Elevated Plasma Aldosterone Concentration Research Articles

7211 Clinical and Molecular Characterization Of An Aldosterone-Producing Adenoma Harboring Double Somatic Mutations In CTNNB1 and GNA11

Abstract Disclosure: A. Blinder: None. K. Nanba: Grant Recipient; Self; AstraZeneca. A. Udager: None. Y. Hirokawa: None. T. Miura: None. H. Okuno: None. K. Moriyoshi: None. Y. Yamazaki: None. H. Sasano: None. A. Yasoda: None. N. Satoh-Asahara: None. W.E. Rainey: None. T. Tagami: None. Background: Somatic activating mutations in CTNNB1, encoding β-catenin, have been detected in a small subset of aldosterone-producing adenomas (APAs). As a possible pathogenesis, an association of CTNNB1-mutated APA with pregnancy and menopause has been proposed. A recent study reported double somatic mutations in CTNNB1 and GNA11/Q, encoding guanine nucleotide-binding protein subunits alpha-11 and alpha-Q, in APA. However, due to its rare incidence, clinical and molecular features of APA associated with these mutations have not been well characterized. Herein, we report a case of APA harboring somatic CTNNB1 and GNA11 mutations. Clinical Case: A 46-year-old Japanese woman presented with hypertension and hypokalemia. She had two pregnancies in the past but had no history of pregnancy-induced hypertension. She had regular menstrual cycles at presentation. Laboratory testing showed elevated plasma aldosterone concentration with suppressed plasma renin activity. She was diagnosed as having primary aldosteronism based on the results of a captopril challenge test. Adrenal computed tomography revealed a 2 cm right adrenal mass. Adrenal venous sampling indicated excess aldosterone production from the right adrenal gland. She underwent right laparoscopic adrenalectomy. Histologic diagnosis of the resected tumor was adrenocortical adenoma based on the criteria of Weiss. Notably, Ki-67 labeling index was high (6% at hotspots). After surgery, her blood pressure and serum potassium both normalized. According to the primary aldosteronism surgical outcome (PASO) study criteria, PA remained clinically and biochemically cured at follow-up 2.5 years after surgery. Results: Immunohistochemistry (IHC) showed high and diffuse expression of aldosterone synthase (CYP11B2) within the tumor, whereas immunoreactivity of 17α-hydroxylase (CYP17A1) and 11β-hydroxylase (CYP11B1), both required for cortisol biosynthesis, was markedly low. VSNL1, a marker for the zona glomerulosa (ZG) where physiologic aldosterone biosynthesis occurs, was highly expressed within the tumor. CYP11B2 IHC-guided tumor capture followed by targeted next-generation sequencing identified double somatic CTNNB1 (p.D32Y) and GNA11 (p.Q209H) mutations. Quantitative real-time RT-PCR revealed high tumor expression of LHCGR (LH receptor) and GNRHR (GNRH receptor) mRNA levels compared with those in adjacent normal adrenal (148-fold and 56-fold, respectively). Immunofluorescence staining of the tumor revealed the presence of activated β-catenin, consistent with features of the normal ZG. Conclusions: Our study indicates that an APA with double somatic mutations in CTNNB1 and GNA11 has characteristics of the ZG and could occur in adults with no clear association with pregnancy or menopause. Presentation: 6/3/2024

Associating plasma aldosterone concentration with the prevalence of MAFLD in hypertensive patients: insights from a large-scale cross-sectional study.

To explore the link between plasma aldosterone concentration (PAC) and the prevalence of metabolic dysfunction-related fatty liver disease (MAFLD) in hypertensive patients. We analyzed data from 41,131 hospitalized patients from January 1, 2014, to December 31, 2023. Multivariate logistic regression models tested associations, with threshold, subgroup, and sensitivity analyses conducted to validate findings. For each 5-unit increase in PAC, the risk of MAFLD rose by 1.57 times, consistent even in the fully adjusted model. The odds ratios for the Q2, Q3, and Q4 groups compared to Q1 were 1.21, 2.12, and 3.14, respectively. A threshold effect was observed at 14 ng/dL, with subgroup and sensitivity analyses supporting these results. This study reveals a significant positive association between elevated PAC levels and the prevalence of MAFLD in hypertensive patients. These findings underscore the imperative for further large-scale, prospective studies to validate and expand upon this correlation.

