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。     

新疆乌鲁木齐地区原发性醛固酮增多症105例临床分析

该文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—07—2005—03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、卧位醛固酮水平增高。醛固酮和肾素活性比值（ARR）〉25者占71％，     

原发性醛固酮增多症的筛查和诊断

自1955年Conn报道首例原发性醛固酮增多症（原醛）患者以后的30多年中,原醛一直被认为是一种少见病。1957年上海瑞金医院诊断了我国首例原醛患者,1957—1985年我院内分泌科住院患者中的原醛患病率为2％。从上世纪90年代起,由于普遍采用血浆醛固酮／血浆肾素活性比值（ARR）作为原醛筛查指标,发现原醛不是少见病。在我科住院患者中,原醛已成为继发性高血压中最常见的病因。     

血浆醛固酮/肾素活性比值——一个敏感的原发性醛固酮增多症的筛查指标

血浆醛固酮／肾素活性比值（ARR）是一个敏感的原发性醛固酮增多症（PA）的筛查指标，ARR的应用使高血压人群中PA的检出率明显增加。但目前ARR仍是一个非标准化的筛选方法，不同研究所采用的ARR切点差别很大，故应对ARR进行更深入和系统的研究，以提高ARR筛查方法的准确性。     

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。     

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。     

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。     

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.     

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.     

呋塞米静脉注射对高血压患者血浆醛固酮肾素比值的影响

目的研究大剂量呋塞米快速静脉注射激发试验对不同人群血浆醛固酮／肾素比值（ARR）的影响。方法10例血压正常人、28例高血压病患者、11例经CT薄层扫描等检查明确为原发性醛固酮增多症的患者入选。入选者在清晨平卧位抽取空腹血后静脉快速注射呋塞米40mg，注射后10、30min各抽血一次查血浆醛固酮水平及肾素活性（PRA）并计算出ARR。结果正常血压组的ARR为18．18，静脉注射呋塞米后，PRA迅速上升（P〈0．01），ARR下降。高血压组患者的空腹血浆醛固酮为（149．01±14．69）ng／L，PRA为（3．45±0．74）ng／（ml·h），ARR为33．45±8．87，静脉注射呋塞米40mg后10、30min，患者的血浆醛固酮不断升高，分别为176．04，200．06ng／L，PRA明显升高，分别为7．11，5．68ng／（ml·h），ARR下降（均P〈0．05）。原发性醛固酮增多症患者组ARR为38．61±15．16，PRA为（3．16±0．4）ng／（ml·h），醛固酮为（165．75±18．56）ng／L，用呋塞米40mg静脉推注后其ARR达41．70±18．46。结论快速静脉注射呋塞米可使正常血压者及高血压病患者醛固酮和PRA快速明显增加，PRA以10min时最明显，醛固酮以30min最明显，ARR有所下降，而原发性醛固酮增多症患者的PRA上升不明显，ARR反而有所增加。     

代谢综合征患者胰岛素抵抗与醛固酮水平的相关性研究

目的探讨代谢综合征（MS）胰岛素抵抗（IR）及高胰岛素血症与血浆醛固酮水平的关系。方法101例原发性高血压（EH）、135例特发性醛固酮增多症（IHA）患者按是否伴MS各分为两个亚组进行比较。结果EH伴MS组血浆卧位醛固硐（ALD）水平、胰岛素曲线下面积（InsAUC）、HOMA-IR及IR所占百分率均显著高于非MS组；IHA伴MS组血浆卧位ALD水平、InsAUC、HOMA-IR及IR所占百分率均显著高于非MS组和EH组。相关分析显示，伴MS两亚组的卧位ALD水平均与InsAUC及HOMA-IR显著正相关。结论MS患者较高的血浆ALD水平与高胰岛素血症及IR显著正相关，在高血压和心血管并发症的发生中起到一定作用。     

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。     

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.     

Detecting and treating primary aldosteronism: primary aldosteronism.

