Glucosteroma

Glucosteroma occurs in 25-30% of patients with signs of total hypercorticism. Among other cortical tumors, it is also the most common. Patients in this group are considered to be the most severe in their condition. Almost half of the patients have a malignant tumor. If benign adenomas predominate in women (4-5 times more often than in men), then malignant tumors occur with equal frequency in both sexes. The increase in symptoms and the development of the disease itself do not depend on the size of the tumor; only its hormonal activity matters.

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Pathogenesis

Glucosteromas are usually solitary and unilateral, and can rarely be bilateral. The size of the tumors varies from 2-3 to 20-30 cm in diameter and more; their weight fluctuates accordingly: from several grams to 2-3 kg. There is a certain relationship between the size, weight, and growth pattern of the tumor. If its weight is up to 100 g and the diameter is up to 5 cm, then it is usually benign; larger tumors and those with greater weight are malignant. Benign and malignant corticosteromas occur with approximately the same frequency. Some tumors occupy an intermediate position in growth pattern.

Adrenal cortex adenomas (glucosteromas) are often rounded, covered with a well-vascularized thin fibrous capsule, through which ochre-yellow areas of atrophic adrenal cortex shine through. They are usually soft, shiny on section, often of a large-lobed structure, of a variegated appearance: ochre-yellow areas alternate with red-brown. Even in small tumors, necrosis and calcifications may be encountered. Tumor-free areas of the adrenal gland have pronounced atrophic changes in the cortex.

Microscopically, the ochre-yellow areas are formed by large and small spongiocytes, their cytoplasm is rich in lipids, especially cholesterol-bound ones. These cells form cords and alveoli, less often - areas of solid structure. The red-brown zones are formed by compact cells with sharply oxyphilic cytoplasm, poor or not containing lipids. Morphological signs of active proliferation of tumor cells are usually absent, but tumor growth, the presence of multinucleated cells, etc. indicate that they are actively dividing, apparently amitotically. There are also specimens, especially in patients with elevated blood androgen levels, with an admixture of cells similar to those of the reticular zone. They contain lipofuscin and form structures resembling the reticular zone of the cortex. In some tumors, there are areas formed by elements of the glomerular zone. Such patients also develop phenomena of hyperaldosteronism. Very rarely, adenomas are formed entirely by cells with oxyphilic cytoplasm containing variable amounts of lipofuscin. The presence of this pigment gives the tumor a black color. Such adenomas are called black.

Malignant tumors are usually large, weighing from 100 g to 3 kg or more, soft, covered with a thin, richly vascularized capsule. Under it, islets of atrophied adrenal cortex are found. In section, they are of a variegated appearance with numerous areas of necrosis, fresh and old hemorrhages, calcifications, cystic areas with hemorrhagic contents of a large-lobed structure. The lobules are separated by layers of fibrous tissue. Microscopically, cancers are distinguished by significant polymorphism both in structure and in cytological features.

In the adrenal gland containing the tumor and in the contralateral adrenal gland, pronounced atrophic changes are observed. The cortex is formed mainly by light cells, the capsule is thickened, often edematous. In the areas of tumor localization, the cortex is almost completely atrophied, only single elements of the glomerular zone are preserved.

Pathological changes in the internal organs, skeletal bones, skin, muscles, etc. are similar to the changes observed in Itsenko-Cushing's disease.

In rare cases, cortisol-secreting adenomas of the adrenal cortex are combined with ACTH-producing pituitary adenomas or focal hyperplasia of ACTH-producing pituitary cells.

Symptoms glucosteromas

In the clinical picture of the disease, disorders of all types of metabolism and other signs of hyperproduction of cortisol can be expressed in very different degrees, so patients differ significantly from each other in appearance and severity of the condition. Disturbance of fat metabolism can be considered one of the characteristic and early signs of glucosteroma. The increase in weight usually goes in parallel with its redistribution, "matronism" appears, a climacteric hump, the limbs become relatively thin. However, obesity is not an obligatory symptom of the disease. Often there is no increase in body weight, but only androgenic redistribution of fat tissue. Along with this, there are patients whose body weight decreases.

In addition to obesity (or fat redistribution), early symptoms include menstrual dysfunction in women, headaches associated with high blood pressure, sometimes thirst and polydipsia. The skin becomes dry, thins, acquires a marbled pattern, folliculitis, pyoderma, and hemorrhages with the slightest injury are common. One of the most common signs is purple stretch marks, usually located on the abdomen, in the armpits, and less often on the shoulders and hips.

Almost half of patients with glucosteromas have some kind of carbohydrate metabolism disorder - from the diabetic nature of the glycemic curve after glucose loading to severe diabetes mellitus, requiring insulin or other hypoglycemic drugs and diet. It should be noted that ketoacidosis is rare, as well as the absence of a decrease in serum insulin activity in these patients. As a rule, carbohydrate metabolism disorder is reversible, and soon after tumor removal, blood glucose levels return to normal.

Of the changes in water-electrolyte balance, hypokalemia has the most important practical significance, which is found in approximately 1/4 of patients with benign and 2/3 of patients with malignant glucosteroma. The reduction in muscle mass and degenerative changes caused by the catabolic action of glucocorticoids leads to the development of severe weakness, which is further aggravated by hypokalemia.

The severity of osteoporosis correlates with the amount of hormones produced by the tumor.

Diagnostics glucosteromas

The characteristic appearance and complaints of patients with total hypercorticism suggest this disease at the first examination. Difficulties lie in the differential diagnosis from Itsenko-Cushing's disease, the syndrome caused by glucosteroma and ectopic ACTH syndrome, which is most often caused by a malignant non-endocrine tumor. Quantitative determination of hormones in the blood or their metabolites in the urine cannot help in this regard (analysis for the presence of steroids). A normal or reduced amount of ACTH in the blood most likely indicates a tumor of the adrenal glands. Pharmacological tests with ACTH, metapyrone, dexamethasone are of great help in differential diagnosis, as they reveal the autonomy of hormone formation, characteristic of the tumor process. In this sense, scanning of the adrenal glands is the most informative. Asymmetry of drug absorption indicates the presence of a tumor, and the side of the lesion is simultaneously diagnosed. This study is indispensable in the case of ectopic glucosteroma, when it is especially difficult to make a diagnosis.

Violation of water-electrolyte balance in patients with glucosteroma is manifested by polyuria, polydipsia, hypokalemia, caused not only by an increase in aldosterone production (proven in some), but also by the influence of glucocorticoids themselves.

As a result of calcium metabolism disorders in patients with glucosteroma, as well as in Itsenko-Cushing disease, osteoporosis develops, expressed in the spine, skull bones and flat bones. Similar skeletal changes were observed in patients receiving steroid drugs or ACTH for a long time, which proves the causal relationship of osteoporosis with excessive production of glucocorticoids.