Defining a clinically relevant thyroglobulin antibody interference threshold for high-sensitivity thyroglobulin immunoassays: a single institution case study.

BACKGROUND: The interpretation of serum thyroglobulin (Tg) levels in differentiated thyroid cancer is complicated by interference from thyroglobulin antibodies (TgAb) and there is no standardized threshold to determine interference. Following implementation of a new instrument, we observed increased TgAb-positive samples which reflex to alternate send-out Tg methods with reduced analytic sensitivity but which are more robust to TgAb interference. This resulted in fewer patients having detectable Tg for monitoring, longer turnaround times, and higher costs. We hypothesized that the TgAb assay limit of detection (LOD) was lower than the clinically meaningful interference threshold.

METHODS: We analyzed 119 serum specimens with an electrochemiluminescent TgAb immunoassay (ECLIA-TgAb) ≥ 10 IU/mL, comparing TgAb measurements by radioimmunoassay (RIA-TgAb) and Tg levels measured via immunometric assay (IMA-Tg) and RIA (RIA-Tg; reference method), and clinical adjudication of discrepant samples.

RESULTS: Of ECLIA-TgAb specimens above the LOD (10 IU/mL), 30 % were positive by RIA-TgAb. Increasing the ECLIA-TgAb threshold to 20 IU/mL improved concordance to 90 %. A 20 IU/mL threshold optimized qualitative agreement between IMA-Tg and RIA-Tg (95 %). Retrospective chart review of patient diagnosis and treatment indicated that there would be no change in patient management with the revised threshold.

CONCLUSIONS: We found that an ECLIA-TgAb threshold of 20 IU/mL allowed more patients to be followed by the high sensitivity IMA-Tg method with no change to clinical decision-making, reducing send-out testing by 66 %. This approach offers an accessible and practical strategy for individual laboratories to define clinically appropriate TgAb thresholds to maximize the samples eligible for highly sensitive Tg measurement.