Revised ATA Thyroglobulin Cutoff May Miss Recurrence in Higher-Risk Thyroid Cancer

A retrospective study in The Journal of Clinical Endocrinology & Metabolism evaluated the revised 2025 American Thyroid Association (ATA) thyroglobulin (Tg) threshold after total thyroidectomy without radioactive iodine for differentiated thyroid cancer. Of 2,781 patients screened from 2001–2023, 205 met inclusion criteria, including more than three years of follow-up, undetectable anti-thyroglobulin antibodies, and negative initial imaging. Mean follow-up was 85 months; 118 patients had ATA low-risk, 42 low-intermediate-risk, and 45 intermediate-high-risk disease.

Using an unstimulated Tg threshold of <2.5 ng/mL rather than the traditional ≤0.2 ng/mL increased excellent response classification from 76% to 98%. No structural recurrences were missed among low-risk patients. However, 3.5% of patients with low-intermediate or higher-risk disease developed structural recurrence despite meeting excellent response criteria; median time to recurrence was 22 months. In this higher-risk population, a postoperative Tg cutoff of 0.3 ng/mL showed 100% sensitivity for structural recurrence. No thyroid cancer-related deaths occurred.

The findings support risk-adapted interpretation of Tg and continued imaging surveillance in patients with low-intermediate or higher recurrence risk, even when biochemical criteria indicate an excellent response. The retrospective design and selected cohort limit generalizability. Only the abstract was available, and it did not report specificity or confidence intervals for the 0.3 ng/mL cutoff.