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

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

doi:10.18632/oncotarget.25418

Mitsuhiro Kometani, Koshiro Nishimoto + Show 6 more

Open Access

https://doi.org/10.18632/oncotarget.25418

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Journal: Oncotarget	Publication Date: May 25, 2018
Citations: 16	License type: cc-by

Affiliation: Kanazawa University, Saitama Medical University

Abstract

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.

Highlights

Primary aldosteronism (PA) is a major cause of secondary hypertension that is associated with severe cardiovascular complications [1]
We analyzed the frequency of a change in diagnosis from pre- to post-Adrenocorticotropic hormone (ACTH) adrenal vein sampling (AVS), as well as the impact of AVS on the treatment strategy decision (Figure 1)
The diagnoses determined by pre- and post-ACTH AVS were in accordance in 83 (53%) of the 158 patients with successful pre- and post-ACTH AVS: unilateral primary aldosteronism (PA) in 14 and bilateral PA in 69 (Table 2)

Summary

Introduction

Primary aldosteronism (PA) is a major cause of secondary hypertension that is associated with severe cardiovascular complications [1]. PA is divided into two subtypes: unilateral PA (i.e., aldosterone-producing adenoma (APA) or unilateral adrenal hyperplasia) and bilateral. Adrenal vein sampling (AVS) is the most reliable procedure used to identify surgically curable PA [1]. Use of adrenocorticotropic hormone (ACTH) stimulation during AVS is recommended to improve the AVS success rate [2]. Numerous criteria for AVS, with and without ACTH stimulation, have been used to define unilateral versus bilateral PA [3], and several studies have reported www.oncotarget.com diagnostic discrepancies in the final diagnosis obtained before versus after ACTH stimulation [4, 5]

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