Diagnosis of Itenko-Cushing's disease

Diagnosis of Itenko-Cushing's disease is based on clinical, radiological and laboratory data.

X-ray methods of investigation are of great importance in diagnosis. With their help, osteoporosis of the skeleton of varying severity is revealed (in 95% of patients). The size of the Turkish saddle can indirectly characterize the morphological state of the pituitary gland, its magnitude. At pituitary microadenomas (about 10% of all cases) the saddle increases in size. Microadenomas can be detected with computer and magnetic resonance imaging (60% of cases) and with surgical adenomectomy (90% of cases).

X-ray examinations of the adrenal glands are performed by various methods: oxygen-suprasarentgenography, angiography, computer and magnetic resonance imaging. Suprarentgenography performed in conditions of pneumoperitoneum is the most accessible way of visualization of the adrenal glands, but it is often difficult to judge their true increase, as they are surrounded by a dense layer of adipose tissue. An angiographic study of the adrenal glands with simultaneous determination of the hormone content in the blood taken from the adrenal veins gives reliable information about the functional state of these glands. But this invasive method is not always safe for patients with Isenko-Cushing's disease.

Visualization of the adrenal glands with the help of computed tomography allows us to determine their shape, size and structure. This method has great potential and can be applied without risk in severe patients and in those cases when other methods are contraindicated. With Isenko-Cushing's disease, hyperplasia of the adrenal gland is found in more than half of the cases. Computed tomography makes it possible to identify single or multiple adenomas (secondary macroadenomatosis) in the thickness or on the periphery of the adrenal gland 0.3-1 cm in size. In cases when the adrenal glands are not enlarged, there is an increase in the density of one or both adrenals.

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

With radioisotope imaging to obtain a radioisotope image of the adrenal glands, a method using intravenous administration of 19-iodine-cholesterol labeled with ^{131I is used}. Radioisotope imaging of the adrenal glands allows one to clarify their bilateral hyperplasia in the case of Itenko-Cushing's disease due to their increased accumulation of the isotope. In cases of tumors glyukosterom) receive an image of only the gland, where there is a tumor, since the opposite adrenal gland is atrophied.

To study the function of the hypothalamic-pituitary-adrenal system, radioimmune methods for determining the content of hormones in the blood and urine are used. With the Itenko-Cushing's disease, the content of cortisol and ACTH in the blood is increased and there is a violation of the rhythm of their secretion (there are no night levels of hormone reduction). The speed of production of cortisol by the adrenal glands gland in patients is increased 4-5 times compared to healthy people.

The widest distribution in the clinic was the determination of daily urinary excretion of 17-hydroxycorticosteroids (17-ACS) - cortisol, cortisone and their metabolites and neutral 17-ketosteroids (17-CS) - dehydroepiandrosterone, androsterone and etiocholanolone. Excretion of 17-ACS with urine in the case of Itenko-Cushing's disease is always increased. The determination of fractions of 17-ACS in patients with Isenko-Cushing's disease showed that the content of free cortisol in the urine is significantly higher than in healthy ones. The content of 17-CS with hyperplasia of the adrenal cortex is either increased, or is within the normal range, the testosterone level in women increases.

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

Differential diagnosis of Itenko-Cushing's disease. Differential diagnosis should be carried out with Isenko-Cushing syndrome caused by a tumor of the adrenal cortex (corticosteroma), or tumors producing ACTH-like substances, or dysplasia of the adrenal cortex observed in adolescents and young adults; with functional hypercorticism with dyspitutirism of the puberty-juvenile period and with obesity, taking place with hypertension, striae, violation of carbohydrate metabolism, and in women - with violation of the menstrual cycle. Functional hypercorticism can be observed with alcoholism and during pregnancy.

