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NEOPLASTIC DISORDERS AFFECTING MULTIPLE ENDOCRINE ORGANS

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Multiple endocrine neoplasia (MEN) syndrome is defined as a disorder with neoplasms in two or more different hormonal tissues in several members of a family. Several distinct genetic disorders predispose to endocrine gland neoplasia and cause hormone excess syndromes (Table 50-1). DNA-based genetic testing is available for these disorders, but effective management requires an understanding of endocrine neoplasia and the range of clinical features that may be manifested in an individual patient.

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TABLE 50-1DISEASE ASSOCIATIONS IN THE MULTIPLE ENDOCRINE NEOPLASIA (MEN) SYNDROMES
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MULTIPLE ENDOCRINE NEOPLASIA TYPE 1

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MEN 1, or Wermer's syndrome, is inherited as an autosomal dominant trait. This syndrome is characterized by neoplasia of the parathyroid glands, enteropancreatic tumors, anterior pituitary adenomas, and other neuroendocrine tumors with variable penetrance (Table 50-1). Although rare, MEN 1 is the most common MEN syndrome, with an estimated prevalence of 2–20 per 100,000 in the general population. It is caused by inactivating mutations of the tumor-suppressor gene MEN1 located at chromosome 11q13. The MEN1 gene codes for a nuclear protein called Menin. Menin interacts with JunD, suppressing JunD-dependent transcriptional activation. It is unclear how this accounts for Menin growth regulatory activity, since JunD is associated with inhibition of cell growth. Each child born to an affected parent has a 50% probability of inheriting the gene. The variable penetrance of the several neoplastic components can make the differential diagnosis and treatment challenging.

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CLINICAL MANIFESTATIONS

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Primary hyperparathyroidism is the most common manifestation of MEN 1, with an estimated penetrance of 95–100%. Hypercalcemia may develop during the teenage years, and most individuals are affected by age 40 years (Fig. 50-1). Hyperparathyroidism is the earliest manifestation of the syndrome in most MEN 1 patients. The neoplastic changes in hyperparathyroidism provide a specific example of one of the cardinal features of endocrine tumors in MEN 1: multicentricity. The neoplastic changes inevitably affect multiple parathyroid glands, making surgical cure difficult. Screening for hyperparathyroidism involves measurement of either ...

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