Expert Consensus on the Primary Aldosteronism Severity Classification and its strategic application in indicating adrenal venous sampling

Masanori Murakami¹, Mitsuhide Naruse², Hiroki Kobayashi³, Mirko Parasiliti-Caprino⁴, Fabio Bioletto⁴, Denise Brüdgam⁵, Isabel Stüfchen⁵, Martin Reincke⁵, Matthieu St-Jean⁶, Ivana Kraljevic^{7

8}, Darko Kastelan^{7

8}, Pasi I Nevalainen⁹, Marta Araujo-Castro¹⁰, Norlela Sukor^{11

12}, Michiel F Nijhoff¹³, Joanna Matrozova¹⁴, Oskar Ragnarsson^{15

16}, Zulfiya Shafigullina¹⁷, Niina Matikainen¹⁸, Athina Markou¹⁹, George Piaditis¹⁹, Shoichiro Izawa²⁰, Takuyuki Katabami²¹, Takamasa Ichijo²², Akiyo Tanabe²³, Mika Tsuiki²⁴, Miki Kakutani²⁵, Norio Wada²⁶, Seizaburo Masuda²⁷, Alessandra Violet Bacca²⁸, Felix Beuschlein^{5

29

30}, Giuseppe Maiolino³¹, Henrik Falhammar^{32

33}, Marianne A Grytaas³⁴, Kristian Løvås³⁴, Madson Q Almeida³⁵, Raluca Maria Furnica³⁶, Troy Puar^{37

38}, Piotr Kmieć^{39

40}, Stefano Masi²⁸, Isabelle Bourdeau⁴¹, Laurence Amar^{42

43}, Michael Conall Dennedy⁴⁴, Francesco Fallo³¹, Jaap Deinum⁴⁵, Sam O'Toole⁴⁶, Tetsuya Yamada¹, Marcus Quinkler⁴⁷, André Lacroix⁴¹, Tomaz Kocjan^{48

49}

Affiliations

¹ Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo 113-8510, Japan.
² Endocrine Center, Ijinkai Takeda General Hospital, Kyoto 601-1495, Japan.
³ Division of Nephrology, Hypertension, and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan.
⁴ Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Turin, Turin 10126, Italy.
⁵ Department of Medicine IV, University Hospital, Ludwig Maximilian University Munich, Munich 80336, Germany.
⁶ Division of Endocrinology, Department of Medicine, Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4.
⁷ Department of Endocrinology, University Hospital Centre Zagreb, Zagreb 10 000, Croatia.
⁸ School of Medicine, University of Zagreb, Zagreb 10 000, Croatia.
⁹ Endocrine Unit, Department of Internal Medicine, Tampere University Hospital, and Faculty of Medicine and Health Technology, Tampere University, Tampere 33521, Finland.
¹⁰ Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Madrid 28034, Spain.
¹¹ Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Center (UKMMC), Cheras, Kuala Lumpur 56000, Malaysia.
¹² Hospital Canselor Tuanku Muhriz, Jalan Yaacob Latif, Bandar Tun Razak, Kuala Lumpur 56000, Malaysia.
¹³ Department of Internal Medicine, Division of Endocrinology and Diabetes, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands.
¹⁴ University Hospital of Endocrinology, Medical University, Sofia 1431, Bulgaria.
¹⁵ Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg 413 45, Sweden.
¹⁶ Wallenberg Center for Molecular and Translational Medicine, University of Gothenburg, Gothenburg 405 30, Sweden.
¹⁷ Department of Endocrinology, North-Western State Medical University Named After I.I. Mechnikov, St. Petersburg 191015, Russia.
¹⁸ Endocrinology, Abdominal Center, Helsinki University Hospital and RPU Clinical and Molecular Medicine, University of Helsinki, Helsinki 00290, Finland.
¹⁹ Endocrinology Department and Diabetes Center, 'G. Gennimatas' General Hospital of Athens, Athens 11527, Greece.
²⁰ Division of Endocrinology and Metabolism, Tottori University Faculty of Medicine, Yonago 683-8504, Japan.
²¹ Department of Metabolism and Endocrinology, St. Marianna University Yokohama Seibu Hospital, Yokohama 241-0811, Japan.
²² Department of Diabetes and Endocrinology, Saiseikai Yokohamashi Tobu Hospital, Yokohama 230-8765, Japan.
²³ Department of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.
²⁴ Department of Endocrinology and Metabolism, NHO Kyoto Medical Center, Kyoto 612-8555, Japan.
²⁵ Department of Diabetes, Endocrinology and Clinical Immunology, School of Medicine, Hyogo Medical University, Nishinomiya, Hyogo 663-8501, Japan.
²⁶ Department of Diabetes and Endocrinology, Sapporo City General Hospital, Sapporo 060-8604, Japan.
²⁷ Department of Endocrinology and Metabolism, Kashiwa City Hospital, Kashiwa 277-0825, Japan.
²⁸ Department of Clinical and Experimental Medicine, University of Pisa, Pisa 56126, Italy.
²⁹ Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Zurich 8091, Switzerland.
³⁰ The LOOP Zurich-Medical Research Center, Zurich 8044, Switzerland.
³¹ Department of Medicine, Clinica Medica 3, University of Padova, Padova 35128, Italy.
³² Department of Endocrinology, Karolinska University Hospital, Stockholm 171 76, Sweden.
³³ Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm 171 76, Sweden.
³⁴ Department of Medicine, Haukeland University Hospital, Bergen 5021, Norway.
³⁵ Adrenal Unit, Laboratory of Molecular and Cellular Endocrinology LIM/25, Division of Endocrinology and Metabolism, Clinics Hospital & Cancer Institute of Sao Paulo State, University of Sao Paulo Medical School, Sao Paulo 01246-903, Brazil.
³⁶ Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels 1200, Belgium.
³⁷ Department of Endocrinology, Changi General Hospital, Singapore 529889.
³⁸ Medical ACP, Duke-NUS Medical School, Singapore 169857.
³⁹ Department of Endocrinology and Internal Medicine, Medical University of Gdańsk, Gdańsk 80214, Poland.
⁴⁰ Department of Endocrinology and Internal Medicine, University Clinical Center, Gdańsk 80214, Poland.
⁴¹ Endocrine Division, Department of Medicine, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Canada H2X 3E4.
⁴² Université Paris Cité, Inserm, PARCC, Equipe Labellisée par la Ligue contre le Cancer, Paris F-75015, France.
⁴³ Hypertension Unit, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris F-75015, France.
⁴⁴ Department of Endocrinology, University Hospital Galway, Galway H91 YR71, Ireland.
⁴⁵ Department of Internal Medicine, Radboud University Medical Center, Nijmegen 6525 GA, Netherlands.
⁴⁶ Department of Endocrinology, The Royal Hallamshire Hospital, Sheffield S10 2JF, United Kingdom.
⁴⁷ Endocrinology in Charlottenburg, Berlin 10627, Germany.
⁴⁸ Department of Endocrinology, Diabetes, and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana 1000, Slovenia.
⁴⁹ Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia.

