Discriminating factors for recurrent hypertension in patients with primary aldosteronism after adrenalectomy.

Patients with primary aldosteronism show relatively high rates of hypertension after adrenalectomy, but the risk factors for postoperative hypertension remain unclear. Forty-six patients with primary aldosteronism (PA) who had undergone adrenalectomy between 1976 and 1998 were enrolled in this study. Follow-up information including blood pressure (BP) and cardiovascular complications was collected by means of correspondence or telephone contact. At discharge BP was normalized in 34 patients (72%); hypertension persisted in the remaining 12 patients, but BP control was significantly improved. The patients who remained hypertensive at discharge had longer durations of hypertension than did those with normalized BP. After an average follow-up period of 12.2 years, 16 of 34 BP-normalized patients (47%) had recurrent hypertension. Age at adrenalectomy, preoperative serum creatinine level and systolic blood pressure at discharge were significantly higher in patients with recurrent hypertension than in those without it. A multivariate logistic regression analysis revealed that only the level of serum creatinine was independently associated with the incidence of recurrent hypertension. Patients with serum creatinine of 0.9 mg/dl or greater had significantly higher rates of recurrent hypertension than those with lower values of serum creatinine. Cardiovascular complications occurred in 5 patients prior to the surgery and in 2 patients during the follow-up period. Although the severity of renal involvement is subclinical, renal damage may play an important role in the development of hypertension during a long period after adrenalectomy in patients with PA.     

Urinary excretion of catecholamines in patients with primary aldosteronism before and after unilateral adrenalectomy

The authors compared urinary excretion of noradrenalin (NA), adrenalin (A) and dopamine (DA) in 12 patients with primary aldosteronism (PA), 54 healthy controls and 17 patients with fixed benign essential hypertension (BEH), and in PA investigated the changes occurring in the catecholamine spectrum after removal of aldosterone-producing adrenal adenoma. The patients with PA before adrenalectomy differed from the controls and patients with BEH by low NA excretion and high DA excretion. After unilateral adrenalectomy, patients with PA presented simultaneously with BP, aldosterone and renin normalization a rise in NA excretion and a drop in urinary DA to similar or lower values than those found in the controls and BEH. The results show that changes in urinary catecholamines excretion in A may be a secondary consequence of hypermineralocorticism. High DA may be the consequence of a mobilization of contra-regulatory natriuretic mechanisms in the course of aldosterone-induced sodium retention. Low NA and A may participate in lowering the plasma renin activity which in PA in suppressed, sometimes disproportionately to the actual body sodium content.     

Laparoscopic adrenalectomy on a patient with primary aldosteronism during pregnancy

A pregnant 26-year-old woman was referred for evaluation and management of progressive hypertension and hypokalemia at 14 weeks of gestation. Her plasma aldosterone level was markedly elevated and magnetic resonance imaging showed a right adrenal tumor. Primary aldosteronism due to an aldosterone producing-adenoma was diagnosed. Because of progressive severe hypertension, a laparoscopic adrenalectomy was performed at 17 weeks of gestation. The procedure was completed without complication, and plasma aldosterone and potassium levels rapidly improved post-operatively. However, her hypertension persisted and the growth retardation of the fetus was found. Regrettably, intrauterine fetal death was confirmed at 26 weeks of gestation. Histological examination of the placenta revealed that the placental artery had very thick walls which had apparently caused a critical failure in fetal blood flow. The optimal timing of laparoscopic surgery during pregnancy and perioperative management were subsequently discussed.     