P009 CORRELATION BETWEEN PLASMA ALDOSTERONE CONCENTRATION AND BONE MINERAL DENSITY IN HYPERTENSIVE PATIENTS: POTENTIAL IMPACT ON OSTEOPOROSIS AND FUTURE FRACTURE RISK

Background: Previous studies have suggested that aldosterone may play a major role in calcium-phosphorus homeostasis and bone metabolism. However, the relationship between plasma aldosterone concentrations (PAC) and bone mineral density (BMD) in hypertensive patients remains unclear. Therefore, this study sought to investigate the relationship between PAC levels and BMD and explore PAC's potential impact on osteoporosis and future fracture risk in hypertensive patients. Methods: Our study included a total of 1430 participants. Associations are tested using multiple linear and logistic regression models. Nonlinearity was investigated using the restricted cubic spline (RCS). We also performed mediating analyses to assess mediating factors mediating the relationship between PAC and osteoporosis. Results: The multiple linear regression showed a negative correlation between PAC and BMD and was generally positively associated with FRAX scores. Meanwhile, logistic regression analyses indicated that osteoporosis was highly correlated with PAC levels. In addition, a clear non-linear dose-response relationship was also shown in the constructed RCS model. Finally, mediation analyses showed that serum potassium played an important role in the development of osteoporosis. Conclusion: This study demonstrates that elevated PAC levels are strongly associated with decreased BMD, increased prevalence of osteoporosis, and the risk of future fractures in hypertensive patients. Further studies are needed to confirm this relationship and reveal its underlying mechanisms.

Diagnosis and Management of Adrenocortical Carcinoma with co-secretion of Cortisol and Aldosterone

Adrenocortical carcinoma (ACC) accounts for 0.05-2% of all malignant tumors. Forty-five percent of ACCs with secretory function have excess glucocorticoids alone and only less than 1% secrete aldosterone. This is a case of a 44-year-old Filipino female with hypertension and a 12-year-history of an incidentaloma of the left adrenal gland, with recent-onset complaints of increasing abdominal girth, purple striae, amenorrhea, moon facies and a dorsocervical fat pad. Laboratory findings revealed low potassium levels, non-suppressed cortisol on dexamethasone test suggesting Cushing’s syndrome and elevated aldosterone-renin ratio and plasma aldosterone concentration pointing to primary hyperaldosteronism. A computed tomography scan revealed a left-sided adrenal mass measuring approximately 23 cm in largest diameter suggestive of carcinoma without metastasis or lymph node involvement. Complete resection via open adrenalectomy was performed and histopathologic assessment revealed Adrenocortical Carcinoma with Weiss score of 4. The Ki-67 proliferative index was found to be >20%. Radiotherapy was done as an adjuvant treatment. Although rare, co-secretion of cortisol and aldosterone can occur in functional tumors of adrenocortical carcinoma. Malignancy should always be considered in patients who present with a history of a unilateral adrenal mass and/ or in those with signs and symptoms of adrenal hormone excess. Thus, a proper assessment derived from a thorough medical history, physical examination and laboratory work-up is warranted in patients with an adrenal mass to ascertain the diagnosis and provide adequate management.

Plasma aldosterone concentrations elevation in hypertensive patients: the dual impact on hyperuricemia and gout.

