生理盐水试验确诊原发性醛固酮增多症临床价值再评价

目的评价生理盐水试验确诊原发性醛固酮增多症的诊断价值。方法收集上海交通大学医学院附属瑞金医院内分泌科2006—2010年590例怀疑原发性醛固酮增多症患者的病例,其中有357例确诊为原发性醛固酮增多症,233例确诊为原发性高血压。回顾分析这些患者输注生理盐水后血醛固酮变化,绘制ROC曲线以找到合适的切点用来诊断原发性醛固酮增多症。结果输注生理盐水后血醛固酮ROC曲线下面积为0.975(0.959～0.986),曲线与参照曲线下面积0.5比较,差异有统计学意义(P<0.01)。生理盐水试验后血醛固酮大于277 pmol/L(100ng/L)时,诊断原醛症的敏感度及特异度分别为93%及97.8%。结论生理盐水抑制试验可作为原发性醛固酮增多症的确诊试验。     

原发性醛固酮增多症的诊疗进展

1955年Conn首次描述了以高血压、低钾血症、低肾素活性和高醛固酮分泌为特点的原发性醛固酮增多症(PA)。过去观点认为原发性醛固酮增多症仅占高血压患者中的0．4％～2％,并且对其认识不足,因而未引起足够的重视,从而使大量的原发性醛固酮增多症患者未得到正确的诊断和合理的治疗。本文将从原发性醛固酮增多症的筛查、诊断以及治疗等方面观点的更新作一综述。     

原发性醛固酮增多症功能诊断试验可靠性分析

原发性醛固酮增多症是最常见的导致继发性高血压的病因之一，在高血压人群中发病率高达10％-18％。在原发性醛固酮增多症的诊断中，功能诊断非常重要。目前临床常用的功能试验有血醛固酮／肾素比值的测定、静脉盐水滴注抑制试验、24h尿醛固酮及其代谢物的测定以及开博通试验等。本文将对此类功能试验的诊断可靠性作一综述。     

原发性醛固酮增多症患病之谜

原发性醛固酮增多症是一种继发性高血压的常见病因.研究发现原发性醛固酮增多症在高血压患者中的检出率可达10％,而且原发性醛固酮增多症患者心脏、脑、肾脏等靶器官的损伤更为严重.但目前原发性醛固酮增多症的患病、诊断仍然不明确,现试图揭示原发性醛固酮增多症患病之谜以及临床意义.     

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。     

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.     

原发性醛固酮增多症

原发性醛固酮增多症(原醛症)是继发性高血压的常见病因之一,部分患者亦可伴有低血钾,醛固酮瘤及特发性醛固酮增多症是其主要的病理亚型。原醛症的诊断包括筛查、确诊及分型诊断3个步骤,传统影像学结合体位刺激的方法进行分型诊断,假阳性及假阴性率均较高,肾上腺静脉插管采血可作为影像学检查的补充。醛固酮瘤及原发性肾上腺增生患者应予手术治疗,特发性醛固酮增多症患者多采用药物治疗,螺内酯是其首选药物。     

原发性醛固酮增多症代谢紊乱及心血管事件研究进展

原发性醛固酮增多症患者中,高血压、胰岛素抵抗等代谢紊乱,以及心血管事件的发生率较原发性高血压患者明显升高,在诊断、治疗原发性醛固酮增多症的同时,关注其可能会引起的代谢紊乱及心血管事件,对改善患者预后有一定的帮助。     

原发性醛固酮增多症慢性肾损伤的研究进展

<正>原发性醛固酮增多症(primary aldosteronism)是指醛固酮的过量产生,以往被认为是罕见疾病。随着诊断方法的进步,原发性醛固酮增多症已被确定为继发性高血压的最常见原因。高血压患者中原发性醛固酮增多症患病率为5%～10%,在难治性高血压患者中患病率甚至更高^[1-2]。醛固酮过量会导致许多问题,包括高血压、电解质失衡以及结构和功能性靶器官变化^[3]。早在20世纪五六十年代就有学者研究醛固酮与肾脏之间的关系。后来,动物实验和临床研究表明,醛固酮水平升高与肾脏疾病的进展有关,甚至有研究发现醛固酮水平与肾小球滤过率呈负相关。     

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.     

Primary aldosteronism: what consensus for the diagnosis

Primary Aldosteronism (PA) is characterized by inappropriate aldosterone production partially autonomous of the renin-angiotensin system. Since the ARR ratio was introduced a much higher prevalence of this disease is recognized. PA could be the most common identifiable, specifically treatable and potentially curable form of hypertension so the need of a clinical practice guideline on primary aldosteronism becomes mandatory. Recently the Endocrine Society USA published clinical practice guidelines for the diagnosis and treatment of patients with primary hyperaldosteronism. Systematic reviews of available evidence were used to formulate the key treatment and prevention recommendations. Actually the Endocrine Society consensus is the most used guidelines in diagnosis and treatment of hyperaldosteronism. However, there remains a few unresolved issues, which unfortunately require more of a detour guide and cannot be easily addressed by a straight forward guideline.     

