Preliminary volume-based optimization of radioactive iodine dose without radioactive iodine uptake in Graves' disease.

Background: Optimal radioactive iodine (RAI) dosing for Graves' disease remains controversial. Conventional calculated regimens require radioactive iodine uptake (RAIU) testing, whereas empiric fixed-dose strategies risk under- or overtreatment. Although activity per gram of thyroid tissue provides an uptake-independent approach, volume-specific minimum effective doses and functional outcomes remain insufficiently defined. This study aimed to determine the minimum RAI activity per gram required to achieve ≥75% remission across stratified thyroid volumes, to identify the activity associated with the highest euthyroid remission, and to evaluate whether dose escalation increases treatment-related adverse events. Methods: This retrospective study included 236 patients with Graves' disease who received initial single-dose RAI therapy between August 2022 and August 2024 at a tertiary center in Thailand. Thyroid volume by ultrasonography was categorized as <25 g, 25-49.9 g, 50-74.9 g, and ≥75 g. Administered activity was grouped as <0.30, 0.30-0.39, 0.40-0.49, 0.50-0.59, and ≥0.60 mCi/g. Outcomes and adverse events were assessed at 6 months. Result: The minimum activity required to achieve ≥75% remission increased with thyroid volume: 0.30-0.39 mCi/g for <25 g glands (90%), 0.40-0.49 mCi/g for 25-49.9 g (77%), and 0.50-0.59 mCi/g for 50-74.9 g (100%). No activity achieved ≥75% remission in glands ≥75 g, with a maximum rate of 45%. Across all volumes, the highest euthyroid rates occurred at the lowest effective activity, whereas dose escalation increased hypothyroidism without improving overall remission. Adverse events were infrequent (5.5-7.6%) and mostly mild. Moderate neck pain was more frequent at higher activities, with a strong positive correlation between administered activity and total adverse events (r = 0.82, p = 0.089). Conclusion: This study demonstrates that volume-stratified radioiodine dosing offers an effective and practical alternative to traditional 24-hour RAIU-based dosimetry for Graves' disease. Adjusting activity according to thyroid volume yields predictable remission while avoiding the logistical burdens of uptake testing. The dose-response relationship also underscores the need to balance efficacy with avoidance of excess toxicity. Overall, this individualized, volume-based strategy provides a scalable and efficient framework for optimizing radioiodine therapy, particularly in resource-limited settings.