A kinetic model of human thyroid hormones and their conversion products

We have examined the in vivo distribution and metabolism of radiolabeled T4 and T3 in 14 normal subjects using a kinetic model. Tracer amounts of [131I]T4 and [125I]T3 were injected simultaneously, and plasma samples were obtained for up to 7 days thereafter. Separation of these samples by thin layer chromatography yielded kinetic curves for 131I- and 125I-labeled T4, T3, iodide, and iodoprotein, which were then used to develop a kinetic model. The model includes several features. 1) Submodels were developed for T4, T3, iodide, and iodoprotein which simultaneously fit the observed data. 2) Two other submodels were needed for data fit, the first representing rT3, the other representing other intermediates, including the various diiodothyronines. The latter submodel was patterned initially after 3,3'-diiodothyronine kinetics. It was required to account for the delay in appearance of labeled iodide produced from the degradation of T4, and rT3 and proved to be essential for the successful fit of the data. 3) The model accounts for the conversion of T4 to T3 and rT3. Even though rT3 is quantitatively significant as a degradation pathway for T4, its presence does not contribute significantly to total plasma radioactivity after T4 administration because of its rapid turnover in comparison with T4. 4) The small amount of iodoprotein formed is a major contributor to total plasma radioactivity within 3 days after T3 administration. 5) The model permits the elimination of two methodological errors: that due to the presence of labeled iodide, T3, or T4 contaminants in the administered labeled hormones, and that due to the small amount of cross-over between thin layer chromatography peaks. The model provides a concise description of our current understanding of thyroid hormone metabolism and suggests areas where further information is required.