Medullary Thyroid Carcinoma (MTC)
A rare thyroid cancer arising from C-cells that produce calcitonin. MTC is relevant to peptide therapeutics because all GLP-1 receptor agonists are contraindicated in patients with personal or family history of MTC or Multiple Endocrine Neoplasia syndrome type 2, due to the thyroid C-cell tumour signal in rodent studies.
Technical Context
MTC arises from thyroid C-cells and accounts for approximately 3-5% of all thyroid cancers. It can be sporadic (~75%) or hereditary (~25%, associated with MEN2A, MEN2B, or familial MTC — all caused by RET proto-oncogene mutations). MTC produces calcitonin (used as tumour marker) and sometimes CEA. Five-year survival varies by stage: localised ~97%, regional ~90%, distant ~40%. The contraindication of GLP-1 RAs in patients with personal/family history of MTC or MEN2 is a precautionary measure based on rodent C-cell tumour findings. Genetic testing for RET mutations is recommended for patients diagnosed with MTC. Pre-treatment screening for MTC before initiating GLP-1 RA therapy is not recommended in general guidelines — the boxed warning relies on patient/family history rather than universal screening.