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Metabolic phenotypes and fatty acid profiles associated with histopathology of primary aldosteronism

Hypertension Research volume 48, pages 1363–1378 (2025)Cite this article

A Comment to this article was published on 16 April 2025

Abstract

Primary aldosteronism (PA) caused by aldosterone hypersecretion is treated by adrenalectomy or medications. Histopathologic examination of resected adrenals reveals diverse histopathologic features. This study aimed to investigate the potential association of peripheral and adrenal tissue metabolic profiles with the histopathologic features of PA. The retrospective study included 105 surgically treated and 43 medically treated patients with PA. Adrenal specimens were categorized according to the HISTALDO (HISTopathology of primary ALDOsteronism) consensus. Peripheral and adrenal tissue metabolic profiles were assessed, including adiposity, adipokines and fatty acid abundances. The distinct fatty acid, arachidonic acid, was further functionally characterized. Surgically treated patients with classical histopathologic findings (n = 71) displayed lower body mass indexes, a lower prevalence of obesity, smaller waist circumference and visceral adipose tissue areas, and lower leptin concentrations compared with operated patients with the nonclassical histopathology (n = 34). No such differences were identified between the nonclassical histopathology group and medically treated group. Distinct concentrations of 18 out of 35 peripheral venous fatty acids, including arachidonic acid, were identified among the 3 groups. Further, accumulation of arachidonic acid was demonstrated in 4 aldosterone-producing adenomas compared with paired adjacent cortex possibly linked with suppressed peroxisomal beta-oxidation. Stimulation of human adrenocortical cells with arachidonic acid or peroxisomal beta-oxidation inhibitor caused 3.8-fold (P = 0.0050) and 1.7-fold (P = 0.0328) amplification of CYP11B2 expression, respectively, which were ablated by BAPTA-AM or KN93, and induced oxidative stress and apoptosis. Our findings show metabolic heterogeneity related to histopathology and support a role for arachidonic acid in PA pathophysiology.

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Acknowledgements

We are grateful to Heng Chen (Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University) for assistance with immunoassay measurements.

Funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China [grant number 82300887, 82203330]; the Natural Science Foundation of Jiangsu Province [grant number BK20220717]; the China Postdoctoral Science Foundation [grant number 2022TQ0132, 2022M711589].

Author information

Author notes

  1. These authors contributed equally: Yuhong Yang, Yuqing Liu, Tracy Ann Williams.

  2. These authors jointly supervised this work: Zhiheng Zhang, Tao Yang, Min Sun.

Authors and Affiliations

  1. Department of Endocrinology, The First Affiliated Hospital With Nanjing Medical University, Nanjing, China

    Yuhong Yang, Yuqing Liu, Maoting Gao, Yutong Yan, Guodong Ma, Min Wang, Zhiqing Xia, Tao Yang & Min Sun

  2. Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, München, Germany

    Tracy Ann Williams

  3. Department of Pathology, The First Affiliated Hospital With Nanjing Medical University, Nanjing, China

    Meiling Bao

  4. Department of Urology, The First Affiliated Hospital With Nanjing Medical University, Nanjing, China

    Jun Tao

  5. Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China

    Zhiheng Zhang

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Correspondence to Zhiheng Zhang, Tao Yang or Min Sun.

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The studies involving humans were approved by The First Affiliated Hospital With Nanjing Medical University, Nanjing, China (approval number 2018-SR-375). The studies were conducted in accordance with the local legislation and institutional requirements.

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Yang, Y., Liu, Y., Williams, T.A. et al. Metabolic phenotypes and fatty acid profiles associated with histopathology of primary aldosteronism. Hypertens Res 48, 1363–1378 (2025). https://doi.org/10.1038/s41440-025-02143-w

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