MON-333 - Optimal Thyroglobulin Cutoff to Define Remission of Thyroid Cancer Following Total Thyroidectomy Without Radioactive Iodine Therapy

Background

Thyroid cancer patients are increasingly treated with total thyroidectomy (TT) without radioactive iodine (RAI). An unstimulated thyroglobulin (Tg) ≤0.2 ng/mL defined remission per 2015 ATA guidelines. The 2025 ATA guidelines recommend a higher threshold of 2.5 ng/mL to define excellent response. We evaluated this cutoff to determine the proportion of cases reclassified as excellent response to therapy.

Methods

Retrospective analysis of patients aged ≥18 years with differentiated thyroid cancer who underwent TT without RAI between 2001 and 2025, referred to our institution for surveillance or management.

Results

Of 205 patients, 162 were low-risk, 34 low-intermediate, and 7 intermediate-high risk per ATA 2025 criteria. Histology was papillary (PTC) in 199, follicular (FTC) in 3, and oncocytic in 3. Median follow-up was 79.5 months; mean age 44.3 years (range 18–74). With a Tg threshold of 2.5 ng/mL, 200 (97.6%) achieved excellent response; the remainder were indeterminate. Using 0.2 ng/mL, 155 (75.6%) had excellent response, 33 (16.1%) indeterminate, and 17 (8.3%) biochemically incomplete. Six patients (2.9%) developed structural recurrence: 4 in the low-intermediate and 2 in the low-risk group, with mean Tg 1.52 ng/mL (range 0.3–3.4). The case with the highest Tg (3.4 ng/mL) was FTC; the remaining five were PTC. Of these, 5 PTC cases would have been classified as biochemically incomplete at 0.2 ng/mL but as excellent response at 2.5 ng/mL. The FTC case (Tg 3.4 ng/mL) would have been biochemically incomplete by both criteria.

Conclusion

The 2025 ATA Tg threshold of 2.5 ng/mL reclassified an additional 22% of patients (75.6% to 97.6%) as excellent response, substantially reducing indeterminate and biochemically incomplete categorizations. None of the 7 intermediate-high risk patients with excellent response at the higher threshold developed structural recurrence. However, 5 of 6 patients with structural recurrence had Tg between 0.3 and 2.5 ng/mL and would have been misclassified as excellent response. Recurrences were concentrated in the low-intermediate risk group (4/34, 11.8%) versus the low-risk group (2/162, 1.2%). While the 2.5 ng/mL threshold reduces overtreatment in most patients after TT without RAI, it may lack sensitivity for structural recurrence in the low-intermediate risk group. Continued imaging surveillance and evaluation of Tg kinetics in this population warrant further study.

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