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Context The current clinical guidelines suggest that confirmatory tests for primary aldosteronism (PA) may be excluded in some of patients who have elevated plasma aldosterone concentration (PAC) under plasma renin suppression. However, this has low-priority evidence and is under debate in use of serum potassium. Objective This study aimed to investigate an appropriate setting for sparing confirmatory tests in PA. Design and Setting A retrospective cross-sectional study in a single referral center. Participants This study included 327 patients who had hypertension under plasma renin suppression and underwent the captopril challenge test (CCT) between January 2007 and April 2019. CCT results were used to diagnose PA. Main Outcome Measure Diagnostic value of PAC and serum potassium in confirmation of PA. Results Of the studied patients, 252 of 327 (77%) were diagnosed with PA. All 61 patients with PAC > 30 ng/dL were diagnosed with PA. In patients with PAC between 20 and 30 ng/dL, 44 of 55 (80%) were diagnosed with PA, while all 26 with PAC between 20 to 30 ng/dL who had spontaneous hypokalemia were diagnosed with PA. The proportion of unilateral PA determined by adrenal vein sampling (AVS) was higher in patients who had PAC > 30 ng/dL or those with spontaneous hypokalemia who had PAC between 20 and 30 ng/dL than those who did not meet the criteria (76% vs. 17%, P < .001). Conclusion Confirmatory tests in PA could be spared in patients who have typical features of PA and these patients had a high probability of unilateral PA on AVS.

Background The Captopril challenge test (CCT) is an easy-conduct confirmatory test for diagnosing primary aldosteronism (PA). Guidelines show that plasma aldosterone is normally suppressed by captopril (> 30%) in primary hypertension (PH) and in healthy people. It is unclear whether this standard is applicable in Chinese subjects. The aim of the present study was to investigate the post-CCT efficacy of plasma aldosterone concentration (PAC) suppression and determine the post-CCT aldosterone renin activity ratio (ARR) and PAC for PA diagnosis. Methods We recruited 110 consecutive patients with PA, 163 with primary hypertension (PH), and 40 healthy volunteers (NC). The CCT was conducted in all patients. Total sodium intake was estimated from 24-h urinary excretions. ROC curves were used to analyze the efficiency of different CCT diagnostic criteria for diagnosing PA. Results In NC and PH patients, PRA was increased and PAC was decreased post-CCT (P

The diagnostic workup for primary aldosteronism includes a screening step using the aldosterone-to-renin ratio (ARR) and a confirmatory step based on dynamic testing of aldosterone secretion autonomy. International guidelines suggest that precise clinical and biochemical conditions may allow the bypassing of the confirmatory step, however, data which validate hormone thresholds defining such conditions are lacking. At our tertiary center, we retrospectively examined a cohort of 173 hypertensive patients screened for PA by the ARR, of whom 120 had positive screening and passed a saline infusion test (SIT) or a captopril challenge test (CCT). Fifty-nine had PA, including 34 Conn adenomas and 25 with idiopathic aldosteronism (IA). Using a threshold of 160 pmol/l, post-SIT plasma aldosterone concentration (PAC) identified PA with 86.4% sensitivity, 94.7% specificity, and a negative predictive value of 92.3%. Of those subjects with a high ARR and a PAC above 550 pmol/l, 93% had a positive SIT, while 100% of subjects with a high ARR, but a PAC under 240 pmol/l had a negative SIT. Our results thus validate the biochemical conditions defined in the French and US guidelines for bypassing the confirmatory step in the workup for PA diagnosis.

BACKGROUND Diagnosis of primary aldosteronism (PA) begins with aldosterone-to-renin ratio (ARR) measurement followed by confirmative tests. However, the ARR has high false positive rates which led to unnecessary confirmatory tests. Captopril challenge test (CCT) has been used as one of confirmatory tests, but the accuracy of it in the diagnosis of PA is still controversial. We aimed to examine the clinical efficacy of CCT as a post-screening test in PA. METHODS In a prospective study, we enrolled subjects with suspected PA who had hypertension and ARR >20 (ng/dL)/(ng/mL/hr). Sixty-four patients who underwent both the saline infusion test and the CCT were included. RESULTS The diagnostic performance of plasma aldosterone concentration (PAC) post-CCT was greater than that of ARR post-CCT and ARR pre-CCT in PA (area under the curve=0.956, 0.797, and 0.748, respectively; P=0.001). A cut-off value of 13 ng/dL showed the highest diagnostic odds ratio considering PAC post-CCT at 60 and 90 minutes. A PAC post-CCT of 19 ng/dL had a specificity of 100%, which can be used as a cut-off value for the confirmative test. Determining the diagnostic performance of PAC post-CCT at 90 minutes was sufficient for PA diagnosis. Subjects with PAC post-CCT at 90 minutes

