Plasma Aldosterone Concentration Values Research Articles

COMPARISON OF SALINE INFUSION TEST AND CAPTOPRIL CHALLENGE TEST IN THE DIAGNOSIS OF PRIMARY ALDOSTERONISM IN DIFFERENT AGE GROUPS

Objective: To explore the diagnostic accuracy and the optimal cut-off value between the saline infusion test (SIT) and captopril challenge test (CCT) (including the value and suppression of plasma aldosterone concentration (PAC)) for PA diagnosing. Design and method: A total of 318 patients with hypertension were consecutive enrolled including 126 patients with PA and 192 patients with essential hypertension (EH). The characteristics of patients and laboratory examinations were collected and compared. The comparison between SIT and CCT was carried by drawing receiver operator characteristic curve (ROC) and calculating area under the curve (AUC) to explore the diagnostic accuracy and the optimal cut-off value. Results: The average age was 51.59±10.43 in PA group and 45.72±12.44 in EA group (P<0.05). The optimal cut-off value was 10.7 ng/dl for post-CCT PAC, 6.8 ng/dl for post-SIT PAC and 26.9% for suppression of post-CCT PAC. The diagnostic value of post-CCT PAC was the highest with 0.831 for the AUC and 0.552 for the Youden index. The optimal cut-off value for patients who were less than 50 years old was 11.5 ng/dl for post-CCT PAC and 8.4 ng/dl for post-SIT PAC. The suppression of post-CCT PAC turned to 18.2% for those of 50 years old or more than 50 years old. Conclusions: Compared with SIT, CCT presented a higher diagnostic value when post-CCT PAC was used as the diagnostic criteria among Chinese people, while the selection of diagnostic thresholds depended on patients at different age stages.

Adrenal venous sampling criteria for chemiluminescent enzyme immunoassay as a preferable alternative to radioimmunoassay in primary aldosteronism.

Plasma aldosterone concentration (PAC) was routinely measured using radioimmunoassay (RIA); however, the RIA kit was discontinued in March 2021 in Japan. This study examined PAC conversion in adrenal venous sampling (AVS) and AVS criteria when measured using chemiluminescent enzyme immunoassay (CLEIA). PAC of 415 adrenal venous blood samples from AVS (including segmental AVS) of 63 patients with primary aldosteronism was measured using RIA (Spac-S aldosterone kit; Fujirebio Inc.) and CLEIA (Lumipulse Presto Aldosterone; Fujirebio Inc.). PAC of 70 AVS samples was also measured using liquid chromatography-mass spectrometry (LC-MS/MS, ASKA Pharma Medical Co., Ltd.). PAC conversion formulas were determined for each AVS sample assay. PAC measured using CLEIA was significantly correlated with that measured using RIA (correlation coefficient = 0.971). The PAC conversion formula was PAC (CLEIA) = PAC (RIA) × 0.772 - 1,199 pg/mL. The PAC of 14,000 pg/mL in RIA was equivalent to 9,613 pg/mL in CLEIA. PAC measured using CLEIA was also correlated with that measured using LC-MS/MS, and the PAC conversion formula was PAC (CLEIA, pg/mL) = 0.97 × PAC (LC-MS/MS, pg/mL) + 211. The inter-assay coefficient of variability (CV) was 1.1-1.3% and intra-assay CV was 1.0-1.7%, measured using CLEIA. The PAC conversion formula for AVS samples was obtained using CLEIA and RIA, and the conversion formula was different from that for peripheral blood. PAC values measured by CLEIA showed preferable accuracy and high concordance with those measured by LC-MS/MS, even in AVS samples. The study outcomes are useful for interpreting AVS results using non-RIA measurement methods.

Impact of gut microbiome on the renin-aldosterone system: Shika-machi Super Preventive Health Examination results.

The renin-angiotensin-aldosterone system (RAAS) is a regulatory mechanism of the endocrine system and is associated with various diseases, including hypertension and renal and cardiovascular diseases. The gut microbiota (GM) have been associated with various diseases, mainly in animal models. However, to our knowledge, no studies have examined the relationship between the RAAS and GM in humans. The present study aimed to assess the association between the systemic RAAS and GM genera and their causal relationships. The study participants were 377 members of the general population aged 40 years or older in Shika-machi, Japan. Plasma renin activity (PRA), plasma aldosterone concentration (PAC), aldosterone-renin ratio (ARR), and GM composition were analyzed using the 16S rRNA method. The participants were divided into high and low groups according to the PRA, PAC, and ARR values. U-tests, one-way analysis of covariance, and linear discriminant analysis of effect size were used to identify the important bacterial genera between the two groups, and binary classification modeling using Random Forest was used to calculate the importance of the features. The results showed that Blautia, Bacteroides, Akkermansia, and Bifidobacterium were associated with the RAAS parameters. Causal inference analysis using the linear non-Gaussian acyclic model revealed a causal effect of Blautia on PAC via SBP. These results strengthen the association between the systemic RAAS and GM in humans, and interventions targeting the GM may provide new preventive measures and treatments for hypertension and renal disease.

