What it is - Itsenko-Cushing syndrome is a condition in which there is an increased concentration of glucocorticoid hormones in the blood of the adrenal cortex.
This is not necessarily a disease of the adrenal glands themselves or their associated hypothalamus or pituitary - most often the syndrome is registered with the prolonged administration of large doses of glucocorticoids for the treatment of various autoimmune pathologies.
Pathology develops more often in women. Depending on the cause of the condition, both conservative and surgical treatment can be applied.
There is also the concept of "Itsenko-Cushing's disease" - excessive production by the hypothalamus and pituitary of those hormones that "give the command" to the adrenal glands to synthesize more and more glucocorticoids. The disease is one of the components of the syndrome.
Causes of Itsenko-Cushing Syndrome
The syndrome develops due to internal or external causes.
1) External causes of the Itsenko-Cushing syndrome is a long-term administration of injection or tablet glucocorticoids: Hydro horizon, Prednisolone, Dexamethasone, Solu-Medrol. Usually, these drugs are prescribed to treat systemic diseases (rheumatoid arthritis, lupus erythematosus, etc.), lung diseases (for example, fibrosis), kidney (glomerulonephritis), blood (leukemia, thrombocytopathy).
2) Causes of internal (organismic) character:
- pituitary tumor that produces the hormone ACTH,
- adrenal gland diseases: a benign or malignant tumor of the bark of this organ, which additionally produces glucocorticoids, an increase in cell mass (hyperplasia) of the adrenal cortex, resulting in an increase in the production of all its hormones,
- tumors in the body that can produce ACTH: small cell and oat cell lung cancer, thymus cancer, testicular or ovarian neoplasms.
You can suspect a diagnosis by the characteristic appearance of a person. But this is not enough, because it is also necessary to determine the severity and cause of the syndrome.
It is important that the tumor, producing hormones, it is not always possible to see, and the level of its location is determined by hormonal tests.
Necessary in the diagnosis of Itsenko-Cushing syndrome are the following studies:
- determining the level of cortisol (the main glucocorticoid hormone) in the blood for several days in a row,
- determining the level of ACTH in the daytime and at night,
- assessment of the level of 17-oxycorticosteroids (substances into which cortisol is converted) in the urine,
- daily excretion of cortisol in the urine,
2) Test with dexazone standard, when this hormone is given in low doses every 6 hours for 2 days in a row, after which the level of cortisol in the blood and oxycorticoid levels in the urine are determined. With this syndrome, cortisol should be lowered,
3) Test with corticoliberin - the hormone of the hypothalamus, which is the main stimulator of cortisol production. If this hormone is introduced into a vein, and after 15 minutes, the blood levels of ACTH and cortisol are determined, then with adrenal genesis, cortisol syndrome will be higher than 1.4 μg%, if there is no answer, this indicates a tumor located in non-endocrine organs (lungs, thymus gonad),
- MRI of adrenal glands, pituitary,
- CT scan of the chest cavity
- radioisotope study, according to which look at the absorption of the administered drug by each of the adrenal glands.
Treatment of Itsenko-Cushing syndrome
Itsenko-Cushing syndrome and its treatment, first of all, will depend on the cause that led to the disease.
- 1) With drug syndrome - gradual cancellation of drugs, perhaps - with their replacement by immunosuppressants,
- 2) With pituitary tumors, lungs, adrenal glands - their surgical removal, which can be performed after prior radiation therapy,
- 3) With cancer with metastases, which produces ACTH, in case of impossibility to remove all these tumors, medical treatment is used with the drugs Mitotan, Aminoglutetimid, Ketoconazole. Additionally, courses of radiation therapy are conducted,
- 4) Introduction of arterial-occluding substances directly into the vessels supplying the tumors.
- insulin - to reduce glucose levels
- blood pressure lowering drugs: Enalapril, Captopril,
- potassium preparations: Asparks, Panangin,
- for reduction of bone tissue destruction - calcium preparations (“Calcium-D3”), “Pamidronat”, “Clodronate”,
- to reduce protein catabolism - anabolic steroids,
Medical expert articles
There are Itsenko-Cushing disease, which has a hypothalamic-pituitary origin, and Itsenko-Cushing syndrome itself is a disease associated with the primary lesion of the adrenal glands. This article discusses only the cerebral form of Itsenko-Cushing disease.
