Clinical and biochemical implications of low thyroid hormone levels (total and free forms) in euthyroid patients with chronic kidney disease

doi:10.1111/j.1365-2796.2007.01865.x

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Wiley InterScience

Journal of Internal Medicine

Volume 262 Issue 6, Pages 690 - 701

Published Online: 1 Oct 2007

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Original Article

Clinical and biochemical implications of low thyroid hormone levels (total and free forms) in euthyroid patients with chronic kidney disease

J. J. Carrero ¹ , A. R. Qureshi ¹ , J. Axelsson ¹ , M. I. Yilmaz ¹ , S. Rehnmark ² , M. R. Witt ² , P. Bárány ¹ , O. Heimbürger ¹ , M. E. Suliman ¹ , A. Alvestrand ¹ , B. Lindholm ¹ & P. Stenvinkel ¹

From the ¹Divisions of Renal Medicine and Baxter Novum; Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden, ²Karo Bio AB, Novum, Huddinge, Sweden

Correspondence to Peter Stenvinkel, Division of Renal Medicine, K56, Karolinska University Hospital at Huddinge, 141 86 Stockholm, Sweden.
(fax: +46 8 7114742; e-mail: peter.stenvinkel@ki.se).

KEYWORDS

chronic kidney disease • inflammation • mortality • Triiodothyronine • wasting

Carrero JJ, Qureshi AR, Axelsson J, Yilmaz MI, Rehnmark S, Witt MR, Bárány P, Heimbürger O, Suliman ME, Alvestrand A, Lindholm B, Stenvinkel P (Karolinska Institutet, Stockholm; and Karo Bio AB, Novum, Huddinge; Sweden). Clinical and biochemical implications of low thyroid hormone levels (total and free forms) in euthyroid patients with chronic kidney disease. J Intern Med 2007; 262: 690–701.

ABSTRACT

Abstract.

Objectives. In this study, we explore the associations of decreased thyroid hormone levels with inflammation, wasting and survival in biochemically euthyroid patients with end-stage renal disease (ESRD).

Design. After exclusion of 23 patients with thyroid-stimulating hormone (TSH) values outside the normal range (0.1–4.5 mIU L⁻¹), 187 clinically and biochemically euthyroid incident ESRD stage 5 patients starting dialysis were followed for a median of 20 (range 1–60) months. Measurements of total and free forms of thyroid hormones, s-albumin, hs-CRP, interleukin (IL)-6, vascular adhesion molecule (VCAM)-1 and insulin-like growth factor 1 (IGF-1) were performed at baseline.

Results. In this population, 17 out of 210 patients (8%) were defined as subclinically hypothyroid. Multivariate analysis, according to receiver operating characteristic (ROC) curves, showed that mortality was best predicted by total triiodothyronine (T3). When using the cut-off levels derived from ROC, low T3 levels were associated with increased inflammation (higher hs-CRP, IL-6 and VCAM-1) and lower concentration of both s-albumin and IGF-1. Finally, low T3 but not low free triiodothyronine was associated with worse all-cause (Likelihood ratio = 45.4; P < 0.0001) and cardiovascular mortality (Likelihood ratio = 47.8; P < 0.0001) after adjustment for confounding factors.

Conclusion. This study showed that low T3 levels are independent predictors of all-cause and also cardiovascular disease mortality in biochemically euthyroid patients, perhaps due to an intimate association with inflammation. Based on these results, the use of T3 levels in studies assessing the relationship between thyroid dysfunction and mortality risk is recommended.

DIGITAL OBJECT IDENTIFIER (DOI)

10.1111/j.1365-2796.2007.01865.x About DOI