PS-BPC08-1: VALIDATION OF PRIMARY ALDOSTERONISM DIAGNOSIS DURING THE TRANSITIONAL PERIOD OF ALDOSTERONE ASSAY AND GUIDELINE CHANGES IN JAPAN

Objectives and Methods: In Japan, the plasma aldosterone concentration (PAC) measurement method was changed from RIA to CLEIA method in April 2021. From then until August 2021, when the 2021 clinical practice guidelines for the diagnosis and management of primary aldosteronism (PA) were published, we diagnosed PA using the RIA-converted PAC value (conversion formula from CLEIA (X) to RIA (Y): Y = 1.174X + 42.3) and the conventional positive decision criteria of the screening and confirmatory tests in PA diagnosis. The new criteria were then used to re-determine and confirm the agreement. Results: PAC(CLEIA) and renin activity (PRA) or active renin concentration (ARC) were measured simultaneously for PA screening at our hospital from April to August 2021 in 122 patients (135 measurements in total). PAC values (CLEIA) were less than 4 pg/mL in 21 measurements (16%). This value was converted to PAC(RIA) at 47 pg/mL based on the formula. (i) PA screening tests: 10% of the measurements were found to be ‘not excluded’ by the conventional criteria and negative by the new criteria. This was due to the fact that the calculated PAC(RIA) values were higher than they should be when the conversion formula to RIA was applied to cases with low PAC(CLEIA) values, resulting in higher estimated ARR values (PAC(RIA)/PRA or PAC(RIA)/ARC ratio). (ii) PA confirmatory tests: In the captopril challenge test, one case was found to be positive by the conventional criteria and negative by the new criteria due to the same reason as that on point (i). In the saline infusion test, PAC(CLEIA) of 12–15 pg/mL was determined to be less than PAC(RIA) 60 pg/mL by the conversion formula, which was deemed negative by the conventional criteria but borderline by the new criteria. (iii) PA diagnosis using the confirmatory tests: In one case, the diagnosis did not match the positive (borderline) classification based on the new criteria, although the patient was deemed negative by the conventional criteria. This was due to discrepancies of the saline infusion test results. Conclusion: During the transition period of PA diagnosis from the RIA to CLEIA method, it was necessary to review the data and retest the patients according to their symptoms because of possible inconsistencies between the new and conventional criteria-based diagnostic results. PA diagnosis and treatment should be judged comprehensively on a case-by-case basis, without relying entirely on the values of the criteria.

Higher plasma aldosterone is associated with increased risk of cardiovascular events in hypertensive patients with suspected OSA: UROSAH data

ObjectiveTo evaluate the association of plasma aldosterone concentration (PAC) with incident cardiovascular disease (CVD) and all-cause mortality in hypertensive patients with suspected obstructive sleep apnea (OSA) and calculate the optimal cut-off value of PAC for this specific population.Patients and methodsParticipants with PAC at baseline in UROSAH in 2011-2013 were enrolled and followed up till 2021. Composite outcome included CVD and all-cause mortality. Cox proportional hazards model was used to evaluate the relationship between PAC and the composite outcome. Time-dependent ROC curve was used to determine the optimal cut-off value of PAC. Besides, we conducted subgroup analyses and sensitivity analyses.Results3173 hypertensive participants aged 18-84 years comprised analytical sample. During a median follow-up of 7.3 years and 22640 person-years, 69 deaths and 343 cases of incident CVD occurred. The incidence of composite outcome was increased with elevation in tertile of PAC. Compared with the first tertile, the risk of CVD and all-cause death was higher in third tertile (HR=1.81, 95%CI: 1.39-2.35, P<0.001). Time-dependent ROC curve showed optimal threshold for PAC was 12.5ng/dl. Whether renin was suppressed or not (≤0.5 or >0.5ng/ml per h), elevated PAC was associated with an increased risk of CVD. Our results remained stable and consistent in sensitivity analyses.ConclusionHigher PAC was associated with increased risk of CVD and all-cause mortality in hypertensives with suspected OSA, even in the absence of primary aldosteronism (PA). Hypertensives with PAC≥12.5ng/dl showed a significantly increased risk of CVD, indicating that special attention and treatment were required in this specific population.

