Plasma Aldosterone Concentration Levels Research Articles

Higher plasma aldosterone concentrations in patients with aortic diseases and hypertension: a retrospective observational study

BackgroundAortic diseases remain a highly perilous macrovascular condition. The relationship between circulating aldosterone and aortic diseases is rarely explored, thus we investigated the difference in plasma aldosterone concentration (PAC) between patients with and without aortic disease in hypertensive people.MethodsWe analyzed 926 patients with hypertension, ranging in age from 18 to 89 years, who had their PAC measured from the hospital's electronic database. The case group and control group were defined based on inclusion and exclusion criteria. The analysis included general information, clinical data, biochemical data, and medical imaging examination results as covariates. To further evaluate the difference in PAC between primary hypertension patients with aortic disease and those without, we used multivariate logistic regression analysis and also employed propensity score matching to minimize the influence of confounding factors.ResultsIn total, 394 participants were included in the analysis, with 66 individuals diagnosed with aortic diseases and 328 in the control group. The participants were predominantly male (64.5%) and over the age of 50 (68.5%), with an average PAC of 19.95 ng/dL. After controlling for confounding factors, the results showed hypertension patients with aortic disease were more likely to have high PAC levels than those without aortic disease (OR = 1.138, 95% CI [1.062 to 1.238]). Subgroup analysis revealed consistent relationship between PAC and primary hypertensive patients with aortic disease across the different stratification variables. Additionally, hypertensive patients with aortic disease still have a risk of higher PAC levels than those without aortic disease, even after propensity score matching.ConclusionsThe results of this study suggest that primary hypertensive patients with aortic diseases have elevated levels of PAC, but the causal relationship between PAC and aortic disease requires further study.

FRI190 Catching A Chimera: A Case Of Suspected Glucocorticoid Remediable Aldosteronism

Abstract Disclosure: A. Khan: None. B. Ramchandani: None. H.B. Aftab: None. Introduction: Familial hyperaldosteronism type 1 (FH-I), also known as glucocorticoid remediable aldosteronism (GRA) is responsible for 1% of cases of primary aldosteronism (PA). It is caused by a chimeric fusion of the CYP11B2 and CYP11B1 genes resulting in ACTH-sensitive aldosterone production. We describe a case of suspected GRA and outline the diagnosis of this rare condition. Case. A 52-year-old female with history of type 2 diabetes mellitus, obesity, sleep apnea, SVT with ablation presented with long-standing history of resistant hypertension (HTN). HTN was diagnosed in her late twenties. She was previously trialed on eight different classes of antihypertensive medications excluding mineralocorticoid antagonists or potassium-sparing diuretics but HTN remained uncontrolled. Current regimen included hydralazine, nebivolol, and furosemide. Her sister had HTN diagnosed in her forties, a nephew with HTN diagnosed in his early twenties and mother with HTN with unclear age of diagnosis. Her systolic and diastolic BP averaged 150 mmHg and 90 mmHg, respectively, on both home and clinic monitoring. Physical examination was significant for mild cushingoid appearance. Screening tests for pheochromocytoma and hypercortisolism were normal. Plasma aldosterone concentration (PAC) was noted to be at 14.4 ng/dl (<39.2) with a plasma renin activity (PRA) of <0.6 ng/mL/h (2.9 - 10.8), with aldosterone to renin ratio (ARR) of 24. Repeat testing showed PAC of 15.1 ng/dl, PRA<0.6 ng/ml/hr (ARR: 25.1) with potassium of 3.3 mmol/L (3.5 -5.1). PAC levels remained unsuppressed above 10 ng/dL following four-hour, seated, 2 L IV saline suppression test with serum potassium of 3.5 mmol/L. CT abdomen showed normal appearance of the adrenal glands. Given early age of onset of HTN and strong family history, 3-day dexamethasone test was performed using 1 mg oral dexamethasone every 12 hours following which PAC suppressed to <1 ng/dl. Patient was started on spironolactone 25 mg twice daily and at the time of writing is awaiting genetic testing to confirm the diagnosis of GRA. Discussion: GRA is a rare subtype of PA which has an increased risk of cardiovascular and cerebrovascular complications. Our case highlights the importance of screening for GRA in patients who have a personal and/or family history of early onset HTN who have screened positive for PA. Genetic testing for chimeric CYP11B1/B2 gene is the confirmatory step of diagnosis, however, a 3-day dexamethasone suppression test can be used to screen for GRA with a high sensitivity. Elevated levels of urine 18-hydroxycortisol and 18-oxocortisol are also noted but these are not widely available tests. Treatment of GRA is with medical management only; since surgical intervention is not required; proper diagnosis can also save the patient from unnecessary and invasive tests such as adrenal vein sampling. Presentation: Friday, June 16, 2023

Relationship Between Plasma Aldosterone Concentrations and Non-Alcoholic Fatty Liver Disease Diagnosis in Patients with Hypertension: A Retrospective Cohort Study.

