Salicylate-induced increases in free triiodothyronine in human serum: Evidence of inhibition of triiodothyronine binding to thyroxine-binding globulin and thyroxine-binding prealbumin

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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.

Authors

P. R. Larsen