Factors affecting the aldosterone/renin ratio

Although the aldosterone/renin ratio (ARR) is the most reliable screening test for primary aldo-steronism, false positives and negatives occur. Dietary salt restriction, concomitant malignant or renovascular hypertension, pregnancy and treatment with diuretics (including spironolactone), dihydropyridine calcium blockers, angiotensin converting enzyme inhibitors, and angiotensin receptor antagonists can produce false negatives by stimulating renin. We recently reported selective serotonin reuptake inhibitors lower the ratio. Because potassium regulates aldosterone, uncorrected hypokalemia can lead to false negatives. Beta-blockers, alpha-methyldopa, clonidine, and nonsteroidal anti-inflammatory drugs suppress renin, raising the ARR with potential for false positives. False positives may occur in patients with renal dysfunction or advancing age. We recently showed that (1) females have higher ratios than males, and (2) false positive ratios can occur during the luteal menstrual phase and while taking an oral ethynylestradiol/drospirenone (but not implanted subdermal etonogestrel) contraceptive, but only if calculated using direct renin concentration and not plasma renin activity. Where feasible, diuretics should be ceased at least 6 weeks and other interfering medications at least 2 before ARR measurement, substituting noninterfering agents (e. g., verapamil slow-release±hydralazine and prazosin or doxazosin) were required. Hypokalemia should be corrected and a liberal salt diet encouraged. Collecting blood midmorning from seated patients following 2-4 h upright posture improves sensitivity. The ARR is a screening test only and should be repeated once or more before deciding whether to proceed to confirmatory suppression testing. Liquid chromatography-tandem mass spectrometry aldosterone assays represent a major advance towards addressing inaccuracies inherent in other available methods.     

Mineralocorticoid Receptor Antagonists Decrease the Rates of Positive Screening for Primary Aldosteronism

Objective: Mineralocorticoid receptor antagonists (MRAs) are effective in patients with resistant hypertension and/or primary aldosteronism (PA). Screening for PA should ideally be conducted after stopping medications that might interfere with the renin-angiotensin-aldosterone system, but this is challenging in patients with recalcitrant hypertension or hypokalemia. Herein, we aimed to evaluate the impact of MRAs on PA screening in clinical practice.Methods: We conducted a retrospective cohort study of patients with hypertension who had plasma aldosterone and renin measurements before and after MRA use in a tertiary referral center, over 19 years.Results: A total of 146 patients, 91 with PA, were included and followed for up to 18 months. Overall, both plasma renin and aldosterone increased after MRA initiation (from median, interquartile range: 0.5 [0.1, 0.8] to 1.2 [0.6, 4.8] ng/mL/hour and from 19.1 [12.9, 27.7] to 26.4 [17.1, 42.3] ng/dL, respectively; P<.0001 for both), while the aldosterone/renin ratio (ARR) decreased from 40.3 (18.5, 102.7) to 23.1 (8.6, 58.7) ng/dL per ng/mL/hour (P<.0001). Similar changes occurred irrespective of the MRA treatment duration and other antihypertensives used. Positive PA screening abrogation after MRA initiation was found in 45/94 (48%) patients. Conversely, 17% of patients had positive PA screening only after MRA treatment, mostly due to correction of hypokalemia. An initially positive screening test was more likely altered by high MRA doses and more likely persistent in patients with confirmed PA or taking beta-blockers.Conclusion: MRAs commonly reduce ARR and the proportion of positive PA screening results. When PA is suspected, screening should be repeated off MRAs.Abbreviations: ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; ARR = aldosterone/renin ratio; DRC = direct renin concentration; MRA = mineralocorticoid receptor antagonist; PA = primary aldosteronism; PAC = plasma aldosterone concentration; PRA = plasma renin activity; RAAS = renin-angiotensin-aldosterone system     

