Impaired Sensitivity to Thyroid Hormone: Defects of Transport, Metabolism, and Action

Resistance to thyroid hormone (RTH), a syndrome of reduced responsiveness of target tissues to thyroid hormone (TH) was identified in 1967 (1). An early report proposed various mechanisms including defects in TH transport, metabolism and action (2). However, with the identification of () gene mutations in 1989 (3, 4), the term RTH became synonymous with defects of this specific gene (5). Subsequent discoveries of genetic defects that reduce the effectiveness of TH through altered cell membrane transport (6, 7) and metabolism (8) have broadened the definition of TH hyposensitivity to encompass all defects that can interfere with the biological activity of a chemically intact hormone secreted in normal or even excessive amounts. In this chapter, we have retained the acronym RTH to denote the syndrome produced by reduced intracellular action of the active TH, triiodothyronine (T). However, with the identification of mutations in the () gene (9), RTH syndromes are designated as RTHα and RTHß. The term of impaired sensitivity to TH (ISTH) has been therefore proposed (10-12) to denote altered effectiveness of TH in a broader sense. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.