High Plasma Aldosterone Concentration Research Articles

Aldosterone is Associated With New-onset Cerebrovascular Events in Patients With Hypertension and White Matter Lesions: A Cohort Study

ObjectiveWhite matter lesions (WMLs) increase the risk of stroke, stroke recurrence, and death. Higher plasma aldosterone concentration (PAC) increases the risk of stroke, acute myocardial infarction, and hypertension. The objective is to evaluate the relationship between PAC and cerebrovascular events in patients with hypertension and WMLs. MethodsWe conducted a retrospective cohort study that included 1041 participants hospitalized. The outcome was new-onset cerebrovascular events including intracerebral hemorrhage and stroke. A Cox regression model was used to evaluate the relationship between baseline PAC and the risk of cerebrovascular events. ResultsThe mean age of participants was 60.9 ± 10.2 years and 565 (53.4%) were males. The median follow-up duration was 42 months (interquartile range: 25-67), and 92 patients experienced new-onset cerebrovascular events. In a multivariate-adjusted model, with PAC as a continuous variable, higher PAC increased the risk of cerebrovascular events; patient risk increased per 1 (hazard ratio [HR: 1.03], 95% confidence interval [CI]: 1.01-1.06, P < .01), per 5 (HR: 1.17, 95% CI: 1.06-1.31, P < .01), and per 10 ng/dL (HR: 1.41, 95%: 1.14-1.75, P < .01) increase in PAC. When PAC was expressed as a categorical variable (quartile: Q1-Q4), patients in Q4 (HR: 2.12, 95% CI: 1.18-3.79, P < .05) exhibited an increased risk of cerebrovascular events compared to Q1. Restrictive spline regression showed a linear association between PAC and the risk of new-onset cerebrovascular events after adjusting for all possible variables. ConclusionsOur study identified a linear association between PAC and the risk of new-onset cerebrovascular events in patients with hypertension and WMLs.

Differences in the clinical and hormonal presentation of patients with familial and sporadic primary aldosteronism.

To compare the clinical and hormonal characteristics of patients with familial hyperaldosteronism (FH) and sporadic primary aldosteronism (PA). A systematic review of the literature was performed for the identification of FH patients. The SPAIN-ALDO registry cohort of patients with no suspicion of FH was chosen as the comparator group (sporadic group). A total of 360 FH (246 FH type I, 73 type II, 29 type III, and 12 type IV) cases and 830 sporadic PA patients were included. Patients with FH-I were younger than sporadic cases, and women were more commonly affected (P = 0.003). In addition, the plasma aldosterone concentration (PAC) was lower, plasma renin activity (PRA) higher, and hypokalemia (P < 0.001) less frequent than in sporadic cases. Except for a younger age (P < 0.001) and higher diastolic blood pressure (P = 0.006), the clinical and hormonal profiles of FH-II and sporadic cases were similar. FH-III had a distinct phenotype, with higher PAC and higher frequency of hypokalemia (P < 0.001), and presented 45 years before sporadic cases. Nevertheless, the clinical and hormonal phenotypes of FH-IV and sporadic cases were similar, with the former being younger and having lower serum potassium levels. In addition to being younger and having a family history of PA, FH-I and III share other typical characteristics. In this regard, FH-I is characterized by a low prevalence of hypokalemia and FH-III by a severe aldosterone excess causing hypokalemia in more than 85% of patients. The clinical and hormonal phenotype of type II and IV is similar to the sporadic cases.

Comparisons of risk factors for post-treatment renal dysfunction between the two major subtypes of primary aldosteronism.

