Abstract
<title>Abstract</title> <p> Background The 2015 ATA pediatric guidelines recommend using risk stratification, stimulated thyroglobulin (sTg), and diagnostic whole-body scintigraphy (DxWBS) to guide postoperative radioactive iodine (RAI) therapy. However, current sTg thresholds are derived from adult studies and may not be optimal for children. This study aimed to establish pediatric-specific, risk-stratified sTg thresholds for RAI decision-making. Methods We analyzed 101 consecutive TgAb-negative pediatric DTC patients (≤ 18 years) undergoing initial RAI therapy. Receiver operating characteristic (ROC) curve analysis with internal bootstrap validation determined optimal postoperative sTg cutoffs for predicting pre-ablation persistent structural disease (PSD) within each ATA pediatric risk group, balancing sensitivity and specificity. The predictive value of these thresholds for 1-year dynamic risk stratification (DRS) and final no evidence of disease (NED) status was assessed. Results Among patients (13.9% low, 34.7% intermediate, 51.5% high-risk), pre-ablation PSD prevalence was significantly higher in high-risk (92.3%) vs. intermediate (48.6%) and low-risk (28.6%) groups ( <italic>p</italic> = 0.001). Median sTg was significantly higher in patients with PSD (172.0 ng/mL) vs. without (11.9 ng/mL) ( <italic>p</italic> < 0.001). sTg predicted PSD with an AUC of 0.917 (95% CI: 0.865–0.969). Risk-stratified optimal sTg thresholds were: 60.2 ng/mL (low-risk; specificity 100%), 41.6 ng/mL (intermediate-risk; sensitivity 84.1%, specificity 90.6%), and 9.1 ng/mL (high-risk; sensitivity 95.7%). Intermediate-risk patients with sTg < 41.6 ng/mL had significantly higher rates of 1-year excellent response (66.7% vs. 14.3%) and final NED (85.7% vs. 42.9%, <italic>p</italic> = 0.011) than those ≥ 41.6 ng/mL. Comparable patterns were observed in low- and high-risk groups. Conclusion This study establishes pediatric-specific, postoperative sTg thresholds stratified by ATA risk: 60.2 ng/mL (low-risk), 41.6 ng/mL (intermediate-risk), and 9.1 ng/mL (high-risk). These risk-adapted thresholds strongly predict pre-ablation PSD and provide evidence to inform personalized RAI decision-making in children. </p>