Genetic alterations in patients with primary aldosteronism.

The syndrome of primary aldosteronism is characterized by hypertension with excessive production of aldosterone, potassium loss, and suppression of the renin-angiotensin system. The most common clinical subtypes of primary aldosteronism are aldosterone-producing adrenocortical adenoma (APA) and bilateral adrenal cortical hyperplasia (idiopathic hyperaldosteronism, or IHA). It has been reported that renin suppression and aldosterone levels are lower and hypokalemia milder in patients with IHA than in patients with APA. In the present study, we investigated the genetic analysis of aldosterone synthase gene, CYP11B2 in patients with primary aldosteronism and review the recent studies. The chimeric CYP11B1/CYP11B2 gene, which is a candidate gene for glucocorticoid-remediable hyperaldosteronism, was not found in either the DNA from aldosteronoma or in the genomic DNA from patients with APA or IHA. Mutations in the CYP21 or CYP11B1 gene were not present in patients with APA. No mutations in the coding region of the CYP11B2 gene were found in patients with IHA or APA. The level of CYP11B2 messenger RNA (mRNA) was much higher in the aldosteronoma portion than in nonadenomatous portion. The overexpression of CYP11B2 mRNA seen in the mononuclear leukocytes of patients with IHA suggests that unidentified aldosterone-stimulating factors or abnormalities of the CYP11B2 promoter region may cause the overproduction of aldosterone characteristic of IHA. The variants of the CYP11B2 gene may also contribute to dysregulation of aldosterone synthesis and lead to susceptibility to IHA.     

两型原发性醛固酮增多症患者胰岛素敏感性的比较及其胰岛素敏感性与病情的关系

目的 分析和比较两型原发性醛固酮增多症（PA）患者胰岛素敏感性及其治疗前后胰岛素敏感性与病情的关系。方法 本院确诊PA患者32例,其中肾上腺皮质腺瘤（APA）20例,特发性醛固酮增多症（IHA）12例,观察治疗前后体质量指数、血压、血浆醛固酮、空腹血糖、空腹胰岛素及胰岛素抵抗指数（HOMA-IR）等指标的变化。结果 PA组患者治疗后收缩压［（140±8.6）mmHg］、舒张压［（82±9）mmHg］、空腹胰岛素［（7.6±1.8）mmol/L）］、空腹血糖［（5.0±0.7）mmol/L］、HOMA-IR（1.6±0.4）均低于治疗前［收缩压（178±10）mmHg、舒张压（105±11）mmHg、空腹胰岛素（10±3）mmol/L、空腹血糖（5.6±1.1）mmol/L、HOMA-IR（2.4±0.9）,均P<0.01］;治疗前IHA组血浆醛固酮水平［（228±52）ng/L］低于治疗前APA组［（344±41）ng/L,P<0.01）］;治疗前IHA组胰岛素抵抗患者所占百分率（58%）显著高于APA组（20%,P<0.05）;APA手术组醛固酮水平（82±23）ng/L低于治疗前［(344±41) ng/L,P<0.01）］;治疗后APA组血钾（4.0±0.4）mmol/L、HIA组血钾（4.1±0.4）mmol/L分别较治疗前［（3.2±0.4）mmol/L、（3.4±0.3）mmol/L］高（P<0.01）。结论 PA患者部分存在胰岛素抵抗。PA患者在进行肾上腺腺瘤切除或应用螺内酯治疗后胰岛素敏感性可有一定程度恢复。     

Sodium transport in the erythrocytes of patients with essential and symptomatic (renal) hypertension

Sodium transport was investigated, using the isotope exchange method, in the erythrocyte membranes of normal subjects and patients with essential and symptomatic (renal) hypertension. In hypertensive patients, the constant of balanced Na/Na exchange rate was increased by more than 60%, and the balance concentration of erythrocytic sodium by 30%, as compared to the controls, in the presence of ouabain. These differences become far less pronounced if furosemide is added to the incubation medium. In patients with secondary (renal) hypertension, the Na/Na exchange rate and erythrocytic balance concentration of sodium are not affected by ouabain as compared to the controls. It is suggested that Na/Na-countertransport plays the principal role in the disruption of erythrocyte membrane permeability by sodium in essential hypertension.     