Re-evaluation of the diagnostic value and optimal cutoff point of captopril challenge test in diagnosis of primary aldosteronism

Objective: The aim of the present study was to re-evaluate the diagnostic value and optimal cutoff point of captopril challenge test (CCT) in diagnosis of primary aldosteronism (PA). Methods: This is a retrospective study. All patients with a high risk for PA underwent screening test, and then proceeded to CCT and fludrocortisone suppression test (FST) on different days. The FST was used as a reference standard for PA. The plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) were measured with an automated chemiluminescence immunoassay. Random number method was performed in the patients with unilateral primary aldosteronism (UPA), in order to make the proportion of the analyzed UPA in PA was 35%. Receiver operating characteristic (ROC) analyses were performed to compare diagnostic accuracy. Results: A total of 543 patients with 400 PA patients and 143 essential hypertension (EH) patients were enrolled. The diagnostic value of post-CCT PAC was significantly higher than that of the post-CCT plasma aldosterone-renin ratio (ARR), and that of the PAC suppression percentage, respectively. The area under the ROC curve (AUCROC) was 0.86 (0.83, 0.89) for PAC, 0.78 (0.74, 0.82) for ARR, and 0.62 (0.56, 0.67) for the PAC suppression percentage (all P<0.01), respectively. The optimal cutoff point of post-CCT PAC for PA was 110 ng/L, in which the sensitivity and specificity were 73.25% and 79.02%, respectively. The diagnostic efficiency of post-CCT PAC was not improved either in combination with PAC suppression percentage or in combination with post-CCT ARR. Conclusions: CCT is a useful test for the confirmation of PA. PAC level of 110 ng/L at 2 h after 50 mg of captopril is recommended as an optimal cutoff point for the diagnosis of PA.

HIGH LEVEL OF PLASMA ALDOSTERONE AFTER SALINE INFUSION TEST IN COMBINATION WITH FINDING OF ADRENAL NODE ON CT SCAN CAN PREDICT ALDOSTERONE-PRODUCING ADENOMA MORE PRECISE THAN FINDING OF NODE ALONE

Objective: Idiopathic aldosteronism due to bilateral hyperplasia and unilateral aldosterone-producing adenoma of adrenal gland are two main forms of primary aldosteronism. The discrimination between unilateral and bilateral aldosterone overproduction is crucial for an appropriate management of patients with primary aldosteronism. This study tests the reliability of plasma aldosterone after the postural stimulation test and after the saline infusion test in combination with finding of adrenal node on CT scan for the identification of these two common forms of primary aldosteronism. Methods: One hundred and fifty patients with laboratory diagnosis of primary aldosteronism (96 patients with confirmed diagnosis of aldosterone producing adenoma and 54 patients with idiopathic aldosteronism were enrolled into the study. All of patients underwent CT scan, the postural stimulation test, the saline infusion test and adrenal venous sampling. Design and method: Plasma aldosterone concentration in the supine or in the standing position and after the saline infusion were higher in patients with aldosterone-producing adenoma than in those with idiopathic aldosteronism (P &lt; 0.001; P &lt; 0.01 and P &lt; 0.001, respectively). The largest area under the curve = 0.83 (for a cut-off of 165 ng/l) suggesting the diagnosis of unilateral aldosterone overproduction was found for finding of adrenal node on CT scan in combination with plasma aldosterone concentration after the saline infusion test with a sensitivity of 83%, specificity of 61%, positive-predictive value of 79% and negative-predictive value of 67%. Results: The study found that the value of plasma aldosterone concentration ?165 ng/l after the saline infusion test in combination with finding of node on CT scan can predict aldosterone-producing adenoma more precise than finding of node alone, nevertheless, results of adrenal venous sampling remain to be crucial in the identification of two common forms of primary aldosteronism. The study found that the value of plasma aldosterone concentration ?165 ng/l after the saline infusion test in combination with finding of node on CT scan can predict aldosterone-producing adenoma more precise than finding of node alone, nevertheless, results of adrenal venous sampling remain to be crucial in the identification of two common forms of primary aldosteronism.

USEFULNESS OF SHORTENED SALINE INFUSION TEST FOR PRIMARY ALDOSTERONISM DIAGNOSTICS

Objective: Primary aldosteronism (PA) is a frequent and remediable cause of endocrine hypertension. Saline infusion test (SIT) is one of the most widely-accepted confirmatory tests for PA, but some patients may not tolerate the standard loading volume of 2 L saline over 4 h. Shortened SIT, loading only 1 L saline over 2 h, has been suggested to be useful and would be more acceptable across wider population if the diagnostic utility proves to be comparable to the standard SIT. Therefore, we compared the diagnostic values of plasma aldosterone concentration after 2 hours of 1 L saline loading (2 h PAC) and those after 4 hours of 2 L saline loading (4 h PAC) for the prediction of unilateral aldosterone hypersecretion and postoperative outcome. Design and method: The retrospective, single-center study involved 555 PA-suspected patients who underwent recumbent SIT, 153 of whom subsequently underwent adrenal vein sampling (AVS). Postoperative blood pressure outcome was also examined in 37 patients. We calculated the defined daily doses (DDD) of anti-hypertensive drugs according to those set by the World Health Organization, and compared the values between before and 1 year after the surgery. Results: The Youden Index of 2 h PAC for receiver operating characteristic (ROC) curves of 4 h PAC &gt; 60 pg/mL (The SIT was considered positive if 4 h PAC was over 60 pg/mL according to the Japan Endocrine Society 2009 guidelines) was 66 pg/mL. The areas under the ROC curves of 2 h and 4 h PAC were comparable (0.80 vs.0.85, 95% CI -0.1035 – 0.0109, P = 0.11) for unilateral aldosterone hypersecretion defined as lateralization index &gt;4. Postoperative reduction of anti-hypertensive drug use and 2 h PAC was significantly correlated (P = 0.04). The areas under the ROC curves of 2 h and 4 h PAC were comparable (0.82 vs.0.78, 95% CI -0.0949 – 0.1706, P = 0.58) for postoperative reduction of anti-hypertensive drug use. Conclusions: Shortened SIT may be similarly useful as standard SIT to select PA patients for AVS and also to predict postoperative blood pressure outcome with reduced burden on patients.

