Daily Versus Weekly Levothyroxine Tablet Replacement in Adults With Hypothyroidism: A Meta-Analysis

Abstract

Abstract Background and Objectives: Hypothyroidism is a common hormone deficiency with a prevalence ranging from 4-5% worldwide. It is a very treatable condition with treatment in the form of thyroid hormone replacement, with an overall excellent prognosis if patients are compliant to regular treatment. Daily levothyroxine (LT4) is the treatment of choice and standard of care, sufficient to restore the thyroid stimulating hormone (TSH) to the normal range. For many patients, daily and lifelong therapy is required, and compliance/adherence then becomes a major issue. In such cases, weekly replacement may be a suitable alternative in terms of improving patient compliance. In this study, we aimed to determine the efficacy and safety of weekly versus daily levothyroxine replacement in patients with hypothyroidism. Methods: Electronic databases were searched, supplemented with manual searches. Two reviewers independently screened the abstracts, reviewed full-text papers, independently critically appraised the quality of included studies and abstracted the data. A meta-analysis was performed using the random-effects model on randomized controlled trials (RCTs) that reported standard doses of daily versus weekly levothyroxine administration in the treatment of hypothyroidism. The primary outcome is the difference in serum TSH levels between daily versus weekly levothyroxine administration, while secondary outcomes included clinical symptoms and adverse events using the hypothyroidism symptom scale. Results: The study included two randomized trials (N = 109) in the primary analysis. The difference in TSH levels was 1.78 mIU/mL higher (95% CI: 1.28, 2.28; P < 0.00001) at 6 weeks and 1.22 mIU/mL higher (95% CI: 0.76,1.67; P < 0.00001) at 12 weeks for the weekly replacement regimen, respectively. There was no significant heterogeneity noted between the two groups. There was no significant difference in terms hyperthyroid symptoms and adverse events measured by the hypothyroid symptom scales and echocardiographic parameters, respectively, before and after LT4 within each group. Conclusions: Our results showed that weekly LT4 administration has less suppression of TSH levels, while still remaining within the reference range of normal. It may be an alternative for patients especially in setting of noncompliance. However, more randomized trials with larger sample sizes and a longer duration of follow-up are needed to firmly establish the definite role of weekly LT4.