Primary Aldosteronism Group Research Articles

Comparative analysis of aldosterone and renin assays for primary aldosteronism screening

The transition from radioimmunoassay (RIA) to chemiluminescent enzyme immunoassay (CLEIA) for plasma aldosterone concentration (PAC) assays has raised concerns over its impact on primary aldosteronism (PA) diagnosis. This study investigated the correlation between PAC and renin values using RIA, CLEIA, and liquid chromatography/mass spectrometry/mass spectrometry (LC–MS/MS), established cutoff values for PA diagnosis using the aldosterone-to-renin ratio (ARR) with PAC_CLEIA, and assessed the differences in PAC values by measuring weak mineralocorticoids (WMs). This retrospective study evaluated 312 serum PAC samples using RIA, CLEIA, and LC–MS/MS, and analyzed 315 plasma renin samples. Method correlations were assessed through Passing-Bablok regression. Receiver operating characteristic curves determined ARR cutoffs for PA diagnosis. WMs were quantified to evaluate their impact on ΔPAC (RIA-LC–MS/MS) through multiple regression analysis. PAC_CLEIA and PAC_LC-MS/MS values were highly correlated. ARRs derived from PAC_RIAs demonstrated more false positives and lower specificity than ARRs using PAC_CLEIA or PAC_LC-MS/MS. WMs significantly influenced ΔPAC in both the PA and non-PA groups. ARRs using PAC_CLEIA are valuable for determining PA cutoffs in clinical practice. The transition to PAC using CLEIA may enhance PA detection rates. WMs were found to interfere with PAC measurements in the RIA method, affecting outcomes.

The prevalence of metabolic syndrome in primary aldosteronism and essential hypertension: A systematic review and meta-analysis.

It remained debates on metabolic-related disorders in patients with primary aldosteronism (PA) and essential hypertension (EH). A systematic review and meta-analysis was conducted to explore the prevalence of metabolic syndrome (MS) and the related indicators in PA and EH. PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials from their commencement to December 2023 were searched for eligible studies. The meta-analysis was performed by Review Manager 5.3 and STATA 15.1 software. A total of 12 studies were included, revealing that there was no significant difference between PA and EH in the prevalence of MS (1.27[0.92, 1.76], p=0.14) with higher heterogeneity (I2=68%, p=0.0002), while it became significant different (1.45[1.17, 1.81], p=0.0008) and lower heterogeneity (I2=26%, p=0.19) in patients who were overweight or obese by subgroup analysis. Higher systolic blood pressure (2.99[0.67, 5.31], p=0.01; I2=43%, p=0.06) and diastolic blood pressure (2.10[0.82, 3.38], p=0.001; I2=36%, p=0.11) with lower heterogeneity, and lower triglyceride in PA group with higher heterogeneity (-0.23[-0.37, -0.09], p=0.001; I2=76%, p<0.0001) were observed. No significant difference was found in other indicators. This study showed a higher prevalence of MS in patients who were overweight or obese with PA. However, it was not the same in these patients who were in normal weight. More researches were needed to explore the relationship between PA and metabolism of glucose and lipid.

Association of Aldosterone, Renin, and Aldosterone to Renin Ratio with Metabolic Profile in Primary Aldosteronism.

This study aimed to investigate the glycometabolism, fat mass, and lean mass in primary aldosteronism (PA) during disease progression. Patients diagnosed with PA and healthy controls (HCs) were enrolled. A flash glucose monitoring system (FGMS) and dual-energy X-ray absorptiometry (DEXA) were used to measure glucose variability and glucose target rate along with fat mass and lean mass. Comparative analysis of FGMS- or DEXA-derived parameters along with correlation analyses between these parameters and PA progression were performed. Increased glucose variability and poor glucose target rate, along with an increased proportion of truncal fat mass, and decreased proportion of appendicular lean mass, were identified in PA group compared to those in HCs. Plasma aldosterone concentration was positively correlated with glucose variability and poor glucose target rate. Plasma renin concentration was positively correlated with the proportion of truncal fat mass and lean mass, and negatively correlated with the proportion of appendicular fat mass. Aldosterone-to-renin ratio was negatively correlated with the proportion of truncal fat mass and lean mass, and positively correlated with the proportion of appendicular fat mass. Patients with PA presented significant differences in glycometabolism, fat mass, and lean mass compared with HCs, and these alterations correlated with PA progression.