To investigate the association between plasma aldosterone concentration (PAC) and non-alcoholic fatty liver disease (NAFLD) diagnosis in Chinese hypertensive patients. We conducted a retrospective study of all patients diagnosed with hypertension between January 1, 2010, and December 31, 2021. We included 3713 hypertensive patients based on the criteria for inclusion and exclusion. PAC measurement was performed using a radioimmunoassay. NAFLD was diagnosed using abdominal ultrasonography. Cox regression analysis was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for univariable and multivariable models. A generalized additive model was used to identify nonlinear relationships between PAC and NAFLD diagnosis. A total of 3713 participants were included in the analysis. Over a median follow-up of 30 months, 1572 hypertensive individuals developed new-onset NAFLD. When PAC was used as a continuous variable, the risk of NAFLD increased by 1.04 and 1.24-fold for each 1 ng/dL and 5 ng/dL increase in PAC, respectively. When PAC was considered a categorical variable, the HR for tertile 3 was 1.71 (95% CI, 1.47-1.98, P < 0.001) compared to tertile 1. Overall, there was a J-shaped relationship between PAC and new-onset NAFLD. By fitting a two-piecewise linear regression model and using a recursive algorithm, we identified a PAC inflection point at 13 ng/dL (log-likelihood ratio test, P = 0.005). In adjusted model 3, for PAC ≥ 13 ng/dL, a 5 ng/dL increase in PAC was associated with a 30% increase in the risk of new-onset NAFLD (95% CI, 1.25-1.35, P < 0.001). The study revealed a non-linear relationship between elevated PAC levels and the incidence of NAFLD in hypertensive patients. Notably, the risk of new-onset NAFLD was significantly increased when PAC levels were ≥13 ng/dL. Larger, prospective studies are necessary to confirm these findings.

RELATIONS OF PLASMA ALDOSTERONE CONCENTRATION TO CARDIAC STRUCTURE AND FUNCTION: ARE THERE ANY ETHNIC-RELATED DIFFERENCES?

Objective: Plasma aldosterone concentration (PAC) is related to left ventricular hypertrophy (LVH) and diastolic dysfunction in primary hyperaldosteronism but conflicting data exists in primary hypertension. Here we investigated whether this association might differ in hypertensive subjects of African-origin background (black) vs Caucasian (white). Design and method: Subjects with hypertension and self-defined ethnicity (SDE) as black or white whose clinical assessment was not suggestive of secondary forms of hypertension and with an aldosterone/renin ratio &lt; 90 pmol/mU were recruited in London (UK) and Pisa (Italy). Transthoracic echocardiography was used to calculate left ventricular mass index (LVMI) and diastolic function using the ratio of early (E)) transmitral filling velocity to tissue Doppler early diastolic velocity (E/e’). Results: 167 black (51% male) and 273 white (69% male) subjects of whom 55% and 73% on pharmacological treatment were recruited. Compared to white individuals, black subjects had higher blood pressure (BP) (mean ± SD) (153/93 ± 15/12 mmHg vs 139/88 ± 15/11 mmHg) and lower prevalence of dyslipidaemia (9 % vs 38 %, both P &lt; 0.05) but the two groups were similar for age, prevalence of diabetes, smoking, duration of hypertension. Compared to white subjects, black individuals had lower renin and PAC level (42.4 ± 11.2mU/L vs 79.5 ± 12.7 mU/L and 312 ± 26.5 pmol/L vs 420 pmol/L respectively) while LVMI and E/E’ were greater (95.9 ± 25.2 g/m2 vs 88.7 ± 20.5 g/m2 and 9.1 ± 2.8 vs 7.8 ± 2.4 respectively) all P &lt; 0.001. In the entire population we found a significant interaction between ethnicity and PAC in relation to LVMI and E/e’. After stratifying the population according to SDE, PAC positively correlated with LVMI (R2 0.249, P = 0.01) and E/e’ (R2 0.207, P = 0.009) in black but not in white subjects. Multivariate adjustment for sex, BP, diabetes, dyslipidaemia, heart rate, pharmacological treatment, body mass index did not alter the relationship. Conclusions: Aldosterone is related to cardiac remodelling and diastolic function in patients with primary hypertension of African origin. The reasons behind the ethnic difference needs to be elucidated.

