Thyroxine and triiodothyronine distribution and metabolism in thyroxine-replaced athyreotic dogs and normal humans.

Abstract

Reported parenteral L-thyroxine (T4) replacement doses (10-20 micrograms.kg-1 x day-1) are larger than T4 production rates (2.5 micrograms.kg-1 x day-1) in athyreotic dogs but not humans. Furthermore, initial volumes of 3,5,3'-triiodothyronine (T3) tracer distribution exceed those for T4 in both species. To evaluate these discrepancies, serum T4 and T3 tracer kinetic studies from T4-replaced athyreotic dogs (5 micrograms.kg-1 x day-1 sc) and euthyroid humans were analyzed in a three-pool model (rapidly and slowly equilibrating pools with serum). Dogs had lower total T4 (41%) and T3 (31%) and higher free fractions of T4 (432%) and T3 (456%) than humans. Initial T3 distribution volumes were 454% those for T4 in dogs and 149% in humans, 498% of predicted plasma volumes in dogs and 121-138% in humans. Thus plasma volumes were used as time 0 estimates for T3 data analysis. Dogs had higher fractional T4 and T3 transfer rates from serum to the rapid pools (440-451%), total T4 clearance (353%) and production rates (147%), similar total T3 clearance, but lower free T3 clearance (32%) and production rates (45%) than humans. These findings suggest: 1) higher fractional transfer rates of T4 and T3 from serum to tissues and total serum T4 clearance rates in dogs than humans relate to lower canine serum T4 and T3 binding, and 2) parenteral L-T4 replacement doses required to achieve upper-normal serum total T4 concentrations in athyreotic dogs (5 micrograms.kg-1 x day-1) correspond to T4 production rates (6.8 micrograms.kg-1 x day-1).