Multiple endocrine neoplasia type 2 historical perspective

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Historical Perspective

• It has been speculated that Abraham Lincoln had MEN 2B given his tall stature, lesions on his lips, weight loss and shape of his head
• In 1954 Wermer noted that this syndrome was transmitted as a dominant trait.
• In 1959 Hazard et al. described medullary (solid) thyroid carcinoma.
• In 1961 Sipple described a combination of a pheochromocytoma, medullary thyroid carcinoma and parathyroid adenoma.
• In 1966 Williams et al. described the combination of mucosal neuromas, pheochromocytoma and medullary thyroid carcinoma.
• In 1968 Steiner et al. introduced the term "multiple endocrine neoplasia" (MEN) to describe disorders featuring combinations of endocrine tumors and proposed the terms 'Wermer syndrome' for MEN 1 and 'Sipple syndrome' for MEN 2.
• In 1974 Sizemore et al. showed that the MEN 2 category included two groups of patients with MTC and pheochromocytoma: one with parathyroid disease and a normal appearance (MEN 2A) and the other without parathyroid disease but with mucosal neuromas and mesodermal abnormalities (MEN 2B).
• In 1993, RET germline mutations were recognized as the causative molecular alterations in MEN 2 syndromes.
• In 1998 the MEN1 gene was cloned