TY - JOUR
T1 - Report from the HarmoSter study
T2 - Inter-laboratory comparison of LC-MS/MS measurements of corticosterone, 11-deoxycortisol and cortisone
AU - Fanelli, Flaminia
AU - Bruce, Stephen
AU - Cantù, Marco
AU - Temchenko, Anastasia
AU - Mezzullo, Marco
AU - Lindner, Johanna M.
AU - Peitzsch, Mirko
AU - Binz, Pierre-Alain
AU - Ackermans, Mariette T.
AU - Heijboer, Annemieke C.
AU - van den Ouweland, Jody
AU - Koeppl, Daniel
AU - Nardi, Elena
AU - Rauh, Manfred
AU - Vogeser, Michael
AU - Eisenhofer, Graeme
AU - Pagotto, Uberto
N1 - Funding Information: Research funding: This study was supported by the Emilia-Romagna Region, Alessandro Liberati Young Researcher Grants (project number PRUA 1-2012-004, granted to FF) and by Deutsche Forschungsgemeinschaft (DFG), German Research Foundation (project number 314061271-CRC/TRR 205, granted to MP and GE). Publisher Copyright: © 2022 the author(s), published by De Gruyter, Berlin/Boston.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - Objectives: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) panels that include glucocorticoid-related steroids are increasingly used to characterize and diagnose adrenal cortical diseases. Limited information is currently available about reproducibility of these measurements among laboratories. The aim of the study was to compare LC-MS/MS measurements of corticosterone, 11-deoxycortisol and cortisone at eight European centers and assess the performance after unification of calibration. Methods: Seventy-eight patient samples and commercial calibrators were measured twice by laboratory-specific procedures. Results were obtained according to in-house and external calibration. We evaluated intra-laboratory and inter-laboratory imprecision, regression and agreement against performance specifications derived from 11-deoxycortisol biological variation. Results: Intra-laboratory CVs ranged between 3.3 and 7.7%, 3.3 and 11.8% and 2.7 and 12.8% for corticosterone, 11-deoxycortisol and cortisone, with 1, 4 and 3 laboratories often exceeding the maximum allowable imprecision (MAI), respectively. Median inter-laboratory CVs were 10.0, 10.7 and 6.2%, with 38.5, 50.7 and 2.6% cases exceeding the MAI for corticosterone, 11-deoxycortisol and cortisone, respectively. Median laboratory bias vs. all laboratory-medians ranged from -5.6 to 12.3% for corticosterone, -14.6 to 12.4% for 11-deoxycortisol and -4.0 to 6.5% for cortisone, with few cases exceeding the total allowable error. Modest deviations were found in regression equations among most laboratories. External calibration did not improve 11-deoxycortisol and worsened corticosterone and cortisone inter-laboratory comparability. Conclusions: Method imprecision was variable. Inter-laboratory performance was reasonably good. However, cases with imprecision and total error above the acceptable limits were apparent for corticosterone and 11-deoxycortisol. Variability did not depend on calibration but apparently on imprecision, accuracy and specificity of individual methods. Tools for improving selectivity and accuracy are required to improve harmonization.
AB - Objectives: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) panels that include glucocorticoid-related steroids are increasingly used to characterize and diagnose adrenal cortical diseases. Limited information is currently available about reproducibility of these measurements among laboratories. The aim of the study was to compare LC-MS/MS measurements of corticosterone, 11-deoxycortisol and cortisone at eight European centers and assess the performance after unification of calibration. Methods: Seventy-eight patient samples and commercial calibrators were measured twice by laboratory-specific procedures. Results were obtained according to in-house and external calibration. We evaluated intra-laboratory and inter-laboratory imprecision, regression and agreement against performance specifications derived from 11-deoxycortisol biological variation. Results: Intra-laboratory CVs ranged between 3.3 and 7.7%, 3.3 and 11.8% and 2.7 and 12.8% for corticosterone, 11-deoxycortisol and cortisone, with 1, 4 and 3 laboratories often exceeding the maximum allowable imprecision (MAI), respectively. Median inter-laboratory CVs were 10.0, 10.7 and 6.2%, with 38.5, 50.7 and 2.6% cases exceeding the MAI for corticosterone, 11-deoxycortisol and cortisone, respectively. Median laboratory bias vs. all laboratory-medians ranged from -5.6 to 12.3% for corticosterone, -14.6 to 12.4% for 11-deoxycortisol and -4.0 to 6.5% for cortisone, with few cases exceeding the total allowable error. Modest deviations were found in regression equations among most laboratories. External calibration did not improve 11-deoxycortisol and worsened corticosterone and cortisone inter-laboratory comparability. Conclusions: Method imprecision was variable. Inter-laboratory performance was reasonably good. However, cases with imprecision and total error above the acceptable limits were apparent for corticosterone and 11-deoxycortisol. Variability did not depend on calibration but apparently on imprecision, accuracy and specificity of individual methods. Tools for improving selectivity and accuracy are required to improve harmonization.
KW - 11-deoxycortisol
KW - calibration
KW - corticosterone
KW - cortisone
KW - harmonization
KW - inter-laboratory performance
KW - liquid chromatography - tandem mass spectrometry
KW - method comparison
KW - steroid hormones
UR - http://www.scopus.com/inward/record.url?scp=85141061342&partnerID=8YFLogxK
U2 - https://doi.org/10.1515/cclm-2022-0242
DO - https://doi.org/10.1515/cclm-2022-0242
M3 - Article
C2 - 36288389
SN - 1434-6621
VL - 61
SP - 67
EP - 77
JO - Clinical chemistry and laboratory medicine
JF - Clinical chemistry and laboratory medicine
IS - 1
ER -