A Progress Report of the IFCC Committee for Standardization of Thyroid Function Tests

Abstract

Background: The IFCC Committee for Standardization of Thyroid Function Tests aims at equivalence of laboratory test results for free thyroxine (FT4) and thyrotropin (TSH). Objectives: This report describes the phase III method comparison study with clinical samples representing a broad spectrum of thyroid disease. The objective was to expand the feasibility work and explore the impact of standardization/harmonization in the clinically relevant concentration range. Methods: Two sets of serum samples (74 for FT4, 94 for TSH) were obtained in a clinical setting. Eight manufacturers participated in the study (with 13 FT4 and 14 TSH assays). Targets for FT4 were set by the international conventional reference measurement procedure of the IFCC; those for TSH were based on the all-procedure trimmed mean. The manufacturers recalibrated their assays against these targets. Results: All FT4 assays were negatively biased in the mid- to high concentration range, with a maximum interassay discrepancy of approximately 30%. However, in the low range, the maximum deviation was approximately 90%. For TSH, interassay comparability was reasonable in the mid-concentration range, but worse in the pathophysiological ranges. Recalibration was able to eliminate the interassay differences, so that the remaining dispersion of the data was nearly entirely due to within-assay random error components. The impact of recalibration on the numerical results was particularly high for FT4. Conclusions: Standardization and harmonization of FT4 and TSH measurements is feasible from a technical point of view. Because of the impact on the numerical values, the implementation needs careful preparation with the stakeholders.

Monitoring the stability of the standardization status of FT4 and TSH assays by use of daily outpatient medians and flagging frequencies

“…The medians of these previous studies were perfectly suited for comparison, because they were calculated from results of method comparison studies with samples from apparently healthy (euthyroid) volunteers. Note that here we again report anonymously on the peer group data -as we did in all previous reports [6,7,14,16] -simply because the current study was only exploratory and did not yet include all manufacturers/instruments test systems. Anyhow, we see the observations in Figure 2 as a first basis of evidence for the utility of the Percentiler to 16 serve the purpose implied by the FDA.…”

“…Note that here we again report anonymously on the peer group data -as we did in all previous reports [6,7,14,16] -simply because the current study was only exploratory and did not yet include all manufacturers/instruments test systems. Anyhow, we see the observations in Figure 2 as a first basis of evidence for the utility of the Percentiler to 16 serve the purpose implied by the FDA. We expect this evidence to increase, the more solid the peer groups become (lower variability of the medians) [19,20].…”

Subclinical hypothyroidism: a ‘laboratory-induced’ condition?

“…Before the standardization of clinical management of subclinical thyroid disorders can be successful, harmonization on a laboratory level is required first. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has recognized this necessity and has recently initiated a project to harmonize results from different TSH and fT 4 assays (18). The inclusion of reference values and TSH-decision points in this harmonization process will allow for laboratoryindependent clinical decision-making regarding thyroid disorders.…”

New Immunoassays of Bioactive TSH Improve Detection of Thyroid Disorders

“…In our opinion, such issue will remain unsolved as long as TSH assays show analytic bias [15]. Efforts are currently done by the IFCC Committee for Standardization of Thyroid Function Tests which recently proposed a mathematical recalibration to harmonize values among manufacturers [50,51]. However, this approach does not take into account the pathophysiological polymorphism of this hormone which may lead to underestimate TSH level in some assays.…”