PS-R07-5: A CASE OF PRIMARY ALDOSTERONISM WITH DECLINED GLOMERULAR FILTRATION RATE AFTER ADRENALECTOMY

Background: Primary aldosteronism (PA) has been known to cause organ damage, such as renal and cardiovascular disorders more frequently than essential hypertension (EH), independently of blood pressure. Among renal disorders, albuminuria is more prevalent in patients with PA than EH, while GFR tends to be higher in PA due to glomerular hyperfiltration. Surgical and medical treatments for PA correct these effects of excess aldosterone, which sometimes uncover preexisting chronic kidney disease (CKD). Here we present a case of PA with CKD who manifested decline of glomerular filtration rate (GFR) and overt renal failure following resection of aldosterone-producing adenoma. Case report: A 53-year-old woman was diagnosed with hypertension at the age of 40. Her primary care physician started treatment with a calcium channel blocker (CCB). At the age of 49, she was diagnosed with Sjogren's syndrome (SS). Blood tests revealed severe hypokalemia and eGFR of 50 mL/min/1.73m2, while 24-hr urine collection showed urinary protein of 0.5 g per day. SS was suspected to underlie her renal disease. A renal biopsy was performed, and suggested nephrosclerosis and IgA nephropathy. On the other hand, a 11mm-sized tumor in the left adrenal gland was discovered during the investigation of secondary hypertension. PA was confirmed based on active renin concentration (ARC) of 4.3 pg/mL, plasma aldosterone concentration (PAC) of 342 pg/mL, an aldosterone-to-renin ratio of 79.5 (&gt; 40), and 24-hr urinary aldosterone levels of 15.9 μg per day under the adequate salt-loaded condition. Adrenal venous sampling yielded aldosterone hypersecretion from the left adrenal vein, which indicated aldosterone-producing adenoma. Laparoscopic partial left adrenalectomy was performed and fully normalized ARC, PAC, and urinary aldosterone levels, which indicated biochemical cure of PA. Consequently, blood pressure had been well controlled with a single CCB. However, while her preoperative serum creatine level ranged from 0.9 to 1.1 mg/dL and eGFR was around 40–50 mL/min/1.73m2, her postoperative serum creatine level increased to 1.4 to 1.9 mg/dL and eGFR decreased to 25 to 35 mL/min/1.73m2 on average. In contrast, urinary protein level improved to less than 0.1 g/day, suggesting that post-treatment increase in creatine level indicated unveiling CKD rather than deterioration of renal function. Conclusion: PA treatment may unmask CKD through improving glomerular hyperfiltration from aldosterone excess.

PS-BPB10-1: INVOLVEMENT OF RENAL TUBULAR NFAT5 IN THE REGULATION OF BLOOD PRESSURE AND BODY FLUID VOLUME

Objective: Nuclear factor of activated T-cells 5 (NFAT5) is an osmoresponsive transcription factor that activates osmoprotective genes to protect cells against hypertonicity. Renal tubular cell-specific NFAT5 knockout (KO) mice have been shown to exhibit polyuria, hypernatremia, low urinary sodium excretion, and increased expression of the epithelial sodium channel (ENaC) in the kidney. In the present study, regulation of blood pressure (BP) as well as that of body fluid volume were examined in the wild type (WT) mice and NFAT5 KO mice. Methods: The BP of KO mice and WT mice was measured using radiotelemetry method. The mice were fed with regular salt diet (RSD, 0.3% NaCl chow) or high salt diet (HSD, 8% NaCl chow) followed by the treatment with amiloride, an ENaC blocker. To assess body fluid volume, the plasma renin activity (PRA) and the plasma aldosterone concentration (PAC) were measured at the condition of RSD and HSD, together with plasma arginine vasopressin (AVP) and hematocrit (Ht) levels. Results: Compared to WT mice, the mean BP was significantly higher in KO mice both at the condition with RSD and that with HSD in dark period, but not in light period. Treatment with amiloride significantly decreased the mean BP in KO mice with HSD to the level of WT mice with HSD in dark period. PRA, PAC, and AVP levels were not significantly different between in WT and KO mice with RSD. HSD significantly decreased PRA and PAC and tended to increase the AVP level both in WT and KO mice. The Ht level was significantly lower in KO mice than in WT mice regardless of RSD or HSD (WT with RSD, 42.6 ± 0.5%; WT with HSD, 42.8 ± 0.6%; KO with RSD, 38.3 ± 0.4%; KO with HSD, 39.0 ± 0.4%, n = 4). Conclusions: The results suggest that the renal tubular cell-specific NFAT5 KO mice exhibit excess body fluid retention induced by sodium reabsorption through ENaC, leading to salt-sensitive hypertension. Such phenotypes seem to be independent of the systemic renin-angiotensin-aldosterone and AVP systems. Renal tubular NFAT5 could integrate urine concentration and sodium reabsorption in the kidney, thus preventing salt-dependent hypertension.