Adrenal venous sampling is considered to be the most reliable diagnostic procedure to lateralize aldosterone excess in primary aldosteronism (PA). However, normative criteria have not been established partially because of a lack of data in non-PA hypertensive patients. The aim of the study was to investigate aldosterone concentration and its gradient in the adrenal vein of non-PA hypertensive patients. We retrospectively studied the results of cosyntropin-stimulated adrenal venous sampling in 40 hypertensive patients who showed positive screening testing but negative results in 2 confirmatory tests/captopril challenge test and saline infusion test. Plasma aldosterone concentration, aldosterone/cortisol ratio, its higher/lower ratio (lateralization index) in the adrenal vein with cosyntropin stimulation were measured. Median plasma aldosterone concentration in the adrenal vein was 25 819 pg/mL (range, 5154–69 920) in the higher side and 12 953 (range, 1866–36 190) pg/mL in the lower side ( P P

Primary aldosteronism (PA) is the most common endocrine cause of resistant hypertension. Individuals with PA are at increased cardiovascular risk, and an appropriate management and treatment would ideally reduce such risk. Screening and diagnosis of PA requires a specific diagnostic test which is considered time- and cost-consuming and, as a result, is underperformed in clinical practice. An online survey reviewing available diagnostic procedures, laboratory testing, and clinical protocols for screening and confirmation of PA diagnosis was conducted among clinical lead of Reference and Excellence centers of the Italian Hypertension Society. A total of 102 questionnaires were sent and 62 centers participated in the survey. Assessment of the plasma renin (plasma renin activity/direct renin concentration) and plasma aldosterone concentration (PAC) was available in all centers. Captopril challenge test (CCT) and saline infusion test (SIT) were available in 60% and 61% of the centers, respectively. Fludrocortisone suppression test was available in 32% of the units. Adrenal vein sampling was accessible in 32% of the centers. We found discrepancies in cutoff levels of aldosterone-to-renin ratio (ARR) and PAC after SIT. Other discrepancies involved the duration of the wash-out period before ARR testing and dosage of captopril administered during CCT. In conclusion, although all centers are sufficiently equipped to perform PA screening, often patients should be referred to other centers to confirm the diagnosis of PA. A greater uniformity across centers to define precise cutoffs for screening and confirmatory testing for the diagnosis of PA would be of utility.

Primary aldosteronism (PA) is caused by excess secretion of aldosterone and is an independent risk factor for cardio-cerebro-vascular (CCV) events. The goal of treatment of PA should include prevention of CCV events. A definitive diagnosis of PA is established by confirmatory tests [saline infusion test (SIT), furosemide upright test (FUT) and captopril challenge test (CCT)]. However, there is no information on whether the hormone levels measured by these confirmatory tests are associated with CCV events. The aim of this retrospective study was to elucidate the relationship between the results of the above confirmatory tests and prevalence of CCV disease in patients with PA. The study subjects were 292 PA patients who were assessed for past history of CCV events at the time of diagnosis of PA. CCV events were significantly higher in patients with positive than negative SIT (12.8% vs. 3.3%, p=0.04). There were no differences in the incidences of CCV events between patients with positive and negative CCT and FUT (CCT: 11.0% vs. 3.9%, p=0.13, FUT: 6.1% vs. 5.7%, p=0.93). Our results demonstrated a higher incidence of CCV disease in PA SIT-positive patients compared to those with negative test. SIT is a potentially useful test not only for the diagnosis of PA but also assessment of the risk of CCV events.

We recently reported that stimulation with high-dose ACTH caused different responses in terms of aldosterone secretion in aldosterone-producing adenomas (APAs) and idiopathic hyperaldosteronism (IHA) in patients with primary aldosteronism (PA). However, the role of endogenous ACTH in aldosterone secretion in PA has not been systematically evaluated. In this study, we examined diurnal changes in plasma aldosterone concentration (PAC), and changes in PAC after dexamethasone administration in patients with suspected PA, in order to evaluate the effect of endogenous ACTH on aldosterone secretion. Seventy-three patients admitted to Kyoto University Hospital with suspected PA were included. The patients were classified into non-PA, IHA, and APA groups according to the results of captopril challenge test and adrenal venous sampling. PAC at 0900 h (PAC0900), 2300 h (PAC2300), and after 1-mg dexamethasone suppression test (PACdex) was measured and compared among the three groups. The PAC2300/PAC0900 and PACdex/PAC0900 ratios were also analyzed. PAC2300 and PACdex were lower than PAC0900 in all three groups. There were no significant differences in PAC2300/PAC0900 among the three groups. However, PACdex/PAC0900 was significantly lower in the APA group compared with the non-PA and IHA groups. The results of this study indicate that aldosterone secretion in APA patients is more strongly dependent on endogenous ACTH than in IHA and non-PA patients. The results also suggest that factors other than ACTH, such as clock genes, may cause diurnal changes in aldosterone secretion in IHA and non-PA patients.

