Multiple endocrine neoplasia type 2A (MEN2A), also known as Sipple syndrome, is an autosomal dominant disorder caused by mutation of the RET gene in cells of neural crest origin. RET codes for receptor tyrosine kinase. Variants within MEN2A include classic MEN2A, MEN2A with cutaneous lichen amyloidosis, MEN2A with Hirschsprung disease, and familial medullary cancer with pheochromocytoma or parathyroid hyperplasia. MEN2A accounts for approximately 70%-80% of all MEN2 cases and has an estimated prevalence of 1 in 40 000.

Patients are at risk of developing tumors in the thyroid, parathyroid, and adrenal glands as well as nerve defects such as neuromas. MEN2A is characterized by medullary thyroid carcinomas, primary hyperparathyroidism, and pheochromocytomas.

MEN2A often manifests before the fourth decade of life (most often between the ages of 5 and 25 years). Diarrhea and medullary thyroid carcinoma are usually the initial presenting symptoms. Other findings include cervical lymphadenopathy, depressed mood, constipation, fatigue, headache, flushing, hypertension, memory impairment, pruritus, and palpitations.

Related topics: MEN1, MEN2B