卡托普利试验在原发性醛固酮增多症诊断中的价值及适宜切点的再评价

目的对卡托普利试验(CCT)在原发性醛固酮增多症(PA)诊断中的价值及适宜切点进行再评价。方法回顾性纳入所有完成了筛查、CCT和氟氢可的松试验(FST)的PA高危患者, 利用随机数法从单侧PA患者中随机抽样, 使纳入分析的单侧PA在PA中的比例达35%, 基于化学发光法测定血浆醛固酮浓度(PAC)和肾素浓度, 以FST作为PA的诊断标准, 构建CCT诊断PA的受试者工作特征(ROC)曲线, 探讨CCT的诊断价值和适宜切点。结果纳入PA共400例, 原发性高血压(EH)143例。CCT后PAC 的ROC曲线下面积(AUCROC)为0.86(0.83, 0.89), 显著高于CCT后醛固酮/肾素浓度比值(ARR)及试验前后PAC抑制率的AUCROC[0.78(0.74, 0.82), 0.62(0.56, 0.67)], 差异均有统计学意义(P<0.01)。以CCT后PAC 110 ng/L作为PA的诊断切点时, 敏感度为73.25%, 特异度为79.02%。分别联合ARR和PAC抑制率并未提高CCT后PAC的诊断效能(P>0.05)。结论 CCT是较好的PA确诊试验, 推荐立...     

Application of captopril challenge test in the diagnosis of primary aldosteronism

正Objective To evaluate the value of captopril challenge test(CCT)in the diagnosis of primary aldosteronism(PA).Methods A total of 674 patients[(45.0±13.7)years,men 341,women 333]admitted to Peking Union Medical College Hospital from 2000 to 2015 were analyzed.Among them,222 subjects were with essential hypertension(EH),28 were with pheochromocytoma(PHEO),246 were with idiopathic hyperaldosteronism     

A new diagnostic test for primary tumoral hyperaldosteronism

Plasma aldosterone levels were measured during two tests of inhibition in 31 hypertensive patients (13 essential hypertension, 6 bilateral adrenal hyperplasia and 12 documented Conn adenomas) on normal salt diets after withdrawal of all therapy: 1--before and after intravenous infusion of 2 I normal saline in two hours; 2--before and three hours after administration of 1 mg/kg of Captopril. Plasma aldosterone levels greater than 360 pmol/I after salt loading, or greater than 748 pmol/I after Captopril is characteristic of primary tumoral hyperaldosteronism. Apart from the rapidity of the test, Captopril is well-tolerated, does not require acute volume expansion and can be carried out in all forms of hypertension, even in severe cases.     

Significance of single-dose captopril test in the differential diagnosis of primary aldosteronism

The captopril test was used to make a differential diagnosis of various types of primary aldosteronism. After captopril, there was no change in the activity of the renin-angiotensin-aldosterone system only in the group of patients with aldosterone-producing adenomas in a histological variant of "adenoma and atrophy". The findings suggest that aldosterone secretion regulation is autonomic in the adenoma unassociated with the function of the renin-angiotensin-aldosterone system only in the case of isolated adenoma with a histological variant of adenoma and atrophy. In patients with aldosterone-producing adenomas in the presence of the variant "adenoma and hyperplasia", aldosterone secretion retains sensitivity to the renin-angiotensin-aldosterone system as in patients with idiopathic hyperplasia and hypertensive disease, which indicates that it is possible to differentiate isolated "adenoma and atrophy" from hypertensive disease and idiopathic hyperplasia, despite its combination with tumor by using the captopril test.     

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。     

两种剂量开博通试验对原发性醛固酮增多症诊断效率评价

目的 探讨两种剂量开博通试验在原发性醛固酮增多症(原醛症)诊断中的诊断效率.方法 回顾性比较1993年1月至2006年12月解放军总医院内分泌科59例原醛症患者、35例原发性高血压患者25 mg开博通试验和27例原醛症患者、42例原发性高血压患者50 mg开博通试验结果.采用受试者操作特征曲线(ROC)比较两种剂量开博通试验的曲线下面积和灵敏度、特异度.结果 以服用开博通后血浆醛固酮405 pmol/L为切点,25 mg开博通试验的灵敏度为83.1%,特异度为88.6%;以437 pmol/L为切点,50 mg开博通试验的灵敏度为88.9%,特异度为83.3%.两种试验的ROC曲线下面积分别为0.879和0.912,大于完全无诊断价值的机会线下面积0.5(P均<0.01),但两者的ROC曲线下面积比较差异无统计学意义(P>0.05).结论 两种剂量开博通试验对于原醛症均有较好的诊断效率,两者之间诊断的准确度相似.     

