OBJECTIVE Primary aldosteronism (PA) is the most common form of secondary and curable hypertension. Different germline and somatic mutations are found in aldosterone-producing adenoma (APA) and familial forms of the disease, while the causes of bilateral adrenal hyperplasia (BAH) remain largely unknown. Adrenalectomy is the recommended treatment for patients with APA; however, 6% of patients are not cured and show persistent PA after surgery suggesting BAH. The objective of this study was to analyze clinical data of patients with APA without biochemical success after adrenalectomy as well as the histological and genetic characteristics of their adrenal glands. DESIGN AND METHODS Clinical data of 12 patients with partial and absent biochemical cure were compared to those from 39 PA patients with hormonal cure after surgery. Histological, morphological, and genetic characterization of the adrenals was carried out by CYP11B2 and CYP11B1 immunostaining and by CYP11B2-guided NGS. RESULTS Patients with absent hormonal cure displayed a longer duration of arterial hypertension and lower lateralization index of aldosterone production. In ten patients, APAs expressing CYP11B2 were identified. No difference in histological and morphological characteristics was observed between patients with or without a hormonal cure. Somatic mutations in APA driver genes were identified in all CYP11B2 positive APAs; CACNA1D mutations were the most frequent genetic abnormality. CONCLUSIONS Patients with partial and absent biochemical cure were diagnosed later and exhibited a lower lateralization index of aldosterone production, suggesting asymmetric aldosterone production in the context of BAH. Somatic mutations in adrenal glands from those patients indicate common mechanisms underlying BAH and APA.

中文翻译：

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肾上腺切除术后未治愈的原发性醛固酮增多症患者的肾上腺体细胞突变表明单侧和双侧疾病之间存在共同的致病机制。

目的 原发性醛固酮增多症 (PA) 是最常见的继发性和可治愈性高血压。在产生醛固酮的腺瘤 (APA) 和家族性疾病中发现了不同的种系和体细胞突变，而双侧肾上腺增生 (BAH) 的原因仍然很大程度上未知。肾上腺切除术是 APA 患者的推荐治疗方法；然而，6% 的患者未治愈并在手术后表现出持续的 PA，提示 BAH。本研究的目的是分析肾上腺切除术后没有生化成功的 APA 患者的临床数据，以及他们肾上腺的组织学和遗传特征。设计和方法 将 12 名部分生化治愈和未治愈的患者的临床数据与 39 名术后激素治愈的 PA 患者的临床数据进行比较。组织学，通过 CYP11B2 和 CYP11B1 免疫染色以及 CYP11B2 引导的 NGS 进行肾上腺的形态学和遗传表征。结果 没有激素治愈的患者表现出更长的动脉高血压持续时间和更低的醛固酮生成偏侧化指数。在 10 名患者中，鉴定出表达 CYP11B2 的 APA。在接受或未接受激素治疗的患者之间未观察到组织学和形态学特征的差异。在所有 CYP11B2 阳性 APA 中都发现了 APA 驱动基因的体细胞突变；CACNA1D 突变是最常见的遗传异常。结论 部分生化治愈和缺乏生化治愈的患者后来被诊断出来，并表现出较低的醛固酮生成偏侧化指数，这表明在 BAH 的情况下醛固酮生成不对称。