Effects of l-thyroxine replacement therapy on serum lipid profiles in patients with mild subclinical hypothyroidism: An open-label, randomized, controlled trial

Background Dyslipidemia is a serious public health problem for its disastrous effects. Subclinical hypothyroidism (SCH), one of the risk factors of dyslipidemia, has attracted the public attention recently. At least 75% of the SCH patients are diagnosed as mild SCH (thyrotropin≤10 mIU/L). However, it is still controversial in the management of mild SCH. It remains a debatable problem whether mild SCH patients could benefit from L-thyroxine replacement therapy on serum lipid profiles. Methods This open-label, randomized, controlled trial was performed in Ningyang County, Shandong Province, China. Mild SCH patients who were diagnosed with twice thyroid function tests were randomly assigned to receive L-thyroxine replacement therapy (25 μg once daily initially, adjusted according to the reevaluation results until thyroid function returned normal) or no treatment for 15 months. The primary outcome was the change in serum total cholesterol (TC) concentrations analyzed in the per-protocol population. Subgroup analyses were also performed in subjects with different thyrotropin or TC concentrations at baseline. This study is registered with ClinicalTrials.gov, number NCT01848171. Results Between July and December 2013, 378 subjects were enrolled and 369 subjects were included in the final analysis (210 in the intervention group and 159 in the control group). With the L-thyroxine replacement therapy, serum TC levels were decreased by 0.41 mmol/L (p<0.001) in the intervention group, while the decline was 0.17 mmol/L (p=0.019) in the control group. The decrease was more obvious in the intervention group than the control group (p=0.012). Subgroup analyses showed that in the subjects with different thyrotropin concentrations at baseline, L-thyroxine resulted in similar decreases of TC levels in each subgroup (all declines were approximately 0.41 mmol/L, p<0.001). In addition, L-thyroxine replacement therapy could also benefit the subjects with different TC concentrations at baseline. Even in the subjects with absolutely normal TC levels (less than 5.18 mmol/L), serum TC concentrations were kept unchanged in the intervention group (p=0.936), while they were increased by 0.35 mmol/Lin the control group (p=0.004). Variation trend for serum lowdensity lipoprotein cholesterol levels was similar with that for serum TC levels. Conclusion Mild SCH patients could benefit from L-thyroxine replacement therapy on serum lipid profiles. Our study might provide reliable and important evidence for evidence-based medicine and help clinicians offer effective treatment advices to the mild SCH patients.