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Approach to therapy in multiple endocrine neoplasia type 1

INTRODUCTION

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder classically characterized by predisposition to tumors of the parathyroid glands (which occur in nearly all patients by age 50 years), anterior pituitary, and pancreatic islet cells (table 1). MEN1 also includes a predisposition to gastrinomas in the duodenum, carcinoids, adrenal adenomas, angiofibromas, and lipomas (table 2). The tumors are generally benign, but malignancy of some carcinoid, islet cell, and gastrointestinal tract tumors are important causes of mortality in MEN1.

This topic will review the treatment of MEN1. The classification, genetics, clinical manifestations, and diagnosis are reviewed separately. (See "Definition and genetics of multiple endocrine neoplasia type 1" and "Clinical manifestations and diagnosis of multiple endocrine neoplasia type 1".)

PRIMARY HYPERPARATHYROIDISM

Primary hyperparathyroidism is the most common manifestation of MEN1, with over 90 percent penetrance by age 40 to 50 years [1]. Multiple gland involvement is common in these patients, and given sufficient time, perhaps universal. Patients with classical MEN1 are at high risk of recurrent hyperparathyroidism after apparently successful subtotal parathyroidectomy.

Indications for surgery — Once the biochemical diagnosis of primary hyperparathyroidism is confirmed in a patient with known or presumed MEN1, the indications for surgical intervention are similar to those in patients with sporadic primary hyperparathyroidism. These include symptomatic or marked hypercalcemia, nephrolithiasis, and evidence of bone disease such as diminished bone density or fracture [2]. Bone density of the lumbar spine and hip can improve after parathyroidectomy in patients with hyperparathyroidism associated with MEN1, as it does in patients with sporadic hyperparathyroidism [3]. (See "Management of primary hyperparathyroidism", section on 'Candidates for surgery'.)

An additional indication for parathyroidectomy in patients with MEN1 is the presence of severe peptic ulcer disease or other symptoms caused by a gastrinoma (the Zollinger-Ellison syndrome) that are difficult to control with medications. Hypercalcemia typically worsens hypergastrinemia, and parathyroidectomy may markedly reduce gastrin secretion in patients with a gastrinoma [4,5]. The typical success of pharmacologic therapy for hypergastrinemia makes this a rare indication for operation.

             

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Literature review current through: 20.6: May 2012
This topic last updated: Apr 20, 2011
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