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Causes of Cushing's syndrome
In addition to ACTH-secreting pituitary tumors (usually basophilic adenomas), the disease rarely develops as a result of neuroinfectious or post-traumatic lesions of the hypothalamic-pituitary region. Quite often revealed decompensation of institutional dysfunction of the hypothalamic-pituitary-adrenal axis under the influence of chronic stress, hormonal rearrangements, intoxications, infectious diseases.
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Pathogenesis of Itsenko-Cushing syndrome
The clinical picture is determined by the increase in plasma levels of ACTH and cortisol. Hypertrophy of the cortical layer of the adrenal glands is secondary, centrally-mediated. ACTH hyperproduction can be determined both by the primary pathology of the hypothalamus (excessive production of the corticotropin-releasing factor) and by the primary lesion of the pituitary (ACTH-secreting pituitary adenomas). It is believed that in the genesis of ACTH-secreting pituitary adenomas, the previous long-term stimulation by an excessively produced corticotropin-releasing factor plays a crucial role.
Symptoms of Itsenko-Cushing syndrome
There is a selective localization of fat on the face (moon face), chest, abdomen, neck, above the VII cervical vertebra ("menopausal hump") in combination with relatively thin limbs. The face is purple-red, the skin is dry, scaly, numerous acne. Characterized by wide dystrophic stretch bands, as a rule, purple-bluish color on the skin of the abdomen, thighs, shoulders, mammary glands. In the clinical picture - arterial hypertension, diabetes mellitus, hirsutism in combination with thinning of hair on the head, osteoporosis and compression fractures, muscle weakness, capillary fragility, poor wound healing, reduced resistance to infections.
Psychopathological disorders are different in nature - from hypersomnia to insomnia, from euphoria to depression, sometimes true psychoses occur. There is a change in morphological and functional sex characteristics. In women, in addition to hirsutism, there is a coarsening of the voice, amenorrhea or oligomenorrhea, decreased sexual desire, and masculinization. In men, feminization, gynecomastia, testicular hypotrophy, a decrease in sexual desire and spermatogenesis are sometimes observed. Often, the skin of patients in areas experiencing pressure around the nipples and in places of scarring darkens.
Differential diagnosis of Itsenko-Cushing syndrome
If there are signs of hyperadrenocorticism, it is necessary to exclude the primary pathology of the adrenal glands, i.e. Itsenko-Cushing syndrome. To this end, determine the levels of ACTH and cortisol in the blood and conduct dexamethasone test. The test with dexamethasone is based on the suppression of endogenous ACTH production on the basis of feedback. With Itsenko-Cushing's disease, dexamethasone is prescribed by mouth for 2 mg every 6 hours for 2 days, while the excretion in urine of 17-OX is reduced by more than 50%, and in Cushing's syndrome, the excretion of 17-ОКС with urine does not change.
It is necessary to exclude cases with ectopic production of ACTH in small cell lung cancer, carcinoid tumors, tumors of pancreatic islets. In ectopic tumors, the course of the syndrome is more malignant, there is no significant increase in body weight, hypokalemia takes a leading role in the clinical picture, as a rule, the dexamethasone test is negative. ACTH- or corticotropin-releasing factor-secreting ectopic tumors are more common in men.
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According to clinical manifestations, it is similar to the Itsenko-Cushing disease. The occurrence of ACTH-secreting pituitary tumors was detected after bilateral adrenalectomy for adrenal hyperplasia. The increased production of corticotropin-releasing factor and increased adrenocorticotropic activity in plasma that appears after adrenalectomy may contribute to the development of ACTH-secreting pituitary tumors in the future.
The main manifestation of the disease - pronounced local fat deposition in the neck. A fat pad that encircles the neck gives patients so specific a look that a differential diagnosis is usually not required. The pathogenesis and etiology is not fully elucidated. Belong to cerebral obesity.
Treatment: sometimes adipose tissue is excised surgically.
Barracker-Simons disease (progressive lipodystrophy)
Only women become ill, as a rule, after reaching puberty. The disease is manifested by an uneven distribution of fat with the disappearance of the fat layer in the upper half of the body and the excessive development of fat deposits in the lower half of the body. The deposition of fat is observed mainly on the hips in the form of a kind of “riding breeches”. The weight loss of the upper half of the body and face is very pronounced. More often observed forms of the disease are symmetrical, however, asymmetrical forms may occur with a predominance of uneven distribution of fat on one side of the body. Locally atrophic form of lipodystrophy is observed, as a rule, in patients with diabetes at the site of insulin administration. There are reports of joining lipodystrophy of bilateral or unilateral atrophy of a person with atrophy of not only the subcutaneous fat layer, but also of the muscles.
