Advancing Immunoassay Precision: A Novel Preanalytical Method for Enhancing Thyroglobulin Measurement in the Presence of Tg Antibodies

Thyroglobulin (Tg) is a reliable marker for detecting recurrence in differentiated thyroid cancer (DTC) patients, but frequently occurring Tg antibodies (TgAbs) can hinder accurate measurement. We aimed to develop a preanalytical protocol for precise Tg detection in TgAb presence using the immunoradiometric assay (IRMA) platform. This study involved forty-five patients who underwent IRMA Tg and radioimmunoassay (RIA) TgAb measurements, including two patients monitored for recurrence and one with confirmed recurrence. All three had undetectable Tg levels. We evaluated three preanalytical methods in aiming to separate Tg from TgAbs: buffer only (Protocol 1), micro-spin filters only (Protocol 2), and a combination of both (Protocol 3). All preanalytical protocols showed high concordance with the original test (r = 0.981, 0.985, 0.971, respectively, <i>p</i> < 0.001), regardless of TgAb values. Protocols 1 and 3 yielded higher Tg levels than the original test (<i>p</i> < 0.001), especially in the group with a high TgAb titer. Protocol 1 managed to detect Tg in two patients under follow up with initially unmeasurable Tg and high TgAb titers and in one confirmed recurrent case. Sample pre-processing positively influenced Tg detection in TgAb-positive cases. These preanalytical approaches show promise, but further testing with larger sample sizes and more investigated conditions is warranted.