Thyroid C-Cell Tumour
A tumour of the thyroid's parafollicular C-cells, including medullary thyroid carcinoma (MTC). GLP-1 receptor agonists carry a black box warning for this risk based on rodent studies showing dose-dependent tumour formation. Whether this risk translates to humans remains uncertain and under long-term surveillance.
Technical Context
Preclinical data: GLP-1 RAs caused dose-dependent, treatment-duration-dependent thyroid C-cell hyperplasia, adenomas, and carcinomas in rats and mice at clinically relevant exposures. Mechanism: sustained GLP-1R activation on rodent C-cells stimulates calcitonin release and C-cell proliferation. Species difference: human thyroid C-cells express far fewer GLP-1 receptors than rodent C-cells, and human C-cells show minimal calcitonin response to GLP-1R agonism. Epidemiological data: large database studies and post-marketing surveillance have not demonstrated a clear increase in MTC incidence in GLP-1 RA-treated patients, though follow-up duration remains limited for detecting rare, slow-growing tumours. Calcitonin monitoring (routine serum calcitonin measurement during GLP-1 RA therapy) is NOT recommended by most guidelines due to low specificity and high false positive rates, but unexplained calcitonin elevation should prompt thyroid investigation.