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Exploring the high prevalence, comorbidities, and indicators of mild autonomous cortisol secretion in primary aldosteronism: a cohort study and systematic review

Hypertension Research volume 48, pages 1716–1729 (2025)Cite this article

A Comment to this article was published on 03 June 2025

Abstract

Emerging evidence has suggested a significant prevalence of mild autonomous cortisol secretion (MACS) among patients diagnosed with primary aldosteronism (PA). However, MACS’s clinical characteristics and implications in PA patients remain largely unexplored. To investigate the prevalence, comorbidities, and indicators of MACS in PA patients, we conducted a retrospective cohort study including 874 PA patients with dexamethasone suppression test results in the Taiwan Primary Aldosteronism Investigators (TAIPAI) cohort between February 2011 and February 2024. Additionally, we performed a systematic review and meta-analysis of 11 studies, encompassing a total of 2882 PA patients (CRD42023486755). After including the TAIPAI cohort data in the meta-analysis, the prevalence of MACS among PA patients was 21.9% (95% confidence interval [C.I.]: 18.1, 26.2), with a negative correlation with estimated glomerular filtration rate (eGFR) (r = –0.028, P < 0.01). The characteristics associated with MACS in PA patients included older age (mean difference [MD] = 5.51 year, P < 0.01), higher plasma aldosterone concentration (MD = 5.36 ng/dL, P < 0.01), lower plasma renin activity (MD = –0.15 ng/mL/h, P < 0.01), lower eGFR (MD = -4.91 mL/min/1.73 m2, P = 0.01), and larger adrenal tumor size (MD = 0.41 cm, P < 0.01). MACS was significantly associated with chronic kidney disease (odds ratio [OR] = 1.96, P < 0.01), diabetes mellitus (OR = 1.60, P = 0.04), and cardiovascular diseases (OR = 1.37, P = 0.02) among PA patients. The high prevalence and strong association of MACS with comorbidities underscore the importance of identifying it in PA patients. Clinical features such as advanced age, significant aldosterone-renin dysregulation, impaired kidney function, diabetes, cardiovascular disease, and large adrenal tumors are indicators for MACS screening in PA patients.

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Data availability

Some or all datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank Mrs. Yi-Jin Hsiao for her assistance in statistical analysis. We also thank the staff of the Second and Seventh Core Labs, Department of Medical Research at National Taiwan University Hospital, for technical assistance. We express sincere gratitude to all staff of the Taiwan Clinical Trial Consortium.

Funding

This work was supported by the National Science and Technology Council, Taiwan (110-2314-B-002-239, 111-2314-B-002-046); National Taiwan University Hospital (UN110-030); Ministry of Health and Welfare, Taiwan (110-TDU-B-212-124005); Mrs. Hsiu-Chin Lee Kidney Research Fund. The funds played no role in the study design, data collection, analysis and interpretation, manuscript writing, or in the decision to submit this manuscript for publication.

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  1. These authors contributed equally: Chieh Huang, Li-Yang Chang.

Authors and Affiliations

  1. School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan

    Chieh Huang & Li-Yang Chang

  2. Department of Urology, National Taiwan University Hospital, Taipei, Taiwan

    Jia-Yuh Sheu

  3. Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan

    Yen-Ta Huang

  4. Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan

    Jui-Yi Chen

  5. Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan

    Jui-Yi Chen

  6. Renal Division, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

    Chun-Fu Lai & Vin-Cent Wu

  7. Primary Aldosteronism Center, National Taiwan University Hospital, Taipei, Taiwan

    Vin-Cent Wu

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Huang, C., Chang, LY., Sheu, JY. et al. Exploring the high prevalence, comorbidities, and indicators of mild autonomous cortisol secretion in primary aldosteronism: a cohort study and systematic review. Hypertens Res 48, 1716–1729 (2025). https://doi.org/10.1038/s41440-025-02172-5

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