Aldosterone-producing adenoma (APA) and bilateral idiopathic hyperaldosteronism (IHA) are the most common subtypes of primary aldosteronism (PA), and the PA subtype dictates the treatment options. This study aimed to identify predictors of declined estimated glomerular filtration rate (eGFR) following each treatment in patients with APA and IHA. We retrospectively investigated 45 patients with APA who had undergone adrenalectomy (ADX) and 37 patients with IHA who had received treatment with a mineralocorticoid receptor antagonist (MRA) to identify pre-treatment risk factors for eGFR decline during the post-treatment follow-up period. Patients with APA who underwent ADX exhibited higher eGFR declines than patients with IHA treated with MRA at the 6-month post-treatment evaluation point. A high preoperative plasma aldosterone concentration (PAC) in patients with APA and a high body mass index (BMI) in patients with IHA were identified as independent predictors of higher eGFR decline at 6 months post-treatment (β=0.42 and β=0.36, respectively). In patients with APA, the cutoff PAC to best predict a 20% decrease in eGFR following ADX, as determined by receiver operating characteristic analysis, was 524 pg/mL. In patients with IHA, the cutoff BMI to best predict a 10% decrease in eGFR following MRA administration was 25.3 kg/m2. In addition, lower preoperative flow-mediated vasodilation was associated with eGFR decline after ADX in patients with APA. Greater attention should be given to the above-mentioned risk factors to prevent renal impairment following each treatment in patients with both APA and IHA.

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.

Bilateral Cortical-sparing Adrenalectomy for the Treatment of Bilateral Aldosterone-producing Adenomas

Abstract Aldosterone-producing adenoma (APA) is 1 of the major subtypes of primary aldosteronism (PA). Although most APA occurs unilaterally, bilateral APAs have rarely been documented. Because of its rarity, optimal management of patients with bilateral APAs has not been established. Here, we report a case of bilateral APAs that was successfully treated with simultaneous bilateral cortical-sparing surgery. A 44-year-old Japanese woman was referred to us for the evaluation of PA. She had typical clinical characteristics of PA, including hypertension, hypokalemia, and high plasma aldosterone concentration with suppressed renin. She was diagnosed as having PA based on the results of confirmatory testing. Computed tomography revealed bilateral adrenal nodules with diameters of 17 and 10 mm on the right and left adrenal gland, respectively. Adrenal venous sampling indicated excess aldosterone production from bilateral adrenal lesions. She underwent simultaneous bilateral laparoscopic partial adrenalectomy that normalized her blood pressure and serum potassium levels. Aldosterone synthase immunohistochemistry on the resected adrenal tumor tissue confirmed the diagnosis of bilateral APAs. Long-term postsurgical follow-up data suggest cure of the disease without the need for glucocorticoid replacement therapy. Bilateral cortical-sparing adrenalectomy appears to be a viable treatment option at least for selected patients with bilateral APAs.

FRI125 Recurrence Of Primary Aldosteronism Long-Term After Adrenalectomy For Aldosterone-Producing Adenoma With KCNJ5 Gene Mutation: A Two-Cases Report

Abstract Disclosure: K. Aiga: None. M. Kometani: None. D. Aono: None. S. Karashima: None. T. Yoneda: None. Primary aldosteronism (PA) is a major cause of secondary hypertension. PA is known to have higher prevalence of cerebral or cardiovascular complications, indicating the importance of early detection and treatment for PA. PA is caused by autonomous secretion of aldosterone in the adrenal glands. PA is characterized by high plasma aldosterone concentration, low plasma renin activity and hypokalemia. PA is classified into unilateral PA (aldosterone-producing adenoma [APA] or unilateral hyperplasia) and bilateral PA (bilateral adrenal hyperplasia). PA with aldosterone excess in bilateral adrenal glands is defined as bilateral PA. On the other hand, PA with aldosterone excess in unilateral adrenal gland is defined as unilateral PA. Strategies for PA treatment depends on the subtype of PA. Medication by mineralocorticoid receptor antagonists is a common treatment for bilateral PA. Adrenalectomy is the most efficient treatment for unilateral PA. In general, patients tend to maintain normal serum potassium level and blood pressure after adrenalectomy, and recurrence of PA is extremely rare. Recently, mutation in the gene named KCNJ5 was found to derive APA. Herein, we report two cases of PA recurrence more than 10 years after surgical treatment for APA. Somatic mutation in KCNJ5 was detected in the first occurrence of PA in both cases. First case, a 52-year-old woman was examined for hypertension 22 years after total adrenalectomy of the right adrenal gland. Recurrent PA was diagnosed based on high aldosterone-renin-ratio (ARR), identification of left adrenal gland tumor by computed tomography (CT), and a confirmatory test. Second case, a 65-year-old man was examined for hypertension 17 years after total adrenalectomy of the left adrenal gland. He had maintained his blood pressure using medication since the onset of hypertension 4 years after the surgery. A year later, a high ARR was observed. PA recurrence was determined by a right adrenal gland tumor noted on CT and a confirmatory test. Tissues of the adrenal gland were obtained from adrenalectomy in both cases. Histopathological analysis revealed presence of one adenoma in the first case, while two adenomas were confirmed in the second case. Somatic mutation in KCNJ5 gene was detected in both cases. To date, there are no specific guidelines established for the management of recurrent PA. Early detection is crucial for the prevention of severe cardiovascular diseases. Long-term follow-up is recommended after the treatment of PA. Presentation: Friday, June 16, 2023

