INTERLABORATORY INTERMETHOD DIFFERENCES IN FUNCTIONAL SENSITIVITY OF IMMUNOMETRIC ASSAYS OF THYROTROPIN (TSH) AND IMPACT ON RELIABILITY OF MEASUREMENT OF SUBNORMAL CONCENTRATIONS OF TSH

Clinically relevant interassay precision profiles for thyrotropin (thy roid-stimulating hormone; TSH) were constructed with human serum pools measured over 4-8 weeks by six immunometric assays, in at least two d ifferent reagent lots, Functional sensitivities (the concentration at which the interassay CV is less than or equal to 20%) were determined in four to eight clinical laboratories plus the respective manufacture r'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 see n with some methods when used to measure certain unrefrigerated low-TS H sera. Measurement of TSH in four human serum pools (TSH <0.05-0.25 m lU/L) by 16 different methods (each in at least eight UK or US laborat ories) showed that some methods could not reliably distinguish subnorm al from normal TSH values. Better pool rankings and fewer misclassific ations of low-TSH sera as ''normal'' were seen with use of assays capa ble of ''third-generation'' functional sensitivity (0.01-0.02 mlU/L) t han with assays with ''second-generation'' functional sensitivity (0.1 -0.2 mlU/L). Because inter- and intramethod differences in functional sensitivity negatively impact the diagnostic accuracy and cost-effecti veness of a TSH-centered thyroid-testing strategy, laboratories should independently establish an assay's functional sensitivity by a clinic ally relevant protocol. Moreover, manufacturers should assess function al sensitivity more realistically and improve the robustness of assays to ensure that their performance potential is consistently met in cli nical practice.