Thyroid function parameters during a selenium repletion depletion study in phenylketonuric subjects

Phenylketonuric (PKU) subjects have a limited supply of selenium (Se) in their phenylalanine-restricted diet. A Se repletion (1 mu g Se/kg/day)/depletion study was conducted in PKU children to determine the effect of Se on thyroid function parameters. The initial plasma Se concentration (mean +/- SD: 0.26+/-0.12 mu mol/L, p < 0.00003, n = 10) and glutathione peroxidase (GSH-Px) activity (140 +/- 58 U/L, p < 0.00003, n = 10) were significantly lower compared to age-matched controls. After 14 weeks of supplementation, the plasma Se concentration (mean +/- SD: 0.74 +/- 0.20 mu mol/L) normalized (normal range: 0.57-1.15 mu mol/L, mean +/- SD: 0.76 +/- 0.13 mu mol/L, n = 32) and remained stable thereafter during repletion. Plasma GSH-Px activity reached normal values after 18 weeks of supplementation (312 +/- 57 U/L; normal range: 238-492 U/L, mean +/- SD: 345 +/- 54 U/L, n = 32) and increased significantly for up to eight weeks thereafter (332 +/- 52 U/L). Individual and mean thyroid parameters were initially normal in all cases. The mean concentrations of plasma thyroxine (T-4: p < 0.025), free T-4 (FT4: p < 0.01) and reverse triiodothyronine (rT(3): p < 0.005) decreased to 75% of their initial value within three weeks of Se supplementation and remained stable thereafter, within a normal physiological range during selenium supplementation. They increased back to their initial values three weeks (T-4: p < 0.05, FT4. p < 0.05) and six weeks (rT(3): p < 0.025) respectively, after the end of the supplementation. In conclusion, Se supplementation modifies thyroid function parameters in Se-deficient PKU subjects most likely by an increase in activity of type I 5'-deiodinase (5'-DIase I).