Role of Thyroxine-Binding Globulin in the Early Distribution of Thyroxine and Triiodothyronine

The thyroxine (T4)-binding capacity of the T4-binding globulin (TBG) affects the distribution within the body and the rate of disappearance from plasma of both labeled T4 and triiodothyronine (T3). Thus, estrogens, which increase T4-binding by TBG, reduce the hepatic incorporation, hepatic volume of distribution (VL) and hepatic clearance (CL) of both hormones in normal adults without altering the extrahepatic fractions of T4 or T3. Conversely, in 2 brothers who lack TBG, the hepatic uptake, VL and CL were much greater than in normals. We infer that increased T4-binding capacity is responsible for the reduced VL and CL produced by estrogens in normal subjects. The qualitatively similar effects of estrogens on the hepatic incorporation and VL of T3 show that TBG also influences the distribution of T3. Comparison of the rates of plasma disappearances of T3 and T4 with the rates of hepatic uptake suggests that the period of time from 20 to 50 min after injection reflects principally hepatic uptake of T4 but extrahepatic uptake of T3.