Resistance to thyroid hormone (RTH)

Resistance to thyroid hormone (RTH), a syndrome of reduced end-organ responsiveness to TH, was identified in 1967.1 The early reports postulated various mechanisms, including defects in TH transport, metabolism and action.2 However, with the subsequent identification of TH receptor (TR) β gene mutations3, 4, the term RTH became synonymous with defects of the TR.5 The recent discoveries of genetic defects that reduce the effectiveness of TH through altered cell-membrane transport*6, *7 and metabolism8 have broadened the definition of TH insensitivity to encompass all defects that can interfere with the biological activity of a chemically intact hormone secreted in normal amounts. In this chapter, use of the acronym RTH is limited to the syndrome produced by reduced intracellular action of the active TH, triiodothyronine (T3). The term ‘reduced sensitivity to TH’ is used to denote reduced effectiveness of TH in the broader sense.