Causes of discordance between thyroglobulin antibody assays

Abstract

Background Anti-thyroglobulin (Anti-Tg) assays show poor concordance. Methods We have investigated concordance and the causes of discordance between Abbott, Roche and Immulite Anti-Tg assays in 606 patients followed up for differentiated thyroid cancer (DTC). The reference range (RR) or lower reporting limit (LRL) was used to classify samples as negative or positive. Results Anti-Tg prevalence ranged between 6% and 55% depending on the method and cut-off. Concordance was 45% using LRL and 75% using RR. Specimens between the RR and LRL using the Immulite and Roche assays were identified that were positive by the Abbott assay and showed poor recovery of Tg in the Tg assay. This suggests misclassification using the RR. Anti-Tg International Reference Preparation (IRP) concentrations measured by the Roche and Abbott methods agreed well but patient samples did not. This is likely to be due to the heterogeneity of Anti-Tg. The Immulite assay appeared less sensitive than the Abbott and Roche based on investigations using the IRP and the low prevalence of Anti-Tg in the DTC patients (6–8%). Interference by Tg (>1000 μg/L) in the Roche assay was also identified as a cause of assay discordance. Conclusions Anti-Tg is used as a tumour marker for DTC and to predict interference in Tg assays themselves and hence inform clinicians of reported Tg concentrations. We have identified several causes of Anti-Tg assay discordance. This includes variation in assay sensitivity and interference from Tg, the heterogeneity of Anti-Tg and the use of different cut-offs to classify samples as antibody-positive or -negative.