Thyroglobulin antibody in differentiated thyroid cancer: international laboratory practice survey and the case for a dual-threshold model

OBJECTIVES: Anti-thyroglobulin antibodies (TgAb) have a dual role during the follow-up of differentiated thyroid cancer (DTC): they may interfere with thyroglobulin (Tg) immunoassays and also serve as surrogate biomarkers of disease status. However, laboratory practices for TgAb measurement and reporting remain poorly standardised. We conducted an international survey to characterize current laboratory approaches and identify opportunities for harmonization. METHODS: A structured questionnaire was distributed to 120 laboratory medicine centres performing Tg and TgAb testing. The survey collected information on analytical platforms, TgAb reporting practices, positivity and interference thresholds, interference assessment strategies, and the interpretation of longitudinal TgAb changes. Results were analysed descriptively. RESULTS: Fifty-one centres from six European countries participated (response rate, 42 %). Most laboratories (88 %) measured Tg and TgAb using assays from the same manufacturer. Marked heterogeneity was observed in quantitative TgAb reporting, definition of pathological TgAb concentrations, and thresholds considered indicative of potential Tg assay interference. Although more than half of the laboratories reported having defined an interference threshold, only two (4 %) implemented and explicitly reported separate thresholds for thyroid autoimmunity and Tg assay interference. Structured interference investigations were uncommon (26 %) and relied mainly on recovery testing, whereas predefined delta-check criteria for longitudinal TgAb interpretation were used by only 8 % of centres. CONCLUSIONS: Current laboratory practice for TgAb testing in DTC is highly heterogeneous and may contribute to inconsistent interpretation of Tg results. A dual-threshold reporting model that clearly distinguishes the diagnostic threshold for thyroid autoimmunity from the analytical threshold indicating potential Tg assay interference promote harmonization. Routine support for longitudinal TgAb interpretation, including serial trend reporting, represents an additional opportunity for laboratory specialists to enhance the management of patients with DTC.