Tissue corticosteroid rhythms are dysregulated predominantly during sleep in primary aldosteronism
Primary aldosteronism affects 5 to 20% of the hypertensive population and is associated with increased cardiovascular and metabolic risk compared with primary hypertension. Alterations in the dynamics of aldosterone secretion are key, but these are not well captured by current diagnostic pathways, and the disease is often missed. In this proof-of-concept study, we used ambulatory microdialysis sampling to continuously monitor tissue corticosteroid dynamics in primary aldosteronism over 24 hours. In a cohort of 60 patients, we found pulsatile nocturnal hypersecretion of aldosterone and the hybrid steroids 18-hydroxycortisol and 18-oxocortisol with a preserved daily rhythm. This was most prominent in unilateral disease, with normalization after adrenalectomy. Our findings confirm that a key pathophysiological feature of primary aldosteronism is disruption of corticosteroid rhythms rather than persistent elevation of hormones. We show that ambulatory dynamic hormone profiling is a viable technique that offers substantially more information than current diagnostic approaches relying on single-time point hormone measurements. In the future, this offers the opportunity to investigate more subtle dynamic phenotypes and potentially earlier detection of disease.
Authors
- Belinda Lombard (ORCID: https://orcid.org/0000-0001-6116-0479)
- Kristian Løvås (ORCID: https://orcid.org/0000-0002-8027-8031)
- Dimitris Margaritopoulos (ORCID: https://orcid.org/0000-0001-9625-7545)
- Bergithe E Oftedal (ORCID: https://orcid.org/0000-0003-4248-7737)
- Stafford L. Lightman (ORCID: https://orcid.org/0000-0002-8546-9646)
- Georgina Russell (ORCID: https://orcid.org/0000-0002-1299-4116)
- Eder Zavala (ORCID: https://orcid.org/0000-0002-5467-6036)
- Stylianos Tsagarakis (ORCID: https://orcid.org/0000-0003-1959-8738)
- Anette Heie
- Marianne Aardal Grytaas (ORCID: https://orcid.org/0000-0001-9016-628X)
- Thea Sjøgren
- Sophie Bensing (ORCID: https://orcid.org/0000-0002-9193-2860)
- Isabella Marinelli (ORCID: https://orcid.org/0000-0003-0415-4851)
- Kateřina Šimůnková (ORCID: https://orcid.org/0000-0002-0430-1084)
- Dimitra A. Vassiliadi (ORCID: https://orcid.org/0000-0002-3403-8977)
- Eystein S. Husebye (ORCID: https://orcid.org/0000-0002-7886-2976)
- Thomas Upton (ORCID: https://orcid.org/0000-0003-0138-3982)
- Maria Balomenaki
- Katarina Berinder (ORCID: https://orcid.org/0000-0003-2488-0375)
- Olle Kämpe (ORCID: https://orcid.org/0000-0001-6091-9914)
- Grethe Åstrøm Ueland (ORCID: https://orcid.org/0000-0001-6116-7689)
- Paal Methlie (ORCID: https://orcid.org/0000-0003-0548-0034)
- Marianne Øksnes (ORCID: https://orcid.org/0000-0002-9824-2088)
- Ileana Ruxandra Botusan (ORCID: https://orcid.org/0000-0002-9803-0325)
- Ida Løvik
Institutions
- Karolinska University Hospital (SE)
- University of Exeter (GB)
- Manchester Academic Health Science Centre (GB)
- Haukeland University Hospital (NO)
- Karolinska Institutet (SE)
- University of Manchester (GB)
- University of Bristol (GB)
- Evangelismos Hospital (GR)
- University of Bergen (NO)
- University of Birmingham (GB)
Publication Details
- Journal
- Science Translational Medicine
- Published
- 2026-08-26
- DOI
- https://doi.org/10.1126/scitranslmed.aeb7517
- Primary Topic
- Hormonal Regulation and Hypertension
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Trond Mohn stiftelse
- Knut och Alice Wallenbergs Stiftelse
- Medicinska Forskningsrådet
- Novo Nordisk Fonden
- Medical Research Council
- Biotechnology and Biological Sciences Research Council
- Above and Beyond