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Context: Primary aldosteronism is a form of low-renin hypertension characterized by dysregulated aldosterone production.
Objective: To investigate the contributions of renin-independent aldosteronism and ACTH-mediated aldosteronism in individuals with a low-renin phenotype representing the entire continuum of blood pressure.
Design/participants: Human physiology study of 348 participants with a low-renin phenotype with severe and/or resistant hypertension, hypertension with hypokalemia, elevated blood pressure and stage I/II hypertension, and normal blood pressure.
Setting: 4 international centers.
Interventions/main Outcome Measures: The saline suppression test (SST) to quantify the magnitude of renin-independent aldosteronism; dexamethasone suppression and ACTH-stimulation tests to quantify the magnitude of ACTH-mediated aldosteronism; adrenal venous sampling to determine lateralization.
Results: There was a continuum of nonsuppressible and renin-independent aldosterone production following SST that paralleled the magnitude of the blood pressure continuum and transcended conventional diagnostic thresholds. In parallel, there was a full continuum of ACTH-mediated aldosteronism wherein post-SST aldosterone levels were strongly correlated with ACTH-stimulated aldosterone production (r = 0.75, P < .0001) and nonsuppressible aldosterone production postdexamethasone (r = 0.40, P < .0001). Beyond participants who met the criteria for primary aldosteronism (post-SST aldosterone of ≥10 ng/dL or ≥277 pmol/L), the continuum of nonsuppressible and renin-independent aldosterone production persisted below this diagnostic threshold, wherein 15% still had lateralizing aldosteronism amenable to surgical adrenalectomy and the remainder were treated with mineralocorticoid receptor antagonists.
Conclusion: In the context of a low-renin phenotype, there is a continuum of primary aldosteronism and dysregulated aldosterone production that is prominently influenced by ACTH. A large proportion of individuals with low renin may benefit from aldosterone-directed therapy.
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http://dx.doi.org/10.1210/clinem/dgae145 | DOI Listing |
Front Mol Biosci
August 2025
Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Recent advances in artificial intelligence (AI) are reshaping the diagnostic and therapeutic of primary aldosteronism (PA). For screening, machine learning models integrate multidimensional data to improve the efficiency of PA detection, facilitating large-scale population screening. For diagnosis, AI-driven algorithms have further enhanced the specificity of PA identification.
View Article and Find Full Text PDFJ Mol Endocrinol
September 2025
INSERM, UMRS 1166, Hôpital La Pitié Salpetriere, Sorbonne Université, Paris, France.
Aldosterone is synthesized by the CYP11B2 enzyme, primarily in the zona glomerulosa of the adrenal gland. It exerts its classical effects on sodium and water balance in the renal distal nephron through binding to the mineralocorticoid receptor (MR). Excess aldosterone production or overactivation of the MR outside the distal nephron leads to cardiac, renal, and vascular injury by increasing oxidative stress and activating the inflammatory and fibrotic pathways.
View Article and Find Full Text PDFBiology (Basel)
August 2025
Key Laboratory of Sichuan Province for Fishes Conservation and Utilization in the Upper Reaches of the Yangtze River, Neijiang Normal University, Neijiang 641000, China.
Based on the limited hepatic hydroxylation efficiency of dietary VD3 in teleosts and the superior bioavailability of its metabolite, 25(OH)D3, this study investigated the regulatory mechanisms of dietary 25(OH)D3 supplementation in yellow catfish-an economically significant species lacking prior nutritional data on this metabolite. A total of 360 fish were divided into three groups-control (basal diet), VD3 (2500 IU/kg VD3), and 25(OH)D3 (2500 IU/kg 25(OH)D3)-and fed for 8 weeks. Compared to the control, both supplemented groups showed elevated superoxide dismutase (SOD), total antioxidant capacity (T-AOC), catalase (CAT), and transforming growth factor-β () activities, alongside reduced malondialdehyde (MDA), interleukin-1β (), and tumor necrosis factor-α () levels.
View Article and Find Full Text PDFAm J Hypertens
September 2025
Department of Medicine, Division of Endocrinology and Metabolism, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Dr John Laragh, a pioneer in the field of hypertension, held a fundamental belief in the need to challenge existing dogmas in medicine to enhance our scientific understanding of disease and advance patient care. Perhaps in no area of hypertension does this ring truer with than primary aldosteronism (PA). Following its initial description in the mid-1950s with an initial surge in diagnoses soon thereafter, PA was ultimately relegated to be considered a "zebra" of hypertension felt to be responsible for only a small percentage of cases.
View Article and Find Full Text PDFJACC Heart Fail
August 2025
Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, Missouri, USA. Electronic address:
Steroidal mineralocorticoid receptor antagonists (MRAs), such as spironolactone and eplerenone, have demonstrated substantial benefits in randomized controlled trials for patients with heart failure with reduced ejection fraction. However, their effectiveness in heart failure with mildly reduced ejection fraction and heart failure with preserved ejection fraction remains uncertain, and the implementation of this class has remained low, in part due to its side effects and tolerability profile. Emerging therapies that target the mineralocorticoid receptor and/or the production of aldosterone may offer alternative strategies to treat the aldosterone-mineralocorticoid receptor axis.
View Article and Find Full Text PDF