Screening parameters for diagnosing primary aldosteronism in patients with moderate to severe obstructive sleep apnea hypopnea syndrome and resistant hypertension.

Patients with obstructive sleep apnea hypopnea syndrome (OSAHS) combined with resistant hypertension (RH) have a high risk of developing primary aldosteronism (PA). This study investigated the aldosterone-renin ratio (ARR), plasma aldosterone concentration (PAC), and plasma renin activity (PRA) to determine the optimal cutoff values for PA diagnosis in patients with OSAHS combined with RH. Patients diagnosed with moderate and severe OSAHS combined with RH were recruited from the inpatient clinic of the Department of Endocrinology at Ji'an Central Hospital between October 2020 and April 2023. The included patients were divided into PA and no-PA groups. Diagnostic accuracy measures were calculated for each group, and receiver operating characteristic (ROC) curves were generated. A total of 241 patients were included, of which 103 had positive ARR screening results in the diagnostic accuracy analysis and 66 were diagnosed with PA. PAC and ARR showed moderate predictive capacity for PA, with area under the curve (AUC) values of 0.66 [95% confidence interval (CI): 0.55-0.77] and 0.72 (95% CI: 0.63-0.82), respectively, while PRA exhibited a limited predictive capacity (AUC = 0.51, 95% CI: 0.40-0.63). Using 45 as the optimal cutoff value for ARR, the sensitivity was 86% and the specificity was 52%. The optimal cutoff value for PAC was 17, with a sensitivity of 78% and a specificity of 55%. Notably, in patients with severe OSAHS, ARR at screening demonstrated significant predictive value for PA, with an AUC of 0.84 (95% CI: 0.72-0.96), a sensitivity of 85%, and a specificity of 76%. Conversely, in patients with moderate OSAHS, only ARR demonstrated significant predictive value for PA diagnosis, while PAC did not demonstrate notable diagnostic value. ARR and PAC are initial screening tools for PA, facilitating early detection, particularly in low-resource settings. In patients with OSAHS and RH, the ARR and PAC thresholds for PA diagnosis may require more stringent adjustment.

Clinical characteristics and prognosis of primary aldosteronism associated with subclinical Cushing syndrome

Objective: To analyze the clinical characteristics and prognosis of patients with primary aldosteronism (PA) associated with subclinical Cushing syndrome (SCS). Methods: This retrospective cohort study was conducted at the First Affiliated Hospital of Chongqing Medical University in China. Patients with PA were included between January 2014 and December 2022. According to the results of 1-mg overnight dexamethasone suppression test, the patients were divided into the PA group and PA associated with SCS (PA/SCS) group. The demographic information, hormone levels, and follow-up results were analyzed. Independent sample t-test, chi-square test and Mann-Whitney U test were used for data comparison. Results: A total of 489 PA patients were enrolled in this study, of which 109 had PA/SCS (22.3%). Patients with SCS were on average older (54.4±10.7 vs. 47.4±11.0, P<0.001); had a larger proportion of women (69.7%, 76/109 vs. 57.4%, 218/380; P=0.020); and a longer duration of hypertension [96 (36, 180) vs. 60 (12, 120) months, P=0.001] than patients without SCS. There were 215 and 51 patients in the PA group and PA/SCS group, who completed adrenalectomy and follow-up, respectively. The remission rate of autonomous cortisol secretion in the PA/SCS group was 85.3% (29/34). There was no significant difference in the remission rate of autonomous aldosterone secretion among patients between the PA/SCS and PA group (94.1%, 48/51 vs. 94.4%, 203/215; P=1.000), while the clinical remission rate in the PA/SCS group was lower than that in the PA group (39.2%, 20/51 vs. 61.9%, 133/215; P=0.003). Conclusions: SCS is common in PA patients (22.3%), and the clinical remission rate is low. Screening using the 1-mg overnight dexamethasone suppression test is recommended for all patients with PA.

