Brian C Netzel1, Stefan K G Grebe1, B Gisella Carranza Leon1, M Regina Castro1, Penelope M Clark1, Andrew N Hoofnagle1, Carole A Spencer1, Adina F Turcu1, Alicia Algeciras-Schimnich1. 1. Department of Laboratory Medicine and Pathology (B.C.N., S.K.G.G., A.A.-S.), Division of Endocrinology, Metabolism, and Nutrition (S.K.G.G., B.G.C.L., M.R.C., A.F.T.), Mayo Clinic, Rochester, Minnesota 55905; Queen Elizabeth Hospital Birmingham (P.M.C.), Birmingham B15 2TH, United Kingdom; Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle, Washington 98108; and University of Southern California (C.A.S.), Los Angeles, California 90089.
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.
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 cancerpatients. 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.
Authors: C A Spencer; M Takeuchi; M Kazarosyan; C C Wang; R B Guttler; P A Singer; S Fatemi; J S LoPresti; J T Nicoloff Journal: J Clin Endocrinol Metab Date: 1998-04 Impact factor: 5.958
Authors: Mark M Kushnir; Alan L Rockwood; William L Roberts; Dev Abraham; Andrew N Hoofnagle; A Wayne Meikle Journal: Clin Chem Date: 2013-02-08 Impact factor: 8.327
Authors: Brian C Netzel; Russell P Grant; Andrew N Hoofnagle; Alan L Rockwood; Christopher M Shuford; Stefan K G Grebe Journal: Clin Chem Date: 2015-10-01 Impact factor: 8.327
Authors: Ari J Wassner; Margaret Della Vecchia; Petr Jarolim; Henry A Feldman; Stephen A Huang Journal: J Clin Endocrinol Metab Date: 2017-09-01 Impact factor: 5.958
Authors: Bing Zhang; Jeffrey R Whiteaker; Andrew N Hoofnagle; Geoffrey S Baird; Karin D Rodland; Amanda G Paulovich Journal: Nat Rev Clin Oncol Date: 2019-04 Impact factor: 66.675