Renin Aldosterone Research Articles

The Diagnostic Value of Captopril Challenge Test for Primary Aldosteronism

To investigate the diagnostic value of different captopril challenge test (CCT) diagnostic criteria for diagnosing primary aldosteronism (PA). We collected the clinical data of 184 patients with hypertension retrospectively in West China Hospital of Sichuan University. Receiver operating characteristic (ROC) curves were used to analyze the post-CCT efficacy of aldosterone renin activity ratio (ARR), plasma aldosterone concentration (PAC), plasma renin activity (PRA) and PAC suppression rate for PA diagnosis. This study included 125 cases of primary aldehyde (PA group) and 59 cases of essential hypertension (EH group), and there were 38 normal renin primary hypertension (NREH group) and 21 low renin primary hypertension (LREH group) in EH group. The post-CCT PAC suppression rate (median (P 25, P 75)) of EH and PA group were 0.190 (0.083, 0.351) and 0.125 (0.024, 0.237), respectively. Compared with the NREH group, the basic and post-CCT PRA of LREH group were lower ( P<0.001), and there were no significant differences compared with the PA group ( P>0.05). We found significant overlap of post-CCT PRA and ARR between PA group and LREH group, while the overlap of post-CCT PAC between the two groups was small. In differential diagnosis of PA and EH, the areas under ROC curve of the post-CCT ARR, PAC, PRA and PAC suppression rate were 0.860 (95% confidence interval ( CI): 0.800-0.907), 0.881 (95% CI: 0.825-0.924), 0.771 (95% CI: 0.703-0.831) and 0.632 (95% CI: 0.558-0.701), respectively. There was no significant difference between the first two indexes ( Z=0.443, P=0.658), and both of them were higher than the latter two ( P<0.05). The optimal post-CCT cut-off values for ARR and PAC in differential diagnosis of PA and EH were 19.24 ng·dL -1 with a sensitivity of 78.4% and a specificity of 88.1%, and 32.47 (ng·dL -1)/(ng·mL -1·h -1) with a sensitivity of 84.17% and a specificity of 72.41%. Both ARR and PAC have higher diagnostic value than the post-CCT PAC suppression rate, post-CCT PAC is especially suitable as a confirmatory testing criterion of PA.

Seated Saline Suppression Test Is Comparable With Captopril Challenge Test for the Diagnosis of Primary Aldosteronism: A Prospective Study

ObjectiveThe saline suppression test (SST) and captopril challenge test (CCT) are commonly used confirmatory tests for primary aldosteronism (PA). Seated SST (SSST) has been reported to be superior to recumbent SST. Whether SSST is better than CCT remains unclear. We aimed to compare the diagnostic accuracy of SSST and CCT in a prospective study. MethodsHypertensive patients at a high risk of PA were consecutively included. Patients with an aldosterone-renin ratio of ≥1.0 ng/dL/μIU/mL were asked to complete SSST, CCT, and the fludrocortisone suppression test (FST). Using FST as a reference standard (plasma aldosterone concentration [PAC] post FST ≥ 6.0 ng/dL), area under the receiver-operating characteristic curve (AUC), sensitivity, and specificity of SSST and CCT were calculated, and multiple regression analyses were performed to identify potential factors leading to false diagnosis. ResultsA total of 196 patients diagnosed with PA and 73 with essential hypertension completed the study. Using PAC post SSST and PAC post CCT to confirm PA, SSST and CCT had comparable AUCs (AUCSSST 0.87 [95% CI 0.82-0.91] vs AUCCCT 0.88 [0.83-0.95], P = .646). When PAC post SSST and post CCT were set at 8.5 and 11 ng/dL, respectively, the sensitivity and specificity of SSST (0.72 [0.65, 0.78] and 0.86 [0.76, 0.93]) and CCT (0.73 [0.67, 0.80] and 0.85 [0.75, 0.92]) were not significantly different. In the multiple regression analyses, 1-SD increment of sodium intake resulted in a 40% lower risk of false diagnosis with SSST. ConclusionSSST and CCT have comparable diagnostic accuracy. Insufficient sodium intake decreases the diagnostic efficiency of SSST but not of CCT. Since CCT is simpler and cheaper, it is preferred over SSST.