原发性醛固酮增多症患者代谢综合征的患病情况

目的 评价原发性醛固酮增多症(原醛症)患者中代谢综合征的患病率.方法 检测180例原醛症(PA)及29例原发性高血压患者(EH)的腰围、血压、血脂、空腹血糖、血、尿醛固酮、血、尿电解质、基础及激发血浆肾素活性,这些指标的结果与58例在我院进行健康体检的人群(对照组,C)的结果进行比较.结果 (1)对所有研究对象进行代谢综合征相关指标的筛查,PA、EH及C3组代谢综合征的患病率分别为40.6%(73/180)、13.8%(4/29)及13.8%(8/58).(2)原醛症组代谢综合征的各项指标,如收缩压及舒张压高于原发性高血压及对照组,而高密度脂蛋白胆固醇低于其余两组,腰围、甘油三酯及空腹血糖高于对照组.(3)PA、EH及C3组代谢综合征相关症状患病率比较以高血压最常见(分别为99.4%、100.0%、48.3%),高甘油三酯血症(分别为37.2%、24.1%、22.4%)及低高密度脂蛋白胆固醇血症(分别为37.8%、20.7%、22.4%)次之,腹型肥胖(分别为26.7%、17.2%、15.5%)及高血糖(分别为25.6%、10.3%、12.1%)最低.(4)伴或不伴代谢综合征的原醛症患者的血、尿醛固酮,PRA基础、激发值及血钾比较均无统计学差异.结论 原发性醛固酮增多症患者代谢综合征的患病率升高.     

原发性醛固酮增多症患者中代谢综合征的患病情况

目的 评价原发性醛固酮增多症（原醛症）患者中代谢综合征(MS)的患病率及其与醛固酮水平的关系。方法 收集2008年10月至2010年7月本院诊治的216例原醛症患者的临床资料并进行回顾性统计,分析该人群中MS的患病情况。结果 (1)原醛症患者的MS患病率为47.69％;在MS各组分中,超重或肥胖、高甘油三酯(TG)血症、糖调节受损、低高密度脂蛋白胆固醇( HDL-C)血症及糖尿病的检出率依次为51.13％、22.52％、19.62％、3.82％和2.94％,中重度高血压为91.87％。(2)在MS各组分中（除高血压外）,位于前3位的组合依次为超重或肥胖+高TG血症、超重或肥胖+低HDL-C血症以及超重或肥胖+糖尿病,检出率分别为35.19％、15.74％和11.57％。(3)随着血醛固酮水平的升高,超重或肥胖及糖调节受损检出率逐渐增高;高TG血症、低HDL-C血症以及MS检出率在醛固酮最高水平组高于低水平组。(4)原醛症患者中MS患病率维吾尔族(64.0％)高于汉族(45.3％),哈萨克族(42.9％)则低于汉族,差异有统计学意义(P＜0.05)。结论原醛症患者MS患病率高,MS及其组分患病率随醛固酮水平增加而增高。     

