Blunted peripheral tissue responsiveness to thyroid hormone in uremic patients

Abstract

To understand the biologic significance of the low triiodothyronine (T3) syndrome in patients with chronic renal failure (CRF), we examined thyroid hormone profile, basal O2 uptake (V̇O2), and peripheral blood mononuclear leukocyte (PBL) ouabain binding in these patients and in the control subjects before and after L-triiodothyronine (T3) and sodium ipodate treatment. In the controls (N = 8), T3 administration increased serum total T3 from 136 ± 15 to 232 ± 11 ng/dl, and reduced total thyroxine (T4) from 8.14 ± 0.56 to 6.08 ± 0.43 μg/dl, free T4 from 1.59 ± 0.12 to 1.03 ± 0.05 ng/dl and thyroid-stimulating hormone (TSH) from 1.74 ± 0.24 to 0.41 ± 0.09 μU/ml. V̇O2 increased from 2.66 ± 0.11 to 3.15 ± 0.09 ml/kg/min. Ipodate treatment, on the other hand, resulted in a reduction of serum total T3 to 102 ± 21 ng/dl, an increase in total T4 to 9.59 ± 0.50 μg/dl, free T4 to 1.91 ± 0.13 ng/dl and TSH to 3.64 ± 1.14 μU/ml. V̇O2 decreased to 2.43 ± 0.06 ml/kg/min. P values ranged from <0.05 to <0.001. In the CRF patients N = 14), T3 treatment also resulted in a rise in serum total T3 from 75 ± 5 to 185 ± 8 ng/dl. Total T4 declined from 6.68 ± 0.34 to 5.18 ± 0.48 μg/dl, free T4 from 0.85 ± 0.1 to 0.67 ± 0.08 ng/dl and TSH from 3.67 ± 0.86 to 0.94 ± 0.3 μU/ml. V̇O2, however, did not change (from 2.91 ± 0.12 to 2.99 ± 0.17 ml/kg/min). Ipodate treatment decreased total T3 to 65 ± 5 ng/dl, and increased total T4 to 8.47 ± 0.52 μg/dl, free T4 to 1.19 ± 0.15 ng/dl, and TSH to 9.82 ± 2.57 μU/ml. V̇O2 remained unchanged and was 2.88 ± 0.2 ml/kg/min. P values, comparing before and after treatment data, were not significant for V̇O2, but ranged from <0.05 to <0.001 for thyroid hormones and TSH. PBL ouabain binding were 0.99 ± 0.22, 0.53 ± 0.10, and 0.43 ± 0.05 pmol/107 cells, respectively, in the control (N = 11), CRF (N = 9), and hypothyroid patients (N = 3). T3 treatment failed to correct the ouabain binding deficiency (0.55 ± 0.06 pmole/107 cells) in the CRF patients even though serum TT3 was restored to normal level. The blunted V̇O2 response to T3 and ipodate and the total lack of correlation between serum T3, T4 and V̇O2 in CRF patients suggest that T3 is not the prime regulator of thermogenesis in these individuals. The pituitary, however, remained sensitive as serum TSH was suppressed by T3 and stimulated by ipodate.