Prior research has highlighted the association between uric acid (UA) and the activation of the renin-angiotensin-aldosterone system (RAAS). However, the specific relationship between aldosterone, the RAAS's end product, and UA-related diseases remains poorly understood. This study aims to clarify the impact of aldosterone on the development and progression of hyperuricemia and gout in hypertensive patients. Our study involved 34534 hypertensive participants, assessing plasma aldosterone concentration (PAC)'s role in UA-related diseases, mainly hyperuricemia and gout. We applied multiple logistic regression to investigate the impact of PAC and used restricted cubic splines (RCS) for examining the dose-response relationship between PAC and these diseases. To gain deeper insights, we conducted threshold analyses, further clarifying the nature of this relationship. Finally, we undertook subgroup analyses to evaluate PAC's effects across diverse conditions and among different subgroups. Multivariate logistic regression analysis revealed a significant correlation between the occurrence of hyperuricemia and gout and the elevation of PAC levels. Compared to the first quartile (Q1) group, groups Q2, Q3, and Q4 all exhibited a significantly increased risk of occurrence. Moreover, the conducted RCS analysis demonstrated a significant nonlinear dose-response relationship, especially when PAC was greater than 14 ng/dL, with a further increased risk of hyperuricemia and gout. Finally, comprehensive subgroup analyses consistently reinforced these findings. This study demonstrates a close association between elevated PAC levels and the development of UA-related diseases, namely hyperuricemia and gout, in hypertensive patients. Further prospective studies are warranted to confirm and validate this relationship.

Associated lifestyle factors of elevated plasma aldosterone concentration in community population, gender-stratified analysis of a cross-sectional survey

BackgroundAldosterone plays important parts in development of cardio-metabolic diseases as end product of renin-angiotensin-aldosterone system. However, factors elevating circulating aldosterone are not clear, and lifestyle-related factors are suggested to be involved, whereas less studied. Therefore, we aimed to explore the association of lifestyle factors with plasma aldosterone concentration (PAC) in community population.MethodsIn this cross-sectional study, we recruited participants using multistage random sampling from Emin China in 2019, and collected data and fasting blood samples. The considered lifestyle factors included obesity parameters (neck circumference, abdominal circumference), alcohol consumption, blood pressure (BP), physical activity, sleep duration, sleep quality, mental state (depression and anxiety), fasting blood glucose (FBG), and lipid profiles (total cholesterol and triglyceride). PAC was measured using radioimmunoassay. We performed sex-stratified linear and logistic regressions to explore associated factors of PAC. Component analysis was further performed to identify the main factors affecting PAC.ResultsTwenty-seven thousand four hundred thirty-six participants with 47.1% men were included. Obesity parameters (neck circumference, abdominal circumference), glucose metabolism (FBG), psychological status (anxiety status in men and women, depression status in men), BP, liver function (in men), lipid metabolism (TC and TG in men), sleep parameters (sleep quality in women), and renal function (in women) are the main factors associated with elevated PAC.Conclusionlower physical activity, alcohol consumption, higher BP, fat accumulation, dyslipidemia, higher fasting blood glucose, and presence of depression and anxiety were the main factors associated with eleveated PAC.

Correlation between plasma aldosterone concentration and bone mineral density in middle-aged and elderly hypertensive patients: potential impact on osteoporosis and future fracture risk.

Previous studies have suggested that aldosterone may play a major role in calcium-phosphorus homeostasis and bone metabolism. However, the relationship between plasma aldosterone concentrations (PAC) and bone mineral density (BMD) in middle-aged and elderly hypertensive patients remains unclear. Therefore, this study sought to investigate the relationship between PAC levels and BMD and explore PAC's potential impact on osteoporosis and future fracture risk in hypertensive patients. Our study included a total of 1430 participants. Associations are tested using multiple linear and logistic regression models. Nonlinearity was investigated using the restricted cubic spline (RCS). We also performed mediating analyses to assess mediating factors mediating the relationship between PAC and osteoporosis. The multiple linear regression showed a negative correlation between PAC and BMD and was generally positively associated with FRAX scores. Meanwhile, logistic regression analyses indicated that osteoporosis was highly correlated with PAC levels. In addition, a clear non-linear dose-response relationship was also shown in the constructed RCS model. Finally, mediation analyses showed that serum potassium played an important role in the development of osteoporosis. This study demonstrates that elevated PAC levels are strongly associated with decreased BMD, increased prevalence of osteoporosis, and the risk of future fractures in middle-aged and elderly hypertensive patients. Further studies are needed to confirm this relationship and reveal its underlying mechanisms.

