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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Endocrinol. | doi: 10.3389/fendo.2019.00666

Prevalence and histopathological characteristics of KCNJ5 mutant aldosterone-producing adenomas in a multi-ethnic Malaysian cohort

 Syahirah K. Mohideen1, Muaatamarulain Mustangin1, Nor Azmi Kamaruddin1, Rohaizak Muhammad1, Rahman Jamal1, Norlela Sukor1, Geok C. Tan1 and  Elena A. Azizan1*
  • 1Tuanku Muhriz Hospital Chancellor Hospital (HCTM), Malaysia

Studies on excised adrenals from primary aldosteronism patients have found somatic mutations in KCNJ5 frequently cause excess aldosterone production in the culprit aldosterone-producing adenoma (APA). KCNJ5 mutant APAs were reported to be peculiarly overrepresented among young females and in Oriental cohorts, compared to their older male or Caucasian counterparts. These larger APAs were also reported to have similarities with the zona fasciculata (ZF) in the adrenal both from steroid production profile and morphology of cell. We therefore aimed to corroborate these findings through characterizing the APAs from a multi-ethnic Malaysian cohort. The prevalence of KCNJ5 mutations was estimated through targeted DNA sequencing of KCNJ5 in fifty-four APAs. Confirmation of APA sample acquisition was performed by CYP11B2 immunohistochemistry (IHC) staining. ZF steroid production profile was based on the ZF enzyme CYP17A1 IHC staining and ZF cell morphology was based on high cytoplasm to nucleus ratio. Seventeen (31.5%) APAs studied harboured a KCNJ5 mutation. No female over-representation was seen in this cohort though females were found to have higher expression of CYP11B2 than males (p=0.009; Mann-Whitney U test). Age at adrenalectomy correlated negatively with the percentage of ZF-like cells in the APA (p=0.01; Spearman’s rho) but not with KCNJ5 genotype. KCNJ5 mutant APAs had high percentage of ZF-like cells (and high CYP17A1 expression) but so did the wild-type APAs. In summary, prevalence of KCNJ5 mutant APAs in this cohort was similar to other Caucasian cohorts however over-representation of females did not occur which is similar to some studies in Oriental cohorts.

Keywords: Aldosterone-producing adenomas, KCNJ5, primary aldosteronism, Malaysia, Asia

Received: 06 May 2019; Accepted: 13 Sep 2019.

Copyright: © 2019 Mohideen, Mustangin, Kamaruddin, Muhammad, Jamal, Sukor, Tan and Azizan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Elena A. Azizan, Tuanku Muhriz Hospital Chancellor Hospital (HCTM), Cheras, Malaysia,