卡托普利试验过程中颈动脉斑块与醛固酮含量相关指标变化的相关性研究

目的:研究卡托普利试验过程中血浆醛固酮(PAC)相关指标的变化与颈动脉斑块的相关性。方法:选择在本院住院进行高血压病因筛查并完成了卡托普利试验,且颈动脉彩超资料完整的83例患者为研究对象。以颈动脉彩超诊断结果为分组标准,有颈动脉斑块者为斑块组(57例),无颈动脉斑块者为无斑块组(26例),分析两组患者PAC、血浆肾素活性(PRA)、PAC与PRA的比值(ARR)等指标的变化与颈动脉斑块之间的相关性。结果:颈动脉斑块检出率为68.67%。与无斑块组比较,斑块组患者的年龄更大,载脂蛋白A1(APOA1)水平更低(P均<0.05),卡托普利试验前后斑块组患者的ARR差值更低,PAC及PRA的差值更大(P均<0.05);其中,斑块组PAC及PRA的差值为正;无斑块组此二差值为负,斑块组ARR的差值为负,无斑块组该差值为正。Logistic回归分析表明,在排除了性别等因素之后,仅年龄、卡托普利试验前后PAC差值及ARR差值为颈动脉斑块形成独立的危险因素。结论:在进行高血压病因筛查的住院高血压患者中,颈动脉斑块的检出率较高,卡托普利试验前后PAC的差值及ARR的差值为颈动脉斑块形成独立的危险因素。     

Diabetes related knowledge among residents and nurses: a multicenter study in Karachi,Pakistan

The existence of unilateral adrenal hyperplasia (AH) has been considered a rare cause of primary hyperaldosteronism (PA). In a prospective study we screened for PA in a non-selected (NSP) and selected hypertensive population (SP), to define the cause of PA. We included 353 consecutive patients with hypertension; age 20 to 88 years, 165 women and 188 men, from a university-based Hypertension and Nephrology Outpatient clinics (123 SP) and two primary care centres, (230 NSP) from the same catch-up area. Serum aldosterone and plasma renin activity (PRA) were measured and the ARR calculated. Verifying diagnostic procedure was performed in patients with both elevated aldosterone and ARR. Patients diagnosed with PA were invited for adrenal venous sampling (AVS) and offered laparoscopic adrenalectomy when AVS found the disease to be unilateral. After screening, 46 patients, 13% of the whole population (22.8% SP and 7.8% NSP) had aldosterone and ARR above the locally defined cut-off limits (0.43 nmol/l and 1.28 respectively). After diagnostic verification, 20 patients (6%) had PA, (14.5% SP and 1.4% NSP). Imaging diagnostic procedures with CT-scans and scintigraphy were inconclusive. AVS, performed in 15 patients verified bilateral disease in 4 and unilateral in 10 patients. One AVS failed. After laparoscopic adrenalectomy, 4 patients were found to have adenoma and 5 unilateral AH. One patient denied operation. The prevalence of PA was in agreement with previous studies. The study finds unilateral PA common and unilateral AH as half of those cases. As may be suspected PA is found in much higher frequency in specialised hypertensive units compared to primary care centers. AVS was mandatory in diagnosis of unilateral PA.     

Unilateral adrenal hyperplasia is a usual cause of primary hyperaldosteronism. Results from a Swedish screening study

ABSTRACT: BACKGROUND: The existence of unilateral adrenal hyperplasia (AH) has been considered a rare cause of primary hyperaldosteronism (PA). METHODS: In a prospective study we screened for PA in a non-selected (NSP) and selected hypertensive population (SP), to define the cause of PA. We included 353 consecutive patients with hypertension; age 20 to 88 years, 165 women and 188 men, from a university-based Hypertension and Nephrology Outpatient clinics (123 SP) and two primary care centres, (230 NSP) from the same catch-up area. Serum aldosterone and plasma renin activity (PRA) were measured and the ARR calculated. Verifying diagnostic procedure was performed in patients with both elevated aldosterone and ARR. Patients diagnosed with PA were invited for adrenal venous sampling (AVS) and offered laparoscopic adrenalectomy when AVS found the disease to be unilateral. RESULTS: After screening, 46 patients, 13% of the whole population (22.8% SP and 7.8% NSP) had aldosterone and ARR above the locally defined cut-off limits (0.43 nmol/l and 1.28 respectively). After diagnostic verification, 20 patients (6%) had PA, (14.5% SP and 1.4% NSP). Imaging diagnostic procedures with CT-scans and scintigraphy were inconclusive. AVS, performed in 15 patients verified bilateral disease in 4 and unilateral in 10 patients. One AVS failed. After laparoscopic adrenalectomy, 4 patients were found to have adenoma and 5 unilateral AH. One patient denied operation. CONCLUSION: The prevalence of PA was in agreement with previous studies. The study finds unilateral PA common and unilateral AH as half of those cases. As may be suspected PA is found in much higher frequency in specialised hypertensive units compared to primary care centers. AVS was mandatory in diagnosis of unilateral PA.     

