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Immunohistochemistry for aldosterone synthase CYP11B2 and matrix-assisted laser desorption ionization imaging mass spectrometry for in-situ aldosterone detection

Zhang, Zhena,b; Sugiura, Yukic; Mune, Tomoatsue; Nishiyama, Mitsuruf; Terada, Yoshiof; Mukai, Kuniakic,d; Nishimoto, Koshiroa,c

Current Opinion in Nephrology and Hypertension: March 2019 - Volume 28 - Issue 2 - p 105–112
doi: 10.1097/MNH.0000000000000487

Purpose of review Immunohistochemistry for aldosterone synthase (CYP11B2) has markedly provided a comprehensive picture of the adrenocortical diseases, particularly primary aldosteronism. The findings from CYP11B2-immunohistochemistry are consistent with the clinical courses of most patients with primary aldosteronism. We herein review the updated pathophysiology and usefulness of the method for understanding individual patients with different subtypes of primary aldosteronism.

Recent findings After our discovery of aldosterone-producing cell clusters (APCCs) using the immunohistochemistry for CYP11B2, we found possible APCC-to-APA transitional lesions (pAATLs) in a few cases that had been hitherto classified as unilateral hyperplasia or multiple nodules. On the basis of morphological and functional features of pAATLs as well as distributions of somatic mutations within the lesions, we have made a hypothesis that APCC grows to APA via pAATL for one of developmental courses of APA. Recently, we successfully performed in-situ detection of aldosterone on adrenal tissue sections using a state-of-the-art technique, matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-imaging). This method revealed in-situ synthesis of aldosterone in APCCs and APAs in addition to several other steroids.

Summary CYP11B2 immunohistochemistry revealed the pathophysiology of aldosterone production in the past decade, especially formation of APCC in normal adrenals and pAATL that is a possible lesion developing from APCC to APA. The term ‘idiopathic hyperaldosteronism’ may soon become obsolete.

aDepartment of Uro-Oncology, Saitama Medical University International Medical Center, Saitama, Japan

bSecond Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China

cDepartment of Biochemistry

dMedical Education Center, Keio University School of Medicine, Tokyo

eDivision of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki

fDepartment of Endocrinology, Metabolism & Nephrology, Kochi Medical School, Kochi University, Kohasu, Okoh-cho, Nankoku City, Kochi, Japan

Correspondence to Koshiro Nishimoto, MD, PhD, Department of Uro-Oncology, Saitama Medical University International Medical Center, Saitama, Japan. Tel: +81 42 984 4111, e-mail:

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