Association of adrenal steroids with metabolomic profiles in patients with primary and endocrine hypertension

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Robin Knuchel - , University of Zurich (Author)
  • Zoran Erlic - , University of Zurich (Author)
  • Sven Gruber - , University of Zurich (Author)
  • Laurence Amar - , Université Paris Cité, Hopital Europeen Georges-Pompidou (Author)
  • Casper K. Larsen - , Université Paris Cité (Author)
  • Anne Paule Gimenez-Roqueplo - , Université Paris Cité, Hopital Europeen Georges-Pompidou (Author)
  • Paolo Mulatero - , University of Turin (Author)
  • Martina Tetti - , University of Turin (Author)
  • Alessio Pecori - , University of Turin (Author)
  • Christina Pamporaki - , Department of Distributed and Data Intensive Computing (VDR), Department of Internal Medicine III, Center for Information Services and High Performance Computing (ZIH), University Hospital Carl Gustav Carus Dresden (Author)
  • Katharina Langton - , Center for Midwifery Sciences, Department of Gynecology and Obstetrics, Medizinische Klinik und Poliklinik III, Bereich Allgemeinmedizin, University Hospital Carl Gustav Carus Dresden (Author)
  • Mirko Peitzsch - , Institute of Clinical Chemistry and Laboratory Medicine (Author)
  • Filippo Ceccato - , University of Padua (Author)
  • Aleksander Prejbisz - , Cardinal Stefan Wyszynski Institute of Cardiology (Author)
  • Andrzej Januszewicz - , Cardinal Stefan Wyszynski Institute of Cardiology (Author)
  • Christian Adolf - , Ludwig Maximilian University of Munich (Author)
  • Hanna Remde - , University of Würzburg (Author)
  • Livia Lenzini - , University of Padua (Author)
  • Michael Dennedy - , University of Galway (Author)
  • Jaap Deinum - , Radboud University Nijmegen (Author)
  • Emily Jefferson - , University of Dundee (Author)
  • Anne Blanchard - , Hopital Europeen Georges-Pompidou (Author)
  • Maria Christina Zennaro - , Université Paris Cité, Hopital Europeen Georges-Pompidou (Author)
  • Graeme Eisenhofer - , Department of Internal Medicine III, University Hospital Carl Gustav Carus Dresden (Author)
  • Felix Beuschlein - , University of Zurich, Ludwig Maximilian University of Munich, The LOOP Zurich Medical Research Center (Author)

Abstract

Introduction: Endocrine hypertension (EHT) due to pheochromocytoma/paraganglioma (PPGL), Cushing’s syndrome (CS), or primary aldosteronism (PA) is linked to a variety of metabolic alterations and comorbidities. Accordingly, patients with EHT and primary hypertension (PHT) are characterized by distinct metabolic profiles. However, it remains unclear whether the metabolomic differences relate solely to the disease-defining hormonal parameters. Therefore, our objective was to study the association of disease defining hormonal excess and concomitant adrenal steroids with metabolomic alterations in patients with EHT. Methods: Retrospective European multicenter study of 263 patients (mean age 49 years, 50% females; 58 PHT, 69 PPGL, 37 CS, 99 PA) in whom targeted metabolomic and adrenal steroid profiling was available. The association of 13 adrenal steroids with differences in 79 metabolites between PPGL, CS, PA and PHT was examined after correction for age, sex, BMI, and presence of diabetes mellitus. Results: After adjustment for BMI and diabetes mellitus significant association between adrenal steroids and metabolites – 18 in PPGL, 15 in CS, and 23 in PA – were revealed. In PPGL, the majority of metabolite associations were linked to catecholamine excess, whereas in PA, only one metabolite was associated with aldosterone. In contrast, cortisone (16 metabolites), cortisol (6 metabolites), and DHEA (8 metabolites) had the highest number of associated metabolites in PA. In CS, 18-hydroxycortisol significantly influenced 5 metabolites, cortisol affected 4, and cortisone, 11-deoxycortisol, and DHEA each were linked to 3 metabolites. Discussions: Our study indicates cortisol, cortisone, and catecholamine excess are significantly associated with metabolomic variances in EHT versus PHT patients. Notably, catecholamine excess is key to PPGL’s metabolomic changes, whereas in PA, other non-defining adrenal steroids mainly account for metabolomic differences. In CS, cortisol, alongside other non-defining adrenal hormones, contributes to these differences, suggesting that metabolic disorders and cardiovascular morbidity in these conditions could also be affected by various adrenal steroids.

Details

Original languageEnglish
Article number1370525
JournalFrontiers in endocrinology
Volume15
Publication statusPublished - 2024
Peer-reviewedYes

External IDs

ORCID /0000-0003-0772-1604/work/184442884

Keywords

Sustainable Development Goals

Keywords

  • adrenal steroids, Cushing’s syndrome, endocrine hypertension, metabolomics, pheochromocytoma, primary aldosteronism, primary hypertension