The role of genetics in the surgical management of familial endocrinopathy syndromes.

Our knowledge of genetics has increased dramatically in recent decades and this has led to important changes in the medical and surgical management of hereditary endocrine diseases. Genetic screening for disease-causing mutations can identify carriers at young ages, which has enabled earlier diagnosis and surgical intervention. For example prophylactic thyroidectomy is now routine in patients with multiple endocrine neoplasia type 2 (MEN2). Appropriately timed surgical intervention will minimize disease-specific morbidity and mortality, but the diagnosis and surgical treatment of disease in presymptomatic patients is much more complex than in symptomatic patients with measurable disease. Surgeons must remain conversant with the developments in genetic technology and the established role for genetic counselors in the multidisciplinary management of hereditary endocrine syndromes. In this article we briefly review the clinically relevant information and indications for genetic testing for the most common hereditary endocrine syndromes including multiple endocrine neoplasia type 1 (MEN1), MEN2, von Hippel-Lindau syndrome (VHL), and hereditary paraganglioma syndrome. We also use several case descriptions to illustrate the impact of genetic counseling on the management of familial cancer. Finally we provide several key genetic counseling resources available for the proper identification and expeditious referral of patients at risk for these familial endocrine syndromes. MULTIPLE ENDOCRINE NEOPLASIA TYPE 1 MEN1 is an autosomal dominant disease that demonstrates nearly complete penetrance in the form of various combinations of endocrine tumors involving the parathyroid glands, pancreatic islet cells and duodenum, and pituitary gland (Table 1). Hyperparathyroidism (HPT) is the most prevalent (90% to 97%) and is usually the first manifestation, typically appearing between the ages of 20 and 25 years but sometimes as late as the fifth decade of life. Anterior pituitary gland tumors in patients with MEN1 are less common (33%) and may be nonfunctioning or may secrete hormones such as prolactin. Tumors of the pancreatic islet cells and duodenum (pancreatic endocrine tumors, PETs) occur in as many as 30% to 80% of patients. Some PETs are nonfunctioning, but many secrete one or more pancreatic hormones. With earlier diagnosis and control of hormone-associated complications such as ZollingerEllison syndrome, metastatic neuroendocrine tumors of the pancreas are now the leading cause of disease-specific mortality in patients with MEN1. Because PETs in MEN1 patients are multifocal and distributed throughout the pancreas, their proper management remains poorly defined. This issue was summarized in a recent consensus statement in which it was concluded that surgical treatment for MEN1-related PETs is controversial except for patients with hypoglycemia secondary to insulinoma syndrome in whom pancreatic resection is indicated. There is currently no consensus on the timing and extent of surgical treatment for gastrinoma and nonfunctioning PETs in patients with MEN1. Less prevalent tumors associated with MEN1 include adrenocortical tumors, lipomas, and foregut carcinoid tumors. Foregut carcinoids are found in 2% to 8% of patients with MEN1, but bronchial carcinoids are more common in women and thymic carcinoids are more common in men. The malignant potential of carcinoids, particularly thymic carcinoids, has led to recent No competing interests declared.