{"entity":{"id":"men2-syndrome","kind":"cancer","name":"Multiple endocrine neoplasia type 2 (MEN2A and MEN2B)","aka":["MEN2","MEN2A","MEN2B","MEN3","Sipple syndrome","Familial medullary thyroid carcinoma (MEN2A variant)","MEN2A (RET; medullary thyroid carcinoma, pheochromocytoma, parathyroid)","MEN2B (RET M918T; early MTC, pheochromocytoma, mucosal neuromas)"],"tldr":"MEN2 is an inherited condition, one of the multiple endocrine neoplasia syndromes, in which a faulty RET gene causes medullary thyroid cancer in almost every carrier, often with adrenal tumours and overactive parathyroids. Because the thyroid cancer is so predictable, children who inherit the gene have the thyroid removed at an age set by which RET mutation they carry.","summary":"MEN2 is caused by germline activating mutations in the RET proto-oncogene. The American Thyroid Association guideline divides it into MEN2A, with medullary thyroid carcinoma, phaeochromocytoma and primary hyperparathyroidism (and the variants with cutaneous lichen amyloidosis or Hirschsprung disease, and familial medullary thyroid carcinoma, now classed as an MEN2A variant), and MEN2B, with earlier and more aggressive medullary thyroid carcinoma, phaeochromocytoma, mucosal neuromas and a marfanoid habitus, almost always from the RET M918T mutation (Wells 2015). The WHO endocrine classification lists MEN2 among the genetic tumour syndromes.\n\nHow it differs from its parent: MEN1 is a menin syndrome centred on parathyroid, pancreas and pituitary; MEN2 is a RET syndrome whose defining cancer is medullary thyroid carcinoma, which the corpus covers on its own page. The guideline stratifies RET mutations into highest risk (M918T), high risk (codon 634 and A883F) and moderate risk, and times prophylactic thyroidectomy accordingly: in the first year of life for the highest-risk group, at or before age five for the high-risk group, and by calcitonin surveillance for the moderate group; phaeochromocytoma is excluded before any operation (Wells 2015).\n\nTreatment of established disease follows the medullary thyroid cancer page: total thyroidectomy with node dissection, and for advanced RET-driven disease the selective RET inhibitor selpercatinib, which beat cabozantinib or vandetanib in the LIBRETTO-531 trial linked from the parent page; phaeochromocytoma and hyperparathyroidism are treated as in sporadic disease. The genotype-phenotype rules hold in practice: a single-centre series of 158 MEN2 patients tested the guideline's predictions against observed ages of onset (Cancers 2024, PMID 38339246).","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Multiple_endocrine_neoplasia_type_2","links":[{"label":"NCI: multiple endocrine neoplasia (MEN) syndromes","url":"https://www.cancer.gov/types/multiple-endocrine-neoplasia"},{"label":"Wells 2015, Thyroid: revised American Thyroid Association guidelines for medullary thyroid carcinoma","url":"https://doi.org/10.1089/thy.2014.0335"},{"label":"Orphanet: multiple endocrine neoplasia type 2 (ORPHA:653)","url":"https://www.orpha.net/en/disease/detail/653"},{"label":"Genotype-specific phenotype in MEN2 against the guideline predictions, Cancers 2024","url":"https://doi.org/10.3390/cancers16030494"}],"tags":["subtype-page","wave4","rare"],"related":["multiple-endocrine-neoplasia","men1-syndrome","medullary-thyroid-cancer","hereditary-ppgl","pheochromocytoma-paraganglioma"],"cancers":[],"sections":[],"technologies":["germline-testing"],"targets":["ret"],"drugs":["selpercatinib","vandetanib","cabozantinib"],"companies":[],"institutions":[],"pathways":[],"terms":["thyroidectomy","hereditary-cancer-syndromes"],"trials":["libretto-531"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"endocrine","burden":"Orphanet lists MEN2 as a rare disease (ORPHA:653). The American Thyroid Association guideline is the source for its clinical figures; no population incidence is given in the sources read, and GLOBOCAN counts medullary thyroid cancer within thyroid cancer.","subtypes":["MEN2A, classical (medullary thyroid carcinoma, phaeochromocytoma, hyperparathyroidism)","MEN2A with cutaneous lichen amyloidosis or Hirschsprung disease","Familial medullary thyroid carcinoma (an MEN2A variant in the ATA classification)","MEN2B (RET M918T; mucosal neuromas, marfanoid habitus)"],"biomarkers":["Germline RET mutation and its ATA risk category (highest, high, moderate)","Serum calcitonin and carcinoembryonic antigen","Plasma or urine metanephrines before any surgery","Calcium and parathyroid hormone"],"standardOfCare":[{"setting":"Gene carriers","approach":"Prophylactic thyroidectomy timed by RET risk category, after excluding phaeochromocytoma (ATA 2015).","refs":["thyroidectomy","ret","medullary-thyroid-cancer"]},{"setting":"Established medullary thyroid carcinoma","approach":"Treated as the medullary thyroid cancer page describes; selpercatinib for advanced RET-driven disease (LIBRETTO-531).","refs":["medullary-thyroid-cancer","selpercatinib","libretto-531"]}],"stateOfArt":[],"history":[],"pipeline":[],"openProblems":[],"parent":"multiple-endocrine-neoplasia"},"route":"/cancers/men2-syndrome/","neighbours":{"cancer":[{"id":"hereditary-ppgl","kind":"cancer","name":"Hereditary pheochromocytoma and paraganglioma (SDHx, VHL, RET, NF1, MAX and TMEM127)","route":"/cancers/hereditary-ppgl/"},{"id":"medullary-thyroid-cancer","kind":"cancer","name":"Medullary thyroid cancer","route":"/cancers/medullary-thyroid-cancer/"},{"id":"multiple-endocrine-neoplasia","kind":"cancer","name":"Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4)","route":"/cancers/multiple-endocrine-neoplasia/"},{"id":"men1-syndrome","kind":"cancer","name":"Multiple endocrine neoplasia type 1 (MEN1)","route":"/cancers/men1-syndrome/"},{"id":"pheochromocytoma-paraganglioma","kind":"cancer","name":"Pheochromocytoma and paraganglioma (PPGL)","route":"/cancers/pheochromocytoma-paraganglioma/"}],"technology":[{"id":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","route":"/technologies/germline-testing/"}],"target":[{"id":"ret","kind":"target","name":"RET","route":"/targets/ret/"}],"drug":[{"id":"cabozantinib","kind":"drug","name":"Cabozantinib","route":"/drugs/cabozantinib/"},{"id":"selpercatinib","kind":"drug","name":"Selpercatinib","route":"/drugs/selpercatinib/"},{"id":"vandetanib","kind":"drug","name":"Vandetanib","route":"/drugs/vandetanib/"}],"term":[{"id":"hereditary-cancer-syndromes","kind":"term","name":"Hereditary cancer syndromes","route":"/terms/hereditary-cancer-syndromes/"},{"id":"thyroidectomy","kind":"term","name":"Thyroidectomy","route":"/terms/thyroidectomy/"}],"trial":[{"id":"libretto-531","kind":"trial","name":"LIBRETTO-531","route":"/trials/libretto-531/"}]}}