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


METHODS
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.
Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China.
Xiang
http://orcid.org/0000-0003-1625-5748
X
Li
Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China.
Yupeng
Y
Wang
Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China.
Qingbo
Q
Guan
Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China.
Jiajun
J
Zhao
Scientific Center, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China.
Ling
L
Gao
D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D050171:Dyslipidemias / Q000188:drug therapy*; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D013974:Thyroxine / Q000494:pharmacology / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D013974:Thyroxine
hypothyroidism; meta-analysis; systematic review; thyroxine