Multiple endocrine neoplasia type 1

Multiple endocrine neoplasia type 1

MEN means multiple endocrine neoplasia and is an autosomal dominant syndrome. In fact, MEN refers to the combination of several different syndromes caused by tumors (benign or malignant) of endocrine glands. Von Hippel Lindau, McCune Albright syndrome and Carney complex could also be considered part of MEN, because they are all autosomal dominant syndromes that includes endocrine tumors and because they have a clinical features which overlap with MEN syndromes.

Types of multiple endocrine neoplasia

There are three types of MEN: MEN1 ( also called Werner syndrome) – pancreatic neuroendocrine tumors, pituitary adenoma, and adenoma or hyperplasia of parathyroid with or without angiofibromas.

MEN 2A syndrome (or Sipple syndrome) includes medullary thyroid carcinoma, pheochromocytoma and hyperparathyroidism.

MEN 2B or MEN 3 (or Shimcke syndrome) includes medullary thyroid carcinoma, pheochromocytoma and neuromas.

It should be noted that MEN is a rare syndrome, each of the two syndromes MEN ( MEN 1 and MEN 2) affects 1 in 30 000/40 000 persons. Among the subtypes of MEN, MEN 2A is the most common and 2 B is the rarest.

Neoplasia

Multiple endocrine neoplasia type 1

Approximately 70-95% of patients with MEN 1 has a MEN1 gene mutation. This gene encodes menin, which is a tumor suppressor, which means it prevents the cells to divide uncontrollably. When the MEN 1 gene mutations occur, it cannot exercise its function and different tumors appear ( parathyroid, pancreatic or pituitary).

Signs and symptoms begin to appear around the age of 20 years (50% of patients) and by the age of 40 years this syndrome becomes clinically manifest in 95% of them. Usually patients with MEN 1 have a family relative with this disorder.  In most cases, MEN 1 is manifested by tumors of the parathyroid, pancreas and pituitary gland. The most important sign that appears in MEN1 is hyperparathyroidism, which causes disturbances of calcium in the body that can lead to kidney stones, weak bones (fractures), nausea, vomiting, hypertension, fatigue.

In MEN 1 syndrome, endocrine or non-endocrine neoplasms can develop such as thyroid, adrenal cancers, visceral and cutaneous lipomas, meningiomas, etc.. There is a great variability in terms of MEN1 phenotype. A patient who has endocrinopathies given by two of the three target endocrine glands (pancreas, pituitary, parathyroid) or endocrinopathy on one ofthe  three typical endocrine glands plus one first-degree relative with MEN1, the MEN 1 syndrome should be suspected.

Typically, tumors in MEN 1 are benign and the symptoms are due to excessive production of hormones or mass effect. However, some patients with MEN 1 have increased risk for cancer, so it is recommended cancer screening in patients with MEN.