Inhibition of Hepatic Binding of Thyroxine by Cholecystographic Agents

James V. Felicetta; William L. Green; Wil B. Nelp

doi:10.1172/JCI109755

Inhibition of Hepatic Binding of Thyroxine by Cholecystographic Agents

James V. Felicetta, William L. Green, and Wil B. Nelp

Published May 1, 1980 - More info

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Abstract

Subsequent to studies indicating that cholecystographic agents and sulfobromophthalein (BSP) inhibit uptake of thyroxine (T₄) by rat liver slices, the effect of such compounds on hepatic storage of T₄ in man has been examined. After intravenous administration of [¹²⁵I]T₄ to five normal subjects, hepatic radioactivity, estimated by external gamma counting, rose to a peak in ∼4 h and then declined in parallel with serum radioactivity. When a 6-g dose of the cholecystographic agent, tyropanoate (Bilopaque), was administered orally 3 d later, estimated hepatic extravascular radioactivity fell 50-60% within 4 h and then rose toward the pretyropanoate value. Concomitant with the fall in hepatic radioactivity, serum radioactivity rose 57-70%, as did stable T₄ levels in serum, suggesting that hormone discharged from the liver entered the serum. Both uptake of T₄ and discharge by tyropanoate were much less in two patients with liver disease.

Ipodate (Oragrafin), 12 g orally in two subjects, caused much smaller changes in hepatic and serum radioactivity. However, ipodate also caused a doubling of the percent free T₄ in the serum as judged by equilibrium dialysis, and the ratio of hepatic radioactivity to free [¹²⁵I]T₄ in serum declined markedly after ipodate, similar to the fall in hepatic:serum ¹²⁵I ratios after tyropanoate. BSP, 20 mg/kg i.v. in three subjects, caused a smaller change; the decline in hepatic T4 content averaged 19%.

We conclude that these organic anions, tyropanoate, ipodate, and BSP, all can displace T₄ from the liver. The results imply a link between T₄ transport and organic anion transport, and indicate a mechanism for altering hepatic T₄ content in man that could be the site of physiologic regulation or of disease. A method is described whereby analysis of the change in hepatic and plasma radioactivity after tyropanoate could be employed to estimate hepatic T₄ content in diverse clinical circumstances.