Effect of sodium-glucose cotransporter-2 inhibitors on aldosterone and renin levels in diabetes mellitus type 2 patients: a systematic review and meta-analysis

The effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on plasma aldosterone concentration (PAC) and plasma renin activity (PRA) levels are still inconclusive. This meta-analysis aimed to demonstrate the changes in PAC and PRA levels after the use of SGLT2i in type 2 diabetes patients. A search for relevant publications was performed using PubMed/Medline, Scopus, Cochrane, and Embase databases from their inception through May 2022. Inclusion criteria were studies that contained data on crude PAC and PRA levels before and after the use of SGLT2i in adult type 2 diabetes patients. Standardized mean difference (SMD) with a 95% confidence interval (95% CI) was calculated. Data was separately analyzed by study design: randomized controlled study (RCT) and non-randomized controlled study (non-RCT). Ten studies involving 380 patients were included with two RCT and eight non-RCT. Serum PAC levels showed no significant change after the use of SGLT2i in both RCT and non-RCT. Significantly higher PRA levels were observed after the use of SGLT2i in both RCT and non-RCT with SMD of 0.40 ng/mL/hr; 95% CI (0.06, 0.74) and SMD of 0.36 ng/mL/hr; 95%CI (0.17, 0.55), respectively. Subgroup analysis found significantly higher PRA levels after the use of SGLT2i (SMD 0.45 ng/mL/hr; 95% CI (0.18, 0.71)) only in subgroups that used for three months or less. The use of SGLT2i in diabetes mellitus type 2 patients can affect PRA levels, especially during short-term use. PRA levels should be interpreted with caution in this population.

Primary aldosteronism with mild autonomous cortisol secretion increases renal complication risk.

In primary aldosteronism (PA), renal impairment has been identified as an important comorbidity. Excess cortisol production also may lead to renal damage; thus, concomitant mild autonomous cortisol secretion (MACS) may predispose PA patients to renal disorders. However, there is limited evidence to support this claim. Therefore, this study aimed to determine whether the concurrence of MACS and PA increases the risk of renal complications. This study is a retrospective cross-sectional study. A total of 1310 patients with PA were stratified into two groups according to 1 mg dexamethasone suppression test (DST) results (cut-off post-DST serum cortisol 1.8 µg/dL): MACS (n = 340) and non-MACS (n = 970). The prevalence of renal complications was compared between the group. We also performed multiple logistic regression analysis to determine factors that increase the risk for renal complications. The prevalence of lowered estimated glomerular filtration rate (eGFR) and proteinuria was nearly twice higher in the MACS group than in the non-MACS group. Not only plasma aldosterone concentration (PAC) but also the presence of MACS was selected as independent factors that were associated with the two renal outcomes. The risk of lower eGFR or proteinuria in patients who had MACS and higher levels PAC was several folds higher than in those who had an absence of MACS and lower levels of PAC. MACS is an independent risk factor for renal complications in patients with PA, and MACS concomitant with higher aldosterone secretion in PA patients causes an increase in the risk of developing renal complications.

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.

Resistant Hypertension Due to Familial Hyperaldosteronism Type III: First Report From Indian Sub-Continent

Background: Familial hyperaldosteronism type III (FH-III) is caused by germline mutations in KCNJ5 gene. FH-III presents with phenotypic variability from spironolactone-responsive hypertension to massive adrenal hyperplasia requiring bilateral adrenalectomy. Till date, seven different pathogenic mutations in KCNJ5 gene have been identified. Here we describe a sporadic FH-III case, due to a Gly151Arg mutation, first from Indian subcontinent, presenting with extremely high plasma aldosterone concentration (PAC) values, further expanding our knowledge of this rare condition. Clinical Case: A 24-year-old female, symptomatic since age of 5 years with periodic limb weakness and gradual increase in frequency of episodes over the years. Her blood pressure (BP) was recorded for first time at 9 years of age, and it was 170/110 mm Hg. On evaluation at this time, PAC was highly elevated at 1007 ng/dL and plasma renin activity (PRA) was suppressed at 0.04 ng/ml/h with aldosterone renin ratio (ARR) of 25,175 ng/dL per ng/mL/h (>20 suggestive of primary aldosteronism). CT scan demonstrated mild enlargement of bilateral adrenal glands. A presumptive diagnosis of Glucocorticoid-remediable aldosteronism was made. She was started on dexamethasone, spironolactone and nifedipine but was not improved. Dexamethasone was stopped after 1 year of initiation. Before presenting to our referral center in 2018, she was having uncontrolled hypertension with recurrent episodes of hypokalemic paralysis. She was on maximal doses on four antihypertensive agents, further increased to six agents (including spironolactone 100 mg BD), and potassium chloride supplementation (120 mEq/day). Despite this, she had a serum potassium of 2.6 mEq/L. Her biochemical investigations demonstrated that PAC was 2070 ng/dL, direct renin concentration (DRC) was 2.35 µIU/mL (PRA 0.2 ng/ml/h) and ARR was 880.9 ng/dL per µIU/mL. CT scan revealed massive bilateral adrenal hyperplasia. Genetic analysis by whole exome sequencing detected KCNJ5 (p.Gly151Arg) mutation, confirming the diagnosis of FH-III. She was subjected to bilateral adrenalectomy and she became normokalemic. Dramatic reduction in antihypertensives with BP control achieved only on amlodipine post-operatively. Genetic testing of family members was not done but they were normotensive and normokalemic. Histopathological examination revealed bilateral adrenal hyperplasia. PAC levels up to 297 ng/dL have been described previously in FH-III but our patient had exceedingly high-level of 2070 ng/dL. Conclusion: This case demonstrates florid clinical and biochemical manifestations of FH-III and gradual worsening of symptoms, consistent with progression of disease with age. It illustrates that proper investigations and treatment can lead to remission of symptoms. Further studies are warranted to elucidate the full clinical and biochemical spectrum of FH-III.

