Unstimulated high-sensitive thyroglobulin is a powerful prognostic predictor in patients with thyroid cancer.

Background Differentiated thyroid carcinoma (DTC) has an excellent prognosis and the role of high-sensitive thyroglobulin measured during levothyroxine (ON-T4 hs-Tg) testing to discriminate patients with structural from not-evidence of disease (SED and NED, respectively) has been investigated. We conducted a systematic review and meta-analysis evaluating the performance of ON-T4 hs-Tg in two clinical scenarios considering its negative predictive value (NPV) as primary outcome: (1) diagnostic performance of Tg when undetectable value and NED status are simultaneously demonstrated; (2) prognostic performance of undetectable Tg in predicting NED in the subsequent follow-up. Methods This systematic review and meta-analysis were registered on PROSPERO (CRD42019125092). PubMed, Scopus, CENTRAL and Web of Science were searched until February 12, 2019. Original articles reporting data on SED/NED in patients with detectable/undetectable ON-T4 hs-Tg were selected. Summary operating points were estimated using a random-effects model. Results Out of 1413 retrieved papers, 10 studies evaluating 1796 patients were included. Participants were outpatients diagnosed with DTC, treated with near-total (NTx) or total thyroidectomy (TTx) with or without radioactive iodine (RAI). The NPV of ON-T4 hs-Tg for diagnostic and prognostic performance was 99.4% (95% CI 98.9-99.9; I2 = 13%) and 99.4% (95% CI 98.8-100; I2 = 0%), respectively. Conclusions Our findings show that ON-T4 hs-Tg is an excellent diagnostic tool and prognostic factor to rule-out SED. A high level of evidence is provided to decrease the intensity and frequency of follow-up in those DTC patients having undetectable high-sensitive Tg.