COMPARISON OF PARTIAL SEATED SALINE INFUSION TEST AND SEATED SALINE INFUSION TEST FOR THE DIAGNOSIS OF PRIMARY ALDOSTERONISM

Objective: Seated saline infusion test (SSIT) has proved to be much more sensitive to recumbent saline infusion test (RSIT) in confirmation of primary aldosteronism (PA), highly specific, much cheaper and less complicated than fludrocortisone suppression testing (FST). However, SSIT requires the subjects to keep sitting position for 4.5 h, which is not comfortable for all patients, especially for the elderly. The purpose of this study was to explore the diagnostic consistency between more free and comfortable partial seated saline infusion test (PSSIT) and SSIT. Design and method: The current study involved 89 hypertensive patients who had positive results in the screening test and underwent both PSSIT and SSST for the confirmation of PA. For SSIT, patients remained sitting posture for 4.5 hours (0.5 h before the basal measurement of PAC at 9am local time and during the whole process of saline infusion). For PSSIT, patients remained sitting posture for 0.5 h before the measurement of basal PAC and 0.5 h before the completion of saline infusion, for the rest of the time in the process of infusion, subjects were permitted to adopted more free and comfortable posture. Two liters of 0.9% NaCl was administered intravenously over 4 h during SSIT or PSSIT. The diagnostic consistency between PSSIT and SSIT was analyzed. Results: The plasma aldosterone concentration (PAC) after PSSIT was significantly lower than that of SSIT (6.06 vs 7.07ng/dL, P &lt; 0.001). Eight patients (9%) who had post-PSSIT PAC less than 10ng/dl had post-SSIT PAC greater than 10ng/dl. The two saline infusion tests had lower correlation coefficient (r = 0.246, P = 0.02) and intra group correlation coefficient (ICC = 0.194, P = 0.015). ROC analysis predicted optimal cut-off aldosterone levels of 5.385 ng/dl for PSSIT with high sensitivity (80%) but low specificity (50%) when use 6 ng/dl for SSIT according to the Endocrine Society Guideline. Conclusions: The optimal cut-off values of PAC for PSSIT were lower than that of SSIT with high sensitivity but low specificity, which need to be noted in clinical application.

The Transitional Changes in Hormones that Have Water Retention Effect after Liver Resection

Background: In Japan, the use of anti-aldosterone drugs for postoperative water retention caused by hyperaldosteronism after liver resection (LR) is standard. Increased values of arginine vasopressin (AVP) are also expected after LR. We examined the transitional changes in values of plasma aldosterone concentration (PAC) and AVP and volume of drained ascites after LR. Methods: 56 patients underwent LR. PAC and AVP values were measured on before (baseline) and after LR, and postoperative-day (POD) 1, 2, 3, and 5. Results: The PAC values on just after LR (p< 0.01), POD1 (p< 0.01) and POD2 (p = 0.02) were higher than baseline, but POD3 and POD5 were not significant. AVP values were higher on just after LR, POD1, POD2, and POD3 (all p< 0.01), and POD5 did not differ from baseline. When classified into two groups, impaired-liver (IL) group and normal-liver (NL) group, based on ICGR15≥10%, AVP values were higher than baseline on just after LR, POD1 (p< 0.01), POD2 (p< 0.01), and POD3 (p=0.02 and 0.01, respectively) in both groups. On the other hand, though the PAC values in IL group were higher on just after LR (p< 0.01), POD1 (p< 0.01) and POD2 (p=0.04), these in NL group were not different from the baseline except on just after LR (p< 0.01). Ascites volume was significantly larger in cases of hemihepatectomy or larger (n=11) than other cases (p< 0.01). Conclusions: The addition of the vasopressin-V2-receptor antagonists may be effective for water retention in the patients with hemihepatectomy or larger.