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

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

Study of appropriate cut-off for diagnosis of primary aldosteronism by seated saline suppression test based on liquid chromatography with tandem mass spectrometry

Objective: To investigate the appropriate cut-off for diagnosis of primary aldosteronism (PA) by seated saline suppression test (SSST) based on liquid chromatography with tandem mass spectrometry (LC-MS/MS). Methods: In this cross-sectional study, patients who underwent SSST for suspected PA in the First Affiliated Hospital of Chongqing Medical University from January 2018 to March 2022 were evaluated. Briefly, 300 patients with PA and 119 with essential hypertension (EH) were included. Plasma aldosterone concentration (PAC) after SSST was determined by LC-MS/MS. Primary aldosteronism confirmatory testing (PACT) score was used as the reference standard for diagnosis of PA, and receiver operating characteristic (ROC) curve was used to explore the cut-off value. Results: The average age of the PA group was (50.8±10.5) years, and males accounted for 53.00% (n=159); the average age of the EH group was (49.4±11.2) years, and males accounted for 26.89% (n=32). The area under the ROC curve of PAC post-SSST was 0.819 (95%CI 0.775-0.862). When 40 pg/ml (110.8 pmol/L) was selected as the appropriate cut-off for diagnosis of PA, the sensitivity was 83.67% (95%CI 78.88%-87.56%) and specificity was 60.50% (95%CI 51.10%-69.21%). Thus, 95.09% (155/163) of patients with unilateral PA could be identified. Conclusion: PAC after SSST determined by LC-MS/MS has high efficacy for diagnosis of PA, and 40 pg/ml is recommended as the appropriate cut-off value.

Characteristics of cardiac arrhythmia and heart rate variability in Chinese patients with primary aldosteronism.

We applied 24-h Holter monitoring to analyze the characteristics of arrhythmias and heart rate variability in Chinese patients with primary aldosteronism (PA) and compared them with age-, sex-, and blood pressure-matched primary hypertension (PH) patients. A total of 216 PA patients and 261 PH patients were enrolled. The nonstudy data were balanced using propensity score matching (PSM), and the risk variables for developing arrhythmias were then analyzed using logistic regression analysis. Before PSM, the proportion of PA patients with combined atrial premature beats and prolonged QT interval was higher than the corresponding proportion in the PH group. After PSM, the PA group had a larger percentage of transient atrial tachycardia and frequent atrial premature beats, and it had higher heart rate variability metrics. The proportion of unilateral PA combined with multiple ventricular premature beats was higher than that of bilateral PA. Older age, grade 3 hypertension, and hypokalemia were independent risk factors for the emergence of arrhythmias in PA patients. PA patients suffer from a greater prevalence of arrhythmias than well-matched PH patients.

THU591 HyperAldosteronism In Pregnancy Predicted Impacts (H.A.P.P.I.): A Retrospective Cohort Study

Abstract Disclosure: D. Oprea: None. F. Lefrançois: None. A.C. Côté: None. M. Roy-Lacroix: None. M. St-Jean: None. N. Sauvé: None. Introduction: Hypertensive disorders of pregnancy (HDP) are increasing worldwide and are associated with a high rate of maternal and fetal morbidity and mortality. Primary aldosteronism (PA) is a frequent and reversible cause of secondary hypertension in young non-pregnant women (18%) (1). Until now, no studies have detailed the prevalence, nor the outcomes associated with PA during pregnancy. Research Question: In HDP, are cases of PA associated with different impacts on maternal-fetal health compared to pregnant women without PA? Methods: This retrospective cohort study compared 252 pregnancies according to their PA status. We included pregnancies that were followed at the Centre Hospitalier Universitaire de Sherbrooke (CHUS) between 2011 and 2022, and who had had an aldosterone/renin ratio (ARR) screening for PA, in a five-year period before or after the analyzed pregnancy. Monofetal and twin pregnancies were included. Concomitant diagnoses of pheochromocytoma, hyperthyroidism or Cushing syndrome were excluded. The primary objective of this study was to describe the occurrence of HDP in women with PA. Secondary objectives were to describe maternal, fetal and neonatal outcomes and compare them according to PA status. Results: Among 252 pregnancies, 15 were diagnosed with a PA (concerning 12 women). Our preliminary analysis showed a greater prevalence of advanced maternal age (53.3% vs 24.5, p = 0.028) and Afro-American ethnicity (60.0 % vs 10.1%, p &amp;lt; 0.001) in the PA group, in addition to a tendency towards class I obesity (40.0% vs 13.1%, p = 0.166) in this group. There were no differences in terms of prevalence of chronic hypertension (26.7% vs 25.7 %, p = 0.936), delivery mode and overall fetal morbidity and mortality. Although not statistically significant, preeclamspia tended to be more frequent (40.0% vs 27.0%, p = 0.276) and gestational hypertension less frequent (0.0 % vs 16.0%, p = 0.092) during pregnancy in the PA group. 40.1% (vs 19.0%, p = 0.052) of PA-associated HDP were diagnosed in post-partum (including 33.4 % of preeclampsia in this group) and required intravenous hypertensive treatment (40.0% vs 23.2%, p = 0.209). Also, 13.3% of pregnancies in the PA group (vs. 3.0 %, p = 0.093) required hospitalization at the intensive care unit (ICU). All cases of PA were diagnosed within 5 years pre-conception or post-partum. Conclusion: Pregnancies with PA diagnosis within a five-year period tended to present more frequently with HDP as preeclampsia, especially in the post-partum period, and often required more intensive antihypertensive treatment and ICU hospitalization. The upcoming second prospective phase of this study will better assess the prevalence of PA in pregnant women experiencing HDP. Reference: (1) Alam S. et al., Clin Endocrinol, June 2021;94(6):895903. Presentation: Thursday, June 15, 2023