Of particular importance are the hereditary factor and mental trauma.
Causes of Itsenko-Cushing syndrome
- Inflammatory processes occurring in the brain (in particular, due to a pituitary tumor).
- In some cases, occurs in the postpartum period in women.
- Tumors of the adrenal glands.
- Tumors of the pancreas, bronchi and lungs, mediastinum, which inevitably entails symptoms of Itsenko-Cushing syndrome.
During the diagnosis of the analyzed disease, it is necessary to remember that Itsenko-Cushing syndrome unites a large number of painful conditions (adrenal cancer, Cushing's disease, an increase in ACTH, etc.). In addition, a patient with Itsenko-Cushing's syndrome should undergo an additional examination and refuse to take drugs that contain glucocorticoids (for example, taking a long time prednisone or similar drugs can cause the development of the disease under study).
After determining the symptoms of Cushing's syndrome, it is impossible to say right away what kind of disease is characteristic of a particular patient: adrenal cancer or still Cushing's disease. Quite often, in men suffering from adrenal cancer, the female hormone begins to prevail in the body, and in women, on the contrary, male signs appear. We should not also forget that in medicine there is pseudo-Cushing syndrome that occurs in patients who become depressed or have been drinking alcohol for a long time. As a result of such diseases, the normal functioning of the adrenal glands is stopped, and they begin to produce glucocorticoid hormones in excess, which leads to the emergence of symptoms of Itsenko-Cushing syndrome.
Ii. Exogenous hypercortisolism.
Prolonged administration of synthetic corticosteroids - Itsenko-Cushing's iatrogenic syndrome.
Pubertal juvenile dispuitarism (adolescent hypothalamic syndrome).
The disease and Itsenko-Cushing syndrome is based on a tumor process (benign or malignant adenomas) in the hypothalamic-pituitary region or the adrenal cortex. In 70-80% of patients, Itsenko-Cushing's disease is detected, in 20-30% - the syndrome.
In some cases, the disease develops after a brain injury or neuroinfection.
Women get sick more often (3-5 times more often than men), between the ages of 20 and 40, but can also be found in children and in people over 50 years of age.
When Itsenko-Cushing's disease violated the mechanisms of control of secretion of ACTH. There is a decrease in dopamine and an increase in serotonergic activity in the CNS, as a result of which the synthesis of CRH (corticotropin-releasing hormone, corticoliberin) by the hypothalamus increases. Under the influence of CRG, the secretion of ACTH by the pituitary gland increases, its hyperplasia or adenoma develops. ACTH increases the secretion of corticosteroids - cortisol, corticosterone, aldosterone, androgens by the adrenal cortex. Chronic prolonged cortisolemia leads to the development of a symptom complex hypercorticoidism - Itsenko-Cushing disease.
In Itsenko-Cushing syndrome tumors of the adrenal cortex (adenoma, adenocarcinoma) produce an excessive amount of steroid hormones, the “negative feedback” mechanism ceases to act, there is a simultaneous increase in the content of corticosteroids and ACTH in the blood.
The clinical picture of the disease and the Itsenko-Cushing syndrome differs only in the severity of individual syndromes.
Patients noted a change in their appearance, the development of obesity with red streaks of stretching on the skin of the abdomen, chest and thighs, the appearance of headache and pain in the bones, general and muscle weakness, impaired sexual function, changes in hair.
Obesity with a peculiar redistribution of fat: its excessive deposition on the face, in the area of the cervical spine (“menopausal hump”), chest, abdomen. Patients face is round ("moon-shaped"), purple-red, often with a cyanotic shade ("meat-red"). Such a person received the name "matron face". The appearance of the patients represents a great contrast: red face, short thick neck, fat body, with relatively thin limbs and flattened buttocks.
Dermatological syndrome. The skin is thin, dry, often scaly, with translucent subcutaneous blood vessels, which gives it a marble appearance ("marbling" of the skin).On the skin of the abdomen, the inner surface of the shoulders, thighs, in the area of the mammary glands appear wide stretch bands - strii of reddish-purple color. Often there is local hyperpigmentation of the skin, often in places of friction of clothing (neck, elbows, abdomen), petechiae and bruises on the skin of the shoulders, forearms, legs.
Acne or pustular rash, erysipelas is often found on the face, back and chest.
Hair on the head often falls out, and in women baldness resembles the male type.
