Prognostic Significance of Detectable Antithyroglobulin Antibodies Based on Analytical Sensitivity in Papillary Thyroid Carcinoma with Undetectable Serum Thyroglobulin after Radioactive Iodine Treatment

Abstract

Background:

Serum thyroglobulin (Tg) is a key tumor marker in papillary thyroid carcinoma (PTC), but its reliability may be compromised by the presence of antithyroglobulin antibodies (TgAb). Utilizing the assay-specific limit of quantification (LOQ) may enhance the detection of TgAb-related interference compared with the traditional reference limit. This study evaluated postoperative TgAb levels based on LOQ as a surrogate marker for tumor monitoring in PTC.

Methods:

A total of 1039 patients with PTC (≥1 cm) who had undetectable unstimulated serum Tg (<0.2 ng/mL) 6–12 months after total thyroidectomy with radioactive iodine (RAI) ablation therapy (2009–2012) were retrospectively analyzed. Simultaneously measured TgAb levels were classified using both the reference limit (60.0 U/mL) and LOQ (43.4 U/mL) into three groups undetectable (<43.4 U/mL), borderline (43.4–60.0 U/mL), and elevated (>60.0 U/mL).

Results:

The median age was 48.2 years, and 188 (18.1%) were male. The median tumor size was 1.5 cm, and lymph node metastases were present in 705 patients (67.8%). During a median follow-up of 12.0 years, recurrence occurred in 4.8%. Based on initial TgAb level, patients were classified as undetectable (65.6%), borderline (23.5%), and elevated (10.9%), with corresponding 10-year progression-free survival rates of 97.9%, 94.6%, and 88.5%, respectively (p < 0.001). Multivariable analysis revealed a significantly higher recurrence risk in the borderline group compared with the undetectable group (adjusted hazard ratio, 2.01; confidence interval, 1.03–3.96; p = 0.043). In the borderline group, TgAb became undetectable in 75.0% of patients over 6.3 years, whereas those who remained borderline exhibited a higher recurrence rate of 12.9% (p = 0.01).

Conclusions:

TgAb levels above the LOQ were associated with a higher recurrence risk in patients with PTC with undetectable Tg after RAI treatment. Classification of TgAb positivity based on the LOQ may improve prognostic assessment compared with evaluation using conventional reference limits. Further studies are needed to validate our findings and refine TgAb thresholds.