FRI176 Integrated Profiling Analysis Of Serum Steroids And Catecholamines In A Single Run With LC-MS

Abstract Disclosure: J. Noh: None. C. Lee: None. S. Park: None. C. Ahn: None. S. Myung: None. J. Kim: None. M. Choi: None. Adrenal steroids and catecholamines are associated with the response against biochemical stress and adrenal disorders. Metabolic alteration of these hormones could be quantitatively evaluated in diagnostic process, but both adrenal cortex and medullary hormones have been measured in different analytical platforms. To increase the bio-analytical validity, liquid chromatography-mass spectrometry (LC-MS) based simultaneous profiling of 29 steroids and 6 catecholamines was developed. After alkyloxycarbonylation with isobutyl chloroformate, catecholamines and steroids were extracted simultaneously in liquid-liquid extraction. The limit of quantification ranged from 0.1 to 25 ng/mL with extraction recoveries of 78.5-97.0%, while the precision and accuracy were 4.8-7.9% and 98.0-110.9%, respectively. The validated LC-MS assay was then applied to serum samples obtained from 20 individual patients with primary aldosteronism (PA), Cushing’s syndrome (CS) and pheochromocytoma and paraganglioma (PPGL). The significantly increased serum levels of 18-hydroxycorticosterone (p &amp;lt; 0.005), corticosterone (p &amp;lt; 0.05), and 18-hydroxycortisol (p &amp;lt; 0.002) were observed in PA group, while PPGL group showed decreased level of 11-deoxycortisol (p &amp;lt; 0.007). Higher levels of glucocorticoids including 21-deoxycortisol (p &amp;lt; 0.002), 6β-hydroxycortisol (p &amp;lt; 0.001), and tetrahydrocortisone (p &amp;lt; 0.001) and lower levels of androgens including DHEA (p &amp;lt; 0.00001) and DHEA sulfate (p &amp;lt; 0.03) were detected in CS group. Catecholamines, such as norepinephrine (p &amp;lt; 0.0001) and normetanephrine (p &amp;lt; 0.0001), were significantly increased in PPGL patients. The present novel assay was successfully applied to discriminate three different adrenal diseases in a single analytical run. Presentation: Friday, June 16, 2023

Using plasma aldosterone concentrations at 1 h of saline infusion test for the diagnosis of primary aldosteronism.

Saline infusion test (SIT) requires 2 l of isotonic saline for intravenous infusion over 4 h to suppress plasma aldosterone concentration (PAC). To shorten the procedure time and minimize the volume load, we study the performance of SIT at 1, 2 and 4 h for diagnosing primary aldosteronism. This is a cross-sectional study. PAC was measured before and 1, 2 and 4 h after saline infusion at a rate of 500 ml/h in patients suspected to have primary aldosteronism. Primary aldosteronism was diagnosed based on 4 h PAC, adrenal imaging and/or adrenal venous sampling (AVS). Of the 93 patients, 32 had primary aldosteronism. The area under the receiver operating characteristic (ROC) curve of the 1, 2 and 4 h PAC were not statistically different. All of the nonprimary aldosteronism group had a 1 h PAC lower than 15 ng/dl and all of the primary aldosteronism group had a 1 h PAC higher than 5 ng/dl. Nearly 30% of the nonprimary aldosteronism and primary aldosteronism groups had a 1 h PAC between 5 and 15 ng/dl (equivocal range) and could be discriminated by using percentage suppression of 1 h PAC from baseline. Using 1 h PAC of more than 15 ng/dl together with percentage suppression of 1 h PAC from baseline of less than 60 when 1 h PAC was 5-15 ng/dl, primary aldosteronism could be detected with a sensitivity of 93.7% and specificity of 96.7%. The 1 h SIT has a similar diagnostic performance to the standard SIT. Using 1 h PAC together with percentage suppression from baseline when 1 h PAC is equivocal, primary aldosteronism can be diagnosed with good accuracy.

