Screening Test For Primary Aldosteronism Research Articles

Abstract P432: Screening for Primary Aldosteronism: Effect of Test and Cutoff Level on Positivity Rate

Background: The 2016 guidelines of the Endocrine Society proposed a screening test for primary aldosteronism (PA) based on an aldosterone renin ratio (ARR) ≥30. However, a plasma renin activity (PRA) suppressed to <1 ng/mL/h may indicate PA status better than the ARR. Methods: We conducted a retrospective analysis to compare the effectiveness of various screening tests for PA in a cohort of 94,829 consecutive patients who underwent ARR testing at Quest Diagnostics. The tests that were compared include ARR ≥20, ARR ≥30, PRA <1 ng/mL/h, and PRA <0.5 ng/mL/h. This comparison was made because the ARR tests may not be highly sensitive, while the PRA tests may not be highly specific. We also analyzed differences in test volume and positivity rate by region, race, ethnicity, and the time of day when the test was performed. Results: We observed that PRA <1 ng/mL/h identified 2.2 times as many PA cases as ARR ≥20 and 3.3 times as many cases as ARR ≥30. Likewise, PRA <0.5 ng/mL/h identified 1.3 times as many cases as ARR ≥20 and 1.9 times as many cases as ARR ≥30 (Table). We also found that PA positivity rates using ARR ≥20, ARR ≥30, PRA <1 ng/mL/h, and PRA <0.5 ng/mL/h were higher for tests performed before noon than after noon. Additionally, positivity rates were similar across US regions, although the Midwest had lower positivity for ARR tests than PRA tests, and the West had lower positivity for PRA tests than ARR tests. The PRA-based test continued to be positive more frequently than the two ARR-based tests regardless of race; however, non-Hispanic Black patients had a higher positivity rate than Hispanic, non-Hispanic White, and Asian patients, irrespective of the test used. Conclusions: Our data show that compared to PRA <1 ng/mL/h and <0.5 ng/mL/h, the ARR screening tool set at ≥20 or ≥30 potentially misses many patients with PA. If future prospective studies confirm this finding, one of the two suppressed PRA-based tests could become the preferred screening tool for PA.

POLYCYSTIC OVARY SYNDROME (PCOS) AND ITS TREATMENT AS CAUSE OF SECONDARY ALDOSTERONISM: A DOG CHASING ITS TAIL

Objective: Polycystic Ovary Syndrome (PCOS) is a complex endocrine-metabolic disorder affecting about 7% of childbearing women. PCOS is characterized by anovulation, hyperandrogenism, insulin resistance and it is associated with an increased cardiovascular risk. PCOS patients may exhibit high blood pressure and signs of hydro-saline retention. Therefore, clinicians would be interested in performing hormonal screening for secondary hypertension. Design and method: We perform the aldosterone/direct renin concentration ratio as a screening test for primary aldosteronism (PA). The test was proceed after serum potassium correction and previous a wash-out period of interfering medications. The recumbent saline suppression test was performed with infusion of 2L NaCl 0.9% in 4 hours under standardized salt intake (9gr/24h). Aldosterone and direct renin were determined by chemiluminescent immunoassay technology (DiaSorin®). Results: A 33yrs old woman attended our renal outpatient clinic because of recurrent episodes of generalized swelling, diuresis contraction and fluid retention. The patient, known for PCOS, was treated with combined oral contraceptives and loop diuretics. She had no history of hypertension, but she repeatedly displayed very high aldosterone values. Clinical examination was unremarkable, in-office and home blood pressure values were normal. Laboratory data showed normal renal function and the absence of acid-base disorders; serum potassium was at lower limit of normal. A CT-scan showed normal adrenal glands. We performed a recumbent saline suppression test, previous a wash-out period of oral contraceptives (> 6 weeks) and loop diuretics (> 2 weeks). The results listed below are consistent with a baseline hyperaldosteronism with normal aldosterone adrenal response to volume expansion, excluding PA. Several years before, the same results were presented, without suspension of the oral contraceptives. Conclusions: In patients with PCOS the increased adrenal production of aldosterone is usually secondary and independent from the renin-aldosterone axis (direct stimulation of adrenal zona glomerulosa via testosterone). Other iatrogenic factors may affect the renin-aldosterone values, such us the use of oral contraceptives and diuretics. Therefore, a confirmatory test performed under standardized conditions is often required, in order to exclude primary versus secondary forms of hyperaldosteronism.