Prevalence, Subtype Classification, and Outcomes of Treatment of Primary Aldosteronism: A Prospective Study in China

ObjectiveTo investigate the prevalence of primary aldosteronism (PA) among participants with hypertension, evaluate the concordance of PA classification between adrenal computed tomography and adrenal venous sampling, and compare the outcomes of surgery and medication for unilateral PA. MethodsA prospective study was conducted among all inpatients with hypertension (n = 7594) at the National Center for Cardiovascular Diseases, China, from May 2016 to April 2018. ResultsOf the 7594 participants, 8.12% (n = 617) with plasma aldosterone-renin ratio ≥3.7 were possible PA cases. Three hundred sixty-seven cases with plasma aldosterone-renin ratio ≥3.7 and plasma aldosterone concentration ≥10 ng/dL were confirmed using the recumbent saline infusion test (69.20%, 182 of 263) or the captopril challenge test (66.5%, 69 of 104, P > .05). The prevalence of PA was 3.31% (n = 251). Of the 251 patients with PA, all of them had multiple comorbidities, and 49.40% (n = 124) had spontaneous hypokalemia. The concordance of PA classification between adrenal computed tomography and adrenal venous sampling was only 47.11%. The patients’ blood pressure declined to normal ranges in the adrenalectomy (85.71%, 30 of 35) and spironolactone (63.04%; 29 of 46) groups (P < .05). Furthermore, hypokalemia was normalized in the adrenalectomy (100.00%; 26 of 26) and spironolactone (94.74%; 18 of 19) groups. ConclusionIt is necessary to incorporate PA screening into routine practice for those with hypertension in the Chinese population. This will assist in ensuring that the best therapeutic schedule based on PA subtypes is devised. Additionally, as a result, it may contribute to restoring the blood pressure levels and reducing the prevalence of comorbidities in these patients with PA.

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.

Masked Uncontrolled Hypertension Is Accompanied by Increased Out-of-Clinic Aldosterone Secretion.

Masked uncontrolled hypertension (MUCH) in treated patients is defined as controlled office blood pressure (BP) but uncontrolled out-of-clinic ambulatory BP. Previously, we have shown that patients with MUCH have evidence of heightened out-of-clinic sympathetic nervous system activity. The aim is to test the hypothesis that MUCH patients have higher aldosterone secretion compared with patients with true controlled hypertension. Two hundred twenty-two patients were recruited after having controlled office BP readings at ≥3 clinic visits. Patients taking MR (mineralocorticoid receptor) antagonists and epithelial sodium channel blockers were excluded. All patients were evaluated by clinic automated office BP and morning serum aldosterone and plasma renin activity. Out-of-clinic ambulatory BP monitoring and 24-hour urinary aldosterone, catecholamines, and metanephrines were also measured. Sixty-four patients had MUCH, and the remaining 48 patients had true controlled hypertension. MUCH patients had significantly higher out-of-clinic levels of 24-hour urinary aldosterone, catecholamines, and metanephrines compared with true controlled hypertension. The 2 groups did not differ in serum aldosterone, plasma renin activity, or aldosterone-renin ratio collected in clinic. In addition, 32.8% of MUCH patients had high out-of-clinic 24-hour urinary aldosterone (≥12 µg) but normal clinic serum aldosterone (<15 ng/dL) and aldosterone-renin ratio (<20). Further, in correlation matrix analysis, higher 24-hour urinary catecholamines and metanephrines were associated with higher 24-hour urinary aldosterone and plasma renin activity levels in MUCH patients. Patients with MUCH have higher out-of-clinic urinary aldosterone levels compared with patients with true controlled hypertension. This study suggests that patients with MUCH likely have higher out-of-clinic sympathetic nervous system tone increases aldosterone secretion mediated by increased renin release that may contribute to their higher out-of-clinic BP.

