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

• DOI: 10.3389/fendo.2024.1370525
• Publication Date: 2024-03-26T05:00:21Z
• Authors: Robin Knuchel; Zoran Erlic; Sven Gruber; Laurence Amar; Casper K. Larsen; Anne-Paule Gimene...; Paolo Mulatero; Martina Tetti; Alessio Pecori; Christina Pamporaki; Katharina Langton; Mirko Peitzsch; Filippo Ceccato; Aleksander Prejbisz; Andrzej Januszewicz; Christian Adolf; Hanna Remde; Livia Lenzini; Michael Dennedy; Jaap Deinum; Emily Jefferson; Anne Blanchard; Maria-Christina Z...; Graeme Eisenhofer; Felix Beuschlein
• Keywords: 0301 basic medicine; primary aldosteronism; endocrine hypertension; 10265 Clinic for Endocrinology and Diabetology; adrenal steroids; 610; 610 Medicine & health; RC648-665; metabolomics; pheochromocytoma; Diseases of the endocrine glands. Clinical endocrinology; Diabetes and Metabolism; primary hypertension; 2712 Endocrinology, Diabetes and Metabolism; 03 medical and health sciences; Endocrinology; Cushing’s syndrome; /dk/atira/pure/subjectarea/asjc/2700/2712; 615; Internal Medicine - Radboud University Medical Center; name=Endocrinology

IntroductionEndocrine 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.MethodsRetrospective 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.ResultsAfter 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.DiscussionsOur 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.