OBJECTIVES In renal denervation (RDN), a wide range in the blood pressure (BP)-lowering effect has been reported. On the basis of the current knowledge of pathophysiology, we hypothesized that the BP-lowering effect of RDN would be inversely related to kidney function. Second, we investigated whether direct and indirect variables of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS) would be related as well. METHODS Sixty-seven patients from a prospective cohort of patients treated with RDN with completed 6 months follow-up were included. Data collected during routine standardized work-up before RDN were used: 24-h urine excretion of creatinine, albumin, sodium and catecholamines, plasma creatinine, renin activity and aldosterone, ambulatory BP-monitoring and a captopril challenge test. When considered well tolerated, antihypertensive drugs were stopped before these investigations. RESULTS The BP-lowering was inversely related to estimated glomerular filtration rate (eGFR) in patients who stopped antihypertensive drugs prior to testing (s: 0.46, P = 0.013). There was a positive relation between SBP at baseline and the BP-lowering effect of RDN (s:-0.55 mmHg per mmHg, P

SummaryObjective The only reliable method for subtyping primary aldosteronism (PA) is adrenal venous sampling (AVS), which is costly and time-consuming. Considering the limited availability of AVS, it would be helpful to obtain information on the diagnosis of bilateral hyperaldosteronism (BHA) from routine tests. We aimed to establish new, simple criteria for outpatients to diagnose BHA from PA before AVS. Design We retrospectively analysed 82 patients who were diagnosed with PA and underwent AVS. Thirty-seven patients were diagnosed with unilateral hyperaldosteronism (UHA), and 36 with BHA and nine were undetermined. Among the variables that were significantly different between UHA and BHA in the univariate analysis, we chose three variables to be included in multivariate logistic regression models and constructed a subtype prediction score. Results The subtype prediction score was calculated as follows: 3 points for no adrenal nodules on computed tomography imaging, 2 for serum potassium of ≥3·5 mmol/l and 2 for aldosterone-to-renin ratio of

Although confirmatory testing to verify aldosterone excess is a key step in the diagnosis of primary aldosteronism (PA), there is no consensus as to whether it is always needed and which of the tests need to be performed.The objective of this study was to investigate the diagnostic significance of confirmatory tests in PA.In group A, 120 hypertensive patients who had positive case detection using the aldosterone to renin ratio (ARR) were subjected to at least one confirmatory test: the captopril challenge test (CCT), furosemide upright test (FUT), or saline infusion test (SIT). Among group A, 57 patients underwent all three confirmatory tests (group B), and 57 patients were differentiated as having either unilateral or bilateral PA based upon adrenal venous sampling, adrenal scintigraphy, and/or adrenal surgery (group C).The percentages of patients with positive CCT and FUT were 86 and 87% in group A, 88 and 88% in group B, and 96 and 94% in group C, respectively. The percentage of patients with positive SIT results was lower than that with other tests (P0.01). The percentage of patients with positive results for the three tests was higher in patients with baseline ARR of at least 1000 or plasma aldosterone concentration (PAC) of at least 250 pg/ml than in those with lower ARR or PAC in all three groups.Most patients with positive case detection also had positive results on the CCT and FUT, especially when ARR was at least 1000 or PAC was at least 250 pg/ml under renin suppresion. Confirmatory testing for PA may not be needed in all patients with positive case detection.

Medical treatment with a mineralocorticoid receptor (MR) antagonist, which has produced spontaneous remission of bilateral primary aldosteronism (PA), may also produce spontaneous remission of unilateral PA, for which laparoscopic adrenalectomy is recommended. However, few reports exist regarding spontaneous remission after MR antagonist therapy in unilateral PA.The aim of this paper is to report a case of unilateral PA with spontaneous remission and reduction of cardiac hypertrophy after long-term spironolactone (SP) therapy.A 41-yr-old Japanese male was treated for hypertension and hypokalemia for 5 yr. Primary aldosteronism was diagnosed by a furosemide and upright posture test and a captopril challenge test. Computed tomography imaging showed a 5-mm left-sided adrenal mass. Adrenal vein sampling demonstrated overproduction of aldosterone from the left adrenal gland. Long-term treatment with SP normalized the plasma aldosterone concentration. After discontinuation of SP, the patient's blood pressure, serum potassium level, and plasma aldosterone concentration remained in the normal range. The associated cardiac hypertrophy also improved and continued to resolve even after discontinuation of SP. Although the left adrenal gland tumor was still present on computed tomography after treatment, a furosemide and upright posture test, a captopril challenge test, and a saline loading test produced no evidence of PA. Adrenal vein sampling demonstrated no sign of lateralization.These results demonstrate that SP not only antagonizes the MR, but also decreases aldosterone synthetic activity, which may produce remission in some patients with unilateral PA.

Primary aldosteronism (PA) has been recognized as a common cause of secondary hypertension and accounts for approximately 5–15% of the hypertensive population in Japan. Screening for PA should therefore be carried out in all hypertensive patients as we have shown the estimated prevalence of PA is 13.6% in pre-hypertensive subjects and 9.1% in stage 1 hypertensive patients. The screening test most advocated is the aldosterone-to-renin ratio (ARR), and when the ARR is >20 the following confirmatory tests should be carried out; the captopril challenge test, frusemide-upright test, or saline infusion test. Adrenal CT is not accurate for distinguishing between an aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA). Adrenal venous sampling (AVS) is therefore essential for selecting the appropriate therapy in patients a high probability of PA who require surgical treatment. Rapid cortisol assays during AVS to monitor cortisol levels can reduce the failure associated with AVS. We have developed a new rapid cortisol assay using immunochromatography, in which cortisol concentration can be measured within 6 min. Using this technique, the success rate of AVS improved to 93%. IHA underlies about one-half of cases with PA; treatment with eplerenone (100 mg twice a daily), a specific mineralocorticoid receptor antagonist, results in substantial improvement in hypertension, with fewer side effects compared to spironolactone.

