Thyroglobulin (Tg) testing revisited: Tg Assays, TgAb assays, and correlation of results with clinical outcomes

Brian C. Netzel, Stefan K.G. Grebe, B. Gisella Carranza Leon, M. Regina Castro, Penelope M. Clark, Andrew N. Hoofnagle, Carole A. Spencer, Adina F. Turcu, Alicia Algeciras-Schimnich

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Abstract

Context: Measurement of thyroglobulin (Tg) by mass spectrometry (Tg-MS) is emerging as a tool for accurate Tg quantification in patients with anti-Tg autoantibodies (TgAbs). Objective: The objective of the study was to perform analytical and clinical evaluations of two Tg-MS assays in comparison with immunometric Tg assays (Tg-IAs) and Tg RIAs (Tg-RIAs) in a cohort of thyroid cancer patients. Methods: A total of 589 samples from 495 patients, 243 TgAb-/252 TgAb+, were tested by Beckman, Roche, Siemens-Immulite, and Thermo-Brahms Tg and TgAb assays, two Tg-RIAs, and two Tg-MS assays. Results: The frequency of TgAb+ was 58%, 41%, 27%, and 39% for Roche, Beckman, Siemens-Immulite, and Thermo-Brahms, respectively. In TgAb- samples, clinical sensitivities and specificities of 100% and 74%-100%, respectively, were observed across all assays. In TgAb+ samples, all Tg-IAs demonstrated assay-dependent Tg underestimation, ranging from 41% to 86%. In TgAb+ samples, the use of a common cutoff (0.5 ng/mL) for the Tg-MS, three Tg-IAs, and the USC-RIA improved the sensitivity for the Tg-MSs and Tg-RIAs when compared with the Tg-IAs. In up to 20% of TgAb+ cases, Tg-IAs failed to detect Tg that was detectable by Tg-MS. In Tg-RIAs false-high biases were observed in TgAb+ samples containing low Tg concentrations. Conclusions: Tg-IAs remain the method of choice for Tg quantitation in TgAb- patients. In TgAb+ patients with undetectable Tg by immunometric assay, the Tg-MS will detect Tg in up to 20% additional cases. The Tg-RIA will detect Tg in approximately 35% cases, but a significant proportion of these will be clinical false-positive results. The undetectable Tg-MS seen in approximately 40% of TgAb+ cases in patients with disease need further evaluation.

Original languageEnglish (US)
Pages (from-to)E1074-E1083
JournalJournal of Clinical Endocrinology and Metabolism
Volume100
Issue number8
DOIs
StatePublished - Jan 1 2015

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Thyroglobulin
Assays
Testing

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Netzel, B. C., Grebe, S. K. G., Leon, B. G. C., Castro, M. R., Clark, P. M., Hoofnagle, A. N., ... Algeciras-Schimnich, A. (2015). Thyroglobulin (Tg) testing revisited: Tg Assays, TgAb assays, and correlation of results with clinical outcomes. Journal of Clinical Endocrinology and Metabolism, 100(8), E1074-E1083. https://doi.org/10.1210/jc.2015-1967

Thyroglobulin (Tg) testing revisited : Tg Assays, TgAb assays, and correlation of results with clinical outcomes. / Netzel, Brian C.; Grebe, Stefan K.G.; Leon, B. Gisella Carranza; Castro, M. Regina; Clark, Penelope M.; Hoofnagle, Andrew N.; Spencer, Carole A.; Turcu, Adina F.; Algeciras-Schimnich, Alicia.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 100, No. 8, 01.01.2015, p. E1074-E1083.

Research output: Contribution to journalArticle

Netzel, BC, Grebe, SKG, Leon, BGC, Castro, MR, Clark, PM, Hoofnagle, AN, Spencer, CA, Turcu, AF & Algeciras-Schimnich, A 2015, 'Thyroglobulin (Tg) testing revisited: Tg Assays, TgAb assays, and correlation of results with clinical outcomes', Journal of Clinical Endocrinology and Metabolism, vol. 100, no. 8, pp. E1074-E1083. https://doi.org/10.1210/jc.2015-1967
Netzel, Brian C. ; Grebe, Stefan K.G. ; Leon, B. Gisella Carranza ; Castro, M. Regina ; Clark, Penelope M. ; Hoofnagle, Andrew N. ; Spencer, Carole A. ; Turcu, Adina F. ; Algeciras-Schimnich, Alicia. / Thyroglobulin (Tg) testing revisited : Tg Assays, TgAb assays, and correlation of results with clinical outcomes. In: Journal of Clinical Endocrinology and Metabolism. 2015 ; Vol. 100, No. 8. pp. E1074-E1083.
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abstract = "Context: Measurement of thyroglobulin (Tg) by mass spectrometry (Tg-MS) is emerging as a tool for accurate Tg quantification in patients with anti-Tg autoantibodies (TgAbs). Objective: The objective of the study was to perform analytical and clinical evaluations of two Tg-MS assays in comparison with immunometric Tg assays (Tg-IAs) and Tg RIAs (Tg-RIAs) in a cohort of thyroid cancer patients. Methods: A total of 589 samples from 495 patients, 243 TgAb-/252 TgAb+, were tested by Beckman, Roche, Siemens-Immulite, and Thermo-Brahms Tg and TgAb assays, two Tg-RIAs, and two Tg-MS assays. Results: The frequency of TgAb+ was 58{\%}, 41{\%}, 27{\%}, and 39{\%} for Roche, Beckman, Siemens-Immulite, and Thermo-Brahms, respectively. In TgAb- samples, clinical sensitivities and specificities of 100{\%} and 74{\%}-100{\%}, respectively, were observed across all assays. In TgAb+ samples, all Tg-IAs demonstrated assay-dependent Tg underestimation, ranging from 41{\%} to 86{\%}. In TgAb+ samples, the use of a common cutoff (0.5 ng/mL) for the Tg-MS, three Tg-IAs, and the USC-RIA improved the sensitivity for the Tg-MSs and Tg-RIAs when compared with the Tg-IAs. In up to 20{\%} of TgAb+ cases, Tg-IAs failed to detect Tg that was detectable by Tg-MS. In Tg-RIAs false-high biases were observed in TgAb+ samples containing low Tg concentrations. Conclusions: Tg-IAs remain the method of choice for Tg quantitation in TgAb- patients. In TgAb+ patients with undetectable Tg by immunometric assay, the Tg-MS will detect Tg in up to 20{\%} additional cases. The Tg-RIA will detect Tg in approximately 35{\%} cases, but a significant proportion of these will be clinical false-positive results. The undetectable Tg-MS seen in approximately 40{\%} of TgAb+ cases in patients with disease need further evaluation.",
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T2 - Tg Assays, TgAb assays, and correlation of results with clinical outcomes