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.

Diagnostic accuracy of adrenal imaging for subtype diagnosis in primary aldosteronism: systematic review and meta-analysis

ObjectivesAccurate subtype classification in primary aldosteronism (PA) is critical in assessing the optimal treatment options. This study aimed to evaluate the diagnostic accuracy of adrenal imaging for unilateral PA classification.MethodsSystematic...

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.

Clinical Evaluation of Assays for Plasma Renin Activity and Aldosterone Measurement by Liquid Chromatography-Tandem Mass Spectrometry.

Aldosterone and renin are pivotal hormones in the regulation of salt and water homeostasis and blood pressure. Measurement of renin and aldosterone in serum/plasma is essential for the investigation of primary hyperaldosteronism (PA) and monitoring of glucocorticoid replacement therapy. We report 2 LC-MS/MS methods developed to measure aldosterone and plasma renin activity (PRA). PRA was determined by endogenous enzymatic generation of angiotensin I using 150 µL of sample. Generated angiotensin I was purified by solid phase extraction prior to chromatographic separation and mass spectrometry. Aldosterone measurement required 300 μL of sample extracted with MTBE prior to LC-MS/MS analysis. The PRA method was linear (1.2-193 nmol/L), sensitive (LLOQ = 1.2 nmol/L), precise (CV = 4.1%), and specific (no cross reactivity for a number of structurally similar steroids). Dilutional linearity and recovery (84%) were acceptable. Accuracy was confirmed by comparison against our current RIA method. The aldosterone method had equally acceptable performance characteristics. Reference ranges in 110 healthy normotensive subjects were: PRA 0.2-3.7 nmol/L/h and aldosterone 50-950 pmol/L. Consecutive patients (n = 62) with adrenal incidentalomas shown to have no functional adrenal disease; their post overnight 1 mg dexamethasone test values were: PRA 0.2-2.6 nmol/L/h and aldosterone 55-480 pmol/L. Serum aldosterone values after 2 liter saline suppression were-normal subjects (n = 17): 78-238 pmol/L and confirmed primary hyperaldosteronism (n = 25): 131-1080 pmol/L. We have developed robust assays for PRA and aldosterone with appropriate clinical evaluation. These assays are now in routine practice in the UK.

A Clinical-Radiomics Nomogram Based on Unenhanced Computed Tomography for Predicting the Risk of Aldosterone-Producing Adenoma

Purpose: To develop and validate a clinical-radiomics nomogram for the preoperative prediction of the risk of aldosterone-producing adenoma (APA) in patients with unilateral adrenal adenoma. Patients and Methods: Ninety consecutive primary aldosteronism (PA) patients with unilateral adrenal adenoma who underwent adrenal venous sampling (AVS) were randomly divided into a training cohort (n=62) and a validation cohort (n=28) by a computer algorithm at a ratio of 7:3, and data were gathered from October 2017 to June 2020. The prediction model was developed in the training cohort. Radiomic features were extracted from unenhanced computed tomography (CT) images of unilateral adrenal adenoma. The least absolute shrinkage and selection operator (LASSO) regression model was used for data dimension reduction, feature selection, and radiomics signature building. Multivariable logistic regression analysis was used to develop the predictive model, integrating the radiomics signature and clinical risk factors, and this model was presented as a clinical-radiomics nomogram. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. Internal validation was performed. Results: By using the LASSO regression model, 358 texture features were reduced to 6 potential predictors. These features were presented in the Radscore calculated by using the formula. The predictors included in the individualized prediction nomogram were Radscore, age, sex, serum potassium and aldosterone-to-renin ratio (ARR). The model showed good discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.900 (95% confidence interval (CI), 0.807 to 0.993), and good calibration. The nomogram still showed good discrimination (AUC, 0.912 [95% CI, 0.761 to 1.000]) and good calibration in the validation cohort. Decision curve analysis demonstrated that the nomogram was clinically useful. Conclusions: This study constructed a clinical-radiomics nomogram integrating a radiomics signature and some clinical factors, which facilitates the accurate detection of the probability of APA in patients with a unilateral adrenal nodule and would be helpful for clinical decision making. Funding Statement: This study was supported by the National Natural Science Foundation of China (grant number 81960088 and 82060557), the Key R & D Projects of Jiangxi Province, China (NO. 20171ACG70002) and Graduate Student Innovation Special Fund Project of Jiangxi Province, China (NO. YC2020-B055). Declaration of Interests: The authors have declared that no competing interest exists. Ethics Approval Statement: This retrospective study was approved by the Second Affiliated Hospital of Nanchang University Medical Research Ethics Committee (Jiangxi, China), and the requirement for informed consent was waived.

