Human Genetics of Thyroid Hormone Receptor Beta: Resistance to Thyroid Hormone Beta (RTHβ)

Resistance to thyroid hormone beta (RTHβ) is a syndrome characterized by reduced responsiveness of peripheral tissues to thyroid hormone (TH). Affected individuals have consistently high TH levels and non-suppressed thyrotropin in the absence of acute illness, drugs, or alterations in TH binding proteins. Depending on the tissue, features of TH excess and deficiency may coexist, although most individuals have a euthyroid, normal metabolic state at the expense of high TH levels. In most cases the disorder is associated with germline mutations in the THRB gene. In the last decades, advances in genetics have expanded our knowledge on the etiology and pathophysiology of the syndrome and have shed more light on the molecular mechanisms of TH action. This review provides an update on the genetics of RTHβ, summarizes the clinical and biochemical presentation of the syndrome, and describes the methodology used to diagnose and manage individuals with RTHβ.