Diagnosis of Icenko-Cushing's disease

The diagnosis of Itsenko-Cushing's disease is made on the basis of clinical, radiological and laboratory data.

X-ray examination methods are of great importance in diagnostics. They help to detect skeletal osteoporosis of varying severity (in 95% of patients). The size of the sella turcica can indirectly characterize the morphological state of the pituitary gland, its size. With pituitary microadenomas (about 10% of all cases), the sella increases in size. Microadenomas can be detected by computed tomography and magnetic resonance imaging (60% of cases) and by surgical adenomectomy (90% of cases).

X-ray examinations of the adrenal glands are performed using various methods: oxygen supraradiography, angiography, computed tomography and magnetic resonance imaging. Supraradiography performed under pneumoperitoneum conditions is the most accessible method of visualizing the adrenal glands, but it is often difficult to judge their true enlargement, since they are surrounded by a dense layer of fatty tissue. Angiographic examination of the adrenal glands with simultaneous determination of the hormone content in the blood taken from the adrenal veins provides reliable information about the functional state of these glands. But this invasive method is not always safe for patients with Itsenko-Cushing's disease.

Visualization of the adrenal glands using computed tomography allows us to determine their shape, size and structure. This method has great potential and can be used without risk in severely ill patients and in cases where other methods are contraindicated. In Itsenko-Cushing's disease, adrenal hyperplasia is detected in more than half of the cases. Computed tomography makes it possible to detect single or multiple adenomas (secondary macroadenomatosis) measuring 0.3-1 cm in the thickness or on the periphery of the adrenal gland. In cases where the adrenal glands are not enlarged, an increase in the density of one or both adrenal glands is noted.

Ultrasound tomography is a simple, non-invasive examination of the adrenal glands, but it is not always possible to reliably detect enlargement of the glands with their hyperfunction using this method.

In radioisotope imaging, a method using intravenous ¹³¹ I-labeled 19-iodine-cholesterol is used to obtain a radioisotope image of the adrenal glands. Radioisotope imaging of the adrenal glands allows for the clarification of their bilateral hyperplasia in the case of Itsenko-Cushing's disease by their increased accumulation of the isotope. In cases of tumors (glucosterone), an image is obtained of only the gland where the tumor is located, since the opposite adrenal gland is atrophied.

Radioimmune methods of determining the hormone content in the blood and urine are used to study the function of the hypothalamic-pituitary-adrenal system. In Itsenko-Cushing's disease, the content of cortisol and ACTH in the blood is elevated and there is a violation of the rhythm of their secretion (there are no nighttime levels of decreased hormones). The rate of cortisol production by the adrenal cortex in patients increases 4-5 times compared to healthy people.

The most widely used method in the clinic is the determination of daily urinary excretion of 17-oxycorticosteroids (17-OCS) - cortisol, cortisone and their metabolites and neutral 17-ketosteroids (17-KS) - dehydroepiandrosterone, androsterone and etiocholanolone. Urinary excretion of 17-OCS in Itsenko-Cushing's disease is always increased. Determination of 17-OCS fractions in patients with Itsenko-Cushing's disease showed that the content of free cortisol in the urine is significantly higher than in healthy people. The content of 17-KS in adrenal cortex hyperplasia is either increased or within the normal range, the testosterone level in women increases.

The content of 17-OCS in urine is determined before and after the introduction of ACTH, metopirone, dexamethasone and CRH. In patients with Itsenko-Cushing's disease, the introduction of ACTH, metopirone and CRH increases the excretion of 17-OCS by 2-3 times compared to the initial level, unlike patients with adrenal cortex tumors. The dexamethasone test is based on the inhibition of ACTH secretion by high concentrations of corticosteroids in the blood according to the principle of the feedback mechanism. Dexamethasone is prescribed at 2 mg every 6 hours for 2 days. In the case of Itsenko-Cushing's disease, a decrease in the excretion of 17-OCS by more than 50% is observed and does not change with tumors.

Differential diagnosis of Itsenko-Cushing's disease. Differential diagnosis should be made with Itsenko-Cushing's syndrome caused by a tumor of the adrenal cortex (corticosteroma), or tumors producing ACTH-like substances, or adrenal cortex dysplasia observed in adolescence and young adulthood; with functional hypercorticism in dyspituitarism of the pubertal-adolescent period and with obesity occurring with hypertension, striae, carbohydrate metabolism disorder, and in women - with menstrual cycle disorder. Functional hypercorticism can be observed in alcoholism and pregnancy.

