在高血压患者中筛选原发性醛固酮增多症国人血浆醛固酮/肾素活性比值标准的探讨

目的血浆醛固酮/血浆肾素活性比值(ARR)测定是目前从高血压患者中检出原发性醛固酮增多症(原醛)患者最常用和有效的筛选方法。ARR 值在不同人种中有很大差别,测定条件对其结果影响较大。本研究在严格控制药物、体位等条件下,建立中国人筛选原醛 ARR 值。方法根据肾上腺增强 CT 检查结果,将110例高血压患者分为原发性高血压组(65例)和肾上腺腺瘤/增生组(45例)。停用对肾素和醛固酮分泌有影响的降压药物至少2周,利尿剂包括螺内酯停用4周。对于不宜停服降压药物的患者,改服非双氢吡啶类钙拮抗剂维拉帕米缓释片(varapamil-SR)和(或)α受体阻滞剂特拉唑嗪(terazosin)。低血钾患者补钾至正常水平。采血日晨起保持立位2 h 后,于上午9～10点立位取肘静脉血测定血浆肾素活性、血浆醛固酮浓度,计算 ARR。结果 ARR 值以醛固酮 pg/ml/肾素活性 ng·ml~(-1)·h~(-1)为单位。立位 ARR 值在原发性高血压组为100.00±48.65,肾上腺腺瘤/增生组为699.33±213.33。由 ROC 曲线所得切割值为240,立位 ARR 较卧位 ARR 更有筛查价值。在肾上腺腺瘤/增生组93.3%(42/45)患者的 ARR 值高于240,原发性高血压组90.7%(59/65)患者ARR 值低于该值。取 ARR 值240为切割点,我们从近178例高血压患者中检出15例原醛患者(手术病理证实),所有15例患者 ARR 均大于240,显示极高的敏感性和特异性。结论采用本研究试验条件,中国人立位 ARR 值为240。ARR 测定是一项简便、有效的原醛筛查方法,测定时须注意体位、药物、血钾的影响。     

原发性醛固酮增多症的内分泌功能诊断

原发性醛固酮增多症(原醛症)是继发性高血压最常见的原因之一,以低肾素和高醛固酮血症为特征,血浆醛固酮/肾素比值(ARR)是筛查原醛症的可靠指标.而口服高钠负荷试验、生理盐水试验、氟氯可的松抑制试验或卡托普利试验中的任何一项均可作为ARR阳性患者的确诊试验;肾上腺静脉插管采血(AVS)是原醛症分型诊断的金标准.     

血钾正常伴高血压的原发性醛固酮增多症患者224例的临床分析

目的探讨血钾正常伴高血压的原发性醛固酮增多症(原醛)患者的临床特点。方法选择2006-01-2010-03在新疆维吾尔自治区人民医院高血压中心住院,经过醛固酮肾素活性比值(ARR)初筛、卡托普利试验或盐水负荷试验确诊的224例血钾正常伴高血压的原醛患者,回顾性分析临床和生化资料。结果血钾正常伴高血压的原醛患者224例中1、2、3级高血压分别占4.5%、18.3%、77.2%;主要症状依次是头痛(52.1%)、头晕(49.7%)、乏力(4.1%)、心悸(3.0%)、肢体麻木(1.8%);心血管并发症中脑梗死的发生率为24.1%,冠状动脉粥样硬化性心脏病的发生率为11.6%;血钠平均为(140.8±2.8)mmol/L,高钠血症患者仅占2.7%;低肾素活性者占97.3%。以ARR≥20(ng/dL)/[μg/(L·h)]且肾素活性减低为标准诊断血钾正常伴高血压的原醛的阳性率明显高于肾素活性降低且醛固酮浓度升高、ARR≥20(ng/dL)/[μg/(L·h)]且醛固酮浓度升高、ARR≥30(ng/dL)/[μg/(L·h)]为标准的阳性率。结论血钾正常伴高血压的原醛患者主要表现为中重度高血压,血浆肾素活性降低,血管并发症中脑梗死比冠状动脉粥样硬化性心脏病更多见,以ARR≥20(ng/dL)/[μg/(L·h)]且肾素活性减低为标准筛查血钾正常伴高血压的原醛可能有助于减少漏诊率。     