Virilizing syndrome - due to an excess of androgens in women: hypertrichosis, i.e. body hair growth (in the form of a rich cannon on the face and on the whole body, mustache and beard height, pubic height male-type growth).
Syndrome of arterial hypertension. Hypertension is usually moderate, but it can be significant, up to 220-225 / 130-145 mm Hg. Hypertension is complicated by cardiovascular insufficiency: shortness of breath, tachycardia, edema in the lower extremities, enlarged liver.
Arterial hypertension is often complicated by damage to the eye vessels: narrowing of the arteries, hemorrhages, reduced vision are detected in the fundus of the eye. Every 4th patient has an increase in intraocular pressure, in some cases turning into glaucoma with visual impairment. Cataracts develop more often than usual.
ECG changes as in hypertension - signs of left ventricular hypertrophy: levogram, RV6 > 25 mm, RV6> RV5> RV4 et al., reduction of ST segment with negative T wave in leads I, aVL, V5-V6 (systolic overload of the left ventricle).
Increased blood pressure is often the only symptom of the disease for a long time, and changes in the cardiovascular system cause disability and most deaths.
Osteoporosis syndrome. Manifested by complaints of pain in the bones of different localization and intensity, pathological fractures. The spine, ribs, sternum, bones of the skull are most often affected. In more severe cases, tubular bones, i.e. limbs. In childhood, the disease is accompanied by a lag in growth.
Changes in bone tissue are associated with hypercorticism: protein catabolism in bone tissue leads to a decrease in bone tissue, cortisol increases Ca ++ resorption from bone tissue, which causes bone fragility. Cortisol also interferes with the absorption of calcium in the intestine, inhibits the conversion of vitamin D to active D3 in the kidneys.
Syndrome of sexual dysfunction. It is caused by a decrease in the gonadotropic function of the pituitary gland and an increase in the formation of androgens by the adrenal glands, especially in women.
In women, menstrual disorders develop in the form of oligo-amenorrhea, secondary infertility, and atrophic changes are observed in the mucous membrane of the uterus and ovaries. In men, there is a decrease in potency, sexual desire.
Astheno-vegetative syndrome. Characterized by fatigue, mood disorders from euphoria to depression. Sometimes acute psychosis, visual hallucinations, epileptoid seizures, convulsions develop.
Muscle weakness syndrome. It is caused by hypercorticism and the increased protein breakdown in the muscles that it causes, and the development of hypokalemia. Patients complain of severe weakness, which is sometimes so pronounced that patients without help cannot stand up from the chair. On examination, an atrophy of the muscles of the extremities, the front wall of the abdomen is detected.
Syndrome of carbohydrate metabolism. It ranges from impaired glucose tolerance to the development of diabetes mellitus ("steroid diabetes"). Glucocorticoids increase gluconeogenesis in the liver, reduce glucose utilization in the periphery (antagonism of insulin action), increase the effect of adrenaline and glucagon on glycogenolysis. Steroid diabetes is characterized by insulin resistance, a very rare development of ketoacidosis, is well regulated by diet and oral sugar-reducing drugs.
Syndrome laboratory and instrumental data
in the general blood test, an increase in the number of erythrocytes and hemoglobin levels, leukocytosis, lymphopenia, eosinopenia, increased ESR,
hypokalemia, hypernatri- and chloremia, hyperphosphatemia, increased calcium levels, alkaline phosphatase activity, hyperglycemia, glycosuria in selected patients.
the content in the urine 17-ACS increased, the content in the urine 17-KS (ketosteroids) increased in some patients,
the content of ACTH in the blood is increased in patients with Itsenko-Cushing's disease, is normal or reduced in Itsenko-Cushing syndrome,
the content of cortisol in the blood is increased in the morning and evening, i.e. the daily rhythm of its secretion is perverted,
X-ray, computed and magnetic resonance imaging of the Turkish saddle, adrenal glands can detect an increase in the Turkish saddle, hyperplasia of the pituitary tissue, adrenal glands, osteoporosis, ultrasound of the adrenal glands is not very informative. In Itsenko-Cushing's disease, narrowing of the visual fields can be detected. Radioimmune scanning reveals a bilateral increase in the absorption of cholesterol by the adrenal glands.
To clarify the diagnosis of the disease or Cushing's syndrome functionalsamples: with Dexamethasone (Liddle's test) and Sinakten depot (ACTH).
Dexamethasone is taken within 2 days by 2 mg in 6 hours. Then, the daily excretion of cortisol or 17-OX is determined and the results obtained are compared with the values before the test. In Itsenko-Cushing disease, the magnitude of the studied parameters decreases by 50% or more (the “feedback” mechanism is preserved), in the case of Itsenko-Cushing syndrome, it does not change.
