Screening For Primary Aldosteronism Research Articles

Comparison of ambulatory blood pressure between patients with primary aldosteronism and other forms of hypertension.

Primary aldosteronism (PA) is a potentially curable cause of hypertension associated with worse cardiovascular prognosis than blood pressure-matched essential hypertension (EH). Effective targeted treatment for PA is available with the greatest benefit seen if treatment is started early, prior to the development of end-organ damage. However, PA is currently substantially under-diagnosed. The standard screening test for PA, the aldosterone-to-renin ratio (ARR), is performed infrequently in both primary and tertiary care. In contrast, ambulatory blood pressure monitoring (ABPM) is frequently utilized in the assessment of hypertension. The aim of this study was to compare ABPM parameters in hypertensive patients with and without PA, in order to identify features of ABPM associated with PA that can prompt screening. Patients with PA (n=55) were identified from a tertiary clinic specializing in the management of endocrine causes of hypertension whilst the controls (n=389) were consecutive patients with hypertension but without a known diagnosis of PA who were referred for ABPM. In this study, PA patients were younger and had higher 24-h, day, and night-time blood pressure compared with controls despite similar number of antihypertensive medications. However, there was no significant difference in nocturnal dipping or day-night blood pressure variability between the two groups. An elevated ambulatory blood pressure in patients on multiple antihypertensives could suggest underlying PA but in the absence of other distinguishing features, ABPM could not reliably differentiate PA from other forms of hypertension. Routine biochemical screening for PA remained the most reliable way of detecting this treatable secondary cause of hypertension.

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

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. 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. 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. MRAs commonly reduce ARR and the proportion of positive PA screening results. When PA is suspected, screening should be repeated off MRAs. 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.

Effect of sodium\u2013glucose cotransporter-2 inhibitors on aldosterone-to-renin ratio in diabetic patients with hypertension: a retrospective observational study

BackgroundPlasma aldosterone-to-renin ratio (ARR) is popularly used for screening primary aldosteronism (PA). Some medications, including diuretics, are known to have an effect on ARR and cause false-negative and false-positive results in PA screening. Currently, there are no studies on the effects of sodium–glucose cotransporter-2 (SGLT2) inhibitors, which are known to have diuretic effects, on ARR. We aimed to investigate the effects of SGLT2 inhibitors on ARR.MethodsWe employed a retrospective design; the study was conducted from April 2016 to December 2018 and carried out in three hospitals. Forty patients with diabetes and hypertension were administered SGLT2 inhibitors. ARR was evaluated before 2 to 6 months after the administration of SGLT2 inhibitors to determine their effects on ARR.ResultsNo significant changes in the levels of ARR (90.9 ± 51.6 vs. 81.4 ± 62.9) were found. Body mass index, diastolic blood pressure, heart rate, fasting plasma glucose, and hemoglobin A1c were significantly decreased by SGLT2 inhibitors. Serum creatinine was significantly increased.ConclusionSGLT2 inhibitor administration yielded minimal effects on ARR and did not increase false-negative results in PA screening in patients with diabetes and hypertension more than 2 months after administration.

High body fat percentage is associated with primary aldosteronism: a cross-sectional study

BackgroundExcess aldosterone has been shown to be associated with obesity; however, there is currently a lack of data regarding the relationship between percentage of body fat and primary aldosteronism (PA), particularly pertaining to Asian populations. Furthermore, essential hypertension may mimic the condition of PA and there needs to be differentiation between the two. This study aimed to assess the association between percentage of body fat and PA.MethodsA cross-sectional study was conducted in the outpatient department of the Endocrine and Metabolism Unit of the tertiary care medical center in Thailand. Data was obtained from 79 patients who had been screened for PA due to hypertension in young-onset, hypokalemia, adrenal incidentaloma or resistance hypertension. Essential hypertension was defined as patients who had high blood pressure and were negative for PA screening. Body fat percentage was assessed by bioelectrical impedance analysis. The relationship between percentage of body fat and a diagnosis of PA was assessed using logistic regression analysis, including adjustment for confounding factors.ResultsThe participants were divided into a PA group (n = 41) and an essential hypertension group (n = 38). After controlling for confounding variables (age, sex, body mass index, cholesterol and insulin resistance status), the odds ratio of having PA in males with a percentage of body fat > 25% and females with percentage > 30% was 1.82 (95%CI = 1.79–1.86, p < 0.001).ConclusionA higher percentage of body fat is associated with an increased risk of PA. Further studies need to be conducted to confirm the relationship between body fat percentage and PA.

