Multiple endocrine adenomatosis: causes, symptoms, diagnosis, treatment

The hormone-active pancreatic tumor can be one of the manifestations of multiple endocrine adenomatosis (MEA) or multiple endocrine neoplasia (MEN). IEA is a relatively rare hereditary disease. It is a multiple hormone-secreting tumor of the endocrine organs in various combinations. There are varieties of MEA syndrome: MEA-I, or Vermeer syndrome, MEA-II, in which MEA-IIA, Sipple syndrome, MEA-IIB, or MEA-III, or Hornlin syndrome, in turn.

P. Wermer in 1954 described cases of familial development of tumors at the same time as the pituitary gland, a pair of thyroid glands, and insulocytes. In the subsequent it was established and the defeat of other endocrine organs. Typical for the syndrome are tumors of parathyroid glands (90%), pancreas (80%), pituitary gland (65%), adrenal cortex (25%) and thyroid gland (20%).

The disease is observed with the same frequency in persons of both sexes. It occurs at any age from the age of 10 years. Autosomal recessive inheritance is noted with a high degree of penetrance and variable expressiveness.

Symptoms of multiple endocrine adenomatosis depend on the location of tumors and the functional state of the affected endocrine glands. The most common symptomatology of hyperparathyroidism with its complications, for example fatal multiple thrombosis. Thyroid tumors with MEA-I are never of C-cell origin, in contrast to MEA-II syndrome.

Functionally active pancreatic insulocyte adenomas can be represented by any type of tumor of the types discussed above. More often it is gastrinoma or insulinoma, less often - vipoma, etc. In a number of cases, it is not a tumor that is determined, but islet hyperplasia or microadenomatosis. The clinical manifestations in this regard are extremely variable.

Of the pituitary hypogens, prolactinomas predominate, although adenomas that secrete ACTH, STH, or a combination thereof are found. Tumors are often benign. Malignant apodomas are most often observed in the pancreas. But malignant tumors often grow slowly.

For the syndrome MEA-IIA is characterized by a triad of lesions: medullary thyroid cancer, pheochromocytoma of the adrenal glands (tumors of both organs, as a rule, bilateral), adenoma or hyperplasia of the parathyroid glands. Apodoma of two of these organs or bilateral pheochromocytoma is also referred to this type of syndrome. Medullary carcinoma of the thyroid gland can secrete not only calcitonin, but also serotonin, prostaglandins, VIP. In these cases, a clinical picture is observed, similar to the manifestations of vipome, carcinoid. But the pancreatic tumor in combination with the apodoma of other organs is referred to as MEA-1.

MEA-IIB (or MEA-III) is a combination of medullary thyroid cancer, bilateral pheochromocytoma, multiple mucosal neuromatosis with a marfan-like body structure and often with intestinal disorders (megacolon, diverticulosis, relapsing diarrhea). Multiple neuromas of the mucous membranes arise already in early childhood, sometimes at the time of birth. Their topography is different, but mainly the mucous membrane of the lips and conjunctiva is affected. Thyroid cancer with MEA-IIB occurs early (mean age when diagnosed 19.5 years) and proceeds particularly malignantly. A tumor is often multicentric. By the time of its recognition, as a rule, already there are metastases. The disease in many cases arises as a consequence of a spontaneous mutation.

There are mixed type MEAs, when symptoms traditionally considered as inherent in different types of syndrome are found simultaneously in one patient (for example, bilateral pheochromocytoma and pancreatic insulocyte adenoma).

Diagnosis of IEA is difficult due to the extreme variety of clinical picture due to the possibility of different combinations of lesions. The general diagnostic rule is that with each hormone-active tumor of the pancreas (as well as other endocrine organs), it is necessary to bear in mind the possibility of developing MEA and to search for appropriate organ manifestations and to study adequate indicators (calcium level in blood, phosphorus, hydroxyproline, parathyroid hormone, thyrocalcitonin, glucose, catecholamines, etc.).

Because of frequent family cases of the disease, a similar examination of the relatives of the patient should be made.

Recognition of MEA-I is based on the detection of hypercalcemia, increasing the level of parathyroid hormone in the presence of signs of simultaneous damage to other endocrine organs, primarily the pancreas.

During the examination period, until the diagnosis is clarified, the localization of tumors, their nature, the presence of metastases, conduct conservative treatment. It is aimed at reducing metabolic disorders and other manifestations of the disease (for example, reducing diarrhea in vipoma, hypoglycemia in insulinoma, hyperglycemia in glucagonome, suppressing excessive production of stomach hydrochloric acid in gastrinoma). The choice of further treatment depends on the location of tumors, the functional state of the endocrine glands, the development of metastases, the patient's condition. The principle of the stage of surgical treatment is observed. First of all, they perform surgery for a tumor, the symptoms of which come to the fore. So, if the picture of the disease is dominated by severe hypoglycemic attacks, first of all they are removed with insulin. Surgical intervention is carried out in the same volume as with an individual tumor. If the manifestations of the Zollinger-Ellison syndrome are the leading ones, the medicamental measures are mainly indicated. In the clinical picture of Cushing's syndrome within the framework of MEA, a tumor of the pituitary gland or adrenal cortex should be differentiated from the ACTH-producing endocrine tumor of the pancreas and carry out surgical treatment or appropriate pharmacotherapy. If the symptomatology of pheochromocytoma comes to the fore, then adrenalectomy is first produced. Then, according to the indications, a second surgical intervention is performed. If necessary, prescribe cytotoxic drugs.

[1], [2], [3], [4], [5], [6]