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  • Review Article
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Primary aldosteronism — a multidimensional syndrome

Nature Reviews Endocrinology volume 18, pages 665–682 (2022)Cite this article

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Abstract

Primary aldosteronism is a common cause of hypertension and is a risk factor for cardiovascular and renal morbidity and mortality, via mechanisms mediated by both hypertension and direct insults to target organs. Despite its high prevalence and associated complications, primary aldosteronism remains largely under-recognized, with less than 2% of people in at-risk populations ever tested. Fundamental progress made over the past decade has transformed our understanding of the pathogenesis of primary aldosteronism and of its clinical phenotypes. The dichotomous paradigm of primary aldosteronism diagnosis and subtyping is being redefined into a multidimensional spectrum of disease, which spans subclinical stages to florid primary aldosteronism, and from single-focal or multifocal to diffuse aldosterone-producing areas, which can affect one or both adrenal glands. This Review discusses how redefining the primary aldosteronism syndrome as a multidimensional spectrum will affect the approach to the diagnosis and subtyping of primary aldosteronism.

Key points

  • Primary aldosteronism is a syndrome of dysregulated aldosterone production, independent of renin and other physiological aldosterone regulators.

  • Primary aldosteronism is an independent risk factor for cardiovascular, renal and metabolic morbidity.

  • Although primary aldosteronism is a common cause of hypertension, it is rarely tested for, and testing typically captures severe disease after serious comorbidities have developed.

  • Primary aldosteronism spans a continuum that evolves from subclinical stages to florid disease and includes single-focal or multifocal aldosterone-producing areas that affect one or both adrenal glands.

  • Early detection and targeted therapy of primary aldosteronism could prevent cardiovascular and renal comorbidity and mortality in many patients with hypertension.

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Fig. 1: The pathophysiology of primary aldosteronism.
Fig. 2: The severity spectrum of primary aldosteronism.
Fig. 3: Pragmatic approach for patients at risk of primary aldosteronism, using available diagnostic tools.
Fig. 4: Adrenal vein sampling principles.
Fig. 5: Spectrum of primary aldosteronism subtypes.

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Acknowledgements

A.F.T. was supported by grants 2019087 from the Doris Duke Charitable Foundation, R01HL155834 from the National Heart, Lung, and Blood Institute, and UL1TR002240 from the Michigan Institute for Clinical and Health Research. A.V. was supported by the National Institute of Diabetes and Digestive and Kidney Diseases under award R01 DK115392-04 and the National Institute of Heart, Lung, and Blood Disorders under award R01 HL153004 and by the Brigham and Women’s Hospital Department of Medicine Innovation Evergreen Fund Award. J.Y. was supported by the National Health and Medical Research Council Investigator Grant APP1194576.

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Authors and Affiliations

  1. Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, USA

    Adina F. Turcu

  2. Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, Victoria, Australia

    Jun Yang

  3. Department of Medicine, Monash University, Clayton, Victoria, Australia

    Jun Yang

  4. Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Anand Vaidya

Authors
  1. Adina F. Turcu
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  2. Jun Yang
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  3. Anand Vaidya
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Contributions

The authors contributed equally to all aspects of the article.

Corresponding author

Correspondence to Adina F. Turcu.

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Competing interests

A.F.T. has received consulting fees from CinCor Pharma and PhaseBio. A.V. reports consulting activities with Mineralys Therapeutics, Corcept Therapeutics, and HRA Pharma, all unrelated to the current work. J.Y. declares no competing interests.

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Nature Reviews Endocrinology thanks Jaap Deinum and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Turcu, A.F., Yang, J. & Vaidya, A. Primary aldosteronism — a multidimensional syndrome. Nat Rev Endocrinol 18, 665–682 (2022). https://doi.org/10.1038/s41574-022-00730-2

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