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The aldosterone/renin ratio (ARR) is currently considered the most reliable approach for case detection of primary aldosteronism (PA). ACE (Angiotensin-converting enzyme) inhibitors are known to raise renin and lower aldosterone levels, thereby causing false-negative ARR results. Because ACE inhibitors lower angiotensin II levels, we hypothesized that the aldosterone/equilibrium angiotensin II (eqAngII) ratio (AA2R) would remain elevated in PA. Receiver operating characteristic curve analysis involving 60 patients with PA and 40 patients without PA revealed that the AA2R was not inferior to the ARR in screening for PA. When using liquid chromatography-tandem mass spectrometry to measure plasma aldosterone concentration, the predicted optimal AA2R cutoff for PA screening was 8.3 (pmol/L)/(pmol/L). We then compared the diagnostic performance of the AA2R with the ARR among 25 patients with PA administered ramipril (5 mg/day) for 2 weeks. Compared with basally, plasma levels of equilibrium angiotensin I (eqAngI) and direct renin concentration increased significantly ( P P P

INTRODUCTION The aldosterone/renin ratio is the initial screening test for primary hyperaldosteronism (PHA), but little data exists regarding ethnic variations in this. METHODS Following clinical observation of a high prevalence of abnormal aldosterone/renin ratio (ARR) in patients of African-origin, we retrospectively reviewed all ARR measurements in a single centre over 10 years. Rates of hypokalaemia, intraventricular septal thickness (IVS, by echocardiography) and adrenal imaging were recorded when available. RESULTS Aldosterone/renin ratio was available in 1473 patients, and abnormal in 374 (25.4%). Abnormal ARR was observed in 305/1349 (22.6%) of European-origin and 69/124 (55.6%) of African-origin patients (P

Background Plasma renin activity (PRA) is generally increased in patients with pheochromocytoma (PCC) due to low circulating plasma volume and activation of β-1 adrenergic receptor signaling. However, there has been no study on the aldosterone renin ratio (ARR) in patients with PCC. To elucidate the issue, this study aimed to determine the PRA, plasma aldosterone concentration (PAC), and ARR in patients with PCC and compare them with those in patients with subclinical Cushing’s syndrome (SCS) and non-functioning adrenal adenoma (NFA). Methods In this retrospective single-center, cross-sectional study, 67 consecutive patients with adrenal tumors (PCC (n = 18), SCS (n = 18), and NFA (n = 31)) diagnosed at Kobe University Hospital between 2008 and 2014 were enrolled. Results PRA was significantly higher in patients with PCC than in those with SCS and NFA (2.1 (1.3 ~ 2.8) vs. 0.7 (0.5 ~ 1.8) and 0.9 (0.6 ~ 1.4) ng/mL/h; p = 0.018 and p = 0.025). Although PACs were comparable among the three groups, ARR was significantly lower in patients with PCC than in those with SCS and NFA (70.5 (45.5 ~ 79.5) vs. 156.0 (92.9 ~ 194.5) and 114.9 (90.1 ~ 153.4); p = 0.001 and p 1.55 ng/mL/h showed a sensitivity of 70.0% and specificity of 80.6%. Interestingly, ARR Conclusions ARR decreased in patients with PCC, which was a more sensitive marker than PRA. Further study is necessary to understand the usefulness of this convenient marker in the detection of PCC. Trial registration This study was not registered because of the retrospective analysis.