Abstract 11389: Circulating Aldosterone is an Independent Risk Marker for Left Main Coronary Artery Disease

Background: Elevated plasma aldosterone concentrations reflect remodeling of the vascular wall and increased cardiovascular risk, whereas data from the left main coronary artery (LMCA) are lacking. Patients with stenosis of the LMCA present difficult challenges. Therefore, the aim of this study was to investigate the relationship between plasma aldosterone concentrations and LMCA in patients with hypertension. Methods: We recruited hypertensive patients with LMCA with assessed plasma aldosterone concentrations before disease onset from the hospital between 2018 and 2022 and set them as the case group. Simultaneously, an age- and gender-matched cohort with plasma aldosterone concentration measurements but without LMCA was selected as the control group using a ratio of 1:3. Multivariable logistic regression analysis was used to assess the relationship of plasma aldosterone concentrations with LMCA. Angiographically significant LMCA stenosis is defined as luminal diameter stenosis ≥ 50%. Results: A total of 608 hypertensive patients were identified in this study, including 152 cases and 456 controls. The mean age of the patients was 60.8 ± 17.5 years, and 389 (64.0%) were men. Compared with the control group, the case group exhibited significantly higher plasma aldosterone concentrations (15.38 versus 9.68 ng/dL, P =0.009). In logistic regression analysis, higher plasma aldosterone concentrations showed 2.73-fold higher odds (95% confidence interval [CI], 1.35-3.68, P =0.003) for the presence of LMCA, which was significant in the adjusted model (odds ratio, 2.02 [95% CI, 1.18-2.97], P =0.008). In a stratified analysis, males with coronary artery disease and women of all ages showed a relationship between the two. The link between the two was unaffected by sensitivity analysis that excluded those who were exposed to interfering substances during the measurement of plasma aldosterone concentration and those who had primary aldosteronism. Conclusions: This study indicated that higher plasma aldosterone levels were associated with an increased risk of LMCA in patients with hypertension, even in the absence of primary aldosteronism. Interventional studies are needed to elucidate the health effect of treatments to lower aldosterone levels.

Activation of the Renin-Angiotensin-Aldosterone System Is Attenuated in Hypertensive Compared with Normotensive Pregnancy.

Hypertension during pregnancy increases the risk of adverse maternal and fetal outcomes, but the mechanisms of pregnancy hypertension are not precisely understood. Elevated plasma renin activity and aldosterone concentrations play an important role in the normal physiologic adaptation to pregnancy. These effectors are reduced in patients with pregnancy hypertension, creating an opportunity to define the features of the renin-angiotensin-aldosterone system (RAAS) that are characteristic of this disorder. In the current study, we used a novel LC-MS/MS-based methodology to develop comprehensive profiles of RAAS peptides and effectors over gestation in a cohort of 74 pregnant women followed prospectively for the development of gestational hypertension and pre-eclampsia (HYP, 27 patients) versus those remaining normotensive (NT, 47 patients). In NT pregnancy, the plasma renin activity surrogate, (PRA-S, calculated from the sum of Angiotensin I + Angiotensin II) and aldosterone concentrations significantly increased from the first to the third trimester, accompanied by a modest increase in the concentrations of angiotensin peptide metabolites. In contrast, in HYP pregnancies, PRA-S and angiotensin peptides were largely unchanged over gestation, and third-trimester aldosterone concentrations were significantly lower compared with those in NT pregnancies. The results indicated that the predominant features of pregnancies that develop HYP are stalled or waning activation of the RAAS in the second half of pregnancy (accompanied by unchanging levels of angiotensin peptides) and the attenuated secretion of aldosterone.

