Thyroglobulin Cutoffs after Total Thyroidectomy Without Radioiodine in Low- to Intermediate-Risk Thyroid Cancer: A Multicenter Cohort Study

<b><i>Background</i>:</b> The prognostic value of unstimulated serum thyroglobulin (Tg) levels for structural recurrence in patients with low- to intermediate-risk differentiated thyroid cancer (DTC) who underwent total thyroidectomy but did not receive radioactive iodine (RAI) therapy remains unclear. This study aimed to determine Tg cutoff values and evaluate the role of dynamic Tg monitoring in risk stratification in these patients. <b><i>Methods:</i></b> We retrospectively analyzed 9753 patients with low- to intermediate-risk DTC who underwent total thyroidectomy without RAI at 11 Korean tertiary hospitals. Serum Tg levels were measured under thyrotropin suppression (<2 mIU/L) at 6, 12, and 24 months postoperatively using high-sensitive assays (functional sensitivity, <0.2 ng/mL). Optimal Tg cutoffs were determined by receiver operating characteristic curves and survival analyses. <b><i>Results:</i></b> Higher postoperative unstimulated Tg levels consistently predicted structural recurrence, with an optimal cutoff of 0.3 ng/mL (area under the curve: 0.815, 0.772, and 0.816 at 6, 12, and 24 months, respectively). A Tg ≥ 0.2 ng/mL, the Korean Thyroid Association (KTA) guideline cutoff for biochemical remission (excellent response), showed high sensitivity for recurrence. Tg ≥ 5.0 ng/mL at 6 months, a KTA-defined threshold for a biochemical incomplete response, independently predicted an elevated recurrence risk. Kaplan-Meier curves showed stepwise declines in recurrence-free survival with increasing Tg levels. Notably, even Tg < 0.2 or < 0.3 ng/mL were associated with recurrence if levels rose over time. <b><i>Conclusion:</i></b> Unstimulated Tg levels are strongly associated with the risk of structural recurrence in patients with DTC who have undergone total thyroidectomy without RAI. The current cutoff values of 0.2 ng/mL and 5.0 ng/mL were clinically relevant, and Tg kinetics over time further improved risk stratification. These findings provide the first large-scale evidence from an East Asian cohort and underscore the importance of early, serial Tg assessment in this growing patient population.