Multiple Endocrine Neoplasias Type 4

Excerpt

Multiple endocrine neoplasia (MEN) constitutes a group of autosomal dominant disorders characterized by a broad spectrum of endocrine and nonendocrine diseases. Depending on the clinical presentations and genetic mutation, MEN is divided into different types. The most common syndrome is MEN type 1 (MEN1), characterized by primary hyperparathyroidism secondary to parathyroid gland hyperplasia, pituitary adenoma, and pancreatic neuroendocrine tumors.

MEN type 2 (MEN2) is less common, divided into MEN2A and MEN2B, depending on clinical phenotype. MEN2A is characterized by medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism; MEN2B is characterized by medullary thyroid cancer, pheochromocytoma, marfanoid features, and neuromas of lips, tongue, and colon.

MEN type 4 (MEN4) is the most recently identified type of MEN. Although it shares a similar phenotype spectrum to MEN1, MEN4 is rare. The difference between MEN1 and MEN4 lies in the germline gene mutation: in MEN1, there is a mutation of the MEN1 gene; in MEN4, there is a mutation in the cyclin-dependent kinase inhibitor 1B gene (CDKN1B). Hyperparathyroidism is the primary clinical manifestation of MEN4, followed by pituitary adenomas. Less frequently, MEN4 may be associated with tumors of the adrenals, kidneys, and reproductive organs. Compared with other types of MEN, such as MEN1, MEN4 is far less reported in the literature.