Vascular remodeling and duration of hypertension predict outcome of adrenalectomy in primary aldosteronism patients

Remodeling of the resistance arteries is a hallmark of arterial hypertension and predicts cardiovascular events, but it was unknown whether it could also predict the blood pressure response to adrenalectomy of patients with an aldosterone-producing adenoma. Therefore, we investigated the outcome of adrenalectomy as a function of vascular remodeling in the context of the preoperative features of aldosterone-producing adenoma patients. At 2 referral centers for hypertension, we prospectively measured the media:lumen ratio of small arteries from fat tissue of 50 consecutive aldosterone-producing adenoma patients treated with adrenalectomy. The blood pressure response to adrenalectomy was assessed by considering the blood pressure values and the number and dosages of antihypertensive medications. Adrenalectomy significantly (P<0.001) lowered plasma aldosterone (from 27.3+/-4.9 ng/dL to 8.3+/-11.2 ng/dL), the aldosterone:renin ratio (from 117+/-35 to 11+/-2), and blood pressure (from 163+/-22/98+/-2 mm Hg to 133+/-2/84+/-1 mm Hg), even despite a reduction (from 141+/-14 to 100+/-15; P=0.02) of the score of antihypertensive treatment. It provided cure of hypertension in 30% of the aldosterone-producing adenoma patients, normotension with less antihypertensive therapy in 52%, and improved blood pressure control in the rest. The media:lumen ratio and the known duration of hypertension significantly predicted the blood pressure response to adrenalectomy at univariate and multivariate analyses. Because a long duration of hypertension and/or the presence of vascular remodeling imply lower chances of blood pressure normalization at long-term follow-up postadrenalectomy, these findings emphasize the importance of an early diagnosis of aldosterone-producing adenoma.     

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。     

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.     

老年原发性醛固酮增多症和高血压患者N末端B型钠尿肽前体及心脏早期损害的研究

目的分析老年原发性醛固酮增多症(PA)和原发性高血压(EH)患者N末端B型钠尿肽前体(NT-proBNP)水平对老年患者早期心脏损害的评价价值。方法连续选择2009年12月~2014年6月在我院接受治疗的149例高血压患者,其中确诊为PA的70例患者为病例组,排除PA并确诊为EH的79例患者为对照组。观察并比较2组患者早期心脏损害指标NT-proBNP和左心室质量指数(LVMI)。结果病例组log NT-proBNP(1.9±0.4 vs1.7±0.5,P=0.001)、LVMI[(116.5±20.8)g/m2 vs(106.3±21.7)g/m2,P=0.004]和左心室肥厚(67.1%vs50.6%,P=0.041)比例明显高于对照组。多元线性逐步回归分析显示,病例组LVMI及激活醛固酮水平与NT-proBNP独立相关,对照组诊室收缩压水平与NT-proBNP独立相关。结论老年PA患者较EH患者有独立于血压水平的更高的log NT-proBNP水平及更早的心脏损害。     

Blood pressure outcome of adrenalectomy in patients with primary hyperaldosteronism with or without unilateral adenoma

OBJECTIVE: To assess blood pressure outcome in patients with primary aldosteronism, who were operated on the basis of a unilateral adenoma detected by computed tomography or a lateralized aldosterone hypersecretion detected by adrenal venous sampling, and to analyze the hormonal and nonhormonal factors associated with the outcome. METHODS: A retrospective study of 168 patients with primary aldosteronism undergoing surgery: 109 patients with a unilateral adenoma detected by computed tomography and 59 without a unilateral adenoma who underwent surgery because of an aldosterone to cortisol ratio at least five times higher on the dominant side than on the nondominant side. RESULTS: Patients with a unilateral adenoma were more likely to be women, had a shorter history of hypertension and had lower blood pressure levels and treatment scores than patients without a unilateral adenoma. The mean systolic blood pressures of patients with and without unilateral adenomas at follow-up were 133 +/- 16 and 137 +/- 16 mmHg, respectively. Hypertension cure or improvement was observed in 77% (95% confidence interval 69-85%) and 68% (95% confidence interval 56-80%) of patients, respectively. Using a linear regression model, baseline urinary aldosterone was positively associated, and baseline serum potassium was negatively associated, with decrease in systolic blood pressure. CONCLUSION: Adrenalectomy improves blood pressure control in patients with primary aldosteronism operated on the basis of either unilateral adenoma detected by computed tomography or a lateralized aldosterone hypersecretion. A high urinary aldosterone excretion and a low serum potassium level predict a more favorable outcome of surgery.     

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。     

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.     

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.