Role of sulfate in thyroid hormone sulfation

Although the identification of T3 sulfate (T3S) in humans was reported in 1958 (1), sulfation has only recently been recognized as a unique pathway of thyroid hormone metabolism (2). Sulfation is a socalled phase II detoxification pathway by which a variety of lipophilic endogenous and exogenous compounds are converted into water-soluble conjugates to facilitate their excretion in bile or urine (3). The sulfotransferases catalyzing these reactions represent a family of homologous enzymes located in the cytoplasm of many tissues, in particular liver (3). Sulfation of the phenolic hydroxyl group of T3 and other iodothyronines has been observed in rat liver, brain and kidney, and in human liver (4–6). Normally, concentrations of iodothyronine sulfates in plasma, bile and urine are low. However, in conditions associated with a low activity of the type I iodothyronine deiodinase (ID-I), such as administration of propylthiouracil or iopanoic acid, selenium deficiency, non-thyroidal illness (NTI) and fetal development, iodothyronine sulfates accumulate in plasma and bile (7–13). The paper by Santini et al. (14) published in this issue of European Journal of Endocrinology deals with the possible mechanisms for the increase in plasma T3S in patients with NTI.