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.

PS-BPR01-7: CONCURRENT SOMATIC MUTATIONS IN CTNNB1 AND GNA11 IN AN ALDOSTERONE-PRODUCING ADENOMA

Background: Aldosterone-producing adenoma (APA) is a major subtype of primary aldosteronism (PA), a common form of secondary hypertension. In the past decade, there has been significant progress in the determination of genetic causes of APA. The use of next-generation sequencing (NGS) has led to the identification of somatic mutations in APA that cause excess aldosterone production. Most of the affected genes encode ion channels or transporters. Somatic activating mutations in CTNNB1 (β;-catenin) have also been detected in 2–5% of APA. As a possible pathogenesis, an association of CTNNB1-mutated APA with pregnancy and menopause has been proposed. A recent study reported double somatic mutations in CTNNB1 and GNA11/Q in APA. However, due to its rare incidence, characteristics of APA with these mutations are not well determined. Herein, we report a case of APA harboring somatic CTNNB1 and GNA11 mutations. Case presentation: A 46-year-old Japanese woman presented with hypertension and spontaneous hypokalemia. She had no history of pregnancy-induced hypertension. She had regular menstrual cycle at presentation. Endocrine testing showed elevated plasma aldosterone concentration (677.5 pg/mL) under suppressed renin (plasma renin activity, 0.3 ng/mL/h). Computed tomography revealed a 2 cm right adrenal mass. Adrenal venous sampling indicated excess aldosterone production from the right adrenal gland. NP-59 scintigraphy further demonstrated increased tracer uptake in the right adrenal lesion. She underwent right laparoscopic adrenalectomy. Histologic diagnosis of the resected tumor was adrenocortical adenoma based on the Weiss criteria. Notably, Ki-67 labeling index was high (6% at hotspots). After surgery, her blood pressure and serum potassium both normalized. Based on the PASO (the primary aldosteronism surgical outcome) study criteria, PA remained clinically and biochemically cured at follow-up 18 months after surgery. Methods: Formalin-fixed, paraffin-embedded adrenal tumor tissue was used for immunohistochemical and genetic analysis. Results: Immunohistochemistry (IHC) showed high and diffuse expression of CYP11B2 (aldosterone synthase) within the tumor, whereas 11β;-hydroxylase (CYP11B1, a steroidogenic enzyme for cortisol biosynthesis) was mostly negative. VSNL1, a marker for the zona glomerulosa where physiologic aldosterone biosynthesis occurs, was highly expressed within the tumor. CYP11B2 IHC-guided targeted NGS identified concurrent somatic CTNNB1 (p.D32Y) and GNA11 (p.Q209H) mutations with similar variant allele frequencies (29.5% and 29.7%, respectively). Conclusions: To best of our knowledge, this is the first Asian case of APA with CTNNB1 and GNA11 mutations. Detailed clinical and histologic examination would provide useful information for better characterization of patients with PA due to these rare mutations.

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.

Normotensive primary hyperaldosteronism due to an adrenocortical adenoma in a dog

AbstractWe present an 8‐year‐old poodle with polyuria, polydipsia and muscle weakness. Physical examination revealed no abnormalities. Laboratory alterations were hypokalemia and hypernatraemia with a low urine specific gravity. Abdominal ultrasound revealed a nodule in the right adrenal gland (diameter 0.95 cm). Systolic blood pressure was normal for several consecutive days (on average 120 mmHg). Elevated plasma aldosterone and undetectable plasma renin concentrations were diagnostic of primary hyperaldosteronism. An uncomplicated adrenalectomy was performed. Histopathological examination revealed an adrenocortical adenoma with positive expression for neuron‐specific enolase but not for synaptophysin and chromogranin on immunohistochemistry. In addition, immunostaining for neuron‐specific enolase was also found in cells from the normal glomerular zone of the same adrenal gland. Therefore, zona glomerulosa origin of the neoplasm was inferred. Adrenalectomy normalised laboratory abnormalities with remission of clinical signs. This report highlights the importance of not excluding the diagnosis of primary hyperaldosteronism in the absence of arterial hypertension.

