Handling of iodothyronines by the liver and kidney in patients with chronic liver disease A. G. C. Bauer, J. H. P. Wilson, S. W. J. Lamberts, R. Docter, G. Hennemann and T. J. Visser Department of Internal Medicine, Erasmus University Medical School, Rotterdam, The Netherlands Abstract. Possible arterio-venous gradients of T4, T3, rT3 and 3,3'-diiodothyronine (3,3'-T2) across the liver and the kidneys were measured in 9 patients with varying degrees of liver failure undergoing diagnostic catheterization. Plasma iodothyronine levels were meas- ured in peripheral, hepatic and renal veins before and at 10-min intervals until 60 min after iv injection of 400 \ of TRH. In 2 patients estimated hepatic plasma flow and effective renal plasma flow were determined as well. In these 2 patients, no significant differences between iodothyronine levels in arterial and peripheral venous plasma were found. T4 and T3 levels were not significantly different between peripheral, renal and hepatic veins. Hepatic vein rT3 and 3,3'-T2 concentra- tions were 10.7 \m=+-\8.3% (mean \m=+-\ SD, P < 0.005) and 36 \m=+-\18% (P < 0.001) lower than those in the peripheral vein (N = 9). Renal vein rT3 was just (6.2 \m=+-\7.5%, P < 0.05) lower than rT3 in peripheral vein, whereas 3,3'-T2 was not different between the two veins. Esti- mates of hepatic and renal plasma flow were in agree- ment with values from the literature. On the basis of these data approximate hepatic clearance rates of 110 and 380 1/day for rT3 and 3,3'-T2 and a renal clearance rate of about 35 1/day for rT3 were calculated. Sixty min after TRH, plasma T3 was increased to 147 \m=+-\56% (P < 0.05) and 3,3'-T2 in peripheral plasma was in- creased to 142 \m=+-\36% (P < 0.025), whereas plasma T4 and rT3 did not change. These data suggest that the liver is the major site of plasma rT3 and 3,3'-T2 clear- ance in patients with mild liver disease and probably also in healthy humans. The kidneys may account for roughly 25% of plasma rT3 clearance. The increase in plasma 3,3'-T2 after TRH may be secondary to the rise in precursor T3, but thyroidal secretion of 3,3'-T2 is not excluded. It is generally believed that T4 is the main secre¬ tory product of the thyroid, and that other iodo¬ thyronines are produced predominantly by se¬ quential deiodination of T4 in peripheral tissues (Engler & Burger 1984; Hennemann 1986). By phenolic or outer ring deiodination T4 is con¬ verted to T3, whereas rT3 is generated by tyrosyl or inner ring deiodination of T4. Both T3 and rT3 are subject to further deiodination to 3,3'-diiodo- thyronine (3,3'-T2). Of all iodothyronines only T3 has significant intrinsic bioactivity. Recent studies in rats have demonstrated at least three different types of iodothyronine-de- iodinating enzymes (Kaplan 1984; Hesch & Koehrle 1986; Leonard & Visser 1986). The type I deiodinase is most abundant in the liver, kidney and thyroid and is inhibited by propylthiouracil (PTU). Type I deiodination of T4 in the liver and kidney is a major pathway of peripheral T3 pro¬ duction in normal rats (Silva et al. 1984). How¬ ever, the type I deiodinase is much more active in the outer ring deiodination of rT3, while studies in rat liver have demonstrated that the same enzyme is also capable of inner ring deiodination (Leonard & Visser 1986). The properties of the type I deiodinase of human liver are very similar to the enzyme of rat liver. Type II deiodinase activity has been detected in rat brain, pituitary and brown adipose tissue and in rat and human placenta (Kaplan 1984; Leonard & Visser 1986). It deiodinates only the outer ring of iodothyroni¬ nes and is not inhibited by PTU. Iodothyronine Downloaded from Bioscientifica.com at 10/24/2018 04:13:00AM via free access