Clinical irrelevance of lower titer thyroglobulin autoantibodies in patients with differentiated thyroid carcinoma

OBJECTIVE: Thyroglobulin(Tg) is an established tumor marker for differentiated thyroid carcinoma (DTC) patients. However, Tg immunoassays can be subject to Tg autoantibody(TgAb) interference resulting in incorrect Tg values. Therefore, Tg measurement with liquid chromatography-tandem mass spectrometry(LC-MS/MS) could be promising in patients with TgAbs. We compared a Tg immunoradiometric assay (Tg-IRMA) and a Tg-LC-MS/MS analytically in the presence of TgAbs. Furthermore, we compared the clinical interpretation of results obtained by both Tg assays in DTC patients with lower TgAbs titers (<10 U/ml) during 131I ablation therapy.METHODS: 118 DTC patients diagnosed between 2006 and 2014 in a University Medical Center were followed with the Tg-IRMA and ARCHITECT Anti-Tg assays. We re-analyzed their samples with a sensitive Tg-LC-MS/MS method (limit of quantification of 0.02 ng/ml). Passing-Bablok regression analysis was performed on samples obtained during 131I ablation therapy and follow-up.RESULTS: In 304 samples with lower TgAb titers, a good analytical agreement was found between both Tg assays (slope of 1.09 (95% CI 1.05 - 1.16)). Fifty-five samples with potentially interfering TgAbs showed higher Tg-LC-MS/MS values than Tg-IRMA (slope of 1.45 (95% CI 1.12->>100)). In patients (n=91) with lower TgAb titers at the time of 131I ablation therapy, the Tg assays showed a clinical concordance of 91.2%, 87.9%, and 98.9%, respectively, using a Tg cut-off value of 1.0 ng/mL, 2.0 ng/mL and 5.0 ng/mL.CONCLUSIONS: In DTC patients with lower titer TgAbs, Tg-IRMA is still a reliable and useful tumor marker. In DTC patients with potentially interfering TgAbs, Tg-IRMA values are decreased due to TgAb interference.