Diagnosis of Multiple Endocrine Neoplasia Syndromes

MEN1, MEN2, and MEN4 comprise a series of familial disorders involving the simultaneous occurrence of tumors in more than one endocrine organ, collectively known as multiple endocrine neoplasia. Patients with this family of disorders develop tumors of the parathyroid gland, pancreas, pituitary gland, adrenal gland, and thyroid gland, along with miscellaneous neuroendocrine tumors of the respiratory and gastrointestinal tracts.

Syndrome Mutated gene Manifestations
MEN1 MEN1 Primary hyperparathyroidism (usually four-gland hyperplasia), anterior pituitary adenomas, tumors of endocrine pancreas and duodenum, foregut carcinoids
MEN subtype 2A RET proto-oncogene Medullary thyroid cancer, pheochromocytoma, primary hyperparathyroidism (usually single adenoma), cutaneous lichen amyloidosis, Hirschsprung disease
MEN subtype 2B RET proto-oncogene Medullary thyroid cancer, pheochromocytoma, marfanoid body habitus, facial features resulting from mucosal neuromas, ganglioneuromatosis of the gastrointestinal tract
Familial medullary thyroid cancer RET proto-oncogene Medullary thyroid cancer in at least four family members, with documented absence of other endocrinopathies
Hyperparathyroidism-jaw tumor syndrome HRPT2 Primary hyperparathyroidism (usually single adenoma), ossifying fibromas of maxilla or mandible, renal cysts and hamartomas, 15% risk of parathyroid carcinoma
Familial isolated hyperparathyroidism MEN1, HRPT2, CASR, other Nonsyndromic primary hyperparathyroidism
Familial hypocalciuric hypercalcemia CASR Benign hypercalcemia; medical management only
von Hippel-Lindau syndrome (VHL) VHL Pheochromocytoma, retinal and central nervous system hemangioblastoma, renal cysts and clear cell carcinoma, pancreatic cysts and islet cell tumors, endolymphatic sac tumors, papillary cystadenomas of the epididymis and broad ligament
Familial pheochromocytoma/ paraganglioma syndrome SDHB, SDHC, SDHD Multiple paragangliomas and pheochromocytoma
Neurofibromatosis type I NF1 Pheochromocytoma, characteristic physical features (eg, café-au-lait spots, neurofibromas, axillary and inguinal freckling)
Cowden syndrome PTEN Nonmedullary thyroid cancer (usually follicular rather than papillary); benign and malignant tumors of skin, oral mucosa, breast, and uterus
Familial adenomatous polyposis APC Hundreds of adenomatous colon polyps, colon cancer, cribriform morular variant of papillary thyroid cancer
Carney complex PRKAR1A Endocrine tumors (including thyroid, pituitary, primary pigmented nodular adrenocortical disease), characteristic skin pigmentation, myxomas, melanotic schwannomas
Familial nonmedullary thyroid cancer Unknown Nonsyndromic nonmedullary thyroid cancer



  1. Callender GG, Rich TA, Perrier ND. Multiple endocrine neoplasia syndromes. Surg Clin North Am. 2008 Aug;88(4):863-95 [Medline]

Created: Nov 01, 2008