88例原发性醛固酮增多症临床回顾分析

目的提高对原发性醛固酮增多症（简称原醛）的诊治水平。方法回顾性分析88例原醛患者的临床资料。结果血压水平、血浆醛固酮浓度（PAC）升高,血浆肾素活性（PRA）、血清钾离子浓度下降。醛固酮瘤占84．09％,特发性醛固酮增多症（简称特醛症）占15．91％。95．45％患者的血浆醛固酮／血浆肾素活性比值（ARR）〉20。醛固酮瘤患者具有更高的血浆醛固酮水平及更低的血浆肾素活性和血清钾离子浓度。结论ARR是原醛的重要筛查方法;卧立位试验及CT有助于肾上腺皮质腺瘤和增生的鉴别。     

原发性醛固酮增多症的分型诊断

目的 探讨用于原发性醛固酮增多症(原醛症)分型诊断检查方法的价值.方法 收集本院近7年来57例临床确诊的原醛症患者[醛固酮瘤22例,特发性醛固酮增多症(特醛症)26例,原发性肾上腺增生9例],检测患者的血电解质、血浆肾素活性及血、尿醛固酮,将结果与19例原发性高血压患者对照.再通过肾上腺CT、体位激发试验及肾上腺静脉采血检查对原醛症患者分型并随访.结果 (1)醛固酮瘤患者血压及血、尿醛固酮较特醛症患者高,血钾及血浆肾素活性则低,而原发性肾上腺增生患者临床及生化改变介于两者之间.肾上腺CT检查在原醛症分型诊断中的符合率为醛固酮瘤86.4%,特醛症73.1%,原发性肾上腺增生22.2%;肾上腺静脉采血检查以两侧醛固酮之比作为判定标准时符合率为86.4%、80.8%和77.8%,以醛固酮与皮质醇之比为判定标准则符合率分别为95.5%、92.3%及100.0%.(2)醛固酮瘤及原发性肾上腺增生患者术后随访血醛固酮均下降,血压恢复正常者分别为22.7%及44.9%,血钾恢复正常者为83.3%及100.0%,而特醛症患者随访中各项测值无明显变化,另有33.3%诊断时血钾正常的患者随访中出现低血钾.结论 原醛症的分型诊断需依靠多种检查手段综合分析,单纯依赖影像学检查或体位激发试验并不可靠,肾上腺静脉采血检查可作为影像学检查的补充,用两侧醛固酮与皮质醇的比值分析较单纯比较两侧醛固酮之比更为可靠;醛固酮瘤及原发性肾上腺增生患者术后临床及生化测值均得以明显改善,而特醛症患者随访中无明显变化.     

新疆乌鲁木齐地区原发性醛固酮增多症105例临床分析

目的分析原发性醛固酮增多症(PA)的临床表现、辅助检查及治疗情况。方法对1999年7月至2005年3月间连续确诊的105例患者的临床资料进行回顾性分析。结果89例患者中有低血钾者占85%,血浆立、卧位肾素活性处于正常低值,立、卧位醛固酮水平均增高。醛固酮和肾素活性比值(ARR)>25者占71%,ARR>50者占8%。81例行B超检查,99例行CT检查,20例行MRI检查,其阳性率分别为:51.9%,80.8%,85%。58例原发性醛固酮增多症患者行手术治疗,其中43例血压均恢复正常,15例仍需要药物继续控制血压。结论血浆肾素活性,血浆醛固酮水平,以及血浆醛固酮和肾素活性比值(ARR)是原发性醛固酮增多症的主要定性诊断方法。CT是原发性醛固酮增多症的主要定位诊断依据。外科手术是治疗原发性醛固酮增多症的重要方法。     

原发性醛固酮增多症

原发性醛固酮增多症(primary aldosteronism,简称原醛)是指由于肾上腺皮质自主性醛固酮分泌增多而导致以高血压、低血浆肾素活性(PRA)、高醛固酮血症和低钾血症为特征的临床综合征,是继发性高血压常见病因之一。原醛最常见的病因是特发性醛固酮增多症和肾上腺腺瘤,分别占65%和3     