Aldosterone/renin ratio (ARR) >200 [(pg/mL)/(ng/mL/hr)] is a widely accepted threshold to screen for primary aldosteronism (PA) (1). Because using ARR as a sole index leads to excessive inclusion of cases with low renin essential hypertension, it may be desirable to combine ARR with a minimum plasma aldosterone concentration (PAC) value to increase diagnostic accuracy, but currently there is no consensus on the minimum PAC value. Therefore, we carried out a single-center, retrospective study to investigate optimal PAC cutoff to be used with ARR >200. The subjects were 385 individuals (240 female and 145 male) with ARR >200 who underwent PA screening tests between 2010 and 2015. They were diagnosed according to the Japan Endocrine Society guideline (2) with either PA or essential hypertension (EH). The optimal cutoff value for baseline PAC that best distinguished between PA and EH was calculated. Of the 385 subjects, 297 were diagnosed with PA and 88 with EH. Of 194 PA patients who underwent adrenal venous sampling, 141 exhibited aldosterone hypersecretion from both adrenal glands, and 53 were diagnosed with aldosterone-producing adenoma (APA) on the basis of adrenalectomy. There was no difference between the PA (n = 194) and EH (n = 88) groups in terms of age, body mass index, or glucose and lipid profiles. Receiver operating characteristic curve analysis found that the optimal baseline PAC for distinguishing between PA and EH was 171 pg/mL, which provided a sensitivity of 0.75 and a specificity of 0.65 (area under the curve 0.718 and 95% confidence interval 0.656-0.780). Baseline PAC was ≥171 pg/mL for all 53 subjects with APA (minimum 171 pg/mL, maximum 943 pg/mL, and median 341 pg/mL), and if the cutoff value for baseline PAC is set at 171 pg/mL, it is unlikely that significant cases of APA will be overlooked in PA screening using ARR >200. Combining PAC ≥171 pg/mL with ARR >200 increases diagnostic accuracy for PA without compromising APA detection. Reference: (1)Hiramatsu et al., Arch Intern Med. 1981 Nov;141(12):1589-93. (2) Nishikawa et al., Endocr J. 2011;58(9):711-21.

The aldosterone-renin ratio is the most popular test for the case detection of primary aldosteronism, which entails the most common, albeit overlooked, form of endocrine secondary hypertension. A major hindrance to the clinical use of the aldosterone-renin ratio depends on the difficulty of achieving the calculation of this ratio, given that laboratories provide plasma aldosterone in different units of measurement, and renin is measured as plasma renin activity or direct active renin. We have therefore developed an App, which can be downloaded from the ESH website and the Apple store, to assist practising physicians in performing this calculation. Our hope is that this simple tool will help in increasing the detection rate of primary aldosteronism and ultimately the long-term cure of many hypertensive patients.

Background Current guidelines recommend use of the aldosterone‐renin ratio ( ARR ) for the case detection of primary aldosteronism followed by confirmatory tests to exclude false‐positive results from further diagnostic workup. We investigated the hypothesis that this could be unnecessary in patients with a high ARR value if the quantitative information carried by the ARR is taken into due consideration. Methods and Results We interrogated 2 large data sets of prospectively collected patients studied with the same predefined protocol, which included the captopril challenge test. We used an unambiguous diagnosis of aldosterone‐producing adenoma as reference index. We also assessed whether the post‐captopril ARR and plasma aldosterone concentration fall furnished a diagnostic gain over baseline ARR values. We found that the false‐positive rate fell exponentially, and, conversely, the specificity increased with rising ARR values. At receiver operating characteristics curves and diagnostic odds ratio analysis, the high baseline ARR values implied very high positive likelihood ratio and diagnostic odds ratio values. The baseline and post‐captopril ARR showed similar diagnostic accuracy (area under the receiver operating characteristics curve) in both the exploratory and validation cohorts, indicating lack of diagnostic gain with this confirmatory test (between‐area under the curve difference, 0.005; 95% CI , −0.031 to 0.040; P =0.7 for comparison, and 0.05; 95% CI , −0.061 to 0.064; P =0.051 for comparison, respectively). Conclusions These results indicate that the ARR conveys key quantitative information that, if properly used, can simplify the diagnostic workup, resulting in saving of money and resources. This can offer the chance of diagnosis and ensuing adrenalectomy to a larger number of hypertensive patients, ultimately resulting in better control of blood pressure.

Recognition that primary aldosteronism (PAL) is a common specifically treatable form of hypertension and that most patients are normokalemic has led to a marked increase in demand for aldosterone/renin ratio (ARR) testing as a means of screening for this disorder. The value of this screening test depends on an appreciation of many factors (such as diet, posture, time of day, presence of hypokalemia, medications, age, and renal function), which can affect the results, on the care with which these factors are either controlled or their effects taken into account, and on access to reliable and reproducible assays for renin and aldosterone. Even then, physiological day-to-day variability reduces the value of a single estimation, and repeated testing is necessary before a decision that PAL is highly likely (warranting further testing) or highly unlikely can be made. Provided that testing of aldosterone suppressibility is always carried out to confirm or exclude the diagnosis, and the subtype is determined by hybrid gene testing and adrenal venous sampling, wide application of the ARR can have a major beneficial clinical impact with improved therapeutic outcomes, including possible cure in those with unilateral disease.

