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. 1977 Sep;60(3):522–534. 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 1, Victor S Fang 1, Adrian I Katz 1, Samuel Refetoff 1
PMCID: PMC372397  PMID: 408377

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.

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Selected References

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