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原发性高血压患者中的原发性醛固酮增多症:患病率、生化特征及分子生物学

Primary hyperaldosteronism in essential hypertensives: prevalence, biochemical profile, and molecular biology.

作者信息

Fardella C E, Mosso L, Gómez-Sánchez C, Cortés P, Soto J, Gómez L, Pinto M, Huete A, Oestreicher E, Foradori A, Montero J

机构信息

Department of Endocrinology, Faculty of Medicine, Catholic University of Chile, Santiago.

出版信息

J Clin Endocrinol Metab. 2000 May;85(5):1863-7. doi: 10.1210/jcem.85.5.6596.

Abstract

There is evidence that primary aldosteronism (PA) may be common in patients with essential hypertension (EH) when determinations of serum aldosterone (SA), plasma renin activity (PRA), and the SA/PRA ratio are used as screening. An inherited form of primary hyperaldosteronism is the glucocorticoid-remediable aldosteronism (GRA) caused by an unequal crossing over between the CYP11B1 and CYP11B2 genes that results in a chimeric gene, which has aldosterone synthase activity regulated by ACTH. The aim of this study was to evaluate the prevalence of PA and the GRA in 305 EH patients and 205 normotensive controls. We measured SA (1-16 ng/dL) and PRA (1-2.5 ng/mL x h) and calculated the SA/PRA ratio in all patients. A SA/PRA ratio level greater than 25 was defined as being elevated. PA was diagnosed in the presence of high SA levels (>16 ng/dL), low PRA levels (<0.5 ng/mL x h), and very high SA/PRA ratio (>50). Probable PA was diagnosed when the SA/PRA ratio was more than 25 but the other criteria were not present. A Fludrocortisone test was done to confirm the diagnosis. GRA was differentiated from other forms of PA by: the aldosterone suppression test with dexamethasone, the high levels of 18-hydroxycortisol, and the genetic detection of the chimeric gene. In EH patients, 29 of 305 (9.5%) had PA, 13 of 29 met all the criteria for PA, and 16 of 29 were initially diagnosed as having a probable PA and confirmed by the fludrocortisone test. Plasma potassium was normal in all patients. The dexamethasone suppression test was positive for GRA in 10 of 29 and 18-hydroxycortisol levels were high in 2 of 29 patients who had also a chimeric gene. In normotensive subjects, 3 of 205 (1.46%) had PA, and 1 of 205 had a GRA. In summary, we found a high frequency of normokalemic PA in EH patients. A high proportion of PA suppressed SA with dexamethasone, but only a few had a chimeric gene or high levels of 18-hydroxycortisol. These results emphasize the need to further investigate EH patients.

摘要

有证据表明,当使用血清醛固酮(SA)、血浆肾素活性(PRA)以及SA/PRA比值进行筛查时,原发性醛固酮增多症(PA)在原发性高血压(EH)患者中可能很常见。原发性醛固酮增多症的一种遗传形式是糖皮质激素可治性醛固酮增多症(GRA),它由CYP11B1和CYP11B2基因之间不等交换导致嵌合基因引起,该嵌合基因具有受促肾上腺皮质激素(ACTH)调节的醛固酮合酶活性。本研究的目的是评估305例EH患者和205例血压正常对照者中PA和GRA的患病率。我们测量了所有患者的SA(1 - 16 ng/dL)和PRA(1 - 2.5 ng/mL·h),并计算了SA/PRA比值。SA/PRA比值大于25被定义为升高。当SA水平高(>16 ng/dL)、PRA水平低(<0.5 ng/mL·h)且SA/PRA比值非常高(>50)时诊断为PA。当SA/PRA比值大于25但不满足其他标准时诊断为疑似PA。进行氟氢可的松试验以确诊。通过地塞米松醛固酮抑制试验、18 - 羟皮质醇水平升高以及嵌合基因的基因检测将GRA与其他形式的PA区分开来。在EH患者中,305例中有29例(9.5%)患有PA,29例中的13例满足PA的所有标准,29例中的16例最初被诊断为疑似PA并通过氟氢可的松试验确诊。所有患者的血浆钾均正常。29例中有10例地塞米松抑制试验对GRA呈阳性,29例中有2例同时具有嵌合基因且18 - 羟皮质醇水平升高。在血压正常的受试者中,205例中有3例(1.46%)患有PA,205例中有1例患有GRA。总之,我们发现EH患者中正常血钾性PA的发生率很高。很大一部分PA患者用地塞米松可抑制醛固酮,但只有少数患者具有嵌合基因或18 - 羟皮质醇水平升高。这些结果强调了对EH患者进行进一步研究的必要性。

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