Multiple endocrine neoplasia (MEN) syndromes
- Topic
Inherited syndromes that cause tumours in several hormone glands. Knowing the gene lets the family be screened and protected.
What it is
Multiple endocrine neoplasia syndromes are autosomal dominant conditions with tumours, often multifocal and earlier in life than sporadic ones, in several endocrine organs. MEN1 comes from loss of the tumour suppressor menin, MEN2A and MEN2B from activation of the RET proto-oncogene, and MEN4 from loss of p27 (CDKN1B). Recognising the pattern leads to germline testing, screening of relatives and, in MEN2, prophylactic thyroidectomy.
Step by step
- A germline mutation is present in every cell (one hit inherited, or one activated allele).
- In MEN1 and MEN4 a second, somatic hit inactivates the remaining allele in endocrine cells; in MEN2 one activated RET allele is enough.
- Hyperplasia appears first in the target glands (C-cell or parathyroid hyperplasia).
- Multifocal tumours develop in several glands, earlier than sporadic tumours.
- Testing relatives finds carriers before cancer: surveillance or prophylactic surgery.
MEN syndromes compared
| Syndrome | Gene | Parathyroid | Pancreas / duodenum | Pituitary | Other |
|---|---|---|---|---|---|
| MEN1 | MEN1 (menin), loss | Hyperplasia, adenomas (most patients) | NETs: gastrinoma, insulinoma, non-functioning | PitNET, often lactotroph | Adrenal cortical nodules, thymic and bronchial carcinoids, skin angiofibromas |
| MEN2A | RET, gain | Hyperplasia (some) | None | None | Medullary thyroid carcinoma, pheochromocytoma; some with lichen amyloidosis or Hirschsprung |
| MEN2B | RET M918T, gain | None | None | None | Aggressive medullary carcinoma, pheochromocytoma, mucosal neuromas, marfanoid habitus |
| MEN4 | CDKN1B (p27), loss | Hyperparathyroidism | NETs | PitNET | MEN1-like |
Clinical notes
- Every patient with medullary thyroid carcinoma, and young or multiple endocrine tumours, is offered germline testing.
- Before thyroid or any surgery in MEN2, pheochromocytoma must be excluded.
Test yourself
Think of the answer, then tap the question to see it.
Which gland is affected first and most often in MEN1?
The parathyroid glands, with hyperparathyroidism.
What is the mechanistic difference between MEN1 and MEN2?
MEN1 is loss of a tumour suppressor (menin) needing a second hit; MEN2 is gain of function of the RET proto-oncogene.
Which features distinguish MEN2B from MEN2A?
Mucosal neuromas and marfanoid habitus, more aggressive medullary carcinoma, and no hyperparathyroidism.
Elsewhere in DurgiPedia
- Hereditary cancer syndromes: the table to know
- Oncogenes: RAS, MYC, HER2, BCR-ABL and the table to know
- Tumour suppressor genes: RB, TP53, APC, BRCA and the two-hit hypothesis
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Multiple endocrine neoplasia: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2025); Hereditary paraganglioma-pheochromocytoma: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2025).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.