Diabetes mellitus itself increases cardio- cerebrovascular risk and renal complications in primary aldosteronism

This is a pre-copyedited, author-produced version of an article accepted for publication in The Journal of Clinical Endocrinology & Metabolism following peer review. The version of record Aya Saiki, Michio Otsuki, Daisuke Tamada, Tetsuhiro Kitamura, Iichiro Shimomura, Isao Kurihara, Takamasa Ichijo, Yoshiyu Takeda, Takuyuki Katabami, Mika Tsuiki, Norio Wada, Toshihiko Yanase, Yoshihiro Ogawa, Junji Kawashima, Masakatsu Sone, Nobuya Inagaki, Takanobu Yoshimoto, Ryuji Okamoto, Katsutoshi Takahashi, Hiroki Kobayashi, Kouichi Tamura, Kohei Kamemura, Koichi Yamamoto, Shoichiro Izawa, Miki Kakutani, Masanobu Yamada, Akiyo Tanabe, Mitsuhide Naruse, Diabetes Mellitus Itself Increases Cardio-Cerebrovascular Risk and Renal Complications in Primary Aldosteronism, The Journal of Clinical Endocrinology & Metabolism, Volume 105, Issue 7, July 2020, Pages e2531–e2537 is available online at: https://doi.org/10.1210/clinem/dgaa177

Heterogeneous circulating miRNA profiles of PBMAH

ObjectivePrimary bilateral macronodular adrenal hyperplasia (PBMAH), a rare cause of Cushing syndrome, is often diagnosed as a bilateral adrenal incidentaloma with subclinical cortisol production. Circulating microRNAs (miRNAs) are a characteristic of adrenocortical adenomas, but miRNA expression in PBMAH has not been investigated. We aimed to evaluate the circulating miRNA expression in patients with PBMAH and compare them with those in patients with non-functioning adrenocortical adenoma (NFA) and cortisol-producing adrenocortical adenoma (CPA).MethodsmiRNA profiling of plasma samples from four, five, and five patients with NFA, CPA, and PBMAH, respectively, was performed. Selected miRNA expressions were validated using quantitative RT-PCR.ResultsPBMAH samples showed distinct miRNA expression signatures on hierarchical clustering while NFA and CPA samples were separately clustered. PBMAH was distinguished from the adenoma group of NFA and CPA by 135 differentially expressed miRNAs. Hsa-miR-1180-3p, hsa-miR-4732-5p, and hsa-let-7b-5p were differentially expressed between PBMAH and adenoma (P = 0.019, 0.006, and 0.003, respectively). Furthermore, PBMAH could be classified into two subtypes based on miRNA profiling: subtype 1 with a similar profile to those of adenoma and subtype 2 with a distinct profile. Hsa-miR-631, hsa-miR-513b-5p, hsa-miR-6805-5p, and hsa-miR-548av-5p/548k were differentially expressed between PBMAH subtype 2 and adenoma (P = 0.027, 0.027, 0.027, and 1.53E-04, respectively), but not between PBMAH, as a whole, and adenoma.ConclusionCirculating miRNA signature was identified specific for PBMAH. The existence of subtype-based miRNA profiles may be associated with the pathophysiological heterogeneity of PBMAH

Adrenal venous sampling guided adrenalectomy rates in primary aldosteronism: results of an international cohort (AVSTAT)

CONTEXT Adrenal venous sampling (AVS) is the current criterion standard lateralization technique in primary aldosteronism (PA). Japanese registry data found that 30% of patients with unilateral PA did not undergo adrenalectomy, but the reasons for this and whether the same pattern is seen internationally are unknown. OBJECTIVE To assess the rate of AVS-guided adrenalectomy across an international cohort and identify factors that resulted in adrenalectomy not being performed in otherwise eligible patients. DESIGN, SETTING, AND PARTICIPANTS Retrospective, multinational, multicenter questionnaire-based survey of management of PA patients from 16 centers between 2006 and 2018. MAIN OUTCOME MEASURES Rates of AVS implementation, AVS success rate, diagnosis of unilateral PA, adrenalectomy rate, and reasons why adrenalectomy was not undertaken in patients with unilateral PA. RESULTS Rates of AVS implementation, successful AVS and unilateral disease were 66.3%, 89.3% and 36.9% respectively in 4818 patients with PA. Unilateral PA and adrenalectomy rate in unilateral PA were lower in Japanese than in European centers (24.0% vs 47.6% and 78.2% vs 91.4% respectively). The clinical reasoning for not performing adrenalectomy in unilateral PA were more likely to be physician-derived in Japan and patient-derived in Europe. Physician-derived factors included non-AVS factors e.g. good blood pressure control, normokalemia, and the absence of adrenal lesions on imaging, which were present before AVS. CONCLUSION Considering the various unfavorable aspects of AVS, stricter implementation and consideration of surgical candidacy prior to AVS will increase its diagnostic efficiency and utility