Thyroid Dysfunction in Chronic Renal Failure: <i>A STUDY OF THE PITUITARY-THYROID AXIS AND PERIPHERAL TURNOVER KINETICS OF THYROXINE AND TRIIODOTHYRONINE</i>

Victoria Sy Lim; Victor S. Fang; Adrian I. Katz; Samuel Refetoff

doi:10.1172/JCI108804

Thyroid Dysfunction in Chronic Renal Failure: A STUDY OF THE PITUITARY-THYROID AXIS AND PERIPHERAL TURNOVER KINETICS OF THYROXINE AND TRIIODOTHYRONINE

Victoria Sy Lim, Victor S. Fang, Adrian I. Katz, and Samuel Refetoff

Published September 1, 1977 - More info

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Abstract

Thyroid function was evaluated in 46 patients with end-stage kidney disease and 42 normal subjects. Patients were studied before and after the institution of maintenance hemodialysis (HD) and after renal transplantation (RT). Serum total triiodothyronine concentrations (TT₃, ng/100 ml, mean±SD) were 63±17 and 83±22 in the non-HD and HD groups, respectively. Values from normal subjects were 128±25 and from RT patients 134±20. The TT₃ was in the hypothyroid range (<78 ng/100 ml; 2 SD below normal mean) in 80% of non-HD and 43% of HD patients. Mean serum total thyroxine concentration (TT₄), although within the normal range, was lower than the control value. T₄-binding globulin capacity was also slightly lower but the difference was not statistically significant. Among patients whose TT₄ was 1 SD below the normal mean, the free T₄ index was equally depressed, suggesting that factors other than decreased binding capacity might be responsible for the low TT₄. In addition, there was a 37% incidence of goiter. Mean serum thyroid-stimulating hormone (TSH) was not elevated and the TSH response to thyrotropin-releasing hormone (TRH) was distinctly blunted, suggesting the possibility of pituitary dysfunction as well. In vivo ¹²⁵I-l-T₄ and ¹³¹I-l-T₃ kinetics during 0.2 mg/day of l-T₄ replacement showed marked reduction in T₃ turnover rate in the uremic patients, both before and during HD; the values (μg T₃/day, mean±SD) for the different groups were as follows: normal, 33.8±6.1; non-HD, 13.5±2.6; HD, 12.9±3.1; and RT, 30.3±7.1. The low T₃ turnover rate was due to impaired extrathyroidal conversion of T₄ to T₃. The mean percent±SD of metabolized T₄ converted to T₃ was 37.2±5.8 in normal subjects, 15.7±3.1 in non-HD, 12.8±1.7 in HD, and 34.0±14.7 in RT patients. In contrast, thyroidal T₃ secretion rate was not different between the control and the three patient groups. Thus, it appears that uremia affects thyroid function at several levels: (a) subnormal pituitary TSH response to TRH; (b) possible intrathyroidal abnormalities as suggested by slightly decreased TT₄ and high incidence of goiter; and (c) abnormal peripheral generation of T₃ from T₄. Restoration of renal function with RT resulted in normalization of all parameters of thyroid function with the exception of blunted or absent TSH response to TRH. The latter may be a direct consequence of glucocorticoid administration.