Glucosteroma

Glucosteroma occurs in 25-30% of patients with signs of total hypercorticism. Among other cortical tumors, it is also the most common. Patients of this group in their status are among the heaviest. Almost half of the patients have a malignant tumor. If women are predominant (4-5 times more often than men) benign adenomas, then malignant tumors occur with the same frequency in people of 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 one-sided, rarely can be bilateral. The sizes of tumors vary from 2-3 to 20-30 cm in diameter and more; respectively, their weight ranges from several grams to 2-3 kg. There is a definite relationship between the size, mass and character of tumor growth. If its mass is up to 100 g and its diameter is up to 5 cm, it is usually benign; tumors of a larger size and larger mass are malignant. Benign and malignant corticosteroids occur approximately at the same frequency. Some tumors occupy an intermediate position by the nature of growth.

Adrenal adrenal glands (glucosters) are often rounded, covered with a well-vascularized fine fibrous capsule, through which ocher-yellow patches of the atrophied adrenal cortex are visible. They are usually soft, glistening on a section, often of a coarse-grained structure, of a motley appearance: ocher-yellow patches alternate with red-brown ones. Even in small tumors, necrosis and calcification may occur. Free from the tumor areas of the adrenal gland have pronounced atrophic changes in the cortical layer.

Microscopically ocher-yellow areas are formed by large and small spongiocytes, their cytoplasm is rich in lipids, especially cholesterol-bound. These cells form strands and alveoli, less often - areas of solid structure. Areas of red-brown color are formed by compact cells with a sharply oxyphilic cytoplasm, poor or lacking lipids. Morphological signs of active proliferation of tumor cells, as a rule, are absent, but tumor growth, the presence of multinucleated cells, etc. Indicate that they actively divide, obviously amitotically. There are also specimens, especially in patients with elevated levels of androgens in the blood, with an admixture of cells similar to the cells of the reticular zone. They contain lipofuscin and form structures resembling the mesh cortex. In some tumors there are areas formed by elements of the glomerular zone. Such patients develop hyperaldosteronism. Very rarely, adenomas are entirely formed by cells with oxyphilic cytoplasm containing a diverse amount 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 the atrophied cortex of the adrenal gland are found. On a cut they are of a variegated species with numerous areas of necrosis, fresh and old hemorrhages, calcifications, cystic patches with hemorrhagic contents of a coarse-lobed structure. Lobules are separated by interlayers 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, pronounced atrophic changes are observed. The bark is formed mainly by light cells, the capsule is thickened, often edematous. In places of tumor localization, the cortex is almost completely atrophied, only single elements of the glomerular zone remain.

Pathological changes in the internal organs, in the bones of the skeleton, in the skin, muscles, etc., are similar to those observed with the Itenko-Cushing disease.

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

Symptoms of the glucosteromas

In the clinical picture of the disease, violations of all types of metabolism and other signs of hyperproduction of cortisol can be expressed in very different degrees, so patients differ significantly in appearance and severity of the condition. The violation of fat metabolism can be considered one of the characteristic and early signs of glucosteroma. The increase in mass is usually parallel to its redistribution, there is "matronism", climacteric hump, limbs are relatively thin. However, obesity is not an obligatory symptom of the disease. Often, there is no increase in body weight, but there is only an androgenic redistribution of fatty tissue. Along with this, there are patients who decrease their body weight.

In addition to  obesity  (or fat redistribution), the early symptoms include menstrual dysfunction in women, as well as headaches associated with increased blood pressure, sometimes thirst and polydipsia. The skin becomes dry, thinned, acquires a marble pattern, frequent folliculitis, pyoderma, hemorrhage with the slightest trauma. One of the common signs is the crimson stretch bands, usually located on the abdomen, in the axillary regions, less often on the shoulders and hips.

Almost half of the patients with glucosteroids have one or another disturbance of carbohydrate metabolism - from the diabetic character of the glycemic curve after loading with glucose to the expressed diabetes, requiring the appointment of insulin or other hypoglycemic drugs and diet. It should be noted the rarity of ketoacidosis, as well as the lack of these patients in reducing serum insulin activity. As a rule, the violation of carbohydrate metabolism is reversible, and soon after removal of the tumor, the glucose content in the blood is normalized.

Of the changes in the water-electrolyte balance, the most important practical value is hypokalemia, which is found in about 1/4 of patients with benign and in 2/3 of patients with malignant glucosteroma. Caused by the catabolic action of glucocorticoids, a decrease in muscle mass and a degenerative change in them leads to the development of a sharp weakness, which is further exacerbated by hypokalemia.

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

Diagnostics of the glucosteromas

The characteristic appearance and complaints of patients with total hypercorticism allow to presume this disease at the first examination. Difficulties lie in the differential diagnosis of the Itenko-Cushing disease, a syndrome caused by a glucosteroma and an ectopic ACTH syndrome caused more often by a malignant non-endocrine tumor. The quantitative determination of hormones in the blood or their metabolites in the urine in this plan can not help (analysis for the presence of steroids). A normal or decreased amount of ACTH blood is more likely to indicate a tumor of the adrenal gland. A great help in differential diagnostics is provided by pharmacological tests with ACTH, metapyron, dexamethasone, as a result of which autonomy of hormone formation characteristic for the tumor process is revealed. In this sense, the most informative is the scanning of the adrenal glands. The asymmetric absorption of the drug indicates the existence of a tumor, and simultaneously the side of the lesion is diagnosed. This study is indispensable in the case of ectopic glucoside, when the diagnosis is particularly difficult.

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

As a result of the violation of calcium metabolism in patients with glucosteroma, as well as with Itenko-Cushing's disease, osteoporosis develops, expressed in the spine, skull bones and flat bones. Similar changes in the skeleton were observed in patients receiving long-term steroid preparations or ACTH, which proves the causal relationship between osteoporosis and excess production of glucocorticoids.