原发性醛固酮增多症:一种并非少见的高血压原因

近年来随着对原发性醛固酮症多症(简称原醛症)认识的提高及诊断技术的改进,原醛症的发病率明显提高。作为一种并非少见的高血压原因,按照一种正确的临床路径诊断原醛症显得尤为重要。本文将就原醛症的筛查试验、确诊试验、分型诊断等进行探讨。     

Prevalence and Diagnosis of Primary Aldosteronism

Primary aldosteronism (PA) is a common cause of arterial hypertension: in the PA Prevalence in Hypertensives (PAPY) Study, the prevalence of PA was 11.2% in consecutive referred hypertensive patients. When adrenal vein sampling (AVS) is available, two thirds of the cases can be attributed to a tumor and one third of cases are idiopathic; the opposite is seen when AVS is unavailable. Thus, AVS influences the relative prevalence rate of the main subtypes of PA. When adrenalectomy is undertaken based on AVS, almost 100% of patients are cured of hyperaldosteronism, one third are cured of hypertension, and 52% are markedly improved in terms of blood pressure control. Persistent hypertension can be predicted by a long history of hypertension and by the presence of excessive cardiovascular damage, including vascular remodeling. Therefore, an early diagnosis is crucial to achieve cure. This review discusses the implications of the high prevalence of PA for its diagnostic strategy.     

原发性醛固酮增多症与高血压（附14例临床分析）

目的 总结我院14例原发性醛固酮增多症(primary hyperaldosteronism，简称PA)的临床表现与诊治，以提高PA引起继发性高血压的诊治水平。方法 对14例以高血压为首发症状的原发性醛固酮增多症患者的临床资料进行分析。结论 高血压合并低血钾，应高度怀疑PA。定位诊断应充分依靠CT，术前应行抗醛固酮治疗，手术治疗效果好。     

Prevalence and characteristics of familial hyperaldosteronism: the PATOGEN study (Primary Aldosteronism in TOrino-GENetic forms)

Primary aldosteronism (PA) is the most frequent cause of secondary hypertension, and patients display an increased prevalence of cardiovascular events compared with essential hypertensives. To date, 3 familial forms of PA have been described and termed familial hyperaldosteronism types I, II, and III (FH-I to -III). The aim of this study was to investigate the prevalence and clinical characteristics of the 3 forms of FH in a large population of PA patients. Three-hundred consecutive PA patients diagnosed in our unit were tested by long-PCR of the CYP11B1/CYP11B2 hybrid gene that causes FH-I, and all of the available relatives of PA patients were screened to confirm or exclude PA and, thus, FH-II. Urinary 18-hydroxycortisol and 18-oxocortisol were measured in all of the familial PA patients. Two patients were diagnosed with FH-I (prevalence: 0.66%), as well as 21 of their relatives, and clinical phenotypes of the 2 affected families varied markedly. After exclusion of families who refused testing and those who were not informative, 199 families were investigated, of which 12 were diagnosed with FH-II (6%) and an additional 15 individuals had confirmed PA; clinical and biochemical phenotypes of FH-II families were not significantly different from sporadic PA patients. None of the families displayed a phenotype compatible with FH-III diagnosis. Our study demonstrates that familial forms of hyperaldosteronism are more frequent than previously expected and reinforces the recommendation of the Endocrine Society Guidelines to screen all first-degree hypertensive relatives of PA patients.     

Primary hyperaldosteronism associated with hypertensive emergencies

There is growing awareness of primary hyperaldosteronism as a cause of secondary hypertension. Usually, it manifests as hypertension and hypokalemia, or as resistant hypertension. Much less often, primary hyperaldosteronism may be detected after a hypertensive emergency has developed. We highlight this association by reporting on eight patients with a clinical diagnosis of primary hyperaldosteronism whose course was complicated by a hypertensive crisis. In all patients, an elevated serum aldosterone, was accompanied by a suppressed plasma renin activity despite the presence of a hypertensive crisis. A good outcome was obtained either with laparoscopic adrenalectomy (1 patient) or with an antihypertensive drug regimen that included an antialdosterone agent (7 patients). The differential diagnosis of hypertensive emergencies should include primary hyperaldosteronism.     

