Overview
Recognizing MEN1 and MEN2
Multiple endocrine neoplasia is an inherited tumour predisposition syndrome.
Multiple endocrine neoplasia is an inherited tumour-predisposition syndrome. The clinical clue is not simply “more than one endocrine tumour”; it is a characteristic combination of tumours developing at younger ages, often across several generations or in several endocrine organs in one person. MEN1 is caused by an autosomal-dominant inactivating germline variant in the MEN1 tumour-suppressor gene, which encodes menin. Loss of menin function permits abnormal proliferation in several endocrine tissues. Its classic pattern is the “3 P’s”: - Parathyroid: primary hyperparathyroidism, usually the earliest and most common manifestation, and characteristically multiglandular. - Pituitary: anterior pituitary adenomas, with prolactinomas occurring most often. - Pancreatic or entero-pancreatic neuroendocrine tumours: gastrinoma is the most common functioning tumour; insulinoma also occurs. MEN1 can also produce adrenocortical tumours, bronchial or thymic carcinoids, angiofibromas, collagenomas, and lipomas. These associated findings support the pattern but do not replace the core diagnostic criteria. MEN2 is caused by an activating, gain-of-function germline variant in the RET proto-oncogene. RET genotype strongly predicts the timing and aggressiveness of medullary thyroid carcinoma (MTC), so the specific variant is clinically actionable. - MEN2A:...