Application of aldosterone/direct renin ratio before drug washout in the screening of primary aldosteronism

Objective: To explore the cut-off point of aldosterone/direct renin ratio (ADRR) before drug washout in the screening for primary aldosteronism (PA) in the Chinese population and reduce the potential risk caused by drug washout during PA screening. Methods: Hospitalized hypertensive patients in the Hypertension Ward of Fuwai Hospital, Chinese Academy of Medical Sciences from January 2017 to October 2019 were enrolled. PA was diagnosed according to the criterion of 2016 American Guideline and 2016 Chinese Consensus for PA. The plasma aldosterone concentration (PAC), direct renin concentration (DRC) and ADRR before and after drug washout were measured. The receiver operating characteristic (ROC) curve of ADRR was drawn and the maximal Youden index was used to determine the best cut-off value. Results: A total of 542 hypertensive patients were included, with 467 patients diagnosed with essential hypertension (EHT) (297 males and 170 females), and 75 patients diagnosed with PA (51 males and 24 females). Patients with PA had higher PAC and ADRR before and after drug washout than those with EHT(150.0 (130.0, 210.0) vs 120.0 (80.0, 170.0) ng/L, 170.0 (120.0, 260.0) vs 130.0 (90.0, 180.0) ng/L; 28.9 (15.9, 63.5) vs 4.3 (1.9, 11.8) (ng/L) / (mU/L) , 55.6 (39.0, 109.0) vs 9.8 (4.5, 21.3) (ng/L) /(mU/L), all P<0.001). However, DRC of PA patients before and after washout were lower than those with EHT (4.0 (2.0, 10.0) vs 27.0 (10.0, 64.0) mU/L, 3.0 (2.0, 4.0) vs 12.2 (5.0, 27.0) mU/L, P<0.001). In EHT and PA groups, PAC and ADRR significantly increased (P=0.001, P<0.001) , but DRC significantly decreased after drug washout (all P<0.001) . The area under the ROC curve of ADRR before drug washout was 0.868 (95%CI 0.836-0.895) with the best cut-off value of 7.8 (ng/L) / (mU/L) for the screening of PA .The sensitivity and specificity was 94.7% and 66.8%, respectively, with the maximal Youden index of 0.615. Conclusion: ADRR before drug washout > 7.8 (ng/L) / (mU/L) can be used as an alternative cut-off point to screen PA when drug washout is not available.

Primary aldosteronism is highly prevalent in patients with hypertension and moderate to severe obstructive sleep apnea.

It has been suggested that there might be a pathophysiological link and overlap between primary aldosteronism (PA) and obstructive sleep apnea (OSA). Therefore, in a prospective study, we evaluated the frequency of PA in hypertensive patients suspected of having OSA. We included 207 consecutive hypertensive patients (mean age 53.2 ± 12.1 years, 133 M, 74 F) referred for polysomnography on the basis of one or more of the following clinical features: typical OSA symptoms, resistant or difficult-to-treat hypertension, diabetes, or cardiovascular disease. PA was diagnosed based on thew saline infusion test. Moderate-to-severe OSA was diagnosed in 94 patients (45.4% of the whole group). PA was diagnosed in 20 patients with OSA (21.3%) compared with 9 patients in the group without OSA (8.0%; P = .006). PA was also frequent in patients in whom symptoms of OSA were a sole indication for PA screening (15.4%) and in patients with and without resistant hypertension (24.5% and 17.8%, respectively). Most patients with PA and OSA were diagnosed with bilateral adrenal hyperplasia (18 patients, 90%). There were no major differences in clinical characteristics between patients with OSA with PA and those without PA. In multivariate models, moderate-to-severe OSA predicted the presence of PA (odds ratio 2.89, P = .018). Patients with clinically important moderate-to-severe OSA are characterized by a relatively high frequency of PA. Our results support the recommendations to screen patients with moderate-to-severe OSA for PA, regardless of the presence of other indications for PA screening.

