TY - JOUR
T1 - Report from the HarmoSter study
T2 - Different LC-MS/MS androstenedione, DHEAS and testosterone methods compare well; However, unifying calibration is a double-edged sword
AU - Fanelli, Flaminia
AU - Peitzsch, Mirko
AU - Bruce, Stephen
AU - Cantù, Marco
AU - Temchenko, Anastasia
AU - Mezzullo, Marco
AU - Lindner, Johanna M.
AU - Hawley, James M.
AU - Ackermans, Mariette T.
AU - van den Ouweland, Jody
AU - Koeppl, Daniel
AU - Nardi, Elena
AU - Mackenzie, Finlay
AU - Binz, Pierre-Alain
AU - Rauh, Manfred
AU - Keevil, Brian G.
AU - Vogeser, Michael
AU - Eisenhofer, Graeme
AU - Heijboer, Annemieke C.
AU - Pagotto, Uberto
N1 - Publisher Copyright: © 2024 Walter de Gruyter GmbH, Berlin/Boston 2024.
PY - 2024
Y1 - 2024
N2 - Current LC-MS/MS applications for circulating androgen measurements are technically diverse. Previously, variable results have been reported for testosterone. Data are scarce for androstenedione and absent for DHEAS. We assessed the agreement of androstenedione, DHEAS and testosterone LC-MS/MS measurements among nine European centers and explored benefits of calibration system unification. Androgens were measured twice by laboratory-specific procedures in 78 patient samples and in EQA materials. Results were obtained by in-house and external calibration. Intra- and inter-laboratory performances were valued. Intra-laboratory CVs ranged between 4.2-13.2 » % for androstenedione, 1.6-10.8 » % for DHEAS, and 4.3-8.7 » % and 2.6-7.1 » % for female and male testosterone, respectively. Bias and trueness in EQA materials were within ±20 » %. Median inter-laboratory CV with in-house vs. external calibration were 12.0 vs. 9.6 » % for androstenedione (p<0.001), 7.2 vs. 4.9 » % for DHEAS (p<0.001), 6.4 vs. 7.6 » % for female testosterone (p<0.001) and 6.8 and 7.4 » % for male testosterone (p=0.111). Median bias vs. all laboratory median with in-house and external calibration were -13.3 to 20.5 » % and -4.9 to 18.7 » % for androstenedione, -10.9 to 4.8 » % and -3.4 to 3.5 » % for DHEAS, -2.7 to 6.5 % and -11.3 to 6.6 » % for testosterone in females, and -7.0 to 8.5 » % and -7.5 to 11.8 » % for testosterone in males, respectively. Methods showed high intra-laboratory precision but variable bias and trueness. Inter-laboratory agreement was remarkably good. Calibration system unification improved agreement in androstenedione and DHEAS, but not in testosterone measurements. Multiple components, such as commutability of calibrators and EQA materials and internal standard choices, likely contribute to inter-laboratory variability.
AB - Current LC-MS/MS applications for circulating androgen measurements are technically diverse. Previously, variable results have been reported for testosterone. Data are scarce for androstenedione and absent for DHEAS. We assessed the agreement of androstenedione, DHEAS and testosterone LC-MS/MS measurements among nine European centers and explored benefits of calibration system unification. Androgens were measured twice by laboratory-specific procedures in 78 patient samples and in EQA materials. Results were obtained by in-house and external calibration. Intra- and inter-laboratory performances were valued. Intra-laboratory CVs ranged between 4.2-13.2 » % for androstenedione, 1.6-10.8 » % for DHEAS, and 4.3-8.7 » % and 2.6-7.1 » % for female and male testosterone, respectively. Bias and trueness in EQA materials were within ±20 » %. Median inter-laboratory CV with in-house vs. external calibration were 12.0 vs. 9.6 » % for androstenedione (p<0.001), 7.2 vs. 4.9 » % for DHEAS (p<0.001), 6.4 vs. 7.6 » % for female testosterone (p<0.001) and 6.8 and 7.4 » % for male testosterone (p=0.111). Median bias vs. all laboratory median with in-house and external calibration were -13.3 to 20.5 » % and -4.9 to 18.7 » % for androstenedione, -10.9 to 4.8 » % and -3.4 to 3.5 » % for DHEAS, -2.7 to 6.5 % and -11.3 to 6.6 » % for testosterone in females, and -7.0 to 8.5 » % and -7.5 to 11.8 » % for testosterone in males, respectively. Methods showed high intra-laboratory precision but variable bias and trueness. Inter-laboratory agreement was remarkably good. Calibration system unification improved agreement in androstenedione and DHEAS, but not in testosterone measurements. Multiple components, such as commutability of calibrators and EQA materials and internal standard choices, likely contribute to inter-laboratory variability.
KW - androstenedione
KW - dehydroepiandrosterone-sulfate
KW - harmonization
KW - inter-laboratory performance
KW - liquid chromatography-tandem mass spectrometry
KW - testosterone
UR - http://www.scopus.com/inward/record.url?scp=85182563203&partnerID=8YFLogxK
U2 - 10.1515/cclm-2023-1138
DO - 10.1515/cclm-2023-1138
M3 - Article
C2 - 38205643
SN - 1434-6621
JO - Clinical chemistry and laboratory medicine
JF - Clinical chemistry and laboratory medicine
ER -