Report from the HarmoSter study: impact of calibration on comparability of LC-MS/MS measurement of circulating cortisol, 17OH-progesterone and aldosterone
Abstract
Objectives: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is recommended for measuring circulating steroids. However, assays display technical heterogeneity. So far, reproducibility of corticosteroid LC-MS/MS measurements has received scant attention. The aim of the study was to compare LC-MS/MS measurements of cortisol, 17OH-progesterone and aldosterone from nine European centers and assess performance according to external quality assessment (EQA) materials and calibration.
Methods: Seventy-eight patient samples, EQA materials and two commercial calibration sets were measured twice by laboratory-specific procedures. Results were obtained by in-house (CAL1) and external calibrations (CAL2 and CAL3). We evaluated intra and inter-laboratory imprecision, correlation and agreement in patient samples, and trueness, bias and commutability in EQA materials.
Results: Using CAL1, intra-laboratory CVs ranged between 2.8-7.4%, 4.4-18.0% and 5.2-22.2%, for cortisol, 17OH-progesterone and aldosterone, respectively. Trueness and bias in EQA materials were mostly acceptable, however, inappropriate commutability and target value assignment were highlighted in some cases. CAL2 showed suboptimal accuracy. Median inter-laboratory CVs for cortisol, 17OH-progesterone and aldosterone were 4.9, 11.8 and 13.8% with CAL1 and 3.6, 10.3 and 8.6% with CAL3 (all p<0.001), respectively. Using CAL1, median bias vs. all laboratory-medians ranged from -6.6 to 6.9%, -17.2 to 7.8% and -12.0 to 16.8% for cortisol, 17OH-progesterone and aldosterone, respectively. Regression lines significantly deviated from the best fit for most laboratories. Using CAL3 improved cortisol and 17OH-progesterone between-method bias and correlation.
Conclusions: Intra-laboratory imprecision and performance with EQA materials were variable. Inter-laboratory performance was mostly within specifications. Although residual variability persists, adopting common traceable calibrators and RMP-determined EQA materials is beneficial for standardization of LC-MS/MS steroid measurements.
Author
Fanelli, Flaminia
Cantù, Marco
Temchenko, Anastasia
Mezzullo, Marco
Lindner, Johanna M
Peitzsch, Mirko
Hawley, James M
Bruce, Stephen
Binz, Pierre-Alain
Ackermans, Mariette T
Heijboer, Annemieke C
Van den Ouweland, Jody
Koeppl, Daniel
Nardi, Elena
MacKenzie, Finlay
Rauh, Manfred
Eisenhofer, Graeme
Keevil, Brian G
Vogeser, Michael
Pagotto, Uberto
Cantù, Marco
Temchenko, Anastasia
Mezzullo, Marco
Lindner, Johanna M
Peitzsch, Mirko
Hawley, James M
Bruce, Stephen
Binz, Pierre-Alain
Ackermans, Mariette T
Heijboer, Annemieke C
Van den Ouweland, Jody
Koeppl, Daniel
Nardi, Elena
MacKenzie, Finlay
Rauh, Manfred
Eisenhofer, Graeme
Keevil, Brian G
Vogeser, Michael
Pagotto, Uberto
Citations
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Date
2022-02-16
Type
Article
Subject
Endocrinology
Collections
Citation
Fanelli F, Cantù M, Temchenko A, Mezzullo M, Lindner JM, Peitzsch M, Hawley JM, Bruce S, Binz PA, Ackermans MT, Heijboer AC, Van den Ouweland J, Koeppl D, Nardi E, MacKenzie F, Rauh M, Eisenhofer G, Keevil BG, Vogeser M, Pagotto U. Report from the HarmoSter study: impact of calibration on comparability of LC-MS/MS measurement of circulating cortisol, 17OH-progesterone and aldosterone. Clin Chem Lab Med. 2022 Feb 16;60(5):726-739. doi: 10.1515/cclm-2021-1028.
Journal / Source Title
Clinical Chemistry and Laboratory Medicine
DOI
10.1515/cclm-2021-1028
PMID
35172417
Publisher
Walter De Gruyter
Publisher’s URL
https://www.degruyter.com/journal/key/cclm/html