SAT-551 Sparing Confirmatory Tests in Primary Aldosteronism

Context: The current clinical guidelines suggest that confirmatory tests for primary aldosteronism (PA) may be excluded in some of patients who have elevated plasma aldosterone concentration (PAC) under plasma renin suppression. However, this has low priority evidence and is under debate in use of serum potassium. Objective: This study aimed to investigate an appropriate setting for sparing confirmatory tests in PA. Design and Setting: A retrospective cross-sectional study in a single referral center. Participants: This study included 327 patients who had hypertension under plasma renin suppression and underwent captopril challenge test (CCT) between January 2007 and April 2019. CCT results were used to diagnose PA. Main outcome measure: Diagnostic value of PAC and serum potassium in confirmation of PA. Results: Of the studied patients, 252 of 327 (77%) were diagnosed with PA. All 61 patients with PAC >30 ng/dl were diagnosed with PA. In patients with PAC between 20 and 30 ng/dl, 44 of 55 (80%) were diagnosed with PA, while all 26 with PAC between 20 to 30 ng/dl who had spontaneous hypokalemia were diagnosed with PA. Areceiver operator curve analysis showed that the sensitivity of diagnosis of PA is 100% in our patients, when PAC set at > 28.8 ng/dl and showed that the sensitivity of diagnosis of PA is 100% in our patients with spontaneous hypokalemia, who had PAC < 30 ng/dl, when PAC was set at > 19.2 ng/dl. While, the prevalence of PA was higher in patients with hypokalemia, who had PAC between 10 and 20 ng/dl than in those with PAC < 10 ng/dl. Collectively, 100 out of 102 (98%) with hypokalemia, who had PAC > 10 ng/dl were diagnosed as PA. The proportion of unilateral PA determined by adrenal vein sampling (AVS) was higher in patients who had PAC >30 ng/dl or those with spontaneous hypokalemia who had PAC between 20 and 30 ng/dl than those who did not meet the criteria (76% vs. 17%, P<0.001). Conclusion: Confirmatory tests in PA could be spared in patients who have typical features of PA and these patients had a high probability of unilateral PA on AVS.

Evaluation of various confirmatory tests for the diagnosis of aldosterone-producing adenoma.

Introduction:Adrenal venous sampling is useful for discriminating unilateral and bilateral hypersecretion in patients with primary aldosteronism, but it is relatively invasive. To determine the site of hypersecretion more non-invasively, we evaluated predictors of unilateral hypersecretion.Materials and methods:We evaluated the baseline characteristics and the results of confirmatory tests of 123 patients with primary aldosteronism who underwent adrenal venous sampling.Results:Unilateral hypersecretion was identified in 22.0%. The plasma aldosterone concentration and aldosterone–renin ratio were significantly higher and serum potassium concentration and plasma renin activity were significantly lower in patients with unilateral hypersecretion. Plasma aldosterone concentrations after captopril challenge test, saline infusion test and rapid adrenocorticotropic hormone stimulation test were significantly higher among patients with unilateral hypersecretion. The plasma aldosterone concentration reduction ratio in saline infusion test and plasma aldosterone concentration elevation ratio during rapid adrenocorticotropic hormone stimulation test were significantly higher in patients with unilateral hypersecretion. However, areas under the curve for these parameters were not superior to the values after confirmatory tests.Conclusions:The plasma aldosterone concentration values after captopril challenge test, saline infusion test and rapid adrenocorticotropic hormone stimulation test were useful for identifying patients with unilateral hypersecretion. However, value changes or ratios during confirmatory tests are less useful for this aim.

Subclinical atherosclerosis due to increase of plasma aldosterone concentrations in essential hypertensive individuals.

The adrenal mineralocorticoid system plays a key role in cardiovascular, metabolic and renal damage. This study aimed to assess the relationship between plasma aldosterone concentration (PAC) and some surrogate markers of subclinical atherosclerosis, such as carotid intima-media thickness (cIMT), ankle-brachial index (ABI) and biochemical parameters in patients with essential hypertension. From January 2014 to December 2017, we consecutively enrolled 804 essential hypertensive patients (407 men and 397 women, mean age 50 ± 14 years) without cardiovascular complications, distinguishing patients in quartiles according to PAC. Compared with the first quartile, the highest PAC quartile was associated with the highest levels of serum uric acid (SUA) (5.3 ± 1.3 vs. 5.0 ± 1.0 mg/dl; P = 0.01), triglycerides (117.5 ± 15.7 vs. 106.8 ± 10.5 mg/dl; P < 0.05), 24-h urinary albumin excretion (UAE) (38.8 ± vs. 7.6 ± mg/24 h; P < 0.05), cIMT (0.87 ± 0.22 vs. 0.80 ± 0.21 mm; P = 0.001) and increased prevalence of carotid plaques (26 vs. 16%; P < 0.005). Moreover, we found that in patients with PAC more than 150 pg/ml, the ABI was significantly lower than those with PAC < 150 pg/ml (1.01 ± 0.09 vs. 1.10 ± 0.09; P < 0.022). PAC was also found to be an independent predictor of the presence of carotid plaques and pathological ABI (<0.9) in essential hypertensive individuals. Our results revealed that higher PAC values are strongly associated with some metabolic variables, as triglycerides, UAE, cIMT, worse ABI and major prevalence of carotid plaques that, together with elevated blood pressure values, are strictly correlated with higher risk of atherosclerosis and cardiovascular complications.

