Analytic bias of thyroid function tests: Analysis of a College of American Pathologists fresh frozen serum pool by 3900 clinical laboratories

Bernard W. Steele, Edward Wang, George G. Klee, Linda M. Thienpont, Steven J. Soldin, Lori J. Sokoll, William E. Winter, Susan A. Fuhrman, Ronald J. Elin

Research output: Contribution to journalReview articlepeer-review

46 Scopus citations


Context.-In proficiency testing surveys, there are differences in the values reported by users of various analytic methods. Two contributors to this variation are calibrator bias and matrix effects of proficiency testing materials. Objectives.-(1) To quantify the biases of the analytic methods used to measure thyroid-stimulating hormone, thyroxine, triiodothyronine, free thyroxine, and free triiodothyronine levels; (2) to determine if these biases are within allowable limits; and (3) to ascertain if proficiency testing materials correctly identify these biases. Design.-A fresh frozen serum specimen was mailed as part of the 2003 College of American Pathologists Ligand and Chemistry surveys. The means and SDs for each analytic method were determined for this sample as well as for a proficiency testing sample from both surveys. In the fresh frozen serum sample, target values for thyroxine and triiodothyronine were determined by isotope dilution/liquid chromatography/ tandem mass spectrometry. All other target values in the study were the median of the means obtained for the various analytic methods. Main Outcome Measures.-Calibration biases were calculated by comparing the mean of each analytic method with the appropriate target values. These biases were evaluated against limits based on intra- and interindividual biological variation. Matrix effects of proficiency testing materials were assessed by comparing the rank of highest to lowest analytic method means (Spearman rank test) for each analyte. Participants.-Approximately 3900 clinical laboratories were enrolled in the College of American Pathologisis Chemistry and Ligand surveys. Results.-The number of methods in the Ligand Survey that failed to meet the goals for bias was 7 of 17 for thyroid-stimulating hormone and 11 of 13 for free thyroxine. The failure rates were 12 of 16 methods for thyroxine, 8 of 11 for -triiodothyronine, and 9 of 11 for free triiodothyronine. The means of the analytic method for the proficiency testing material correlated significantly (P < .05) only with the fresh frozen serum means for thyroxine and thyroid-stimulating hormone in the Chemistry Survey and free triiodothyronine in the Ligand Survey. Conclusions.-A majority of the methods used in thyroid function testing have biases that limit their clinical utility. Traditional proficiency testing materials do not adequately reflect these biases.

Original languageEnglish (US)
Pages (from-to)310-317
Number of pages8
JournalArchives of Pathology and Laboratory Medicine
Issue number3
StatePublished - Mar 2005

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology


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