multiple endocrine neoplasia
Summary
Multiple endocrine neoplasia (MEN) syndromes are autosomal dominant disorders causing hyperplasia and tumors in multiple endocrine glands. MEN1 involves the pituitary, parathyroid, and pancreas (3 P's); MEN2A involves parathyroid, medullary thyroid carcinoma (MTC), and pheochromocytoma; MEN2B involves MTC, pheochromocytoma, and mucosal neuromas/marfanoid habitus. Early recognition is critical since MTC and pheochromocytoma can be life-threatening but are treatable if caught early.
Detail
MEN1 is caused by mutations in the MEN1 gene (menin, a tumor suppressor) on chromosome 11q13, leading to the '3 P's': Pituitary adenomas (often prolactinoma), Parathyroid hyperplasia/adenomas (causing primary hyperparathyroidism—the most common feature), and Pancreatic neuroendocrine tumors (gastrinoma causing Zollinger-Ellison syndrome, or insulinoma). MEN2A and MEN2B result from gain-of-function mutations in the RET proto-oncogene (a receptor tyrosine kinase) on chromosome 10. MEN2A includes medullary thyroid carcinoma (arising from parafollicular C-cells, secreting calcitonin), pheochromocytoma, and primary hyperparathyroidism. MEN2B includes medullary thyroid carcinoma, pheochromocytoma, mucosal neuromas, and a marfanoid body habitus, but notably lacks parathyroid involvement. Because RET mutations are highly penetrant for MTC, prophylactic thyroidectomy is recommended in children with confirmed mutations. Diagnosis involves genetic testing (RET for MEN2, MEN1 gene sequencing for MEN1) and biochemical screening (calcium, PTH, calcitonin, catecholamines, gastrin, prolactin) in at-risk family members. Clinical vignettes often combine hypercalcemia, kidney stones, peptic ulcers refractory to therapy, and family history to point toward MEN1, or hypertension with palpitations plus thyroid nodule for MEN2. These syndromes are classic examples of tumor suppressor loss (MEN1) versus oncogene activation (RET in MEN2) in oncogenesis.
Sources
- First Aid for the USMLE Step 1
- Robbins and Cotran Pathologic Basis of Disease
- UpToDate: Multiple Endocrine Neoplasia Type 1 and Type 2
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