Current guidelines recommend use of the aldosterone-renin ratio (ARR) for the case detection of primary aldosteronism (PA), the most common cause of secondary hypertension, in selected hypertensive patients. "Confirmatory" tests are then recommended in patients who tested positive at the ARR to exclude from further diagnostic work-up false positive results. Based on our experience we hypothesized that the ARR carries quantitative information, which can avoid the need of confirmatory tests. We herein describe a study protocol to identify the ARR cut-off value with a high specificity for the exclusion of aldosterone-producing adenoma (APA) based on analysis of two large prospectively collected datasets of patients in which a conclusive diagnosis of APA was made by the four corners criteria. This will also serve to investigate the diagnostic gain provided over this ARR cut-off value by one confirmatory test, the captopril challenge test. Hence, with this protocol we expect to identify an ARR cut-off value that might prevent further testing in patients with either a low or a high probability of APA. This could translate in a higher diagnostic accuracy and, by preventing unnecessary invasive testing, into a substantial saving of money, time, and resources.

Objectives We prospectively investigated the prevalence of curable forms of primary aldosteronism (PA) in newly diagnosed hypertensive patients. Background The prevalence of curable forms of PA is currently unknown, although retrospective data suggest that it is not as low as commonly perceived. Methods Consecutive hypertensive patients referred to 14 hypertension centers underwent a diagnostic protocol composed of measurement of Na+and K+in serum and 24-h urine, sitting plasma renin activity, and aldosterone at baseline and after 50 mg captopril. The patients with an aldosterone/renin ratio >40 at baseline, and/or >30 after captopril, and/or a probability of PA (by a logistic discriminant function) ≥50% underwent imaging tests and adrenal vein sampling (AVS) or adrenocortical scintigraphy to identify the underlying adrenal pathology. An aldosterone-producing adenoma (APA) was diagnosed in patients who in addition to excess autonomous aldosterone secretion showed: 1) lateralized aldosterone secretion at AVS or adrenocortical scintigraphy, 2) adenoma at surgery and pathology, and 3) a blood pressure decrease after adrenalectomy. Evidence of excess autonomous aldosterone secretion without such criteria led to a diagnosis of idiopathic hyperaldosteronism (IHA). Results A total of 1,180 patients (age 46 ± 12 years) were enrolled; a conclusive diagnosis was attained in 1,125 (95.3%). Of these, 54 (4.8%) had an APA and 72 (6.4%) had an IHA. There were more APA (62.5%) and fewer IHA cases (37.5%) at centers where AVS was available (p = 0.002); the opposite occurred where AVS was unavailable. Conclusions In newly diagnosed hypertensive patients referred to hypertension centers, the prevalence of APA is high (4.8%). The availability of AVS is essential for an accurate identification of the adrenocortical pathologies underlying PA.

Correction to: Journal of Human Hypertension (2017) 31, 760; doi:10.1038/jhh.2017.41; published online 25 May 2017 Post online publication the authors realised that the following sentence in the footnote: ARR>200 was classified as positive for screening for PA. ARR after 60 min>200 was classified as positive in the captopril challenge test.

Background: Hypokalemia is not a sensitive marker of primary aldosteronism (PA) , and method for screening PA by routine clinical parameters has not yet been established. Objective: We examined whether serum uric acid (UA) or urine pH alone, or their combination with serum K+ level is usable for PA screening . Design and Setting: Cross-sectional analyses were retrospectively performed on consecutive patients who visited a single general hospital from April 2012 to September 2013. Participants: Entry criteria were age Main Outcome Measures: Diagnosis of PA was made in accordance with the guideline of Japanese Society of Hypertension: patients with aldosterone-to-renin activity ratio (ARR) > 20 and one or more positive results in captopril challenge test, furosemide-upright test, saline infusion test and/or ACTH stimulation test. Results: We enrolled 103 patients (PA = 29, essential hypertension [eHT] = 74). PA has lower serum K+ (3.5±0.32 vs 3.8±0.23 mEq/L, p Conclusions: PUK2 score is easy to use and useful for screening PA in hypertensive patients.

