Predictors of false−negative serum thyroglobulin in persistent/recurrent Papillary Thyroid Carcinoma cervical lymph nodes

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Purpose Serum thyroglobulin (Tg) is the primary biomarker for monitoring disease persistence and recurrence in papillary thyroid carcinoma (PTC). However, some patients with structurally confirmed persistent/recurrent cervical lymph nodes (LNs) have low or undetectable Tg. This study aimed to identify predictors of false−negative unstimulated serum Tg (<0.2 ng/mL) and develop a predictive model. Patients and methods This retrospective study enrolled 215 Papillary Thyroid Carcinoma patients who underwent total thyroidectomy and were confirmed to have persistent/recurrent cervical LNs. Multivariable logistic regression identified independent predictors associated with serum Tg <0.2 ng/mL. A nomogram was developed and validated by AUC, calibration curve, decision curve analysis (DCA). Results Among the 215 patients (50 persistent, 165 recurrent), 48 (22.3%) had unstimulated serum Tg <0.2 ng/mL. Independent predictors of false−negative Tg (<0.2 ng/mL) were central LN compartment (p = 0.039), smaller LN size ( p = 0.019), and higher Tg−Ab level ( p < 0.001). In Tg−Ab negative patients (≤115 IU/mL, n=158), higher Tg−Ab remained associated with false−negative Tg ( p < 0.001). The nomogram showed good discrimination (AUC = 0.87) and calibration. DCA demonstrated net clinical benefit at a threshold ≥0.1, defining high risk for false−negative Tg. Conclusion Central LN location, small LN size, and elevated Tg−Ab predict false−negative Tg in Papillary Thyroid Carcinoma patients with persistent/recurrent LNs. The nomogram identifies high−risk individuals (≥0.1), in whom serum Tg alone is unreliable and adjunct imaging and biopsy should be considered.