Thyroglobulin (Tg) Recovery Testing with Quantitative Tg Antibody Measurement for Determining Interference in Serum Tg Assays in Differentiated Thyroid Carcinoma (Technical Briefs) (Clinical Report‪)‬

Serum thyroglobulin (Tg) measurements play a key role in the postsurgical follow-up of patients with differentiated thyroid cancer (DTC) (1), but these measurements are severely hampered by the presence of Tg antibodies (TgAbs), which can cause under- or overestimation of Tg concentration depending on the Tg assay format (2, 3). The National Academy of Clinical Biochemistry guideline (4) recommends the use of sensitive TgAb immunoassays to detect TgAbs in favor of Tg recovery (TgR) testing because TgR testing fails to differentiate TgAb-positive and -negative sera (5, 6). The differences in immunoreactivity between endogenous Tg and Tg added to patient serum, as well as the amount of Tg added and the duration of incubation, all appear critical to the TgR result (5,7). However, limitations of TgAb testing are also recognized: TgAb concentrations do not correlate with the degree of interference (3, 8); TgAb positivity does not indicate interference per se; substances other than TgAbs can interfere with Tg measurement (9); and TgAb detection is strongly method dependent (10). A reliable hallmark of TgAb interference is the presence of RIA/immunometric assay discordance (4,10), but intermethod comparisons are impractical because few RIAs are available (10). Therefore, the technical problem of TgAb interference in Tg measurements has not been overcome. The release of a new TgR assay enabled us to reassess the clinical utility of recovery testing in detecting interference in serum Tg measurements by comparing the TgR assay with a quantitative TgAb test and the methodologic benchmark for TgAb interference, RIA/immunometric assay discordance (10), in relation to the clinical status of the patient.