Prevalence and clinical characteristics of obstructive sleep apnea in patients with primary hyperaldosteronism

Objective: To explore the proportion of obstructive sleep apnea (OSA) in primary aldosteronism (PA) in Chinese population and compare the clinical characteristics between PA patients with OSA and those without. Methods: A total of 96 patients diagnosed with PA from September 2015 to November 2018 were recruited in this study. OSA was screened by cardio-respiratory polygraphy. According to the apnea hypopnea index (AHI), the patients were divided into PA with OSA group (AHI ≥5 times) and PA without OSA group (AHI<5 times). Results: Among all patients (96), 69 (71.9%) were with OSA, among them 22 patients (22.9%) were with mild OSA, 17 patients (17.7%) were with moderate OSA and 30 patients (31.3%) were with severe OSA. Compared with the patients without OSA, the patients with OSA were elder, and had higher levels of body mass index (BMI), waist circumference (WC), hip circumference (HC), creatinine (CR) and glycosylated haemoglobin (HbA1c) (P<0.05), but lower concentrations of plasma aldosterone (PAC), supine aldosterone renin concentration ratio(ARR) and the PAC after the diagnosis test (P<0.05). Spearman correlation analyses showed that BMI, WC, HC, CR and HbA1c were positively correlated with AHI (P<0.05), while high-density lipoproteincholesterol (HDL-C), supine-PAC and saline infusion test(SIT)-post PAC were negatively correlated with AHI (P<0.05). Conclusions: The proportion of OSA in PA patients is relatively high (71.9%). Metabolic abnormalities are more common in PA patients with OSA, indicating that screening for OSA should be carried out routinely in PA patients.

Volumetric Modeling of Adrenal Gland Size in Primary Bilateral Macronodular Adrenocortical Hyperplasia.

Radiological characterization of adrenal size in primary bilateral macronodular adrenocortical hyperplasia (PBMAH) has not been previously investigated. We hypothesized that volumetric modeling of adrenal gland size may correlate with biochemical disease severity in patients with PBMAH. Secondary analysis of patients with concurrent primary aldosteronism (PA) was performed. A retrospective cross-sectional analysis of 44 patients with PBMAH was conducted from 2000 to 2019. Tertiary care clinical research center. Patients were diagnosed with PBMAH based upon clinical, genetic, radiographic and biochemical characteristics. Clinical, biochemical, and genetic data were obtained. Computed tomography scans were used to create volumetric models by manually contouring both adrenal glands in each slice using Vitrea Core Fx v6.3 software (Vital Images, Minnetonka, Minnesota). 17-hydroxycorticosteroids (17-OHS), ARMC5 genetics, and aldosterone-to-renin ratio (ARR) were retrospectively obtained. Pearson test was used for correlation analysis of biochemical data with adrenal volume. A cohort of 44 patients with PBMAH was evaluated, with a mean age (±SD) of 53 ± 11.53. Eight patients met the diagnostic criteria for PA, of whom 6 (75%) were Black. In the Black cohort, total adrenal volumes positively correlated with midnight cortisol (R = 0.76, P = 0.028), urinary free cortisol (R = 0.70, P = 0.035), and 17-OHS (R = 0.87, P = 0.0045), with a more pronounced correlation with left adrenal volume alone. 17-OHS concentration positively correlated with total, left, and right adrenal volume in patients harboring pathogenic variants in ARMC5 (R = 0.72, P = 0.018; R = 0.65, P = 0.042; and R = 0.73, P = 0.016, respectively). Volumetric modeling of adrenal gland size may associate with biochemical severity in patients with PBMAH, with particular utility in Black patients.

