell (diabetogenic effect), "hypokalemic nephropathy" with polyuria.
5) alkalosis- a shift in the acid-base balance to the alkaline side (in the distal convoluted tubules, Na + reabsorption occurs in exchange for the release of K + and H +) is accompanied by hypocalcemia with possible tetany.
The main link in the pathogenesis secondary hyperaldosteronism is a very high activity of the renin-angiotensin-aldosterone system, which occurs with severe hyperreninemia and hyperangiotensinemia, which are in antagonistic relationships with natriuretic peptides. Therefore, very high hypernatremia and systemic edema are formed.
adrenogenital syndrome. It is considered as a partial excessive secretion in the adrenal glands of sex hormones. (hyperandrogenism ).
Violations of the production of sex hormones of the adrenal glands is the cause of sexual disorders, collectively called - adrenogenital syndrome. These include:
1. Acquired forms associated with various tumors:
Itsenko-Cushing's disease and syndrome , including glucoandrosteroma,
androsteromes ,
corticoestroms (described individual cases in men).
2. Congenital forms. They are part of the structure of adrenogenital syndrome called "congenital adrenogenital syndrome" or (VDKN). The reason is the variety of gene mutations that block different stages of genetically determined steroidogenesis.
Pathogenesis. Typical female symptoms hyperandrogenism : hirsutism, dysmenorrhea, virilism and acne. In children, the tumor leads to early puberty. Children's growth stops. In girls, the congenital syndrome proceeds according to the heterosexual type and forms pseudohermaphroditism, in boys - according to the isosexual type. In 75% of cases, hypocorticism manifests itself and is accompanied by congenital hyperpigmentation of the skin, loss of salt in the urine (polyuria, hyponatremia, muscle hypotension, hyperkalemia, hypochloremia, acidosis, hypotension), vomiting with a fountain, cravings for salty foods. In 25% of cases, hypocorticism is latent.
Virilism is formed in women: hirsutism, masculinization of the physique, redistribution of fat according to the male type, a rough voice, baldness, atrophy of the mammary glands, oligomenorrhea and amenorrhea, clitoral hypertrophy, physical endurance, changes in sexual behavior stereotypes. In men, such tumors remain unrecognized. They have well-recognized corticoesteromas - malignant tumors with mutant estrogen production that cause feminization - gynecomastia, female body type and behavior, testicular hypotrophy. Congenital forms of adrenogenital syndrome with a metabolic block in the synthesis of cortisol in the direction of androgens require the greatest attention. There are many hereditary causes. They require differential diagnostic differences from true and false hermaphroditism of extra-adrenal and non-endocrine causes and determination of chromosomal sex. Adrenal congenital forms of hyperandrogenism (adrenogenital syndrome) can occur as part of the hypocorticism syndrome with symptoms of gluco- and mineralocorticoid deficiency.
The classic forms of hyperandrogenism are known: virilizing plus salt-losing but only virilizing . The non-classical form is characterized by a late onset of the disease.
The leading link in pathogenesis is the enzymatic block of the conversion of 17-hydroxyprogesterone to 11-deoxycortisol, which leads to excessive conversion of metabolites into androstenedione. Hyperandrogenism develops in utero. At the same time, a deficiency in the synthesis of mineral and glucocarticoids is formed. Against this background, the secretion of ACTH increases according to the feedback mechanism and the growth of the adrenal cortex and androsteroidogenesis is stimulated. The adrenal cortex increases due to the glomerular and reticular zones and resembles the cortex of the cerebral hemispheres. Clinically, adrenogenital syndrome consists of two syndromes – hyperandrogenism and hypocorticism , and predominantly in the form of hypoaldosteronism.
Erased and light forms [ "congenital hyperplasia (dysplasia) of the adrenal cortex" ] occur up to 30%. They are the cause of hirsutism and adrenarche. Hirsutism is a compelling reason to look for 21-hydroxylase defect syndrome. A defect in other steroidogenesis enzymes that create an innate picture of adrenogenital syndrome is extremely rare and is given in special guidelines.
The content of the article
Hypercortisolism (disease and Itsenko-Cushing's syndrome) observed with excessive release of glucocorticoids by the adrenal cortex and is characterized by the development of obesity, arterial hypertension, hyperglycemia and other metabolic disorders. The disease is more common in women.Etiology and pathogenesis of hypercortisolism
There are primary hypercortisolism due to damage to the adrenal cortex, and secondary hypercorticism associated with impaired function of the hypothalamic-pituitary system. In 75-80% of cases, hypercortisolism is caused by excessive secretion of ACTH (Itsenko-Cushing's disease), which leads to hyperplasia of the adrenal cortex. In 10% of such patients, an adenoma of the anterior pituitary gland is found. In other cases, there is a dysfunction of the hypothalamus, which secretes a large amount of corticoliberin. Itsenko-Cushing's syndrome can be caused by adenoma or adenocarcinoma of the adrenal cortex. In addition, hyperplasia of the adrenal cortex is caused by peptides that are biologically and chemically inseparable from ACTH, which are produced by cells of some malignant tumors of extra-adrenal localization (cancer of the lung, thymus, pancreas, etc.). Syndrome of ectopic ACTH production is more common in middle-aged and elderly men. Adenocarcinoma of the adrenal cortex is often the cause of hypercortisolism in children. Itsenko-Cushing syndrome also develops with prolonged use of glucocorticoids in diseases of an autoimmune and allergic nature, blood diseases, etc.Clinic of hypercortisolism
Patients complain of headaches, fatigue, weakness, sexual dysfunction. Obesity is characteristic with a predominant deposition of fat on the face, which acquires a rounded "moon-shaped" shape, torso, in the back of the neck, above the collarbones. At the same time, the limbs become thinner due not only to the redistribution of fat, but also to muscle atrophy (the catabolic effect of glucocorticoids on protein metabolism). Atrophy of the skin develops, on which hemorrhages easily appear - ecchymosis. On the skin of the abdomen, mainly in the lower lateral sections, pinkish stripes are formed - striae. Glucocorticoids also cause the development of osteoporosis, which is manifested by pain in the bones and joints, and sometimes by spontaneous fractures of tubular bones, ribs, and spine. In 3/4 of patients, arterial hypertension is observed, which can be quite persistent. The increase in blood pressure is due to an increase in the volume of circulating blood and an increase in the action of catecholamines under the influence of glucocorticoids. Many patients develop myocardial dystrophy, accompanied by changes in the ECG, and in 1/4 patients - heart failure. Water-electrolyte metabolism is disturbed - edema and hypokalemia appear, calcium excretion increases and its absorption in the intestine is disturbed, which contributes to the progression of osteoporosis. Most patients have psycho-emotional disorders - irritability, irritability, emotional lability, sometimes severe depression and psychosis. An increase in androgen secretion leads to hirsutism, acne, and menstrual irregularities in women. In men, impotence develops, libido decreases as a result of the inhibitory effect of hydrocortisone on Leydig cells. Abdominal pains are often observed, stomach ulcers develop more often, which is especially characteristic of Itsenko-Cushing drug syndrome. Glucose tolerance is usually reduced, some patients develop diabetes mellitus, which, as a rule, is relatively mild and rarely complicated by ketoacidosis. Moderate neutrophilia, sometimes erythrocytosis, hypokalemia, hypochloremia, and metabolic alkalosis are found in the blood. X-ray reveals generalized osteoporosis, especially of the spine and pelvic bones.Diagnosis and differential diagnosis of hypercortisolism
Cushing's disease and syndrome should be suspected in the presence of obesity, striae, hirsutism, arterial hypertension, and osteoporosis. In such patients, the content of hydrocortisone and 17-hydroxycorticosteroids in the blood and the excretion of 17-hydroxycorticosteroids in the urine are increased. In some patients, the excretion of 17-ketosteroids is also increased. For the differential diagnosis of the disease and Itsenko-Cushing's syndrome, samples with dexamethasone (small and large Liddle test) and metopyrone are used. When conducting a small Liddle test, the patient is prescribed dexamethasone, which blocks the secretion of ACTH, 0.5 mg every 6 hours for 2 days. In the presence of hypercorticism, the excretion of 17-hydroxycorticosteroids before and after taking the drug does not differ significantly, while in healthy people after the test it decreases. A simpler method of diagnosing hypercortisolism is to determine the level of hydrocortisone in the blood at 8 am after taking 1 mg of dexamethasone around midnight. In healthy people, the level of hydrocortisone is significantly lower than in hypercortisolism. When conducting a large Liddle test, the patient takes dexamethasone 2 mg every 6 hours for 2 days. With Itsenko-Cushing's disease, the excretion of 17-hydroxycorticosteroids in the urine falls by 50% or more compared to the initial level, while with tumors of the adrenal glands and the syndrome of ectopic ACTH production, it does not change. Metopyrone, which blocks 11-hydroxylase, is administered orally at 750 mg every 6 hours for 2 days. With Itsenko-Cushing's disease, taking the drug leads to an increase in the excretion of 17-hydroxycorticosteroids in the urine, and with Itsenko-Cushing's syndrome, it does not change.Of great diagnostic importance is the determination of the level of ACTH in the blood using RIA. With a tumor of the adrenal cortex, it is reduced, and with Itsenko-Cushing's disease and, to an even greater extent, the syndrome of ectopic production of ACTH, it is increased. With damage to the pituitary gland, the excretion of 17-hydroxycorticosteroids and 17-ketosteroids increases, since in such patients the secretion of all steroid hormones, including androgens, increases. In the syndrome of ectopic ACTH production, the excretion of 17-hydroxycorticosteroids predominantly increases. With a benign tumor of the adrenal cortex, the release of 17-ketosteroids is normal, and with adenocarcinoma, it is usually increased.
