Urine steroid metabolomics as a diagnostic tool in primary aldosteronism
Year: 2023
Type: article
Study design: Observational Study
Abstract: Primary aldosteronism (PA) causes 5-10% of hypertension cases, but only a minority of patients are currently diagnosed and treated because of a complex, stepwise, and partly invasive workup. We tested the performance of urine steroid metabolomics, the computational analysis of 24-hour urine steroid metabolome data by machine learning, for the identification and subtyping of PA. Mass spectrometry-based multi-steroid profiling was used to quantify the excretion of 34 steroid metabolites in 24-hour urine samples from 158 adults with PA (88 with unilateral PA [UPA] due to aldosterone-producing adenomas [APAs]; 70 with bilateral PA [BPA]) and 65 sex- and age-matched healthy controls. All APAs were resected and underwent targeted gene sequencing to detect somatic mutations associated with UPA. Patients with PA had increased urinary metabolite excretion of mineralocorticoids, glucocorticoids, and glucocorticoid precursors. Urine steroid metabolomics identified patients with PA with high accuracy, both when applied to all 34 or only the three most discriminative steroid metabolites (average areas under the receiver-operating characteristics curve [AUCs-ROC] 0.95-0.97). Whilst machine learning was suboptimal in differentiating UPA from BPA (average AUCs-ROC 0.65-0.73), it readily identified APA cases harbouring somatic KCNJ5 mutations (average AUCs-ROC 0.79-85). These patients showed a distinctly increased urine excretion of the hybrid steroid 18-hydroxycortisol and its metabolite 18-oxo-tetrahydrocortisol, the latter identified by machine learning as by far the most discriminative steroid. In conclusion, urine steroid metabolomics is a non-invasive candidate test for the accurate identification of PA cases and KCNJ5-mutated APAs.
Institutions: University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, NIHR Birmingham Biomedical Research Centre, University of Birmingham, University of Groningen, LMU Klinikum, Hôpital Foch, Ludwig-Maximilians-Universität München, UCSF Benioff Children's Hospital, University of Würzburg, Universitätsklinikum Würzburg, Radboud University Medical Center, University of Zurich, University Hospital Zurich, Imperial College London, Medical Research Council
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,490
Funders: Chicago Executive Pilots Association, University Hospitals Birmingham NHS Foundation Trust, National Institute for Health and Care Research, Department of Health and Social Care, Diabetes UK, European Commission, University of Birmingham, Deutsche Forschungsgemeinschaft, ZonMw, Else Kröner-Fresenius-Stiftung, Universität Zürich, Friedrich-Baur-Stiftung, Medical Research Council, European Research Council, Birmingham Biomedical Research Centre, H2020 European Research Council
Awards: G1070500708, G277302614, G3158482870, G3589644081, G4002980589, G4979018447, Pathophysiology of Primary Aldosteronism, Application of omics-based strategies for improved diagnosis and treatment of endocrine hypertension, G600920662, G6413755006, Purchase of 2 x Mass Spectrometers and Associated Works, G8922451413, Selective CYP11B1 inhibitors as a novel treatment option for endogenous cortisol excess
OpenAlex ID: W4389778344