Inappropriate left ventricular mass in patients with primary aldosteronism

Assessment of appropriateness of left ventricular mass (LVM) for a given workload may better stratify hypertensive patients. Inappropriate LVM may reflect the interaction of genetic and neurohumoral factors other than blood pressure playing a significant role in myocardial growth. Primary aldosteronism (PA) represents a clinical model useful in assessing the effect of aldosterone increase on LVM. The aim of this study was to evaluate the inappropriateness of LVM in patients with PA. In 125 patients with PA (54 females; adrenal hyperplasia in 73 and adenoma in 52 patients) and in 125 age-, sex-, and blood pressure-matched, essential hypertensive patients, echocardiography was performed. The appropriateness of LVM was calculated by the ratio of observed LVM to the predicted value using a reference equation. In all of the subjects plasma renin activity and aldosterone, as well as clinic and 24-hour blood pressure, were measured. The prevalence of inappropriate LVM was greater in patients with traditionally defined left ventricular hypertrophy (70% and 44%, respectively; P=0.02) but also in patients without left ventricular hypertrophy (17% and 9%, respectively; P=0.085). In PA patients, a correlation was observed between the ratio of observed:predicted LVM and the ratio of aldosterone:plasma renin activity levels (r=0.29; P=0.003) or the postinfusion aldosterone concentration (r=0.44; P=0.004; n=42). In conclusion, in patients with PA, the prevalence of inappropriate LVM is increased, even in the absence of traditionally defined left ventricular hypertrophy. The increase in aldosterone levels could contribute to the increase of LV mass exceeding the amount needed to compensate hemodynamic load.     

Cardiovascular outcomes in patients with primary aldosteronism after treatment

BACKGROUND: Experimental and human studies demonstrate that long-term exposure to elevated aldosterone levels results in cardiac and vascular damage. METHODS: We investigated long-term cardiovascular outcomes in patients with primary aldosteronism after surgical or medical treatment. Fifty-four patients with or without evidence of adrenal adenomas were prospectively followed up for a mean of 7.4 years after treatment with adrenalectomy or spironolactone. Patients with primary aldosteronism were compared with patients with essential hypertension and were treated to reach a blood pressure of less than 140/90 mm Hg. The main outcome measure was a combined cardiovascular end point comprising myocardial infarction, stroke, any type of revascularization procedure, and sustained arrhythmias. RESULTS: At baseline, the prevalence of cardiovascular events was greater in primary aldosteronism (35%) than in essential hypertension (11%) (odds ratio, 4.61; 95% confidence interval, 2.38-8.95; P< .001), with odds ratios of 4.93, 4.36, and 2.80 for sustained arrhythmias, cerebrovascular events, and coronary heart disease, respectively. Blood pressure during follow-up was comparable in the primary aldosteronism and essential hypertension groups. Ten patients in the primary aldosteronism group and 19 in the essential hypertension group reached the primary end point (P= .85). Cox analysis indicated that older age and longer duration of hypertension were factors independently associated with the cardiovascular end point. Cardiovascular outcome was comparable in patients with aldosteronism treated with adrenalectomy vs aldosterone antagonists (P= .71). CONCLUSION: Primary aldosteronism is associated with a cardiovascular complication rate out of proportion to blood pressure levels that benefits substantially from surgical and medical treatment in the long term.     

Diurnal blood pressure pattern in patients with primary aldosteronism

BACKGROUND: The aim of the study was to evaluate diurnal blood pressure (BP) profiles in patients with primary aldosteronism and to compare them to those in subjects with essential hypertension. The effects of specific therapy on the circadian BP profiles have been studied. MATERIALS AND METHODS: Sixty-four patients with primary aldosteronism were included in the study. Thirty of them revealed an aldosterone-producing adenoma (APA) and 34 had idiopathic hyperaldosteronism (IHA) due to bilateral adrenal hyperplasia. RESULTS: We did not find any significant differences in ambulatory BP monitoring (ABPM) between patients with APA and IHA. However, the circadian BP variation in the patients with primary hyperaldosteronism due to APA was preserved, while the patients with IHA showed lower nocturnal decline in comparison with patients with essential hypertension. There was a significant decline in office and ambulatory BP levels after treatment in the patients with both APA and IHA. The awake-sleep BP difference in patients with APA remained unchanged after surgical treatment, while in patients with IHA the night-time systolic and diastolic BP decline was significantly higher after spironolactone treatment. CONCLUSIONS: Primary hyperaldosteronism due to APA was associated with normal circadian BP variability and the surgical treatment led to highly significant decline in all BP parameters but had no influence on the extent of nocturnal BP variation. Spironolactone therapy restored normal nocturnal BP decline in patients with IHA. Reduction of night-time BP decline in patients with IHA is more likely to be related to the duration of the disease rather than to the aldosterone levels.     