Computed tomography combined with confirmatory tests for the diagnosis of aldosterone-producing adenoma.

Primary aldosteronism (PA) is the most common cause of secondary hypertension, and a simpler non-invasive method for identification of aldosterone-producing adenoma (APA) is required to improve the standard of medical treatment for PA patients. We retrospectively analyzed the clinical data of hypertensive patients with an aldosterone/renin ratio (ARR) ≥30 (ng/dL)/(ng/mL/h), and surgical and/or adrenal venous sampling (AVS) results served as the gold standard for APA diagnosis. The study aimed to determine whether positive CCT and SIT results plus a unilateral adrenal nodule found by CT allow unambiguous identification of an APA with high diagnostic specificity. Clinical data from 71 APA and 47 non-APA patients were collected, and logistic regression analysis was performed to construct models. Receiver operating characteristic (ROC) curves were used to analyze the efficacy of diagnostic tests. The areas under the ROC curves (AUCs) were similar between the post-SIT plasma aldosterone concentration (PAC) and post-CCT PAC (p > 0.05). The optimal post-SIT and post-CCT PAC cutoff values were 17.2 and 21.2 ng/dL, respectively. Positive CT findings combined with a post-SIT PAC >17.2 ng/dL or post-CCT PAC >21.2 ng/dL provided specificities of 97.8% and 95.7% for predicting APA, respectively. Logistic diagnostic models 1 (M1, CT finding + post-SIT PAC) and 2 (M2, CT finding + post-CCT PAC) were built, which showed equivalent diagnostic value (AUC = 0.959 and 0.932, respectively) (p > 0.05). The models combining CT findings with post-SIT PACs or post-CCT PACs represent an easier method to distinguish APA patients from other hypertensive patients with positive upright ARR results, especially in primary care where AVS may be unavailable.

The value of the post-captopril aldosterone/renin ratio for the diagnosis of primary aldosteronism and the influential factors: A meta-analysis.

Objective:The procedure for the captopril challenge test (CCT) in diagnosing primary aldosteronism (PA) is not standardized. We performed a meta-analysis to evaluate the controversial diagnostic value and influential factors of the post-captopril aldosterone/renin ratio (ARR).Methods:We searched literature in databases for eligible studies (until October 1, 2020). We extracted information regarding study and patient characteristics, CCT methods, outcome data. We pooled studies using the random-effect model. We performed meta-regression and six pre-specified subgroup analyses to explore heterogeneity.Results:Nineteen studies involving 4568 subjects were included. The pooled sensitivity and specificity were 0.825 (95% CI 0.804–0.844) and 0.919 (95% CI 0.908–0.928). The area under the summary receiver operating characteristic curve was 0.9487 (95% CI 0.9207–0.9767). Meta-regression revealed that heterogeneity might derive from time interval (p = 0.0117) and study population (p = 0.0033). Subgroup analyses showed significant differences between the subgroups stratified by the dose, posture, study region, time interval, cut-off value and study population for sensitivity and/or specificity (p < 0.05).Conclusion:Post-captopril ARR is comparably valuable for diagnosing PA at cut-offs from 12.0 to 50.0. Conducting the CCT in the supine position with 25 mg of captopril may attain greater sensitivity. Conducting the CCT in the seated position with 50 mg of captopril may attain greater specificity. A 90-min time interval may perform best in both the sensitivity and specificity.