Monoexponential, biexponential, stretched-exponential and kurtosis models of diffusion-weighted imaging in kidney assessment: comparison between patients with primary aldosteronism and healthy controls.

This study used various diffusion-weighted imaging (DWI) models (including monoexponential, biexponential, stretched-exponential and kurtosis models) in renal magnetic resonance imaging (MRI) to compare whether there were differences in each diffusion parameter between patients with primary aldosteronism (PA) and healthy volunteers. Twenty-two (female:male, 14:8; age, 48 ± 10years) patients with PA and 22 age- and sex-matched healthy controls (HCs) underwent MRI examinations of the kidneys. The independent-sample t test or the Mann‒Whitney U test was used to detect differences in the diffusion metrics of the kidneys between the two groups. Univariable and multivariable linear regression were applied to analyze the correlations between diffusion parameters and the clinical indicators. The mean diffusivity (MD, p < 0.001) and radial diffusivity (Dr, p < 0.001) values in the medulla were lower in the PA group than in the HC group. The medullary fractional anisotropy (FA, p < 0.001) was higher than that of HCs. The FA (p < 0.001) and axial diffusivity (Da, p < 0.001) values in the cortex were lower in the PA group. The cortical α (anomalous exponent term, p = 0.016) was higher in the PA patients than in the HCs. Linear regression analysis showed that log(plasma aldosterone concentration) and the estimated glomerular filtration rate (eGFR) were correlated with medullary FA. The stretched-exponential model (cortical α) and the kurtosis model (FA, MD and Dr in the medulla and FA and Da in the cortex) showed significant differences between PA patients and healthy volunteers and may have potential for noninvasive renal assessment in PA patients.

Primary Aldosteronism and COVID-19-related Management, Disease Severity, and Outcomes: A Retrospective Cohort Study.

The SARS-CoV-2 virus is dependent on components of the renin-angiotensin-aldosterone system for infectivity. Primary aldosteronism (PA) is a form of secondary hypertension mediated by autonomous aldosterone production. The intersection of COVID-19 and PA, both which may involve components of the renin-angiotensin-aldosterone system, remains unknown. We assessed PA as a risk factor for COVID-19 infection and compared management, severity of disease, and outcomes during COVID-19 with a matched population of patients with essential hypertension (EH) by conducting a retrospective observational cohort study. Of the patients with PA, 81 had a negative PCR test for COVID-19, whereas 43 had a documented positive PCR test for COVID-19. Those patients with PA who tested positive for COVID-19 tended to be female (P = .08) and the majority of those with COVID-19 infection identified as non-White race (P = .02) and Hispanic ethnicity (P = .02). In a subanalysis, 24-hour urine aldosterone on initial PA diagnosis tended to be higher those in the PA group who developed COVID-19 compared with those in the PA group who did not develop COVID-19 [median (interquartile range): 36.5 (16.9, 54.3) vs 22.0 (15.8, 26.8) mcg, P = .049] and was an independent predictor of COVID-19 infection controlling for sex, race, and ethnicity. Angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, and mineralocorticoid receptor antagonist use did not differ between those patients with PA who did and did not have COVID-19 infection. Comparing those patients with PA and matched patients with EH (n = 286) who were COVID-19 PCR positive, there was a significantly higher incidence of cardiovascular complications (12 vs 2%, P = .004) in the PA vs EH group. These data begin to inform us as to whether PA should be a newly identified subpopulation at risk for COVID-19-related cardiovascular disease sequelae.

Diagnostic value of the fractional excretion of urine potassium for primary aldosteronism.

