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Discordance in thyroglobulin measurements by radioimmunoassay and immunometric assay: a useful means of identifying thyroglobulin assay interference

Background Serum thyroglobulin (Tg) is useful for monitoring patients with differentiated thyroid cancer (DTC) but is limited by interference from anti-Tg antibodies (TgAb). We determined Tg assay discordance between a radioimmunoassay (RIA) and one of two immunometric assays (IMA) in DTC patients over a 9-year period to gauge assay performance against evidence of recurrent/progressive DTC. Methods Patients with DTC monitored for >1 year attending local clinics between September 2000 and January 2010 were included. All samples were analysed for Tg using both RIA and IMA. TgAb were measured on all Tg requests made after May 2006. Bias plots comparing RIA against IMA were established to calculate a 2-SD outlier limit. Clinical records were viewed to compare discordant Tg results against clinical evidence of recurrent/progressive DTC. Results Discordant Tg results were observed in 53/433 patients (12.2%). Four were discordant owing to a higher IMA result, one of which demonstrated recurrence. The remaining 49 patients demonstrated a disproportionately higher RIA result, of which four had recurrent/persistent disease. Twelve patients with a higher RIA result but no evidence of recurrence underwent thyrogen stimulation testing, which was negative in all 12. In many cases, assay discordance appeared more sensitive at indicating interference than direct measurement of TgAb. Conclusions Interference was evident with both Tg assays, such that neither could be solely relied upon to provide the correct result in the presence of TgAb. The concomitant measurement of Tg by RIA and IMA methods should be considered as an alternative to monitoring TgAb status.