Patients with pheochromocytoma exhibit low aldosterone renin ratio-preliminary reports

BackgroundPlasma 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).MethodsIn 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.ResultsPRA 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 < 0.001). Receiver operating characteristic curve analysis demonstrated that, in differentiating PCC from NFA, PRA > 1.55 ng/mL/h showed a sensitivity of 70.0% and specificity of 80.6%. Interestingly, ARR < 95.4 showed a sensitivity of 83.3% and specificity of 86.7%, which were higher than those in PRA.ConclusionsARR 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 registrationThis study was not registered because of the retrospective analysis.

Adrenal Vein Sampling Without Discontinuation of Mineralocorticoid Receptor Antagonist Therapy

Objective: Guidelines recommend withdrawing mineralocorticoid-receptor antagonists (MRAs) for 4 weeks prior to adrenal vein sampling (AVS), but this is not always feasible because of hypertension and hypokalemia. This retrospective study of primary aldosteronism (PA) patients who underwent AVS between 2008 and 2018 assessed the effect of continuing MRA on the AVS procedure.Methods: Clinical data including antihypertensive regimen defined by the World Health Organization Daily Defined Dose (DDD) system were collected for 19 patients with adequate cannulation and lateralization during AVS. Results were compared between 5 patients who continued and 14 patients who discontinued MRA therapy (MRA and non-MRA groups).Results: At diagnosis, plasma renin activity, plasma aldosterone concentration (PAC), potassium (K) doses, and DDD were not significantly different between groups. Aldosterone-renin ratio was significantly higher in the MRA group (median, 375.0; interquartile range [IQR], 224.8 to 544.3 vs. 148.7, 118.4 to 192.1; P = .034). No difference was found in lateralization index (median 48.3; IQR, 23.6 to 52.1 vs. 8.7; 4.9 to 20.2; P = .10). Contralateral suppression, defined as aldosterone-cortisol ratio of unaffected adrenal to periphery, trended lower in the MRA group (median, 0.17; IQR, 0.03 to 0.39 vs. 0.51; 0.27 to 1.1; P = .056). All five MRA patients underwent successful adrenalectomy with at least 50% reduction in DDD and PAC and normal K postoperatively. One MRA patient did not lateralize, which was confirmed on repeat AVS, after MRA withdrawal.Conclusion: Continuation of MRA may not interfere with AVS lateralization or affect contralateral adrenal suppression. Continuation of MRA in preparation for AVS may be considered, especially in patients with severe PA, to avoid uncontrolled hypertension and severe hypokalemia.

Abstract P234: Pre- And Post-treatment Analysis Of Pendrin In The Urinary Exosome In Primary Aldosteronism

Background and Aim: Pendrin is a Cl/HCO3 exchanger that is selectively present at the apical membrane in non-α intercalated cells of the renal tubules in the kidney. Besides its role in acid/base homeostasis, accumulating studies provided evidence that pendrin regulates extracellular fluid volume and electrolyte balance. Experimental studies using animal models also indicate that pendrin is upregulated in a high aldosterone state, along with the induction of NaCl cotransporter and epithelial Na channel. However, the regulation of pendrin in human is unclear. The present study was conducted to examine the levels of pendrin in subjects with primary aldosteronism. Methods: Sixteen patients who were diagnosed as primary aldosteronism at Teikyo University Hospital and Yokohama Rosai Hospital were enrolled in this study. We isolated exosomes from pre- and post-treatment urine samples by the ultracentrifugation method, and the levels of pendrin was evaluated by Western blotting. The loading amount was adjusted by creatinine concentration. Purification of exosomal fraction was confirmed by electron microscopy and also by the presence of alix, a marker of exosome. Results and Discussion: Among 16 patients, six received unilateral adrenalectomy and 10 received MR antagonist as the treatment. Mean aldosterone-to renin ratio was 1085. We excluded two subjects because alix was not detected in the pre-treatment samples, and the analysis was done in 14 subjects. In human urine, pendrin was detected at ~110kDa and ~220kDa, the latter likely representing a dimer. We found that pendrin abundance was significantly reduced by 49.8% (P&lt;0.01) in post-treatment samples compared with pre-treatment samples. Therefore, pendrin is altered in primary aldosteronism, likely contributing to the pathophysiology of aldosterone excess in humans.