Role of Aldosterone and Potassium Levels in Sparing Confirmatory Tests in Primary Aldosteronism.

The current clinical guidelines suggest that confirmatory tests for primary aldosteronism (PA) may be excluded in some of patients who have elevated plasma aldosterone concentration (PAC) under plasma renin suppression. However, this has low-priority evidence and is under debate in use of serum potassium. This study aimed to investigate an appropriate setting for sparing confirmatory tests in PA. A retrospective cross-sectional study in a single referral center. This study included 327 patients who had hypertension under plasma renin suppression and underwent the captopril challenge test (CCT) between January 2007 and April 2019. CCT results were used to diagnose PA. Diagnostic value of PAC and serum potassium in confirmation of PA. Of the studied patients, 252 of 327 (77%) were diagnosed with PA. All 61 patients with PAC > 30 ng/dL were diagnosed with PA. In patients with PAC between 20 and 30 ng/dL, 44 of 55 (80%) were diagnosed with PA, while all 26 with PAC between 20 to 30 ng/dL who had spontaneous hypokalemia were diagnosed with PA. The proportion of unilateral PA determined by adrenal vein sampling (AVS) was higher in patients who had PAC > 30 ng/dL or those with spontaneous hypokalemia who had PAC between 20 and 30 ng/dL than those who did not meet the criteria (76% vs. 17%, P < .001). Confirmatory tests in PA could be spared in patients who have typical features of PA and these patients had a high probability of unilateral PA on AVS.

SUBCLINICAL ATHEROSCLEROSIS, SERUM URIC ACID AND PLASMA ALDOSTERONE IN HYPERTENSIVE ADULTS

Objective: aldosterone has long been classically considered to play a central role in the regulation of electrolyte and fluid volume and the maintenance of blood pressure (BP) homeostasis. Moreover, the aldosterone/mineralocorticoid system plays a key role in cardiovascular, metabolic and renal damage. This study aimed to assess the relationship between plasma aldosterone concentration (PAC) and some surrogate markers of subclinical atherosclerosis, such as carotid intima-media thickness (cIMT), ankle-brachial index (ABI) and biochemical parameters (i. e. serum uric acid – SUA, 24-h urinary albumin excretion - UAE) in subjects with essential hypertension (EH). Design and method: from January 2014 to December 2017 we consecutively enrolled 804 EH patients (407 males and 397 females, mean age 50 ± 14.5 yrs) without evident cardiovascular complications. Patients were divided in quartiles according to PAC levels. Results: Compared to the first quartile, the highest PAC quartile was associated with the highest levels of SUA (5.3 ± 1.34 vs 5.0 ± 1 mg/dl; p = 0.01) triglycerides (117.5 ± 15.7 vs 106.8 ± 10.5 mg/dl; p < 0.05), UAE (38.8 vs 17.6 mg/24ore; p < 0.05) and cIMT (0.87 ± 0.22 mm vs 0.8 ± 0.21 mm; p = 0.001). Patients of the fourth quartile also exhibited increased prevalence of carotid plaques, compared to the first quartile (26% vs. 16%; p < 0.005). Moreover, we found that in patients with PAC >160 pg/ml ABI was significantly lower compared to those with PAC < 160 pg/ml (1.01 ± 0.09 vs 1.1 ± 0.09; p < 0.022). Binary logistic regression analysis showed that PAC was an independent predictor of the presence of carotid plaques and pathological ABI (< 0.9) in the population examined. Conclusions: These findings suggest that higher values of PAC are strongly associated with higher values of SUA, triglycerides, UAE, cIMT, worse ABI and major prevalence of carotid plaques that, together with elevated BP values, are strictly correlated with higher risk of atherosclerosis and cardiovascular complications.

SAT-073 A Case of Williams Syndrome Associated with Aldosterone Producing Adrenal Adenoma Mimicking Hepatic Adrenal Rest Tumor