AU - Netzel, Brian C.

AU - Grebe, Stefan K.G.

AU - Leon, B. Gisella Carranza

AU - Castro, M. Regina

AU - Clark, Penelope M.

AU - Hoofnagle, Andrew N.

AU - Spencer, Carole A.

AU - Turcu, Adina F.

AU - Algeciras-Schimnich, Alicia

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N2 - Context: Measurement of thyroglobulin (Tg) by mass spectrometry (Tg-MS) is emerging as a tool for accurate Tg quantification in patients with anti-Tg autoantibodies (TgAbs). Objective: The objective of the study was to perform analytical and clinical evaluations of two Tg-MS assays in comparison with immunometric Tg assays (Tg-IAs) and Tg RIAs (Tg-RIAs) in a cohort of thyroid cancer patients. Methods: A total of 589 samples from 495 patients, 243 TgAb-/252 TgAb+, were tested by Beckman, Roche, Siemens-Immulite, and Thermo-Brahms Tg and TgAb assays, two Tg-RIAs, and two Tg-MS assays. Results: The frequency of TgAb+ was 58%, 41%, 27%, and 39% for Roche, Beckman, Siemens-Immulite, and Thermo-Brahms, respectively. In TgAb- samples, clinical sensitivities and specificities of 100% and 74%-100%, respectively, were observed across all assays. In TgAb+ samples, all Tg-IAs demonstrated assay-dependent Tg underestimation, ranging from 41% to 86%. In TgAb+ samples, the use of a common cutoff (0.5 ng/mL) for the Tg-MS, three Tg-IAs, and the USC-RIA improved the sensitivity for the Tg-MSs and Tg-RIAs when compared with the Tg-IAs. In up to 20% of TgAb+ cases, Tg-IAs failed to detect Tg that was detectable by Tg-MS. In Tg-RIAs false-high biases were observed in TgAb+ samples containing low Tg concentrations. Conclusions: Tg-IAs remain the method of choice for Tg quantitation in TgAb- patients. In TgAb+ patients with undetectable Tg by immunometric assay, the Tg-MS will detect Tg in up to 20% additional cases. The Tg-RIA will detect Tg in approximately 35% cases, but a significant proportion of these will be clinical false-positive results. The undetectable Tg-MS seen in approximately 40% of TgAb+ cases in patients with disease need further evaluation.

AB - Context: Measurement of thyroglobulin (Tg) by mass spectrometry (Tg-MS) is emerging as a tool for accurate Tg quantification in patients with anti-Tg autoantibodies (TgAbs). Objective: The objective of the study was to perform analytical and clinical evaluations of two Tg-MS assays in comparison with immunometric Tg assays (Tg-IAs) and Tg RIAs (Tg-RIAs) in a cohort of thyroid cancer patients. Methods: A total of 589 samples from 495 patients, 243 TgAb-/252 TgAb+, were tested by Beckman, Roche, Siemens-Immulite, and Thermo-Brahms Tg and TgAb assays, two Tg-RIAs, and two Tg-MS assays. Results: The frequency of TgAb+ was 58%, 41%, 27%, and 39% for Roche, Beckman, Siemens-Immulite, and Thermo-Brahms, respectively. In TgAb- samples, clinical sensitivities and specificities of 100% and 74%-100%, respectively, were observed across all assays. In TgAb+ samples, all Tg-IAs demonstrated assay-dependent Tg underestimation, ranging from 41% to 86%. In TgAb+ samples, the use of a common cutoff (0.5 ng/mL) for the Tg-MS, three Tg-IAs, and the USC-RIA improved the sensitivity for the Tg-MSs and Tg-RIAs when compared with the Tg-IAs. In up to 20% of TgAb+ cases, Tg-IAs failed to detect Tg that was detectable by Tg-MS. In Tg-RIAs false-high biases were observed in TgAb+ samples containing low Tg concentrations. Conclusions: Tg-IAs remain the method of choice for Tg quantitation in TgAb- patients. In TgAb+ patients with undetectable Tg by immunometric assay, the Tg-MS will detect Tg in up to 20% additional cases. The Tg-RIA will detect Tg in approximately 35% cases, but a significant proportion of these will be clinical false-positive results. The undetectable Tg-MS seen in approximately 40% of TgAb+ cases in patients with disease need further evaluation.

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