Establishing the Adequate Levothyroxine Dose After Total Thyroidectomy: A Systematic Review With Meta-analysis

Background: Total thyroidectomy requires lifelong levothyroxine (LT4) therapy. Achieving optimal thyroid hormone replacement at the first postoperative follow-up might be harder than expected. Despite the various LT4 dose-choosing strategies tested, there is no consensus on the most effective approach to achieve early euthyroidism. Materials and Methods: We performed a systematic review and meta-analysis, including studies published between 2000 and 2024 that reported the proportion of patients achieving euthyroidism at first follow-up after total thyroidectomy. Data from 11 studies comprising 2577 patients were analyzed. LT4 dosing strategies included fixed-dose, weight-based (dose/kg), and individualized algorithm-based methods. Meta-regression and subgroup analyses were used to explore sources of heterogeneity. Results: The pooled euthyroidism rate at first follow-up was 33.9%, with high heterogeneity across studies (I2 = 82.68%). No dosing strategy consistently outperformed others: dose/kg methods achieved 29% euthyroidism, while fixed or algorithm-based approaches achieved 40%, though without statistical significance. Meta-regression analysis did not identify any statistically significant predictor. No significant differences emerged between patients treated for benign or malignant thyroid diseases or between retrospective and prospective study designs. Conclusion: Only about one-third of patients achieve euthyroidism at first follow-up after thyroidectomy, regardless of LT4 dosing strategy. The current guidelines recommendation of applying a pro/kg dose may not be adequate, and even personalized algorithms yield inconsistent results. Future prospective studies are needed to refine individualized dosing protocols and identify additional factors influencing LT4 requirements.