Bit · Endo
Multiple Endocrine Neoplasia - MEN 1, 2A, 2B
Three autosomal dominant syndromes that produce tumors in multiple endocrine glands. Each has a signature combination and a signature gene.
Mechanism#
The MEN syndromes are autosomal dominant; each caused by a different gene with a stereotypical tumor portfolio:
- MEN 1 - MEN1 tumor suppressor gene mutation. 'Diamond mnemonic': 3 Ps - Pituitary, Parathyroid, Pancreatic islet cells (most commonly gastrinoma or insulinoma). Hyperparathyroidism is usually the earliest finding.
- MEN 2A - RET proto-oncogene gain-of-function mutation. Medullary thyroid carcinoma (C cells, calcitonin) + Pheochromocytoma + Parathyroid hyperplasia ('2 Ps + medullary').
- MEN 2B - also RET, different codon. Medullary thyroid carcinoma + Pheochromocytoma + Mucosal/intestinal neuromas + Marfanoid habitus. No hyperparathyroidism.
Critical clinical point: in any patient with MEN 2A or 2B, prophylactic total thyroidectomy is recommended in early childhood (timing depends on specific RET codon) because medullary thyroid carcinoma is almost universal.
Differentiator Table#
| MEN 1 | MEN 2A | MEN 2B | |
| Gene | MEN1 (tumor suppressor) | RET (oncogene) | RET (oncogene) |
| Pituitary | YES | No | No |
| Parathyroid | YES (hyperparathyroidism) | YES | No |
| Pancreatic islet | YES (gastrinoma, insulinoma) | No | No |
| Medullary thyroid carcinoma | No | YES | YES |
| Pheochromocytoma | No | YES | YES |
| Mucosal/intestinal neuromas + marfanoid | No | No | YES |
| Mnemonic | 3 Ps | 2 Ps + medullary | 1 P + medullary + Mucosal neuromas + Marfan |
The Pivot#
Pattern match the tumor portfolio:
- Hyperparathyroidism + pituitary adenoma + gastrinoma/insulinoma? → MEN 1.
- Medullary thyroid CA + pheo + parathyroid hyperplasia? → MEN 2A.
- Medullary thyroid CA + pheo + mucosal neuromas + tall thin habitus? → MEN 2B.
Whenever you see a young patient with pheo, screen for MEN 2A/2B (RET) and von Hippel-Lindau and NF1.
NBME-Style Stem#
A 24-year-old man presents with episodic headaches, palpitations, and sweating. Examination reveals a tall, lanky build with long fingers, thickened lips with visible nodules on his tongue and lips, and a thyroid mass. 24-hour urinary metanephrines are elevated. Calcitonin is markedly elevated. Which of the following is the most likely diagnosis?
Concept Anchor
Three MEN syndromes, three predictable tumor combinations: MEN1 (3 Ps), MEN2A (medullary + pheo + parathyroid), MEN2B (medullary + pheo + neuromas + marfanoid). RET mutations drive 2A/2B; MEN1 mutation drives MEN1.