To detect tumors of the adrenal glands, computed tomography is used, which is a more informative method compared to arteriography and radioisotope scanning of the adrenal glands using iodocholesterol. If the size of the adrenal gland exceeds 4 cm, then the diagnosis of adenocarcinoma is most likely, if it is less than 4 cm - adenoma of the gland. With a high level of ACTH in the blood, computed tomography of the pituitary gland is performed. In the absence of a pituitary tumor, an extra-adrenal tumor producing ACTH should be suspected. A feature of the syndrome of ectopic ACTH production is the frequent absence of pronounced clinical signs of hypercortisolism. The characteristic symptom is hypokalemia.
Separate manifestations of Itsenko-Cushing's syndrome are observed in obesity, chronic alcoholism. With exogenous obesity, fat is usually distributed evenly. The content of hydrocortisone and its metabolites in the blood and urine changed slightly, the daily rhythm of hydrocortisone secretion was preserved. In patients with alcoholism, cessation of alcohol intake usually leads to the disappearance of symptoms resembling those of Itsenko-Cushing's disease.
Itsenko-Cushing's disease- a disease resulting from lesions at the level of the brain in the hypothalamus or pituitary gland. This causes an increase in the production of ACTH (adrenocorticotropic hormone produced by the pituitary gland), which excessively increases the work of the adrenal glands (paired glands that lie on the upper side of the kidneys). In a person with this pathology, blood pressure rises, the skin becomes marble-colored, and the face becomes moon-shaped, crimson-red stripes appear in the abdomen and thighs, fat deposits occur in certain areas of the body, the menstrual cycle is disturbed, etc. The disease is 5-10 times more common in women than in men aged 20-40 years. It can occur in adolescents during puberty and sometimes in children and people over 50 years of age. The symptoms of the disease were first described in 1924 by the Odessa neuropathologist Nikolai Itsenko and in 1932 by the Canadian neurosurgeon Harvey Cushing. The first scientist suggested that the reason lies in the disruption of the hypothalamus, and the second - associated it with a pituitary tumor. It has now been proven that pathology occurs after failures in the functions of both brain structures.
How do the hypothalamus, pituitary and adrenal glands work?
In order to understand how the symptoms of Itsengo-Cushing's disease are related to the hypothalamus - pituitary - adrenal glands, we will talk a little about the anatomy and physiology of these body structures. Let's start with a few words:- A hormone is a biologically active substance produced by special organs or cells in one part of the body and regulating the activity of organs and tissues in other parts of the body.
- An endocrine gland (endocrine gland) is an organ that produces and releases hormones or other substances into the blood.
- The hypothalamus is a part of the brain weighing 4 g that controls metabolism, the work of the endocrine and gonads.
- The pituitary gland is an endocrine gland located at the base of the human brain and affects the growth, development, and metabolic processes of the body.
- The adrenal glands are paired human endocrine glands that lie on the upper side of the kidneys.
The hypothalamus regulates the following processes in the body:
- Feelings of thirst, hunger and satiety.
- Sleep and emotional states.
- sexual function.
- Respiration and blood supply.
- The processes of memorization and learning.
- Thermoregulation - a set of physiological processes aimed at maintaining a relatively constant temperature of the human body.
- Diuresis - the amount of urine excreted in a certain time. In humans, daily diuresis averages 1200-1600 ml.
The anterior lobe accounts for 75% of the total mass of the pituitary gland. It contains 3 types of cells:
- Acidophilic (eosinophilic) - cells contained in 30-35%, which are stained with acid dyes in red and orange.
- Basophilic - cover up to 10% of the total mass. Alkaline dyes are used to detect them. Some of the cells - corticotropocytes - produce ACTH (adrenocorticotropic hormone).
- Chromophobic - precursors of eosinophilic and basophilic cells. Their adenohypophysis contains 60%.
ACTH (adrenocorticotropic hormone, corticotropin) produced by the anterior pituitary gland. It stimulates the function of the adrenal cortex. Thus, it controls metabolic processes and increases the resistance of the human body under the influence of adverse conditions. In addition, it contributes to the formation of melanin, a pigment that gives the skin a brownish tint. The production of ACTH by the pituitary gland is under the action of a special releasing factor of the hypothalamus - corticoliberin. Under its influence, there is an increase in the formation of corticotropin.
adrenal glands are laid at 6-8 weeks of gestation. Their final formation occurs in the third year of life. They have a different shape: the left one is presented in the form of a crescent, the right one is in the form of a pyramid. The size of each is approximately 6 × 3 × 1 cm, weight - about 4-5 g. In the adrenal glands, the surface (cortical layer) and internal (medulla) parts are isolated. Both glands are encased in a connective tissue capsule. The cortical layer is divided into 3 areas:
- Glomerular (outer) zone - occupies 15% of the cortex, forms mineralocorticoids.
- The bundle (middle) zone - makes up 75% of the cortical layer, produces glucocorticoids and a small amount of androgens.
- The reticular (lower) zone - produces androgens, a little estrogens and glucocorticoids.
- Androgens (androstenedione, dehydroepiandrosterone, testosterone, etc.),
- Estrogens (estrogen, estradiol, estrone, etc.),
- Mineralocorticoids (aldosterone, deoxycorticosterone),
- Glucocorticoids (corticosterone, hydrocortisone, cortisol).
Each of the above groups performs its functions:
- Androgens - in women and men develops secondary sexual characteristics, libido.
- Estrogens - stimulate the growth and development of female genital organs and secondary sexual characteristics in women.
- Mineralocorticoids - retain water in the body (in the space between cells).
- Glucocorticoids - contribute to the decomposition of proteins and fats into simpler components, reduce calcium absorption from the intestines and the body's immunity, increase blood pressure, increase the secretion of gastric juice, forming "steroid" ulcers.
