Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto, 612-8555, Japan.
J Clin Endocrinol Metab. 2022 Aug 18;107(9):2473-2482. doi: 10.1210/clinem/dgac408.
Due to its rare incidence, molecular features of primary aldosteronism (PA) in young adults are largely unknown. Recently developed targeted mutational analysis identified aldosterone-driver somatic mutations in aldosterone-producing lesions, including aldosterone-producing adenomas (APAs), aldosterone-producing nodules (APNs), and aldosterone-producing micronodules, formerly known as aldosterone-producing cell clusters.
To investigate histologic and genetic characteristics of lateralized PA in young adults.
Formalin-fixed, paraffin-embedded adrenal tissue sections from 74 young patients with lateralized PA (<35 years old) were used for this study. Immunohistochemistry (IHC) for aldosterone synthase (CYP11B2) was performed to define the histopathologic diagnosis. Somatic mutations in aldosterone-producing lesions were further determined by CYP11B2 IHC-guided DNA sequencing.
Based on the CYP11B2 IHC results, histopathologic classification was made as follows: 48 APAs, 20 APNs, 2 multiple aldosterone-producing nodules (MAPN), 1 double APN, 1 APA with MAPN, and 2 nonfunctioning adenomas (NFAs). Of 45 APAs with successful sequencing, 43 (96%) had somatic mutations, with KCNJ5 mutations being the most common genetic cause of young-onset APA (35/45, 78%). Of 18 APNs with successful sequencing, all of them harbored somatic mutations, with CACNA1D mutations being the most frequent genetic alteration in young-onset APN (8/18, 44%). Multiple CYP11B2-expressing lesions in patients with MAPN showed several aldosterone-driver mutations. No somatic mutations were identified in NFAs.
APA is the most common histologic feature of lateralized PA in young adults. Somatic KCNJ5 mutations are common in APAs, whereas CACNA1D mutations are often seen in APNs in this young PA population.
由于原发性醛固酮增多症（PA）的罕见发病率，年轻人中 PA 的分子特征在很大程度上尚不清楚。最近开发的靶向突变分析在醛固酮产生病变中鉴定了醛固酮驱动的体细胞突变，包括醛固酮产生腺瘤（APAs）、醛固酮产生结节（APNs）和醛固酮产生微结节，以前称为醛固酮产生细胞簇。
研究年轻人单侧 PA 的组织学和遗传学特征。
本研究使用了 74 例单侧 PA（<35 岁）年轻患者的福尔马林固定、石蜡包埋的肾上腺组织切片。进行醛固酮合酶（CYP11B2）免疫组织化学（IHC）以定义组织病理学诊断。进一步通过 CYP11B2 IHC 指导的 DNA 测序确定醛固酮产生病变中的体细胞突变。
根据 CYP11B2 IHC 结果，组织病理学分类如下：48 例 APA、20 例 APN、2 例多发性醛固酮产生结节（MAPN）、1 例双 APN、1 例 APA 伴 MAPN 和 2 例无功能腺瘤（NFA）。在 45 例成功测序的 APA 中，有 43 例（96%）存在体细胞突变，其中 KCNJ5 突变是年轻人 APA 的最常见遗传原因（35/45，78%）。在 18 例成功测序的 APN 中，所有 APN 均存在体细胞突变，其中 CACNA1D 突变是年轻人 APN 中最常见的遗传改变（8/18，44%）。MAPN 患者的多个 CYP11B2 表达病变显示出几种醛固酮驱动突变。在 NFA 中未发现体细胞突变。
APA 是年轻人单侧 PA 最常见的组织学特征。在这个年轻的 PA 人群中，APAs 中常见体细胞 KCNJ5 突变，而 APNs 中常见 CACNA1D 突变。
