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Screening For Primary Aldosteronism In 1,181 Swedish Primary Care Patients With Hypertension
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Department of Surgery, Karlstad Central Hospital, Karlstad, Sweden; Center for Clinical Research and Education, Karlstad, Sweden.ORCID iD: 0009-0002-7866-677X
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Department of Surgery, Uppsala University Hospital, Uppsala, Sweden.ORCID iD: 0000-0002-5562-6081
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.ORCID iD: 0000-0003-3748-3176
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2025 (English)In: Frontiers in Endocrinology, E-ISSN 1664-2392, Vol. 16, article id 1555572Article in journal (Refereed) Published
Abstract [en]

Objective: Primary aldosteronism (PA) is a common cause of hypertension. It entails elevated morbidity and mortality that do not sufficiently improve with conventional antihypertensive therapy. Screening for PA by plasma aldosterone–renin ratio (ARR) enables discovery and specific treatment of affected patients. By screening primary care patients with hypertension and evaluating them further according to the Endocrine Society guidelines, we aimed to assess the prevalence of PA, the factors affecting biochemical diagnostics, and the outcome of lateralization studies and of specific treatment of the discovered PA cases.

Design, patients, and methods: Prospective evaluation of screening for PA was conducted in 1,181 patients. Screening by ARR was performed under current therapy, but without mineralocorticoid receptor antagonists (MRA), under normokalemia, and confirmed by the intravenous saline suppression test, SST#1. Those with results in a defined gray zone underwent therapy adjustment and then completed SST#2. Plasma aldosterone and ARR were compared under different stages of the diagnostic process. All patients with PA were offered adrenal venous sampling, or, in certain cases, adrenocortical-specific positron emission tomography. Lateralizing cases were offered laparoscopic adrenalectomy. Patients with bilateral disease were treated with MRA. Treatment results were assessed after a minimum of 6 months.

Results: A total of 53 discovered cases of (mostly mild) PA corresponded to its prevalence of 4.5%. Initial seated ARR was higher than recumbent ARR before SST#1. At SST#2, initial ARR and final aldosterone were higher than at SST#1. Localizing studies (accepted by 45 patients) found 14 lateralized cases. Of the 11 operated cases, 4 had aldosterone-producing adenoma, and the remainder had micro- and macronodular histopathology. A total of 31 patients had bilateral PA. Both surgical and conservative treatments were well tolerated and led to improved blood pressure and higher renin, indicating risk amelioration.

Conclusions: PA is prevalent among primary care patients with hypertension and can be screened for under current antihypertensive therapy. Aldosterone-producing adenoma was rare in this cohort. The study results support active screening of primary care patients with hypertension for PA in order to offer appropriate treatment options.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2025. Vol. 16, article id 1555572
Keywords [en]
primary aldosteronism, screening, hypertension, outpatients, aldosterone, renin, therapeutics
National Category
Surgery Endocrinology and Diabetes
Research subject
Medical Science
Identifiers
URN: urn:nbn:se:uu:diva-554033DOI: 10.3389/fendo.2025.1555572ISI: 001476399600001PubMedID: 40297172Scopus ID: 2-s2.0-105003811480OAI: oai:DiVA.org:uu-554033DiVA, id: diva2:1950191
Funder
Sjukvårdsregionala forskningsrådet Mellansverige, 651241Sjukvårdsregionala forskningsrådet Mellansverige, 842171Sjukvårdsregionala forskningsrådet Mellansverige, 930708Region Värmland, 637541Region Värmland, 741191Region Värmland, 840631Region Värmland, 930327Region Värmland, 939850Region Värmland, 967684Region Värmland, 980171Region Värmland, 993231Available from: 2025-04-05 Created: 2025-04-05 Last updated: 2025-05-09Bibliographically approved
In thesis
1. Primary aldosteronism: improving screening-based diagnostics and treatment
Open this publication in new window or tab >>Primary aldosteronism: improving screening-based diagnostics and treatment
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Primary aldosteronism (PA, non-physiologic adrenal overproduction of aldosterone) causes about 10% of arterial hypertension, and substantially elevates morbidity and cardiovascular mortality compared to primary hypertension (HT) alone.  PA often lacks specific clinical traits, and remains mostly undiagnosed. Its diagnosis requires biochemical screening and confirmatory tests - which are quite difficult to perform and/or to interpret correctly. About a quarter of PA cases are lateralized (or unilateral, uPA) – and can be cured or significantly ameliorated by surgery, which gives the best long-term prognosis. Bilateral subtype (bPA) can be controlled by mineralocorticoid receptor antagonists. Even the current lateralizing procedures are technically demand-ing and invasive. The challenge of identifying PA and its subtypes to guide the treatment requires more straightforward and sensitive diagnostic methods.

Our first paper describes the project of screening of 1181 unselected primary care hypertensive patients for PA. The 53 found cases of PA (corresponding to a prevalence of 4,5%) were further evaluated and treated (surgically or medically) according to the current guidelines. The pathophysiologic and clinical aspects of the recommended diagnostic and treatment principles, and the follow-up results after at least 6 months after treatment initiation were presented and analyzed.

Our second and third papers present research of new peripheral blood markers that may support diagnostics of PA among hypertensive individuals, including differentiation between its lateralized and bilateral subtype. MicroRNAs (second paper) and proteomic profile (third paper) were analyzed in groups of well clinically studied patients with HT, bPA and uPA.

MicroRNAs have been shown to regulate both aldosterone production and its effects in the target-tissues. Using machine learning (ML), we demonstrate the potential of both microRNAs (analyzed by NGS) and proteomics (analyzed by Olink® Explore 384 Cardiometabolic Panel based on proximity extension assay) to differentiate PA from HT, and uPA from bPA. Further validating studies are needed to evaluate the constructed ML-models and the clinical utility of both microRNA and proteomic analysis in hypertensive patients.

The theoretic and practical experience of these studies confirms the necessity to actively screen hypertensive patients for PA and to further develop its diagnostic methods as specific treatment ameliorates the long-term prognosis. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2025. p. 47
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 2159
Keywords
primary aldosteronism, diagnostics, treatment, surgery, screening, primary care, biomarkers, microRNA, proteomics, prevalence
National Category
Surgery
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-554431 (URN)978-91-513-2501-9 (ISBN)
Public defence
2025-06-12, H:son Holmdahlsalen, Akademiska sjukhuset, ingång 100, Uppsala, 13:00 (Swedish)
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Supervisors
Available from: 2025-05-21 Created: 2025-04-24 Last updated: 2025-05-21

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Makhnov, NikitaÅkerström, TobiasAxling, FredrikHellman, Per

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