A Case of Adrenocortical Carcinoma With Severe Hypertension and Hypokalemia

Abstract Case: 70 years old woman was pointed out for hypertension at a medical checkup and visited a primary physician. Severe hypokalemia (2.4 mmol/L) was noted, and abdominal CT scan revealed a right 99 mm diameter adrenal tumor adjacent to a 80 mm diameter liver tumor. She was referred to our hospital for further management. Despite treatment with antihypertensive agents, including ARB, MRB, and CCB, her blood pressure remained around 170/90 mmHg. In the meantime, 120 meq of potassium chloride treatment was needed to keep her serum potassium levels around 3.5 mmol/L. Both her plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were high (6.4 ng/mL/h and 376 pg/mL), indicating renin-dependent hypertension. Since CT angiography revealed the right renal artery compressed downward by the adrenal tumor, renovascular hypertension was suspected. Moreover, both early morning plasma ACTH levels and serum cortisol levels were suppressed (8.5 pmol/L and 5.3 μg/dL), despite elevated urinary free cortisol levels (350 μg/day). Urinary steroid profile analysis detected various elevated precursor steroid metabolites, including deoxycorticosterone (DOC) and corticosterone. DOC levels were 5 folds more than the upper normal limit, suggesting one of the causes of her hypertension with hypokalemia, while elevated corticosterone levels were thought to be contributed to suppressing ACTH. After the right adrenalectomy and hepatic segmentectomy, both of her hypertension and hypokalemia rapidly improved with declining PRA and PAC levels to 0.2 ng/mL/h and &amp;lt; 0.7 pg/mL, respectively. Urinary DOC levels also fell into the normal range. From the pathological findings, she was diagnosed with adrenocortical carcinoma (ACC) infiltrating the liver (pT4N0M0, stage IV). The immunohistochemistry analysis showed disorganized expression of steroidogenic enzymes, including CYP11B1, CYP11B2, and 3β-HSD, supporting a variety production of steroid metabolites from the ACC. Although mitotane was initiated as a adjuvant chemotherapy, multiple metastasis was found at her lung, liver, and vertebrae, 6 months after the operation. Along with that, hypertension and hypokalemia recurred gradually with both of PRA and PAC elevation. However, CT angiography detected no apparent renovascular stenosis. We performed renin immunostaining of ACC specimen revealed partially positive, demonstrating renin production from this ACC. Conclusion: Although juxtaglomerular cell tumor is the most common renin-producing tumor, some cases of renin secreting ACC have been reported as a quite rare case. In the present case, renin secretion from ACC might be contributed to severe hypertension and hypokalemia, and both renal artery stenosis and DOC secretion induced by the ACC are considered to be a major cause.

PLASMA RENIN ACTIVITY AND ALDOSTERONE IN RENAL TRANSPLANT PATIENTS

(Background) It has become evident in recent year that aldosterone has a pathogenic role in hypertension, heart failure and renal disease. Elevation of aldosterone occurs in a certain fraction of hemodialysis patients, and the adverse effects of hyperaldosteronism could pose a problem after kidney transplantation. Long-term effects of aldosterone level in renal transplant recipients remain unknown. (Materials and methods) All recipients underwent transplantation between 1996 and 2018 in Niigata university hospital were included in the study. Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were retrospectively analyzed in 210 recipients before and after kidney transplantation. (Results) Sixty percent of recipients had higher PRA than normal upper limit before and after transplantation. The use of angiotensin receptor blocker (ARB) or angiotensin-converting-enzyme inhibitor (ACEI) was significantly more frequent in the patients with hyperreninemia than those without one after transplantation. Sixty percent of recipients had higher PAC than normal upper limit before transplantation and it spontaneously decreased to normal level after transplantation in most of them. There was no significant correlation between PAC and blood pressure, recipient age, and renal graft function after transplantation. We divided the patients into two groups, with and without post-transplant hyperaldosteronemia. The patients with post-transplant hyperaldosteronemia (n=29) had higher diastolic blood pressure and less use of renin-angiotensin-aldosterone system (RAAS) inhibitors than those with normal PAC level. (Conclusions) The use of RAAS inhibitors should be considered in post-transplant hyperaldosteronemia patients to control blood pressure and to save their long-term renal graft and heart function.