Prevelence of Primary Aldosteronism in an Urban Hypertensive Population

Objective: To determine the prevalence of primary aldosteronism (PA) in hypertensive patients presenting to the primary care clinic at The Mount Sinai Hospital, regardless of the degree of hypertension and to identify clinical criteria that should prompt screening for PA.Methods: An aldosterone:renin ratio (ARR, cutoff ≥20, with plasma aldosterone concentration [PAC] ≥10 and suppressed renin) was used to prospectively screen 296 hypertensive patients (blood pressure [BP] ≥140/90) over the age of 18 from August 2012 through May 2013. Subjects who screened positive then underwent confirmatory oral salt load testing (OSLT).Results: Of the 296 patients, 14 screened positive for PA, an overall prevalence of 4.7%. Six of the 14 cases underwent confirmatory OSLT, upon which 2 were confirmed positive, for a prevalence of 0.7%. Overall, patients with confirmed PA were more likely to have resistant hypertension (42.9% vs. 18.1% (P =.0334)) and require more antihypertensive agents (2.8 ± 1.2 agents vs. 2.1 ± 1.1 agents, P =.0213). There was a trend toward lower potassium values in the cases.Conclusion: The prevalence of PA in our clinic is much lower than in reports from certain “at-risk” populations. PA screening is indicated in patients with resistant hypertension, regardless of serum potassium levels.Abbreviations:ARR = aldosterone:renin ratioACTH = adrenocorticotropic hormoneAVS = adrenal venous samplingBP = blood pressureMRA = mineralocorticoid receptor antagonistOSLT = oral salt load confirmatory testPA = primary aldosteronismPAC = plasma aldosterone concentrationPCP = primary care providerPRA = plasma renin activity     

Comparison of the saline infusion test and the fludrocortisone suppression test for the diagnosis of primary aldosteronism

For the diagnosis of primary aldosteronism (PA), confirmatory testing is mandatory and different function tests can be employed. There are, however, sparse data comparing the fludrocortisone suppression test (FST) and the saline infusion test (SIT). Patients with PA (n=90) or essential hypertension (n=65) were studied. They underwent one or the other test or both of them. Using the DPC Siemens aldosterone radioimmunoassay, we found that the SIT led to a stronger suppression of aldosterone than the FST. Post-test aldosterone-to-renin ratios (ARRs) and the percentage of suppression of aldosterone serum concentrations performed worse. The same results were observed in patients who underwent both FST and SIT. Some patients had divergent results in both tests. For the SIT, a lower cutoff value should be used than for the FST for the adequate identification of patients with unilateral PA. Long-term prospective studies are needed to address the question at what cutoff values patients benefit from subtype differentiation of PA. We discuss here possible explanations for divergent results obtained with both tests.     

Genetics of Primary Aldosteronism

Objective: The American Association of Clinical Endocrinologists Adrenal Scientific Committee has developed a series of articles to update members on the genetics of adrenal diseases.Methods: Case presentation, discussion of literature, table, and bullet point conclusions.Results: Primary aldosteronism (PA) is the most common form of secondary hypertension. Early detection, surveillance, and treatment of PA may mitigate future cardiovascular risk. The genetics of PA are rapidly evolving, and the consideration for genetic causes of PA are growing. Three inheritable forms of PA are now recognized: familial hyperaldosteronism type I (glucocorticoidremediable aldosteronism), familial hyperaldosteronism type II, and familial hyperaldosteronism type III. The recent discovery of familial hyperaldosteornism type III spurred a flurry of international and collaborative research that is identifying more genetic and molecular causes of PA that relate to mutations in membrane electrolyte transport channels of zona glomerulosa cells.Conclusion: This article reviews the various genetic forms of PA, including a focus on the molecular mechanisms involved, diagnosis, and treatment.Abbreviations: ACTH = adrenocorticotropic hormone ARR = aldosterone to renin ratio FH-I = familial hyperaldosteronism type I FH-II = familial hyperaldosteronism type II FH-III = familial hyperaldosteronism type III GRA = glucocorticoidremediable aldosteronism PA = primary aldosteronism PRA = plasma renin activity     