THU568 The Impact of Surgical versus Medical Therapy on Renin Plasma Activity, Renal Function, and Hypertension Control in Patients with Primary Aldosteronism

Abstract Disclosure: S. Rolak: None. N. Venkatesan: None. R. Gregg Garcia: None. W.F. Young: None. I. Bancos: None. Background: Bilateral primary hyperaldosteronism (PA) is treated with mineralocorticoid receptor antagonist (MRA) therapy. However, the best way to monitor the success of MRA therapy is unclear. Aims: To compare the impact of curative adrenalectomy versus MRA therapy in patients with PA on plasma renin activity (PRA), renal function, and hypertension control. Methods: Single center retrospective study of patients with unilateral PA treated with adrenalectomy or bilateral PA treated with MRAs, 2017-2021. Patients underwent adrenal vein sampling to confirm laterality. Hypertension control was defined based on blood pressure measurements and the standardized hypertension daily dose (HDD). Minimum follow-up was defined as first nonsuppressed PRA or &amp;gt;1 month from therapy. Results: Of 73 patients, 53 underwent unilateral adrenalectomy for unilateral PA (median age 57, range 25-71 years, 36% women) and 20 had bilateral PA treated with MRA (median age 49, range 30-70 years, 70% women). At baseline, when compared to the bilateral PA, patients with unilateral PA had higher plasma aldosterone concentrations (median 31 ng/dL vs 19 ng/dL, P= 0.001), similarly suppressed PRA, and similar estimated glomerular filtration rate (eGFR). Uncontrolled hypertension (&amp;gt;130/90 mmHg) was seen in 40 (75%) of patients with unilateral PA and 14 (70%) patients with bilateral PA, despite a more intensive antihypertensive regimen in unilateral PA (median HDD 5, range 1-18 vs median HDD 3.5 in bilateral PA, range 0.5-9; P=0.016). Hypokalemia was present in 50 (94%) patients with unilateral PA and 15 (75%) in bilateral PA, P = 0.02.Following treatment, hyperkalemia developed in 10 (19%) patients post-adrenalectomy and in 2 (10%) patients treated with MRAs, P = 0.36. At a median follow up of 108 days, 24 (45%) patients treated with adrenalectomy and 16 (80%) patients treated with MRAs demonstrated PRA &amp;gt;1.5 ng/mL/hr, P = 0.008. eGFR decreased by at least 10 points in 15 (30%) patients treated with adrenalectomy vs in 11 (59%) patients treated with MRAs (P=0.033). Post-adrenalectomy, antihypertensive management lessened by a median of 2.5 HDD, while HDD increased in patients treated with MRAs by a median of 1.25, P&amp;lt;0.0001. Hypertension control improved, with a mean decrease in systolic blood pressure of -11 mmHg (95%CI -16.5-(-5.5)) without between group differences. Diastolic blood pressure decreased by a mean of -4.7 mmHg (95%CI -8.7-(-0.7)) in the adrenalectomy group but did not change in those treated with MRAs. Conclusions: Following curative adrenalectomy in unilateral PA, more than half of patients continue to have suppressed PRA. Despite less severe PA at baseline, patients treated with MRAs, as compared to those treated with adrenalectomy, demonstrate a higher prevalence of non-suppressed PRA, lower eGFR, similar hypertension control, and a more intense antihypertensive regimen during follow up. Presentation: Thursday, June 15, 2023

High aldosterone levels in the renal capsular vein from the left aldosterone-producing adenoma on adrenal venous sampling.

