Anti-Thyroglobulin Antibodies as a Surrogate Tumor Marker for the Follow-Up of the Differentiated Thyroid Carcinoma: Clinical Implications and Pitfalls

Antithyroglobulin antibodies (TgAb) are present in 10–25% of patients with differentiated thyroid cancer (DTC) and significantly affect the reliability of serum thyroglobulin (Tg) measurements during follow-up. Beyond causing assay interference, TgAb have emerged as independent surrogate tumor markers with prognostic implications. This review summarizes the current evidence on antithyroglobulin antibody biology, measurement methodologies, interference dynamics, and clinical utility as surrogate tumor markers in DTC surveillance. A narrative synthesis of the relevant English-language literature was performed, focusing on key clinical studies and recent guidelines. TgAb can lead to the underestimation of Tg levels in immunometric assays, potentially masking residual disease. Trend monitoring, rather than absolute antithyroglobulin antibody values, provides superior prognostic information; declining trends indicate favorable outcomes, whereas rising trends are associated with disease persistence or recurrence. De novo antithyroglobulin antibody positivity does not appear to serve as an early biomarker of recurrence. In antithyroglobulin antibody–positive patients, imaging-based surveillance, particularly neck ultrasonography, remains the cornerstone of follow-up. In conclusion, TgAb act as both interferents and surrogate tumor markers in DTC surveillance, and the integrated use of antithyroglobulin antibody trends and imaging is necessary for the optimal management of antithyroglobulin antibody–positive patients.