The requirement for TH varies with

The requirement for TH varies with tissue, cell type and time. Control of TH entry into the cell through membrane transporters is apparently insufficient to provide the proper hormone supply. Further fine-tuning is achieved by the generation of active TH or by its inactivation at the site of action. D1 and D2 are 5′-iodothyronine deiodinases that catalyze TH activation by converting T4 to T3. D3, a 5-deiodinase, is the main TH inactivator through conversion of T4 to rT3 and T3 to T2.Etiology and variantsUntil recently, all known defects of TH metabolism observed in man were acquired. The most frequent defect produces the ‘low T3 syndrome’ of nonthyroidal illness.89 In 2005, the first inherited disorder of iodothyronine metabolism was described, caused by a reduction in the synthesis rather than structure of deiodinases.8 The mutant gene, the selenocysteine insertion sequence-binding protein2 (SECISBP2, in short SBP2), affects the synthesis of selenoproteins including the deiodinases. It is anticipated that mutations in other genes causing defective thyroid metabolism will have different phenotypes.