Postoperative thyroglobulin antibodies in differentiated thyroid cancer: predictors and associations with persistent and recurrent disease

Anti-thyroglobulin antibodies (TgAb) are present in up to 25% of patients with differentiated thyroid cancer (DTC) and interfere with thyroglobulin (Tg) measurement, a key biomarker used to monitor for persistent or recurrent disease (PRD). Despite its clinical significance, risk factors for postoperative TgAb-positivity in DTC are not well established. Furthermore, while TgAb-positivity has been associated with PRD, its prognostic implications relative to Tg level and radioactive iodine (RAI) treatment status remain unclear. We conducted a retrospective cohort study of 329 patients with DTC who underwent total thyroidectomy. Predictors of post-operative TgAb-positivity were evaluated using a proportional hazards model for interval-censored data. The association between TgAb-positivity and PRD was assessed using a Cox model with time-dependent covariates. Analyses were further stratified by Tg status (detectable vs. undetectable) and whether patients had undergone RAI. Approximately 39% of patients in this study were TgAb-positive. Lymphocytic thyroiditis (HR 2.28, 95% CI 1.55–3.33), stage > 1 ( p = 0.009), family history of thyroid cancer (HR 2.27, 95% CI 1.02–5.05), and younger age (HR per year 0.98, 95% CI 0.97–1.00) were independently associated with TgAb-positivity. TgAb-positivity was associated with an increased hazard of PRD (HR 2.8, 95% CI 1.5–5.3), with similar estimates observed in patients treated with radioactive iodine (HR = 2.8 [95% CI, 1.3–6.3]) and those not treated (HR = 2.8 [95% CI, 1.3–6.3]). When stratified by Tg status, all groups with detectable Tg or positive TgAb demonstrated a higher hazard of PRD compared to Tg-undetectable, TgAb-negative patients. The highest hazard was observed in patients with both detectable Tg and positive TgAb (HR 29.6, 95% CI 6.3–138.1). We identified risk factors for the development of TgAb-positivity and demonstrated its independent association with persistent or recurrent disease in DTC, including when stratified by Tg levels and RAI treatment. Patients with both detectable Tg and positive TgAb may represent a particularly high-risk subgroup. These findings support incorporating TgAb status into postoperative risk stratification, irrespective of Tg levels or RAI treatment in patients who have undergone total thyroidectomy.