title: Thyroglobulin (Tg) Testing Revisited: Tg Assays, TgAb Assays, and Correlation of Results With Clinical Outcomes.
abstract: BACKGROUND
  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.
authors.affiliation: 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.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Netzel
authors.affiliation: 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.
authors.forename: Stefan K G
authors.initials: SK
authors.lastname: Grebe
authors.affiliation: 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.
authors.forename: B Gisella
authors.initials: BG
authors.lastname: Carranza Leon
authors.affiliation: 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.
authors.forename: M Regina
authors.initials: MR
authors.lastname: Castro
authors.affiliation: 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.
authors.forename: Penelope M
authors.initials: PM
authors.lastname: Clark
authors.affiliation: 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.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Hoofnagle
authors.affiliation: 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.
authors.forename: Carole A
authors.initials: CA
authors.lastname: Spencer
authors.affiliation: 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.
authors.forename: Adina F
authors.initials: AF
authors.lastname: Turcu
authors.affiliation: 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.
authors.forename: Alicia
authors.initials: A
authors.lastname: Algeciras-Schimnich
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000032:analysis* / Q000097:blood; D002853:Chromatography, Liquid; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011863:Radioimmunoassay / Q000379:methods; D053719:Tandem Mass Spectrometry; D013954:Thyroglobulin / Q000032:analysis* / Q000097:blood; D013960:Thyroid Function Tests / Q000379:methods / Q000592:standards; D013964:Thyroid Neoplasms / Q000097:blood / Q000175:diagnosis*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; C006606:anti-thyroglobulin; D013954:Thyroglobulin