Diagnostic Accuracy of Computed Tomography in Predicting Primary Aldosteronism Subtype According to Age.

BackgroundGuidelines by the Endocrine Society Guideline on bypassing adrenal vein sampling (AVS) in patients <35 years old with marked primary aldosteronism (PA) (hypokalemia and elevated plasma aldosterone concentration [PAC]) and a unilateral lesion on computed tomography (CT) are based on limited number of studies. We aimed to determine the accuracy of CT in PA patients according to age.MethodsIn this retrospective study, we investigated the concordance between CT and AVS in 466 PA patients from two tertiary centers who successfully underwent AVS.ResultsCT had an overall accuracy of 64.4% (300/466). In the group with unilateral lesion, patients with hypokalemia had higher concordance than those without hypokalemia (85.0% vs. 43.6%, P<0.001). In the group with marked PA (hypokalemia and PAC >15.9 ng/dL) and unilateral lesion, accuracy of CT was 84.6% (11/13) in patients aged <35 years; 100.0% (20/20), aged 35 to 39 years; 89.4% (59/66), aged 40 to 49 years; and 79.8% (79/99), aged ≥50 years. Cut-off age and PAC for concordance was <50 years and >29.6 ng/dL, respectively. The significant difference in accuracy of CT in 198 patients with marked PA and a unilateral lesion between the <50-year age group and ≥50-year age group (90.9% vs. 79.8%, P=0.044) disappeared in 139 of 198 patients with PAC > 30.0 ng/dL (91.9% vs. 87.7%, P=0.590).ConclusionPatients with hypokalemia, PAC >30.0 ng/dL, and unilateral lesion were at high risk of unilateral PA regardless of age.

Normotensive presentation in primary aldosteronism: A report of two cases

Normotensive patients with primary aldosteronism (PA) are relatively rare. Herein, we report two patients with normotensive PA and present a literature review to improve an understanding of the disease. Patient 1, a 56-year-old man, presented with recurrent hypokalemia that lasted for more than 2 years. Patient 2 was a 33-year-old man who presented with sexual dysfunction and was diagnosed with a prolactinoma combined with adrenal insufficiency and hypogonadism. Neither of these patients had hypertension that was detectable on repeated manual measurements. In both patients, a typical biological profile of PA was demonstrated that included hypokalemia with kaliuresis, elevated plasma aldosterone concentration (PAC), suppressed plasma renin concentration, and a high aldosterone-to-renin ratio. Both patients did not have sufficiently suppressed PAC on the saline infusion test, confirming the diagnosis of PA. Computed tomography of the adrenal gland and adrenal venous sampling suggested an aldosteronoma, which was confirmed by lateralized hypersecretion of aldosterone. After removal of the benign adenoma, the biochemical abnormalities were corrected. As hypertension is not necessarily a sign of PA, we propose that all patients with hypokalemia should be screened for PA in order to prevent cardiovascular complications while balancing economics and effectiveness.

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.

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.

Association between elevated plasma aldosterone concentration and left atrial conduit function in hypertension

Aldosterone affects myocardial fibrosis and remodeling. The aim was to investigate the relationship between plasma aldosterone concentration (PAC) and left atrial (LA) function in hypertension. 148 hypertensive patients were studied. LA phasic function was evaluated by strain and strain rate imaging. Patients were divided into two groups based on PAC. LA early diastolic strain and strain rate (LAS-E and LASR-E) were lower in group II compared with group I (P ​< ​0.05). Multivariate regression analysis showed that LAS-E was independently related to PAC (β ​= ​−0.581, P ​< ​0.001). In conclusion, PAC is associated with LA conduit function in hypertension.

