Resistance to Thyrotropin Caused by Mutations in the Thyrotropin-Receptor Gene

Abstract

Hormone-resistance syndromes can be broadly defined as conditions resulting from reduced or absent end-organ responsiveness to biologically active hormones. They are caused by defects in hormone receptors or post-receptor defects.1–3 Mutations in the thyroid hormone–receptor β gene cause resistance to thyroid hormone, which is characterized by elevated serum thyroid hormone concentrations with few or no clinical and biochemical manifestations of thyroid hormone excess and, most notably, normal or slightly increased thyrotropin secretion.1 Mutations that inactivate the thyrotropin receptor or the G (guanine nucleotide–binding) protein that couples the receptor to adenylate cyclase should cause thyrotropin resistance, resulting in either hypothyroidism . . .