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 w omen on two occasions each, once while they were taking oral T-3 (30 m u 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, r epresenting the plasma volume, the fast and slow peripheral exchange c ompartments, the iodide pool (as a delay compartment prior to appearan ce in the urine), the intestine (as a delay compartment before appeara nce in the feces), and the urine and feces. Modeling was done by the S AAM methodology. All data sets, and also the mean data treated as thou gh 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 oth er of the exchange compartments. The mean data set was also fitted to a solution in which limits were imposed on the excretion parameters an d the partition of metabolism between the 2 peripheral exchange compar tments was estimated. We found that steady-state parameters for remova l of T-3 from the circulation (the MCRs and DRs) were increased during the iv T-3 replacement period compared with the oral replacement peri od, 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 correspond ed to similar differences in the circulating T-3 levels projected from the model, although the T-3 values projected from the model were grea ter than the measured T-3 levels for unknown reasons. Immediately afte r 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 do se were higher during the iv study than the oral study in 3 of the 4 s ubjects (NS). It would appear from these findings that the intermitten t 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 s tudy. On the other hand, TSH may be stimulated by the periods of decre ased ciculating T-3 levels during the intervals between doses.