Use of Steroid Profiling Combined With Machine Learning for Identification and Subtype Classification in Primary Aldosteronism

Most patients with primary aldosteronism, a major cause of secondary hypertension, are not identified or appropriately treated because of difficulties in diagnosis and subtype classification. Applications of artificial intelligence combined with mass spectrometry-based steroid profiling could address this problem. To assess whether plasma steroid profiling combined with machine learning might facilitate diagnosis and treatment stratification of primary aldosteronism, particularly for patients with unilateral adenomas due to pathogenic KCNJ5 sequence variants. This diagnostic study was conducted at multiple tertiary care referral centers. Steroid profiles were measured from June 2013 to March 2017 in 462 patients tested for primary aldosteronism and 201 patients with hypertension. Data analyses were performed from September 2018 to August 2019. The aldosterone to renin ratio and saline infusion tests were used to diagnose primary aldosteronism. Subtyping was done by adrenal venous sampling and follow-up of patients who underwent adrenalectomy. Statistical tests and machine-learning algorithms were applied to plasma steroid profiles. Areas under receiver operating characteristic curves, sensitivity, specificity, and other diagnostic performance measures were calculated. Primary aldosteronism was confirmed in 273 patients (165 men [60%]; mean [SD] age, 51 [10] years), including 134 with bilateral disease and 139 with unilateral adenomas (58 with and 81 without somatic KCNJ5 sequence variants). Plasma steroid profiles varied according to disease subtype and were particularly distinctive in patients with adenomas due to KCNJ5 variants, who showed better rates of biochemical cure after adrenalectomy than other patients. Among patients tested for primary aldosteronism, a selection of 8 steroids in combination with the aldosterone to renin ratio showed improved effectiveness for diagnosis over either strategy alone. In contrast, the steroid profile alone showed superior performance over the aldosterone to renin ratio for identifying unilateral disease, particularly adenomas due to KCNJ5 variants. Among 632 patients included in the analysis, machine learning-designed combinatorial marker profiles of 7 steroids alone both predicted primary aldosteronism in 1 step and subtyped patients with unilateral adenomas due to KCNJ5 variants at diagnostic sensitivities of 69% (95% CI, 68%-71%) and 85% (95% CI, 81%-88%), respectively, and at specificities of 94% (95% CI, 93%-94%) and 97% (95% CI, 97%-98%), respectively. The validation series yielded comparable diagnostic performance. Machine learning-designed combinatorial plasma steroid profiles may facilitate both screening for primary aldosteronism and identification of patients with unilateral adenomas due to pathogenic KCNJ5 variants, who are most likely to show benefit from surgical intervention.

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.

Taiwan mini-frontier of primary aldosteronism: Updating detection and diagnosis

To update information about the internationally accepted standards and clinical recommendations for the detection and diagnosis of primary aldosteronism (PA). The Taiwan Society of Aldosteronism (TSA) Task Force reviewed the latest literature and reached a consensus after group meetings. The nine critical issues were recognized to provide updated information and internationally acceptable protocols. When screening for PA by using the plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio (ARR), withdrawal or adjustment of antihypertensive medication is not always necessary on the first patient visit. Hypokalemia should be corrected before ARR screening. In spontaneous hypokalemia, plasma renin below detection levels, and PAC higher than 20 ng/dL (550 pmol/L), further confirmatory testing is unnecessary for PA diagnosis. Direct renin concentration (DRC) could be used for PA diagnosis if PRA is unavailable. Although additional confirmatory tests are suggested, the result of a single test is still reliable. For patient safety, discontinuation or adjustment of antihypertensive medications is indicated before adrenal venous sampling (AVS). ACTH could be beneficial for successful adrenal vein cannulation but is not necessary for determining lateralization in AVS. Simultaneous technique is preferred for AVS. Adrenal NP-59 scintigraphy integrated with SPECT/CT could guide PA management. With introduction of these new concepts to the clinicians, we expect better identification, management and treatment of PA patients.

Annals for Educators - 7 July 2020.

Annals for Educators - 7 July 2020.

