Salsalate administration--a potential pharmacological model of the sick euthyroid syndrome

This study examined salsalate ingestion as a model of the sequelae of acute inhibition of thyroid hormone binding to serum protein. One dose of salsalate (60-65 mg/kg) was administered to healthy volunteers. Serum salsalate concentrations peaked at 2 h (82 micrograms/mL), then declined at 8 h to 1.2 micrograms/mL. Serum total T4 (TT4) and total T3 (TT3) concentrations declined for 4 h, then recovered by 96 h, while T4 binding protein concentrations remained unchanged. TT3 was reduced to a greater extent than TT4 between 2 h and 72 h, and serum total reverse(r)T3 (TrT3) was transiently increased at 8 h. TSH concentrations fell while TT4 and TT3 fell, then recovered while TT4, TT3, and free T3, but not free T4, were still reduced. Subsequently, TSH overshot basal levels and continued to rise after 96 h while TT4, TT3, free T4, free T3, and TrT3 were all at basal levels. We postulate that an acute release of T4 and T3 from circulating transport proteins, induced by an inhibitor of binding, can result in large and rapid redistribution of T4 and T3 into tissue compartments associated with transiently reduced peripheral tissue 5'-monodeiodination and deranged TSH regulation.