Performance of aldosterone-to-renin ratio before washout of antihypertensive drugs in screening of primary aldosteronism.

The aim of this study is to evaluate performance of aldosterone-to-renin ratio (ARR) before washout of antihypertensive drugs as a screening test for primary aldosteronism (PA). This retrospective analysis included consecutive patients suspected of having secondary hypertension during a period from January 2017 to May 2022 at authors' institute. For inclusion in the final analysis, ARR must be available prior to as well as after discontinuation of antihypertensives. Patients with ARR ≥2.4(ng/dL)/(μIU/mL) after washout proceeded to confirmatory tests. Diagnosis of PA was established based on positive result of the confirmatory test. Diagnostic accuracy of ARR prior to the washout in predicting PA are shown as sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). The analysis included a total of 1306 patients [median age of 50.2 (41.0-59.0) years, 64.0% male]. Confirmatory tests showed PA in 215(16.5%) patients and essential hypertension (EH) in the remaining 1091(83.5%) patients. In comparison to the second screening test, the first screening test (before washout of antihypertensives) yielded lower plasma aldosterone and higher renin, and consequently lower ARR in both the PA and EH groups. At a cutoff of 0.7(ng/dL)/(μIU/ml), ARR before washout had 96.3% sensitivity, 61.2% specificity, 0.33 PPV and 0.99 NPV. At a lower cutoff of 0.5(ng/dL)/(μIU/ml), the sensitivity, specificity, PPV and NPV are 97.7%, 52.0%, 0.29 and 0.99. ARR prior to washout of antihypertensives is a sensitive screening test for PA. Washout of antihypertensives could be omitted and further investigation for PA is not warranted if ARR was ≤ 0.7(ng/dL)/(μIU/ml) before washout.

Comparison of plasma aldosterone measured by chemiluminescence immunoassay and liquid chromatography-tandem mass spectrometry in screening test for primary aldosteronism

BackgroundWhether chemiluminescence immunoassay (CLIA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for plasma aldosterone concentration (PAC) measurement can be used interchangeably in primary aldosteronism (PA) screening is still controversial. The purpose of this study was to compare CLIA to LC-MS/MS for PAC measurement in PA screening. MethodsAll participants underwent aldosterone-to-renin ratio (ARR) testing. PA was diagnosed by captopril challenge test or saline infusion test. PAC in screening test was measured with CLIA and LC-MS/MS. Plasma direct renin concentration in screening and confirmatory test was measured with CLIA. The concordance between CLIA and LC-MS/MS for PAC measurement in PA screening was analyzed. ResultsTwenty-one healthy volunteers, 61 patients with essential hypertension (EH) and 43 PA patients were enrolled. Median PAC by CLIA was 84.7 % higher than that by LC-MS/MS in screening test (P < 0.001). A positive correlation of PAC was observed between the two assays (Pearson r coefficient 0.770, P < 0.001). When ARR was used in differentiating PA from EH, there was no difference in the area under the receiver operating characteristic curve between CLIA and LC-MS/MS for PAC measurement (0.968 vs 0.950, P = 0.249). ConclusionCLIA and LC-MS/MS for PAC measurement exhibited high and comparable efficacy in PA screening. CLIA is a reliable and feasible alternative in PA screening test.

Long-Term Follow-Up of Patients With Elevated Aldosterone-to-Renin Ratio but Negative Confirmatory Test: The Progression of Primary Aldosteronism Phenotypes.