In the present issue of The Journal of Clinical Hypertension, Kline and colleagues propose a fundamental change in the diagnostic workup of patients evaluated for potential primary hyperaldosteronism (PH). Traditionally, the diagnosis of PH is predominantly considered in the presence of hypertension with hypokalemia; severe or resistant hypertension; adrenal incidentaloma, particularly when associated with hypertension; and hypertension of early onset, especially in the context of familial hypertension with early cerebrovascular events. That screening for PH should be initiated by the determination of the Aldosterone-Renin Ratio (ARR) is now widely recommended. A high ARR is followed by one of several confirmatory forms of testing, all of which are based on the principle that contrary to physiological control of aldosterone secretion, autonomous aldosterone secretion cannot be properly turned off in response to salt/volume loading or acute reduction in circulating angiotensin II. Although the need for confirmatory testing is widely accepted, views on the most adequate procedure vary. Reflecting this area of disagreement, the Endocrine Society’s guidelines endorse the use of one of several forms of tests: the oral sodium loading test, saline infusion test, fludrocortisone suppression test, or the captopril challenge test. In principle, only individuals with evidence of autonomous aldosterone secretion in any of these tests are presumed to have “true PH” and are thus referred for further evaluation, including computed tomography (CT) or magnetic resonance imaging scans, followed by adrenal venous sampling (AVS). Individuals with unilateral disease, mostly aldosterone-producing adenoma, are usually referred for surgery and are likely to benefit from adrenalectomy, whereas patients with bilateral adrenal hyperplasia are treated medically. In their present article, Kline and coworkers challenge the need for confirmatory testing and offer an alternative single-step, ARR-based approach to the diagnosis of PH, to be directly followed, when a preset critical ARR is surpassed, by adrenal imaging and AVS. Because of the inconsistent performance of the confirmatory tests, the authors abandoned this phase altogether. Having accumulated considerable experience with this approach, this group now submits evidence from a single referral center that a systematic omission of confirmatory testing has virtually no discernible impact on the clinical outcome of patients evaluated for PH. In the course of 6 years (2005–2011), Kline and associates evaluated 83 hypertensive patients whose initial ARR exceeded 550 pmol/L irrespective of their medication status. Patients with resistant hypertension and normal ARR were re-evaluated after the withdrawal of all medications known to affect aldosterone and/or plasma renin activity (PRA) and maintained on doxazocin and either nifedipine or diltiazem, supplemented, when needed, only by oral potassium-containing tablets. In all, 83 patients whose ARR exceeded 550 pmol/L were considered to have PH. All were referred for adrenal CT and AVS, using a protocol in which adrenal vein aldosterone was measured both before and after the administration of 250 lg of cosyntropin (a synthetic derivative of adrenocorticotropic hormone [ACTH]). Patients whose post-ACTH interadrenal aldosterone/cortisol ratio gradient was higher than 3 were considered to have unilateral disease. In terms of outcome, AVS was technically successful in 80 of 83 (96%) of the patients and an unequivocal AVS-based lateralization was established in 48 patients. Notably, 88% of the lateralized patients had a congruent CT finding, whereas unilateral anomalous CT adrenal was seen in

Primary aldosteronism (PA) is common in young or middle-aged hypertensive patients, but PA among the elderly has recently become more common. As salt sensitivity increases with age, plasma renin activity (PRA) tends to decrease, whereas the aldosterone-to-renin ratio (ARR) tends to increase in the elderly. The aim of this study was to clarify the influence of aging on the diagnosis of PA. We retrospectively evaluated 155 consecutively admitted patients who were not taking antihypertensive medications or calcium channel blockers and α blockers that underwent PRA and plasma aldosterone concentration (PAC) measurements. The study subjects included 13 PA and 69 essential hypertensive (EHT) patients aged over 65 years, and 32 PA and 41 EHT patients under aged 65 years. Our study clarified the influence of aging through screening and confirmatory tests for the diagnosis of PA. Our results showed the ARR cutoff value for a screening test to be 556 (area under the curve: AUC=0.906), its sensitivity and specificity to be 84.6% and 89.9%, respectively, and the likelihood ratio to be 8.34 in the elderly, whereas the ARR cutoff value was 272 in the non-elderly. In the saline infusion test, the mean PAC was 86.6 ± 41.8 pg ml(-1) in the elderly and 158.1 ± 116.5 pg ml(-1) in the non-elderly (P = 0.04). There was no influence from age in both the captopril challenge test and the furosemide upright test. Aging may influence PA screening and saline infusion tests; thus, we should consider the influence of aging in the diagnosis of elderly subjects with PA.

Abstract —This prospective study was designed to compare the captopril suppression test with the salt-loading approach to confirm the diagnosis of primary aldosteronism. A total of 49 patients were referred with a presumed diagnosis of primary aldosteronism. The captopril test was performed in the morning with patients in the seated position after overnight fasting. Blood samples for plasma aldosterone were obtained before captopril administration (25 mg PO) and again 2 hours later. Patients were then subjected to a high salt diet (300 mmol sodium per day for 3 days). On the third day, urinary sodium (24 hours) was measured, and plasma aldosterone levels were measured at 8:00 am (recumbent) and at noon (standing). Of the 49 patients, 44 had nonsuppressible aldosterone concentrations with all the clinical characteristics of primary aldosteronism: 22 patients had surgically confirmed unique adenoma, and 22 patients had presumed bilateral hyperplasia. There was a significant correlation between plasma aldosterone values of salt-loaded patients (mean of 8:00 am and noon results) and the values 2 hours after captopril administration ( r =0.8, P

