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

In order to examine the question of whether thyroxine-binding globulin (TBG) influences significantly the peripheral metabolism of 3,3',5-triiodo-L-thyronine (T(3)) in vivo, paired studies of the effects of a large intravenous load of L-thyroxine (T(4)) on the kinetics of (131)I-labeled T(3) metabolism were carried out in five normal subjects. After the T(4) load, both the early distributive loss of labeled T(3) from serum and the volume of T(3) distribution, observed after distribution equilibrium had been attained, were greatly increased. These alterations were consistent with those to be expected from displacement of T(3) from its extracellular binding sites. After the T(4) load, however, the fractional rate of T(3) turnover was decreased. This finding is ascribed either to competition between T(3) and T(4) for common intracellular pathways of degradation or excretion or to displacement of T(3) 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 T(3), together with those previously reported by others, are consistent with the interpretation that T(3) is significantly bound by TBG in vivo. However, it is suggested that the effects of alterations in the T(3)-TBG binding interaction on the metabolism of T(3) are obscured by alterations in the extracellular-cellular partitioning of T(4) that would result from concurrent alterations in T(4)-binding by TBG.