Primary aldosteronism (PA) is a common form of secondary hypertension, which usually manifests low blood potassium levels. The fractional excretion of urine potassium (FEK) has been proposed as a useful tool to measure urinary potassium excretion. However, the role of the FEK in PA remains unclear. In the current study, we assessed the diagnostic value of FEK in PA. A total of 155 hypertension patients were included in this cross-sectional study, of which 62 were confirmed by a positive screening test for PA. We collected the serum, 24-hr urine samples, and spot urine samples to evaluate the diagnostic value of the spot and 24-hr FEK in the diagnosis of PA and renal potassium loss compared to other indices. The sensitivity and specificity of the related diagnostic indexes were analyzed using receiver operating characteristic (ROC) curves, and the optimal cut-point value of the diagnostic index was determined according to the Youden index (YI) (sensitivity + specificity - 1). Correlation analysis was performed between the spot FEK and 24-hr FEK using Pearson's correlation coefficient. The spot FEK (7.3 vs. 5.9) and 24-hr FEK (9.3 vs. 8.0) levels were statistical differences between the PA and essential hypertension groups. PA patients had a significant tendency to lose potassium through the kidneys. We found that FEK from spot urine distinguished renal potassium loss with a sensitivity of 86.7% and a specificity of 87.1% at a cut-off of 9.8%. The sensitivity and specificity of the spot FEK in screening PA were 51.6% and 76.3%, respectively. FEK is significantly related to renal potassium loss. Spot FEK and 24-hr FEK performed a certain diagnostic value for PA, which may be potential indicators for the differential diagnosis of PA.

Meta-analysis of blood parameters related to lipid and glucose metabolism between two subtypes of primary aldosteronism.

It remains unclear whether metabolic profiles differ within the subtypes of primary aldosteronism (PA). This meta-analysis aimed to compare the blood parameters related to lipid and glucose metabolism at baseline between unilateral PA and bilateral PA. A search was performed using PubMed, Web of Science, and Sciencedirect databases, supplemented by hand-searching of related references. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated for each parameter. Twenty-one studies involving 4197 patients with PA were included. Compared with bilateral PA groups, unilateral PA groups demonstrated significantly lower low-density lipoprotein cholesterol (LDL-C, SMD: -.14mmol/L, 95% CI: -.20, -.07), total cholesterol (TC, SMD: -.16mmol/L, 95% CI: -.23, -.09), triglyceride (TG, SMD: -.22mmol/L, 95% CI: -.29, -.16), fasting blood glucose (FBG, SMD: -.11mmol/L, 95% CI: -.18, -.04), hemoglobin A1c (HbA1c, SMD: -.21%, 95% CI: -.30, -.13), and homeostasis model assessment-insulin resistance (HOMA-IR, SMD: -.40, 95% CI: -.58, -.23). No significant difference was found in high-density lipoprotein cholesterol (HDL-C) level between the two groups (SMD: .40mmol/L, 95% CI: -.02, .11). To sum up, comparison of several blood metabolic parameters between the two subtypes suggested that the bilateral PA may associate with a higher prevalence of impaired glucose and lipid metabolism than unilateral PA; however, results should be treated with caution. Additional well-designed studies are needed to prove the present results and better elucidate the link between metabolic abnormalities and etiologies of each PA subtype.

RF32 | PSUN49 To Repeat or Not to Repeat: The Question of Aldosterone and Renin Variability

Abstract Plasma aldosterone concentration (PAC), renin levels and aldosterone-renin ratio (ARR) are used to screen for primary aldosteronism (PA). A recent study (Yozamp et al. Hypertension 2021) reported substantial intraindividual variability of PAC and ARR (using plasma renin activity) in the context of usual antihypertensive therapy. The intraindividual variability of PAC and direct renin concentration (DRC), a more widely used measurement of renin, in the absence of interfering medications is unknown but important where a single ARR is used to screen for PA. The aim of this study was to evaluate the intraindividual variability of PAC, DRC and ARR in a cohort of patients with and without PA. Patients who attended an Endocrine Hypertension Service from May 2017 to July 2021 with at least two ARR measurements off interfering medications were retrospectively evaluated. While the measurements were performed at several hospital and community laboratories, the same analyser was used. PA was confirmed using the seated saline suppression test following an abnormal ARR &amp;gt;70 pmol/L: mU/L. PAC and DRC variability was calculated as coefficient of variation (CV=standard deviation/mean×100) and percent difference (PD=difference between highest and lowest values/mean×100). A total of 223 patients were analysed (55% female, median age 52 years), including 162 with PA (25% with unilateral disease). Significant variability in both PAC and DRC was observed in the PA group (CV: 24%, 41%; PD: 46%, 76% respectively) and non-PA group (CV: 22%, 40%; PD: 38%, 65% respectively), which was higher than the assays’ analytical variability. The ARR was also highly variable within individuals, in both the PA group (CV: 42%; PD: 74%) and non-PA group (CV: 37%; PD: 61%). Variability was not significantly different between PA subtypes, and persisted irrespective of age, gender and degree of hypertension. Sixty-two patients (39%) with PA could have had a missed diagnosis if the ARR had not been repeated, i.e., had at least one ARR &amp;lt;70 pmol/L: mU/L, while 28 (46%) without PA had at least one abnormal ARR &amp;gt; 70. Intraindividual variability in PAC, DRC and ARR occurs in a significant number of patients being investigated for PA. These results support the need for at least two ARR on separate occasions before PA is excluded or further investigated. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 1:06 p.m. - 1:11 p.m.