Background: Williams syndrome (WS) is a microdeletion disorder caused by heterozygous loss of approximately 1.5-Mb pairs of DNA from chromosome 7. Patients with WS have a characteristic constellation of medical and cognitive findings, with a hallmark feature of generalized arteriopathy presenting as stenoses of elastic arteries and hypertension. We present here a case of WS associated with primary aldosteronism (PA), whose source of aldosterone excess was difficult to locate. Clinical case: A 31-year-old man suspected having PA was referred to our Hospital. He was diagnosed as having Williams syndrome at 2 months of age. He had been hypertensive for 9 years. At the age of 31 years old, low serum potassium (K) and high aldosterone to renin ratio were pointed out. His plasma renin activity (PRA) was 0.2 ng/ml/h, plasma aldosterone concentration (PAC) was 456 pg/ml, serum K level was 3.1 mEq/l at admission. Diagnosis of PA was confirmed according to positive captopril challenge test. CT scan revealed a 13mm tumor with low density in posterosuperior segment of right hepatic lobe, but adrenal tumor was not detected. Venography of adrenal vein sampling (AVS) showed an extended tributary of the right adrenal vein to the liver that surrounded the tumor. Segmental AVS was performed for right adrenal vein and showed a high value of PAC (377000 pg/ml) in superior tributary which was drained from the tumor. PAC in other tributaries of right adrenal vein and left adrenal vein was suppressed. Laparoscopic partial hepatectomy was performed as a liver tumor. After surgery, serum K level was normalized, PAC decreased to 67 pg/ml. Pathological examination revealed a golden-yellow tumor separated from the liver by fibrous septum. The tumor was attached to an adrenal cortex embedded in the liver. The tumor was composed of clear cells, positive for 3βHSD2 and CYP11B2 using immunohistochemistry, diagnosed as aldosterone producing adrenal adenoma. Conclusion: To the best of our knowledge, this is the first report of WS associated with PA. Since WS is a disease with high prevalence of hypertension, measurement of PRA and PAC for screening of PA is recommended for patients with WS associated with hypertension. According to CT findings, hepatic adrenal rest tumor was suspected because the tumor was not continuous with the right adrenal gland, but pathological findings demonstrated that an adrenal adenoma was originated from right adrenal cortex rather embedded in the liver. Segmental AVS was useful to distinguish adrenal tumor from hepatic adrenal rest tumor.

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

BackgroundWe report a rare case of a juxta-adrenal schwannoma that could not be discriminated from an adrenal tumor before surgical resection and was complicated by bilateral hyperaldosteronism. To the best of our knowledge, this is first case in which both a juxta-adrenal schwannoma and hyperaldosteronism co-existed.Case presentationA 69-year-old male treated for hypertension was found to have a left supra-renal mass (5.8 × 5.2 cm) by abdominal computed tomography. His laboratory data showed that his plasma aldosterone concentration (PAC) was within the normal range, but his plasma renin activity (PRA) was reduced, resulting in an increased aldosterone/renin ratio (ARR). Load tests of captopril or furosemide in the standing position demonstrated autonomous aldosterone secretion and renin suppression. Adrenal venous sampling (AVS) with ACTH stimulation indicated bilateral hypersecretion of aldosterone. A left supra-renal tumor was resected because of the possibility of malignancy and was found to be a benign schwannoma arising from the juxta-adrenal region together with an adrenal gland. The dissected left adrenal gland was morphologically hyperplastic in the zona glomerulosa, but was immunohistochemically negative for CYP11B2 (aldosterone synthase). Multiple CYP11B2-positive adrenocortical micronodules were detected in the adrenal gland, indicating micronodular hyperplasia. Although bilateral aldosteronism was indicated by AVS before the operation, the PRA, PAC and ARR values were within their respective reference ranges after resection of the unilateral tumor, suggesting that the slight increase in hormone secretion from the remaining right-sided lesion could not be detected after resection.ConclusionA clinical and morphologic diagnosis of juxta-adrenal schwannoma is difficult, particularly in a case of hyperaldosteronism, as shown in this case. These data suggest the complexity and difficulty diagnosing adrenal incidentaloma.

OS 31-03 CLINICAL EFFECTIVENESS OF ANTI-HYPERTENSIVE THERAPY WITH ACEI OR ARB ASSESSED BY PLASMA RENIN ACTIVITY/PLASMA ALDOSTERONE CONCENTRATION RATIO

ACE inhibitors and angiotensin receptor blockers (ARB) modulate the renin-angiotensin system (RAS) leading to an increase in plasma renin activity (PRA) together with a reduction of plasma aldosterone concentration (PAC), likely proportional to the pharmacological effect. Aim: to evaluate the efficacy of therapy based on ACEI or ARB, using PRA/PAC ratio values in real-life clinical-practice. We studied 184 essential hypertensives (59.2 ± 11.9 years, 63% males) in stable treatment for at least three months with an ACEI or ARB as part of the treatment. PRA was expressed as ng/ml and PAC as ng/dl, and then the ratio was multiplied by 100. Tertiles of PRA/PAC ratio were considered for the analysis. ABPM was performed to evaluate the BP control. Tertiles of PRA/PAC: 1st 0.2 to 5.7; 2nd 5.9 to 28.4; 3rd 29.4 to 509.8. There was no difference by age, sex, BMI and eGFR between PRA/PAC tertiles. A significant reduction in 24hour, daytime and night-time BP values was associated with increasing PRA/PAC tertiles (all p < 0.05). An increase of PRA/PAC tertiles was associated with a higher prevalence of controlled patients during the night-time period (1st: 14.5%; 2nd: 43.3%; 3rd: 45.9%; p < 0.001). PRA/PAC ratio was also a predictor of night-time BP control, as shown by ROC curve (AUC: 0.664, 95% CI: 0.582–0.745; p < 0.001). An increasing PRA/PAC ratio reflects reduced values of PAC despite higher values of PRA as expression of a more effective RAS blockade by ACEIs or ARBs. These findings are associated with lower BP values and better BP control, especially in night-time period, highlighting the effectiveness and compliance to the anti-hypertensive therapy with ACEI or ARB. Therefore, PRA/PAC ratio may be not only a useful biomarker of effective treatment based on ACEI or ARB, but also can be used an indirect index of drug intake and therapy compliance.

