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At a glance

This defines a large spectrum of diseases characterized by multiple endocrine neoplasia. It consists of benign, and sometimes malignant, tumors (often multiple in a tissue) of the parathyroids, enteropancreatic neuroendocrine system, anterior pituitary, and other tissues. Skin angiofibromas and skin collagenomas are common. Typically, tumors begin two decades earlier than sporadic tumors.

Synonyms

Multiple Endocrine Adenomatoses; MEN; Multiple Endocrine Adenomas.

Classification

There are several types of MEN characterized by the type and location of the tumors. They consist of:

  • MEN Type I (Wermer Syndrome): Autosomal dominant disorder characterized by a high frequency of peptic ulcer disease and primary endocrine abnormalities involving the pituitary, parathyroid, and pancreas.

  • MEN Type IIA (Sipple Syndrome): Autosomal dominant syndrome including medullary thyroid carcinoma, pheochromocytoma, and parathyroid adenomas.

  • MEN Type IIB (Wagenmann-Froboese Syndrome; Mucosal Neuroma Syndrome): Characterized by multiple true nervous neuromas, pheochromocytoma, and thyroid carcinoma without parathyroid adenomas. The thyroid cancer is a medullary type, as in MEN IIA. Although the association of pheochromocytoma with neurofibromatosis is well known, the nervous tumor reported in the MEN IIB is a true neuroma, consisting only of nerve cells.

History

The history associated with the identification of these medical conditions is important as it delineates the numerous researchers and clinicians involved in the identification of this disorder. The sequence of events over the past 115 years involves:

  • In 1903, Erdheim described an acromegalic patient with a pituitary adenoma and three enlarged parathyroid glands.

  • In 1953, Underdahl et al reported eight patients with multiple tumors involving the pituitary, parathyroid, and pancreas glands. The tumors were adenomas.

  • In 1954, Wermer (1898-1975) identified a genetic association with the syndrome bearing his name. It was determined that it was inherited as an autosomal dominant trait.

  • In 1959, Hazard et al identified for the first time the presence of a solid (carcinoma) tumor in the thyroid gland.

  • In 1961, Sipple was the first to associate a medullary thyroid carcinoma, parathyroid adenoma, and a pheochromocytoma. Their presence of the latter raised significant concerns about cardiovascular involvement.

  • In 1966, Williams et al described another variant of an association between pheochromocytoma, medullary thyroid carcinoma, and mucosal neuromas.

  • In 1968, Steiner et al introduced the term “multiple endocrine neoplasia” to describe this clinical presentation. He also proposed the name “Wermer Syndrome” for MEN I and “Sipple Syndrome” for MEN II.

  • In 1974, Sizemore et al observed that MEN II included two subgroups of patients affected with MTC and pheochromocytoma: (1) parathyroid disease and a normal appearance (MEN IIA); (2) no parathyroid disease but with mucosal neuromas and mesodermal abnormalities (MEN IIB).

  • In 1988, the first direct genetic association was identified on Chromosome 11 (11q13).

  • In 1993, Lois Mulligan confirmed the presence of mutations with RET oncogene as a cause of MEN IIA.

  • In 1998, the MEN I gene ...

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