Unidade de Adrenal, Laboratório de Hormônios e Genética Molecular Laboratório de Investigação Médica 42 (LIM/42), Serviço de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Divisão de Oncologia Endócrina, Instituto do Câncer do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Front Endocrinol (Lausanne). 2022 Jun 23;13:927669. doi: 10.3389/fendo.2022.927669. eCollection 2022.
Primary aldosteronism (PA) is the most common form of secondary arterial hypertension, with a prevalence of approximately 20% in patients with resistant hypertension. In the last decade, somatic pathogenic variants in , and genes, which are involved in maintaining intracellular ionic homeostasis and cell membrane potential, were described in aldosterone-producing adenomas (aldosteronomas). All variants in these genes lead to the activation of calcium signaling, the major trigger for aldosterone production. Genetic causes of familial hyperaldosteronism have been expanded through the report of germline pathogenic variants in and genes. Moreover, and variants were associated with bilateral PA and increased the spectrum of genetic etiologies of PA. Of great importance, the genetic investigation of adrenal lesions guided by the CYP11B2 staining strongly changed the landscape of somatic genetic findings of PA. Furthermore, CYP11B2 staining allowed the better characterization of the aldosterone-producing adrenal lesions in unilateral PA. Aldosterone production may occur from multiple sources, such as solitary aldosteronoma or aldosterone-producing nodule (classical histopathology) or clusters of autonomous aldosterone-producing cells without apparent neoplasia denominated aldosterone-producing micronodules (non-classical histopathology). Interestingly, mutational status and classical histopathology of unilateral PA (aldosteronoma) have emerged as relevant predictors of clinical and biochemical outcome, respectively. In this review, we summarize the most recent advances in the pathogenesis of PA and discuss their impact on clinical outcome.
原发性醛固酮增多症（PA）是继发性高血压最常见的形式，在难治性高血压患者中的患病率约为 20%。在过去的十年中，与维持细胞内离子稳态和细胞膜电位有关的 、 和 基因中的体发性致病变体在醛固酮分泌腺瘤（aldosteronomas）中被描述。这些基因中的所有变体都会导致钙信号的激活，这是醛固酮产生的主要触发因素。通过报告 和 基因中的种系致病性变体，家族性醛固酮增多症的遗传原因得到了扩展。此外， 和 变体与双侧 PA 相关，并增加了 PA 的遗传病因谱。非常重要的是，CYP11B2 染色指导的肾上腺病变的遗传研究强烈改变了 PA 的体细胞遗传发现的格局。此外，CYP11B2 染色允许更好地描述单侧 PA 中的醛固酮分泌肾上腺病变。醛固酮的产生可能来自多个来源，如孤立性醛固酮瘤或醛固酮分泌结节（经典组织病理学）或无明显肿瘤的自主醛固酮分泌细胞簇，称为醛固酮分泌微结节（非经典组织病理学）。有趣的是，单侧 PA（醛固酮瘤）的 突变状态和经典组织病理学已分别成为临床和生化结局的相关预测因子。在这篇综述中，我们总结了 PA 发病机制的最新进展，并讨论了它们对临床结局的影响。