Sinakten depot (ACTH) is injected intramuscularly in a dose of 250 mg at 8 am and after 30 and 60 minutes the content of cortisol and 17-ACS in the blood are determined. With Itsenko-Cushing's disease (and normal), the content of the determined parameters increases 2 or more times, with Itsenko-Cushing syndrome, it does not. In doubtful cases, conduct so-called. “Big test”: Sinakten depot is injected into a / m at 8 am in the dose of 1 mg and the content of cortisol and 17-ACS in the blood is determined after 1, 4, 6, 8, 24 hours. The result is evaluated as in the previous sample.
Sometimes surgical adrenalectomy with histological examination of the material is used.
Cushing's disease and syndrome
It occurs with a frequency of 1: 100 000 - 1: 1 million of population per year, most often develops between the ages of 20 and 45, sometimes in childhood, women are sick 5 times more often than men.
The disease is named after scientists who independently from each other in different years described it:
- Soviet neurologist Nikolai Mikhailovich Itsenko in 1924 reported two patients with a lesion in the interstitial-pituitary area,
- American surgeon Harvey Cushing in 1932 described the clinical syndrome, which he called "pituitary basophilism".
The term "Itsenko-Cushing's disease" is used to denote the pathology of the hypothalamic-pituitary-adrenal system, that is, a neuroendocrine disease. From Itsenko - Cushing's disease should be distinguished hypercortisol syndrome (Cushing's syndrome) is a term used to refer to a benign or malignant tumor of the adrenal gland or an ectopic tumor of various organs (bronchi, thymus, pancreas, liver) secreting glucocorticoids.
The etiology of the disease Itsenko - Cushing is not installed. In the history of patients of both sexes head injuries, concussion, traumatic brain injury, encephalitis, arachnoiditis and other CNS (corticotropinoma) lesions occur. In women, Itsenko-Cushing's disease occurs more often after childbirth.
The pathogenetic basis of Itsenko-Cushing's disease is a change in the mechanism for controlling the secretion of ACTH. As a result of a decrease in dopamine activity, which is responsible for the inhibitory effect on the secretion of corticotropin-releasing hormone (CRH, corticoliberin) and adrenocorticotropic hormone (ACTH) and an increase in the tone of the serotonin system, the mechanism of regulating the function of the hypothalamic-pituitary-adrenal system is disturbed. —Cortisol, the “feedback” mechanism ceases to function, with a simultaneous increase in the concentration of ACTH, overproduction of cortisol, corticosterone, aldosterone, androgen by the cortex dochechnikov, disappears reaction to stress - increased levels of cortisol on the background of exposure to insulin hypoglycemia. Chronic long-term cortisolemia leads to the development of hypercorticoidism symptom complex.
In most cases, a pituitary adenoma is detected. Macroadenomas are found in 10% of cases, the rest are represented by pituitary microadenomas, which are visualized only by computed tomography or surgical diagnostic adenomectomy (in a small number of patients the tumor is not detected - histological examination reveals only hyperplasia of basophilic pituitary cells). At present, it is not definitively proven whether pituitary adenomas in Itsenko-Cushing's disease are the primary lesion of the adenohypophysis or their development is associated with disorders of the upper parts of the CNS.
The main signs of the disease:
- Obesity: fat is deposited on the shoulders, abdomen, face, breasts and back. Despite the fat body, the patients' arms and legs are thin. The face becomes moonlike, round, cheeks red.
- Pink-purple or purple stripes (striae) on the skin.
- Excessive body hair growth (women have a mustache and a beard on their face).
- In women, menstrual disorders and infertility, in men, a decrease in sexual desire and potency.
- Muscle weakness.
- Fragility of bones (osteoporosis develops), up to pathological fractures of the spine, ribs.
- Blood pressure rises.
- Impaired insulin sensitivity and the development of diabetes.
- Possible development of urolithiasis.
- Sometimes there is a sleep disturbance, euphoria, depression.
- Reduced immunity. Manifested by the formation of trophic ulcers, pustular skin lesions, chronic pyelonephritis, sepsis, etc.
Conducted with hypercortisolism syndrome (corticosteroma or corticoblastoma), hypothalamic syndrome and adolescent dispituitarism (hypothalamic syndrome of the youthful period), hypercortisolemia, exogenous obesity, adrenogenital syndrome: