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.     

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临床诊治规范

原发性醛固酮增多症是一种常见的继发性高血压,发病率为10%～20%,与原发性高血压患者相比,原醛症患者心、脑等靶器官损害更为严重,因而此类高血压的早期诊断至关重要。本文将就原发性醛固酮症多症的患病率、筛查指标、确诊试验、分型诊断及治疗方案进行探讨。     

原发性醛固酮增多症合并肾动脉狭窄的临床特点和诊断

目的分析肾动脉狭窄合并原发性醛固酮增多症患者的临床特点及预后。方法回顾性分析10例确诊为肾动脉狭窄合并原发性醛固酮增多症的患者的临床基线资料、实验室检查结果、影像学检查特点、治疗情况以及随访资料。结果所有患者均因3级高血压入院,70%的患者合并有低钾血症。50%的患者入院时原发性醛固酮增多症的筛查试验结果为阴性。4例患者同时进行了肾动脉支架植入术和经腹腔镜肾上腺切除术或肾上腺消融术。4例患者仅行肾动脉支架置入术。2例患者未接受任何手术或介入治疗。后续随访表明,同时针对两种疾病进行药物或手术治疗后,患者高血压情况均得到有效控制。结论在合并肾动脉狭窄的患者中行原发性醛固酮增多症的筛查试验,应谨慎解读结果。建议对于在解除肾动脉狭窄后依然存在难治性高血压的患者复查筛查实验,以明确有无合并原发性醛固酮增多症。     

家族性醛固酮增多症的分子遗传学研究进展

家族性醛固酮增多症（FH）是由家族性肾上腺皮质分泌过多醛固酮引起的一类单基因遗传性高血压，占原发性醛固酮增多症5%，多为常染色体显性遗传，临床上多表现为高血压、低血钾，伴或不伴肾上腺增生。根据其致病基因的不同分为四种亚型，近年来FH 的致病基因研究取得了不少新发现。本文对家族性醛固酮增多症的分子遗传学研究进展进行综述。     

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分子遗传学研究进展

原发性醛固酮增多症是继发性高血压最常见的原因,主要可分为家族性和散发性.已知家族性醛固酮增多症Ⅰ型与CYP11B1和CYP11B2基因的融合有关,不同的融合位点有不同的临床表现.家族性醛固酮增多症Ⅱ型的致病基因定位于7p22,G蛋白耦联的雌激素受体基因值得关注.家族性醛固酮增多症Ⅲ型和散发性原发性醛固酮增多症均与KNCJ5基因突变相关,分别为种系突变及体系突变,但可能并非唯一致病机制.动物实验中,弱整流型钾通道Task1和Task3的敲除制造了近年较成功的高醛固酮血症小鼠模型.     

原发性醛固酮增多症的分子机制研究进展

<正>原发性醛固酮增多症是继发性高血压最常见的形式,早期诊断和治疗对预防不良心血管结局至关重要。近年来,随着分子诊断进展,发现驱动醛固酮合成的基因胚系和体系突变是导致疾病发生的主要机制。本文将阐述原发性醛固酮增多症的分子机制及基于机制的动物模型。     

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。     

血浆醛固酮/肾素活性比值在诊断原发性醛固酮增多症患者的价值

目的采用血浆醛固酮/肾素活性比值(ARR)在高血压患者中筛选原发性醛固酮增多症(原醛)病例,治疗和随访患者、分析其临床特点,从而探讨原醛的临床特点和 ARR 在原醛诊断中的价值。方法收集门诊和住院的高血压患者902例(其中3级高血压609例),空腹采血并用放射免疫方法测定血浆肾素和醛固酮水平及血生化指标,计算 ARR。对比值大于25(ng/dl 比ng·ml~(-1)·h~(-1))的126例疑诊为原醛的病例进行肾上腺薄层 CT 扫描,分析其临床特点、用抗醛固酮药物治疗并进行随访。结果原醛在高血压人群中占14%(126/902),肾上腺 CT 见54例单侧或双侧增生和25例腺瘤;原醛合并低血钾占39%(49/126);25例患者接受外科治疗,有效率100%,其中48%(12/25)能达到治愈;用螺内酯治疗有效率为89%(48/54),单药控制率为24%(13/54)。结论中国人原醛占高血压10%以上,ARR 应作为高血压尤其是重度和难治性高血压患者的常规检查,ARR 在原醛诊断中有重要意义,可以提高原醛的诊断率。     

