What is Cushing’s Disease?
Itsenko-Cushing’s disease (N.Itsenko, sov.neuropathologist, 1889-1954; N.W. Gushing, American neurosurgeon, 1869-1939) is a neuroendocrine disease caused by constant excess production of adrenocorticotropic hormone by the pituitary and glucocorticoid hormones by the adrenal cortex. Women of reproductive age are predominantly ill.
Pathogenesis during Itsenko-Cushing Disease
I. – K. b is associated with impaired regulatory mechanisms controlling the function of the hypothalamic-pituitary-adrenal system. When I. – K. b. The sensitivity of the hypothalamic-pituitary system to the inhibitory effect of cortisol decreases (possibly as a result of a decrease in the binding ability of dopamine receptors of the central nervous system), which leads to an increase in the secretion of ACTH and cortisol simultaneously. History of patients I. – K. b. Frequent indications of craniocerebral traumas draw attention to themselves, in women the onset of the disease is often associated with childbirth. In many cases, the immediate cause of the disease cannot be established. Patients I. – K. b. Hyperplasia or hormone-active pituitary adenomas are often found (in most cases, these adenomas are very small in size), producing ACTH and peptides similar in structure – b-lipotropic hormone, melanocytostimulating hormone, endorphins. Adrenal glands in patients I. – K. b. enlarged, revealed diffuse hyperplasia of the cortex, mainly its beam zone, sometimes with areas of adenomatosis.
Symptoms Itsenko-Cushing’s Disease
The severity of the main symptoms of the disease depends on the degree of hypersecretion of glucocorticoids, which leads to a decrease in the intensity of anabolic and increased activity of catabolic processes in the body, the development of steroid diabetes, hypokalemia, metabolic alkalosis, impaired immunity, hypertension, and osteoporosis. As a result of dystrophic changes in muscles and hypokalemia, muscle weakness develops. In severe osteoporosis, bone pain and pathological fractures appear. For the sick in childhood is characterized by growth retardation. Disorder of carbohydrate metabolism in patients I. – K. b. associated with increased gluconeogenesis processes, which is clinically manifested by symptoms of diabetes mellitus, insulin resistance is noted, ketoacidosis rarely develops. Frequent, but not constant symptom I. – K. b. in women is a violation of the menstrual cycle, in men, usually sexual potency decreases.
Appearance of patients I. – K. b. so characteristic that the disease can be suspected already at the first examination. For I. – K. b. Typically excessive fat deposition in the neck, abdomen, body, fat deposition in the upper thoracic vertebrae, rounded (moon-shaped), bluish-reddish face. Red-violet on the skin of the abdomen, thighs, breasts stretch bands (striae). The skin is dry, with visible manifestations of trophic disturbances, in some patients hyperpigmentation, petechial hemorrhages are observed. Loss of hair on the head is often observed, sometimes simultaneously with increased hair growth on the chin general hypertrichosis.
Subjective complaints of patients I. – K. b. mainly due to arterial hypertension (headache, flickering “flies” before the eyes) and catabolic syndrome (severe muscle weakness, lower back pain, inability to perform physical work), as well as sexual disorders. Despite specific changes in appearance, they rarely make cosmetic complaints (unless women develop significant hypertrichosis).
The disease often has a chronic course. At the same time, the full picture of I. – K. b. with complications detected approximately 5-10 (sometimes 15) years after the onset of the disease. However, in some cases, severe symptoms develop very quickly, complications of the cardiovascular system appear, and sharp osteoporosis makes the condition of the patients heavier (the so-called galloping form I. – K. b.). Current I. – K. b. can be mild, moderate and severe. If manifestations of the disease are limited to obesity, a moon-shaped face, transient arterial hypertension, speak of a light course I. – K. b. The appearance of osteoporosis, persistent arterial hypertension is characteristic of I. – K. b. moderately severe. Pathological vertebral compression fractures, sepsis, hemorrhages in the brain, the so-called steroid psychosis, uremia indicate that the disease has taken a severe course.
