Exp Clin Endocrinol Diabetes 2014; 122 - P146
DOI: 10.1055/s-0034-1372163

Role of 3,5-diiodothyronine in chronic kidney disease

I Lehmphul 1, J Anselmo 2, J Koehrle 1
  • 1Charité-Universitätsmedizin Berlin, Institut für Experimentelle Endokrinologie, Berlin, Germany
  • 2Hopital Divino Espiríto Santo, Unit of Endocrinology, Ponta Delgada, Portugal

Introduction: Kidney is not only a target for thyroid hormone (TH) action, but also significantly contributes to TH storage, metabolism & elimination. The nephrotic syndrome is associated with urinary protein loss, including TH binding proteins. Uremic patients exhibit low T3 syndrome, described by low circulating T3 levels in combination with normal reverse T3 (rT3) & thyroxine (T4). As 3,5-diiodothyronine (3,5-T2) has been postulated to be formed from T3 by 5'-deiodination we tested, whether patients on dialysis exhibit increased 3,5-T2 concentrations in the circulation and to what extent this may contribute to their pathophysiological outcome.

Methods: We analysed 61 patients (19 – 84 years; 38 male, 23 female; 2 – 19 years on dialysis) with mixed diagnostic background (17 hypertensive nephroangiosclerosis; 14 diabetic nephropathy; 15 with other illnesses; 13 with unknown diagnosis). The control population (n = 6) doesn't receive dialysis. Free T3, free T4 & TSH were routinely measured. We used a newly developed monoclonal antibody based immunoassay to measure 3,5-T2 in the sera of all patients on dialysis & the control group.

Results: Patients on dialysis showed a significant decrease in serum free T3 (2.0 ± 0.1 vs. 3.4 ± 0.1 ng/l; P < 0.0001; reference range 2.3 – 4.2 ng/l) & serum free T4 (0.9 ± 0.02 vs. 1.2 ± 0.1 ng/l; P < 0.0001, reference range 0.9 – 1.8 ng/l; mean ± SE). 3,5-T2 serum concentrations are significantly increased in patients on dialysis with respect to the control group (1.5 ± 0.1 nM vs. 0.4 ± 0.04 nM; P < 0.0004).

Conclusion: We conclude that in patients on dialysis not only uremia contributes to low circulating free THs. We propose that TH metabolism to 3,5-T2 is enhanced, thereby contributing to the manifestation of the low T3 syndrome. In comparison to rT3 3,5-T2 is metabolically active especially on mitochondrial function and may contribute to renal metabolic homeostasis in the pathophysiology of chronic kidney disease.

Supported by DFG GK 1208 – 2 TP3 (J.K.)