Threshold Effect of Serum Thyroglobulin Levels on the Detection Rate of Recurrent Differentiated Thyroid Carcinoma by ¹⁸ F-FDG PET/CT: A Systematic Review and Meta-Analysis

Background: The optimal serum thyroglobulin (Tg) threshold for performing ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in patients with recurrent differentiated thyroid carcinoma (DTC) and negative radioiodine scintigraphy (TENIS syndrome) remains controversial. This study aimed to systematically evaluate the relationship between Tg levels and PET/CT detection rates and to determine if a clinically meaningful threshold exists. Methods: A systematic literature search was conducted in Web of Science, PubMed, and Cochrane Library up to January 2026 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies reporting Tg-stratified PET/CT detection rates in adult patients with suspected recurrent DTC were included. The primary outcome was the per-patient detection rate, which was pooled using a random-effects model. Risk of bias was assessed using QUADAS-2. Results: Eight studies met the inclusion criteria, with six contributing to the quantitative synthesis. The overall pooled detection rate was 0.54 (95% CI 0.29–0.78), with significant heterogeneity across studies (I² = 93.4%). A pronounced threshold effect was observed: detection rates were negligible in low-Tg strata (<5 ng/mL), increased substantially in intermediate strata (5–10 ng/mL), and were consistently high in high-Tg strata (>10 ng/mL). Specifically, the pooled detection rate was 0.71 (95% CI 0.00–1.00) for patients with Tg >10 ng/mL and increased to 0.97 (95% CI 0.90–0.99) in the subgroup with Tg ≥18 ng/mL, although this estimate was based on a limited number of studies. Conclusion: ¹⁸F-FDG PET/CT diagnostic yield demonstrates a monotonic increase with rising serum Tg levels. A Tg threshold in the range of approximately 10–18 ng/mL appears promising for identifying structural disease, although the upper bound of this threshold warrants further validation in larger cohorts. These findings support a Tg-guided, risk-stratified approach to selecting candidates for 18F-FDG PET/CT.