Primary aldosteronism (PA) is the most common cause of mineralocorticoid hypertension. Different studies, using the plasma aldosterone concentration to plasma renin activity ratio (PAC/PRA) for the screening of patients with hypertension, have shown a marked increase in the detection rate of PA. Idiopathic bilateral adrenal hyperplasia (IHA) and aldosterone-producing adrenal adenoma (APA), are the leading causes of primary aldosteronism. Glucocorticoid-remediable aldosteronism (GRA), also called familial hyperaldosteronism type I, familial hyperaldosteronism type II and carcinomas are rare causes of PA. Patients with hypertension and hypokalemia, those with a family history of hypertension and stroke at an early age, or patients with medication-resistant hypertension should be screened for PA using the PAC/PRA ratio. If a high ratio is found, a sodium loading test or a captopril test is warranted to confirm the diagnosis. Adrenal gland imaging is important in subtype differentiation (APA vs IHA). Adrenal venous sampling should be used when other tests prove inconclusive. Genetic testing has facilitated detection of GRA. Surgery is considered the treatment of choice for patients with APA, while bilateral hyperplasia subtypes are treated medically. Normalization of aldosterone levels or aldosterone receptor blockade are necessary to prevent the morbidity and mortality associated with hypertension, hypokalemia, and cardiovascular damage.     

Unique cases of unilateral hyperaldosteronemia due to multiple adrenocortical micronodules, which can only be detected by selective adrenal venous sampling

Primary aldosteronism is classified as aldosterone-producing adenoma (APA), idiopathic hyperaldosteronism (IHA), unilateral adrenal hyperplasia (UAH), primary adrenal hyperplasia (PAH), adrenal cancer, and glucocorticoid-remediable aldosteronism. We describe here 4 cases of primary aldosteronism due to unilateral hyperaldosteronemia, demonstrating unique histopathologic findings, such as unilateral multiple adrenocortical micronodules in the affected adrenals. Thirty-three patients with primary aldosteronism were consecutively admitted; 27 of them were treated by unilateral adrenalectomy. Four of them also had unilateral adrenal hypersecretion of aldosterone by selective adrenal venous sampling and adrenocortical multiple micronodules without an adenoma. These patients had hyporeninemic hyperaldosteronism with normokalemic hypertension. In these patients, furosemide plus upright test failed to increase plasma renin activity (PRA); the ratio of plasma aldosterone concentration (PAC) to PRA at 90 minutes after captopril administration was similar to that in patients with IHA and APA. Aldosterone concentrations were increased in each unilateral adrenal vein, and poorly encapsulated multiple adrenocortical micronodules from 2 to 3 mm in diameter were microscopically detected in the resected adrenal glands. Immunohistochemical analysis of steroidogenic enzymes, including cholesterol side chain cleavage, 3beta-hydroxysteroid dehydrogenase, 21-hydroxylase, 17alpha-hydroxylase, and 11beta-hydroxylase, indicated that the cortical cells within these micronodules were active in aldosterone production, while the non-nodular zona glomerulosa cells were inactive. We conclude that the clinical and pathologic characteristics of our 4 cases with unilateral multiple adrenocortical micronodules (UMN) are distinct from those of APA, IHA, UAH, and PAH. Furthermore, unilateral hyperaldosteronemia induced by UMN may be frequently misdiagnosed, because standard imaging tests, which cannot always detect tiny abnormalities of adrenals, showed "normal adrenal glands" in these patients. Thus, primary aldosteronism due to UMN should be carefully examined for differential diagnosis of each form of hyperaldosteronemia.     

