Yujiro Nakano, Takanobu Yoshimoto, Ryo Watanabe, Masanori Murakami, Tatsuya Fukuda, Kazutaka Saito, Yasuhisa Fujii, Takumi Akashi, Toshihiro Tanaka, Tetsuya Yamada, Mitsuhide Naruse and Yoshihiro Ogawa
The pathophysiology of aldosterone-producing adenomas (APAs) has been intensively investigated using genetic and epigenetic approaches. However, the role of miRNAs in APA is not fully understood. The present study profiled miRNAs in APAs as an exploratory approach to elucidate their pathophysiological roles in APAs.
Tissues of APAs and other adrenocortical adenomas were obtained from patients who underwent adrenalectomy.
Candidate miRNAs differentially detected from samples were examined by whole miRNA sequencing. The expression of candidate miRNAs in APA tissues were further validated by real-time quantitative polymerase chain reaction (qPCR). Further, differential miRNA expression between APAs with and without KCNJ5 somatic mutations was examined. Prediction of miRNA target genes was performed by bioinformatics analysis. For specific miRNAs, correlation analysis between the levels of their target genes and CYP11B2 was analyzed in APA tissues.
Our study determined differential expression of six miRNAs in APA or APA with KCNJ5 mutations. We further demonstrated that miR299 levels were negatively correlated with mRNA levels of CACNB2, which encodes the beta-subunit of the L-type calcium channel. Additionally, we found significant correlations among miR299, CACNB2, and CYP11B2 levels in APA tissues.
Our study suggests the possible pathophysiological involvement of specific miRNAs in calcium signaling and aldosterone hypersecretion in APAs. Further studies, including in vitro analyses, are required to clarify these findings.
Hiroki Kobayashi, Yoshihiro Nakamura, Masanori Abe, Isao Kurihara, Hiroshi Itoh, Takamasa Ichijo, Yoshiyu Takeda, Takashi Yoneda, Takuyuki Katabami, Mika Tsuiki, Norio Wada, Yoshihiro Ogawa, Ryuichi Sakamoto, Junji Kawashima, Masakatsu Sone, Nobuya Inagaki, Takanobu Yoshimoto, Tetsuya Yamada, Ryuji Okamoto, Yuichi Matsuda, Megumi Fujita, Minemori Watanabe, Kouichi Tamura, Akiyo Tanabe, Mitsuhide Naruse and JPAS/JRAS Study Group
We investigated the clinical significance of ACTH stimulation during adrenal venous sampling (AVS) by surgical outcome of primary aldosteronism (PA).
Multicenter retrospective study by Japan PA study.
We allocated 314 patients with both basal and ACTH-stimulated AVS data who underwent adrenalectomy to three groups: basal lateralization index (LI) ≥2 with ACTH-stimulated LI ≥4 on the ipsilateral side (Unilateral (U) to U group, n = 245); basal LI <2 with ACTH-stimulated LI ≥4 (Bilateral (B) to U group, n = 15); and basal LI ≥2 with ACTH-stimulated LI <4 (U to B group, n = 54). We compared surgical outcomes among the groups using the Primary Aldosteronism Surgical Outcome (PASO) criteria.
Compared with U to U group, U to B group had poor clinical and biochemical outcomes and low rates of adrenal adenoma as pathological findings (P = 0.044, 0.006, and 0.048, respectively), although there were no significant differences between U to U and B to U groups. All patients in U to B group with clinical and biochemical benefits, however, had adrenal adenoma as pathological findings and could be well differentiated from those with poor surgical outcomes via basal LI (>8.3), but not ACTH-stimulated LI. These results were similar even when we defined each group based on a cut-off value of 4 for basal LI.
Although PA patients in U to B group had worse surgical outcomes than did those in U to U group, basal LI could discriminate among patients with better surgical outcomes in U to B group.