In addition, one of the important functions is the control of the hormone of the hypothalamus - corticoliberin. The high content of glucocorticoids, namely cortisol in the blood, delays the production of corticoliberin, in turn, it reduces the formation of ACTH in the pituitary gland. Ultimately, ACTH inhibits the work of the adrenal cortex, and the content of cortisol in the blood decreases. If there are few glucocorticoids in the blood, then the whole process described above will go the other way around. The hormone of the hypothalamus will increase, it in turn will increase the production of ACTH, and the latter will increase cortisol in the blood. This is the mechanism of regulation of the hypothalamic-pituitary-adrenal system.
Causes of Itsenko-Cushing's disease
It is often difficult to find out the source of the disease. But over the course of many years of practice of highly qualified specialists, several factors have been identified. First of all, these are periods of rapid restructuring of the body, which can cause damage at the level of the hypothalamus or pituitary gland: puberty, pregnancy, childbirth, menopause. Secondly, severe bruises, severe craniocerebral and mental injuries of the skull, various infections of the brain and intoxication (poisoning) of the body contribute to the appearance of this pathology. Thirdly, scientists consider the tumor (adenoma) formed from basophilic and chromophobic cells of the anterior pituitary gland to be the main cause. In people suffering from Itsego-Cushing's disease, it occurs in 85%.Each of these factors can trigger the following mechanism: corticoliberin (the hormone of the hypothalamus) begins to be produced in large volumes, by which it causes increased production of ACTH (the pituitary hormone), and the latter increases the work of the adrenal cortex by 4-5 times. Normally, elevated blood levels of cortisol (adrenal hormone) should reduce the formation of corticoliberin. But the reason that caused the disease does not allow it to be done. As a result, all hormones continue to be synthesized in large quantities.
Symptoms of Itsenko-Cushing's disease
There are many clinical signs of this pathology. In order to remember everything and not to miss anything, we will consider them in stages for all body systems.Leather. The skin becomes dry, purple-marble, flaky. In places of strong friction, increased pigmentation is noted. In the area of the buttocks, thighs, abdomen, mammary glands, armpits, wide bands of blue-violet to dark red shades stand out. Their appearance is associated with the destruction of proteins under the influence of increased production of glucocorticoids (adrenal hormones). The skin thins to the point where blood vessels are visible. The vessels themselves are breaking, that any impact on them causes damage. For this reason, the patient can see bruises and wounds of various sizes and depths, which take a very long time to heal. It should be noted 2 important symptoms - hirsutism and virilism - both develop as a result of an increased content of androgens. Hirsutism is male-pattern hair growth in women. Mustaches, a beard, vegetation on the chest and abdomen appear.
virilism- a phenomenon when the face and body of a person, regardless of gender, is covered with a large amount of hair, exceeding the norm by several times. And on the head they fall out and form bald patches. Often on the body you can notice pustular rashes, ulcers and boils (inflammation of the sweat and sebaceous glands of the skin).
Subcutaneous adipose tissue and obesity. Obesity is one of the main symptoms and occurs in 95% of cases. Its redistribution throughout the body is not the same. The face acquires a rounded shape resembling the moon ("moon face"). Another distinguishing feature may be the deposition of fat in the region of the seventh cervical vertebra in the form of a small mound ("climacteric hump" or "buffalo type"). This vertebra, or rather its process, can be felt at the back of the neck (the most protruding part), if you tilt your head strongly forward. A significant thickening of the subcutaneous fat layer also occurs in the abdomen and chest. All these signs are explained by the action in the increased content of cortisol (adrenal hormone), which contributes to the accelerated formation of lipids (fats) in the body.
Bone system. With Itsengo-Kushin's disease, the skeletal system is affected in 95%. The increased content of glucocorticoids (adrenal hormones), on the one hand, destroys the proteins that are the basis of the bone, and on the other hand, reduces the absorption of calcium in the intestine. Thus, calcium, which gives strength to the skeletal system, enters it in small quantities. As a result, a disease called osteoporosis develops. It covers mainly the bones of the face, skull, spine, feet and hands. There is a change in their size and shape, which is most often accompanied by severe fractures and severe pain. In adults, there is a decrease in growth by 10-20 cm, and in children - its complete delay.
Muscular system. As in the previous case, an increased amount of glucocorticoids also destroys muscle proteins. This leads to weight loss of the arms and legs, weakness appears in them to such an extent that the patient cannot lift a small load or stand up without someone else's support.
Respiratory system. Immunity is reduced under the influence of adrenal hormones. The body becomes susceptible to all infections. Against this background, bronchitis (inflammation of the bronchi), pneumonia (a disease that affects the lungs and small bronchi), tuberculosis (an infectious disease, often chronic, caused by a special Koch bacterium and affecting the lungs, bones, joints, intestines and other organs) develop.
The cardiovascular system. One of the first signs of Itsenko-Cushing's disease in 95% of cases is an increase in blood pressure. If measures are not taken to lower it to normal, a person may develop heart failure. It is characterized by the following: the heart, contracting less often, slows down the movement of blood through the vessels of the body, and all organs and tissues begin to experience a lack of oxygen necessary for their work. This condition of the patient can lead to death.
Digestive system. With this disease, there is heartburn (burning) in the esophagus, "steroid" ulcers of the stomach and the initial part of the intestine, caused by glucocorticoids. The liver also suffers: it cannot perform all its proper functions.
Urinary system. There are several causes that create problems in the kidneys and urinary tract. One of them - reduced immunity increases their susceptibility to infections. Pyelonephritis is formed - a disease that affects the kidneys and is characterized by high body temperature and back pain. The second reason is the leaching of calcium from the bones, which enhances its excretion in the urine. This contributes to the formation of stones in the urinary system and the development of urolithiasis. The third factor - high blood pressure destroys the kidneys in such a way that connective tissue grows in their place. This is how nephrosclerosis develops, which raises the pressure. A vicious circle is formed and all processes are repeated one after another, worsening the general condition of the body.
Nervous system and psyche. In previous systems, osteoporosis was described, which destroys the bones, presses on the nerves passing near them. This action causes such severe pain, especially in the upper parts of the arms and legs, that the patient cannot make the slightest movement. On the part of the psyche, there is a decrease in memory and intelligence, frequent depression, increased emotionality, or vice versa - indifference to everything around. With a long course of the disease with a significant deterioration, thoughts of suicide appear.
Endocrine and reproductive systems. In 35-40% of patients, "steroidal" diabetes mellitus caused by glucocorticoids is observed. Diabetes mellitus is a disease resulting from endocrine disorders that increase blood sugar and disrupt the metabolism of proteins, fats, carbohydrates, minerals, water and salts. With Itsenko-Cushing's disease, both sexes experience a decrease in libido. In women, in 70% of cases, there is no menstruation, the organs themselves (uterus, ovaries) decrease in size. Pregnancy in such situations is almost impossible. And in the case when it happens, it always ends in a miscarriage. If this pathology manifests itself in childhood, the sexual development of the child stops.
Diagnosis of Cushing's disease
- To make a diagnosis of Itsenko-Cushing's disease, our first step will be to assess the presence of the symptoms listed above. The most common of them: obesity, high blood pressure, specific hair growth and skin coloration, osteoporosis and pain, menstrual disorders and decreased libido, mental disorders. This pathology has several forms of manifestation of symptoms: mild (symptoms are mild), moderate (most symptoms can be detected, but complications will not be observed), severe (all symptoms with complications). According to the course of the disease, two forms are distinguished: progressive (develops for several months) and torpid (lasts for several years).
- The second step will be the study of blood and urine by various methods, which will reveal an increased content of hormones from the hypothalamus - pituitary gland - adrenal glands and their end products of decomposition.
- The third is examination methods that should confirm Itsenko-Cushing's disease and exclude all other pathologies, which are very similar to it. These include: radiography of the bones of the skull, spine, limbs; magnetic resonance imaging (MRI) and computed tomography (CT) of the brain - can confirm the destruction of the skeletal system and the presence of a pituitary tumor. Ultrasound, MRI, CT, angiography, radioisotope imaging of the adrenal glands will show an increase in their size and assess the degree of functioning of each layer. Diagnostic tests with metopyrone and dexamethasone will finally eliminate doubts about the correctness of the diagnosis.
