Revisiting Thyroglobulin Measurement: Current Methods and Future Perspectives Using Dried Blood Spot Sampling for Enhanced Clinical Practice

In contemporary medical practice, human thyroglobulin (Tg) stands out as the primary serum biomarker for detecting recurrence or persistence (presence of residual tumor) of differentiated thyroid carcinoma (DTC) in patients post-thyroidectomy. Immunoassays (IMAs) and radioimmunoassays (RIAs) have been implemented in clinical settings to gauge Tg levels. However, these methods can be unreliable because anti-thyroglobulin antibodies (Tg-Abs) and heterophile antibodies (HAs) interfere with assay binding, leading to either under- or overestimation of true Tg concentrations. Liquid chromatography tandem mass spectrometry (LC-MS/MS) has emerged as a distinctive alternative tool for Tg measurements. Despite its potential, the effectiveness of LC-MS/MS is under ongoing investigation. This review aims to provide a clear overview of existing follow-up procedures for Tg quantification and evaluate the potential of mass spectrometry (MS) in Tg analysis. The distinctive contribution of this review is the introduction of an emerging approach combining dried blood spots (DBSs) with LC-MS/MS for Tg measurement, emphasizing their translational potential for clinical follow-up of DTC patients.