A 42-year-old female patient was referred to our hospital with hypertension and hypokalemia and was diagnosed with primary aldosteronism. Dynamic contrast-enhanced computed tomography images revealed a 13-mm nodule on the lateral segment of the left adrenal gland and a fine venous connection between the nodule and the prominent renal capsular vein running nearby. The venograms in the left lateral tributary with a microcatheter confirmed alternative drainage to the left renal capsular vein during adrenal venous sampling, and the left renal capsular vein sampling was added. The patient was diagnosed with a left aldosterone-producing adenoma (APA) using the lateralization index (48.3) and a higher plasma aldosterone concentration (PAC) of the left lateral tributary (66 700 pg/mL) than other tributary samples after adrenocorticotropic hormone stimulation. Furthermore, markedly higher PAC (224 000 pg/mL) was observed in the left renal capsular vein blood than in the left adrenal central vein (45 000 pg/mL) and tributaries, confirming the diagnosis. Laparoscopic left partial adrenalectomy and following histopathological analysis revealed a CYP11B2-positive adrenocortical adenoma. Complete clinical and biochemical success for primary aldosteronism was achieved after 6 months. Direct evidence of APA blood venous drainage into the renal capsular vein has been demonstrated. Sampling from an alternative drainage pathway could be beneficial for APA diagnosis if such APA blood drainage is assumed. Aldosterone-producing adenomas may drain blood into an alternative pathway but for the adrenal vein. The presence of alternative venous drainage could be assumed by contrast-enhanced computed tomography or venogram during adrenal venous sampling. Sampling in the alternative drainage veins and demonstrating elevated aldosterone levels could help in diagnosing aldosterone-producing adenoma.

High plasma aldosterone concentration is associated with worse 24-h ambulatory blood pressure profile in patients with primary aldosteronism.

Patients with primary aldosteronism (PA) have a higher risk of cardiovascular disease (CVD) than essential hypertension due to underlying hyperaldosteronism. However, the association between high plasma aldosterone concentrations (PACs) and diurnal blood pressure (BP) variation has not been fully elucidated. Because abnormal ambulatory blood pressure monitoring (ABPM) profiles are associated with increased CVD risk, we investigated the association between PACs and the ABPM profile in 36 patients with PA diagnosed by confirmatory tests who underwent adrenal venous sampling (AVS). The clinical parameters were measured during hospitalization for AVS. The dietary salt intake of hospitalized patients was controlled at 6 g/day. During AVS, blood samples were collected from the inferior vena cava before and 1 h after adrenocorticotropic hormone (ACTH) stimulation to measure the PACs. The post-stimulation PAC had a significant negative correlation with nocturnal BP dipping rates (R = -0.387, p = 0.020), whereas pre-stimulation PAC did not (R = -0.217, p = 0.204). The nocturnal BP dipping rates were significantly lower in the high PAC group (PAC higher than the median) than low PAC group (PAC lower than the median) (p = 0.009). Multiple regression analysis revealed that high PAC was an independent factor contributing to low nocturnal BP dipping rates (β = -0.316, p = 0.038). In conclusion, in patients with PA, hyperaldosteronism is associated with nocturnal hypertension, which is an important risk factor for CVD. Additionally, ACTH stimulation may improve the sensitivity of PACs as a clinical indicator of nocturnal hypertension.

Effect of the interaction between the visceral-to-subcutaneous fat ratio and aldosterone on cardiac function in patients with primary aldosteronism.