Exploration Of The Seated Saline Suppression Test For The Diagnosis Of Primary Aldosteronism In The Chinese Population

Objective: We prospectively investigated the accuracy of the seated saline suppression test (SSST) in 113 patients with hypertension (including 93 primary aldosteronism [PA] and 20 essential hypertension patients) in the Department of Endocrinology and Metabolism.Methods: Each patient underwent a recumbent saline suppression test (RSST) and SSST. The accuracy of the SSST for a confirmative PA diagnosis and subtype classification was evaluated and compared with the RSST.Results: The area under the receiver operating characteristic (ROC) curve of plasma aldosterone concentration (PAC) for the SSST was significantly greater than that for the RSST (0.945 ± 0.0199 vs. 0.828 ± 0.0404; P<.05). The ROC analysis showed that the optimal PAC cut-off values were 12.94 ng/dL for the SSST (sensitivity 86.02%, specificity 95%; Youden index [YI] 0.810) and 12.04 ng/dL for the RSST (sensitivity 83.15%, specificity 57%; YI 0.401). The optimal PAC cut-off value for classifying aldosterone-producing adenoma and idiopathic hyperaldosteronism was 18.12 ng/dL for the SSST (sensitivity 73.5%, specificity 79.5%). No patients experienced adverse events during the SSST.Conclusion: The SSST is safe and convenient for PA diagnosis. The accuracy of the SSST for a confirmatory diagnosis of PA was better than that of the RSST. The SSST is a reliable alternative for PA confirmation in Chinese individuals.Abbreviations: APA = aldosterone-producing adenoma; ARR = aldosterone to renin ratio; AVS = adrenal vein sampling; CT = computed tomography; EH = essential hypertension; IHA = idiopathic hyperaldosteronism; MRI = magnetic resonance imaging; PA = primary aldosteronism; PAC = plasma aldosterone concentration; PRA = plasma renin activity; ROC = receiver operating characteristic; RSST = recumbent saline suppression test; SSST = seated saline suppression test; YI = Youden index     

Personalized Treatment of Patients With Primary Aldosteronism

Primary aldosteronism (PA) is a highly prevalent yet underdiagnosed secondary cause of hypertension. PA is associated with increased cardiovascular and renal morbidity compared with patients with primary hypertension. Thus, prompt identification and targeted therapy of PA are essential to reduce cardiovascular and renal morbidity and mortality in a large population with hypertension. Unilateral adrenalectomy is preferred for lateralized PA as the only potentially curative therapy. Surgery also mitigates the risk of cardiovascular and renal complications associated with PA. Targeted medical therapy, commonly including a mineralocorticoid receptor antagonist, is offered to patients with bilateral PA and those who are not surgical candidates. Novel therapies, including nonsteroidal mineralocorticoid receptor antagonists and aldosterone synthase inhibitors, are being developed as alternative options for PA treatment. In this review article, we discuss how to best individualize therapy for patients with PA.     

Case report: schwannoma arising from the unilateral adrenal area with bilateral hyperaldosteronism

Background

We report a rare case of a juxta-adrenal schwannoma that could not be discriminated from an adrenal tumor before surgical resection and was complicated by bilateral hyperaldosteronism. To the best of our knowledge, this is first case in which both a juxta-adrenal schwannoma and hyperaldosteronism co-existed.

