Salicylate-induced increases in free triiodothyronine in human serum

Abstract

Addition of sodium salicylate to human serum at concentrations often obtained during aspirin therapy causes 100-200% increases in free triiodothyronine (T₃) and free thyroxine (T₄) as estimated by ultrafiltration. The increase in free T₃ was unexpected since previous data had suggested that salicylate inhibits binding of T₄ only to thyroxine-binding prealbumin (TBPA) and that T₃ is not bound to this protein. Using ultrafiltration techniques, we demonstrated binding of T₃ to TBPA. The affinity constant for T₃-TBPA binding appears to be slightly greater than that for albumin-T₃ binding. While salicylate inhibits the binding of T₃ (and T₄) to TBPA, it can be predicted that little change will be observed in the free T₃ (or free T₄) without inhibition of thyroid hormone binding to thyroxine-binding globulin (TBG). Using a competitive-binding protein displacement technique, it has been shown that sodium salicylate, like diphenylhydantoin (DPH), inhibits the binding of T₃ and T₄ to TBG. The magnitude of the increase in free T₃ and free T₄ induced by salicylates suggests that interference with TBG binding is its major effect. Aspirin was administered orally to two normal subjects in quantities sufficient to obtain serum salicylate levels of 20-25 mg/100 ml. This resulted in a decrease of 20-30% in total serum T₃ and T₄ levels. This decrease in T₄ levels is similar in magnitude to that previously observed in subjects receiving DPH. Unlike what has been observed with DPH treatment, therapeutic salicylate levels are associated with increases of 50-75% in the unbound fraction of both T₃ and T₄ which persist throughout an 8-10 day treatment period.