Inhibition of Hepatic Binding of Thyroxine by Cholecystographic Agents

Abstract

A B S T R A C T 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 T, in man has been examined. After intravenous administration of [1'251]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 extravasctilar 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 ofT4 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 percenit free T4 in the serum as judged by equilibrium dlialvsis, and the ratio of hepatic radioactivity to free I' I]T4 in serum declined markedly after ipodate, similar to the fall in hepatic:serum 1251 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 restults 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.

The effects of amiodarone on thyroid function

“…This does not, however, explain the raised thyroxine levels in our patients on amiodarone, and in the 12 patients described by Pritchard et al (1975). Raised thyroxine levels could be due to inhibition of hepatic uptake of thyroxine as has been observed with radiographic contrast agents (Felicetta, Green and Nelp, 1980). Alternatively, raised thyroxine levels may be due to enzyme inhibition by amiodarone, since the same enzyme is required both for in vitro conversion of thyroxine to tri-iodothyronine and for the completion of the alternative pathway from rT3 to one of its metabolites, di-iodothyronine (Kaplan and Utiger, 1978).…”

The Use of Oral Radiographic Contrast Agents in the Management of Hyperthyroidism

“…Inhibition of secretion leads to a decrease in serum T 4 levels. On the other hand, ORCAs can also impede hepatic uptake of T 4 and displace it from hepatic binding sites, causing a rise in serum T 4 (39). In addition, free T 4 may be elevated due to inhibition of T 4 binding to plasma proteins (40).…”

Clinical associations between thyroid and liver diseases

“…Corticosteroid, propranolol in high doses (> 160 mg/day) and cholecystographic agents [iopanoic acid (telepaque) and ipodate (oragrafim)] could inhibit the hepatic enzymatic monodeiodination of T4 to T3 and result in an increased serum T4 and decreased serum T3.57-59 Cholecystographic agents may even result in a rise in serum TSH secondary to impaired T4 conversion in the pituitary. 59 It is clear, then, that the conventional thyroid tests may be difficult to interpret in the presence of liver disease. Since FT4 and TSH are usually normal in these settings, in general it can be assumed that most patients are euthyroid if they have normal TSH and FT4 levels no matter how remarkable the changes of other thyroid tests are.…”