Syndrome Itenko-Cushing's clinical manifestations does not differ from the disease, therefore, in the diagnosis of these diseases, radiographic and adrenal gland studies, as well as functional tests with ACTH, CRH, methopyron and dexamethasone are of great importance. X-ray and radioisotope methods make it possible to determine the localization of the tumor, which is important for the surgical method of treatment. Samples with ACTH, methopyron, dexamethasone, and CRH do not lead to a change in the 17-OC content in urine, as the production of hormones by the tumor does not depend on hypothalamic-pituitary relationships.

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

From the Itenko-Cushing's disease, hypercorticism, which is observed at a young age, should be distinguished. The so-called family forms are described, characterized by nodular dysplasia of the adrenal gland and a decrease in the secretion of ACTH. The leading manifestations of the disease include severe osteoporosis, short stature, slowing of sexual development, lagging behind the age of the bone. When studying 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, a lack of adrenal cortex response to the introduction of ACTH, methopyrone and dexamethasone, indicating the autonomy of hormone secretion with the adrenal cortex. It is suggested that this form of the syndrome is associated with a congenital defect.

From the disease and the syndrome of Itenko-Cushing also should differentiate functional hypercorticism, which develops in patients with obesity, adolescent dyspititarism, in pregnant women and in persons suffering from chronic alcoholism.

From the Itenko-Cushing's disease, puberty and youthful dyspititarism, which is manifested by dysfunction of the hypothalamic-pituitary system, also differs. It is characterized by uniform obesity, pink, thin striae, arterial hypertension, most often transient. Strias and hypertension can disappear spontaneously or with weight loss. In contrast to the Itenko-Cushing disease, patients are always normal or of high growth. With the disease there are no changes in bone structure, differentiation and growth of the skeleton are accelerated. All this indicates the predominance of anabolic processes in dyspituitarism, while in the disease and the syndrome of Itenko-Cushing, developed at pubertal age, catabolic processes predominate: stunting of the growth and development of the skeleton, slowing of the ossification of the "growth zones," and the atrophy of the muscular apparatus. With dyspituitarism, there is a normal or slightly elevated rate of cortisol secretion, no increase in urinary content of unchanged cortisol and a decrease in 17-ACS after the administration of small doses of dexamethasone (8 mg of the drug for 2 days).

In adults, it is necessary to differentiate the symptom complex, characterized by obesity and striae, from the Itenko-Cushing disease. As a result of a significant increase in body weight, carbohydrate metabolism is disrupted in patients and hypertension syndrome develops. It should be emphasized that in this disease, unlike the Itenko-Cushing disease, osteoporosis is never found. In the formulation of the diagnosis, decisive importance is attached to the definition of the function of the adrenal cortex. With obesity in patients, the daily rate of cortisol secretion by the adrenal cortex is increased by a factor of 1.5-2 compared to healthy people with normal body weight. But there is a normal reaction to a small trial with dexamethasone, which, together with other symptoms, excludes the Itenko-Cushing disease. Hypercortisism in obesity is also called reactive, as with adiposity the function of the adrenal glands is normalized.

When pregnancy is usually increased function of the pituitary-adrenal system. It is shown that the average proportion of the pituitary gland, which is not sufficiently functional in adults, increases in volume during pregnancy, and the secretion of ACTH increases. Symptoms of hypercortisosis in pregnant women do not appear, since excess cortisol is deposited as a result of increased secretion of transcortin protein binding glucocorticoids. Very rarely after childbirth, one can observe incomplete manifestations of hypercorticism, which, as a rule, can regress independently.

With chronic alcoholism, the so-called false hypercorticism develops with clinical manifestations of Itenko-Cushing's disease. The emergence of hypercorticism in these cases is associated with impaired liver function and a perverse metabolism of hormones. In addition, it is possible that alcohol metabolites can cause stimulation of the function of the adrenal cortex and alter the concentrations of biogenic brain amines involved in the regulation of ACTH secretion by the pituitary gland. Alcohol withdrawal is sometimes accompanied by a reduction in the symptoms of hypercortisy.

[1], [2], [3], [4]