Primary aldosteronism is the most frequent secondary hypertensive disease and is characterized by an elevated risk for cardiovascular disease. The current standard treatments are adrenalectomy and/or administration of mineralocorticoid receptor blockers, both of which are effective at ameliorating hypertension via intervention for hyperaldosteronism. However, both of these approaches have side effects and contraindications, and mineralocorticoid receptor blockers also have limited preventive efficacy against cardiovascular events. Recently, in vitro experiments have shown that aldosterone regulation is closely related to abdominal fat accumulation and that there is crosstalk between aldosterone and visceral fat tissue accumulation. We previously reported that this interaction was clinically significant in renal dysfunction; however, its effects on the heart remain unclear. Here, we analyzed data from 49 patients with primary aldosteronism and 29 patients with essential hypertension to examine the potential effect of the interaction between the ratio of visceral-to-subcutaneous fat tissue volume and the plasma aldosterone concentration on echocardiographic indices, including the tissue Doppler-derived E/e' ratio. A significant interaction was found in patients with primary aldosteronism (p < 0.05), indicating that patients with the combination of a high plasma aldosterone concentration and high visceral-to-subcutaneous fat ratio show an increased E/e' ratio, which is a well-known risk factor for future cardiovascular events. Our results confirm the clinical importance of the interaction between aldosterone and abdominal fat tissue, suggesting that an improvement in the visceral-to-subcutaneous fat ratio may be synergistically and complementarily effective in reducing the elevated risk of cardiovascular disease in patients with primary aldosteronism when combined with conventional therapies for reducing aldosterone activity. A significant effect of the interaction between plasma aldosterone concentration and the visceral-to-subcutaneous fat ratio on the tissue Doppler-derived E/e' ratio in patients with primary aldosteronism.

PS-BPR01-1: SUCCESSFUL TREATMENT WITH ESAXERENONE IN A PREGNANT WOMAN WITH PRIMARY ALDOSTERONISM AND SUPERIMPOSED PREECLAMPSIA

Background: During pregnancy, there is no established treatment for idiopathic hyperaldosteronism (IHA), the most common form of primary aldosteronism (PA) due to bilateral adrenal hyperplasia. Here, we report the case of a pregnant patient with IHA who was successfully treated with esaxerenone, a non-steroidal mineralocorticoid receptor (MR) antagonist. Case: A 39-year-old woman was referred to our outpatient clinic for hypertension with high plasma aldosterone concentration (PAC). Her PAC was 204 pg/mL (radioimmunoassay) and plasma renin activity was 1.2 ng/mL/h at the time of referral. She was diagnosed with PA since the saline-loading test for PA was positive. She had no hypokalemia and computed tomography scans showed no adrenal tumors. Adrenal vein sampling indicated overproduction of aldosterone in both adrenal glands leading to the diagnosis of IHA. She was commenced on nifedipine controlled release (CR) 20 mg daily because she desired to be pregnant. After one year, she became pregnant. Her blood pressure was well controlled until 34 weeks of gestation when her home blood pressure became elevated up to 140/90 mmHg. Although the dose of nifedipine CR was increased to 80 mg daily, her blood pressure increased to 151/97 mmHg and urinary test showed proteinuria of 2 + in 35 weeks of gestation. She was diagnosed with superimposed preeclampsia (SPE) and additionally treated with esaxerenone. Her blood pressure decreased to 120–140/98–100 mmHg and the proteinuria improved to +/-. A successful cesarean section at 37 weeks resulted in the delivery of a healthy baby boy. Esaxerenone was discontinued 2 weeks after delivery, because she was eager to breast-feed the baby and no safety data of esaxerenone in breast-feeding woman was available. Her blood pressure has been well controlled by nifedipine CR 80 mg daily even after 100 days of postpartum. Conclusions: This is the first case of a pregnant woman who was successfully treated with esaxerenone despite being an elderly pregnant woman who had been diagnosed with IHA and developed SPE. Further studies are needed to investigate the efficacy and safety of non-steroidal selective MR antagonist in similar pregnant patients with IHA, to establish better treatment strategy for these patients.