Summary: Hypertension in the presence of renal artery stenosis may not necessarily be renovascular hypertension. the two conditions may simply co-exist. Some features of renovascular hypertension include: a worse prognosis than essential hypertension, less amenable to drug treatment, a greater risk of dose-dependent side effects, a higher risk of progression to accelerated hypertension and it may result in irreversible ischaemic failure of the affected kidney. Renovascular hypertension is usually symptomless, while hypertension that is difficult to control with antihypertensive therapy is probably the best indication as to whether further diagnostic evaluation is indicated. A clue is a rise in the plasma creatinine concentration following the introduction of an angiotensin converting enzyme inhibitor (ACEI). Renal artery stenosis may be present in up to 30% of drug resistant hypertensive patients. Arteriosclerotic renovascular disease is an increasingly important cause of renal failure. In this institution from 1 January 1988 to 31 December 1993,491 patients were referred with a plasma creatinine of ≥0.30 mmol/L. Hypertension/nephrosclerosis/renal artery stenosis was the diagnosis in 75 of 372 (20%) of those patients who had chronic renal failure. of the last 427 patients entering our renal replacement programme, 23 were due to hypertensive nephrosclerosis and an additional five due to renal artery stenosis (6.6% of the total). Functional diagnostic tests for renovascular hypertension such as rapid sequence intravenous urography have now been superseded by the captopril challenge test and in particular scintigraphy following captopril provocation. Tests of prediction as to whether correction of a demonstrated renal artery stenosis will lead to an improvement in the blood pressure include renal vein renin estimations and scintigraphy. the key diagnostic procedure is renal angiography. the approaches to management primarily include appropriate antihypertensive therapy, while there is an increasing place for percutaneous transluminal angioplasty, with or without stenting of an occluding lesion. There is still a small place for corrective surgery. Renal ischaemia due to atherosclerotic renovascular disease is becoming an increasing problem in nephrology. Treatment should be directed at preserving or even restoring renal function.

The peroxisome proliferator-activated receptor gamma (PPAR γ) agonists have been reported to have antiproliferative and tumor-suppressive effects. We report a case of 55-year-old man with primary aldosteronism (PA) whose hyperaldosteronism was suppressed with the PPAR γ agonist pioglitazone. He had drug-resistant hypertension, hypokalemia, and diabetes mellitus. The diagnosis of PA was confirmed by the oral sodium loading test (20.5 μg/d of urinary aldosterone) and Captopril challenge test (19.5 ng/dL of plasma aldosterone). Computed tomography imaging revealed no apparent adrenal mass. The result of the posture stimulation test was consistent with the diagnosis of idiopathic adrenal hyperplasia. On administration of pioglitazone (30 mg/d) and nifedipine (40 mg/d), hypertension and hypokalemia improved and plasma aldosterone decreased for more than 6 months. The sodium loading test done after 6 months of the administration revealed the near normal results (11.2 ng/dL of plasma aldosterone and 13.1 μg/d of urinary aldosterone). The findings indicated that pioglitazone suppressed PA.

Background : Prediction of improvement following surgical or radiologic intervention in patients thought to have renovascular hypertension (RVH) is often unreliable. Use of the angiotensin-converting enzyme inhibitor captopril in conjunction with measurement of peripheral renin levels or radioisotope renograms is thought to detect patients with functionally significant renal artery stenosis. However, it is unclear whether these tests can identify patients whose hypertension will significantly improve after renal artery repair. Patients and methods : The records of 52 consecutive hypertensive patients undergoing captopril studies followed by renal artery repair were reviewed. All patients had either renal artery stenosis > 75% or renal artery occlusion. Preprocedure evaluation included a captopril challenge test (measurement of peripheral renin levels after captopril ingestion) (n = 12) or a captopril renogram (determination of renal blood flow and glomerular filtration rate before and after captopril administration) (n = 40). Either renal artery bypass/nephrectomy (n = 41) or balloon angioplasty (n = 11) was done in all patients (18 bilateral/34 unilateral). No periprocedural deaths occurred. All surgically placed bypass grafts were shown to be patent by contrast or carbon dioxide arteriography before hospital discharge. Results : Preprocedure captopril tests were positive (suggestive of RVH) in 39 patients (75%) and negative in 13 (25%). All patients with positive captopril tests had improvement in their RVH after intervention (17 cured, 22 improved) while 8 of 13 patients with negative captopril tests had no improvement in blood pressure control. Four of five false-negative tests were associated with a unilateral total renal artery occlusion, making detection of a postcaptopril effect impossible. If these 4 patients are excluded from analysis, preprocedure captopril testing was 98% accurate in predicting postprocedure outcome. Conclusions : Preprocedure captopril testing permits extremely accurate selection of patients with renal artery stenosis who will benefit from renal artery repair.

The Japan Endocrine Society (JES) attempted to develop guidelines for the diagnosis and treatment of primary aldosteronism (PA). The Task Force Committee (TFC) was composed of a chair, selected by the JES, and additional experts. Systematic reviews of available evidence for Japanese patients were used to recommend the key treatment and prevention. We have evaluated the methods of screening, confirmatory tests and imaging, plus adrenal vein sampling (AVS). Consensus was guided by systematic review of evidence and discussion during each annual meeting of the JES, plus its related meetings, and by e-mail communication. The drafts prepared by TFC were reviewed successively by the members of Research on Intractable Diseases provided by the Japanese Ministry of Health, Labour and Welfare, and in comments from the JES's councilors. At each stage of review, TFC received written comments and incorporated suggested changes. In conclusion, all patients with hypertension should be screened for PA, because of the high prevalence of cardiovascular disease and the current low case-detection rate in Japan. Case detection can be performed in hypertensive patients and those with hypokalemia by determining the aldosterone/renin ratio, and the diagnosis of PA can be confirmed by two of three confirmatory tests. The presence of a unilateral aldosterone-producing adenoma should be established/excluded by AVS by an experienced radiologist, optimally followed by laparoscopic adrenalectomy. In contrast, patients with bilateral adrenal hyperplasia, or those unsuitable for surgery, are optimally treated medically with mineralocorticoid receptor antagonists.

