Multiple Endocrine Neoplasia Type 1 and 2

Neoplastic syndromes inherited in an autosomal dominant pattern; variable penetrance and rare incidence. Syndromes involve more than one endocrine gland.

MEN tumors and their effects may be underdiagnosed and unrecognized when pt presents for nonrelated surgery (MEN 2a and 2b associated with pheochromocytoma).

Medullary carcinoma of thyroid (MEN 2a and 2b) is inherited, with almost 100% penetrance; prophylactic thyroidectomy is recommended. Genetic screening tests are available.

See specific syndrome topics; risk related to functional components of tumors.

MEN 1 “Werner syndrome” includes parathyroid hyperplasia (95%), anterior pituitary tumors (30%), pancreas (insulinoma, glucagonoma) (50%), and gastrinoma (“Zollinger-Ellison”) (20–60%).

MEN 2 has three distinct clinical subtypes: 2a, 2b, and FMTC.

MEN 2a: “Sipple syndrome” includes medullary carcinoma of the thyroid (97%), parathyroid hyperplasia (20%), pheochromocytoma (50%).

MEN 2b: Extremely rare subtype (5% of all MEN 2 syndrome) includes medullary carcinoma of thyroid, pheochromocytoma, neuromas of oral mucosa, intestinal ganglioneuromas, marfanoid body habitus, rare parathyroid hyperplasia.

MEN 1/2: Autosomal dominant, variable penetrance. MEN 1 caused by mutation in MEN-1 gene (tumor suppressor/regulatory); men and women equally affected. MEN 2 caused by oncogenic mutation in c-Ret gene (regulatory). Incidence of MEN 2a >FMTC >MEN 2b.

MEN 1: Parathyroid hyperplasia; treat hypercalcemia medically; surgical resection of hyperplastic tissue with parathyroid reimplantation. Pituitary adenoma; prolactinoma (58%) treated medically with dopamine agonist, growth hormone adenoma/acromegaly (23%), and nonsecreting adenoma (10%); treated surgically with transsphenoidal resection. Pancreatic tumors treated surgically with glucose management (insulinomas); gastrinoma treated medically, then surgery.

MEN 2a: Parathyroid hyperplasia; treat as in MEN 1. Medullary carcinoma treated with total thyroidectomy and neck dissection. Pheochromocytoma pts must be medically optimized with alpha-adrenergic blockade first, then beta-blockade, before surgical resection of tumor is attempted, otherwise high morbidity and mortality. Pts with Hx of pheochromocytoma and parathyroid hyperplasia should have prophylactic total thyroidectomy.

MEN 2b: Treatment for medullary carcinoma is total thyroidectomy; pheochromocytoma. Same treatment as in MEN 2a.