Evaluation of the clinical effectiveness of ACEI or ARB in hypertension using plasma renin activity/plasma aldosterone concentration ratio

Renin-angiotensin system (RAS) modulation is considered a cornerstone of hypertension therapy and ACE inhibitors and angiotensin receptor (AR) blockers are among the most widely used anti-hypertensive drugs. The expected effects on the RAS are an increase in plasma renin activity (PRA) together with a reduction of plasma aldosterone concentration (PAC), proportional to the efficacy of ACE or AR blockade. Aim: evaluation of real-life clinical-practice efficacy of stable therapies based on ACE or AR blockers, using PRA / PAC ratio values. We studied 184 essential hypertensives (59.2 11.9 years, 63% males) in stable treatment for at least three months with an ACEI or ARB as part of the treatment. PRA was expressed as ng/ml and PAC as ng/dl, then the ratio was multiplied by 100. Tertiles of PRA/PAC ratio were considered for the analysis. ABPM was performed to evaluate the BP control. Tertiles of PRA/PAC: 1st 0.2 to 5.7; 2nd 5.9 to 28.4; 3rd 29.4 to 509.8. There was no difference by age, sex, BMI and eGFR between PRA/PAC tertiles. A significant reduction in 24hour, daytime and nighttime BP values was associated with increasing PRA/PAC tertiles (all p<0.05). An increase of PRA/ PAC tertiles was associated with a higher prevalence of controlled patients during the nighttime period (1st: 14.5%; 2nd: 43.3%; 3rd: 45.9%; p<0.001 for trend). PRA/PAC ratio was also a predictor of nighttime BP control, as shown by ROC curve (AUC: 0.664, 95% CI: 0.582-0.745; p<0.001). An increasing PRA/PAC ratio reflects, in most cases, reduced values of PAC despite higher values of PRA as expression of a more effective RAS blockade by ACEIs or ARBs. These findings are associated with lower BP values and better BP control, especially in nighttime period, highlighting the effectiveness and compliance to the anti-hypertensive therapy with ACEI or ARB. Therefore, PRA/PAC ratio may be not only a useful biomarker of effective treatment based on ACEI or ARB, but also it can be used as an indirect index of drug intake and therapy compliance.

Trends in antihypertensive medication use among persons with resistant hypertension in the U.S. from 2008-2013

Renin-angiotensin system (RAS) modulation is considered a cornerstone of hypertension therapy and ACE inhibitors and angiotensin receptor (AR) blockers are among the most widely used anti-hypertensive drugs. The expected effects on the RAS are an increase in plasma renin activity (PRA) together with a reduction of plasma aldosterone concentration (PAC), proportional to the efficacy of ACE or AR blockade. Aim: evaluation of real-life clinical-practice efficacy of stable therapies based on ACE or AR blockers, using PRA / PAC ratio values. We studied 184 essential hypertensives (59.2 11.9 years, 63% males) in stable treatment for at least three months with an ACEI or ARB as part of the treatment. PRA was expressed as ng/ml and PAC as ng/dl, then the ratio was multiplied by 100. Tertiles of PRA/PAC ratio were considered for the analysis. ABPM was performed to evaluate the BP control. Tertiles of PRA/PAC: 1st 0.2 to 5.7; 2nd 5.9 to 28.4; 3rd 29.4 to 509.8. There was no difference by age, sex, BMI and eGFR between PRA/PAC tertiles. A significant reduction in 24hour, daytime and nighttime BP values was associated with increasing PRA/PAC tertiles (all p<0.05). An increase of PRA/ PAC tertiles was associated with a higher prevalence of controlled patients during the nighttime period (1st: 14.5%; 2nd: 43.3%; 3rd: 45.9%; p<0.001 for trend). PRA/PAC ratio was also a predictor of nighttime BP control, as shown by ROC curve (AUC: 0.664, 95% CI: 0.582-0.745; p<0.001). An increasing PRA/PAC ratio reflects, in most cases, reduced values of PAC despite higher values of PRA as expression of a more effective RAS blockade by ACEIs or ARBs. These findings are associated with lower BP values and better BP control, especially in nighttime period, highlighting the effectiveness and compliance to the anti-hypertensive therapy with ACEI or ARB. Therefore, PRA/PAC ratio may be not only a useful biomarker of effective treatment based on ACEI or ARB, but also it can be used as an indirect index of drug intake and therapy compliance.