Unstimulated Highly Sensitive Thyroglobulin in Follow-up of Differentiated Thyroid Cancer Patients: A Meta-Analysis

Abstract

Serum thyroglobulin (Tg) is an indicator of differentiated thyroid cancer (DTC) relapse. Our objective was to conduct a meta-analysis of published data about the diagnostic performance of highly sensitive serum Tg (hsTg) during levothyroxine therapy in DTC follow-up. We performed a comprehensive literature search of PubMed/MEDLINE and Scopus for studies published until July 2013. Studies investigating the diagnostic performance of basal hsTg in monitoring DTC were eligible. Exclusion criteria were 1) articles not within the field of interest; 2) reviews, letters, or conference proceedings; 3) articles evaluating serum Tg measurement with a functional sensitivity >0.1 ng/mL; 4) overlap in patient data; and 5) insufficient data to reassess diagnostic performance of basal serum hsTg. Information was collected concerning basic study data, patient characteristics, and technical aspects. For each study, the number of true-positive, false-positive, true-negative, and false-negative findings for basal hsTg, considering stimulated Tg measurement as a reference standard, were recorded. Pooled data demonstrated that the negative predictive value of hsTg was 97% and 99% considering a stimulated Tg measurement >1 ng/mL and >2 ng/mL as cutoffs for positivity, respectively. Despite the high pooled sensitivity of basal hsTg, the pooled specificity, accuracy, and positive predictive value were insufficient to completely substitute for a stimulated Tg measurement. Basal hsTg measurement has a very high negative predictive value but an insufficient positive predictive value for monitoring DTC patients. Therefore, a Tg stimulation test can be avoided in patients with an undetectable basal hsTg, whereas a stimulated Tg measurement should be considered when hsTg levels are detectable.