MON-215 Clinical Factors Associated with Insulin Secretion and Sensitivity in Patients with Primary Aldosteronism

Introduction: Primary aldosteronism (PA) is associated with an increased risk of impaired glucose tolerance or type 2 diabetes mellitus. Previous studies have reported that impaired insulin secretion and insulin sensitivity in PA may lead to impaired glucose tolerance. However, the relationship between PA and glucose tolerance, and the factor associated with these glucose metabolism abnormalities is not well understood. In particular, few studies have analyzed the association between aldosterone excess and insulin sensitivity or resistance after the adjustment for other clinical variables. In this study, we analyzed the associations between multiple clinical variables observed in PA and the indices of insulin sensitivity and resistance, using the result of 75 g oral glucose tolerance test (OGTT).Method: This was a retrospective observational study that analyzed the data of 646 patients with PA who underwent adrenal venous sampling and 75 g OGTT. The insulinogenic index and Matsuda index, indices of insulin secretion and sensitivity, respectively, were calculated from the results of a 75 g OGTT. Correlations between these indices and the multiple clinical variables were analyzed. In addition, we performed multiple regression analyses to identify the independent explanatory variables of these indices.Results: Insulinogenic index had positive correlations with the body mass index (BMI), alanine aminotransferase (ALT) level, triglyceride (TGL) level, and potassium level, and negative correlations with both age and plasma aldosterone concentration (PAC). In a multiple regression analysis, both the age (β = -0.231, p < 0.001) and potassium level (β = 0.175, p = 0.002) were selected as the independent explanatory factors. The Matsuda index had positive correlations with the PAC and cortisol level after a 1 mg dexamethasone suppression test (DST), and negative correlations with BMI, ALT level, TGL level, plasma renin activity (PRA), and potassium level. In a multiple regression analysis, BMI (β = -0.216, p < 0.001), ALT level (β = -0.290, p < 0.001), TGL level (β = -0.225, p < 0.001), the cortisol level after 1 mg DST (β = 0.124, p = 0.009), and PRA (β = -0.119, p = 0.019) were selected as the independent explanatory factors.Conclusion: In PA patients, older age and decreased potassium levels were associated with impaired insulin secretion. An increase in the variables associated with metabolic abnormalities such as BMI, ALT, and TGL were associated with decreased insulin sensitivity. In addition, we found that decreased PRA was associated with increased insulin sensitivity.

Changes in plasma aldosterone level after weight loss by bariatric surgery in morbidly obese patients

BackgroundOveractivation of renin-aldosterone-angiotensin system (RAS) is part of the pathogenesis of obesity-associated hypertension. Evidences have shown that weight loss can result in reduction in blood pressure and RAS. This study was aim to investigate changes of plasma aldosterone concentration (PAC) after bariatric surgery.MethodsA prospective study was done in 14 morbidly obese patients undergoing bariatric surgery. Patients who were taking medications that can interfere with PAC and renin levels were excluded. Collection of blood samples were done at baseline and at 3 and 6-month post-bariatric surgery.ResultsFour out of 14 patients had hypertension at baseline. Mean body mass index (BMI) was 56.7 ± 13.5 kg/m2. PAC were significantly decreased at 3-and 6-month post-bariatric surgery from 14.3 ± 8.0 to 7.5 ± 5.5 [reduction of 36% from baseline (P < 0.01)] and 8.0 ± 6.6 ng/dl [reduction of 32% from baseline (P < 0.05)] respectively. The reduction of PAC at 3-month post-surgery was correlated with the reduction of body weight (r = 0.46, P < 0.05), waist circumference (r = 0.73, P < 0.05) and percent of body fat (r = 0.58, P < 0.05).ConclusionsMaximal reduction of PAC in obese patients underwent bariatric surgery occurred during the first 3 months after bariatric surgery. The reduction of PAC was associated with the reduction of body weight, waist circumference and percent of body fat suggesting the link between RAS and obesity-mediated hypertension.

PD31-02 WHAT TIMING IS APPROPRIATE FOR A BIOCHEMICAL EVALUATION AFTER LAPAROSCOPIC ADRENALECTOMY FOR UNILATERAL ALDOSTERONE-PRODUCING ADENOMA?