Clinical evaluation of the captopril screening test for primary aldosteronism

In order to investigate the validity of angiotensin converting enzyme inhibition with captopril as a screening test for primary aldosteronism (PA), 50 mg of captopril were administered orally to 7 patients with PA, 17 with essential hypertension (EH), 5 with renovascular hypertension (RVH), 2 with renoparenchymal hypertension (RH) and 8 normal volunteers. The plasma aldosterone concentration (PAC) was suppressed to less than 15 ng/dl in all of the EH, RVH and RH patients and normal subjects 90 min after administration of captopril, but not suppressed in 6 of 7 patients with PA. In addition, the plasma renin activity (PRA) was increased to greater than 1 ng/ml/h in 10 of 17 patients with EH and in all with RVH, RH and the normal controls, but to less than that in 6 of 7 PA and the remaining EH patients. The PAC to PRA ratio after captopril was greater than 20 in all patients with PA, while it remained below 20 in EH, RVH and RH patients and normal controls. From these results, we conclude that the PAC to PRA ratio in the captopril administration test is a simple and useful tool to detect PA in hypertensive patients. In addition, the test has a great advantage in that it can be safely applied to outpatients with relatively severe hypertension.     

Effects of sodium intake on the captopril test for primary aldosteronism

The validity of the captopril test for primary aldosteronism (PA) was tested in patients with surgically verified PA (n = 12) or essential hypertension (EHT, n = 20) with different levels of sodium intakes. The patients were scheduled on 7 days each of three regimes of the prepared diet containing 34, 120 and 340 mEq of sodium chloride per day, and the captopril test was repeated in each period. For the test, captopril (50 mg) was administered orally at 9:00 A.M. after 1 hour of rest in a supine position, and venous blood samples were obtained before and 90 min after drug administration. Plasma aldosterone concentration (PAC; ng/dl) and plasma renin activity (PRA; ng/ml/h) were measured by radioimmunoassay. Under the three different sodium intakes, a PAC/PRA ratio greater than 20 at 90 min after captopril administration was sufficiently sensitive (0.95, 19/20) and specific (0.92, 55/60) to identify PA. Similarly, PA was associated with a PAC above 15 ng/dl 90 min after captopril. There were no complaints associated with the antihypertensive effects of the drug even when patients were sodium-restricted. These results confirmed that the captopril test is safe and useful for screening out-patients for PA, independent of individual differences in sodium intake.     

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目的评价原发性醛固酮增多症(PA)诊断中多项临床试验方法的作用。方法收集1995～2000年上海第二医科大学附属瑞金医院104例PA患者的临床资料,统计分析生化检查、体位激发试验、影像学检查与肾上腺静脉插管在诊断中的阳性率及符合率。结果(1)血醛固酮升高为筛选PA阳性率最高的检测指标。(2)醛固酮腺瘤患者生化异常较明显。(3)与手术病理比较,B超在醛固酮腺瘤和双侧肾上腺增生中的诊断符合率分为95.77%及73.33%;CT为98.51%及31.03%;体位激发试验以升幅30%为标准时在醛固酮腺瘤和双侧肾上腺增生中的符合率分别为61.11%及57.14%,以50%为标准时为72.22%及42.86%;肾上腺静脉插管的符合率为83.33%及100%。结论PA的诊断中,典型患者经血钾、血尿醛固酮及血浆肾素活性等筛查可明确诊断,但部分患者上述生化改变并不典型。体位激发试验结果在醛固酮腺瘤及双侧肾上腺增生中有部分重叠。影像学未能发现明显占位灶者可行肾上腺静脉插管检查。     