Sodium transport kinetics in erythrocytes from spontaneously hypertensive rats

Rat erythrocytes with five different amounts of Na+ content have been prepared by using a new, nondetrimental Na+-loading method (net NaHPO4-influx through the anion carrier). This method allowed the determination of 1) maximal translocation rates and apparent dissociation constants for internal Na+ of the Na+-K+ pump, outward Na+-K+ cotransport, and Na+-Li+ countertransport and 2) rate constants of Na+ leak in erythrocytes from spontaneously hypertensive rats of the Okamoto strain and Wistar-Kyoto normotensive controls aged 2 to 26 weeks. Two major abnormalities were found in erythrocytes from spontaneously hypertensive rats: 1) a decreased cotransport affinity for internal Na+, which was constantly observed from 2 to 26 weeks of age (mean intracellular Na+ content for half-maximal stimulation of outward Na+-K+ cotransport = 33.1 +/- 7.0 [SD] mmol/L cells in spontaneously hypertensive rats vs 16.7 +/- 4.7 mmol/L cells in Wistar-Kyoto rats; p less than 0.001), and 2) a decreased maximal pump rate in adult (15- to 26-week-old) spontaneously hypertensive as compared with that for age-matched Wistar-Kyoto rats (9-37 vs 34-70 mmol/L cells/hr). Therefore, the low cotransport affinity for internal Na+ appears to be a stable, possibly genetic defect of spontaneously hypertensive rats. Conversely, the decreased maximal pump rate may be a secondary event, possibly reflecting the appearance of endogenous pump inhibitors in the plasma of adult spontaneously hypertensive rats.     

Sodium and calcium cation transport of erythrocytes in essential hypertension

The sodium and calcium transport of erythrocyte and the influencing factors were studied in essential hypertensive (EH) subjects. The result showed that plasma endogenous digitalis-like compound (EDLC) increased and sodium pump depressed in some EH patients, but there were no parallel correlation between EDLC and sodium pump. The patients with normal sodium pump mainly showed their maximal Ca2+ pump activity and decreased calmodulin (CaM) content of erythrocyte. Thus there may be different types of ion transport defect in EH, and the abnormalities of these cation transports have an important role in the pathogenesis of EH.     

Diagnostic accuracy of adrenal venous sampling in comparison with other parameters in primary aldosteronism

This retrospective study was aimed 1) to compare the difference of the findings between adrenal CT scan and adrenal venous sampling (AVS) in 35 cases with definite primary aldosteronism (PA) for assessment of the diagnostic efficacy of PA subgroup (unilateral and bilateral adrenal hypersecretion: UAH and BAH), and 2) to determine the clinical and biochemical parameters as potential predictors for PA subgroup. There were significant discordant results based on AVS and CT scan in subgrouping PA; 9 of 17 BAH patients (53%) had unilateral lesion on CT scan, while 4 of 18 UAH patients (22%) had no apparent or bilateral lesions on CT scan. Among three diagnostic criteria, absolute values of plasma aldosterone concentration (PAC) in both adrenal veins, lateralized and contralateral ratios of aldosterone/cortisol after ACTH stimulation during AVS to determine the laterality, none of them showed 100% diagnostic accuracy if applied alone. Among several clinical and biochemical parameters, hypokalemia (<3.4 mEq/l), younger age (<52 y) and poor response of PAC (<1.45) after furosemide-upright posture, proved to be significant predictors for UAH, with higher specificities (100%, 88%, 94%, respectively). Therefore, despite AVS as a gold standard method to determine the laterality of aldosterone hypersecretion in PA, our study shows that no single criterion could provide definite diagnostic value for its laterality by AVS. It is also suggested that most PA patients, if not all, with a distinct unilateral adrenal lesion on CT accompanied by hypokalemia, younger age and poor aldosterone response to renin stimulation, could undergo adrenalectomy without prior AVS.     