Renal cysts and hypokalemia in primary aldosteronism: results of long-term follow-up after treatment

BACKGROUND: Cross-sectional studies have reported an elevated prevalence of renal cysts in patients with primary aldosteronism. The nature of this association could be related to hypokalemia and/or hypertension and has never been evaluated in prospective studies. METHODS: A consecutive sample of 54 patients with tumoral or idiopathic primary aldosteronism was followed after adrenalectomy or treatment with aldosterone antagonists. At baseline, renal cysts were evaluated by renal ultrasound and patients with primary aldosteronism were compared with 323 essential hypertension patients with the same severity and duration of disease, and 113 age- and sex-matched normotensive subjects. RESULTS: The adjusted prevalence and average number of renal cysts were significantly greater in patients with primary aldosteronism than in patients with essential hypertension and normotensive subjects. Multivariate analysis revealed that age and plasma potassium levels were independently associated with the presence of renal cysts in patients with primary aldosteronism. Treatment of primary aldosteronism decreased blood pressure (BP) and restored normal potassium concentrations. After a median follow-up of 6.2 years, no significant change from baseline of cyst number and cyst total volume was observed in patients with both tumoral and idiopathic aldosteronism and in a subset of 100 patients with essential hypertension. In patients with primary aldosteronism, stepwise logistic analysis showed that the presence of renal cysts was associated with worse BP outcome after treatment. CONCLUSION: Renal cystic disease is highly frequent in patients with primary aldosteronism and either surgical or medical treatment halt its progression, supporting the contention that hypokalemia and its severity are the main contributors to cyst formation in these patients.     

A comprehensive review of the clinical aspects of primary aldosteronism

Primary aldosteronism is much more common than previously thought. The high prevalence of primary aldosteronism, the damage this condition does to the heart, blood vessels and kidneys (which causes a high rate of cardiovascular events), along with the notion that a timely diagnosis followed by an appropriate therapy can correct the arterial hypertension and hypokalemia, justify efforts to search for primary aldosteronism in many patients with hypertension. Most centers can use a cost-effective strategy to screen for patients with primary aldosteronism. By contrast, the identification of primary aldosteronism subtypes, which involves adrenal-vein sampling, should only be undertaken at tertiary referral centers that have experience in performing and interpreting this test. The identification of a curable form of primary aldosteronism can be beneficial for the patient. In some subgroups of patients with hypertension who are at high risk of primary aldosteronism or can benefit most from an accurate diagnosis, an aggressive diagnostic approach is necessary.     

Effect of spironolactone on fluid volumes and adrenal steroids in primary aldosteronism

Plasma volume (PV) and extracellular fluid volume (ECF) were determined in 7 patients with essential hypertension (controls) and in 10 patients with primary aldosteronism, while on a high Na diet (342 mEq/day) and on a low Na diet (12 mEq/day). The volume studies were repeated in 6 of the primary aldosteronism patients during treatment with spironolactone for over 3 months. Plasma renin activity (PRA), plasma aldosterone concentration (PAC), cortisol concentration, and serum Na and K concentrations were measured in all patients while on a Na-restricted diet (85 mEq/day) as well as on high-Na and low-Na diets. There were no significant changes in arterial pressure during different Na diets in any groups of patients with essential hypertension, or primary aldosteronism with and without spironolactone therapy. Spironolactone treatment normalized the arterial pressure in patients with primary aldosteronism at all Na intakes. These patients had greater values for PV and ECF than did those with essential hypertension. Spironolactone treatment reduced PV during the low-Na diet, but did not alter it during the high-Na diet. Spironolactone did not produce significant changes in ECF during either the high-Na or low-Na diets. Although there were no changes in PV and ECF in patients with primary aldosteronism due to changes in Na intake, both PV and ECF were significantly less in these patients during spironolactone treatment and in patients with essential hypertension during low-Na intake than during high-Na intake. With primary aldosteronism, PRA was depressed and PAC was elevated when compared to essential hypertension, these were not altered by different Na diets in the patients with primary aldosteronism as they were in those with essential hypertension. During treatment with spironolactone the PRA was restored to normal and showed normal changes with variations in dietary Na, but PAC remained elevated during spironolactone. Plasma cortisol was the same among those with essential hypertension and patients with untreated and spironolactone-treated primary aldosteronism. Serum K was less in untreated primary aldosteronism during all Na diets than in essential hypertension, but during spironolactone it was restored to normal. These results suggest that in primary aldosteronism the reduction in arterial pressure by spironolactone treatment does not occur simply by reductions in body fluid volumes. The long-term treatment of patients with primary aldosteronism with spironolactone does not inhibit the production of aldosterone, possibly because of enhanced activity of the renin-angiotensin system and an increase in serum K.     