Abstract P232: Dilated Cardiomyopathy With Electrocardiographic Changes And Coronary-Pulmonary Fistula: An Uncommon Presentation Of Primary Aldosteronism In The Covid-19 Era

Primary aldosteronism is the most frequent forms of curable hypertension and elevated aldosterone levels have been associated with endothelial proliferation and pathological remodeling of the heart and arteries; however, coronary arterial abnormalities have never been reported in patients with primary aldosteronism. We report the case of a 53-year-old Caucasian obese man (BMI 37 Kg/m 2 ) with recent history of hypertension, fatigue and subjective dyspnea who was admitted to our hospital after performing an outpatient echocardiography that showed hypertensive and ischemic heart disease in dilated phase (LVEDVI 95 mL/m 2 ; LVEF 43%). His laboratory results showed hypokalemia (3 mmol/L) and an elevated aldosterone-renin ratio [(294 ng/L)/(1μU/mL)]. After case confirmation with saline infusion test, the abdominal CT scan showed a subcentimeter adenoma in the right adrenal gland. Surprisingly we noticed that, after oral potassium correction, the electrocardiogram revealed a symmetrical T-wave inversion and subsequently a coronary angiography detected a coronary artery fistula between the left anterior descending artery and the pulmonary artery in the absence of significant stenosis. In the Italy's CoViD-19 pandemic full spread, we preferred to postpone the diagnosis of the lateralization of aldosterone hypersecretion by adrenal vein sampling and we started a mineralocorticoid receptor antagonist with a clinical follow-up of cardiovascular symptoms for the optimal treatment of coronary artery fistula. After about two months of follow-up, the patient remains asymptomatic with good blood pressure control, normal potassium levels and significant echocardiographic improvement (LVEDVI 67 mL/m 2 ; LVEF 51%). Our case highlights a possible association between hypertensive patients with coronary artery fistulas and primary aldosteronism. We recommend cardiologists and clinicians to maintain a high level of suspicion of primary aldosteronism in these patients.

Clinical characteristics of primary aldosteronism in newly diagnosed diabetes mellitus with hypertensive patients.

To investigate the prevalence of primary aldosteronism (PA) in newly diagnosed diabetic patients with hypertension and to compare clinical differences between newly diagnosed diabetes mellitus with essential hypertension (EH) and PA, and to explore the relationship between plasm aldosterone concentration (PAC) and clinical biochemical variables. A total of 270 newly diagnosed diabetic patients with hypertension were prospectively enrolled in this study. All patients were screened for PA. The positive patients in the screening test were further confirmed by captopril challenge test (CCT) to determine the prevalence of PA. Clinical biochemical indexes were detected. The prevalence of PA in 270 newly diagnosed diabetic patients with hypertension was 18.5%. Compared with patients in the EH group, patients in the PA group had higher systolic blood pressure (SBP), PAC, aldosterone to renin ratio (ARR), and carbondioxide binding force, but lower plasma renin activity (PRA) and serum potassium. Correlation analysis showed that the PAC was positively correlated with homeostasis model assessment-insulin resistance (HOMA-IR) in the EH group (r=0.139, P<0.05), but the correlation was not found in the PA group. Compared with patients with SBP<140 mmHg, patients with SBP≥160 mmHg had the significantly decreased PRA and potassium (P<0.05, P<0.001, respectively), but increased ARR and proportion in the PA patients (P<0.05, P<0.01, respectively). The prevalence of PA is relatively high in newly diagnosed diabetic patients with hypertension. Patients with hypertension above grade 2 should be actively screened for aldosterone. Newly diagnosed diabetic patients with hypertension combined with PA has a higher hypertension compared with the patients without PA.In newly diagnosed diabetic patients with hypertension, PAC may be related to insulin resistance.