Case presentation

A 69-year-old male treated for hypertension was found to have a left supra-renal mass (5.8?×?5.2 cm) by abdominal computed tomography. His laboratory data showed that his plasma aldosterone concentration (PAC) was within the normal range, but his plasma renin activity (PRA) was reduced, resulting in an increased aldosterone/renin ratio (ARR). Load tests of captopril or furosemide in the standing position demonstrated autonomous aldosterone secretion and renin suppression. Adrenal venous sampling (AVS) with ACTH stimulation indicated bilateral hypersecretion of aldosterone. A left supra-renal tumor was resected because of the possibility of malignancy and was found to be a benign schwannoma arising from the juxta-adrenal region together with an adrenal gland. The dissected left adrenal gland was morphologically hyperplastic in the zona glomerulosa, but was immunohistochemically negative for CYP11B2 (aldosterone synthase). Multiple CYP11B2-positive adrenocortical micronodules were detected in the adrenal gland, indicating micronodular hyperplasia. Although bilateral aldosteronism was indicated by AVS before the operation, the PRA, PAC and ARR values were within their respective reference ranges after resection of the unilateral tumor, suggesting that the slight increase in hormone secretion from the remaining right-sided lesion could not be detected after resection.

Conclusion

A clinical and morphologic diagnosis of juxta-adrenal schwannoma is difficult, particularly in a case of hyperaldosteronism, as shown in this case. These data suggest the complexity and difficulty diagnosing adrenal incidentaloma.

     

Polycystic ovary syndrome: Implications of measurement of plasma aldosterone, renin activity and progesterone

A positive correlation between aldosterone, inflammatory parameters, blood pressure and metabolic abnormalities in polycystic ovary syndrome (PCOS) has been reported in the early estrogenic phase. The aim of the study was to measure plasma aldosterone, plasma renin activity (PRA) and progesterone on the 21st day of the cycle, in women with PCOS and to consider the interrelationships between these hormones. Sixty-six consecutive normal BMI women with PCOS (median age 24 years, range 21-28 years) and 53 age- and body mass index-matched healthy controls were enrolled in the study. Aldosterone, aldosterone/PRA ratio (ARR) and Homeostasis Model Assessment (HOMA) index were significantly higher (p<0.0001) in PCOS women than controls. Positive correlations were found in PCOS but not in controls between (i) progesterone and aldosterone, (ii) aldosterone and PRA, (iii) PRA and progesterone. Mean blood pressures were within the normal range but significantly higher in PCOS than controls. The increase of plasma aldosterone, ARR and blood pressure in PCOS compared with controls is consistent with an increased mineralocorticoid effector mechanism in PCOS; prolonged therapy with spironolactone could counteract both the hyperandrogenism and reduce future cardiovascular risk.     

Effect of L-dopa and bilateral nephrectomy on the aldosterone response to metoclopramide

The dopaminergic antagonist, metoclopramide (MCP) causes an increase in plasma aldosterone (PA) by a processnot well delineated. To investigate the mechanism of action of metoclopramide (MCP), studies were performed in rats after pre-treatment with L-dihydroxy-phenylalanine (L-dopa) and after bilateral nephrectomy. Intra-arterial MCP (200 μg/kg) resulted in a significant elevation in PA and prolactin (PRL) at 5 min and plasma renin activity (PRA) at 10 min without altering serum potassium levels. Pre-administration of L-dopa (30 mg/kg) delayed and markedly blunted PA, PRL and PRA resonses to MCP. In 7 rats, studied 30 hours after bilateral nephrectomy, the PRA was measurable (2.5 ± 0.4 ng/ml h^?1) but displayed no response to MCP. In contrast, the PA and PRL responses to MCP were not significantly affected. L-dopa induced suppression of PRA and PA was prevented by pre-administration of MCP. These results suggest that dopaminergic modulation of PA secretion occurs independently of the renin-angiotensin system.     

Structure-based design of aliskiren,a novel orally effective renin inhibitor

Hypertension is a major risk factor for cardiovascular diseases such as stroke, myocardial infarction, and heart failure, the leading causes of death in the Western world. Inhibitors of the renin-angiotensin system (RAS) have proven to be successful treatments for hypertension. As renin specifically catalyses the rate-limiting step of the RAS, it represents the optimal target for RAS inhibition. Several peptide-like renin inhibitors have been synthesized previously, but poor pharmacokinetic properties meant that these compounds were not clinically useful. We employed a combination of molecular modelling and crystallographic structure analysis to design renin inhibitors lacking the extended peptide-like backbone of earlier inhibitors, for improved pharmacokinetic properties. This led to the discovery of aliskiren, a highly potent and selective inhibitor of human renin in vitro, and in vivo; once-daily oral doses of aliskiren inhibit renin and lower blood pressure in sodium-depleted marmosets and hypertensive human patients. Aliskiren represents the first in a novel class of renin inhibitors with the potential for treatment of hypertension and related cardiovascular diseases.     

