A clinician’s guide to understanding resistance to thyroid hormone due to receptor mutations in the TRα and TRβ isoforms

Abstract

There are two genes that express the major thyroid hormone receptor isoforms. Mutations in both these genes have given rise to Resistance to Thyroid Hormone (RTH) syndromes (RTHβ, RTHα) that can have variable phenotypes for mutations of the same receptor isoform as well as between the two receptor isoforms. In general, the relative tissue-specific distribution of TRβ and TRα determine RTH in different tissues for each form of RTH. These differences highlight some of the isoform-specific roles of each TR isoform. The diagnosis of RTH is challenging for the clinician but should be considered whenever a patient presents with unexplained elevated serum free T4 (fT4) and unsuppressed TSH levels, as well as decreased serum free T4/T3 ratio. Here we provide a guide for the clinician to diagnose and treat both types of RTH.