TY  - JOUR
A1  - Bliziotis, Nikolaos G.
A1  - Kluijtmans, Leo A. J.
A1  - Tinnevelt, Gerjen H.
A1  - Reel, Parminder
A1  - Reel, Smarti
A1  - Langton, Katharina
A1  - Robledo, Mercedes
A1  - Pamporaki, Christina
A1  - Pecori, Alessio
A1  - Van Kralingen, Josie
A1  - Tetti, Martina
A1  - Engelke, Udo F. H.
A1  - Erlic, Zoran
A1  - Engel, Jasper
A1  - Deutschbein, Timo
A1  - Nölting, Svenja
A1  - Prejbisz, Aleksander
A1  - Richter, Susan
A1  - Adamski, Jerzy
A1  - Januszewicz, Andrzej
A1  - Ceccato, Filippo
A1  - Scaroni, Carla
A1  - Dennedy, Michael C.
A1  - Williams, Tracy A.
A1  - Lenzini, Livia
A1  - Gimenez-Roqueplo, Anne-Paule
A1  - Davies, Eleanor
A1  - Fassnacht, Martin
A1  - Remde, Hanna
A1  - Eisenhofer, Graeme
A1  - Beuschlein, Felix
A1  - Kroiss, Matthias
A1  - Jefferson, Emily
A1  - Zennaro, Maria-Christina
A1  - Wevers, Ron A.
A1  - Jansen, Jeroen J.
A1  - Deinum, Jaap
A1  - Timmers, Henri J. L. M.
T1  - Preanalytical pitfalls in untargeted plasma nuclear magnetic resonance metabolomics of endocrine hypertension
JF  - Metabolites
N2  - Despite considerable morbidity and mortality, numerous cases of endocrine hypertension (EHT) forms, including primary aldosteronism (PA), pheochromocytoma and functional paraganglioma (PPGL), and Cushing’s syndrome (CS), remain undetected. We aimed to establish signatures for the different forms of EHT, investigate potentially confounding effects and establish unbiased disease biomarkers. Plasma samples were obtained from 13 biobanks across seven countries and analyzed using untargeted NMR metabolomics. We compared unstratified samples of 106 PHT patients to 231 EHT patients, including 104 PA, 94 PPGL and 33 CS patients. Spectra were subjected to a multivariate statistical comparison of PHT to EHT forms and the associated signatures were obtained. Three approaches were applied to investigate and correct confounding effects. Though we found signatures that could separate PHT from EHT forms, there were also key similarities with the signatures of sample center of origin and sample age. The study design restricted the applicability of the corrections employed. With the samples that were available, no biomarkers for PHT vs. EHT could be identified. The complexity of the confounding effects, evidenced by their robustness to correction approaches, highlighted the need for a consensus on how to deal with variabilities probably attributed to preanalytical factors in retrospective, multicenter metabolomics studies.
KW  - confounders
KW  - metabolomics
KW  - multicenter
KW  - plasma NMR
KW  - preanalytical conditions
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-282930
SN  - 2218-1989
VL  - 12
IS  - 8
ER  -