Prevalence of primary aldosteronism in hypertensive kidney transplant recipients: A cross-sectional study.

Due to high prevalence of primary aldosteronism (PA) in the general hypertensive population, and its association with worse cardiovascular and renal outcomes, the 2016 Endocrine Society Guidelines explicitly recognize PA as a major public health issue requiring urgent attention. Its prevalence in hypertensive kidney transplant recipients (KTRs) is unknown. In this cross-sectional study, we screened KTRs with hypertension who were on ≥4 antihypertensive medications, on 3 antihypertensive medications with BP≥140/90, and on potassium supplements, or were hypokalemic. 172 of 280 eligible patients successfully completed the testing. A positive screen for PA defined by an aldosterone-to-renin ratio of ≥20 and a plasma aldosterone concentration of >15ng/dL yielded a prevalence of 15.7%. Potassium supplement requirement (52% vs 27%, P=.01) and hypokalemia (25.9% vs 4.8%, P<.01) were more common in patients who screened positive compared with those who screened negative. 67% of patients who screened positive were on potassium supplements and/or were hypokalemic. Our study is the first to systematically explore the prevalence of PA among the hypertensive KTR population, which has inherently high cardiovascular risk. Further studies are needed to determine the cardiovascular and renal risk attributable to PA, and define optimal therapy for KTRs with PA.

Effects of Ramipril on the Aldosterone/Renin Ratio and the Aldosterone/Angiotensin II Ratio in Patients With Primary Aldosteronism.

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<0.01 or P<0.05) after ramipril treatment, whereas eqAngII and ACE activity (eqAngII/eqAngI) decreased significantly (P<0.01). The changes of plasma renin activity and plasma aldosterone concentration in the current study were not significant. On day 14, 4 patients displayed false-negative results using ARR_direct renin concentration (plasma aldosterone concentration/direct renin concentration), 3 of whom also showed false-negative ARR_plasma renin activity (plasma aldosterone concentration/plasma renin activity). On day 15, 2 patients still demonstrated false-negative ARR_plasma renin activity, one of whom also showed a false-negative ARR_direct renin concentration. No false-negative AA2R results were observed on either day 14 or 15. In conclusion, compared with ARR which can be affected by ACE inhibitors causing false-negative screening results, the AA2R seems to be superior in detecting PA among subjects receiving ACE inhibitors.

Primary Aldosteronism: More Common Than Previously Reported

Guideline-recommended screening for primary aldosteronism in patients with resistant hypertension usually is accomplished by measuring serum

Primary aldosteronism - why is it still underdiagnosed in clinical practice?

Primary aldosteronism (PA) represents the leading cause of endocrine hypertension, accounting for 4-13 % of all cases. Simultaneously, it is the most common endocrine form of hypertension that can be cured by surgery. Estimates suggest that 2.5million people in Germany are affected, yet only 8 % of hypertensive patients undergo the proper diagnostic screening for PA. The diagnosis of PA is evidently not taken into account sufficiently when it comes to the everyday management of hypertension. Since PA patients carry an increased risk of cardio- and cerebrovascular events as well as metabolic comorbidities, early screening and diagnosis is crucial.This manuscript highlights the current guidelines of screening and diagnosing PA and addresses some currently published findings regarding this area. The aim is to raise awareness when it comes to diagnosing and screening for PA in the everyday management of hypertensive patients.

Development and Validation of Criteria for Sparing Confirmatory Tests in Diagnosing Primary Aldosteronism.

