Interlaboratory/intermethod differences in functional sensitivity of immunometric assays of thyrotropin (TSH) and impact on reliability of measurement of subnormal concentrations of TSH

Abstract

Clinically relevant interassay precision profiles for thyrotropin (thyroid-stimulating hormone; TSH) were constructed with human serum pools measured over 4-8 weeks by six immunometric assays, in at least two different reagent lots. Functional sensitivities (the concentration at which the interassay CV is < or = 20%) were determined in four to eight clinical laboratories plus the respective manufacturer's laboratory. These studies revealed that the manufacturer's stated functional sensitivity limit is rarely duplicated in clinical practice. Loss of specificity (indicated by artifactually high values) was seen with some methods when used to measure certain unrefrigerated low-TSH sera. Measurement of TSH in four human serum pools (TSH < 0.05-0.25 mIU/L) by 16 different methods (each in at least eight UK or US laboratories) showed that some methods could not reliably distinguish subnormal from normal TSH values. Better pool rankings and fewer misclassifications of low-TSH sera as "normal" were seen with use of assays capable of "third-generation" functional sensitivity (0.01-0.02 mIU/L) than with assays with "second-generation" functional sensitivity (0.1-0.2 mIU/L). Because inter- and intramethod differences in functional sensitivity negatively impact the diagnostic accuracy and cost-effectiveness of a TSH-centered thyroid-testing strategy, laboratories should independently establish an assay's functional sensitivity by a clinically relevant protocol. Moreover, manufacturers should assess functional sensitivity more realistically and improve the robustness of assays to ensure that their performance potential is consistently met in clinical practice.

Clinical performance evaluation of the new hematology analyzer Mindray BC‐6000

“…25 The precision profile 13 is a very useful evaluation method for functional detection limit (functional sensitivity). 14 In comparison studies, all routinely used CBC parameters were comparable and showed very high correlations between BC-6000 and Sysmex XN with the same samples in terms of clinical usefulness by the Passing-Bablok 20 and Bland-Altman analyses. 22 And also, for the leukocyte differential parameters, BC-6000 and manual microscopy have more consistent results, especially for monocytes and immature granulocytes when compared to the previous report.…”

“…to fit the datasets 13 : %CV = C 0 X C1 . The functional detection limit (functional sensitivity) 14 was defined as "the lowest concentration at which an assay can report clinically useful results." Most laboratories use an imprecision coefficient of variation (CV) of 20% to define the lowest reportable concentration.…”

Evaluation of the Sysmex XT‐4000i for the automated body fluid analysis

“…Functional sensitivity of WBC count was defined by running a BF sample ten times and calculating the CV%. The point where the CV exceeded 20% was defined as the functional detection limit, which is considered the lowest concentration at which an assay can report clinically useful results .…”

Levels of Thyroid Hormones and Human Chorionic Gonadotropin in Normotensive Pregnant Women

“…4,5 Third-generation TSH and hCG concentrations were measured by solid-phase, two site chemiluminescent immunometric assay. 6…”