Baudrand Rene, Guarda Francisco J, Fardella Carlos, Hundemer Gregory, Brown Jenifer, Williams Gordon, Vaidya Anand
From the Program for Adrenal Disorders and Endocrine Hypertension, Department of Endocrinology, School of Medicine, Pontificia Universidad Catolica De Chile, Santiago (R.B., F.J.G., C.F.); and Division of Renal Medicine (G.H.) and Center for Adrenal Disorders, Division of Endocrinology, Diabetes and Hypertension (J.B., G.W., A.V.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Hypertension. 2017 May;69(5):950-956. doi: 10.1161/HYPERTENSIONAHA.116.08952. Epub 2017 Mar 13.
Primary aldosteronism is a severe form of autonomous aldosteronism. Milder forms of autonomous and renin-independent aldosteronism may be common, even in normotension. We characterized aldosterone secretion in 210 normotensives who had suppressed plasma renin activity (<1.0 ng/mL per hour), completed an oral sodium suppression test, received an infusion of angiotensin II, and had measurements of blood pressure and renal plasma flow. Continuous associations between urinary aldosterone excretion rate, renin, and potassium handling were investigated. Severe autonomous aldosterone secretion that was consistent with confirmed primary aldosteronism was defined based on accepted criteria of an aldosterone excretion rate >12 μg/24 hours with urinary sodium excretion >200 mmol/24 hours. Across the population, there were strong and significant associations between higher aldosterone excretion rate and higher urinary potassium excretion, higher angiotensin II-stimulated aldosterone, and lower plasma renin activity, suggesting a continuum of renin-independent aldosteronism and mineralocorticoid receptor activity. Autonomous aldosterone secretion that fulfilled confirmatory criteria for primary aldosteronism was detected in 29 participants (14%). Normotensives with evidence suggestive of confirmed primary aldosteronism had higher 24-hour urinary aldosterone excretion rate (20.2±12.2 versus 6.2±2.9 μg/24 hours; <0.001) as expected, but also higher angiotensin II-stimulated aldosterone (12.4±8.6 versus 6.6±4.3 ng/dL; <0.001) and lower 24-hour urinary sodium-to-potassium excretion (2.69±0.65 versus 3.69±1.50 mmol/mmol; =0.001); however, there were no differences in age, aldosterone-to-renin ratio, blood pressure, or renal plasma flow between the 2 groups. These findings indicate a continuum of renin-independent aldosteronism and mineralocorticoid receptor activity in normotension that ranges from subtle to overtly dysregulated and autonomous. Longitudinal studies are needed to determine whether this spectrum of autonomous aldosterone secretion contributes to hypertension and cardiovascular disease.
原发性醛固酮增多症是自主性醛固酮增多症的一种严重形式。自主性且不依赖肾素的醛固酮增多症的较轻形式可能很常见，甚至在血压正常者中也是如此。我们对210名血压正常者的醛固酮分泌情况进行了特征分析，这些人血浆肾素活性受到抑制（<1.0 ng/mL每小时），完成了口服钠抑制试验，接受了血管紧张素II输注，并测量了血压和肾血浆流量。研究了尿醛固酮排泄率、肾素和钾代谢之间的持续关联。根据醛固酮排泄率>12 μg/24小时且尿钠排泄>200 mmol/24小时这一公认标准，定义了与确诊的原发性醛固酮增多症一致的严重自主性醛固酮分泌。在整个人群中，较高的醛固酮排泄率与较高的尿钾排泄、较高的血管紧张素II刺激的醛固酮以及较低的血浆肾素活性之间存在强烈且显著的关联，提示存在不依赖肾素的醛固酮增多症和盐皮质激素受体活性的连续谱。在29名参与者（14%）中检测到符合原发性醛固酮增多症确诊标准的自主性醛固酮分泌。正如预期的那样，有证据提示确诊原发性醛固酮增多症的血压正常者24小时尿醛固酮排泄率更高（20.2±12.2对6.2±2.9 μg/24小时；<0.001），但血管紧张素II刺激的醛固酮也更高（12.4±8.6对6.6±4.3 ng/dL；<0.001），24小时尿钠钾排泄更低（2.69±0.65对3.69±1.50 mmol/mmol；=0.001）；然而，两组之间在年龄、醛固酮肾素比值、血压或肾血浆流量方面没有差异。这些发现表明，在血压正常者中存在不依赖肾素的醛固酮增多症和盐皮质激素受体活性的连续谱，范围从轻微到明显失调和自主。需要进行纵向研究以确定这种自主性醛固酮分泌谱是否会导致高血压和心血管疾病。