The prevalence of primary aldosteronism in diabetic patients

Increased plasma aldosterone concentrations (PACs) are associated with higher cardiovascular risk and target organ damage (TOD). Hyperglycemia can potentiate the cellular effects of aldosterone, and the prevalence of diabetes in primary aldosteronism (PA) is 7%-59%. The prevalence of PA in hypertensive individuals is estimated to be 10%-14%. This study of 61 hypertensive diabetic patients not taking spironolactone and with serum creatinine values <2.5 mg/dL sought to establish the prevalence of PA in hypertensive diabetics and compare the prevalence of PA in patients with TOD with those patients without TOD. PA was suspected if PACs were >15 ng/dL and plasma renin activity was <1 ng/dL/h (ratio >30). Although 14 patients had suppressed renin with PACs >8 ng/dL (including two with PACs >11 ng/dL), none met our criteria for PA. There was no correlation between PAC and TOD. This study indicates that routine screening for PA in hypertensive diabetic patients is not justified and that PAC does not correlate with TOD. Further study is needed.     

原发性醛固酮增多症患者左室结构损害的研究

目的 探讨原发性醛固酮增多症(PA)患者左室结构损害的特点.方法 将2007年1月至2010年6月住院行PA筛查最终确诊为PA(213例)及原发性高血压(EH)的患者(225例)纳入研究,依据超声心动图结果评价两组患者的左室结构.结果 PA组的病程、醛固酮水平明显高于EH组(P＜0.01),而血钾、肾素活性明显低于EH组(P＜0.01).协方差分析校正病程后,PA组患者的室间隔厚度、左室舒张末期内径、左室重量指数、左室舒张末期容积和每搏输出量均高于EH组(P＜0.01).PA组患者左室肥厚的发生率明显高于EH组(53.1％对33.8％,x2=16.57,P＜0.01);PA组患者正常构型、向心性重构、向心性肥厚及离心性肥厚的构成比分别是:24.9％、22.1％、22.1％和30.9％.多元逐步回归分析显示收缩压、坐位醛固酮水平是影响PA患者左室重量指数的主要因素,回归系数分别为0.45 (P＜0.01)、0.43 (P＜0.01);病程是影响相对室壁厚度的主要因素,回归系数是0.011 (P＜0.05).结论 PA患者左室肥厚的发生率高于EH患者,其左室构型以离心性肥厚最多见.     

原发性醛固酮增多症与原发性高血压代谢异常的比较

目的 探讨原发性醛固酮增多症的代谢异常.方法 入选已确诊的原发性醛固酮增多症(原醛)患者220例(男117例,女103例)与性别、年龄及高血压病程相匹配的同期住院原发性高血压(EH)患者200例(男104例,女96例).记录入选者一般临床资料和生化指标,在两组间行代谢综合征患病率及两组代谢异常特点比较.结果 (1)原醛组代谢综合征患病率显著高于同期住院EH组(47.3％对31.5％,P=0.009).(2)原醛患者整体血压水平显著高于EH患者[24 h平均收缩压(150.67±15.45)mm Hg对(145.69±17.13)mm Hg,P=0.042;24 h平均舒张压(93.03±10.51)mm Hg对(85.83±14.44)mm Hg,P=0.037],且原醛组以2、3级高血压为主.(3)原醛患者腹型肥胖和胰岛素抵抗发生率显著高于EH患者[86.8％(191/220)对78.5％(157/200),P=0.024;胰岛素抵抗指数42.42±16.11对49.58±22.43,P=0.008].结论 原醛以腹型肥胖、中重度高血压及严重的胰岛素抵抗为主要特征,直接导致其代谢综合征患病率显著高于EH患者.