Effect of bromocriptine on the control of plasma aldosterone diurnal variation in normal supine man.

In order to investigate the role of prolactin in the control of the circadian rhythm of plasma aldosterone (PA), plasma renin activity (PRA), cortisol (PC), aldosterone and prolactin (PRL) levels were determined in samples at 4-hour intervals from 5 normal supine men over a period of 24 h under basal conditions and subsequently over a period of 24 h during suppression of prolactin release by bromocriptine (CB-154). After suppression of prolactin, statistically signific1nt circadian rhythms in PC and PA have been detected with a moderate decrease of PA concentration, while the PC level remained unalterated. PRA rhythmicity persisted with a significant shift of acrophase and remarkable reduction of plasma levels. Moreover, during CB administration a significant correlation was obtained between PA and PC, while no correlation was detected between PA and PRA. These data are consistent with the following concepts: (a) the prolactin does not play a significant role in the regulation of circadian rhythm and concentration of plasma aldosterone in normal supine men, and (b) bromocriptine induces a remarkable reduction of PRA and a variable decrease in plasma aldosterone, but it does not influence the secretion of cortisol in normal subjects.     

Effect of atrial natriuretic peptide on adrenal renin and aldosterone

The effect of atrial natriuretic peptide (ANP) on adrenal renin and aldosterone was investigated in anesthetized rats. Under pentobarbital anesthesia 40 mg/kg), intravenous infusion of ANP (0.25 micrograms/kg/min) for 45 min failed to alter the adrenal renin, adrenal aldosterone, and plasma aldosterone (PA). In this condition, intraperitoneal injection of ACTH (10 micrograms/kg) significantly increased the adrenal renin (from 2.4 +/- 0.1 to 5.0 +/- 0.08 ng/mg protein/h, P less than 0.05), adrenal aldosterone (from 13.6 +/- 1.3 to 22.7 +/- 2.3 ng/mg protein, P less than 0.01) and PA (from 59.8 +/- 5.8 to 75.5 +/- 7.4 ng/dl, P less than 0.05), respectively. Under ACTH stimulation, ANP infusion induced significant decreases in adrenal renin (from 5.0 +/- 0.08 to 2.8 +/- 0.2 ng/mg protein/h, P less than 0.05), adrenal aldosterone (from 22.7 +/- 2.3 to 16.2 +/- 1.8 ng/mg protein, P less than 0.05) and PA (from 75.5 +/- 7.4 to 61.6 +/- 4.9 ng/dl). These results suggest a possible role for adrenal renin in the mechanism underlying the inhibitory effect of ANP on aldosterone production in vivo.     

Effect of prolonged ACTH stimulation on adrenal renin and aldosterone

Changes in adrenal renin, which have been regarded as mediator of aldosterone secretion in the adrenal gland, following prolonged ACTH treatment were investigated in male Wistar rats. After 2 days of daily sc injection of ACTH (Cortrosyn-Zinc, 50 micrograms/day), parallel increases in adrenal renin and aldosterone, and plasma aldosterone (PA) were induced. The plasma renin activity (PRA) was slightly but not significantly decreased. Prolonged treatment with ACTH for 8 days increased the adrenal renin, causing a marked reduction in the adrenal aldosterone concentration. The degree of decrease in the PRA was again not significant and similar to that after 2 days of ACTH treatment. Contrary to previout reports which have indicated participation of adrenal renin in the regulation of aldosterone secretion in the adrenal gland, the present results showed reciprocal changes in adrenal renin and aldosterone after prolonged treatment with ACTH. The present findings suggest a complicated relation between adrenal renin and aldosterone secretion in the adrenal gland.     

