Efficacy and Safety of Once Weekly Thyroxine as Compared to Daily Thyroxine in Managing Primary Hypothyroidism: A Systematic Review and Meta-Analysis

AIMS: No meta-analysis is available which has holistically analyzed efficacy and safety of once weekly thyroxine (OWT) vs. standard daily therapy (SDT) with regards to managing primary hypothyroidism. We undertook this meta-analysis to address this knowledge gap. METHODS: Electronic databases were searched for clinical trials involving hypothyroid patients receiving OWT in intervention arm, and SDT in control arm. Primary outcome was to evaluate changes in serum thyroid stimulating hormone. Secondary outcomes were to evaluate alterations in total tetra-iodothyronine (TT4), total tri-iodothyronine (TT3), free T4 (FT4), free T3 (FT4), heart rate (HR), cardiac function, symptomatology, and adverse events. RESULTS: From initially screened 159 studies, data from four trials involving 294 patients were analyzed. Patients of OWT had significantly higher thyroid stimulating hormone (TSH) [mean difference (MD) +1.85 mU/L (95% confidence interval, CI: 0.95–2.75); P < 0.01; I(2) = 63%], comparable TT4 [MD -0.87 mcg/dl (95% CI: -2.98–1.24); P = 0.42; I(2) = 65%], and significantly lower TT3 [MD -15.7 ng/dl (95% CI: -29.9–1.51); P = 0.03; I(2) = 90%], following 6-weeks therapy. TT4 [MD 3.05 mcg/dl (95% CI: 1.44–4.66); P < 0.01], and FT4 [MD 0.56 ng/dl (95% CI: 0.04–1.08); P = 0.03; I(2) = 66%] were significantly higher 2 h after thyroxine intake, in people on OWT compared to SDT. TT4 levels were significantly higher 4 h after thyroxine intake in OWT as compared to SDT [MD 0.70 ng/dl (95% CI: 0.52–0.88); P < 0.01]. Following 4–8 h of intake of thyroxine, isovolumetric contraction time [MD 3.62 ms (95% CI: 1.93–5.31); P < 0.01; I(2) = 0%] and aortic ejection time/pre-ejection period ratio [MD 0.01 (95% CI: 0.00–0.02); P = 0.02; I(2) = 0%], were significantly higher in people on OWT as compared to SDT. CONCLUSION: OWT is associated with less efficient control of hypothyroidism at 6 weeks and may be associated with supraphysiologic elevation of thyroid hormone levels along with transient echocardiographic changes in some patients following 2-4 h of thyroxine intake.