About 10% of patients with arterial hypertension have a positive screening test for primary aldosteronism (PA) and 50% to 70% of them have a negative confirmatory test: the appropriate follow-up of these patients is currently unknown. We investigated the incidence of PA in patients with previous negative confirmatory testing, after at least a 2-year follow-up. One hundred eighty-four patients with a previously elevated aldosterone-to-renin ratio followed by a negative confirmatory test were recruited in 2 hypertension centers (Torino and Munich). We repeated the screening test for PA and, if positive, the confirmatory test (seated saline infusion test or captopril challenge test). Primary end point of the study was the incidence of newly diagnosed overt PA, as defined by a positive confirmatory test. After a mean follow-up of 5 years, 20% of patients developed overt PA. When subtype diagnosis was offered systematically, one-third of patients displayed unilateral PA. Patients who developed PA showed worsening of blood pressure control and a higher rate of cardiac organ damage, despite similar implementation of antihypertensive therapy, compared with patients without PA. A mild progression of autonomous aldosterone secretion was evident even in patients without confirmed PA but with relatively stable control of blood pressure levels over time. About one-fifth of patients with a negative confirmatory test develop overt PA over time. A clinical follow-up of patients with a negative confirmatory test is advisable, along with the repetition of PA investigation, primarily in patients with worsening of blood pressure control.

Practical recommendations for antihypertensive therapy during the primary aldosteronism screening test.

The aldosterone-to-renin activity ratio (ARR) is recommended as a screening test for primary aldosteronism (PA). The use of antihypertensive medication is one of the most important factors to take into account when interpreting the ARR. The goal of this study was to compare the effect of various antihypertensive drug classes on biochemical testing and provide practical recommendations for antihypertensive medication regimens in patients suspected of having PA. We retrospectively investigated 4218 hypertensive patients who underwent PA detection between January 2020 and February 2023. Finally, 25 patients with essential hypertension (EH) and 39 with PA were involved. The enrolled EH patients were selected from EH patients with at least two screening tests with interfering medication changes for at least 4 weeks. A total of 2/18 (11.1%) EH patients had opposite screening results after angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), dihydropyridine-calcium channel blockers (DHP-CCBs) and diuretics were withdrawn. A total of 3/3 (100%) of the patients were initially screened as positive but had results that tested negative after β-blockers withdrawal. A total of 3/39 (7.7%) PA patients were misdiagnosed with EH with drug effects. Only plasma renin activity was markedly reduced after antihypertensive medication washout (P = 0.0173). Not every patient receiving β-blockers, ACEIs, ARBs and DHP-CCBs with negative reports needed withdrawal or switching antihypertensive drugs. We recommend that patients be left on a regimen that includes β-blockers, ACEIs, ARBs, DHP-CCBs and spironolactone when determining the ARR during the initial test.

The effect of age, sex and BMI on the aldosterone-to-renin ratio in essential hypertensive individuals.

The aldosterone-to-renin ratio (ARR) is widely used as a screening test for primary aldosteronism, but its determinants in patients with essential hypertension are not fully known. The purpose of the present investigation is to identify the impact of age, sex and BMI on renin, aldosterone and the ARR when measured under strict, standardized conditions in hypertensive patients without primary aldosteronism. We analysed the data of 423 consecutive hypertensive patients with no concomitant cardiac or renal disorders from two different hospitals (Rotterdam and Maastricht) who had been referred for evaluation of their hypertension. Those who were diagnosed with secondary causes of hypertension, including primary aldosteronism, were excluded from analysis. Patients who used oral contraceptives or had hormonal replacement therapy were excluded as well. Plasma aldosterone concentration (PAC), active plasma renin concentration (APRC) and the ARR were measured under standardized conditions. All measurements were taken in the supine position at 10.00 h in the morning, with one subgroup of patients adhering to a sodium-restricted diet (55 mmol/day) for no less than 3 weeks, and the other subgroup maintaining an ad libitum diet. In those who were receiving antihypertensive treatment, all medications were discontinued at least 3 weeks before testing. In neither group did aldosterone correlate with age. Renin, however, was inversely related to age both during low-salt diet ( P < 0.001) and during ad lib salt intake ( P = 0.05). This resulted in a significant positive correlation between age and the ARR in both groups. Although on both dietary regimens, PAC and APRC were significantly higher in men when compared with women, the ARR was not significantly different between the two sexes. The age-relationships of renin and the ARR were comparable in men and women on both diets, albeit with greater variability in women. There was an upward trend between BMI and the ARR, which reached statistical significance only in men on low-salt diet. In multivariable regression analysis, age remained the only independent determinant of the ARR. In our essential hypertensive population, the ARR increased significantly with age but was not affected by sex or BMI.