PMID: 40485198
DOI: 10.1093/ejendo/lvaf117

Multicenter Study

Expert Consensus on the Primary Aldosteronism Severity Classification and its strategic application in indicating adrenal venous sampling

Masanori Murakami et al. Eur J Endocrinol. 2025.

. 2025 Jun 30;193(1):85-96.

doi: 10.1093/ejendo/lvaf117.

Authors

Affiliations

¹ Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo 113-8510, Japan.
² Endocrine Center, Ijinkai Takeda General Hospital, Kyoto 601-1495, Japan.
³ Division of Nephrology, Hypertension, and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan.
⁴ Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Turin, Turin 10126, Italy.
⁵ Department of Medicine IV, University Hospital, Ludwig Maximilian University Munich, Munich 80336, Germany.
⁶ Division of Endocrinology, Department of Medicine, Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4.
⁷ Department of Endocrinology, University Hospital Centre Zagreb, Zagreb 10 000, Croatia.
⁸ School of Medicine, University of Zagreb, Zagreb 10 000, Croatia.
⁹ Endocrine Unit, Department of Internal Medicine, Tampere University Hospital, and Faculty of Medicine and Health Technology, Tampere University, Tampere 33521, Finland.
¹⁰ Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Madrid 28034, Spain.
¹¹ Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Center (UKMMC), Cheras, Kuala Lumpur 56000, Malaysia.
¹² Hospital Canselor Tuanku Muhriz, Jalan Yaacob Latif, Bandar Tun Razak, Kuala Lumpur 56000, Malaysia.
¹³ Department of Internal Medicine, Division of Endocrinology and Diabetes, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands.
¹⁴ University Hospital of Endocrinology, Medical University, Sofia 1431, Bulgaria.
¹⁵ Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg 413 45, Sweden.
¹⁶ Wallenberg Center for Molecular and Translational Medicine, University of Gothenburg, Gothenburg 405 30, Sweden.
¹⁷ Department of Endocrinology, North-Western State Medical University Named After I.I. Mechnikov, St. Petersburg 191015, Russia.
¹⁸ Endocrinology, Abdominal Center, Helsinki University Hospital and RPU Clinical and Molecular Medicine, University of Helsinki, Helsinki 00290, Finland.
¹⁹ Endocrinology Department and Diabetes Center, 'G. Gennimatas' General Hospital of Athens, Athens 11527, Greece.
²⁰ Division of Endocrinology and Metabolism, Tottori University Faculty of Medicine, Yonago 683-8504, Japan.
²¹ Department of Metabolism and Endocrinology, St. Marianna University Yokohama Seibu Hospital, Yokohama 241-0811, Japan.
²² Department of Diabetes and Endocrinology, Saiseikai Yokohamashi Tobu Hospital, Yokohama 230-8765, Japan.
²³ Department of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.
²⁴ Department of Endocrinology and Metabolism, NHO Kyoto Medical Center, Kyoto 612-8555, Japan.
²⁵ Department of Diabetes, Endocrinology and Clinical Immunology, School of Medicine, Hyogo Medical University, Nishinomiya, Hyogo 663-8501, Japan.
²⁶ Department of Diabetes and Endocrinology, Sapporo City General Hospital, Sapporo 060-8604, Japan.
²⁷ Department of Endocrinology and Metabolism, Kashiwa City Hospital, Kashiwa 277-0825, Japan.
²⁸ Department of Clinical and Experimental Medicine, University of Pisa, Pisa 56126, Italy.
²⁹ Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Zurich 8091, Switzerland.
³⁰ The LOOP Zurich-Medical Research Center, Zurich 8044, Switzerland.
³¹ Department of Medicine, Clinica Medica 3, University of Padova, Padova 35128, Italy.
³² Department of Endocrinology, Karolinska University Hospital, Stockholm 171 76, Sweden.
³³ Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm 171 76, Sweden.
³⁴ Department of Medicine, Haukeland University Hospital, Bergen 5021, Norway.
³⁵ Adrenal Unit, Laboratory of Molecular and Cellular Endocrinology LIM/25, Division of Endocrinology and Metabolism, Clinics Hospital & Cancer Institute of Sao Paulo State, University of Sao Paulo Medical School, Sao Paulo 01246-903, Brazil.