Effect of a calcium inhibitor, nicardipine, on aldosterone secretion in primary hyperaldosteronism

The purpose of the study was to evaluate the effects of a dihydropyridine calcium antagonist, nicardipine (N), on blood pressure (BP) and aldosterone secretion in hypertensive patients (pt) with primary aldosteronism. The study concerned 8 pts, mean age 55.6 +/- 7.7 years, 1 pt with aldosterone-producing adenoma (APA) and 7 pts with idiopathic aldosteronism: plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were respectively 0.30 +/- 0.2 ng/ml/h) and 314 +/- 109 pg/ml. Acute administration of 12 mg of nicardipine during 90 mn (three periods of N infusion during 30 mn: 0.4 mg/mn-5 mn; then 0.08 mg/mn-25 mn) significantly decreased BP, with an increase in heart rate (HR); the levels of PAC were significantly reduced with a slight but not significant increase in PRA, 60 mn after N: (table; see text) N decreased also PAC in the pt with APA [600 to 410 pg/ml] but did not improve hypokalemia (3.1 vs 3.3 mmol/l, n = 8 N.S.). In contrast, PAC levels were not modified 2 hours after acute oral administration of captopril (1 mg/kg): 302 +/- 164 pg/ml vs 332 +/- 191 pg/ml (NS). This study demonstrated the antihypertensive efficacy of acute infusion of nicardipine in primary aldosteronism; the decrease of PAC under this calcium antagonist suggested its potential interest in the management of idiopathic aldosteronism.     

Acute and Chronic Effect of Nifedipine in Primary Aldosteronism

Since calcium entry blocker drugs can interfere with aldosterone secretion in vitro, a similar effect in vivo, in man, has been suggested and partially confirmed. The data available in primary aldosteronism are more controversial. Therefore, we have studied the acute and chronic effect of nifedipine in 7 patients with idiopathic hyperaldosteronism (IHA) and 8 with aldosterone producing adenoma (APA). On 2 different days, 10 mg of nifedipine or placebo were given sublingually to the patients and blood pressure and heart rate were recorded every 5 min. for 60 min. Plasma aldosterone, cortisol, PRA and serum K were measured at 0, 30 and 60 min. 5 patients with IHA and 6 with APA received nifedipine 20 mg per os bid for 3 months; the same parameters were evaluated on days 0, 30, 60 and 90; urinary aldosterone was measured on days 0, 30, 60 and 90. BP decreased in both groups both after acute and chronic administration of nifedipine. Plasma aldosterone showed a similar trend either after acute nifedipine or placebo; however, during chronic treatment it was slightly decreased in IHA patients. Cortisol, PRA, urinary aldosterone and K⁺ remained unchanged. In conclusion, nifedipine is an effective antihypertensive agent also in primary aldosteronism; its aldosterone inhibiting properties are minimal and seem to be present only during long-term therapy in IHA.     

Effects of naloxone on adrenal cortex regulation in patients with primary aldosteronism

Excess production of proopiomelanocortin (POMC)-derived peptides with aldosterone-stimulating activity has been suggested to play a pathogenetic role in idiopathic hyperaldosteronism (IHA). To further investigate this issue, the opiate receptor antagonist naloxone was administered to 14 patients with primary aldosteronism, 6 with an aldosterone-producing adenoma (APA) and 8 with IHA. Clinical and hormonal effects of iv administration of naloxone (10 mg as a bolus) were compared with those obtained in 8 normal subjects. In normals as well as in APA and IHA patients, naloxone caused a significant increase in plasma cortisol, and no change in ACTH, plasma renin activity (PRA) and aldosterone levels. All subjects were retested after 2 mg dexamethasone. ACTH and cortisol were reduced and PRA was unchanged in all groups, without modifications after naloxone. Baseline aldosterone showed no significant changes in all groups. While normal subjects and APA failed to show any aldosterone response to naloxone after dexamethasone, IHA patients demonstrated a significant decrease. beta-endorphin concentrations were in the normal range before and after dexamethasone. In conclusion, naloxone may have a direct action upon adrenal zona fasciculata increasing the cortisol responsiveness to physiological levels of ACTH in either normals or APA and IHA patients. The decrease of aldosterone induced by naloxone in IHA may be due to an intraadrenal opioid control of zona glomerulosa in this disorder.