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All but a few studies concerned with the peripheral metabolism of labeled thyroxine 1 in man have ignored the early phase of equilibration of labeled with unlabeled hormone in the tissues (see review in reference 1). Lennon, Engbring, and Eng-strom (2) measured the rate of disappearance of radioactivity from the blood during the initial 50 minutes after intravenous injection of T4-131I in humans. They found that the rate of decline in the level of circulating tracer was abnormally slow in patients with hepatic disease and in untreated cases of hypothyroidism and abnormally rapid in thyrotoxic individuals. Haddad (3) analyzed the plasma curve in normal subjects and fit the data to a two compartment kinetics model representing plasma and tissue pools of thyroxine. More recently , Blomstedt and Plantin (4), using only the time curve of plasma disappearance and the rate of excretion of tracer, proposed a four compartment system to describe the distribution and metabolism of labeled T4 in normal humans. Hepatic localization of radioactivity within hours after the intravenous administration of labeled T4 was observed in several studies in man (5-9). The purpose of the present investigation was to study in a quantitative manner the rate of exchange of labeled T4 between plasma and liver in humans with neither thyroid nor hepatic disease. The method involves body sector counting with externally placed detectors and simultaneous measurement of the plasma concentration of protein-bound 131J. Analysis of the data is based upon a two compartment kinetics model in which no restrictions are placed on the behavior of the plasma compartment. In the course of this study we encountered two unrelated adult males in whose plasma T4 binding by TBG was lacking, apparently on an idiopathic basis. These individuals offered an unusual opportunity to study the effects of alterations in plasma T4 binding on the distribution of labeled T4 in vivo. The results of the kinetics study and in vitro measurements of serum free T4 are presented in these two patients and in nine control subjects with normal levels of TBG. Portions of this work have already appeared in preliminary form (10). Methods The specific activity of sodium L-thyroxine,2 labeled with

the journal of clinical investigation/the journal of clinical investigation

The kinetics of distribution between plasma and liver of 131-I-labeled L-thyroxine in man: observations of subjects with normal and decreased serum thyroxine-binding globulin.