Serum Reverse Triiodothyronine and Thyroxine Kinetics in Patients with Chronic Renal Failure*

Abstract

Patients with chronic renal failure (CRF) have reduced serum total T3 (TT3) but normal total rT3 (TrT3) concentrations. These findings contrast with those of nonrenal nonthyroidal illnesses and malnutrition where low TT3 levels are associated with elevated TrT3 values. To evaluate the mechanisms for the normal TrT3 concentrations in CRF patients, iv bolus serum kinetic studies of labeled rT3 were carried out in 13 CRF and 8 normal subjects. In addition, T4 kinetics were studied in 7 CRF and 20 normal individuals. The CRF patients had normal or minimally reduced serum albumin [3.8 ± 0.2 (SE) g/dl] and transferrin (281 ± 17 mg/dl) levels and normal relative BW (95 ± 4%) and body mass index (23.0 ± 0.9 kg/m2) values, indicating adequate protein nutritional status. The mean serum TT3 levels were decreased to 62% of the normal mean (P < 0.001). There were significant increases in the mean values of the percent free fraction of rT3 (135% of normal mean, P < 0.001), free rT3 (131%, P < 0.001) and T4 binding globulin (TBG) (131%, P < 0.001) concentrations. The total and free serum T4 and percent free fraction values of T4 were normal, whereas the TT4/TBG ratio was reduced (75%, P < 0.025). Noncompartmental analysis of the rT3 kinetic data indicated that the apparent serum production and serum MCR of rT3 were normal in the CRF patients. The apparent total volume of distribution was increased to 242% of the normal mean (P < 0.001), the hormone pool to 232% (P < 0.005), the extravascular binding to 192% (P < 0.005), and the fractional rate of rT3 exit from serum (Kii) was increased to 235% (P < 0.005). The increase in Kii was greater than the increment in the free fraction of rT3 suggesting increased permeability of the hypothetical membrane enclosing the tissue space. The residence time was prolonged (258%, P < 0.001) despite reduced serum binding and the free or cellular rT3 clearance rate was reduced to 65% of the normal mean (P < 0.02) indicating decreased tissue degradation of rT3. The T4 kinetics showed normal serum production, MCR, residence time, total volume of distribution and pool size, and decreased Kii (48% of the normal mean, P < 0.005). The latter in association with a normal free fraction of T4 suggests the presence of impaired T4 transport out of serum. The alterations of rT3 and T4 metabolism in CRF can be accounted for by 1) decreased serum rT3 and T4 binding to TBG, 2) increased rT3 and reduced T4 transport out of serum due to factors in addition to reduced hormone binding to serum carrier proteins, 3) increased extravascular binding of rT3, and 4) impaired 5′-deiodination of T4 and rT3. The changes in T4 metabolism resemble those found in patients with nonrenal nonthyroidal illnesses. The increased fractional rate of rT3 exit from serum in CRF contrasts with the decrease found in nonrenal nonthyroidal disorders. A shift of rT3 from vascular to extravascular sites may account for the normal serum MCR and total serum rT3 concentrations observed in patients with CRF. These differences are probably related to the metabolic consequences or uremia.