Summary

MEN 1 syndrome is an autosomal dominant-inherited tumor disorder caused by mutations in the MEN1 tumor suppressor gene (chromosome 1 lql3). The diagnosis is made in probands by documenting two of the three major manifestations (multigland primary HPT [>95%], pancreatic neuroendocrine tumors [50% to 75%], or pituitary tumors [30% to 55%]) or by demonstrating one major manifestation in an at-risk family member of a known MEN 1 kindred. Genetic testing identifies a mutation in up to 90% of MEN 1 kindreds. Other overrepresented tumors include adrenal neoplasia, foregut carcinoid tumors, and a number of unusual cutaneous abnormalities. Primary HPT is the most common manifestation and is seen in more than 95% of MEN 1 patients. Palliation of HPT is best achieved with subtotal parathyroidectomy and transcervical thymectomy. Prolactinomas are most often managed with dopamine agonists. Failures of medical therapy and large (compressive) macroadenomas, both functioning or nonfunctioning, are best managed with endonasal transsphenoidal adenomectomy. Pancreatic and duodenal neuroendocrine tumors are the most frequent cause of tumor-related deaths in MEN 1. Nonfunctioning islet cell tumors are most frequent in screened patients, and duodenal gastrinomas are the most frequent cause of a functioning syndrome (ZES). This is followed by hyperinsulinism and, less often, the glucagonoma or VIP tumor syndromes. Pancreatic resection is clearly indicated and beneficial for patients with hyperinsulinism, glucagonomas, VIP tumors, and larger nonfunctioning tumors. There is increasing evidence suggesting that early surgical intervention for MEN 1/ZES patients and patients with subclinical pancreatic neuroendocrine tumors does result in prolonged palliation and a reduction in the rate of malignant transformation. Since biochemical abnormalities can be detected decades prior to the development of overt clinical symptoms, genetic testing, biochemical screening, and imaging of appropriately selected patients appear warranted.

Acknowledgments

The authors thank Abbie L. Young, MS, and Dr. Britt Skogseid for their critique of this chapter.

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