The value of scintigraphy and computed tomography for the differential diagnosis of primary hyperaldosteronism

Adrenocortical adenoma is the most common cause of primary hyperaldosteronism. Most tumours are small, less than 2 cm in diameter and, therefore, their localization may be difficult. We have compared two different methods, adrenal scintigraphy (AS) and computed tomography (CT) in the differential diagnosis of 12 patients with primary hyperaldosteronism. AS was performed using either [131I]cholesterol or 6-iodomethyl-19-norcholesterol during dexamethasone suppression. Of the patients, five showed a normal CT and symmetrical uptake of the isotope as AS. They were considered representative of bilateral hyperplasia. All showed good therapeutic response to spironolactone. Seven patients had an adrenocortical adenoma verified at operation. The CT finding indicated a tumour in five patients. This was correct in four, but in one patient the adenoma was found in the contralateral adrenal gland. In two patients with an adenoma, CT was considered normal. AS correctly indicated the tumour in all seven patients. The uptake was unilateral in six, and bilateral but clearly asymmetrical in one patient. The results indicate that AS is superior to CT in the pre-operative localization of aldosteroma. Although CT remains the primary method for the investigation of these patients, AS should be applied always when CT does not unequivocally indicate the presence and localization of an adrenal tumour.     

Single dose captopril as a diagnostic test for primary aldosteronism

Most diagnostic tests for primary aldosteronism use maneuvers to expand the extracellular fluid volume, thereby suppressing the renin-angiotensin system. This results in a decline in plasma aldosterone concentrations in normal subjects and essential hypertension (EH) patients, but not in patients with primary aldosteronism. Captopril blocks angiotensin II synthesis and might be used as a diagnostic test for primary aldosteronism. We have measured plasma aldosterone concentrations 2 h after the administration of 25 mg captopril in 9 normotensive subjects, 10 patients with EH, and 12 patients with primary aldosteronism while they were ingesting an unrestricted diet. The plasma aldosterone concentration decreased to less than 15 ng/dl in all normotensive subjects and in 9 of 10 patients with EH, but remained greater than 15 ng/dl in 4 of 5 patients with idiopathic hyperaldosteronism and in all patients with an aldosterone-producing adenoma. The aldosterone to renin ratio was greater than 50 in 4 of 5 patients with idiopathic hyperaldosteronism and in all adenoma patients, but less than 50 in all normotensive subjects and EH patients. A nomogram comparing the plasma aldosterone concentration with the aldosterone to renin ratio clearly separated primary aldosteronism patients from EH patients.     

Renal scintigraphic captopril test in the diagnosis of renovascular hypertension

Angiotensin converting enzyme (ACE) inhibitor-induced renal failure has been reported in bilateral renal artery stenosis and in stenosis in solitary kidneys, but not in unilateral renal artery stenosis. In these patients, however, a functional impairment of the kidney ipsilateral to the stenosis can often be detected after ACE inhibition by scintigraphic techniques employing glomerular radionuclide tracers like 99mTc-diethylenetriamine pentaacetic acid (DTPA). Dynamic renal scintigraphy with 99mTc-DTPA before and 1 hour after administration of captopril, 25 mg (renal scintigraphic captopril test; RSCT), was performed in a selected series of 39 hypertensive subjects with suspected renovascular hypertension. Changes in glomerular filtration rate induced by captopril on the individual kidney were estimated by assessing the early (120-180 seconds) DTPA uptake by the kidney. Values were expressed as the ratio between the kidney with the lower uptake and the contralateral one in 34 patients and as the ratio of the kidney counts to the injected dose in five patients with solitary kidneys, aortic coarctation, or both. Compared with precaptopril values, postcaptopril uptake decreased markedly in 14 subjects (-62.42 +/- 30.94 [SD]%; range, -25 to -100%) and decreased modestly or even increased in the other 25 (+0.57 +/- 9.83%; range, +28 to -13%). Of the 14 subjects considered to be RSCT-positive diagnostic workup revealed either established (10) or strongly suspected (2) renal artery stenosis in 12 and aortic coarctation in 2 subjects. In another patient with established renovascular hypertension, results of the RSCT were negative when performed in the supine position but became positive when repeated in the sitting position.(ABSTRACT TRUNCATED AT 250 WORDS)     