Effect of Oral Contraception on Screening Tests for Primary Aldosteronism: A 10-Year Longitudinal Study.

Primary aldosteronism (PA) and oral contraception (OC) can both cause hypertension in young women. However, the effect of OC on the screening test for PA, the aldosterone to renin ratio (ARR), is not clear. We evaluated the impact of OC on the screening test for PA. In this retrospective cohort study, we analyzed data from the female offspring (Gen2) of women enrolled in the Raine Study, a population-based birth cohort, who had blood pressure (BP) measurements, blood samples, and information about OC use at age 17 years (N = 484) and/or age 27 years (N = 486). Aldosterone concentration was significantly higher in OC users than nonusers at 17 years (median 486 pmol/L vs 347 pmol/L, P < 0.001). Renin concentration was significantly lower in OC users at both 17 years (13.4 mU/L vs 20.6 mU/L) and 27 years (9.2 mU/L vs 11.8 mU/L), hence the ARR was significantly higher in OC users compared to nonusers at both 17 years (31.5 vs 18.3) and 27 years (27.3 vs 21.1). The proportion of participants with ARR > 70 pmol/mU (current threshold for PA detection) was significantly higher in OC users at both 17 years (12.6% vs 2.1%) and 27 years (6.4% vs 0.4%); however, they had comparable BP to those with ARR < 70. OC use at any age abolished the relationship between ARR and BP that is observed in nonusers. OC can increase the ARR and cause a false positive PA screening result. Until more reliable criteria for PA screening in OC users are established, alternative contraception should be considered during screening.

EFFECTS OF MINERALOCORTICOID RECEPTOR ANTAGONISTS ON ALDOSTERONE TO RENIN RATIO IN PATIENTS WITH PRIMARY ALDOSTERONISM

Objective: Current guidelines recommend to withdraw interfering antihypertensive drugs before to perform a screening test for primary aldosteronism (PA). Recent studies suggested that diagnostic work-up of PA might be performed without withdrawing mineralocorticoid receptor antagonist (MRA) treatment in selected patients, especially when severe hypertension and hypokalemia are difficult to control. We designed a prospective study to evaluate the effects of MRA treatment on aldosterone to renin ratio (ARR) in patients with PA. Design and method: We prospectively recruited 121 patients with confirmed PA and started on canrenone treatment. Eighteen patients were enrolled in a short-term treatment cohort to assess the effects of MRA on aldosterone to renin ratio (ARR) and potassium after 2 and 8 weeks of canrenone therapy. One hundred and two patients were recruited in the long-term treatment cohort to evaluate the effects of canrenone on ARR after 2 to 12 months of MRA therapy. Results: Plasma renin activity and potassium displayed a significant increase, and ARR showed a significant reduction compared with baseline in patients with PA after MRA initiation. These effects were observed both after a short- and a long-term treatment with canrenone, and were progressively more significant after longer periods of therapy and with greater doses of MRA. We demonstrated that canrenone assumption severely impacts on the rate of false-negative screening tests for PA, which raised from 16.7% to 72.5% after 2 weeks and 7–12 months of MRA treatment, respectively. Conclusions: ARR testing for PA screening should not be performed under MRA therapy.

Aldosterone/direct renin concentration ratio as a screening test for primary aldosteronism: a systematic review and meta-analysis.

