The effects of an acute load of thyroxine on the transport and peripheral metabolism of triiodothyronine in man

Abstract

In order to examine the question of whether thyroxine-binding globulin (TBG) influences significantly the peripheral metabolism of 3,3′,5-triiodo-L-thyronine (T₃) in vivo, paired studies of the effects of a large intravenous load of L-thyroxine (T₄) on the kinetics of ¹³¹I-labeled T₃ metabolism were carried out in five normal subjects. After the T₄ load, both the early distributive loss of labeled T₃ from serum and the volume of T₃ distribution, observed after distribution equilibrium had been attained, were greatly increased. These alterations were consistent with those to be expected from displacement of T₃ from its extracellular binding sites. After the T₄ load, however, the fractional rate of T₃ turnover was decreased. This finding is ascribed either to competition between T₃ and T₄ for common intracellular pathways of degradation or excretion or to displacement of T₃ from sites of more rapid to sites of less rapid metabolism. These effects of alterations in the binding activity of TBG on the peripheral metabolism of T₃, together with those previously reported by others, are consistent with the interpretation that T₃ is significantly bound by TBG in vivo. However, it is suggested that the effects of alterations in the T₃-TBG binding interaction on the metabolism of T₃ are obscured by alterations in the extracellular-cellular partitioning of T₄ that would result from concurrent alterations in T₄-binding by TBG.