Treatment of Itsenko-Cushing's disease
There are two types of treatment: etiopathogenetic (eliminates the cause of the disease and restores the normal functioning of the hypothalamus - pituitary - adrenal glands) and symptomatic (correction of the work of all affected organs).- Treatment of the causative factor of the disease can be divided into surgical, radiation and medical methods, which can be combined or used individually, depending on the form and severity of the disease.
- Of the surgical ones, adrenalectomy is distinguished (unilateral or bilateral removal of the adrenal glands), destruction of the adrenal glands (by introducing a contrast agent that destroys their structure) and excision of the pituitary tumor.
- From radiation - use X-ray, gamma and proton therapy.
- The drug method includes two groups of drugs: dopamine receptor agonists (bromocriptine (parlodel), reserpine, difenin, cyproheptadine), and antitumor agents, steroid synthesis inhibitors (chloditan, elipten, mitotane, mamomit). The first group of drugs activates the dopamine receptors of the nervous system, and the hypothalamus begins to "understand" that there are too many corticosteroids in the blood, so it needs to reduce the release of its corticoliberin in order to reduce the work of the pituitary gland, which will depress the function of the adrenal glands. The second - delays the synthesis of all hormones of the adrenal cortex.
- symptomatic treatment. In the presence of diabetes, they follow a strict diet and take drugs that reduce blood sugar - bigunides and sulfonamides. In severe cases, use insulin. With arterial hypertension, antihypertensive substances of central action (reserpine, adelfan, etc.) and diuretic drugs are prescribed. In heart failure, cardiac glycosides or digitalis preparations are required. For the treatment of osteoporosis, vitamin D, calcitonins, bisphosphonates are used, which restore the protein structure of the bone, increase calcium absorption from the intestine and thereby increase its inclusion in protein matrices. Fluorine salts and anabolic steroids increase bone formation. With a decrease in immunity, drugs are prescribed that increase it due to increased growth and maturation of the main components - lymphocytes.
What is the difference between Cushing's disease and Cushing's syndrome?
Cushing's syndrome and Itsenko-Cushing's disease are often confused not only because of the similar name, but also because of very similar symptoms. However, these concepts in medicine are far from identical. In both cases, we are talking about hypercortisolism - increased secretion of hormones from the cells of the adrenal cortex ( primarily cortisol.). It is these hormones that begin to affect various organs and entire systems, change metabolism ( metabolism of certain substances). These changes lead to the appearance of certain symptoms. Cushing's syndrome is understood as the totality of all changes that occur in the body with increased release of corticosteroids, as well as the external manifestations of this disorder. From the point of view of medicine, this concept coincides with the concept of "hypercorticism". Cushing's syndrome can have various causes. We are talking about any internal or external effect on the body that stimulates the production of corticosteroids.
The causes of Cushing's syndrome may be the following disorders:
- hormone-producing adrenal gland tumor;
- paraneoplastic syndrome ( rare, with tumors of the lungs, mediastinum and some other organs);
- long-term use of large doses of corticosteroid drugs - the so-called drug hypercorticism;
- pituitary tumor ( Cushing's disease).
In Itsenko-Cushing's disease, the effect on the cells of the adrenal glands occurs as follows:
- The hypothalamic-pituitary system in the brain normally produces the so-called adrenocorticotropic hormone (ADH). ACTH). With Itsenko-Cushing's disease in the pituitary gland ( the pineal gland of the brain that controls the endocrine system) a microtumor is formed, which increases the release of ACTH.
- ACTH enters the bloodstream and acts on cells in the adrenal cortex. With an excess of this hormone, cells increase in volume and number.
- Spurred on by adrenocorticotropic hormone, the adrenal cortex produces more corticosteroid hormones and hypercortisolism occurs ( Cushing's syndrome).
- An increase in blood corticosteroid levels should be picked up by the pituitary gland and cause a decrease in ACTH production ( feedback mechanism). However, due to a tumor or pathological changes in the gland, this does not happen.
- Gradually increases both the level of ACTH and the level of corticosteroids in the blood. They act on target cells, causing disturbances in the functioning of various organs and systems and leading to the appearance of characteristic symptoms.
Differential diagnosis of the causes of hypercortisolism
| Criterion | Itsenko-Cushing's disease | Other Causes of Hypercortisolism (Cushing's syndrome) |
| Blood ACTH level | Increased due to pathological changes in the pituitary gland. | Normal or reduced ( because the feedback mechanism can operate). |
| Instrumental Research | Magnetic resonance imaging ( MRI) often reveals tumors or hyperplasia ( cell proliferation) pituitary gland. | CT scan ( CT), MRI and X-ray reveal hyperplasia or tumor of the adrenal glands, but no changes in the pituitary gland. |
| Large dexamethasone test | The level of corticosteroids after the introduction of dexamethasone is reduced by more than half, compared with the original. | The introduction of dexamethasone does not cause a pronounced decrease in the level of corticosteroids. |
| Influence of other factors | Unable to identify the influence of other factors ( besides ACTH) on the adrenal glands. | Careful examination reveals other tumors ( causing paraneoplastic syndrome) or any other causes of the syndrome. |
Thus, Itsenko-Cushing's disease is only one of the possible causes of Cushing's syndrome. These concepts cannot be identified, since there are differences in the mechanism of their development, diagnosis and treatment tactics, although the external manifestations in both cases completely coincide.
Does hypercortisolism occur in children?
Hypercortisolism ( Cushing's syndrome) in children is considered a fairly rare disease. Its cause in childhood and adolescence is more often hyperplasia ( increase and increase in activity) adrenal glands or incorrect intake of corticosteroid drugs ( drug-induced hypercortisolism). Itsenko-Cushing's disease, which is also a variant of hypercortisolism, is very rare in childhood and adolescence. Cushing's syndrome is a significant increase in the concentration of corticosteroid hormones in the blood. These hormones regulate many metabolic processes in the body and can affect the functioning of a variety of organs. In childhood, when many tissues of the body are still at the stage of growth and development, hypercortisolism is especially dangerous.
Most often, doctors or doctors can reduce the level of corticosteroid hormones with medication or surgery. However, if their action was long enough, some complications and residual effects may develop, which will affect health and life in general in the future. That is why it is believed that hypercortisolism in children is more severe, although statistically lethal outcome in children and adolescents is less common than in adults.
The consequences of hypercortisolism in children may be the following disorders:
- Bone curvature. The hormone that causes major problems in the body in Cushing's syndrome is cortisol. Under its influence, calcium begins to be washed out of the bones ( osteoporosis develops). Because of this, the bone tissue loses its strength. The growth centers that are in the bones of children and adolescents disappear, and the bones themselves become more fragile. Usually flat bones are affected first ( skull bones, pelvic bones) and only in severe cases - tubular ( limb bones). In the midst of the disease, cases of bone fractures are not uncommon. Due to poor absorption of calcium, these fractures heal slowly and the bones may not heal properly. Therefore, people who suffered from hypercortisolism in childhood may show visible cosmetic defects associated with bone curvature.
- growth retardation. Growth retardation is also associated with osteoporosis, described above. The problem is that not only flat and tubular bones stop growing, but also the vertebrae. Without urgent effective treatment, they can change their shape, shrink, causing pain associated with infringement of the spinal nerves. Since the full treatment of hypercortisolism and the normalization of metabolic processes in the body usually require a certain amount of time ( months, sometimes years, depending on the cause of Cushing's syndrome), children begin to lag far behind their peers in growth.
- Morbid obesity. Under the influence of cortisol, there is a redistribution of fatty tissue in the body. The child begins to gain weight despite the stunting). Obesity can remain after the normalization of hormone levels and present certain problems in the future. At the same time, muscle tissue gradually atrophies, due to which the limbs become somewhat thinner.
