National comparability and inter-laboratory performance of cortisol immunoassays and LC-MS/MS methods

Objectives Cortisol measurements are often performed as part of dynamic testing for endocrine disorders. However, considerable variation between cortisol assays may prevent the interchangeability of dynamic test results and interpretation. This study evaluated the comparability and inter-laboratory performance of cortisol immunoassays with that of analytically preferred LC-MS/MS cortisol assays.Methods Serum samples from 45 participants were analyzed using Roche Cobas, Abbott Architect/Alinity, Siemens Atellica (including Siemens Atellica CSI), Beckman Coulter DxI/access immunoassays, and LC-MS/MS in 4-6 laboratories per assay. Passing-Bablok regression and Bland-Altman analyses were performed and inter-laboratory performance was determined for each immunoassay.Results Roche, Abbott and Beckman Coulter immunoassays showed good agreement with LC-MS/MS (bias -3.2 , -6.7 and -5.6 %). The original Siemens immunoassay showed poor agreement (bias 25.3 %), which improved substantially with the Siemens CSI assay (bias 4.9 %). Inter-laboratory performance was acceptable for Roche and Abbott, intermediate for Siemens CSI, but poor for the Beckman Coulter assay. Respectively 0, 2.3, 12.5 and 56.8 % of the cortisol measurements exceeded the maximal allowable imprecision.Conclusions Assay comparability and inter-laboratory performance were acceptable for the Roche and Abbott cortisol immunoassays. The Beckman Coulter immunoassay showed high imprecision necessitating improvement. The bias of the Siemens immunoassay vs. LC-MS/MS was strongly reduced following immunoassay improvement (Siemens CSI), demonstrating that significant efforts can lead to much-needed assay improvements. Based on our findings using human sera primarily within the basal cortisol concentration range, we conclude that there is no need for a national standardization program for serum cortisol measurements.