BackgroundPrimary aldosteronism (PA) refers to a spontaneous increase in adrenal aldosterone secretion, and is considered the main cause of secondary hypertension. The main aldosterone screening methods include plasma aldosterone-to-renin ratio (ARR) and plasma aldosterone/direct renin concentration ratio (ADRR). The ARR method has many limitations such as complex operation, several influencing factors, and difficulty in standardization. Relatively speaking, ADRR has gradually attracted attention due to its simple operation, stable results, and easy standardization. However, different research results have suggested that the diagnostic efficacy of ADRR in the screening of primary aldosteronism varies greatly. Meta-analysis may be a way to provide evidence-based medicine. Therefore, it is necessary to conduct a meta-analysis of the diagnostic efficacy of ADRR in primary aldosteronism to clarify the role of ADRR in the screening of PA.MethodsThe words “primary aldosteronism”, “primary hyperaldosteronism”, “aldosterone”, “renin concentration”, “hypertension” and “screening test” were used as search terms. Literature searches were conducted in the databases of PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu. According to the PICOS principles studies exploring the effectiveness of ADRR in screening for PA were included in the analysis. The research data were independently extracted and analyzed by 2 researchers. Quality assessment of diagnostic accuracy studies (QUADAS-2) was used to analyze the risk bias of the included studies.ResultsThe results showed that 10 studies met the inclusion criteria, with a total of 2,806 subjects. The meta-analysis found that the overall sensitivity and specificity were 0.87 [95% confidence interval (CI): 0.85–0.89], 0.85 (95% CI: 0.83–0.86), respectively. The area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve was 0.9333. The pooled positive likelihood ratio (PLR), pooled negative likelihood ratio (NLR), and pooled diagnostic odds ratio (DOR) were 5.84 (3.67–9.30), 0.16 (0.12–0.22), and 39.82 (22.84–69.44), respectively.DiscussionThis study confirmed that ADRR screening for PA has good sensitivity and specificity. Therefore, ADRR can be used to screen for PA. But the risk and problematic control should be considered.

Conn's syndrome-Frequent and still too rarely diagnosed to underdiagnosed

Conn's syndrome represents the most common cause of endocrine hypertension and is associated with an increased cardiovascular risk, a series of comorbidities (including type 2 diabetes mellitus) and with their frequent occurrence. Therefore, acorrect and rapid diagnosis is of essential importance. Measurement of the aldosterone-renin ratio is used as afirst screening test for primary aldosteronism. This should ideally be evaluated under optimized conditions (e.g. at rest), after adjustment of the blood pressure medication and with an equilibrated potassium balance. In cases of elevated aldosterone to renin ratio, further confirmatory testing as well as imaging of the adrenal glands is needed. After confirmation of Conn's syndrome a differentiation between a unilateral and bilateral adrenal disease is necessary for further treatment planning. The current gold standard is still selective adrenal vein catheterization. Promising alternatives to an adrenal vein catheter, such as functional imaging techniques and measurement of steroid profiles are currently being investigated in clinical trials. In cases of lateralization of aldosterone production, unilateral laparoscopic adrenalectomy of the affected side is the treatment of choice. In contrast, patients with bilateral disease or patients with contraindications for adrenalectomy should receive life-long treatment with mineralocorticoid receptor antagonists.

Performance of the Aldosterone to Renin Ratio as a Screening Test for Primary Aldosteronism.

The aldosterone to renin ratio (ARR) is the guideline-recommended screening test for primary aldosteronism. However, there are limited data in regard to the diagnostic performance of the ARR. To evaluate the sensitivity and specificity of the ARR as a screening test for primary aldosteronism. We searched the MEDLINE, Embase, and Cochrane databases until February 2020. Observational studies assessing ARR diagnostic performance as a screening test for primary aldosteronism were selected. To limit verification bias, only studies where dynamic confirmatory testing was implemented as a reference standard regardless of the ARR result were included. Study-level data were extracted and risk of bias and applicability were assessed using the QUADAS-2 tool. Ten studies, involving a total of 4110 participants, were included. Potential risk of bias related to patient selection was common and present in half of the included studies. The population base, ARR positivity threshold, laboratory assay, and reference standard for confirmatory testing varied substantially between studies. The reported ARR sensitivity and specificity varied widely with sensitivity ranging from 10% to 100% and specificity ranging from 70% to 100%. Notably, 3 of the 10 studies reported an ARR sensitivity of <50%, suggesting a limited ability of the ARR to adequately identify patients with primary aldosteronism. ARR performance varied widely based on patient population and diagnostic criteria, especially with respect to sensitivity. Therefore, no single ARR threshold for interpretation could be recommended. Limitations in accuracy and reliability of the ARR must be recognized in order to appropriately inform clinical decision-making.