The Endocrine Society Guidelines for the diagnosis of primary aldosteronism (PA) suggest that confirmatory tests (CFT) are not required when the following criteria are met: plasma aldosterone concentration (PAC) is >20 ng/dL, plasma renin is below detection levels, and hypokalemia is present. The evidence for the applicability of the guideline criteria is limited. To develop and validate optimized criteria for sparing CFT in the diagnosis of PA. The optimized criteria were developed in a Chinese cohort using the captopril challenge test, verified by saline infusion test (SIT) and fludrocortisone suppression test (FST), and validated in an Australian cohort. Hypertensive patients who completed PA screening and CFT. Diagnostic value of the optimized criteria. In the development cohort (518 PA and 266 non-PA), hypokalemia, PAC, and plasma renin concentration (PRC) were selected as diagnostic indicators by multivariate logistic analyses. The combination of PAC >20 ng/dL plus PRC <2.5 μIU/mL plus hypokalemia had much higher sensitivity than the guideline criteria (0.36 vs 0.11). The optimized criteria remained superior when the SIT or FST were used as CFT. Non-PA patients were not misdiagnosed by either criteria, but the percentage of patients in whom CFT could be spared was higher with the optimized criteria. In the validation cohort (125 PA and 81 non-PA), the sensitivity of the optimized criteria was also significantly higher (0.12 vs 0.02). Hypertensive patients with PAC >20 ng/dL, PRC <2.5 μIU/mL, plus hypokalemia can be confidently diagnosed with PA without confirmatory tests.

SAT-544 Primary Aldosteronism in Intracerebral Hemorrhage. Not Intracerebral Hemorrhage in Primary Aldosteronism

Background: Patients with primary aldosteronism (PA) are more prone to cardiovascular complications including intracerebral hemorrhage (ICH) than those with essential hypertension. But how about PA in ICH patients - not ICH in PA patients? Since ICH patients with PA are at high risk for recurrent hemorrhage and other complications, diagnosis of PA is important even after the occurrence of ICH. Here we aimed to clarify the clinical features of PA in ICH patients at the largest scale ever and to evaluate the efficacy of PA screening with machine learning. Methods: Out of 181 ICH patients admitted to our hospital between June 2016 and February 2017, 126 patients of hypertensive ICH were enrolled in this study. Plasma aldosterone concentration (PAC), plasma renin activity (PRA) and other hormones were measured in the morning two days after admission. Results: After leaving out those who had been taking medications which could intervene with PAC or PRA on admission, nine patients were positive for PA screening (PAC/PRA ratio >200 and PAC >120 pg/mL) and 53 were negative. Age (68.6 vs 68.5 y), sex (male 66.7 vs 69.8 %) and blood pressure (172/97 vs 177/100 mmHg) were similar between these two groups. Bleeding volume (14.6 vs 16.2 mL) was also similar, but the lesion was more common in thalamus rather than putamen in PA positive group. Serum potassium was slightly lower in positive group (3.6 vs 3.9 mmol/L; P=0.096) on admission, and the difference became more evident two days later (3.7 vs 4.0 mmol/L; P=0.040). There were no differences in other hormones including cortisol and catecholamine. As for prognosis, PA positive patients had more severe motor or cognitive impairments. Dimension reduction procedure using t-SNE certainly divided these patients into clusters compatible with PA screening tests. Further, we extrapolated this result to 21 patients who had been taking medications which could lower PAC/PRA ratio such as ACE inhibitors, ARB or diuretics and were excluded from the analysis above. K-nearest neighbor method revealed that even in those who had been taking PAC/PRA lowering medications, PAC/PRA ratio >160 could be regarded as positive for PA screening. Discussion: This is the largest study ever that investigated the clinical features of PA in ICH patients. Contrary to expectations, ICH patients with PA were not necessarily younger than those with essential hypertension. But they were more likely to have severe outcomes even though blood pressure and bleeding volume were similar. This may be partly because of higher aldosterone. The difference in serum potassium was masked on admission probably due to increased sympathetic activity. But about two days later, when its activity peaked out, lower serum potassium in PA positive group became more evident. This can support the efficacy of PA screening tests even in ICH patients, so PA screening should not be awaited just because they have developed ICH.

SAT-561 Effects of Mineralocorticoid Receptor Antagonists on Primary Aldosteronism Screening