640例高血压患者中原发性醛固酮增多症患病率及临床特点

目的　探讨高血压患者中原发性醛固酮增多症（PA）的患病率,并分析PA患者的临床特点。方法　选择就诊于东莞市中医院内科门诊高血压患者640例,于清晨9∶30～10∶30患者起床2小时后,取坐位5～15　min后采血测定血浆醛固酮（ALD）水平和肾素活性（PRA）,计算血浆醛固酮/血浆肾素活性比值（ARR）。ARR≥30且ALD水平≥15　ng／dL的患者接受开博通试验,服开博通后2小时血浆醛固酮水平抑制程度≤30%,则试验结果为阳性,诊断为原发性醛固酮增多症^［1］。进一步分型时,PA患者均进行肾上腺薄层增强CT检查,诊断为特发性醛固酮增多症（IHA）的患者加用盐皮质激素受体拮抗剂（螺内酯）治疗,诊断为醛固酮瘤（APA）患者予以在腹腔镜下行单侧肾上腺切除术。结果　640例患者中112例（17.5%）ARR≥30,其中87例（13.59%）ARR≥30且ALD水平≥15　ng／dL的患者接受开博通试验。服用开博通2　h后血ALD水平抑制≤30%者32例,确诊为PA（5%）,其中20例诊断为APA（3.125%）,另外12例（1.875%）诊断为IHA。诊断为IHA的患者加用螺内酯治疗,醛固酮瘤患者予以在腹腔镜下行单侧肾上腺切除术。结论　高血压人群中原发性醛固酮增多症的患病率较高,要重视高血压患者中原发性醛固酮增多症的筛查,原发性醛固酮增多症患者临床具有高血压、低血钾、高尿钾、高醛固酮、低肾素、高ARR的典型临床特点。     

应重视在高血压患者中开展原发性醛固酮增多症的筛查、确诊和分型定位检查

自1955年Conn等报道首例原发性醛固酮增多症（简称原醛）患以后的30多年中,原醛一直被认为是一种少见疾病,在高血压人群中原醛患病率不到1％。1981年Hiramatsu等首次采用血浆醛固酮／血浆肾素活性比值（ARR）作为原醛筛查指标,在348例未经选择的高血压患中发现9例（2．6％）醛固酮腺瘤（APA）患。从20世纪90年代起,国外普遍采用ARR作为原醛筛查指标,目前达成以下共识：原醛不是少见病,多数报道原醛占高血压患的5％-15％。低血钾不是原醛必须具备的特征,在确诊的原醛患中,低血钾发生率仅为9％-37％。澳大利亚Princess Alexandra医院高血压科自1991年起对所有高血压就诊患进行ARR测定,使原醛的检出率提高了10倍,肾上腺腺瘤手术数增加了4倍。     

醛固酮/肾素比值在原发性醛固酮增多症筛查中的临床价值

目的 回顾分析瑞金医院内分泌科近5年怀疑原发性醛固酮增多症患者的资料,用受试者工作特征( receiver operating characteristic,ROC)曲线下面积评估醛固酮/肾素比值(aldosterone to renin ratio,ARR)在诊断原发性醛固酮增多症(原醛症)中的临床价值.方法 收集瑞金医院内分泌科2006年1月至2010年8月行卧位及立位ARR测定的590例怀疑原发性醛固酮增多症入院患者的临床资料,其中确诊为原醛症的患者357例,确诊为原发性高血压的患者233例.分析瑞金医院内分泌科2010年9月至2011年4月行随机及立位ARR测定的100例怀疑原醛症患者的临床资料,其中确诊为原醛症的患者29例,确诊为原发性高血压的患者71例.综合分析卧位、立位及随机ARR ROC曲线,以确定合适的切点用于诊断原发性醛固酮增多症.结果 2006年1月至2010年8月行卧位及立位ARR测定的590例患者卧位ARRROC曲线下面积为0.838(0.805～0.867),立位ARR ROC曲线下面积为0.873(0.843 ～0.899),两曲线下面积比较有显著差异(P＜0.01).2010年9月至2011年4月行立位及随机ARR测定的100例患者立位及随机ARR ROC曲线下面积分别为0.962(0.928 ～0.995)及0.944(0.893 ～0.994),两者比较无显著差异(P＞0.05).立位ARR切点为400(pg· ml-1)/(ng·ml-1·h-1)时,诊断原醛症患者的敏感性为91.9％,特异性为64.2％.结论 立位ARR比卧位ARR更适应作为原醛症的筛查指标,随机ARR与立位ARR在原醛症诊断中具有相似的临床价值.本研究认为,在严格控制患者药物、体位、检测时间条件下,ARR切点400( pg·ml-1)/(ng·ml-1·h-1)是原醛症筛查试验比较合适的切点.     

