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.