Research Papers:

Impact of aldosterone-producing cell clusters on diagnostic discrepancies in primary aldosteronism

Mitsuhiro Kometani, Takashi Yoneda _, Daisuke Aono, Shigehiro Karashima, Masashi Demura, Koshiro Nishimoto, Masakazu Yamagishi and Yoshiyu Takeda

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Oncotarget. 2018; 9:26007-26018. https://doi.org/10.18632/oncotarget.25418

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Mitsuhiro Kometani1, Takashi Yoneda1,2, Daisuke Aono1, Shigehiro Karashima1, Masashi Demura3, Koshiro Nishimoto4, Masakazu Yamagishi1 and Yoshiyu Takeda1

1Division of Endocrinology and Hypertension, Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa 920-8641, Japan

2Program Management Office for Paradigms Establishing Centers for Fostering Medical Researchers of the Future, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan

3Department of Hygiene, Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa 920-8641, Japan

4Department of Uro-Oncology, Saitama Medical University International Medical Center, Hidaka 350-1241, Japan

Correspondence to:

Takashi Yoneda, email: [email protected]

Keywords: primary aldosteronism; adrenal vein sampling; aldosterone-producing cell clusters

Received: August 23, 2017     Accepted: May 02, 2018     Published: May 25, 2018


Adrenocorticotropic hormone (ACTH) stimulation is recommended in adrenal vein sampling (AVS) for primary aldosteronism (PA) to improve the AVS success rate. However, this method can confound the subtype diagnosis. Gene mutations or pathological characteristics may be related to lateralization by AVS. This study aimed to compare the rate of diagnostic discrepancy by AVS pre- versus post-ACTH stimulation and to investigate the relationship between this discrepancy and findings from immunohistochemical and genetic analyses of PA. We evaluated 195 cases of AVS performed in 2011–2017. All surgical specimens were analyzed genetically and immunohistochemically. Based on the criteria, AVS was successful in 158 patients both pre- and post-ACTH; of these patients, 75 showed diagnostic discrepancies between pre- and post-ACTH. Thus, 19 patients underwent unilateral adrenalectomy, of whom 16 had an aldosterone-producing adenoma (APA) that was positive for CYP11B2 immunostaining. Of them, 10 patients had discordant lateralization between pre- and post-ACTH. In the genetic analysis, the rate of somatic mutations was not significantly different between APA patients with versus without a diagnostic discrepancy. In the immunohistochemical analysis, CYP11B2 levels and the frequency of aldosterone-producing cell clusters (APCCs) in APAs were almost identical between patients with versus without a diagnostic discrepancy. However, both the number and summed area of APCCs in APAs were significantly smaller in patients with concordant results than in those whose diagnosis changed to bilateral PA post-ACTH stimulation. In conclusion, lateralization by AVS was affected by APCCs in the adjacent gland, but not by APA-related factors such as somatic gene mutations.

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