Mineralocorticoid Receptor Antagonist Effect on Aldosterone to Renin Ratio in Patients With Primary Aldosteronism.

Although current international guidelines recommend to avoid mineralocortcoid receptor antagonists in patients undergoing screening test for primary aldosteronism, a recent report suggested that mineralocorticoid receptor antagonist treatment can be continued without significant influence on screening results. We aimed to evaluate the effect of mineralocorticoid receptor antagonists on the aldosterone to renin ratio in patients with primary aldosteronism. We prospectively enrolled 121 patients with confirmed primary aldosteronism who started mineralocorticoid receptor antagonist (canrenone) treatment. Eighteen patients (11 with unilateral and 7 with bilateral primary aldosteronism) constituted the short-term study cohort and underwent aldosterone, renin, and potassium measurement after 2 and 8 weeks of canrenone therapy. The long-term cohort comprised 102 patients (16 with unilateral and 67 with bilateral primary aldosteronism, and 19 with undetermined subtype) who underwent hormonal and biochemical re-assessment after 2 to 12 months of canrenone therapy. Renin and potassium levels showed a significant increase, and the aldosterone to renin ratio displayed a significant reduction compared with baseline after both a short- and long-term treatment. These effects were progressively more evident with higher doses of canrenone and after longer periods of treatment. We demonstrated that canrenone exerted a deep impact on the diagnostic accuracy of the screening test for primary aldosteronism: the rate of false negative tests was raised to 16.7%, 38.9%, 54.5%, and 72.5% after 2 weeks, 8 weeks, 2 to 6 months, and 7 to 12 months of mineralocorticoid receptor antagonist treatment, respectively. Mineralocorticoid receptor antagonists should be avoided in patients with hypertension before measurement of renin and aldosterone for screening of primary aldosteronism.

THE EFFECT OF AGE, BMI, AND SEX ON ALDOSTERONE, RENIN AND THE ALDOSTERONE-TO-RENIN RATIO IN ESSENTIAL HYPERTENSIVES

Abstract Objective: The aldosterone-to-renin ratio (ARR) is widely used as a screening test for primary aldosteronism (PA) in patients with hypertension. The purpose of the present investigation is to identify the impact of age, body mass index (BMI) and sex on renin, aldosterone, and the ARR, when measured under strictly standardised conditions. Design and method: We measured plasma aldosterone, plasma renin concentration and the ARR in 190 essential hypertensive patients (120 males, 70 females). All measurements were taken in the supine position at 9am. A low sodium diet (55mmol/day) was in place for no less than two weeks prior to screening. In those who were receiving antihypertensive medications, all medications were discontinued at least 2 week before testing. Results: Renin and aldosterone were significantly higher in men, and remained so when controlling for BMI and age. However, the ARR was not significantly affected by sex. Aldosterone was not significantly influenced by age but renin correlated inversely with age, with and without controlling for BMI (r = -0.285, p &lt; 0.001). The ARR was positively correlated with age (r = 0.236, p &lt; 0.001), with and without controlling for BMI. Subgroup analysis demonstrated a significant effect on the ARR in males only, with and without controlling for BMI (p &lt; 0.001 and p0.004, respectively). Although renin and aldosterone individually were not significantly influenced by BMI, the ARR showed a positive correlation (p = 0.022). However, this effect was not seen when age was controlled for nor was it seen in the subgroup analysis of males and females (p = 0.125, p = 0.515, p = 0.207, respectively) Conclusions: Under strictly standardized conditions, advanced age is associated with an increased ARR in male essential hypertensives. BMI when controlling for age does not influence the ARR. The impact of sex on the ARR appears negligible.