The major role of the aldosterone/renin ratio (ARR) test is in screening hypertensive patients for primary aldosteronism (PA). Although currently the most reliable and popular approach, the value of this screening test depends on an appreciation of factors (such as antihypertensive and other medications, posture, time of day, age, gender, phase of menstrual cycle, diet, presence of hypokalemia, medications, and renal function) which can affect the results, on the care with which either these factors are controlled or their effects taken into account, and on access to reliable and reproducible assays for renin and aldosterone. Even then, physiological day-to-day variability reduces the value of a single estimation, and repeated testing is advisable before deciding whether or not to proceed to further diagnostic work-up. Provided that testing of aldosterone suppressibility is always carried out in order to confirm or exclude the diagnosis, and adrenal venous sampling is employed to differentiate unilateral from bilateral forms, wide application of the ARR can have a major beneficial clinical impact, with improved therapeutic outcomes, including possible cure in those with unilateral disease and improved quality of life.

ummaryIntroduction From an early age, hypertension can damage blood vessels through multiple mechanisms. The aim of this study was to evaluate the presence of vascular damage and whether it is associated with the mineralo- and glucocorticoid profiles of hypertensive children. Subjects and methods We studied 64 hypertensive children. Anthropometric parameters and serum aldosterone (SA), plasma renin activity (PRA), aldosterone/renin ratio (ARR), cortisol (F) and cortisone (E) were measured. The serum F/E ratio was calculated to estimate the activity of the enzyme 11β-HSD2. Vascular damage was determined by carotid intima-media thickness (cIMT) and flow-mediated dilation of the brachial artery (FMD) on ultrasound. Results (median; Q1–Q3) Of the patients observed, 39% were females, and the median value for age (years) was 11·2 (9·1–13·3), for BMI (SDS) was 1·36 (0·84–1·80), for body fat mass (%) was 28·3 (17·8–36·0), for SBP index was 1·17 (1·12–1·25) and for the DBP index was 1·27 (1·16–1·36). Measurements revealed an SA level higher than 491 pmol/l in 4/64 patients, a PRA value lower than 0·5 ng/ml/h in 2/64, an ARR higher than 10 in 3/64 and serum F/E ratio higher than 4·3 in 10/64. The median brachial FMD (%) was 8·41 (5·61–10·91), and the median cIMT (mm) was 0·40 (0·37–0·43). The ARR was the only variable that explained changes in cIMT (β = 0·571, R2 = 0·315, P

This letter1 reveals some confusion on what is reproducible in clinical terms and a poor understanding of what the plasma aldosterone concentration to renin ratio (ARR) is used for, that is the screening of primary aldosteronism based on an arbitrary cutoff. In the largest prospective study available that used a conclusive diagnosis of aldosterone-producing adenoma as the referent, this cutoff was determined to be 25.86 (with plasma aldosterone concentration in nanograms per deciliter and plasma renin activity in nanograms per milliliter per hour).2 Therefore, the fact that, “the upper of the 2 ‘limits of agreement’ in plot B is 2.1” was high1 is totally irrelevant, because any value exceeding this cutoff is considered to suggest the presence of primary …

To the Editor: Rossi et al recently concluded that the aldosterone:renin ratio (ARR) is reproducible.1 However, we think that several common errors were performed in their data interpretation, as described below. In the Bland-Altman plot B (Figure 1 in Reference 1), the large differences in repeat measurements are overlooked on the basis that only 7% of points lay outside of the between-test “95% CIs,” by which they imply the Bland-Altman “limits of agreement.” These are constructed using the mean difference ±1.96 SDs, and so by definition alone, will always contain ≈95% of …

The plasma aldosterone concentration:renin ratio (ARR) is widely used for the screening of primary aldosteronism, but its reproducibility is unknown. We, therefore, investigated the within-patient reproducibility of the ARR in a prospective multicenter study of consecutive hypertensive patients referred to specialized centers for hypertension in Italy. After the patients were carefully prepared from the pharmacological standpoint, the ARR was determined at baseline in 1136 patients and repeated after, on average, 4 weeks in the patients who had initially an ARR ≥40 and in 1 of every 4 of those with an ARR r =0.69; P