INTRODUCTION AND OBJECTIVE: The over-secretion of plasma aldosterone by unilateral aldosterone-producing adenoma (APA) can be cured by adrenalectomy. However, the time needed for the endocrine environment to normalize remains unclear. The aim of this study is to clarify adequate timing for a biochemical evaluation in unilateral APA patients after adrenalectomy. METHODS: A total of 166 unilateral APA patients were retrospectively reviewed. We evaluated renin-angiotensin axis agents: the plasma aldosterone concentration (PAC) (pg/ml), active renin concentration (ARC) (pg/ml) and aldosterone-renin ratio (ARR: PAC/ARC), serum potassium concentration, and estimated glomerular filtration rate (eGFR) at 1, 3, and 6 post operation months (POM). By applying the Primary Aldosteronism Surgical Outcome criteria, which is based with ARR, PAC and serum potassium levels, biochemical outcomes were also evaluated. RESULTS: PAC was significantly lower at 1POM than at pre-surgery (pre-surgery; 407.2, 1 POM; 90.0 pg/mL, p<0.001) (Fig. A). ARC did not increase from baseline at 1POM, but significantly increased at 3POM (pre-surgery; 4.43, 1POM; 4.87, 3POM; 11.3 pg/mL, p<0.001) (Fig. B). The patients who didn’t achieve the ARC normalization at 1POM had lower pre-surgery ARC (p<0.001) and higher pre-surgery 24-hour urinary aldosterone excretion (p=0.042). Although ARC did not significantly increase at 1POM, ARR significantly decreased at 1POM (pre-surgery; 146.9, 1 POM; 26.3, p<0.001) (Fig. C). Among the 34 patients who had hypokalemia pre-surgery, it was resolved in 28 (82%) at 1POM and in all (100%) at 3POM (Fig. D). The biochemical outcomes at 1POM were 131 (79%) complete, 20 (12%) partial, and 15 (9%) absent successes, while at 3POM, 147 (89%) were complete, 9 (5%) partial, and 10 (6%) absent. Twenty-three (14%) patients were changed biochemical outcomes between 1 and 3POM, whereas only 5 (3%) changed between 3 and 6POM. CONCLUSIONS: The appropriate timing for a biochemical evaluation of unilateral APA patients treated with laparoscopic adrenalectomy appears to be 3 months or more after surgery.Source of Funding: None

Determining the Prevalence of Primary Aldosteronism in Patients With New-Onset Type 2 Diabetes and Hypertension

Despite a high prevalence of hypertension in diabetes and close relationship between primary aldosteronism (PA) and glucose metabolism, few study concerns the prevalence of PA in diabetes with hypertension. This study aimed to detect the prevalence of PA in patients with new-onset type 2 diabetes (T2D) and hypertension and to explore the association between PA and diabetes. A total of 256 outpatients with new-onset T2D and hypertension were screened for PA. Plasma aldosterone concentration (PAC), plasma renin activity (PRA) were measured. Patients with an aldosterone renin activity ratio (ARR) ≥ 30 ng/dL/ng/mL/h and PAC ≥ 15 ng/dL underwent confirmatory captopril challenge test (CCT) for PA. The diagnostic criteria for PA were, after CCT, (1) PAC decreased < 30%, (2) ARR maintained ≥ 30 ng/dL/ng/mL/h, and (3) PAC was ≥ 11 ng/dL. Of 256 consecutive patients, 99 (39%) were positive for the screening test, and 49 (19%) were diagnosed with PA. Compared with those in groups A (screening test -) and B (screening test +, CCT -), patients in group C (diagnosed with PA) had a higher percentage of systolic blood pressure of ≥ 160 mmHg, less family history of hypertension, and lower serum potassium. Patients in group B and C had higher PAC and ARR levels, but lower PRA than those in group A. Homeostatic model assessment for insulin resistance (HOMA-IR) was positively associated with PAC level among the diabetic patients. The prevalence of PA in new-onset T2D patients with hypertension is at least 19%. Higher aldosterone may be related with insulin resistance in patients with diabetes.

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-071 Usefulness of NP-59 SPECT/CT for Lateralization in Primary Aldosteronism

Introduction: Adrenal venous sampling (AVS) is recommended for subtype diagnosis of primary aldosteronism (PA). However, successful cannulation of the right adrenal vein (R-AV) is difficult and leads to failed AVS in some cases. Even in successful AVS, results are sometimes discordant with other clinical findings. Herein we describe two patients with unilateral aldosterone-producing adenoma (APA) that was confirmed by 131-I-6-betaiodomethylnorcholesterol (NP-59) single-photon emission CT/CT (SPECT/CT). Clinical Case: Case 1 was a 45-year-old Japanese woman with hypertension and hypokalemia (serum K = 2.0 mEq/l). Plasma renin activity (PRA) = 0.1 ng/ml/h, plasma aldosterone concentration (PAC) = 43.9 ng/dl, and urine aldosterone excretion (uAldo) = 44 mcg/d (urine Na 188 mEq/d). PA was confirmed by the saline infusion test. CT scan showed a low density 11 mm right adrenal nodule. Although the R-AV was visualized with multidetector CT, AVS with cosyntropin stimulation showed unsuccessful cannulation of the R-AV; the serum cortisol (C) levels in IVC, the R-AV and the left adrenal veins (L-AV) were 17.1, 15.1 and 122.6 mcg/dl, respectively. Case 2 was a 47-year-old Japanese woman with hypertension and hypokalemia (serum K = 2.8). PRA = 0.8, PAC = 56.9, and uAldo = 34 (urine Na 226). PA was confirmed by the captopril challenge test. CT scan demonstrated a low density 16 mm right adrenal nodule. AVS with cosyntropin stimulation showed successful cannulation of both adrenal vain (the C levels in IVC, the R-AV and the L-AV were 20.9, 930 and 1040, respectively), however the result was inconclusive with lateralized ratio 2.6 (PAC levels the R-AV and the L-AV were 2814.3 and 1229.8, PAC/C in the R-AV and the L-AV were 3.0 and 1.2, respectively). Instead of repeating AVS, NP-59 SPECT/CT scan with dexamethasone (DEX)-suppression were obtained in those cases. The patients took oral DEX (3 mg/day for 4 days before and 2 mg/day for 7 days after NP-59 intravenous injection) to suppress cortisol production in normal adrenal gland. The patient was also treated with iodine tablets for 9 days to block thyroidal uptake of free 131-I. SPECT/CT images were obtained at 5 and 7 days after NP-59 administration. NP-59 SPECT/CT revealed intense uptake within the right adrenal gland without significant uptake in left adrenal gland in both cases. After laparoscopic right adrenalectomy, serum K, PAC and PRA were normalized. Their blood pressure normalized without antihypertensive medications. Conclusion: The role of NP-59 planar scintigraphy has been thought to be limited for subtype diagnosis of PA because sensitivity is not high. However, with the development of SPECT technology the resolution of scintigraphy has been improved. NP-59 SPECT/CT with DEX-suppression should be reconsidered as an effective test to determine the clinical significance of CT-detected adrenal nodules in patients with PA.