THE EFFECT OF THE MENSTRUAL CYCLE ON RENIN, ALDOSTERONE AND ALDOSTERONE-TO-RENIN RATIO IN FORMERLY PREECLAMPTIC AND HEALTHY WOMEN

Abstract Objective: The aldosterone-to-renin ratio (ARR) is widely used as a screening test for primary aldosteronism (PA) in patients with hypertension. The purpose of the present original investigation is to identify the impact hormonal changes have on renin, aldosterone, and the ARR during the menstrual cycle of premenopausal women when measured in strict standardised conditions. Design and method: We analysed 59 women with a history of preeclampsia and 6 healthy parous controls. Blood values were determined during both follicular and luteal phases of the menstrual cycle (days 1 and 14 respectively). Plasma aldosterone, active plasma renin concentration (APRC) and the ARR were measured under standardised conditions. All measurements were taken in the supine position at 9am, all patients maintained a standardised sodium diet (100 mmol/day) for no less than two weeks. In those who were receiving antihypertensive medications (n = 2), all medications were discontinued at least 1 week prior to screening. Results: When performing the Friedman's Test and the Wilcoxon signed rank test in formerly preeclamptic women (n = 59), aldosterone and renin were both significantly elevated in the luteal phase (mean rank aldosterone 1.2 and 1.8 p0.000 Z-4.7, mean rank renin 1.23 and 1.77 p0.000 Z -4.5, respectively), however the ARR values did not significantly differ between phases (mean rank 1.53 and 1.47 p0.7 Z-0.14). When performing the Friendman's Test in the control group (n = 6), the difference in aldosterone, renin and the ARR between the follicular and luteal phase was not significant (p0.059 for all parameters). Wilcoxon signed test revealed a significant difference in aldosterone (Z-2.02 p0.04), but the difference in renin and the ARR remained insignificant (p0.06). Conclusions: In this study of premenopausal women we found that both renin and aldosterone are significantly affected by the menstrual cycle. However the resulting ARR was not statistically significantly altered. Our study indicates that it is not necessary to take the menstrual phase of patients into account when performing and interpreting the ARR as a screening test for PA in patients with a history of preeclampsia.

Aldosterone-producing adenoma associated with non-suppressed renin: a case series.

Although the aldosterone/renin ratio (ARR) is the preferred screening test for primary aldosteronism (PA), patients with non-suppressed renin and a falsely negative ARR on non-interfering medications have occasionally been reported. This report describes the clinical characteristics and outcomes of seven patients with proven aldosterone-producing adenoma (APA) and non-suppressed renin.Chart review of seven PA patients with an APA and a non-suppressed plasma renin concentration (PRC > 8.4 mU/L) was undertaken to collect data on anthropometric and biochemical characteristics, diagnostic evaluation and postsurgical outcomes.Seven patients (two women and five men) with a proven APA had median (range) PRC, plasma aldosterone and ARR of 20 (9-43) mU/L, 750 (270-1940) pmol/L and 45 (8-62, normal <70), respectively, on non-interfering medications. Six patients had two consecutive ARR measurements and in five of them both were normal. Renal artery stenosis was carefully excluded in all patients. Further evaluation for PA was pursued because of high clinical suspicion (either hypokalaemia and/or a known adrenal mass lesion on imaging). All underwent adrenal vein sampling confirming unilateral PA which was managed by unilateral adrenalectomy. Postsurgical follow-up data either confirmed or were highly suggestive of cure of PA.Strict control of factors known to influence the ARR is crucial to avoid false-negative results. Other causes that could explain a non-suppressed renin should be excluded. In patients with a consistently non-suppressed renin further diagnostic workup for PA should be considered if clinical suspicion remains high.

The effect of medication on the aldosterone-to-renin ratio. A critical review of the literature.

The aldosterone‐to‐renin ratio (ARR) is a common screening test for primary aldosteronism in hypertensives. However, patients often use medications that could confound the ARR and, thereby, reduce the interpretability of the test. Since it is not always feasible to stop such medication, several drugs that are supposedly neutral with respect to the ARR have been recommended as alternative treatment. The objective of the present review is to explore whether sufficient evidence exists to justify the recommendations. To this end, we performed a systematic PubMed and Cochrane literature search regarding medications that may influence the ARR. Our review revealed that many commonly prescribed antihypertensives seem to have significant effects on renin, aldosterone, and resulting ARR values. However, the magnitude of these effects is poorly quantifiable with the present level of research. We conclude that several medications can affect the ARR. Not taking this into account could lead to misinterpretation of the ARR. Therefore, standardization of the medications used during ARR measurement is advisable for a reliable and accurate interpretation. Further research is needed to ascertain how to best optimize these medications.

