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

Abstract

BackgroundSubclinical 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.AimTo evaluate the effect of L-T4 therapy on endothelial function as determined by C-IMT in patients with SCH.MethodsBeforeJuly 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.ResultsThree 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).ConclusionThis 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.

Evaluation of a three-month trial of thyroxine replacement in symptomatic subclinical hypothyroidism: An impact on clinical presentation, quality of life and adoption of long-term therapy

“…A double-blind, placebo-controlled study by Monzani et al showed the existence of functional disorder of the left ventricle which was resolved by LT4 treatment (22). After the already mentioned work of Razvi et al who demonstrated the beneficial effect of LT4 on cardiovascular risk factors and endothelial function, recent meta-analysis supports the positive influence of the treatment on the progression of carotid intima-media thickness, possibly by reducing risk factors for its occurrence in SCH (10,23). The limitation of this analysis is a small number of randomized controlled trials with the overall small number of respondents included, indicating that there is still a need for larger interventional studies to confirm those findings.…”

Levothyroxine supplementation for obesity-associated thyroid dysfunction in children: a prospective, randomized, case control study

“…In addition, there are several areas in obesity associated thyroid dysfunction which require further research [4]. For example, it is not fully known if addition of levothyroxine to the weight loss interventions has additional benefits on body composition, energy expenditure, insulin sensitivity, lipid and glucose metabolism, NAFLD as well as other cardiometabolic factors such as blood pressure and cardiac status [4,30]. It is thought that the elevation of TSH in obese children and adolescents might have a negative influence on the cardiac status due to its association with a higher TC and blood pressure [31].…”

The current debate over treatment of subclinical hypothyroidism to prevent cardiovascular complications

“…Also, controversial statements from some studies that “subclinical hypothyroidism is a mild thyroid failure and should be treated”, 65 and from other that “the treatment of subclinical hypothyroidism is seldom necessary”, 66 make the decision to treat or not to treat these patients difficult. At present, because of the lack of long‐term outcomes studies regarding the beneficial or not effects of treatment of patients with SCH we should err on the beneficial aspect of treatment, since treatment of SCH with levothyroxine is simple, cheap and easy to administer, and is also, associated with improvement in BP, lipid changes and decreased incidence of CHD and HF 33,48‐49,51‐53,65‐72 . Overall, treatment of SCH is more beneficial in younger patients, but les beneficial in older patients (≥75 years of age).…”

“…In contrast to the previous studies, there are several other studies that demonstrate a beneficial effect of treatment in patients with SCH 47‐53 . The data from these studies are summarised in Table 3 and they will be, briefly, discussed here.…”

“…In addition to lipid changes, favourable effects of treatment were shown in FMD, IMT, PWV, CRP, ANP and BNP, which could add to the favourable CV effects of lipid changes. The study by Zhao et al, 53 is a review and meta‐analysis of 9 short studies involving 277 patients with SCH mean ages 35.9‐50.0 years on the effects of treatment with levothyroxine on serum lipids, carotid IMD (C‐IMT), FMD and BP. The levothyroxine dose ranged from 25 to 100 μg/d and the duration of treatment was 2‐18 months, which resulted in significant decreases in C‐IMT ( P = .05), SBP ( P < .001), DBP ( P < .001), TC ( P = .02), LDL‐C ( P < .001), TGs ( P = .031), LP(a) ( P < .001) and increase in FMD ( P < .001), but no significant change in BMI, serum glucose, HDL‐C, ApoA, and ApoB.…”