PS-BPR03-11: A CASE OF MALIGNANT PHASE HYPERTENSION ASSOCIATED WITH PRIMARY ALDOSTERONISM

Background: Primary aldosteronism is associated with low plasma renin levels, while malignant phase hypertension is generally associated with raised renin activity. Therefore, these two conditions are at opposite ends of the renin spectrum, so in theory their co-existence would be unusual. Case presentation: We present a case of a 41-year-old male with uncontrolled hypertension on multiple antihypertensive drugs. He discontinued these drugs for three days, thereafter he admitted to our hospital with congestive heart failure and acute ischemic stroke. He manifested malignant phase hypertension (blood pressure 216/130 mmHg; Keith-Wagener IV) accompanying renal dysfunction (serum creatinine 2.4 mg/dL), high plasma aldosterone concentration (PAC, 221 pg/mL) and mildly elevated plasma renin activity (PRA, 3.0 ng/mL/hr). A computed tomography did not reveal the presence of adrenal mass. After the treatment for congestive heart failure, the reassessment for endocrine causes of hypertension showed high level of PAC (468 pg/mL) and low level of PRA (0.2 ng/mL/hr), resulting in a high PAC/PRA ratio under the treatment with angiotensin-converting enzyme inhibitor. Adrenal venous sampling (AVS) confirmed the excessive aldosterone secretion from bilateral adrenal glands. Given these findings, we diagnosed him with idiopathic aldosteronism. After an addition of the mineralocorticoid receptor antagonist, he could keep his blood pressure under control. Conclusions: PRA in patients with primary aldosteronism could be increased under the conditions in which renin release from the kidney is overstimulated by glomerular ischemia, leading to an incorrect diagnosis of primary aldosteronism. Repeated endocrine assessment including the measurement of PRA and PAC should be considered to reveal the cause of malignant phase hypertension.

PS-R07-10: A MOTHER AND HER DAUGHTER CASES OF PRIMARY ALDOSTERONISM

The majority of cases of primary aldosteronism (PA) occur sporadically. Familial forms of PA are rare with four subtypes defined. We reported a case of familial cluster of primary aldosteronism in two members, daughter and her mother. Case presentation Case 1: Daughter A 20-year-old woman with a history of hypertension and proteinuria for three years without treatment, was admitted for the treatment of accelerated hypertension of 182/121 mmHg and end stage kidney disease. Blood examination revealed low plasma renin activity (PRA) of 0.7 ng/ml/h, and high plasma aldosterone concentration (PAC) of 349 pg/mL, high aldosterone/renin ratio (ARR) of 498.6, and serum potassium (sK) of 4.9 mEq/L. (Plasma ACTH 12.9 pg /mL, plasma cortisol 7.4 mcg/dL) These findings suggested PA. Abdominal CT scan showed no adrenal mass. After control of accelerated hypertension with nifedipine GITS and alpha adrenoceptor blocker, confirmatory tests for PA, saline infusion test (SIT) were carried out and was positive test (PAC 240 min after infusion 264pg/mL). Adrenal venous sampling revealed bilateral hyper-aldosterone secretion. She was given diagnosis of bilateral adrenal hyperaldosteronism. Her blood pressure was decreased to 118/77 along with administration of spironolactone 25 mg/day. Her parents have hypertension. We investigate the cause of hypertension in her parents. Blood test of her father revealed PRA 3.4 ng/m/h, PAC 18.3 pg/ml, and sK 4.7 mEq/L. Case 2: Mother A 45-year-old women with hypertension treated with amlodipine 5 mg was referred to our hospital to examine the renal function after renal donation to her daughter. Blood test revealed mild renal dysfunction (eGFR 72,2), normal sK(4.0 mEq/L), low PRA (0.9 ng/ml/h), high PAC (118 pg/mL) for high salt intake (11.6 g/day as high as salt loading test). Abdominal CT scan showed no adrenal mass. SIT was positive (PAC 240 min after infusion 60.0 pg/mL). She was given diagnosis of PA. Discussion: Potential factors leading to BHA include rare disease-predisposing germline variants, circulating angiotensin II type 1 receptor autoantibodies, and paracrine activation of aldosterone production by adrenal mast cells have been reported. Primary hyperaldosteronism in 2 family members, a mother and daughter, suggests familial hyperaldosteronism which caused by germline mutation. We now investigate germline variants for BHA.

