Disposal and distribution of rT3 in humans: a new double-tracer kinetic study

A satisfactory definition of reverse 3,3',5'-triiodothyronine (rT3) kinetics in humans cannot be obtained if the plasma disappearance curve of the injected labeled hormone is the only experimental data available; most of the kinetic parameters can only be bounded within ranges showing unacceptable variabilities. To gain additional experimental data a double-tracer approach is proposed. After simultaneous injection of [125I]rT3 and 131I the following three experimental curves were determined in plasma: 1) the disappearance of [125I]rT3, 2) the disappearance of 131I, and 3) the appearance of 125I generated in vivo from labeled rT3 degradation. Combined analysis of these three curves, based on a complex six-compartment model, was developed and applied to data obtained in a group of normal subjects. Through this new analysis, fractional disposal rates and fractional exchange rates between the plasma compartment and the periphery are uniquely determined. The main physiologically interesting information on the degradation of the hormone that emerges from these studies are 1) all degradative pathways of rT3 generate iodide, being in all cases the [125I]rT3 dose completely recovered as 125I in plasma; and 2) most rT3 is degraded (65-90%) in peripheral tissues rapidly exchanging with the plasma pool. The extended experimental base is not yet sufficient to compute unique values for production rate (PR) and body mass (Qt); the validity of estimates of PR and Qt is based on the assumption that injected [125I]rT3 is able to trace all rT3 peripherally produced (from thyroxine). The new approach yields ranges for PR and Qt (1.12-2.15 micrograms/h and 2.88-8.24 micrograms) much narrower than those computable from the [125I]rT3 disappearance curve only (1.12-5.07 micrograms/h for PR and 2.88-23.7 micrograms for Qt).