Multicompartmental analysis of triiodothyronine kinetics in hypothyroid patients treated orally or intravenously with triiodothyronine.

Kinetic studies were performed with iv I-125 T-3 in, four athyreotic women on two occasions each, once while they were taking oral T-3 (30 mu g T-3 every 12 h) and again while on iv T-3 replacement (same dosage schedule). The kinetic data were analyzed by a 7-compartment model, representing the plasma volume, the fast and slow peripheral exchange compartments, the iodide pool (as a delay compartment prior to appearance in the urine), the intestine (as a delay compartment before appearance in the feces), and the urine and feces. Modeling was done by the SAAM methodology. All data sets, and also the mean data treated as though they were data from a single subject, were fitted for the two limit solutions in which all metabolism was assumed to be in one or the other of the exchange compartments. The mean data set was also fitted to a solution in which limits were imposed on the excretion parameters and the partition of metabolism between the 2 peripheral exchange compartments was estimated. We found that steady-state parameters for removal of T-3 from the circulation (the MCRs and DRs) were increased during the iv T-3 replacement period compared with the oral replacement period, especially in the fast exchange compartment. Measured serum stable T-3 levels (RIA) were lower in the iv than in the oral study, both at 8 and at 12 h after the most recent T-3 dose. These values corresponded to similar differences in the circulating T-3 levels projected from the model, although the T-3 values projected from the model were greater than the measured T-3 levels for unknown reasons. Immediately after the iv dose, serum T-3 peaked at markedly supraphysiological levels. Serum TSH levels in serum collected 12 h after the most recent T-3 dose were higher during the iv study than the oral study in 3 of the 4 subjects (NS). It would appear from these findings that the intermittent high peak T-3 levels after each iv T-3 dose are responsible for the increases in the exchange and disposal kinetics of T-3 during the iv study. On the other hand, TSH may be stimulated by the periods of decreased ciculating T-3 levels during the intervals between doses.