Effective therapy is available but the diagnosis of renovascular hypertension is often elusive. Those affected constitute a minority of the hypertensive population, and traditional screening tests have poor sensitivity and specificity. The merits and limitations of the captopril challenge test and the captopril renogram, alone or in combination, are discussed.

Background Two variants of the CYP2C9 gene, CYP2C9*2 and CYP2C9*3, have been indicated to have impaired enzyme function, and thus suspected to reduce the formation of the active metabolite of losartan. Cytochrome P450 (CYP) enzymes are also involved in eicosanoid biosynthesis and regulation of blood pressure (BP) and sodium homeostasis. Methods We studied the impact of these variants on BP response to losartan and three other antihypertensive drugs and on baseline indicators of the activity of the renin-angiotensin-aldosterone system. The participants were 217 moderately hypertensive Finnish men that participated in the double-blind, cross-over, placebo-controlled GENRES Study. Results BP responses to losartan did not differ between CYP2C9*2 or CYP2C9*3 allele carriers and CYP2C9*1*1 patients. A suggestive finding of less pronounced ambulatory BP response to losartan in CYP2C9*1*3 patients with low-normal kidney function was made. At baseline of the GENRES Study, CYP2C9*1*3 patients had significantly lower plasma renin activity and aldosterone levels than CYP2C9*1*1 patients (both P values 0.004). In a replication study in patients with treatment-resistant hypertension, men with CYP2C9*3 allele also had lower plasma renin activity (P = 0.03) and aldosterone levels (P = 0.18). In addition, these men had attenuated renin and aldosterone responses in captopril challenge test (P = 0.29 and 0.006, respectively). Conclusion The CYP2C9*3 allele was associated with lower activity of the renin-angiotensin-aldosterone system in hypertensive men, which may reflect a more efficient sodium reabsorption capacity. CYP2C9*2 and CYP2C9*3 alleles do not influence the antihypertensive effect of losartan in men with essential hypertension and normal kidney function.

We performed a prospective head-to-head comparison of the accuracy of the captopril test (CAPT) and the saline infusion test (SAL) for confirming primary aldosteronism due to an aldosterone-producing adenoma (APA) in patients with different sodium intake. A total of 317 (26.9%) of the 1125 patients screened in the Primary Aldosteronism Prevalence in Italy Study underwent both CAPT and SAL. They were composed of the patients with a high aldosterone/renin ratio baseline and 1 every 4 patients without such criterion. The accuracy of post-CAPT or post-SAL plasma aldosterone values for diagnosing APA was estimated with the area under the receiver operator characteristics curves. Primary aldosteronism was found in 120 patients, of which 46 had an APA. No untoward effect occurred with either test. The area under the receiver operator characteristics curve of plasma aldosterone for both tests was higher ( P P =0.054). The optimal aldosterone cutoff value for identifying APA was 13.9 and 6.75 ng/dL for the CAPT and SAL, respectively. Even at these cutoffs, sensitivity and specificity were moderate because of overlap of values between patients with and without APA. When examined in relation to sodium intake, the accuracy of the SAL surpassed that of the CAPT in the patients with a sodium intake ≤130 mEq per day; this difference waned at a higher Na + intake. Thus, both the CAPT and the SAL are safe and moderately accurate for excluding APA; at a sodium intake >7.6 g per day, the SAL offers no advantage over the easier-to-perform CAPT.

Primary aldosteronism (PA) is the most frequent cause of secondary hypertension responsible for an increased rate of cardiovascular events. According to the Endocrine Society Guidelines, up to 50% of hypertensive patients should be screened for PA, using the aldosterone to renin (or plasma renin activity, PRA) ratio (AARR and ARR, respectively). The automated Diasorin LIAISON® chemiluminescent immunoassay for renin and aldosterone measurement became available and in many laboratories is currently used instead of the classical radioimmunometric PRA and aldosterone assay. Aim of the study was to prospectively compare the diagnostic accuracy of AARR and ARR as screening test for PA and the two aldosterone assays also during confirmatory test in patients with a positive screening test. One hundred patients were screened for PA and 44 patients underwent confirmatory test (either by intravenous saline load or by captopril challenge test). We considered as cut off for the AARR 2.7 (ng/dL/mU/L) and for the ARR 30 (ng/dL/ng/mL/h). All patients positive to one of the two screening test underwent confirmatory test; patients with positive confirmatory test underwent subtype diagnosis by CT scanning and adrenal vein sampling. Seventy three patients were diagnosed as essential hypertensives, 22 had bilateral adrenal hyperplasia and 5 had an aldosterone producing adenomas (APA). The AARR displayed a sensitivity of 78% and a specificity of 100%, whereas the ARR had a sensitivity of 96% and a specificity of 90%. Of the 6/27 PA patients missed by AARR, none resulted to be affected by APA. All PA patients were correctly diagnosed by chemiluminescence at confirmatory test. In the overall sample of 181 measurements available both the correlation for the PRA with renin and for aldosterone in chemiluminescence and radioimmunoassay were highly significant (Rho = 0.66, p