Ratio of serum aldosterone to plasma renin concentration in essential hypertension and primary aldosteronism.

The ratio of serum aldosterone to plasma renin activity (PRA) has been proposed as sensitive screening method in the diagnosis of primary aldosteronism under random conditions. However, the method for determination of renin activity is hampered by the necessity of ice cooling during storage and transport. The present study was therefore conducted to examine the ratio of serum aldosterone to plasma renin concentration (ARR) and its usefulness in diagnosis of primary aldosteronism under ambulatory conditions and given antihypertensive medication. 146 patients with arterial hypertension who consecutively attended the outpatient clinic were studied prospectively. Patients with secondary hypertension besides primary aldosteronism were not included in the series. 37 normotensive patients served as control. Also, 17 patients with known primary aldosteronism were retrospectively examined. Among the hypertensive group 2 patients with Conn's syndrome were newly detected (1.4%). ARR was 7.92 +/- 6.04 [pg/ml]/[pg/ml] in normotensive controls (range from 2.03 to 26.98), 14.61 +/- 18.50 [pg/ml]/[pg/ml] in patients with essential hypertension (n = 144, range from 0.41 to 115.45) and 155.92 +/- 127.84 [pg/ml]/[pg/ml] in patients with primary aldosteronism (n = 19, range from 6.75 to 515). 17 of the 19 patients with Conn's syndrome had an ARR of more than 50. Under ongoing drug treatment this represents a sensitivity of 89% and a specificity of 96%. Sensitivity decreased to 84% and specificity increased to 100% when a second criteria (aldosterone > or = 200 pg/ml) was included. In summary, ARR using renin concentration is a useful screening parameter for primary aldosteronism.     

QT interval in patients with primary aldosteronism and low-renin essential hypertension

INTRODUCTION: QT interval prolongation increases the risk of sudden death in several medical conditions. Patients with primary aldosteronism and salt-sensitive hypertension experience more cardiovascular events than those with normal-renin essential hypertension. QT interval prolongation might represent one of the risk factors for cardiovascular events in these patients. The aim of the present study was to evaluate the QT interval in patients with primary aldosteronism and low-renin essential hypertension (LREH). METHODS: Twenty-seven patients with primary aldosteronism, 17 patients with LREH, 117 patients with essential hypertension and 25 healthy individuals were studied. Plasma aldosterone, plasma renin activity, and aldosterone to plasma renin activity ratio (ARR) were determined. Corrected QT intervals (QTcs) were measured from a 12-lead electrocardiogram. RESULTS: The QTc was longer in primary aldosteronism (434 +/- 23 ms) and LREH (430 +/- 18 ms) compared with essential hypertension (419 +/- 22 ms) and healthy controls (412 +/- 19 ms) (P = 0.0004). The prevalence of QTc longer than 440 ms was higher in primary aldosteronism (48%) and LREH (23%) compared with essential hypertension (11%) and healthy controls (4%) (P < 0.0001). QTc correlated with plasma aldosterone (P = 0.01), ARR (P = 0.02), and diastolic blood pressure (P = 0.01). ARR (P = 0.01) and systolic blood pressure (P = 0.01) were identified as independent predictors of QTc. CONCLUSIONS: We postulate that the elevated aldosterone secretion contributes to the prolongation of the QT interval in patients with primary aldosteronism and LREH through both a depletion of intracellular potassium concentration and higher blood pressure values. QTc measurement might represent one simple, non-invasive and reproducible index to characterize the cardiovascular risk in patients with primary aldosteronism and LREH.     

