A deep dive into four thyroglobulin immunoassays from analytical perspective.

Abstract

Backgrounds: Serum thyroglobulin immunometric assays (sTg) are crucial for monitoring differentiated thyroid cancer (DTC) treatment. However, challenges such as anti-thyroglobulin autoantibodies (TgAb) and assay variability hinder evaluations. This study assessed four sTg methods-three second-generation (Architect, Access, Elecsys) and one first-generation (Immulite)-following Clinical and Laboratory Standards Institute (CLSI) and American Thyroid Association (ATA) guidelines.

Methods: The study compared sTg_(Architect), sTg_(Access), sTg_(Elecsys), and sTg_(Immulite). Precision was evaluated per CLSI EP05-A3, while the lower limits of detection (LLD) were assessed using EP17-A2. Passing-Bablok and Bland-Altman analyses were conducted as per EP09c, and semi-quantitative comparisons used Kappa statistics.

Results: The second-generation sTgs (Architect, Access, Elecsys) exhibited satisfactory precision (<7% coefficient of variation, CV%), unlike sTg_(Immulite), which showed significant deviations and inadequate sensitivity for DTC recurrence (Limit of quantitation, LoQ = 4.59 μg/L). Second-generation sTgs had strong correlations (r > 0.884) across all concentration ranges (≤1, 1-10, >10 μg/L), with biases (slope: 1.131-2.027). sTg_(Immulite) correlated well with second-generation methods for concentrations >10 μg/L (r > 0.945) but less so for <10 μg/L (r < 0.642). TgAb significantly impacted sTg_(Immulite). Kappa statistics revealed strong agreement among second-generation methods (κ > 0.800) but lower concordance with sTg_(Immulite), especially in TgAb(+) samples (κ: 0.562-0.653). Agreement ratios were high for second-generation methods (0.667-1.000) but variable for sTg_(Immulite), particularly at lower concentrations and in TgAb(+) cases (0.097-0.727).

Conclusions: sTg_(Immulite) did not meet LLD and precision criteria for DTC monitoring, facing issues with TgAb interference. Second-generation sTgs demonstrated consistent performance across all concentrations.