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

Reported parenteral L-thyroxine (T₄) replacement doses (10-20 μg · kg^{- 1} · day^-1) are larger than T₄ production rates (2.5 μg · kg^-1 · 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 μg · kg^-1 · 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 μg · kg^-1 · day^-1) correspond to T₄ production rates (6.8 μg · kg^-1 · day^-1).