Confounders of the aldosterone‐to‐renin ratio when used as a screening test in hypertensive patients: A critical analysis of the literature

The aldosterone‐to‐renin ratio (ARR) is a common screening test for primary aldosteronism in hypertensives. However, there are many factors which could confound the ARR test result and reduce the accuracy of this test. The present review's objective is to identify these factors and to describe to what extent they affect the ARR. Our analysis revealed that sex, age, posture, and sodium‐intake influence the ARR, whereas assay techniques do not. Race and body mass index have an uncertain effect on the ARR. We conclude that several factors can affect the ARR. Not taking these factors into account could lead to misinterpretation of the ARR.

High Efficiency and Problems of Chemiluminescence Assay-Detected Aldosterone-To-Renin Ratio in Practical Primary Aldosteronism Screening.

Primary aldosteronism is a main cause of secondary hypertension which can be effectively treated. The screening test for primary aldosteronism is benefit for minimizing damage to the patient. In the previous retrospective study, we obtained the optimal cutoff value of aldosterone-to-renin ratio detected by chemiluminescence assay, a newly developing method, and prompted its high efficiency in primary aldosteronism screening in upright position. In this study, we want to evaluate its efficiency in practical work. We used this ratio to continuously screen 238 patients, and 58 patients were finally diagnosed with primary aldosteronism. We found it had 86.13% accuracy rate in the upright position compared with the final clinical diagnosis. False negative and positive rates were 13.79% and 13.89%. Diagnostic sensitivity and specificity were 86.21% and 86.11%, which are slightly different from results in our previous study. False negative rate can be improved by combining the aldosterone-to-renin ratio with aldosterone concentration. We also found impaired glucose tolerance may be a reason for high false positive rate. Besides, chemiluminescence assay may be interfered in aldosterone detection. Although it has some shortcomings, chemiluminescence assay-detected aldosterone-to-renin ratio is a highly effective index for screening primary aldosteronism in practice.

Diagnostic Accuracy of the Aldosterone-to-Active Renin Ratio for Detecting Primary Aldosteronism.

ContextThe aldosterone–to–active renin ratio (AARR) is the recommended screening test for primary aldosteronism (PA), but prospective study data on its sensitivity and specificity are sparse.ObjectiveTo investigate the diagnostic accuracy of the AARR for detecting PA.DesignProspective diagnostic accuracy study.SettingThis study was conducted from February 2009 to August 2015 at the outpatient clinic of the Department of Endocrinology and Diabetology of the Medical University of Graz, Austria.ParticipantsFour hundred patients with arterial hypertension who were referred to a tertiary care center for screening for endocrine hypertension.InterventionParticipants had a determination of the AARR (index test) and a second AARR determination followed by a saline infusion test (SIT) after 2 to 6 weeks. PA was diagnosed in individuals with any AARR ≥3.7 ng/dL/µU/mL [including a plasma aldosterone concentration (PAC) of ≥9 ng/dL] who had a PAC ≥10 ng/dL after the SIT. We did not substantially alter antihypertensive drug intake.Main Outcome MeasuresPrimary outcome was the receiver-operating characteristic (ROC) curve of the AARR in diagnosing PA.ResultsA total of 382 participants were eligible for analyses; PA was diagnosed in 18 (4.7%) patients. The area under the ROC curve of the AARR in detecting PA was 0.973 (95% CI, 0.956 to 0.990). Sensitivity and specificity for a positive AARR in diagnosing PA were 100% (95% CI, 81.5% to 100.0%) and 89.6% (95% CI, 86.0% to 92.5%), respectively.ConclusionsThe AARR has good diagnostic accuracy for detecting PA.