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. 1972 May;51(5):1125–1134. doi: 10.1172/JCI106905

Salicylate-induced increases in free triiodothyronine in human serum

Evidence of inhibition of triiodothyronine binding to thyroxine-binding globulin and thyroxine-binding prealbumin

P R Larsen 1
PMCID: PMC292242  PMID: 4623165

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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