Department of Medicine, Faculty of Medicine, The National University of Malaysia (UKM), Kuala Lumpur, Malaysia.
Endocrine Hypertension, Department of Clinical Pharmacology and Precision Medicine, William Harvey Research Institute, Queen Mary University of London, London, United Kingdom.
Nat Rev Nephrol. 2023 Dec;19(12):788-806. doi: 10.1038/s41581-023-00753-6. Epub 2023 Aug 23.
Primary aldosteronism is the most common single cause of hypertension and is potentially curable when only one adrenal gland is the culprit. The importance of primary aldosteronism to public health derives from its high prevalence but huge under-diagnosis (estimated to be <1% of all affected individuals), despite the consequences of poor blood pressure control by conventional therapy and enhanced cardiovascular risk. This state of affairs is attributable to the fact that the tools used for diagnosis or treatment are still those that originated in the 1970-1990s. Conversely, molecular discoveries have transformed our understanding of adrenal physiology and pathology. Many molecules and processes associated with constant adrenocortical renewal and interzonal metamorphosis also feature in aldosterone-producing adenomas and aldosterone-producing micronodules. The adrenal gland has one of the most significant rates of non-silent somatic mutations, with frequent selection of those driving autonomous aldosterone production, and distinct clinical presentations and outcomes for most genotypes. The disappearance of aldosterone synthesis and cells from most of the adult human zona glomerulosa is the likely driver of the mutational success that causes aldosterone-producing adenomas, but insights into the pathways that lead to constitutive aldosterone production and cell survival may open up opportunities for novel therapies.
原醛症是高血压最常见的单一病因，当仅一个肾上腺是罪魁祸首时，其具有潜在可治愈性。尽管常规治疗控制血压不佳且心血管风险增加，但由于公众健康对原醛症的认识不足，其巨大的漏诊率（估计不到所有受影响个体的 1%）仍令人担忧。这种情况归因于用于诊断或治疗的工具仍然是那些起源于 20 世纪 70 年代至 90 年代的工具。相反，分子发现改变了我们对肾上腺生理学和病理学的理解。许多与肾上腺皮质不断更新和区域间变形相关的分子和过程也存在于产生醛固酮的腺瘤和产生醛固酮的微结节中。肾上腺具有最高的非沉默体细胞突变率之一，经常选择那些驱动自主醛固酮产生的突变，大多数基因型的临床表现和结果也截然不同。大多数成年人类球状带的醛固酮合成和细胞消失可能是导致产生醛固酮的腺瘤的突变成功的驱动因素，但了解导致醛固酮持续产生和细胞存活的途径可能为新的治疗方法提供机会。