RF09 | PSUN05 Increased Frailty in Patients With Functioning Adrenal Adenomas

Abstract Introduction Frailty is characterized by multisystem function decline related to aging and can be measured using frailty Index (FI). FI is constructed based on the proportion of deficits present in an individual out of the total number of health variables considered. FI in various populations has been shown to predict adverse health outcomes. We aimed to determine the impact of hormone excess on frailty in a prospective cohort of patients with adrenal adenomas. Methods We conducted a multicenter prospective observational study of adult patients with adrenal adenomas and referent subjects without adrenal disorders (Jan 2019-Dec 2021). Adrenal adenomas comprised non-functioning adrenal adenomas (NFA), adenomas with mild autonomous cortisol secretion (MACS), defined as dexamethasone suppression test (DST)&amp;gt;1.8 mcg/dL, Cushing syndrome (CS), and primary aldosteronism (PA). FI was calculated as a sum of 47 variables (20 comorbidities, 13 symptoms, 14 activities of daily living) divided by 47.1 Frailty was defined as FI&amp;gt;0.25. In a subset of patients (n=176), functional measurements (handgrip strength, timed up and go test, gait speed) were performed and compared to FI. Results Of 233 patients (72.1% women), 71 were diagnosed with NFA (median age 64.5 years), 108 with MACS (median age 60.7 years), 11 with CS (median age 58.0 years), 46 with PA (median age 52.4 years), and 33 were referent subjects (median age 51.3 years). When compared to referent subjects, age- and sex-adjusted frailty prevalence was highest in CS (OR 29, 95%CI 4.3-202), followed by MACS (OR 16, 95%CI 3.5-73.7), and PA (OR 11.7, 95%CI 2.4-56), but not in patients with NFA (OR 5.1, 95%CI 0.99-25.8). Compared to patients with NFA, age- and sex-adjusted frailty prevalence was higher in CS (OR 5.8, 95%CI 1.4-24.4) and in MACS (OR 3.2, 95%CI 1.5-6.7), but not in PA (OR 2.3, 95%CI 0.9-6.1) group. Subgroup-analysis based on DST demonstrated a similar increase in age- and sex-adjusted frailty prevalence in patients with DST&amp;gt;5 mcg/dL (OR 3.1, 95%CI 1.2-8.2) and DST 1.9-5 mcg/dL (OR 3.3, 95%CI 1.5-7.4) when compared to patients with DST&amp;lt;1.8 mcg/dL. Higher FI was associated with lower handgrip measurement (P&amp;lt;0.0001), longer time during timed up and go test (P &amp;lt;0.0001), and decreased gait speed (P&amp;lt;0.0001). Conclusions Patients with functional adrenal adenomas are more likely to be frail. In patients with MACS, the prevalence of frailty was not associated with the degree of DST abnormality. FI correlated with currently validated but more cumbersome functional measurements and is a valuable tool that could be easily used in clinical practice and help individualize management decisions in patients with adrenal adenomas. 1 Singh S et al. Frailty in Patients With Mild Autonomous Cortisol Secretion is Higher Than in Patients with Nonfunctioning Adrenal Tumors. JCEM 2020 Presentation: Saturday, June 11, 2022 1:30 p.m. - 1:35 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Aldosterone, Renin, and Aldosterone-to-Renin Ratio Variability in Screening for Primary Aldosteronism.