PS-R04-5: A CASE OF SEVERE RENAL FAILURE WITH HYPERTENSIVE EMERGENCY WHO SUCCEEDED IN HEMODIALYSIS WITHDRAWAL BY STRICT CONTROL OF BLOOD PRESSURE

Introduction: Hypertensive emergency is a condition in which progressive and irreversible organ damages occur as a result of extremely elevated blood pressure. Although the prognosis for renal outcomes has been improved by advances in antihypertensive therapy, the cases who result in maintenance dialysis are still not uncommon. We herein report a case of hypertensive emergency who was successfully withdrawn from hemodialysis by intensive treatment. Case presentation: A 55-year-old woman, whose systolic blood pressure was 150–160 mmHg constantly for at least 2 years, was seen by her primary care physician due to nocturnal cough and respiratory distress. She exhibited marked hypertension (diastolic blood pressure, 120–130 mmHg) and renal dysfunction (serum creatinine (sCr), 2.76 mg/dL, baseline 0.5 mg/dL). She was diagnosed as hypertensive emergency and was treated with antihypertensive agents immediately. Despite the treatment, her renal function did not improve, so that she was transferred to our hospital for further examination and intensive treatment. While imaging examination revealed a right adrenal tumor, for which primary aldosteronism was suspected, endocrinological examinations showed high plasma aldosterone concentration with high plasma renin activity; therefore it was assumed that the hormonal changes were secondary to hypertensive emergency. Although funduscopic findings were relatively mild (KW-IIb), the condition was considered as accelerated-malignant hypertension caused by essential hypertension. A renal biopsy revealed extensive interstitial damage with onion skin-like lesions, which led to a diagnosis of malignant nephrosclerosis. While continuing strict antihypertensive management including the renin-angiotensin system blockade, hemodialysis was started on day 17 due to progressive renal dysfunction (sCr 9.27 mg/dL). Continuous intensive treatment gradually alleviated renal dysfunction, and hemodialysis was finally withdrawn on day 38. There was no further deterioration seen, and the patient was discharged on day 55. After discharge, her renal function was kept improved and her sCr was 2.5 mg/dL 6 months after the discharge. Discussion and Conclusion: Hypertensive emergency may cause irreversible kidney damage without appropriate antihypertensive therapy. In particular, acute tubular damages have been suggested to correlate with both systolic and diastolic blood pressures. Controlling blood pressure appropriately is crucial to protect kidneys against disease progression and even reverse kidney damage upon acute renal failure with hypertensive emergency.

Adrenal Vein Sampling Results and Surgical Outcomes in Patients with a Normal Plasma Aldosterone Concentration

PurposeTo determine the utility of adrenal vein sampling (AVS) and outcomes after adrenalectomy in patients with normal plasma aldosterone concentration (PAC) and elevated aldosterone-to-renin ratio (ARR). Materials and MethodsThe study sample included 106 patients with ARR greater than 20 and PAC between 5 and 15 ng/dL (normal PAC group) who underwent AVS from 2005 to 2021. These patients were compared with a cohort of 106 patients with ARR >20 and PAC >15 ng/dL (high PAC group) who underwent AVS during the same period. Data regarding baseline clinical characteristics, lateralization indices from AVS, and outcomes after adrenalectomy were analyzed. ResultsAVS was technically successful in 210 patients (210/212, 99%). A smaller proportion of patients in the normal PAC group showed a lateralization index of >4 compared with those in the high PAC group (44% vs 64%, P <.01). A similar proportion of patients in the normal PAC group experienced improved or cured hypertension after adrenalectomy compared with that in the high PAC group (94% vs 88%, P =.31). Hypokalemia was cured in all patients in the normal PAC group after adrenalectomy compared with 98% of patients in the high PAC group (100% vs 98%, P = 1). ConclusionsAlthough lateralization is less frequent for patients with normal PAC, patients who do lateralize show similar blood pressure response and correction of hypokalemia after adrenalectomy, regardless of initial plasma aldosterone levels. Therefore, patients with PAC <15 ng/dL should still be considered for AVS provided the ARR is elevated.

Association Between Aldosterone and Hypertension Among Patients With Overt and Subclinical Hypercortisolism.

