Circulating thyroid hormones in progressive renal failure in the baboon (Papio ursinus)

In order to examine the effects of developing renal failure on circulating thyroid hormones, serum concentrations of thyroxine (T4), free T4 (FT4), triiodothyronine (T3) and reverse T3 (rT3) and TBG capacity were measured in 9 baboons before and during the progress of acute (mean survival 12 days), subacute (32 days) and chronic (120 days) renal failure following allogeneic renal transplantation. Irrespective of the rate of development of renal failure, there were significant, non linear (power functions) negative correlations between serum creatinine or urea concentrations and levels of T4, FT4 and T3; rT3 levels remained unchanged, but the T4: T3 molar ratio fell from 236.5 ± 61 (± SE) to 121.8 ± 30.9 (p 250 μmol/l (2.8 mg/dl), but FT4 was subnormal only in chronic renal failure. Thyroxine binding globulin (TBG) capacity did not change significantly; thus the TBG: T4 ratio increased from 3.4 ± 0.2 (basal) to 10.4 ± 3.4 before death (p 25 days after transplantation, a significant linear correlation between FT4 and T3 was found as uremia progressed. Polyacrylamide gel electrophoresis (pH 7.4) of (125I)-T4 labelled preoperative and uremic serum showed a consistent decline in the proportion of tracer bound to TBG, from 67.0 ± 0.8% to 58.9 ± 1.0% (p < 0.001), with a 48% reduction in TBG saturation (p < 0.02). In contrast, tracer bound thyroxine binding prealbumin (TBPA) increased from 20.8 ± 2.7% to 30.4 ± 2.0% (p < 0.02); albumin-bound tracer did not change. These data suggest that, in the development of uremia: 1)T4 binding to TBG is reduced; 2) T4 binding to TBPA is relatively increased; 3) the peripheral conversion of T4 to T3 is reduced: these disturbances probably occur relatively early in the course of renal failure; 4) rT3 deiodination is impaired; 5) the lower T3 levels may be related to reduced FT4 concentrations.