The lipid-lowering effect of levothyroxine in patients with subclinical hypothyroidism: A systematic review and meta-analysis of randomized controlled trials

Objectives: Dyslipidaemia is common in patients with subclinical hypothyroidism (SCH). To date, there is no universal agreement regarding the lipid-lowering effect of substitution treatment with L-T4 in patients with SCH. We aimed to clarify the effect by conducting this systematic review and meta-analysis of randomized controlled trials (RCTs).

Design: We systematically searched PubMed, the Cochrane Library, ClinicalTrials.gov and EMBASE for RCTs comparing substitution treatment to placebo treatment or observation. We focused on the primary outcomes of changes from baseline of total, low-density lipoprotein and high-density lipoprotein cholesterol (TC, LDL-C and HLD-C) and triglycerides. Subgroup analyses were performed, assessing the effect of treatment duration, disease severity and ethnicity on the occurrence of discrepancy.

Results: Twelve trials, with 940 participants, were eligible for analysis. Compared with the control group, levothyroxine substitution yielded a mean reduction in TC (-0.29 mmol/L, [-0.42 to -0.16]) and LDL-C (-0.22 mmol/L, [-0.36 to -0.09]), with no significant effects on HDL-C (-0.04 mmol/L, [-0.08 to 0.01]) or triglycerides (-0.04 mmol/L, [-0.08 to 0.00]). Trials in which only patients with mild SCH (thyrotropin <10 mIU/L) were enrolled showed equivalent effects. The lowering effects were weaker, but still significant, in long-term treatment (>6 months) compared with short-term treatment (≤6 months) for TC (-0.19 mmol/L [-0.35, -0.03] vs -0.50 mmol/L [-0.68, -0.31], P=.047) and LDL-C (-0.09 mmol/L [-0.16, -0.02] vs -0.46 mmol/L [-0.68, -0.25], P=.006).

Conclusions: Levothyroxine treatment has clear benefits on TC and LDL-C in SCH patients, including those with mild SCH.