Primary aldosteronism (PA) is a common form of endocrine hypertension previously believed to account for less than 1% of hypertensive patients. Hypokalemia was considered a prerequisite for pursuing diagnostic tests for PA. Recent studies applying the plasma aldosterone/plasma renin activity ratio (ARR) as a screening test have reported a higher prevalence. This study is a retrospective evaluation of the diagnosis of PA from clinical centers in five continents before and after the widespread use of the ARR as a screening test. The application of this strategy to a greater number of hypertensives led to a 5- to 15-fold increase in the identification of patients affected by PA. Only a small proportion of patients (between 9 and 37%) were hypokalemic. The annual detection rate of aldosterone-producing adenoma (APA) increased in all centers (by 1.3–6.3 times) after the wide application of ARR. Aldosterone-producing adenomas constituted a much higher proportion of patients with PA in the four centers that employed adrenal venous sampling (28–50%) than in the center that did not (9%). In conclusion, the wide use of the ARR as a screening test in hypertensive patients led to a marked increase in the detection rate of PA.

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/Ror =35 were 95.4% and 28.3% at baseline, compared with 100% and 67.9% after captopril. Using postcaptopril A/Ror =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 (chi(2) = 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%, chi(2) = 0.086, P =.770). Serum potassiumor =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.

We describe a patient with a rare combination of acromegaly and primary aldosteronism. A 37 year-old female patient was diagnosed with acromegaly on the basis of typical clinical, hormonal and image characteristics. She presented also with one of the most common co-morbidities – arterial hypertension. The patient has been regularly followed-up and after three surgical interventions, irradiation and adjuvant treatment with a dopamine agonist, acromegaly was finally controlled in 2008 (20 years after diagnosis). Arterial hypertension however, remained a therapeutic problem even after prescription of four antihypertensive drugs. She had normal biochemical parameters, except for low potassium levels 3.2 (3.5-5.6) mmol/l. This raised the suspicion of primary hyperaldosteronism, confirmed by a high aldosterone to plasma rennin activity ratio, high aldosterone level after a Captopril challenge test and visualization of a 35 mm left adrenal nodule on a CT scan. After an operation, the patient recovered from hypokalemia and antihypertensive therapy was reduced to a small dose of a Ca blocker.Co-morbid arterial hypertension is common in acromegaly, though it is rare for this to be caused by Conn’s adenoma. The association of Conn’s adenoma with acromegaly has been interpreted in two lines: as a component of multiple endocrine neoplasia type (MEN1) syndrome or as a direct mitogenic effect of hyperactivated GH-IGF1 axis.

Objectives To investigate the clinical characteristics of patients with normokalemic and hypertensive primary aldosteronism. Methods The clinical data of 224 cases with normokalemic and hypertensive primary aldosteronism from 2006 to 2010 in the hypertension department of the peoplel9s hospital of Xinjiang Uygur autonomous region were analysed retrospectively. Primary aldosteronism was diagnosed by aldosterone-to-rennin activity ratio(ARR) screening and confirmation tests(including Captopril challenge test and sodium infusion test) Results The prevalence of 1, 2 and 3 stage hypertension in all subjects were 4.47%, 18.3% and 77.23%, respectively. The main symptoms were headache (52.07%), dizzy (49.7%), fatigue (4.14%), palpitation (2.96%), limbs numbness (1.78%), respectively. The average serum sodium level was (140.75±2.75) mmol/l. The incidence of hypernatremia was only 4.91%. The proportion of the patients with normokalemic and hypertensive primary aldosteronism who had the renin activity of less than 1 ng ml −1 h −1 was 97.32%. To screen the patients with normokalemic and hypertensive primary aldosteronism, the diagnostic positive rate of ARR≥20 (ng/dl)/[ug/(L·h)]combined with low renin activity was significantly higher than that of the low renin activity combined with high aldosterone level, ARR ≥20 (ng/dl)/(μg/(L·h) combined with high aldosterone level and ARR≥30 (ng/dl)/(μg/(L·h) as a screening standard (χ 2 =18.95, p 2 =31.13, p 2 =29.25, p Conclusions The majority present moderate to severe hypertension with low rennin activity and normal serum sodium level in normokalemic and hypertensive primary aldosteronism patients. Cerebial vascular complication is relatively more common than coronary heart disease. It is helpful to decrease the missed diagnosis rate for ARR combined with low renin activity as a screening index of the patients with normokalemic and hypertensive primary aldosteronism.

A captopril challenge test (CCT) for renovascular disease in adults was described recently. We used it in 20 consecutive, untreated hypertensive children and adolescents. All had a normal urinalysis and glomerular filtration rate and non-diagnostic renal sonograms or intravenous urograms. Plasma renin activity (PRA) was measured before and 1 h after administration of captopril (0.76 +/- 0.17 mg/kg). The CCT was positive in 10 patients. Renal arteriograms were performed in 7 patients with a positive CCT and in 2 with a negative CCT. Renovascular disease was found in 4 patients, 1 of whom had a negative CCT. The PRA response to captopril was the same in patients with true- and the false-positive tests. The predictive value of the positive test was 43%. In conclusion, we did not find the CCT, as described for adults, to be of value in children and adolescents.

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.