³⁶ Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels 1200, Belgium.
³⁷ Department of Endocrinology, Changi General Hospital, Singapore 529889.
³⁸ Medical ACP, Duke-NUS Medical School, Singapore 169857.
³⁹ Department of Endocrinology and Internal Medicine, Medical University of Gdańsk, Gdańsk 80214, Poland.
⁴⁰ Department of Endocrinology and Internal Medicine, University Clinical Center, Gdańsk 80214, Poland.
⁴¹ Endocrine Division, Department of Medicine, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Canada H2X 3E4.
⁴² Université Paris Cité, Inserm, PARCC, Equipe Labellisée par la Ligue contre le Cancer, Paris F-75015, France.
⁴³ Hypertension Unit, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris F-75015, France.
⁴⁴ Department of Endocrinology, University Hospital Galway, Galway H91 YR71, Ireland.
⁴⁵ Department of Internal Medicine, Radboud University Medical Center, Nijmegen 6525 GA, Netherlands.
⁴⁶ Department of Endocrinology, The Royal Hallamshire Hospital, Sheffield S10 2JF, United Kingdom.
⁴⁷ Endocrinology in Charlottenburg, Berlin 10627, Germany.
⁴⁸ Department of Endocrinology, Diabetes, and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana 1000, Slovenia.
⁴⁹ Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia.

PMID: 40485198
DOI: 10.1093/ejendo/lvaf117

Abstract

Objective: Severity classifications are essential for many diseases to prioritize patient management tasks such as diagnosis, treatment, and follow-up. Primary aldosteronism (PA), a common cause of secondary hypertension, lacks a standardized severity scale despite generally requiring invasive diagnostics like adrenal venous sampling (AVS). This study aimed to develop a global expert consensus-based classification for PA severity to improve clinical decision-making.

Methods: A panel of 45 international experts from 40 centers across four continents used the Delphi method to create a consensus severity classification for PA. This classification was then applied retrospectively to 2593 PA patients from 26 centers to assess its association with the disease subtype.

Results: After four rounds, the Primary Aldosteronism Severity Classification (PASC), which integrates biochemical and clinical parameters including serum potassium, blood pressure, and basal plasma aldosterone concentration, was established. Primary Aldosteronism Severity Classification classifies PA into mild (3 and 4 points), moderate (5-7 points), and severe (8 and 9 points). Among the cohort from 26 centers, 13.9%, 63.0%, and 23.1% were classified as mild, moderate, and severe, respectively, aligning with lateralized subtype prevalence rates of 14.7%, 44.6%, and 72.6%.

Conclusion: Primary Aldosteronism Severity Classification is a newly developed simplified, semi-quantitative classification of PA severity. The correlation between PASC and lateralized PA subtype supports its potential to provide graded recommendations of AVS prior to surgical indication in each patient.

Keywords: adrenal venous sampling; expert consensus; hypertension; primary aldosteronism; severity classification.

© The Author(s) 2025. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.

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Conflict of interest statement

Conflict of interest: The authors declare no conflicts of interest associated with this manuscript. Co-author Felix Beuschlein is on the editorial board of EJE. He was not involved in the review or editorial process for this article, on which he is listed as author.

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Expert Consensus on the Primary Aldosteronism Severity Classification and its strategic application in indicating adrenal venous sampling

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Expert Consensus on the Primary Aldosteronism Severity Classification and its strategic application in indicating adrenal venous sampling

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