Predictors of false-negative serum thyroglobulin in persistent/recurrent Papillary Thyroid Carcinoma cervical lymph...

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.

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).

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.

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.