Endocrine Abstracts

Background: Thyroglobulin (Tg) plays a crucial role in managing patients with differentiated thyroid cancer (DTC). The utility of Tg in early and long-term follow-up of DTC patients has been well-documented. Although third-generation Tg immunoassays have improved accuracy, limitations persist, such as interference from antithyroglobulin antibodies and variability in measurements. Changes in DTC treatment approaches necessitate reevaluation of Tg thresholds. This study aims to assess the validity of serum Tg testing in the contemporary setting, focusing on two patient populations: those receiving traditional therapy (total thyroidectomy and radioiodine treatment) and those treated solely with thyroidectomy. We aimed to identify a data-derived threshold (measured approximately 1 year after initial treatment) based on actual outcomes within the first 5 years of follow-up.

Methods: A total of 540 DTC patients included in the Italian Thyroid Cancer Observatory (ITCO) database meeting specific criteria, were selected, excluding those with anti-Tg antibodies. Serum Tg levels, assessed using highly-sensitive assays, were examined at 1-year intervals post-treatment. Statistical analysis included the determination of the 97th percentile of disease-free individuals to establish potential cutoffs for structural disease.

Results: Serum Tg levels evaluated in 540 patients revealed a consistent distribution across treatment modalities. After excluding 26 patients with structural disease detected at any time point, the median TSH did not differ between patients treated with RRA and those who did not. We identified two potential thresholds (97th percentile of apparently disease-free individuals): 1.97 ng/mL in patients who underwent thyroidectomy alone (lower than proposed by the MSKCC protocol and ESMO Guidelines, but able to reliably rule out malignancy, given its NPV of 98%) and 0.84 ng/mL for patients who received after surgery a radioiodine treatment. Diagnostic performance demonstrated high sensitivity and negative predictive value, validating the potential thresholds in ruling out structural disease.

Discussion: Current guidelines for thyroglobulin (Tg) thresholds haven’t been fully validated in the context of contemporary differentiated thyroid cancer (DTC) treatment strategies, which often involve less intensive approaches. Our real-world study support the reliability of serum Tg levels measured one year after treatment across various treatment settings We propose data-driven Tg thresholds that can inform clinical decision-making for patients undergoing total thyroidectomy and radioiodine ablation, as well as those receiving thyroidectomy alone.