I. – K. b. can be suspected on the basis of the characteristic appearance of the patient and the presence of symptoms of hypercorticism (arterial hypertension, carbohydrate metabolism). Laboratory and diagnostic signs of hypercortisolism, detected during clinical and biochemical examination of the patient, can be indirect and direct. Indirect signs include leukocytosis with a shift of the blood formula to the left, aneosinophilia, hypokalemia, alkaline reaction of urine. Direct signs of hypercortisolism are an increase in the daily secretion of 17-hydroxycorticosteroids (cortisol, cortisone and their metabolites), neutral 17-ketosteroids (dehydroepiandrosterone, androsterone, etoicholanone), and an increase in the concentration of cortisol and ACTT in the blood. There are violations of the rhythm of their daily secretion. The rate of formation of cortisol by the adrenal cortex during hypercortisism increases by 4-5 times. X-ray detection of osteoporosis is another indication of the possibility of I. – K. b. or syndrome Itsenko – Cushing. Osteoporosis of the lumbar vertebrae is accompanied by flattening and deformation of their bodies (“fish” vertebrae).
Determined in 10% of patients I. – K. b. an increase in the Turkish saddle is characteristic of large pituitary adenoma. More often, however, radiological signs I. – K. b. are minimal and consist in the deformation of the back of the Turkish saddle and the swelling of its bottom, which indirectly indicates the presence of a pituitary microadenoma. The growth and differentiation of the skeleton in children with I. – K. b. an average of 3 years behind passport age.
The prognosis for life under I. – K. b. mild or moderate favorable. Remission can only be achieved at the onset of the disease with adequate therapy. Working capacity at I. – K. b. always reduced. In severe form I. – K. b. The prognosis is serious even with all modern treatment methods. Galloping form I. – K. b. without adequate treatment leads to complete disability and death of the patient 1-2 years after the onset of the disease.
Diagnosis Itsenko-Cushing’s Disease
Differential diagnosis is carried out in a specialized endocrinological hospital.
I. – K. b. differentiate with Itsenko – Cushing’s syndrome, pubertal youth disorder, neuroendocrine form of the hypothalamic syndrome, some variants of Stein – Leventhal syndrome, galactorrhea – amenorrhea syndrome. Externally, patients with type II diabetes may sometimes resemble patients I. – K. b. Cushingic changes in appearance are also observed during alcoholism (the so-called alcohol pseudo-kushing). In all these conditions, violations of glucocorticoid secretion and biochemical signs of hypercorticism may occur. Therefore, a significant differential diagnostic value is the result of a small dexamethasone test, which is negative in the case of the disease and Itsenko-Cushing syndrome. An important point in the differential diagnosis of corticosteromas, I. – K. b. and ectopic ACTH syndrome is the determination of the size of the adrenal glands; in the last two cases, bilateral adrenal enlargement is noted, corticosteromas are characterized by an increase in one and atrophy of the other adrenal glands. For the differential diagnosis of the disease and the Itsenko-Cushing syndrome, a large dexamethasone test is also used, which is negative with the Itsenko-Cushing syndrome. To establish the size of the adrenal glands, radiography with layered tomography under pneumoperitoneum conditions, computed tomography, NMR tomography, radioisotope examination of the adrenal glands with labeled cholesterol are used; ultrasound is less informative in this case.
Treatment Itsenko-Cushing’s Disease
Treatment for mild I. – K. b. usually limited to radiation therapy, which consists in the irradiation of the hypothalamic-pituitary region, in combination with drug therapy. When I. – K. moderate to radiation therapy add drug treatment aimed at suppressing the function of the pituitary gland using a dopamine agonist Parlodel (bromkriptina) and serotonin antagonist cyproheptadine (peritola). Functional blockers of the hypothalamic-pituitary system usually do not contribute to long-term remission, so they are prescribed in combination with therapy with blockers of the function of the adrenal cortex (chloditan, aminoglutethimide) after radiation therapy. In more severe cases, treatment begins with unilateral adrenalectomy.
With a heavy course I. – K. b. recommend bilateral adrenalectomy, which allows you to quickly remove the phenomenon of hypercortisolism in patients, followed by lifelong hormone replacement therapy. After bilateral adrenalectomy, the development or progression of an existing pituitary tumor (Nelson syndrome) is possible. At the same time, patients noted an increase in skin pigmentation, the development of hypocorticism is characterized by a labile course. The treatment of Nelson’s syndrome consists in the appointment of blockers of the function of the hypothalamic-pituitary system, radiation therapy, which consists in irradiating the hypothalamic-pituitary region or removing the pituitary adenoma.