BACKGROUND Renin-independent aldosterone production in normotensive people increases risk for developing hypertension. In parallel, normotensive adrenal glands frequently harbor aldosterone-producing micronodules with pathogenic somatic mutations known to induce primary aldosteronism (PA). A deeper understanding of these phenomena would inform the origins of PA and its role in hypertension pathogenesis. METHODS Prospectively recruited normotensives underwent detailed characterization of PA features via the following: oral sodium suppression test to evaluate renin-independent aldosterone production, dexamethasone suppression and adrenocorticotropic hormone-stimulation tests to evaluate adrenocorticotropic hormone-mediated aldosterone production, and 24-hour ambulatory blood pressure monitoring. The magnitude of renin-independent aldosterone production was defined via using tertiles of 24-hour urinary aldosterone production during the oral sodium suppression test to create unbiased categorizations of the magnitude of PA. Serum aldosterone, serum 18-hybrid steroids, urine tetrahydroaldosterone (biomarkers of aldosterone synthase activity), urinary potassium, and blood pressure (biomarkers of mineralocorticoid receptor activation) were evaluated across tertiles. RESULTS There was a spectrum of autonomous, nonsuppressible, and renin-independent production of aldosterone, 18-hybrid steroids, and 24-hour urinary tetrahydroaldosterone (P-trend <0.01). Correspondingly, there was a continuum of adrenocorticotropic hormone-mediated aldosterone production and 18-hybrid steroid production that also paralleled renin-independent aldosterone production. The spectrum of PA pathophysiology was associated with higher ambulatory daytime systolic BP (P-trend <0.05), even within the normotensive range, and greater urinary potassium excretion (P-trend <0.05), indicating a continuum of mineralocorticoid receptor activation. CONCLUSIONS The pathophysiologic continuum of PA, characterized by renin-independent and adrenocorticotropic hormone-mediated aldosterone production, and enhanced aldosterone synthase and mineralocorticoid receptor activity, is evident in normotensive people. These findings provide mechanistic explanations to implicate PA in the pathogenesis of a substantial proportion of hypertension.

中文翻译：

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表征原发性醛固酮增多症的起源。


背景 血压正常人群中不依赖肾素的醛固酮产生会增加患高血压的风险。同时，血压正常的肾上腺经常含有产生醛固酮的微结节，这些微结节具有已知可诱发原发性醛固酮增多症 （PA） 的致病性体细胞突变。对这些现象的更深入理解将告知 PA 的起源及其在高血压发病机制中的作用。方法 前瞻性招募的血压正常者通过以下方式对 PA 特征进行详细表征： 口服钠抑制试验以评估不依赖肾素的醛固酮产生，地塞米松抑制和促肾上腺皮质激素刺激试验以评估促肾上腺皮质激素介导的醛固酮产生，以及 24 小时动态血压监测。通过在口服钠抑制试验中使用 24 小时尿醛固酮产生的三分位数来确定肾素非依赖性醛固酮产生的量级，以创建 PA 量级的无偏倚分类。血清醛固酮、血清 18 杂交类固醇、尿液四氢醛固酮（醛固酮合酶活性的生物标志物）、尿钾和血压（盐皮质激素受体激活的生物标志物）在三分位数中进行评估。结果 醛固酮、 18-杂交类固醇和 24 小时尿四氢醛固酮的自主、不可抑制和肾素非依赖性产生 （P 趋势 <0.01）。相应地，存在一个连续的促肾上腺皮质激素介导的醛固酮产生和 18 种杂交类固醇的产生，它们也与不依赖肾素的醛固酮产生平行。PA 病理生理学范围与较高的动态日间收缩压相关 （P 趋势 <0.05），即使在正常血压范围内，尿钾排泄量增加 （P 趋势 <0.05），表明盐皮质激素受体激活的连续性。结论 PA 的病理生理连续体，其特征是肾素非依赖性和促肾上腺皮质激素介导的醛固酮产生，醛固酮合酶和盐皮质激素受体活性增强，在血压正常人群中很明显。这些发现提供了机制解释，表明 PA 与很大一部分高血压的发病机制有关。