Role of the renin-angiotensin-aldosterone system in collecting duct-derived endothelin-1 regulation of blood pressure

Renal collecting duct (CD)-specific knockout of endothelin-1 (ET-1) causes hypertension and impaired Na excretion. A previous study noted failure to suppress the renin-angiotensin-aldosterone axis in these knockout (KO) mice, hence the current investigation was undertaken to examine the role of this system in CD ET-1 KO. Renal renin content was similar in kidneys from CD ET-1 KO and control mice during normal Na intake; high-Na intake suppressed renal renin content to a similar degree in KO and control. Plasma renin concentrations paralleled changes in renal renin content. Valsartan, an angiotensin receptor blocker (ARB), abolished the hypertension in CD ET-1 KO mice during normal Na intake. High-Na intake + ARB treatment increased blood pressure in CD ET-1 KO, but not in controls. High-Na intake was associated with reduced Na excretion in CD ET-1 KO animals, but no changes in water excretion or creatinine clearance were noted. Spironolactone, an aldosterone antagonist, also normalized blood pressure in CD ET-1 KO mice during normal Na intake, whereas high-Na intake + spironolactone raised blood pressure only in CD ET-1 KO animals. In summary, hypertension in CD ET-1 KO is partly due to angiotensin II and aldosterone. We speculate that CD-derived ET-1 may regulate, via a novel pathway, renal renin production.     

Increased aldosterone/renin quotient in obese hypertensive women: a novel role for low-density lipoproteins?

Obesity, especially visceral obesity, is strongly associated with arterial hypertension. Indeed, obesity hypertension has to be considered as the most common form of essential hypertension. However, the exact nature of the relationship between obesity and increased blood pressure remains poorly understood. Involvement of renin-independent mechanisms has been suggested in adrenal stimulation of aldosterone secretion in obese patients. This investigation examined the plasma levels of renin, aldosterone, insulin, and HDL and LDL in obese hypertensive and obese normotensive women. The group of hypertensive obese women showed significantly reduced plasma levels of renin and increased aldosterone/renin quotient (ARQ) compared to obese normotensive women. Plasma aldosterone levels were not significantly different between hypertensive and normotensive obese women. In addition, plasma levels of LDL-cholesterol in the hypertensive obese group were significantly increased in comparison to the obese normotensive group. No differences were observed in HDL-cholesterol or total cholesterol/HDL-C ratios between the two groups. We therefore examined the effect of LDL on angiotensin II-stimulated aldosterone release from human adrenocortical H295R cells. Treatment of adrenocortical cells with LDL led to a sensitization towards stimulation by angiotensin II, dramatically increasing angiotensin II-induced aldosterone production, so the increased aldosterone/renin ratio observed in the hypertensive group may be due to the enhanced LDL levels in these patients and/or other adipocyte-derived mineralocorticoid-stimulating factors.     

Comparison of 24-h Urinary Aldosterone Level and Random Urinary Aldosterone-to-Creatinine Ratio in the Diagnosis of Primary Aldosteronism

Background

Historically, urinary aldosterone level measurement was a commonly employed confirmatory test to detect primary aldosteronism (PA). However, 24-h urine collection is inconvenient and cumbersome. We hypothesized that random urinary aldosterone measurements with correction for creatinine concentration might be comparable to 24-h urinary aldosterone levels (Uald-24 h) in the diagnosis of PA.

Methods

The non-concurrent prospective study was conducted between June 2006 and March 2008 in patients admitted for confirmation of aldosteronism by salt loading test. A 24-h urine sample, which was collected during hospitalization on the day before saline infusion testing after restoration of serum hypokalemia, was collected from all subjects. Moreover, participants were asked to collect a first bladder voiding random urine sample during clinic visits. Uald-24 h and the random urinary aldosterone-to-creatinine ratio (UACR) were calculated accordingly.

Results

A total of 102 PA patients (71 patients diagnosed of aldosterone-producing adenoma, 31 with idiopathic hyperaldosteronism) and 65 patients with EH were enrolled. The receiver operating characteristic curve showed comparable areas under the curves of UACR and Uald-24 h. The Bland-Altman plot showed mean bias but no obvious heteroscedasticity between the two tests. When using random UACR >3.0 ng/mg creatinine as the cutoff value, we obtained a specificity of 90.6% to confirm PA from essential hypertension.

Conclusions

Our study reinforce that the diagnostic accuracy of random UACR was comparable to that of Uald-24 h in PA patients. With the quickness and simplicity of the UACR method and its equivalence to Uald-24 h, this assay could be a good alternative diagnostic tool for PA confirmation.