Risk-Stratified Outcomes Using the 2025 ATA Thyroglobulin Cutoff After Total Thyroidectomy in Differentiated Thyroid Cancer.

BACKGROUND

Differentiated thyroid cancer (DTC) is increasingly managed with total thyroidectomy (TT) without radioactive iodine (RAI). An unstimulated thyroglobulin (Tg) ≤ 0.2 ng/mL has traditionally defined remission. The 2025 American Thyroid Association (ATA) guideline raised the threshold to 2.5 ng/mL to reduce overtreatment. We evaluated the performance of this cutoff in clinical practice.

METHODS

We performed a retrospective study of patients with DTC treated with TT without RAI between 2001 and 2023. Eligible patients had more than 3 years of follow-up, undetectable anti-thyroglobulin antibody, and negative initial imaging.

RESULTS

Of 2,781 screened patients, 205 met inclusion criteria: 118 were ATA low-, 42 low-intermediate, and 45 intermediate-high risk disease. Mean follow-up was 85 months. Using the revised Tg threshold (<2.5 ng/mL) increased the excellent response group from 76% to 98%. Among ATA low-risk patients, no structural recurrences were missed. However, 3.5% of patients with low-intermediate or higher-risk disease developed structural recurrence despite meeting excellent response criteria. The median time to recurrence was 22 months. In these patients, a postoperative Tg cutoff of 0.3 ng/mL demonstrated 100% sensitivity for structural recurrence. No thyroid cancer-related deaths occurred.

CONCLUSIONS

The 2025 ATA Tg threshold increased excellent response classification without missing recurrence in low-risk patients. However, structural recurrences occurred in patients with higher-risk disease below the revised cutoff, suggesting that Tg thresholds may require risk-adapted interpretation. Continued imaging surveillance remains important for patients with low-intermediate or higher recurrence risk, even when Tg criteria for excellent response are met under the 2025 ATA guidelines.