- Skin problems. Excess corticosteroids can cause dry skin, flaking, and acne in adolescents. In severe cases, more serious infectious processes develop ( pyoderma etc.). As a rule, these diseases do not pose a serious danger to health or life, but they can affect the psychological state of a child and, especially, a teenager.
- Psycho-emotional disorders. In part, their appearance is facilitated by cosmetic defects that accompany the course of the disease. On the other hand, with hypercortisolism, there is also a direct effect of hormones on the central nervous system. A number of patients develop depression, depression, and sometimes thoughts of suicide ( more typical for teenagers). In these cases, the intervention of a psychologist in the treatment process is not enough. It is important to reduce the level of hormones, because without this psychological help will not have the desired effect.
- Puberty disorders. Patients with hypercortisolism often develop excessive and early hair growth. Moreover, hair grows in a male pattern. With a high concentration of hormones and the absence of treatment, the development of hirsutism is possible. This syndrome consists in the growth of male-type hair in girls ( on the upper lip, chin, chest, back). Hypertrophy may be seen increase) genital organs - clitoris and penis. At the same time, puberty itself is often delayed or, conversely, accelerated.
Treatment of children with hypercortisolism requires special attention. They are usually handled by a pediatric endocrinologist. The main directions in treatment are similar to those in adults. However, accompanying psychological support should be provided. For a long time limit sports and exercise in general. The fact is that they increase the risk of fractures or bone deformities, slow down the growth of the child. Timely diagnosis and intervention of doctors, as well as a properly selected course of treatment, can prevent complications or residual effects in the future.
What is the diet for Itsenko-Cushing's disease?
Itsenko-Cushing's disease is characterized by an increase in the blood level of corticosteroid hormones ( cortisol and others), which cause significant changes in the functioning of various organs and tissues. Diet therapy cannot greatly affect the production of these hormones, so its role in treatment is often underestimated. However, in many cases it is dietary changes that allow patients to improve their health. This is due to the fact that cortisol affects the metabolism of various substances. This can cause various complications, which lead to the appearance of severe symptoms of the disease. Compliance with a certain diet partly regulates metabolism. Thus, diet therapy can be considered a symptomatic treatment of complications, although it does not directly affect hormonal disruptions in Itsenko-Cushing's disease. A specific diet should be followed in case of the following complications:
- Osteoporosis and urolithiasis ( stones in the kidneys) . Both of these complications are associated with leaching of calcium from bone tissue ( demineralization) and its accumulation in the renal pelvis after blood filtration. To normalize calcium levels, it is recommended not to consume saturated fatty acids ( main sources - margarine, butter, mayonnaise). The proportion of foods containing vitamin D should be increased, since it is it that promotes the absorption of calcium. Such products are eggs, dairy products, cheese. The use of cottage cheese, milk and other foods rich in calcium will have an ambiguous effect. On the one hand, it can strengthen bones, on the other hand, it can accelerate the formation of kidney stones.
- Obesity. Excess cortisol affects the formation of adipose tissue and electrolyte balance, contributing to edema. To alleviate the condition, it is recommended to reduce the amount of sodium consumed ( First of all, salt), animal fats, and in severe cases, fluids ( up to 1.5 - 2 liters per day).
- peptic ulcer. Diet for peptic ulcer caused by hypercortisolism ( elevated levels of corticosteroids), does not differ from the diet for ulcers of other origins. Frequent fractional meals are recommended. When choosing products, you should focus on table number 1, 1a and 1b according to Pevzner. He excludes rich, salty, sour, smoked or fatty foods, as they stimulate the secretion of gastric juice and aggravate the course of the disease. Also, you can not drink strong tea, coffee, alcohol. During an exacerbation, boiled meat, cereals, low-fat soups and other light foods are recommended.
- Heart failure. In heart failure, the goal of the diet is to normalize the volume of circulating blood. To alleviate the symptoms, you should “unload” the heart, which cannot cope with its work. Patients need to follow the treatment table number 10 according to Pevsner. First of all, limit salt intake ( up to 1.5 - 2 g per day) and water ( up to 1 - 1.5 liters per day).
- steroid diabetes. Steroid diabetes occurs due to disturbances in the production of insulin and insensitivity of tissue receptors to the action of this hormone. The basic principles of diet therapy for this disease correspond to table number 9 according to Pevzner. The patient's diet should be slightly increased in protein content ( 100 - 110 g), but the proportion of carbohydrates is reduced ( no more than 200 g) and fats ( no more than 40 g).
It should be understood that with Itsenko-Cushing's disease, all of the above processes ( calcium leaching, electrolyte disturbances, ulcer formation, and increased sugar levels) occurs simultaneously, although the patient may not have as many symptoms. In this regard, to prevent possible complications, the final diet is discussed with the attending physician. Usually it is focused on the complication that is most pronounced in a particular patient.
Also, in parallel with dieting, it is necessary to fight the increased level of hormones with medicinal or surgical methods. Without eliminating the underlying cause of the disease, diet therapy will only be a temporary measure that will allow for some time to eliminate the symptoms and manifestations of the disease.
Is it possible to treat hypercortisolism with folk remedies?
Hypercortisolism is an increase in the level of corticosteroid hormones in the blood. In about 70% of cases, this syndrome is caused by Itsenko-Cushing's disease or improper use of hormonal drugs. Often, tumors in the pituitary gland are the root cause of the disease ( iron in the brain), adrenal cortex or other organs. It is impossible to eliminate such a serious pathology only by traditional medicine methods. This requires a serious and long course of drug treatment, and often surgery. However, traditional medicines can sometimes help to relieve the symptoms and manifestations of the disease. Certain medicinal plants can, for example, lower blood sugar levels in steroid diabetes, relieve stomach ulcers, and improve heart function in heart failure. However, all these measures will be only auxiliary. Traditional medicine is much weaker in effect than modern pharmaceuticals.
For auxiliary treatment for hypercortisolism, the following folk remedies can be used:
- Sea buckthorn juice. Drink 40 - 50 ml an hour before meals ( three times a day). Due to its enveloping properties, it protects the gastric mucosa from the action of gastric juice, relieves the symptoms of peptic ulcer.
- Sea buckthorn oil. The mechanism is similar to the action of sea buckthorn juice. It is also taken 3 times a day before meals, but 0.5 - 1 teaspoon.
- Kefir. Before going to bed, it is recommended to drink 1 glass of fresh kefir at room temperature. Before use, add a tablespoon of vegetable oil to it and mix well. The tool promotes healing of ulcers within 30 - 40 days. However, for a good effect, hypercortisolism, the cause of their formation, should also be fought.
- Linden honey. Just like sea buckthorn juice, it has enveloping properties and protects the gastric mucosa. To relieve peptic ulcer, it is enough to drink 3 cups of warm boiled water a day, in which 1 tablespoon of honey is dissolved.
- Radish juice with honey. Used for urolithiasis kidney stones). Freshly squeezed radish juice is mixed with honey in equal proportions. The remedy is taken 1 teaspoon three times a day ( before meals).
- watermelon rinds. Dried watermelon peels are crushed, poured with boiling water and continue to simmer for another 20-25 minutes. The remedy is drunk chilled to room temperature, 1 glass three times a day. For 1 - 2 weeks of admission, the symptoms of gallstone disease are removed.
- Potato poultices. Used for severe back pain renal colic). After easing the pain, you need to take a warm bath, take a horizontal position and put on your back ( in the area of the kidneys) warm squashed boiled potatoes ( do not peel off).
- Infusion of garlic. It is used in steroid diabetes to lower sugar levels. A few cloves of garlic are rubbed, poured with boiling water ( half liter) and insist for 20 - 30 minutes. The infusion is drunk half a cup 2-3 times a day in small sips.