Postmenopausal osteoporosis is associated with elevated aldosterone/renin ratio.

Plasma aldosterone/renin ratio (ARR) is a useful method for primary aldosteronism (PA) screening. However some confounders, such as medications and dietary, affect plasma renin and aldosterone levels, resulting in false-negative or -positive plasma ARR. This study investigated the association between postmenopausal osteoporosis (PMO) and plasma ARR. Bone mineral density (BMD) was measured by dual-energy X-ray-absorptiometry (DXA) in 324 normotensive postmenopausal women. Based on clinical characteristics and BMD, 186 and 96 subjects were diagnosed as PMO and osteopenia respectively, and the remaining 42 subjects were grouped as normal BMD. Plasma aldosterone concentration (PAC), plasma renin concentration (PRC), parathyroid hormone (PTH), bone alkaline phosphatase (BALP) and 25-Hydroxyvitamin D(25-(OH)D) were determined. Subjects with PMO showed significantly higher levels of PAC (121.0 ± 78.8 vs. 81.8 ± 71.5 pg/ml, p < 0.01 and 121.0 ± 78.8 vs. 91.7 ± 56.2 pg/ml, p < 0.01) and ARR (32.0 ± 53.6 vs. 9.0 ± 9.3 pg/μU, p < 0.01 and 32.0 ± 53.6 vs. 16.3 ± 32.1 pg/μU, p < 0.01) compared to women with normal BMD and osteopenia, respectively. Using ARR ≥ 37.0 pg/μU as the cutoff for positive screening, more false-positive was found in the PMO group when compared to the normal BMD group (24 vs. 2%) and osteopenia group (24 vs. 7%), respectively. PAC was negatively associated with lumbar spine BMD T-score (r = -0.239, p < 0.001), femur neck BMD T-score (r = -0.234, p < 0.001) and total hip BMD T-score (r = -0.228, p < 0.001). PTH was positively associated with PAC (r = 0.119, p < 0.05) and ARR (r = 0.136, p < 0.05). PAC and ARR are elevated in women with PMO, which might increase the risk of false-positive for case detection of PA.

Serum Soluble (Pro) Renin Receptor Level is Increased in Association with Impaired Renal Function in Patients with Autosomal Dominant Polycystic Kidney Disease

Background: The aim of this study was to examine the relationship between the serum soluble prorenin receptor [(P)RR] levels and various clinical parameters of autosomal dominant polycystic kidney disease (ADPKD) patients. Methods: A total of 79 patients with ADPKD were enrolled and their serum soluble (P)RR levels were measured with ELISA kits. Serum creatinine (Cr), urea nitrogen (UN), uric acid (UA), and albumin levels, blood haemoglobin (Hb) concentration, plasma renin activity (PRA), plasma aldosterone concentration (PAC), and urinary protein/Cr ratio were also measured. Results: Univariate analyses showed positive correlations between soluble (P)RR levels and age (P=0.02, r=0.27), serum Cr (P<0.0001, r=0.50), UN (P<0.0001, r=0.45), UA (P=0.04, r=0.23) levels and urinary protein/Cr ratio (P<0.001, r=0.42), negative correlations with estimated glomerular infiltration rate (eGFR) (P<0.0001, r=-0.49) and Hb concentrations (P=0.02, r=-0.26), and no correlation with PRA or PAC levels. Soluble (P)RR levels were positively correlated with total kidney volume (TKV, P<0.01, r=0.35). There was no correlation between soluble (P)RR levels and prescription of renin-angiotensin system inhibitors. Finally, multiple regression analyses showed that serum soluble (P)RR concentration was significantly associated with eGFR after correction TKV. Conclusions: The serum soluble (P)RR levels correlated with their kidney function of the ADPKD patients, suggesting that soluble (P)RR may be involved in kidney injury and promote the progression of renal dysfunction of ADPKD patients.