Background: Mineralocorticoid receptor antagonists (MRAs) are the mainstay of medical therapy for primary aldosteronism (PA), and MRAs also benefit patients with other forms of resistant hypertension and cardiovascular disorders. MRAs impact the renin-angiotensin-aldosterone system (RAAS), raising concerns regarding the accuracy of PA screening. The rate of false negative and/or false positive screening for PA in patients taking MRAs has not been systematically evaluated. Herein, we assessed the alterations of both renin and aldosterone after MRA initiation in a large cohort of patients with hypertension. Patients and Methods: We conducted a retrospective cohort study of patients with hypertension seen in a tertiary referral center. We employed our center’s database search engine to identify adults with hypertension who were treated with MRAs. Of these, we included patients who had renin and aldosterone measured both before and after MRA treatment. We excluded patients with adrenal cortical cancer, end-stage renal disease, exogenous glucocorticoids, and critically ill. PA screening was considered positive when plasma aldosterone concentration (PAC) was 10 ng/dL, plasma renin activity (PRA) was 1.0 ng/mL/h, and the aldosterone-to renin ratio (ARR) was 20. Mann-Whitney test and Wilcoxon signed rank test were employed to compare independent or paired groups, respectively. Results: In total, 109 patients (57 women), mean age 55+/-13 years were included. Of these, 40% had confirmed PA (14% unilateral and 26% bilateral); in 38% PA was excluded; and in the remaining 22%, testing for PA was incomplete. On average, patients were on 3 +/- 1.6 antihypertensive agents; 60% of patients were prescribed beta blockers, 49% K+-wasting diuretics and 35% were on K+ supplements. Both PAC and PRA increased after MRA treatment (from 19.0 [12.6, 26.7] to 26.3 [17.2, 36.2]; and from 0.6 [0.10, 0.80] to 1.00 [0.60, 2.80], respectively, p < 0.0001 for both), while ARR decreased from 42.5 [18.5, 109.8] to 24.0 [10.9, 55.5] (p = 0.003). Of 71 patients with positive PA screening at baseline, 31 (43.7 %) no longer met positive screening criteria during MRA therapy. Conversely, 7 of 38 patients (18 %) with negative screening at baseline met criteria for positive PA screening while on MRA treatment, including 5 patients with a PAC > 20 ng/dL along with suppressed renin. The impact on PA screening accuracy remained similar irrespective of the MRA dose, duration of treatment, changes in concomitant antihypertensive drugs, or hypertension type. Conclusions: Commonly, MRA treatment leads to renin elevation, ARR reduction, and consequential false negative PA screening. In a minority of patients, MRA therapy can be followed by aldosterone elevations asynchronous from renin, possibly via short feedback loops, mimicking PA. Whenever possible, PA testing should be conducted after MRA discontinuation.

MON-217 New Methods for Primary Aldosteronism Screening by Exploring the Values of Different Indicators and in Combination with Predictive Model

Background: Primary Aldosteronism (PA) is the most common cause of secondary hypertension. The endocrine society guidelines recommend case detection of PA by determining the aldosterone-renin ratio (ARR) under standard conditions, but the cut-off value of upright ARR varies greatly. In addition, as with all other biochemical tests, there are false positives and false negatives for upright ARR. In order to avoid false negative, some researchers have proposed plasma renin activity (PRA) < 1.0 ng/ml/h as a screening indicator. In order to avoid false positive caused by low PRA, Professor Young of the Mayo Clinic have proposed that the ARR combined with the plasma aldosterone concentration (PAC) > 15 ng / dL for PA screening. In 2019, Professor Young proposed PA screening positive when PAC≥10ng/dL and PRA<1.0 ng/ml/h. In addition, angiotensin II (AT-II) directly stimulates the synthesis of aldosterone. Compared with renin, the decrease of AT-II level and the increase of aldosterone to AT-II ratio (AA2R) may reflect the aldosterone autonomy secretion. However, whether these screening indicators are superior to upright ARR remains to be further verified. Therefore, either exploring the diagnostic efficacy of PAC, PRA, or AA2R as a screening indicator or even better developing a clinical prediction model combined with multiple indicators may provide a more accurate method for PA screening. Objective: To explore the value of different indicators and the logistic regression model (nomogram) for primary aldosteronism screening. Methods: The clinical data of 499 patients with PA and 479 patients with essential hypertension (EH) diagnosed by West China Hospital from 2009 to 2018 were retrospectively analyzed. The diagnostic performance of different screening methods was compared by plotting receiver operating characteristic curves (ROC). Results: The proportion of low potassium in PA group was higher than that in the EH group (86.20% vs. 36.50% P<0.001). The area under the ROC curve (AUC) of upright ARR was greater than that of upright AA2R, upright PRA, upright PAC, supine ARR, and lowest blood potassium (P<0.05); The AUC of logistic regression model (nomogram) [which consists of the upright PAC, the upright PRA, and the lowest blood potassium] was greater than that of upright ARR (96.3% vs. 94.6%, P<0.05). Conclusion: The upright ARR is the best single screening indicator; AA2R (radioimmunoassay) is not recommended for PA screening. Ultimately, the logistic regression model (nomogram) is superior to the upright ARR.

