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Studies on excised adrenals from primary aldosteronism patients have found that 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 the steroid production profile and the morphology of the cell. We therefore aimed to corroborate these findings by characterizing the APAs from a multi-ethnic Malaysian cohort. The prevalence of  KCNJ5  mutations was estimated through targeted DNA sequencing of  KCNJ5  in 54 APAs. Confirmation of APA sample acquisition was performed by CYP11B2 immunohistochemistry (IHC) staining. The ZF steroid production profile was based on the ZF enzyme CYP17A1 IHC staining, and ZF cell morphology was based on a high cytoplasm to nucleus ratio. Seventeen (31.5%) APAs studied, harbored a  KCNJ5  mutation. No female over-representation was seen in this cohort though females were found to have a 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 the  KCNJ5  genotype.  KCNJ5  mutant APAs had a 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.

Prevalence and Histopathological Characteristics of KCNJ5 Mutant Aldosterone-Producing Adenomas in a Multi-Ethnic Malaysian Cohort