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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
The MEN syndromes are inherited faults in a single gene that cause tumours in several hormone glands over a lifetime. Because the gene can be found in childhood, at-risk relatives can be tested, watched and in MEN2 have the thyroid removed before cancer develops; and for MEN2 thyroid cancer that does spread there is now a precise pill, selpercatinib, that blocks the faulty RET protein.
MEN1 is caused by germline loss-of-function mutations in MEN1, encoding the tumour suppressor menin, and produces parathyroid hyperplasia (nearly universal), duodenopancreatic neuroendocrine tumours (gastrinoma, insulinoma, non-functioning PanNETs, the main cause of death), anterior pituitary tumours, and adrenal, thymic and bronchial neuroendocrine tumours. MEN2 is caused by germline activating mutations in the RET receptor tyrosine kinase: MEN2A (codon 634 most often) causes medullary thyroid carcinoma (MTC), pheochromocytoma and parathyroid disease; MEN2B (M918T) causes early aggressive MTC, pheochromocytoma, mucosal neuromas and a marfanoid habitus. MEN4 (CDKN1B) is a rare MEN1 phenocopy. These syndromes are on the NCI list because their management is oncological: surveillance, prophylactic surgery and, when tumours spread, targeted therapy.
Management is genotype-driven. In MEN2, the American Thyroid Association (2015) assigns RET codons to risk levels that set the age of prophylactic thyroidectomy (within the first year for M918T, before age 5 for codon 634, later with calcitonin monitoring for moderate-risk codons), an intervention that prevents MTC in carriers identified early. Pheochromocytoma must be excluded before any surgery. Advanced RET-mutant MTC is treated with selpercatinib, which outperformed cabozantinib or vandetanib in the randomised LIBRETTO-531 trial (NEJM 2023), with pralsetinib as an alternative. In MEN1, surveillance (calcium and PTH, gastrin and fasting gut hormones, pituitary hormones, pancreatic MRI or endoscopic ultrasound) begins in childhood; parathyroidectomy, proton pump inhibitors for gastrinoma, and surgery for PanNETs above about 2 cm or functioning; advanced PanNETs are treated as sporadic NETs with somatostatin analogues, everolimus, sunitinib and 177Lu-DOTATATE.
| Setting | Approach | Guideline |
|---|---|---|
| MEN2 carriers (RET-positive) | Prophylactic total thyroidectomy timed by ATA risk level (highest risk within the first year, high risk before age 5, moderate risk guided by calcitonin); annual screening for pheochromocytoma and hyperparathyroidism. | not mapped |
| Advanced RET-mutant medullary thyroid carcinoma | Selpercatinib (LIBRETTO-531: superior to cabozantinib or vandetanib); pralsetinib, cabozantinib or vandetanib as alternatives. | NCCN Category 1 (selpercatinib) |
| MEN1 carriers | Surveillance from childhood; subtotal or total parathyroidectomy with autotransplantation for hyperparathyroidism; proton pump inhibitors for gastrinoma; resection of functioning or larger PanNETs; sporadic NET pathways (somatostatin analogues, everolimus, sunitinib, PRRT) for advanced disease. | not mapped |