Minireview: primary aldosteronism--changing concepts in diagnosis and treatment

Primary aldosteronism affects 5-13% of patients with hypertension. Patients with hypertension and hypokalemia and most patients with treatment-resistant hypertension should undergo screening for primary aldosteronism with a plasma aldosterone concentration to plasma renin activity ratio. A high plasma aldosterone concentration to plasma renin activity ratio is a positive screening test result, a finding that warrants confirmatory testing. For those patients that want to pursue a surgical cure, the accurate distinction between the subtypes (unilateral vs. bilateral adrenal disease) of primary aldosteronism is a critical step. The subtype evaluation may require one or more tests, the first of which is imaging the adrenal glands with computed tomography, followed by selective use of adrenal venous sampling. Because of the deleterious cardiovascular effects of aldosterone, normalization of circulating aldosterone or aldosterone receptor blockade should be part of the management plan for all patients with primary aldosteronism. Unilateral laparoscopic adrenalectomy is an excellent treatment option for patients with unilateral aldosterone-producing adenoma. Bilateral idiopathic hyperaldosteronism should be treated medically. In addition, aldosterone-producing adenoma patients may be treated medically if the medical treatment includes mineralocorticoid receptor blockade.     

Active renin versus plasma renin activity to define aldosterone-to-renin ratio for primary aldosteronism

BACKGROUND: In recent years, the assessment of the plasma aldosterone-to-renin ratio (ARR) has become an established screening method for the diagnosis of primary aldosteronism. Plasma renin activity (PRA) is usually measured to define ARR although, increasingly, renin concentration alone is often measured in clinical routine. OBJECTIVE: To determine the threshold of ARR using active renin concentration to screen for primary aldosteronism. DESIGN AND PARTICIPANTS: To determine the ARR threshold based on plasma immunoreactive renin concentration (irR), we measured plasma aldosterone concentration (PAC), irR and PRA in 36 hypertensive patients, nine thereof with adrenal adenoma, and compared ARRs calculated from irR and PRA, respectively. SETTING: Single-centre, hypertension clinic in a tertiary care hospital. RESULTS: PRA ranged from 0.41-14.9 ng/ml per h and irR from 1.1-72 ng/l. There was an excellent correlation between PRA and irR (r = 0.98, P < 0.0001) and between ARRPRA and ARRirR (r = 0.96, P < 0.0001). An ARRPRA > 750 pmol/l per ng/ml per h was previously found to be highly predictive of primary aldosteronism because 90% of the corresponding patients failed to suppress PAC upon saline infusion or fludrocortisone. The corresponding threshold value for ARRirR was 150 pmol/ng in our patients. Using these cut-offs, nine subjects had both increased ARRPRA and ARRirR while, in three patients, either ARRPRA or ARRirR were increased. The nine patients with increased ARRPRA and ARRirR also had PAC > 650 pmol/l. Only these patients had adrenal adenomas. CONCLUSIONS: The ARR threshold to screen for primary aldosteronism may be based on measurement of irR. An ARRirR > 150 pmol/ng may indicate primary aldosteronism.     

原发性醛固酮增多症筛查中血浆醛固酮/肾素活性比值的影响因素

血浆醛固酮水平/肾索活性比值(ARR)是筛查原发性醛固酮增多症的实用指标.由于影响肾素和醛同酮分泌的因素众多,ARR切点值变异范围较大,至今仍然是一个缺乏标准化的指标.本文综述这些因素,旨在临床上提高ARR的诊断效力.     

Prevalence of primary aldosteronism among unselected hypertensive patients: a prospective study based on the use of an aldosterone/renin ratio above 25 as a screening test.