Localization of primary hyperaldosteronism

After diagnosis of primary aldosteronism on the basis of biochemical evidence, the detection of the tumour is of crucial importance in the management of the disease. We reviewed the efficacy of CT-Scan, Iodo-Cholesterol Scintigraphy, digitalized phlebography, adrenal vein sampling for steroid measurements (AVS), and Nuclear Magnetic Resonance (NMR) in 160 hypertensive patients with primary aldosteronism. Diagnosis of Conn's adenoma (n = 96) or Adrenal Hyperplasia (n = 40) was confirmed by surgery or at least two concordant tumour localization tests. Scintigraphy gave a correct diagnosis in 53% of the 51 exams, CT-Scan in 82% of the 85 exams, and phlebography in 79% of 61 exams. Plasma Aldosterone/Cortisol ratio was 5 times higher on the side of adenoma in 55% of the 47 cases but this ratio was also present in 23% of 22 patients with adrenal hyperplasia. Each procedure exhibited few false positive and false negative cases. NMR performed in 15 patients with Conn's adenoma identified all the cases. But tumours displayed a signal close to the liver signal and identical to the normal adrenal. These results and the risk of invasive procedure (failure of catheterization of the right adrenal vein (n = 6) and adrenal haematoma (n = 2) lead us to propose a schema of exploration of patients with primary aldosteronism. The CT-Scan could be performed at the first step once the biological diagnosis confirmed. Phlebography and AVS will be performed only if tumour was less than 1 cm at the CT-Scan despite important biological abnormalities. This schema requires to be validated by a prospective evaluation.     

肾上腺静脉采血在原发性醛固酮增多症分型诊断中的应用

目的探讨肾上腺静脉采血（AVS）检查在原发性醛固酮增多症（原醛症）分型诊断中的应用价值。方法收集瑞金医院近4年来39例临床确诊的原醛症患者[23例特发性醛固酮增多症（特醛症），16例醛固酮瘤]，经肾上腺静脉插管检查，取双侧肾上腺静脉以及肾静脉水平下的下腔静脉血液，测各点醛固酮和皮质醇水平，并将结果与影像学检查、体位激发试验（PST）及术后病理结果进行比较。结果（1）23例特醛症患者体位激发后血醛固酮较基础值均升高；16例醛固酮瘤患者血醛固酮升高者占56．3％（9／16）；（2）特醛症患者肾上腺B超检查符合率为69．6％（16／23），醛固酮瘤患者为56．3％（9／16）；肾上腺CT检查特醛症患者符合率为73．9％（17／23），醛固酮瘤患者为81．3％（13／16）；（3）AVS检查以两侧醛固酮之比作为判定标准时符合率为71．8％，以醛固酮与皮质醇之比为判定标准则达到100％。醛固酮瘤患者生化异常程度较特醛症患者明显。PST在特醛症及醛固酮瘤中有部分重叠；体位激发后血醛固酮升高者不能排除醛固酮瘤，而血醛固酮下降者可诊断为醛固酮瘤。结论单纯依赖影像学检查对于原醛症患者进行分型诊断易发生误诊。AVS检查的准确性高，对于影像学检查未能发现明显占位性病变者须进行该检查以明确诊断；对于AVS结果，用两侧醛固酮与皮质醇的比值之比分析较单纯比较两侧醛固酮之比更为可靠。     

Aldosterone in primary hyperaldosteronism

The conditions which must be respected to ensure the validity of the biochemical diagnostic criteria of primary hyperaldosteronism, conditions of blood sampling, timing posture and age of the patient, sodium intake and intercurrent drug therapy. As none of the tests is 100 p. 100 specific in distinguishing adrenal adenoma from hyperplasia, an association of several investigations has to be used. In cases of adenoma, the authors recommend the investigations which demonstrate the autonomy of secretion and the prevalence of circadian rhythm over the influence of change in posture. The measurement of aldosterone levels may be completed by that of its precursor, 18-hydroxy-corticosterone (18 OH CS).