Multiple endocrine adenomatosis: causes, symptoms, diagnosis, treatment

A hormonally active tumor of the pancreas may be one of the manifestations of multiple endocrine adenomatosis (MEA) or multiple endocrine neoplasia (MEN). MEA is a relatively rare hereditary disease. It is multiple hormone-secreting tumors of the endocrine organs in various combinations. There are varieties of MEA syndrome: MEA-I, or Wermer syndrome, MEA-II, which in turn distinguishes MEA-IIA, or Sipple syndrome, and MEA-IIB, or MEA-III, or Hornlin syndrome.

In 1954, P. Wermer described cases of familial development of tumors of the pituitary gland, parathyroid glands, and islet cells simultaneously. Subsequently, damage to other endocrine organs was also established. Tumors of the parathyroid glands (90%), pancreas (80%), pituitary gland (65%), adrenal cortex (25%), and thyroid gland (20%) are considered typical for the syndrome.

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

Symptoms of multiple endocrine adenomatosis depend on the location of the tumors and the functional state of the affected endocrine glands. The most common symptoms are those of hyperparathyroidism with its complications, such as fatal multiple thrombosis. Thyroid tumors in MEA-I are never of C-cell origin, unlike in MEA-II syndrome.

Functionally active adenomas of pancreatic islet cells may be represented by any type of tumor discussed above. Most often, this is gastrinoma or insulinoma, less often - vipoma, etc. In some cases, it is not a tumor that is determined, but islet hyperplasia or microadenomatosis. Clinical manifestations in this regard are extremely variable.

Prolactinomas predominate among pituitary apudomas, although adenomas secreting ACTH, STH, or a combination of them can also occur. Tumors are usually benign. Malignant apudomas are most often observed in the pancreas. But malignant tumors often grow slowly.

The MEA-IIA syndrome is characterized by a triad of lesions: medullary thyroid cancer, adrenal pheochromocytoma (tumors of both organs, usually bilateral), adenoma or hyperplasia of the parathyroid glands. Apudomas of two of the above organs or bilateral pheochromocytoma are also classified as this type of syndrome. Medullary thyroid carcinoma can secrete not only calcitonin, but also serotonin, prostaglandins, and VIP. In these cases, a clinical picture similar to that of VIPoma and carcinoid is observed. However, a pancreatic tumor in combination with apudomas of other organs is classified as MEA-1.

MEA-IIB (or MEA-III) is a combination of medullary thyroid cancer, bilateral pheochromocytoma, multiple neuromatosis of the mucous membranes with a Marfan-like body structure and often with intestinal disorders (megacolon, diverticulosis, recurrent diarrhea). Multiple neuromas of the mucous membranes occur in early childhood, sometimes by the time of birth. Their topography varies, but the mucous membrane of the lips and conjunctiva are predominantly affected. Thyroid cancer in MEA-IIB occurs early (the average age at diagnosis is 19.5 years) and is especially malignant. The tumor is often multicentric. By the time it is recognized, as a rule, metastases are already present. In many cases, the disease occurs as a result of spontaneous mutation.

Mixed-type MEA occurs when signs traditionally considered as inherent to different types of the syndrome occur simultaneously in one patient (for example, bilateral pheochromocytoma and pancreatic islet cell adenoma).

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

Due to frequent familial cases of the disease, similar examination of the patient's relatives should be carried out.

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

During the examination period, while the diagnosis, localization of tumors, their nature, presence of metastases are being specified, conservative treatment is carried out. It is aimed at reducing metabolic disorders and other manifestations of the disease (for example, reducing diarrhea in vipoma, hypoglycemia in insulinoma, hyperglycemia in glucagonoma, suppressing excessive production of hydrochloric acid by the stomach in gastrinoma). The choice of further treatment depends on the localization of tumors, the functional state of the endocrine glands, the development of metastases, the patient's condition. The principle of staged surgical treatment is observed. First of all, an operation is performed for the tumor, the symptoms of which come to the fore. Thus, if severe hypoglycemic attacks prevail in the picture of the disease, insulinoma is removed first. Surgical intervention is carried out in the same volume as for a separate tumor. If the leading manifestations are Zollinger-Ellison syndrome, mainly drug measures are indicated. In the clinical picture of Cushing's syndrome, within the framework of the MEA, it is necessary to differentiate a tumor of the pituitary gland or adrenal cortex from an ACTH-producing endocrine tumor of the pancreas and perform surgical treatment or appropriate pharmacotherapy. If the symptoms of pheochromocytoma come to the forefront, then adrenalectomy is performed first. Then, according to indications, a second surgical intervention is performed. If necessary, cytostatic agents are prescribed.

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