The aldosterone-renin ratio (ARR) is widely used to screen for primary aldosteronism, and may reflect a relative excess of aldosterone secretion compared with renin secretion. Excess aldosterone may have a detrimental effect on vascular stiffness. We therefore hypothesized that ARR and aldosterone are independently correlated with pulse wave velocity (PWV) in hypertensive patients.The study consisted of 438 hypertensive patients. Serum aldosterone and plasma renin activity were measured in a sitting position using standard techniques. The PWV was determined by measuring the heart to femoral PWV (hfPWV) and brachial to ankle PWV with a VP-2000 pulse wave unit.Group 1 was defined as patients with ARR of at least 20 (n = 53) with serum aldosteroneor= 12 ng/dl, while the remainder comprised group 2. Comparisons between the two groups reveal group 1 tended to have higher age, significantly higher proportion of women and higher systolic/diastolic blood pressure. Patients in group 1 also had a significantly higher index of central arterial stiffness (hfPWV 1048 +/- 202 vs 978 +/- 182, P = 0.010) compared with group 2. Multiple linear regression revealed that aldosterone, but not the ARR, is significantly associated with hfPWV but not brachial to ankle PWV, after controlling for age, systolic blood pressure and heart rate at the time of PWV measurement, body mass index, gender, low-density lipoprotein-cholesterol, triglyceride, high-density lipoprotein-cholesterol, blood pressure medication and statins.Serum aldosterone is significantly associated with central aortic PWV in hypertensive patients. The results demonstrate a possible role for aldosterone in developing central aortic stiffness and increased PWV in hypertensive patients.

The ratio of aldosterone to renin in plasma was measured in samples collected from 79 hypertensive patients. Eighteen patients with primary aldosteronism had ratios ranging from 25 to 677 (mean 183) when measured on 34 occasions, while 16 normal subjects had ratios of 3.3-21 (mean 11.3). Of the remaining 61 patients with ratios ranging from 1.8 to 184, 15 patients have ratios greater than 25 and are under investigation for primary aldosteronism, which appears highly likely in five and has been excluded in two. The aldosterone/renin ratio appears promising as a screening test for primary aldosteronism. Consistency and the effects of sodium and potassium balance and of antihypertensive medications require further study.

Plasma aldosterone measurements using a new radioimmunoassay technique were included in a component analysis of the renin-aldosterone-sodium system. The studies involved 27 normal subjects and 51 patients with essential hypertension characterized by low, normal or high plasma renin activity. Noon plasma aldosterone concentrations closely reflected the state of aldosterone secretion. Thus, in normal subjects, plasma aldosterone values exhibited a relationship to the daily urinary sodium excretion similar to that for urinary aldosterone excretion. Moreover, plasma aldosterone levels and the simultaneously measured plasma renin activity were linearly correlated over a wide range of sodium balance, again pointing to a key role for renin in the control of plasma aldosterone levels. In 21 patients with normal renin essential hypertension, the absolute levels of plasma aldosterone and their relation to plasma renin levels were similar to those observed in normal subjects. In 14 patients with high renin hypertension concurrent plasma aldosterone levels were commensurately elevated. A deflection of this renin-aldosterone interaction observed in some high renin patients appeared consequent to potassium depletion. In contrast, in 14 of 16 patients with low renin essential hypertension, noon plasma aldosterone concentrations, under conditions of normal or moderately high dietary sodium, were higher relative to simultaneous plasma renin activity, resulting in an abnormal plasma aldosterone to renin ratio above 10. This abnormal renin-aldosterone interrelation could prove useful for identifying and further characterizing patients within the low renin hypertension category. In hypertensive patients, plasma aldosterone measurements can be used interchangeably with urinary aldosterone excretion rates but for full meaning they must still be related to an index of sodium balance such as the daily rate of sodium excretion. Moreover, they have special value for short-term studies and for evaluating aldosterone secretion in states of hepatic or renal insufficiency and perhaps in edematous states in which impaired aldosterone metabolism or renal excretion occurs.

SummaryIn pancreatectomized or ne-phrectomized dogs K+-loading by infusion of 2 mEq KCl/kg/hr produces ECG evidence of prelethal hyperkalemic cardiotox-icity when serum K+ reaches about 10 mEq/ liter. If, however, the operations are combined and the KC1 infused into nephrecto-mized-pancreatectomized animals, there is a highly significant increase in cardiac sensitivity to hyperkalemia; prelethal ECG changes appear when mean serum K+ is ∼7.7 mEq/liter (P < 0.001), a level almost identical with that found in dogs loaded with K+ 4 hr after bilateral adrenalectomy. Treatment of nephrectomized-pancreatectomized dogs with aldosterone, renin, or insulin decreases cardiac sensitivity to K+ and raises the prelethal cardiotoxic level of serum K+ to the range found in controls. The results suggest the possibility of a role for insulin in stimulation of aldosterone secretion by KC1 infusion.