18-Oxocortisol Synthesis in Aldosterone-Producing Adrenocortical Adenoma and Significance of KCNJ5 Mutation Status

Yuta Tezuka, Yuto Yamazaki, Masaaki Kitada, Ryo Morimoto, Masataka Kudo, Kazumasa Seiji, Kei Takase, Yoshihide Kawasaki, Koji Mitsuzuka, Akihiro Ito, Jun Nishikawa, Noriko Asai, Yasuhiro Nakamura, Celso E. Gomez-Sanchez, Sadayoshi Ito, Mari Dezawa, Hironobu Sasano, Fumitoshi Satoh

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Peripheral 18-oxocortisol (18oxoF) level could contribute to the detection of aldosterone-producing adenoma (APA) in patients with primary aldosteronism. However, peripheral 18oxoF varies among such patients, which is a big drawback concerning its clinical application. We studied 48 cases of APA, 35 harboring KCNJ5 mutation, to clarify the significance of clinical and pathological parameters about peripheral 18oxoF. Peripheral 18oxoF concentration ranged widely from 0.50 to 183.13 ng/dL and correlated positively with intratumoral areas stained positively for steroidogenic enzymes ( P<0.0001). The peripheral 18oxoF level also correlated significantly with that of circulating aldosterone ( P<0.0001) but not with that of cortisol, a precursor of 18oxoF. However, a significant correlation was detected between peripheral 18oxoF and intratumoral glucocorticoids ( P<0.05). In addition, peripheral 18oxoF correlated positively with the number of hybrid cells double positive for 11β-hydroxylase and aldosterone synthase ( P<0.0001). Comparing between the cases with and those without KCNJ5 mutation, the KCNJ5-mutated group demonstrated a significantly higher concentration of peripheral 18oxoF (28.4±5.6 versus 3.0±0.9 ng/dL, P<0.0001) and a larger intratumoral environment including the hybrid cells ( P<0.001), possibly representing a deviation from normal aldosterone biosynthesis. After multivariate analysis, KCNJ5 mutation status turned out to be the most associated factor involved in 18oxoF synthesis in APA ( P<0.0001). Results of our present study first revealed that enhanced 18oxoF synthesis in APA could come from a functional deviation of aldosterone biosynthesis from the normal zona glomerulosa and the utility of peripheral 18oxoF measurement could be influenced by the prevalence of KCNJ5 mutation in an APA.

Original languageEnglish
Pages (from-to)1283-1290
Number of pages8
JournalHypertension (Dallas, Tex. : 1979)
Volume73
Issue number6
DOIs
Publication statusPublished - 2019 Jun 1

Keywords

  • 18-oxocortisol
  • KCNJ5 mutation
  • adrenocortical adenoma
  • hybrid cells
  • hyperaldosteronism

ASJC Scopus subject areas

  • Internal Medicine

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