TRHRencodes the thyrotropin-releasing hormone receptor, a G-protein-coupled receptor expressed on anterior pituitary thyrotropes that mediates TRH-stimulated TSH secretion. Pathogenic variants reported include biallelic missense and nonsense mutations leading to reduced or abolished receptor function. Defective TRHRimpairs TRH binding and Gq-mediated signal transduction, resulting in inadequate TSH synthesis/bioactivity and subsequent central congenital hypothyroidism. Compared with TSHB defects, TRHRmutations often have a milder phenotype due to retained partial TSH production and alternative upregulatory mechanisms on thyrotropes. Autosomal recessive inheritance is the norm; disease typically manifests in homozygotes or compound heterozygotes.
TRHR