Prevalence of primary hyperaldosteronism in moderate to severe hypertension in the Central Europe region

Recently published studies from different parts of the world report significantly higher prevalence of primary hyperaldosteronism (PH) in hypertensives (ranging from 5 to 25%) than the previously accepted figures. There have been no data so far about the prevalence of PH in Central Europe. Therefore, we have undertaken this study to evaluate the prevalence of PH in patients with moderate to severe hypertension referred to a hypertension unit in the Czech Republic, together with the determination of the percentage of different subtypes of PH including familial forms. In addition to that, we have evaluated the prevalence of other types of secondary forms of hypertension.A total of 402 consecutive patients (230 females and 172 males) with hypertension, referred to our hypertension unit, were studied. Positive aldosterone/renin ratio (ARR, (ng/100 ml)/(ng/ml/h)) >/=50 as a more strict marker of PH was found in 87 patients (21.6%), 30% of them were normokalaemic. The diagnosis of PH was later confirmed in 77 cases (89%); the total prevalence of PH was thus 19%. PH consisted of the following forms: idiopathic hyperaldosteronism 42%, unilateral aldosterone-producing adenoma 36%, unilateral hyperplasia 7%, nonclassifiable PH (refused operation/adrenal venous sampling) 13%, familial hyperaldosteronism type 1.2%. The prevalence of other types of secondary hypertension was as follows: pheochromocytoma 5%, renovascular 4.5%, hypercortisolism 2%, renal 0.75%. In conclusion, we have noted that PH in the Central Europe region (Czech Republic) is the most frequent form of endocrine hypertension with a considerably high prevalence in moderate to severe hypertension. Application of more strict criteria raises the probability of correct diagnosis of PH including the early normokalaemic stages of PH.     

Primary hyperaldosteronism: a frequent cause of residual hypertension after successful endovascular treatment of renal artery disease

BACKGROUND: Poor blood pressure control in renal artery disease patients after percutaneous renal angioplasty (PTRA), with or without stenting (PTRAS), may be due to pre-existing hypertension. Primary hyperaldosteronism is much more frequent than was previously suspected. We hypothesized that residual hypertension observed in some renal artery disease patients after technically successful endovascular treatment may be due to primary hyperaldosteronism. METHODS: Only patients free of significant residual artery stenosis were included in the study. Aldosterone and renin were measured in 52 renal artery disease patients (8 with fibrodysplastic and 44 with atherosclerotic lesions), in whom successful PTRA/PTRAS had been performed previously. An aldosterone-to-renin ratio > or = 23 pg/ml per pg/ml was considered as the cut-off value for performing tests to confirm the diagnosis of primary hyperaldosteronism. RESULTS: Residual hypertension (blood pressure > or = 160/90 mmHg) was observed in 24/52 patients (46%) after revascularization. A raised aldosterone-to-renin ratio was found in nine subjects (17.3%), eight of whom had poor blood pressure control (33% of patients with residual hypertension). A diagnosis of primary hyperaldosteronism was confirmed in seven patients (four atherosclerotic, three fibrodysplastic). All fibrodysplastic subjects with unresponsive blood pressure after PTRA were affected by primary hyperaldosteronism. Primary hyperaldosteronism was confirmed in 9% (4/44) of the atherosclerotic patients (19% of subjects with residual hypertension). No specific clinical features were associated with the subsequent blood pressure control. CONCLUSIONS: Primary hyperaldosteronism is a frequently neglected cause of residual hypertension despite technically successful endovascular treatment of renal artery disease.     

High prevalence of primary aldosteronism using postcaptopril plasma aldosterone to renin ratio as a screening test among Italian hypertensives

The prevalence of primary aldosteronism (PA) was assessed in a specialized hypertension center. Baseline and postcaptopril (50 mg orally) aldosterone to plasma renin activity ratio (A/R) as a screening tool were preliminarily tested in a sample including 22 patients with histories of PA and 53 patients with low-renin essential hypertension (EH). Sensitivity and specificity of A/R ≥35 were 95.4% and 28.3% at baseline, compared with 100% and 67.9% after captopril. Using postcaptopril A/R ≥35 and confirmation by acute saline loading, a PA prevalence of 6.3% was found among 1046 consecutive hypertensive patients with normal renal function. Of those 66 PA patients, 16 (24.2%) had a unilateral adenoma, whereas 50 (75.8%) had idiopathic hyperaldosteronism. At presentation, 45.4% of the PA and 16.3% of EH patients were treated with two or more antihypertensive drugs (χ² = 33.117, P < .0001). However, among untreated patients (n = 553), the prevalence of mild-to-moderate hypertension (ie, <180/110 mm Hg) was not different between patients with PA and those with EH (70.6% v 76.7%, χ² = 0.086, P = .770). Serum potassium ≥3.6 mEq/L was found in 60.6% of PA patients. In conclusion, we observed the following: 1) postcaptopril compared with baseline A/R is a better screening tool for PA; 2) PA is relatively frequent among hypertensive individuals; 3) PA is not necessarily associated with severe hypertension; and 4) hypokalemia is an insensitive screening criterion for PA.