- Buckwheat. Also effective in lowering sugar levels. The grains are crushed ( in a coffee grinder or mortar) and pour kefir. For 200 ml of kefir, 3-4 full teaspoons of chopped buckwheat are needed. The remedy should be taken twice a day half an hour before meals. For a visible effect, treatment is continued for at least 2 weeks.
- Infusion of blueberries. For 4 teaspoons of dried berries, you need 1 cup of boiling water. Infusion lasts 8 - 10 hours, after which the infusion is drunk during the day in small portions. This medicine lowers blood pressure often elevated in hypercortisolism) and protects the retina from degeneration due to diabetes. In addition, a large amount of vitamins from blueberries will strengthen weakened immunity.
- Infusion of rowan fruits. For 1 tablespoon of dried fruits, you need a glass of boiling water. The infusion lasts until the water cools to room temperature. The remedy is taken three times a day for half a cup. The action is similar to the infusion of blueberries ( without such pronounced protection of the retina).
Why is hypercortisolism dangerous?
Hypercortisolism is a very serious disease, which under certain conditions can lead to the death of the patient. The problem is that the adrenal glands start to produce too much corticosteroid hormones ( mainly cortisol). These substances in excess can seriously disrupt the functioning of various organs and systems in the body. The longer the period of hypercortisolism lasts ( due to late diagnosis or incorrect treatment), the greater the risk of serious complications. Hypercortisolism is dangerous for the following reasons:
- Violation of calcium metabolism. Excess cortisol affects the absorption of calcium by the body. Because of it, this substance is not absorbed by the bones, and with prolonged hypercortisolism it is even washed out of the bone tissue. This leads to the development of osteoporosis, a disease in which the patient's bones become more fragile. Excess calcium travels through the bloodstream to the kidneys, where it often contributes to the formation of stones ( urolithiasis). Osteoporosis and urolithiasis are rarely fatal ( there is a risk only with the addition of an infection and the absence of medical care), but often cause disability.
- Increase in glucose levels. Under the influence of cortisol, insulin production worsens, and blood sugar levels begin to rise. This condition is called steroid diabetes. It is not as severe as ordinary diabetes mellitus, but still, without adequate treatment, it can greatly worsen the patient's condition. In particular, small vessels are affected, blood supply to tissues worsens, and the work of the nervous system is affected. It also increases the risk of a heart attack.
- Stunted growth in children and adolescents. Growth retardation is associated mainly with osteoporosis of the vertebrae. Normally, bones should grow and gain strength, however, against the background of hypercortisolism, they often break, bend, which can lead to irreversible deformities after the disease itself has been cured. In addition, children and adolescents often suffer from obesity. Long-term treatment leaves an imprint on the development of the psyche.
- Damage to the cardiovascular system. Patients with hypercortisolism most often develop hypertension ( increased blood pressure). With concomitant atherosclerosis or other vascular and heart diseases, this greatly increases the risk of myocardial infarction or the development of cardiomyopathy. The result can be chronic heart failure and heart rhythm disturbances. Complications related to the work of the heart are the most common causes of death in hypercortisolism.
- Gastrointestinal tract injury gastrointestinal tract) . At the level of the gastrointestinal tract, a number of serious complications can develop, the most common of which are gastritis and peptic ulcer. Since these diseases are characterized by structural changes in the mucous membrane of the organ, they will not go away even after a decrease in the level of corticosteroid hormones. The immediate danger lies in the fact that, without the necessary treatment, the ulcer may be complicated by perforation ( perforation of the stomach wall), peritonitis ( inflammation of the peritoneum) and other surgical problems.
- Immune suppression. Cortisol in large quantities can have a depressing effect on the immune system. The danger lies in the fact that the body becomes more susceptible to various infectious diseases. The person becomes sickly, often catches a cold. The problem is that with a weak immune system, even a common cold can lead to pneumonia and pose a threat to life.
Thus, hypercortisolism can be considered a very dangerous disease. This is due to multiple disorders and the need for long, difficult treatment. Statistically, almost half of patients die within the first 5 years of diagnosis. Most often this is due to the severe course of the disease ( for example, Itsenko-Cushing's disease, not responding to treatment) or errors in diagnosis and treatment.
What is drug-induced hypercortisolism?
Medical ( or iatrogenic) hypercortisolism is a disease caused by excessive or improper use of medications based on corticosteroid hormones. This disease is characterized by an increase in the level of these hormones in the blood and the development of Cushing's syndrome. By and large, drug-induced hypercortisolism can be considered a side effect or possible complication from the use of certain pharmacological drugs. This disease is most often associated with taking the following drugs:
- prednisolone;
- hydrocortisone;
- betamethasone;
- dexamethasone.
Cushing's syndrome, which combines the manifestations of hypercortisolism, develops gradually. The higher the dose of drugs entering the body, the faster the disease will manifest. As a rule, the highest doses come when they are administered as injections ( injections) or inside ( in tablets or capsules). It is important that these high doses are taken regularly over a period of several months. During this period, there are corresponding changes in the hypothalamic-pituitary system and adrenal glands. Hormones, on the other hand, begin to have a pronounced effect on other systems, causing the development of drug-induced hypercortisolism.
Long-term treatment with corticosteroid drugs is usually prescribed for the following diseases:
- chronic hirsutism, virilism), obesity develops, osteoporosis ( demineralization of bones with their gradual weakening). Other organs and systems are also affected.
The problem is that in some cases, when no medical errors were made, and the patient strictly followed the specialist's instructions, it is still not possible to cancel corticosteroid drugs. They hold back the development of another, more dangerous disease. In these cases, it is necessary to look for compromise doses or prescribe symptomatic treatment. Patients are managed by endocrinologists. At the first symptoms of hypercortisolism, it is checked for other causes ( Itsenko-Cushing's disease, tumors of the adrenal glands). The dose of corticosteroid drugs that the patient is taking is recalculated and rechecked.
What is the prognosis for Itsenko-Cushing's disease?
Itsenko-Cushing's disease is a rather serious disease in which it is difficult to make a specific prognosis for the patient. This is due to the fact that the hormones of the adrenal cortex, the level of which is elevated in this disease, can cause disturbances in the work of various organs and systems. With a severe course of the disease and the absence of qualified treatment, it may well end in death or serious irreversible changes in the patient's body. At the same time, a timely appeal to a specialist often helps to save not only life, but also the ability to work. It is statistically shown that mortality among patients with Itsenko-Cushing's disease is about 40 - 50% within 5 years ( in the absence of treatment). Most often this is due to the gradual development of diabetes mellitus, suppression of the immune system and disorders in the functioning of the cardiovascular system. In other words, the most severe consequences are observed not from Itsenko-Cushing's disease itself, but from secondary developed diseases.
The development of the following complications can greatly affect the prognosis for the patient:
- Osteoporosis. Caused by leaching of calcium from bone tissue. It can lead to chronic pain, contributes to frequent bone fractures, curvature of the spine. May lead to disability.
- Heart failure. Caused by irreversible changes in the heart muscle. Left untreated, it can lead to disability and even death.
- Stomach ulcer. Caused by metabolic disorders at the level of the gastric mucosa. Causes chronic epigastric pain central upper quadrant of the abdomen), periodic bleeding, digestive problems.
- Obesity. Increases the risk of diseases such as heart attack or stroke. Reduces the quality of life of patients.
- Mental changes. A long-term increase in cortisol levels often leads to the development of depression in patients.
- Weakened immunity. Leads to frequent pustular skin lesions, which are a cosmetic defect. Also, patients with Itsenko-Cushing's disease more often than ordinary people suffer from infectious diseases.
Regarding the prognosis for children, it can be noted that for them the period of onset of irreversible changes is shorter. This is due to the rapid growth of the body in childhood and accelerated metabolism. The leaching of calcium from the bones, for example, leads to stunted growth and curvature of the bones. This creates a serious cosmetic defect that cannot be corrected in the future. In addition, inhibition of the development of the spine or chest can affect the functioning of internal organs. With a prolonged increase in the level of corticosteroids, mental retardation is also possible. In children, all the same complications can occur as in adults, but they usually come on faster.
