Effect of levothyroxine on the progression of carotid intima-media thickness in subclinical hypothyroidism patients: a meta-analysis

BMJ Open. 2017 Oct 22;7(10):e016053. doi: 10.1136/bmjopen-2017-016053.

Abstract

Background: Subclinical hypothyroidism (SCH) has been associated with increased carotid intima-media thickness (C-IMT) in recent studies, but the effects of levothyroxine (L-T4) therapy on C-IMT in SCH patients are still controversial.

Aim: To evaluate the effect of L-T4 therapy on endothelial function as determined by C-IMT in patients with SCH.

Methods: BeforeJuly 2016, we searched the PubMed, Embase, Cochrane Library and Google Scholar databases, selecting published randomised controlled trials (RCTs) and self-controlled trials for the meta-analysis.

Results: Three RCTs with 117 patients were considered appropriate for the meta-analysis. The results of the meta-analysis indicated that L-T4 significantly decreased the development of C-IMT (weighted mean difference (WMD) -0.05 mm, 95% CI -0.08 to -0.01 mm; p=0.025). We also analysed nine studies (self-controlled trials) with 247 patients and extracted the IMT of SCH patients before and after L-T4 treatment. After L-T4 therapy, the pooled estimate of the WMD of decreased C-IMT was -0.04 mm (95% CI -0.07 to -0.02 mm; p=0.05). Subgroup analysis showed that L-T4 therapy was associated with a decrease in C-IMT among patients of mixed genders (WMD -0.03 mm, 95% CI -0.06 to -0.01 mm; p=0.145). L-T4 therapy was associated with a decrease in C-IMT among female patients (WMD -0.07 mm, 95% CI -0.14 to -0.01; p=0.186). Longer treatment (>6 months) also resulted in a significant decrease in C-IMT (WMD -0.05 mm, 95% CI -0.08 to -0.02; p=0.335).

Conclusion: This meta-analysis indicates that L-T4 treatment of SCH patients can reduce C-IMT, possibly as a result of the reduction of total cholesterol, triglyceride, low density lipoprotein, systolic blood pressure, diastolic blood pressure, lipoprotein(a), and flow-mediated dilatation. Decreased C-IMT was observed in SCH patients after long-term (>6 months) L-T4 treatment. RCTs with larger samples are needed to verify these observations.

Keywords: cardiovascular risk; carotid intima-media thickness; subclinical hypothyroidism; thyroxin.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Blood Pressure / drug effects
  • Carotid Intima-Media Thickness*
  • Humans
  • Hyperlipidemias / blood
  • Hyperlipidemias / complications
  • Hypertension / complications*
  • Hypothyroidism / drug therapy*
  • Randomized Controlled Trials as Topic
  • Thyroxine / therapeutic use*
  • Triglycerides / blood

Substances

  • Triglycerides
  • Thyroxine