Multicompartmental Analysis of Triiodothyronine Kinetics in Hypothyroid Patients Treated Orally or Intravenously with Triiodothyronine

Abstract

Kinetic studies were performed with iv ^l25I T₃ in four athyreotic women on two occasions each, once while they were taking oral T₃ (30 μg T₃ every 12 h) and again while on iv T₃ 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 T₃ from the circulation (the MCRs and DRs) were increased during the iv T₃ replacement period compared with the oral replacement period, especially in the fast exchange compartment. Measured serum stable T₃ levels (RIA) were lower in the iv than in the oral study, both at 8 and at 12 h after the most recent T³ dose. These values corresponded to similar differences in the circulating T₃ levels projected from the model, although the T₃ values projected from the model were greater than the measured T₃ levels for unknown reasons. Immediately after the iv dose, serum T₃ peaked at markedly supraphysiological levels. Serum TSH levels in serum collected 12 h after the most recent T₃ 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 T₃ levels after each iv T₃ dose are responsible for the increases in the exchange and disposal kinetics of T₃ during the iv study. On the other hand, TSH may be stimulated by the periods of decreased circulating T₃ levels during the intervals between doses.