# Multiple endocrine neoplasia type 2 (MEN2A and MEN2B)

Source: https://onco.cc/cancers/men2-syndrome/  
OnCo record `men2-syndrome` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

How 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).

Treatment 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).

## Fields

- Kind: Cancer
- Last checked: 2026-09-24
- Also known as: 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)
- Tags: subtype-page; wave4; rare
- 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

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/men2-syndrome/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/men2-syndrome/#overview
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/men2-syndrome/#what-it-is [4 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/men2-syndrome/#finding-it [4 biomarkers]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/men2-syndrome/#treating-it [2 settings]
- Evidence (on the hub): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/men2-syndrome/#evidence [1 trial]
- The science (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/men2-syndrome/#science [4 targets]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/men2-syndrome/where-you-are/
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/men2-syndrome/#living-with-it [10 questions, 3 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/men2-syndrome/coming/ [3 medicines]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/men2-syndrome/data/ [17 connected records]

## Standard of care

- Gene carriers: Prophylactic thyroidectomy timed by RET risk category, after excluding phaeochromocytoma (ATA 2015). ([Thyroidectomy](https://onco.cc/terms/thyroidectomy/), [RET](https://onco.cc/targets/ret/), [Medullary thyroid cancer](https://onco.cc/cancers/medullary-thyroid-cancer/))
- Established medullary thyroid carcinoma: Treated as the medullary thyroid cancer page describes; selpercatinib for advanced RET-driven disease (LIBRETTO-531). ([Medullary thyroid cancer](https://onco.cc/cancers/medullary-thyroid-cancer/), [Selpercatinib](https://onco.cc/drugs/selpercatinib/), [LIBRETTO-531](https://onco.cc/trials/libretto-531/))

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Multiple_endocrine_neoplasia_type_2
- NCI: multiple endocrine neoplasia (MEN) syndromes: https://www.cancer.gov/types/multiple-endocrine-neoplasia
- Wells 2015, Thyroid: revised American Thyroid Association guidelines for medullary thyroid carcinoma: https://doi.org/10.1089/thy.2014.0335
- Orphanet: multiple endocrine neoplasia type 2 (ORPHA:653): https://www.orpha.net/en/disease/detail/653
- Genotype-specific phenotype in MEN2 against the guideline predictions, Cancers 2024: https://doi.org/10.3390/cancers16030494

## Connected records

- cancers: [Hereditary pheochromocytoma and paraganglioma (SDHx, VHL, RET, NF1, MAX and TMEM127)](https://onco.cc/cancers/hereditary-ppgl/), [Medullary thyroid cancer](https://onco.cc/cancers/medullary-thyroid-cancer/), [Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4)](https://onco.cc/cancers/multiple-endocrine-neoplasia/), [Multiple endocrine neoplasia type 1 (MEN1)](https://onco.cc/cancers/men1-syndrome/), [Pheochromocytoma and paraganglioma (PPGL)](https://onco.cc/cancers/pheochromocytoma-paraganglioma/)
- technologies: [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/)
- targets: [RET](https://onco.cc/targets/ret/)
- drugs: [Cabozantinib](https://onco.cc/drugs/cabozantinib/), [Selpercatinib](https://onco.cc/drugs/selpercatinib/), [Vandetanib](https://onco.cc/drugs/vandetanib/)
- terms: [Hereditary cancer syndromes](https://onco.cc/terms/hereditary-cancer-syndromes/), [Thyroidectomy](https://onco.cc/terms/thyroidectomy/)
- trials: [LIBRETTO-531](https://onco.cc/trials/libretto-531/)

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JSON: https://onco.cc/api/v1/entities/men2-syndrome.json