Gao Xin, Yamazaki Yuto, Ono Yoshikiyo, Satoh Fumitoshi, Li Faping, Zhou Honglan, Sasano Hironobu
Department of Urology, The First Hospital of Jilin University, Changchun, Jilin, P.R. China.
Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Vitam Horm. 2025;129:125-141. doi: 10.1016/bs.vh.2024.09.001. Epub 2024 Oct 15.
Primary aldosteronism (PA) is composed of different aldosterone-producing lesions including aldosterone-producing adenoma (APA), aldosterone-producing micronodules (APM), aldosterone-producing nodules (APN) and aldosterone-producing diffuse hyperplasia (APDH), all of which could result in hypertensive status and electrolyte imbalances. These aldosterone-producing lesions above are frequently accompanied by somatic mutations, including those of KCNJ5, CACNA1D, ATP1A1, and ATP2B3. APA is a neoplasm which frequently harbors KCNJ5 somatic mutations in tumor cells, especially those arising in East Asian patients. Histologically, APAs with KCNJ5 and ATP2B3 mutations presented with more clear cells, whereas those with ATP1A1 and CACNA1D mutations with more compact cells. In addition, the expression levels of steroidogenic enzymes such as aldosterone synthase (CYP11B2) in APAs varied among those with different patterns of somatic mutations, suggesting a potential association between specific mutations and altered aldosterone synthesis in APAs. In contrast, CACNA1D mutation was the most frequent subtype in non-neoplastic lesions including APM and APN, suggesting the possible correlation of KCNJ5 mutation with neoplastic aldosterone-producing lesions. This review provides pivotal insights into the histopathological diversity of aldosterone-producing lesions in PA patients and emphasizes the significance of genetic mutations in constituting the histological landscape of the lesion in order to better understand the detailed pathogenesis of primary aldosteronism.
原发性醛固酮增多症（PA）由不同的醛固酮生成性病变组成，包括醛固酮生成腺瘤（APA）、醛固酮生成微结节（APM）、醛固酮生成结节（APN）和醛固酮生成弥漫性增生（APDH），所有这些病变均可导致高血压状态和电解质失衡。上述醛固酮生成性病变常伴有体细胞突变，包括钾通道内向整流蛋白5（KCNJ5）、L型钙离子通道α1D亚基（CACNA1D）、钠钾ATP酶α1亚基（ATP1A1）和质膜钙ATP酶3（ATP2B3）的突变。APA是一种肿瘤，肿瘤细胞中常存在KCNJ5体细胞突变，尤其是东亚患者中出现的那些突变。组织学上，具有KCNJ5和ATP2B3突变的APA表现为更透明的细胞，而具有ATP1A1和CACNA1D突变的APA表现为细胞更致密。此外，APA中醛固酮合成酶（CYP11B2）等类固醇生成酶的表达水平在具有不同体细胞突变模式的APA中有所不同，这表明特定突变与APA中醛固酮合成改变之间可能存在关联。相比之下，CACNA1D突变是包括APM和APN在内的非肿瘤性病变中最常见的亚型，这表明KCNJ5突变与肿瘤性醛固酮生成性病变可能存在相关性。本综述对PA患者醛固酮生成性病变的组织病理学多样性提供了关键见解，并强调了基因突变在构成病变组织学格局中的重要性，以便更好地理解原发性醛固酮增多症的详细发病机制。