In general, the following factors influence the prognosis for Itsenko-Cushing's disease:
- Patient's age. As mentioned above, children have a number of serious complications that are more common than adults. For them, the prognosis is usually worse.
- Development of complications. Serious complications can lead to disability or death of the patient. Of course, their development worsens the prognosis.
- Timely treatment. The sooner the diagnosis is made, the shorter the period of hypercortisolism. Hormones do not have time to have a significant impact on the body and lead to irreversible changes in tissues. This improves the prognosis.
- Type of neoplasm. Most often, Itsenko-Cushing's disease is caused by neoplasms in the pituitary gland ( iron in the brain). The type of formation, its size and location predetermine the method of treatment ( surgical removal, symptomatic treatment).
- Treatment tactics. Symptoms of hypercortisolism in Itsenko-Cushing's disease can be eliminated in several ways. They largely affect the prognosis for the patient. For example, surgical removal of pituitary tumors is associated with certain risks during surgery ( complications occur in 2-3% of cases, and postoperative mortality reaches 1%) and a difficult postoperative period, but the disease can be completely defeated. Removal of the adrenal gland adrenalectomy) reduces hormone levels, relieving symptoms, but is only a partial solution to the problem. If it is impossible to fight the disease, the patient will have to constantly take medications for symptomatic treatment ( blood pressure lowering, blood sugar lowering, etc.).
- Compliance with doctor's orders. Treatment of Itsenko-Cushing's disease can last for months and even years. During this period, the patient must strictly follow all the prescriptions and recommendations of the doctor, regularly come for consultations and take tests, take a large number of different medications. In this case, we are talking about cases where the problem cannot be quickly solved by surgery. Interruption of treatment, even for a short time, again leads to an increase in cortisol levels, the return of symptoms and the risk of severe complications.
What are the complications of Itsenko-Cushing's disease?
Itsenko-Cushing's disease is manifested by the so-called Cushing's syndrome or hypercortisolism. This syndrome includes a variety of symptoms and manifestations caused by elevated levels of cortisol in the blood. The problem is that prolonged exposure to this hormone can cause serious changes in the structure and function of various organs and tissues. Because of this, disorders that were previously regarded as symptoms turn into full-fledged independent complications of the disease. Some of them do not go away even after the cure of Itsenko-Cushing's disease itself and require a separate course of treatment. It is the development of complications that becomes the most common cause of disability or even death in patients with this disease. The most serious complications of this disease are:
- Diabetes. Against the background of Itsenko-Cushing's disease, the so-called steroid diabetes mellitus may develop. This usually occurs in 10-20% of patients. The disease proceeds much easier than ordinary diabetes mellitus. Glucose levels can often be controlled with the right diet, without regular medication. However, in advanced cases, the level of sugar can rise greatly, leading to serious violations. After fixing the problem neoplasms in the pituitary gland) and curing Itsenko-Cushing's disease, the sugar level may still fluctuate for some time, but gradually stabilizes.
- Osteoporosis. Osteoporosis is one of the most common complications, the signs of which are found in almost 90% of patients. Under the action of hormones, calcium is washed out of the bones, and they lose strength. In this regard, fractures and curvature of bones become more frequent. Against the background of changes in the vertebrae, severe pain may appear due to compression of the spinal roots. Bone changes in osteoporosis are irreversible, that is, they do not disappear after the treatment of Itsenko-Cushing's disease and the normalization of cortisol levels. Therefore, patients with this complication often lose their ability to work and become disabled.
- Heart failure. It is the most dangerous of the complications of Itsenko-Cushing's disease. Hormonal failure affects heart cells, causing cardiomyopathy and rhythm disturbances. Because of this, the blood is pumped worse through the vessels, and heart failure occurs. It is she who usually causes death in patients who have not received the necessary treatment. If the disease was cured, the changes in the myocardium still do not disappear, and the patient suffers from chronic heart failure until the end of his life. He is not able to perform heavy physical exertion, he gets tired faster from everyday work.
- Weakened immunity. The increased release of corticosteroids depresses the immune system over time. Because of this, the body becomes more susceptible to various infections. Patients often suffer from pustular skin diseases, respiratory infections. The immune system is not able to quickly produce enough antibodies to defeat microbes. Even the treatment of such banal infections with antibiotics lasts longer than in healthy people. After curing and normalizing the level of cortisol in the blood, immunity is gradually restored.
- stomach ulcer. Metabolic disorders also affect the gastric mucosa. It becomes more susceptible to the aggressive effects of hard, spicy and acidic foods, as its defense mechanisms are weakened. First of all, the production of mucus, which normally envelops the walls of the stomach, decreases. The rate of regeneration of mucosal cells also slows down. As a result, patients with hypercortisolism may develop gastric ulcers or ( less often) of the duodenum. An additional factor that accelerates this process is malnutrition and non-compliance with the diet prescribed by the doctor. After the normalization of hormone levels, the patient will have to treat an ulcer for a long time, which does not disappear immediately. However, the prognosis for this complication will already be favorable, because the root cause that caused disturbances at the level of the gastric mucosa has been eliminated.
- Obesity. Obesity is one of the most common symptoms of hypercortisolism ( including in Itsenko-Cushing's disease). In some cases, it can be regarded as a specific complication of this disease. The fact is that excess body weight increases the risk of myocardial infarction and a number of other diseases. In addition, after fixing the problem ( pituitary neoplasms) excess weight comes off gradually, and the patient does not always return to his former forms.
- Urolithiasis of the kidneys. The formation of kidney stones, like osteoporosis, is due to the leaching of calcium compounds from the bones. Calcium enters the bloodstream, is not absorbed by bone tissue and is filtered in large quantities in the kidneys. In the renal pelvis, where urine accumulates before entering the bladder, stones begin to form from calcium compounds. If the period of hypercortisolism lasts several years, then very large formations form in the kidneys. They injure the delicate epithelium of the renal pelvis, disrupt the outflow of urine into the ureters, cause severe pain ( renal colic) and predispose to the development of infections ( pyelonephritis). Usually, the symptoms of urolithiasis appear on one side, but a careful examination always reveals damage to both kidneys.
The adrenal gland is a small paired organ that plays an important role in the functioning of the body. Often, Itsenko-Cushing's syndrome is diagnosed, in which the cortex of the internal organ produces an excess of glucocorticoid hormones, namely cortisol. In medicine, this pathology is called hypercortisolism. It is characterized by severe obesity, arterial hypertension and various metabolic disorders. Most often, the deviation is observed in women under 40 years old, but often hypercortisolism is diagnosed in men.
general information
Hypercortisolism is a disease of the adrenal glands, which results in a significant increase in the level of cortisol in the body. These glucocorticoid hormones are directly involved in the regulation of metabolism and many physiological functions. The adrenal glands are controlled by the pituitary gland through the production of adrenocorticotropic hormone, which activates the synthesis of cortisol and corticosterone. In order for the pituitary gland to function normally, sufficient production of specific hormones by the hypothalamus is necessary. If this chain is broken, then the whole organism suffers and this affects the state of human health.
Hypercortisolism in women is diagnosed ten times more often than in the representatives of the stronger sex. Medicine also knows Itsenko-Cushing's disease, which is associated with primary damage to the hypothalamic-pituitary system, and the syndrome has a secondary degree. Often, doctors diagnose a pseudo-syndrome that occurs against the background of alcohol abuse or severe depression.
Classification
Exogenous
The development of exogenous hypercorticism is affected by prolonged use of synthetic hormones, resulting in an increase in the level of glucocorticoids in the body. This is often observed if a person is very sick and needs to take hormonal drugs. Often exogenous syndrome manifests itself in patients with asthma, arthritis of the rheumatoid type. The problem can occur in people after organ transplants.
