MEN1 is three Ps; MEN2A is two Cs and a P; MEN2B adds mucosal neuromas
Mnemonic
Count the Ps and Ms:
- MEN 1 - the three Ps: Parathyroid, Pituitary, Pancreas (gastrinoma, insulinoma). Gene MEN1 (menin), chromosome 11
- MEN 2A - two Ps and an M: Parathyroid, Phaeochromocytoma, Medullary thyroid carcinoma. Gene RET, chromosome 10
- MEN 2B - one P and two Ms: Phaeochromocytoma, Medullary thyroid carcinoma, Mucosal neuromas, with a marfanoid habitus. Also RET
“1 is menin, 2 is RET”, and all are autosomal dominant.
Medullary thyroid carcinoma is the constant in both type 2 syndromes, arises from parafollicular C cells, secretes calcitonin, and warrants prophylactic thyroidectomy in gene carriers, in infancy for 2B and early childhood for 2A.
Phaeochromocytoma must be excluded and treated first before any other surgery in these patients.
Expansion
MEN1 (the three Ps) - MEN1 tumour suppressor gene
- Parathyroid hyperplasia, the commonest and usually first
- Pancreatic islet tumours: gastrinoma, insulinoma, VIPoma
- Pituitary adenoma, often prolactinoma
MEN2A - RET proto-oncogene
- Medullary thyroid carcinoma (C cells)
- Phaeochromocytoma
- Parathyroid hyperplasia
MEN2B - RET
- Medullary thyroid carcinoma
- Phaeochromocytoma
- Mucosal neuromas and marfanoid habitus
- No parathyroid disease
All are autosomal dominant.
Two management principles follow. Medullary thyroid carcinoma is the main determinant of survival in MEN2, so prophylactic thyroidectomy is offered in childhood to RET carriers, timed by the specific mutation. And in any MEN2 patient requiring surgery, phaeochromocytoma must be excluded and treated first, since anaesthesia in an untreated case can precipitate a fatal hypertensive crisis.