Effects of L-thyroxine treatment on early markers of atherosclerotic disease in children with subclinical hypothyroidism

Abstract

Objective: To investigate the effect of levothyroxine (L-T4) treatment on early markers of atherosclerotic disease in children with mild idiopathic subclinical hypothyroidism (SH). Design: Two-year, open, case-control prospective study. Methods: A total of 39 children, aged 9.18 ± 3.56 years, with SH and 39 healthy controls were enrolled in the study. Waist-to-height ratio (WHtR), blood pressure, triglycerides, total cholesterol (total-C), HDL-C, LDL-C, non-HDL-C, triglycerides/HDL-C, atherogenic index (AI), homocysteine (Hcy), asymmetric dimethylarginine (ADMA), flow-mediated dilation (FMD) and intima-media thickness (IMT) were evaluated at baseline and after 2 years of L-T4 treatment in SH children and after 2 years of follow-up in controls. Results: At study entry WHtR was higher in SH subjects compared with controls (0.56 ± 0.08 vs 0.49 ± 0.07, P = 0.04) and significantly decreased after 2 years of treatment (0.50 ± 0.06, P < 0.0001). Mean HDL-C levels (50.47 ± 11.43 vs 61.06 ± 13.83 mg/dL, P = 0.002) were lower, while triglycerides/HDL-C (1.63 ± 1.07 vs 1.19 ± 0.69, P = 0.05), AI (3.32 ± 0.90 vs 2.78 ± 0.68, P = 0.005), and Hcy (9.35 ± 2.61 vs 7.71 ± 1.94 μmol/L, P = 0.01) were higher in SH subjects compared with controls and improved after 2 years of treatment (HDL-C 56.26 ± 13.76 mg/dL, P < 0.0001; triglycerides/HDL-C 1.23 ± 0.78, P = 0.006; AI 2.82 ± 0.68, P < 0.0001; and Hcy 8.25 ± 2.09 μmol/L, P = 0.06). ADMA concentrations at baseline were higher in SH subjects compared with controls (0.77 ± 0.21 vs 0.60 ± 0.16 μmol/L, P = 0.001) and decreased after therapy (0.58 ± 0.13 μmol/L, P < 0.0001). FMD, IMT and other metabolic parameters were not different among SH subjects and controls at baseline and after 2 years. Conclusions: Children with SH may have subtle pro-atherogenic abnormalities. Although L-T4 treatment exerts some beneficial effects, the long-term impact of therapy on metabolic outcomes in SH children still remains unclear.