The plasma aldosterone concentration (PAC), renin, and aldosterone-to-renin ratio (ARR) are used to screen for primary aldosteronism (PA). Substantial intra-individual variability of PAC and ARR using plasma renin activity in the context of usual antihypertensive therapy has been described, but there is no data on ARR variability calculated using direct renin concentration (DRC). To describe the intra-individual variability of PAC, DRC, and ARR in the absence of interfering medications in patients with and without PA. Retrospective cohort study. Hypertensive patients referred for investigation of PA, with at least 2 ARR measurements while off interfering medications. Endocrine hypertension service of a tertiary center, from May 2017 to July 2021. PAC, DRC, and ARR variability was calculated as coefficient of variation (CV) and percent difference (PD). Analysis of 223 patients (55% female, median age 52 years), including 162 with confirmed PA, demonstrated high variability with a sample CV of 22-25% in the PAC and sample CV of 41% to 42% in the DRC and ARR in both the PA and non-PA groups. The degree of variability was substantially higher than the assays' analytical CV. Sixty-two patients (38%) with PA had at least one ARR below 70 pmol/L:mU/L (2.4 ng/dL:mU/L), a cut-off for first-line screening of PA. Significant intra-individual variability in PAC, DRC, and hence ARR occurs in a large proportion of patients being investigated for PA. These findings support the need for at least 2 ARR before PA is excluded or further investigated.

Evaluation of arterial stiffness and serum endocan levels in patients with primary aldosteronism with new-onset hypertension and long-term hypertension.

There is growing evidence that prolonged exposure to high serum aldosterone concentrations results in target organ damage to the heart, kidney, and arterial wall, and that primary aldosteronism (PA) is associated with increased cardiovascular risk. In this study, we aimed to evaluate cardiovascular disease (CVD) risk indicators such as arterial stiffness [with pulse wave velocity (PWV) measurement] in PA patients and endocan levels, which is a biomarker of endothelial dysfunction. 28 patients with PA were included in our study. As the control group, 14 patients with essential hypertension (EHT) and 28 normotensive healthy volunteers were included. Height, weight, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), serum fasting glucose, insulin, hemoglobin A1c (HbA1c), C-reactive protein (CRP), lipids and endocan levels of all subjects in the PA, EHT and control groups were measured. PWV measurements were performed to assess arterial stiffness. In the PA group, PWV levels were similar to the EHT group, and endocan levels were lower than the EHT group. In the PA group, PWV levels were higher than the control group, and endocan levels were lower than the control group. When we compared the PA group with new-onset HT with the PA group with long-term HT, PWV levels were higher in the PA group with long-term HT. When we compared the long-term HT group with the EHT group, PWV levels were higher in the long-term HT PA group and endocan levels were higher in the EHT group. When we compared the PA group with long-term HT with the control group, PWV levels were higher in the PA group with long-term HT, and endocan levels were similar in both groups. In our study, it was determined that arterial stiffness increased in PA cases with long-term HT compared to PA cases with new-onset HT, EHT cases and normotensive healthy cases. We found that endocan levels in PA patients were also lower than both EHT patients and healthy controls.

Prevalence and clinical characteristics of primary aldosteronism in a tertiary-care center in Korea.

Approximately 29% of Korean adults have hypertension; however, the prevalence of primary aldosteronism among the hypertensive population is largely unknown. The aim of our study was to evaluate the prevalence and clinical characteristics of primary aldosteronism in a tertiary-care center in Korea. We retrospectively analyzed 1173 patients with newly diagnosed or preexisting hypertension who were referred to our tertiary-care hospital between January 2013 and December 2018. Patients were screened for primary aldosteronism with the aldosterone-renin ratio and underwent a saline infusion test for diagnostic confirmation. Adrenal computed tomography and adrenal venous sampling were performed for subtype classification for primary aldosteronism. Among the 1173 patients (mean age, 51.8 years; women, 53.2%), 360 (30.7%) had positive screening-test results, of whom 71 (6.1%) were finally diagnosed with primary aldosteronism. Conclusive subtype differentiation was made in 55 patients, of whom 15 (27%) had an aldosterone-producing adenoma, 4 (7%) had unilateral adrenal hyperplasia, and 36 (66%) had bilateral adrenal hyperplasia. Patients with primary aldosteronism had a higher ambulatory blood pressure, left ventricular mass index, and urinary albumin-to-creatinine ratio than those without. Moreover, the primary aldosteronism group had a higher prevalence of left ventricular hypertrophy and albuminuria than the non-primary aldosteronism group. Primary aldosteronism may be more common (6.1%) among Korean patients with hypertension than generally recognized. Primary aldosteronism was associated with a higher degree and prevalence of target organ damage and a higher blood pressure level. Wide application of screening tests for primary aldosteronism may be beneficial in detecting this potentially curable cause of hypertension.