Endogenous
The development of the endogenous type of the syndrome is influenced by disorders that occur inside the body. Most often, endogenous hypercorticism manifests itself in Itsenko-Cushing's disease, as a result of which the amount of adrenocorticotropic hormone (ACTH) produced by the pituitary gland increases. The development of endogenous hypercortisolism is affected by malignant tumors (corticotropinomas) that form in the testicles, bronchi or ovaries. In some cases, primary deviations of the organ cortex can provoke pathology.
Functional
Functional hypercortisolism or pseudo-syndrome is a temporary condition. A functional deviation may be associated with intoxication of the body, pregnancy, alcoholism or mental disorders. Juvenile hypothalamic syndrome often leads to functional hypercortisolism.
With a functional disorder, the same symptoms are observed as with the classical course of hypercortisolism.
The main causes of Itsenko-Cushing's syndrome
To date, doctors have not been able to fully study the causes that affect the dysfunction of the adrenal glands. It is only known that with any factor that provokes an increase in the production of hormones by the adrenal glands, a disease develops. The provoking factors are:
- adenoma that has arisen in the pituitary gland;
- the formation of tumors in the lungs, pancreas, bronchial tree, which produce ACTH;
- long-term use of glucocorticoid hormones;
- hereditary factor.
In addition to the above factors, the occurrence of the syndrome can be affected by such circumstances:
- injury or concussion;
- traumatic brain injury;
- inflammation of the arachnoid membrane of the spinal cord or brain;
- inflammatory process in the brain;
- meningitis;
- bleeding into the subarachnoid space;
- damage to the central nervous system.
Development mechanism
If at least one of the above factors is noticed in a person, then a pathological process can be started. The hypothalamus begins to produce a large amount of the hormone corticoliberin, which leads to an increase in the amount of ACTH. Thus, hyperfunction of the adrenal cortex occurs, it is forced to produce glucocorticoids 5 times more. This provokes an overabundance of all hormones in the body, as a result, the function of all organs is disrupted.
External manifestations and symptoms
Adrenal Cushing's syndrome is manifested by many symptoms that are difficult to ignore. The main characteristic sign of hypercortisolism is increased weight gain. A person can acquire a 2nd or 3rd degree of obesity in a short period. In addition to this symptom, the patient has the following deviations:
- The muscles of the legs and upper limbs atrophy. The person complains of fatigue and constant weakness.
- The condition of the skin is deteriorating: they dry out, acquire a marble shade, and the elasticity of the skin is lost. A person may notice stretch marks, pay attention to the slow healing of wounds.
- Sexual function also suffers, which is manifested by a decrease in libido.
- In the female body, hypercortisolism is manifested by male-type hair growth, the menstrual cycle is disturbed. In some cases, periods may disappear altogether.
- Osteoporosis develops, in which bone density decreases. At the first stages, the patient is worried about pain in the joints, over time, unreasonable fractures of the legs, arms, and ribs occur.
- The work of the cardiovascular system is disrupted, which is associated with negative hormonal effects. Diagnosed with angina pectoris, hypertension, heart failure.
- In most cases, hypercortisolism provokes steroid diabetes mellitus.
Cushing's syndrome negatively affects the patient's hormonal background, an unstable emotional state is observed: depression alternates with euphoria and psychosis.
Pathology of the adrenal glands in children
In a child's body, abnormalities in the work of the adrenal glands occur for the same reasons as in adults. In children with hypercortisolism, dysplastic obesity is observed, in which the face becomes "moon-shaped", the fat layer increases on the chest and abdomen, and the limbs remain thin. The disease is characterized by myopathy, hypertension, systemic osteoporosis, encephalopathy. In children, there is a lag in sexual development, as well as a secondary type of immunodeficiency. Hypercortisolism in children causes them to grow more slowly. In a teenage girl, after the onset of the menstrual cycle, amenorrhea is possible, in which menstruation may be absent for several cycles.
When contacting a specialist, the first thing he will pay attention to is the enlarged face of the child, the cheeks will be painted purple. Due to the fact that there is an overabundance of androgens in the body, the teenager develops increased acne, the voice becomes rougher. The child's body becomes weaker and more susceptible to infectious lesions. If you do not pay attention to this fact in a timely manner, then sepsis may develop.
Possible Complications
Cushing's syndrome, which has become chronic, can lead to the death of a person, since it provokes a number of serious complications, namely:
- heart decompensation;
- stroke;
- sepsis;
- severe pyelonephritis;
- chronic kidney failure;
- osteoporosis, in which numerous fractures of the spine occur.
Hypercortisolism gradually leads to an adrenal crisis, in which the patient experiences disturbances in consciousness, arterial hypotension, frequent vomiting, and pain in the abdominal cavity. The protective properties of the immune system are reduced, resulting in furunculosis, suppuration and fungal infection of the skin. If a woman is in a position and she has been diagnosed with Itsenko-Cushing's syndrome, then in most cases a miscarriage occurs or the pregnancy ends in a difficult birth with many complications.
Diagnostics
If at least one of the signs of adrenal disease occurs, you should contact a medical facility and undergo a comprehensive diagnosis to confirm or refute the diagnosis. It is possible to detect hypercortisolism using the following procedures:
- Submission of urine for analysis of the determination of free cortisol.
- Ultrasound examination of the adrenal glands and kidneys.
- Checking the adrenal glands and pituitary gland using computed tomography and magnetic resonance imaging. Thus, the presence of a neoplasm can be detected.
- Examination of the spine and chest organs using radiography. This diagnostic procedure is aimed at identifying pathological bone fractures.
- Donating blood for biochemistry to find out what state the electrolyte balance of the serum is in, to determine the amount of potassium and sodium.
Treatment should be prescribed by a specialized specialist after the diagnosis is made, since it is extremely dangerous to self-medicate hypercortisolism.
Treatment Methods
Treatment of hypercortisolism is aimed at eliminating the root cause of the adrenal abnormality and balancing the hormonal background. If you do not pay attention to the symptoms of the disease in a timely manner and do not engage in treatment, then a fatal outcome is possible, which is observed in 40-50% of cases.
It is possible to eliminate pathology in three main ways:
- drug therapy;
- radiation treatment;
- carrying out the operation.
Medical treatment
Drug therapy involves taking drugs that are aimed at reducing the production of hormones by the adrenal cortex. Drug therapy is indicated in combination with radiation or surgical, as well as in cases where other therapeutic methods have not brought the desired effect. Often the doctor prescribes Mitotan, Trilostan, Aminoglutethimide.
Radiation therapy
Radiation therapy is prescribed when the syndrome is provoked by a pituitary adenoma. In this case, radiation exposure is applied to the affected area, which provokes a decrease in the production of adrenocorticotropic hormone. Radiation therapy is combined with medical or surgical treatment. Thus, it is possible to achieve the most positive result in the treatment of hypercortisolism.
Surgical intervention
Pituitary Cushing's syndrome in the later stages needs surgical therapy. The patient is prescribed a transsphenoidal revision of the pituitary gland and the adenoma is removed using microsurgical techniques. This therapeutic method brings the greatest effect and is marked by a rapid improvement in the condition after the operation. In severe cases, during surgery, patients remove two adrenal glands. These patients are treated with lifelong glucocorticoids.
Prognosis for hypercortisolism
The prognosis depends on the severity of the syndrome and when therapeutic measures were taken. If the pathology is detected in a timely manner and the correct treatment is prescribed, then the prognosis is quite comforting. Negative outcomes are affected by various complications. So, patients in whom hypercortisolism has led to cardiovascular abnormalities are at risk of death. The prognosis is disappointing if a person has osteoporosis, pathological fractures have appeared and motor activity has been impaired as a result of myopathy. In the case of diabetes mellitus joining hypercortisolism with subsequent complications, the outcome is extremely disappointing.