ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 P32 | DOI: 10.1530/endoabs.63.P32

18-oxocortisol synthesis in aldosterone-producing adrenocortical adenoma and significance of KCNJ5 mutation status

Fumitoshi Satoh1,2, Yuto Yamazaki3, Ryo Morimoto2, Masataka Kudo2, Celso E Gomez-Sanchez4, Sadayoshi Ito2, Hironobu Sasano3 & Fumitoshi Satoh1,2

1Division of Clinical Hypertension, Endocrinology and Metabolism, Tohoku University Graduate School of Medicine, Sendai, Japan; 2Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Hospital, Sendai, Japan; 3Department of Pathology, Tohoku University Hospital, Sendai, Japan; 4Division of Endocrinology, University of Mississippi Medical Center, Jackson, USA.

Peripheral 18-oxocortisol level could contribute to the detection of aldosterone-producing adenoma in patients with primary aldosteronism. However, peripheral 18-oxocortisol varies among such patients, which is a big drawback concerning its clinical application. We studied 48 cases of aldosterone-producing adenoma, 35 harboring KCNJ5 mutation, to clarify the significance of clinical and pathological parameters regarding peripheral 18-oxocortisol. Peripheral 18-oxocortisol concentration ranged widely from 0.50 to 183.13 ng/dL and correlated positively with intra-tumoral areas stained positively for steroidogenic enzymes (P<0.0001). The peripheral 18-oxocortisol level also correlated significantly with that of circulating aldosterone (P<0.0001) but not with that of cortisol, a precursor of 18-oxocortisol. However, a significant correlation was detected between peripheral 18-oxocortisol and intra-tumoral glucocorticoids (P<0.05). In addition, peripheral 18-oxocortisol correlated positively with the number of hybrid cells double positive for CYP11B1 and CYP11B2 (P<0.0001). Comparing between the cases with and those without KCNJ5 mutation, the KCNJ5-mutated group demonstrated a significantly higher concentration of peripheral 18-oxocortisol (28.4±5.6 ng/dL vs 3.0±0.9 ng/dL, P<0.0001) and a larger intra-tumoral environment including the hybrid cells (P<0.001), possibly representing a deviation from normal aldosterone biosynthesis. Following multivariate analysis, KCNJ5 mutation status turned out to be the most influential factor involved in 18-oxocortisol synthesis in aldosterone-producing adenoma (P<0.0001). Results of our present study firstly revealed that enhanced 18-oxocortisol synthesis in aldosterone-producing adenoma could come from a functional deviation of aldosterone biosynthesis from the normal zona glomerulosa and the utility of peripheral 18-oxocortisol measurement could be influenced by the prevalence of KCNJ5 mutation in an aldosterone-producing adenoma.

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