Thyroglobulin Liquid Chromatography–Tandem Mass Spectrometry Has a Low Sensitivity for Detecting Structural Disease in Patients with Antithyroglobulin Antibodies

Abstract

Background: Thyroglobulin (Tg) measurement in patients with positive antithyroglobulin antibodies (antiTgAbs) is not reliable. Tg measurement using liquid chromatography-tandem mass spectrometry (LC/MS) may be useful in this setting. Methods: This is a retrospective study with the objective of determining the accuracy of Tg-LC/MS in patients with thyroid cancer with anti-TgAbs. All patients with follicular cell-derived thyroid cancer (TC) who had thyroglobulin measured using LC/MS assay from November 1, 2013, to November 7, 2014, were evaluated. The frequency of detectable Tg-LC/MS was evaluated, with a functional sensitivity (FS) of 0.5 ng/mL in patients with structural disease. Then performance of Tg-LC/MS versus Tg immunometric assay (IMA) was compared using either Immulite assay (Tg-1) with a FS of 0.9 ng/mL or Beckman assay (Tg-B) with a FS of 0.1 ng/mL in detecting structural disease in patients with positive anti-TgAbs. Results: A total of 154 consecutive patients were included in this evaluation. Of these, 116 (75%) patients were positive for anti-TgAbs. In patients with structural disease and positive anti-TgAbs, Tg-LC/MS was undetectable in 43.7% of patients. Then the diagnostic accuracy for structural disease of Tg-LC/MS was compared with each Tg-IMA assay separately. In the 26 patients with positive anti-TgAbs where a Tg-I assay was used, the sensitivity and specificity for detecting structural disease were 33.3% and 88.2%, respectively, for the Tg-I assay, and 44.4% and 94.1%, respectively, for the Tg-LC/MS assay. In the 74 patients with positive anti-TgAbs where Tg-B was used, the sensitivity and specificity for detection of structural disease were 72.7% and 71.4%, respectively, for the Tg-B assay, and 62.6% and 93.7%, respectively, for the Tg-LC/MS assay. Conclusion: In patients with thyroid cancer with positive anti-TgAbs, Tg-LC/MS was frequently undetectable and was less sensitive for detecting disease than a Tg assay was with a functional sensitivity of 0.1 ng/mL. For patients with detectable Tg-LC/MS and anti-TgAbs, use of the assay for monitoring requires further prospective studies.

Effect of Thyroglobulin Autoantibodies on the Metabolic Clearance of Serum Thyroglobulin

“…We have recently reported that the rise in TgAb IgG observed after 131 I treatment for Graves' hyperthyroidism is restricted to IgG1 and IgG3 (29). The present findings, in addition to previous data, support the concept that, in patients with TgAb, the lower than expected Tg concentrations observed when Tg is measured by IMA and tandem mass spectroscopy (2,6,8,9,27) is mainly due to a truly low This paper has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.…”

Follow-up of low risk thyroid cancer patients: can we stop follow-up after 5 years of complete remission?

“…The presence of specific somatic tumor mutations has been integrated into the ATA risk stratification classification (9). Although the presence of BRAFV600E mutation has been associated with higher recurrence rates in tumors of >1 cm (53) that are considered as at intermediate risk of recurrence, this is not true for intrathyroidal microPTCs (54).…”

Recent advances in managing differentiated thyroid cancer

“…Novel biomarkers are emerging as replacements for serum Tg in these difficult cases, such as circulating microRNAs and other nucleic acids, but still need to be standardized and clinically validated 42 – 44 . The use of mass spectrometry for measuring serum Tg levels in the presence of TgAb also needs to be validated 45 , 46 . Sensitive Tg assays that can detect serum concentrations as low as 0.1 ng/mL are currently used and provide similar information on disease status as rhTSH-stimulated Tg obtained in the past with assays that had a sensitivity of 1 ng/mL.…”