An international cooperative study evaluating serum thyroglobulin standards.

A number of research laboratories have reported great variability in the levels of serum thyroglobulin (Tg) in normal subjects, the reason for which is not immediately apparent. The present study was designed to determine how important these variations were by submitting three identical standards to all participating laboratories. Three lyophilized human sera (standards A, B, and C) with increasing concentrations of Tg (5.3, 30.6, and 80.6 ng/ml, respectively) were submitted to 37 laboratories (40 assays) in 18 different countries. Standard A gave detectable values in 19 assays. The mean serum Tg concentration was 6.3 +/- 1.4 (+/- SEM) ng/ml (n = 18). Standard B was detected in all but 3 assays. The mean serum Tg concentration in standard B was 15.7 +/- 1.4 ng/ml (n = 37). All laboratories were able to detect Tg in standard C, and reported a mean serum Tg concentration of 36.5 +/- 3.2 ng/ml (n = 40). Lyophilization affected the recovery of Tg in our assay. This was confirmed by a study in which lyophilized standards A, B, and C and frozen standards were analyzed in the same assays. The remarkable finding was that the variability in serum Tg values reported by the various assays was great despite the submission of an identical set of standards of each of the laboratories. Wide interassay variation raises problems with respect to the applicability of threshold levels proposed by certain studies. The latter is particularly germane to the follow-up of patients with differentiated thyroid cancer. It is concluded that the development of a world standard for Tg may be a first and important step toward standardization of Tg assays, and that other components of the assays may need standardization as well.

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.