Abstract
A method is described for the kinetic analysis of exchange of thyroxine (T4)-131I between plasma and extravascular space of the liver in humans. Single intravenous injection of tracer was followed by frequent sampling of peripheral blood and continuous monitoring of hepatic radioactivity using externally placed scintillation detectors. Nine euthyroid subjects with normal levels of thyroxine-binding serum globulin (TBG) were studied as controls. Distribution equili-brium of T4-131I between plasma and liver was approached by 4 hr. after injection of tracer. The hepatic T4 distribution volume (space) averaged 3.80 L [plus or minus] 0.50 (S.D.), which was 30% of the total T4 space, after complete equilibration. The mean hepatic clearance (one-way) was 48 ml plasma/min. [plus or minus] 5 (S.D.). In 2 euthyroid individuals whose plasma was virtually devoid of TBG, estimates of the hepatic T4 space were higher than in the controls but varied widely. The hepatic T4 clearances were similar in these patients and nearly 2.7 times the mean control value. The calculated plasma to liver flux was approximately normal due to the low serum concentration of T4 in these subjects. The proportion of free T4 in serum, measured in vitro, correlated with the hepatic T4 clearance in patients with low TBG, indicating that the level of free rather than bound T4 determines the entry of hormone into liver. The large rapidly exchangeable pool of thyroid hormone in the liver of the normal individual acts as a buffer-reservoir to modulate sudden changes in the level of circulating T4.