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

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.

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.

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).

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.