Primary aldosteronism (PA) has been considered a rare cause of hypertension. The introduction of the aldosterone/renin ratio (ARR) as a screening test has led to an increase in the detection rate. The aim of this study was to evaluate the prevalence of PA among unselected hypertensive patients by using an ARR >25 as a screening test. We studied 3,000 consecutive unselected hypertensive patients. Blood samples for the determination of plasma renin activity (PRA), aldosterone (ALD) and electrolytes were drawn in the morning, and patients with an ARR >25 underwent intravenous saline infusion as a confirmatory test. Adrenal CT and a dexamethasone suppression test were performed in patients with confirmed PA. Patients with a positive dexamethasone test underwent genetic testing for glucocorticoid-remediable aldosteronism (GRA). Out of 3,000 hypertensives, 684 (22.8%) showed an ARR >25 and 177 of them (5.9% of the whole population) had a positive saline loading test. Only 44 of them (24.8%) were hypokalemic. CT was performed in all the patients with confirmed PA and 53 of them (29.9%) had a solitary adrenal macroadenoma, 112 (63.3%) had bilateral adrenal enlargement and 12 (6.8%) had normal appearing adrenal glands. Of 177 patients given dexamethasone to identify GRA, 8 (4.5%) showed aldosterone suppression but only one (0.1%) tested positive for the chimeric gene. In conclusion, our findings indicate that standardized application of an ARR >25 to unselected hypertensive patients, followed by i.v. saline loading as a confirmatory test, can result in the detection of a large number of patients with PA (5.9% of the studied population), most of whom are normokalemic. Bilateral adrenal hypertrophy represents the more common form of PA.     

血浆醛固酮与肾素活性比值在原发性醛固酮增多症筛查中的应用现状及影响因素

血浆醛固酮与肾素活性比值(ARR)是原发性醛固酮增多症(PA)的一个敏感筛查指标,也是评价PA手术预后的指标之一。探讨血浆醛固酮与肾素活性比值测定的影响因素特别是药物、盐负荷和体位的影响对提高ARR的筛查效率具有重要意义。本文就ARR目前的应用情况,测定条件的优化做一介绍。     

Outpatient Screening Tests for Primary Aldosteronism

Summary: Outpatient screening tests for primary aldosteronism. P. J. Dunn and E. A. Espiner, Aust. N.Z. J. Med. , 1976, 6 , pp. 131–135.
The assessment of basal plasma aldosterone and renin concentrations, and urinary aldosterone excretion has been compared with their values after a suppressive test employing mineralocorticoid induced volume expansion in five patients with primary aldosteronism and in patients with essential hypertension. Reliance upon measurements of basal plasma aldosterone concentration, plasma renin/aldosterone ratio and urine aldosterone excretion alone proved unsatisfactory for distinguishing patients with primary aldosteronism. However these patients, in contrast to those with essential hypertension, showed elevated values or no decrease in plasma aldosterone concentration following three days treatment with 400 μg fludrocortisone (florinef) daily. It is proposed that the assessment of basal plasma renin activity together with florinef suppression of plasma aldosterone are the most effective and convenient outpatient screening procedures in the diagnosis of primary aldosteronism.     

The pattern of plasma renin activity and aldosterone secretion in normal and hypertensive subjects before and after saline infusions

The pattern of plasma renin activity and aldosterone secretion was studied in 56 unselected patients with essential hypertension and in 10 hypertensive patients with renal complications. The results were compared to responses found in 17 normal subjects and 6 patients with verified primary aldosteronism. In all cases, plasma renin activity and aldosterone secretion rates were measured under precise conditions of metabolic balance, initially during dietary salt restriction and then after physiologic saline infusions.

Abnormally low responses in plasma renin activity to salt restriction were found in 13 patients with essential hypertension (25 percent), and in 4 there was no significant increase with standing. The expected increase in aldosterone secretion also failed to occur in 9 patients, 6 of whom demonstrated low plasma renin activity. The great majority of patients with essential hypertension responded normally to saline infusions with decreased plasma renin activity and aldosterone secretion, but in 4 patients the latter was greater than 300 μg/day after saline infusion. The response of hypertensive patients with renal complications was not different from that seen in uncomplicated cases.

Although there was great variation in the responses seen in individual patients with essential hypertension, the combination of suppressed plasma renin activity and autonomous, excessive aldosterone secretion was found in only 1 patient. In this unselected series, the maximal incidence of primary aldosteronism (using the currently accepted criteria) was less than 5 percent.