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- ACTH Adrenocorticotropic hormone
- CT Computed tomography
- GDNF Glial cell line-derived neurotrophic factor
- GDNFR Glial cell line-derived neurotrophic factor receptor
- GNAS Gene encoding the alpha subunit of a stimulatory G protein
- MCT Medullary carcinoma of thyroid
- MEN Multiple endocrine neoplasia
- MRI Magnetic resonance imaging
- PCR Polymerase chain reaction
- PTH Parathyroid hormone
- RET Rearranged during transfection proto-oncogene
- VIP Vasoactive intestinal peptide
- ZES Zollinger-Ellison syndrome
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A group of heritable syndromes characterized by aberrant growth of benign or malignant tumors in a subset of endocrine tissues have been given the collective term multiple endocrine neoplasia (MEN). The tumors may be functional (ie, capable of elaborating hormonal products that result in specific clinical findings characteristic of the hormone excess state) or nonfunctional. There are three major syndromes: MEN1 is characterized by tumors involving the parathyroid glands, the endocrine pancreas, and the pituitary; MEN 2A includes medullary carcinoma of the thyroid (MCT), pheochromocytoma, and hyperparathyroidism; and MEN 2B, like MEN 2A, includes MCT and pheochromocytoma, but hyperparathyroidism is typically absent.
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MEN1, also known as Wermer syndrome, is inherited as an autosomal dominant trait with an estimated prevalence of 2 to 20 per 100,000 in the general population. Approximately 10% of MEN1 mutations arise de novo. The term sporadic MEN1 has been applied to this group. MEN1 has a number of unusual clinical manifestations (Table 22–1) that occur with variable frequency among individuals within affected kindreds. The earliest age at which manifestations of MEN1 have been reported is 5 years; penetrance is maximal by the fifth decade of life.
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Hyperparathyroidism is the most common feature of MEN1, with an estimated penetrance of 95% to 100% over the lifetime of an individual harboring the MEN1 gene. The diagnosis of hyperparathyroidism is usually made through a combination of clinical and laboratory criteria similar to those used in the identification of sporadic disease (see Chapter 8). It is typically the first clinical manifestation of MEN1, although this varies as a function of the patient population being examined. Hyperparathyroidism in MEN1 is due to hyperplasia of all four parathyroid glands (or more, if supernumerary glands are present). However, involved glands may undergo metachronous enlargement, and selective resection of these glands often results in sustained clinical remissions. MEN1 is a rare cause of hyperparathyroidism, accounting for only 2% to 4% of cases in the general population.
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Enteropancreatic tumors in MEN1 (∼50% of all MEN1 patients) can be either functional (ie, capable of producing a secreted product with biologic activity) or nonfunctional. Gastrinomas, frequently associated with Zollinger-Ellison syndrome (ZES), represent approximately 40% to 60% of the enteropancreatic tumors associated with this syndrome. Of equal importance, ...