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

Front Endocrinol (Lausanne). 2024 Mar 26:15:1370525. doi: 10.3389/fendo.2024.1370525. eCollection 2024.

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.

Keywords: Cushing’s syndrome; adrenal steroids; endocrine hypertension; metabolomics; pheochromocytoma; primary aldosteronism; primary hypertension.

Publication types

  • Multicenter Study

MeSH terms

  • Adrenal Gland Neoplasms* / complications
  • Catecholamines
  • Cortisone*
  • Cushing Syndrome* / complications
  • Dehydroepiandrosterone
  • Diabetes Mellitus*
  • Female
  • Humans
  • Hydrocortisone / metabolism
  • Hypertension* / complications
  • Male
  • Middle Aged
  • Paraganglioma* / complications
  • Pheochromocytoma* / complications
  • Retrospective Studies
  • Steroids

Substances

  • Hydrocortisone
  • Cortisone
  • Steroids
  • Catecholamines
  • Dehydroepiandrosterone

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 633983 (ENSAT-HT to all authors, except MD), by the Clinical Research Priority Program of the University of Zurich for the CRPP HYRENE (to FB), the Deutsche Forschungsgemeinschaft project number 314061271 (CRC/Transregio 205/1 “The Adrenal: Central relay of health and disease” to GE, MP, CP, FB) and the Philhuman Stiftung Vaduz, Lichtenstein (to ZE).