MON-211 Prevalence, Characteristics and Outcomes of Primary Aldosteronism in Newly Diagnosed Hypertensives in China (Pa China)

Background 44.7% adults in China have hypertension but the prevalence of primary aldosteronism (PA) in Chinese hypertensives is unknown. Objective We prospectively investigated the prevalence of PA in newly diagnosed hypertensives and tested the hypothesis that these PA patients have less severe cardiovascular complications and better outcomes when compared to those diagnosed after established (or prolonged) hypertension. Method In a community health center, consecutive hypertensive patients with an aldosterone-renin ratio≥2 (ng∙dL−1/mIU∙L−1) and plasma aldosterone concentration >10ng/dL underwent captopril challenge test and/or saline infusion test for confirmation. Adrenal CT scan and adrenal vein sampling were used for subtyping. PA patients were followed up for one year and clinical outcomes were compared with PA patients from an established hypertensive cohort. Results 1020 newly diagnosed hypertensive patients were screened over 16 months. Forty were diagnosed with PA, 948 with non-PA, resulting in a prevalence of 4.0%. Thirty-two patients were diagnosed as “possible PA” due to positive screening but failure to complete the confirmatory test. Compared to non-PA, PA patients more frequently displayed microalbuminuria (P=0.031), but the incidence of cardiovascular events was not different (P=0.927). For patients treated with surgery, complete clinical success rate was 85.7%, 28% higher than that of PA patients diagnosed after prolonged hypertension. For patients treated with medication, blood pressure control rate was 79.3%, 30% higher than that of PA patients diagnosed after prolonged hypertension. Conclusions The prevalence of PA in patients with newly diagnosed hypertension in China was at least 4.0%. PA screening in newly diagnosed hypertensive patients can lead to better clinical outcomes.

SUN-LB98 RAAS Triple-A Analysis for the Screening of Primary Aldosteronism

Primary aldosteronism (PA) is recognized as the most frequent cause of secondary hypertension, and its screening is expected to become a routine evaluation in most patients with hypertension. The interference of antihypertensive therapies with the aldosterone-to-renin ratio (ARR) during screening process is a major confounder. Renin-Angiotensin-Aldosterone System Triple-A (RAAS Triple-A) testing is a novel mass-spectrometry based assay for quantification of Angiotensin I (Ang I), Angiotenisn II (Ang II) and Aldosterone in a single sample of serum by RAAS equilibrium analysis. Obtained hormone levels are used to calculate markers for plasma-renin-activity (PRA-S, Ang I + Ang II), plasma angiotensin-converting-enzyme activity (ACE-S, Ang II-to-Ang I ratio) and adrenal function (AA2-Ratio, Aldosterone-to-Ang II ratio), with the latter being useful to screen for PA in hypertension. We performed a comparative evaluation of the diagnostic performance of the AA2-Ratio and 5 renin-based diagnostic ratios, differing in methods to determine aldosterone levels and renin activity in a cohort of 110 patients with hypertension (33 patients with confirmed primary aldosteronism and 77 with essential hypertension). All ratios showed comparable areas under the curves ranging between 0.924 and 0.970 without significant differences between each other. The evaluation of the ACE-S revealed persistent drug intake in some patients as cause for suppressed renin-based diagnostic ratios, while the AA2-Ratio remained unaffected. The Youden index optimal cutoff value for the AA2-Ratio was 6.6 ([pmol/L]/[pmol/L]) with a sensitivity of 90% and a specificity of 93%, proving non-inferiority compared with the ARR while pointing to the potential for an interference-free application in patients under ACE inhibitor therapy. This study shows for the first time the accuracy and reliability of RAAS Triple-A analysis for the screening of primary aldosteronism that can be applied in clinical routine.