Prevalence and characteristics of the metabolic syndrome in primary aldosteronism

CONTEXT: Patients with hypertension have a high prevalence of concurrent metabolic abnormalities, including obesity, dyslipidemia, and hyperglycemia. Clustering of these cardiovascular risk factors, defined as metabolic syndrome, causes a more pronounced target organ damage. Aldosterone excess has been found to be associated with glucose disorders and may contribute to cardiovascular damage. OBJECTIVE: The aim of our study was to assess the prevalence and the characteristics of the metabolic syndrome in a group of patients with hypertension due to primary aldosteronism compared with patients with essential hypertension. METHODS: The National Cholesterol Education Program Adult Treatment Panel III definition of the metabolic syndrome was used. Eighty-five patients with primary aldosteronism and 381 patients with essential hypertension were studied. Most patients were not receiving antihypertensive therapy during the investigation. RESULTS: Blood glucose and systolic blood pressure were higher (P < 0.05 and P < 0.01, respectively) and duration of hypertension was longer (P < 0.05) in primary aldosteronism than in essential hypertension. The prevalence of metabolic syndrome was higher in primary aldosteronism than in essential hypertension (41.1% vs. 29.6%; P < 0.05). Distribution of single components of the metabolic syndrome other than hypertension showed a higher prevalence of hyperglycemia in primary aldosteronism than in essential hypertension (27.0% vs. 15.2%; P < 0.05). CONCLUSIONS: Our findings confirm a negative effect of aldosterone excess on glucose metabolism and suggest that the recently reported higher rates of cardiovascular events in primary aldosteronism than in essential hypertension might be due to increased prevalence of the metabolic syndrome in the former condition.     

Ambulatory blood pressure monitoring in secondary arterial hypertension due to adrenal diseases

The aim of this study was to evaluate ambulatory blood pressure monitoring in patients with essential hypertension and hypertension caused by adrenal pathology. Sixty-six patients with primary aldosteronism, 37 with pheochromocytomas, and 45 with adrenal incidentalomas were included. These patients were compared with 152 essential hypertensive patients and 64 normotensive subjects. Ambulatory blood pressure monitoring evaluated daytime and nighttime systolic and diastolic blood pressure and heart rate. The authors found that the "nondipper" phenomenon was present in 51.5% of patients with primary aldosteronism, 43.2% with pheochromocytomas, 42.2% with incidentalomas, 34.2% with hypertension, and 15% of subjects who were normotensive. In 58% of primary aldosteronism patients with idiopathic adrenal hyperplasia, there was an absence of the physiologic blood pressure nocturnal fall (nondipper), which was statistically significant (P<.001) compared with nondipper primary aldosteronism patients with adrenocortical adenoma (38%). In conclusion, the prevalence of the nondipping pattern was higher in patients with adrenal hypertension compared with patients with essential hypertension, suggesting an independent cardiovascular risk factor.     

Left heart morphology and function in primary aldosteronism

Primary aldosteronism is the most frequent cause of secondary hypertension, accounting for up to 11% of cases in selected populations. Patients affected by primary aldosteronism have shown higher prevalence of cardiovascular and cerebrovascular events compared with patients with essential hypertension, despite similar blood pressure levels. Several studies have been performed over past years aiming to explain these data; many of these evaluated echocardiographic differences in hypertension-related cardiac organ damage between primary aldosteronism and essential hypertension. This article summarizes the present knowledge about structural and functional alteration of the human left heart in 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.     

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.