Itsenko-Cushing syndrome does not differ from the disease in its clinical manifestations, therefore, in the diagnosis of these diseases, X-ray examinations and scanning of the adrenal glands, as well as functional tests with ACTH, CRH, metopirone and dexamethasone are of great importance. X-ray and radioisotope methods allow us to determine the tumor localization, which is important for the surgical method of treatment. Tests with ACTH, metopirone, dexamethasone and CRH do not lead to a change in the content of 17-OCS in the urine, since the production of hormones by the tumor does not depend on the hypothalamic-pituitary relationship.

The most difficult is the diagnosis of the syndrome caused by tumors of extra-adrenal and extra-pituitary localization. Sometimes the X-ray method allows to detect a tumor of one or another localization, for example, of the mediastinum and lungs.

Hypercorticism, which is observed at a young age, should be distinguished from Itsenko-Cushing's disease. So-called familial forms characterized by nodular dysplasia of the adrenal glands and decreased secretion of ACTH have been described. The leading manifestations of the disease include pronounced osteoporosis, short stature, delayed sexual development, and a lag in bone age from the actual age. When examining the function of the hypothalamic-pituitary-adrenal system, a high level of cortisol in the plasma during the day and a reduced content of ACTH, the absence of a reaction of the adrenal cortex to the introduction of ACTH, metopirone and dexamethasone are revealed, indicating the autonomy of hormone secretion by the adrenal cortex. It is assumed that this form of the syndrome is associated with a congenital defect.

Functional hypercorticism, which develops in patients with obesity, juvenile dyspituitarism, pregnant women and people suffering from chronic alcoholism, should also be differentiated from Itsenko-Cushing's disease and syndrome.

Pubertal-juvenile dyspituitarism, which manifests itself in dysfunction of the hypothalamic-pituitary system, also differs from Itsenko-Cushing's disease. It is characterized by uniform obesity, pink, thin striae, arterial hypertension, most often transient. Striae and hypertension may disappear spontaneously or with weight loss. Unlike Itsenko-Cushing's disease, patients are always of normal or tall stature. With the disease, there are no changes in the bone structure, differentiation and growth of the skeleton are accelerated. All this indicates the predominance of anabolic processes in dyspituitarism, while in Itsenko-Cushing's disease and syndrome, which developed in puberty, catabolic processes predominate: delayed growth and development of the skeleton, slow ossification of the "growth zones", atrophy of the muscular apparatus. In dyspituitarism, there is a normal or slightly increased rate of cortisol secretion, no increase in the content of unchanged cortisol in the urine, and a decrease in 17-OCS after the administration of small doses of dexamethasone (8 mg of the drug for 2 days).

In adults, Itsenko-Cushing's disease should be differentiated from a symptom complex characterized by obesity and striae. As a result of a significant increase in body weight, patients experience a disruption of carbohydrate metabolism and develop hypertension syndrome. It should be emphasized that osteoporosis is never detected in this disease, unlike Itsenko-Cushing's disease. In making a diagnosis, determining the function of the adrenal cortex is of crucial importance. In obesity, patients have an increased daily rate of cortisol secretion by the adrenal cortex by 1.5-2 times compared to healthy people with normal body weight. However, a normal reaction to a small dexamethasone test is noted, which, together with other signs, excludes Itsenko-Cushing's disease. Hypercorticism in obesity is also called reactive, since with a decrease in body weight, the function of the adrenal glands is normalized.

During pregnancy, the function of the pituitary-adrenal system usually increases. It has been shown that the middle lobe of the pituitary gland, which is poorly functioning in adults, increases in volume during pregnancy, and the secretion of ACTH increases. Symptoms of hypercorticism in pregnant women do not appear, since excess cortisol is deposited as a result of increased secretion of the protein transcortin, which binds glucocorticoids. Very rarely, incomplete manifestations of hypercorticism can be observed after childbirth, which, as a rule, can regress on their own.

Chronic alcoholism causes the development of so-called false hypercorticism with clinical manifestations of Itsenko-Cushing's disease. The occurrence of hypercorticism in these cases is associated with liver dysfunction and perverted hormone metabolism. In addition, it is possible that alcohol metabolites can stimulate the function of the adrenal cortex and change the concentrations of biogenic amines of the brain involved in the regulation of ACTH secretion by the pituitary gland. Refusal of alcohol is sometimes accompanied by a decrease in the symptoms of hypercorticism.

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