Improvement of Cardiac Function by Laparoscopic Adrenalectomy in a Patient with Severe Heart Failure Attributable to Primary Aldosteronism

Aldosterone affects various systems and organs, including the cardiovascular system, through mineralocorticoid receptors. We here report a primary aldosteronism patient with severe cardiac dysfunction who showed dramatic improvement after laparoscopic adrenalectomy. The 57-year-old man presented with acute heart failure exacerbation. Performance status was 4, and New York Heart Association classification was 4. Echocardiography showed diffuse hypokinetic wall motion with an ejection fraction of 20%. The patient was found to have a high plasma level of brain natriuretic peptide (4,935 pg/mL), hypokalemia (2.7 mEq/L), an extremely elevated plasma aldosterone concentration (1,804 pg/mL), and high aldosterone-to-renin ratio [plasma aldosterone concentration (pg/mL)/plasma renin activity (ng/mL/hr)] (9,002). Computed tomography revealed a tumor 42 mm in diameter in the right adrenal gland. Primary aldosteronism was diagnosed with adrenal venous sampling. Medical treatment for heart failure was continued for several months, but the cardiac function was not sufficiently improved, suggesting the indication of heart transplantation. However, the patient could not be considered a candidate because of the adrenal tumor. Laparoscopic adrenalectomy was therefore performed. Immediately after surgery, echocardiography showed improved wall motion with an ejection fraction of 36%. Performance status and New York Heart Association classification were improved to 0 and 2, respectively. The present case has shown the efficacy of laparoscopic adrenalectomy for primary aldosteronism patients with severe heart failure.

Speckle-Tracking Echocardiographic Layer-Specific Strain Analysis on Subclinical Left Ventricular Dysfunction in Patients With Primary Aldosteronism.

Primary aldosteronism (PA) may cause myocardial injury. We investigated myocardial dysfunction using speckle-tracking echocardiographic (STE) layer-specific strain in patients with PA. Our study included 62 patients with PA (33 aldosterone-producing adenoma [APA] and 29 idiopathic hyperaldosteronism [IHA]) and 30 patients with primary hypertension. STE was acquired using the GE Vivid E9 equipment. The longitudinal (LS) and circumferential (CS) layer-specific strains of the endocardium, midmyocardium, and epicardium (LSendo, LSmid, LSepi, CSendo, CSmid, and CSepi) were obtained using the EchoPAC BT13 workstation. Patients with APA, compared with those with primary hypertension and IHA, had a significantly (P < 0.001) lower serum potassium concentration and plasma renin activity, and higher 24-h urinary aldosterone, plasma aldosterone concentration, and aldosterone-to-renin ratio. Left ventricular ejection fraction was normal in all patients (58-60%). Layer-specific strain showed decreasing gradient from the endocardium to epicardium in all 3 groups (P < 0.01). However, LSendo and CSendo were lowest in APA (-20.2 ± 2.3% and -33.3 ± 3.2%), intermediate in IHA (-22.1 ± 1.9% and -35.7 ± 2.8%) and highest in primary hypertension (-24.1 ± 2.1% and -38.9 ± 3.1%, P < 0.001). Similar trends were observed for LSmid, LSepi, CSmid, and CSepi, but statistical significance was only reached for the comparison between APA and primary hypertension (P < 0.001), but not others (P > 0.05). Layer-specific strain was significantly correlated with plasma aldosterone concentration for all echocardiographic parameters (r = -0.69 to -0.53, P < 0.001) in all 3 groups. Patients with PA, especially APA, had impaired regional systolic function with myocardial deformation changes at similar levels of blood pressure, probably because of elevated plasma aldosterone concentration.