Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2012) 29 P1784

ICEECE2012 Poster Presentations Thyroid cancer (108 abstracts)

Mass spectrometry allows accurate measurement of serum thyroglobulin (Tg) in the presence of anti-thyroglobulin auto-antibodies (TgAB)

R. Taylor , B. Netzel , J. Theobald , D. Barnidge , B. McIver , A. Algeciras-Schimnich , R. Singh & S. Grebe


Mayo Clinic, Rochester, Minnesota, USA.


Background: Serum thyroglobulin (Tg) measurements are one of the main pillars of thyroid cancer follow-up, because of the high organ and disease specificity of Tg in athyrotic patients. However, 20–25% of patients have detectable serum anti-Tg auto-antibodies (TgAB), which might cause false low Tg measurements in immunometric assays (IMA). This can lead to significant challenges in patient management. Measurement of Tg by liquid chromatography-tandem mass spectrometry (LC–MS/MS) after tryptic digestion can in theory overcome this problem, as TgAB and Tg are both digested equally, and Tg-specific tryptic fragments can be detected selectively. Proof of concept for such a LC–MS/MS Tg assay was shown for TgAB-negative patients in 2008 (Clin Chem 54:1796–1804). We extended these observations to TgAB-positive patients.

Methods: Samples were depleted of albumin and other low/mid molecular weight proteins, trypsin digested, and purified by solid phase extraction after addition of synthetic non-radioactive isotopic peptide internal standard (IS). The extracts were analyzed by LC–MS/MS for a highly ionizable proteotypic Tg fragment and its corresponding IS. Purified Tg, matched to the international Tg reference preparation, was used for calibration.

Results: The assay’s limit of detection was 2 ng/mL. Inter-assay imprecision (CV) was 4–12% (Tg range: 3.8–150 ng/ml). Method agreement with the Beckman Coulter Tg IMA in 119 TgAB-negative patients with detectable Tg showed a slope of 0.75, intercept: +3.8, R-squared: 0.87. By contrast, in 20 TgAB-positive patients with detectable Tg, the slope was 1.77, consistent with under-recovery of Tg in the IMA. Consistent with these observations, a comparison of Tg recovery between LC–MS/MS and IMA, following addition of high TgAB concentrations to Tg samples, showed under-recovery in the IMA.

Conclusion: Tryptic digest-based LC–MS/MS assays can measure Tg accurately in the presence of TgAB that lead to false low IMA measurements.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Volume 29

15th International & 14th European Congress of Endocrinology

European Society of Endocrinology 

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