Hypertension is one of the most common clinical features of patients with overt and subclinical hypercortisolism. Although previous studies have shown the coexistence of autonomous cortisol and aldosterone secretion, it is unclear whether aldosterone plays a role in hypertension among patients with hypercortisolism. Therefore, we examined the associations of plasma aldosterone concentrations (PACs) with hypertension among patients with overt and subclinical hypercortisolism. This single-center retrospective cohort study included patients with adrenal tumor and serum cortisol levels after 1-mg dexamethasone suppression test >1.8 µg/dL (50 nmol/L). Using multivariable regression models adjusting for baseline characteristics, we investigated the association of PACs with systolic blood pressure and postoperative improvement of hypertension after the adrenalectomy. Among 89 patients enrolled in this study (median age, 51 years), 21 showed clinical signs of Cushing syndrome (overt hypercortisolism) and 68 did not show clinical presentations (subclinical hypercortisolism). We found that higher PACs were significantly associated with elevated systolic blood pressure among patients with subclinical hypercortisolism (adjusted difference [95% CI] = +0.59 [0.19-0.99], P = 0.008) but not among those with overt hypercortisolism. Among 33 patients with subclinical hypercortisolism and hypertension who underwent adrenalectomy, the postoperative improvement of hypertension was significantly associated with higher PACs at baseline (adjusted risk difference [95% CI] = +1.45% [0.35-2.55], P = 0.01). These findings indicate that aldosterone may contribute to hypertension among patients with subclinical hypercortisolism. Further multi-institutional and population-based studies are required to validate our findings and examine the clinical effectiveness of the intervention targeting aldosterone for such patients.

Comparison of Echocardiographic Changes Between Surgery and Medication Treatment in Patients With Primary Aldosteronism.

BackgroundPrimary aldosteronism can cause cardiac dysfunction, including left ventricular hypertrophy, left ventricular diastolic dysfunction, and left atrial enlargement. A few studies have compared the cardioprotective effects between surgery and medication for primary aldosteronism, although most have not adjusted for baseline disease status. In this study, we investigated the difference in cardiovascular outcomes between surgery and medication treatment for primary aldosteronism after adjusting for baseline clinical characteristics, including aldosterone level and pretreatment echocardiographic information.Methods and ResultsWe retrospectively analyzed 220 patients diagnosed with primary aldosteronism who underwent adrenalectomy (n=144) or medication treatment (n=76) between 2009 and 2019. Echocardiographic changes were evaluated pretreatment and 1 year posttreatment. The surgery group had lower potassium, lower plasma renin activity, and higher plasma aldosterone concentration than the medication group, indicating a severe primary aldosteronism phenotype in the former. The decrease in left ventricular mass index after treatment was significantly greater in the surgery group than in the medication group (P=0.047). However, this relationship was not noted after multivariable regression analysis (standard β=−0.08, P=0.17). Additionally, decreased parameter values related to left ventricular diastolic dysfunction and left atrial enlargement were not different between the groups. Pretreatment echocardiographic values were most associated with changes in all echocardiographic parameters. The findings were consistent in the propensity score‐matched analysis.ConclusionsThis study's findings suggest that there is no difference in cardioprotective efficacy between surgical and medication treatment under similar disease severity; however, it should be considered that several study participants with severe hyperaldosteronism were managed surgically.

Autonomous cortisol secretion is associated with worse arterial stiffness and vascular fibrosis in primary aldosteronism: a cross-sectional study with follow-up data.

The presence of autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA) is common and potentially associated with poor outcomes. The aim of this study was to investigate the association between ACS and vascular remodeling in PA patients. We prospectively enrolled 436 PA patients from October 2006 to November 2019. ACS (defined as a cortisol level >1.8 μg/dL after a 1 mg dexamethasone suppression test) was detected in 23% of the PA patients. Propensity score matching (PSM) with age, sex, systolic and diastolic blood pressure was performed. The brachial-ankle pulse wave velocity (baPWV) was examined at baseline and 1 year after targeted treatment. Small arteries of periadrenal fat in 46 patients were stained with Picro Sirus red to quantify the severity of vascular fibrosis. After PSM, the PA patients with ACS had a significantly higher prevalence of diabetes mellitus, higher plasma aldosterone concentration and higher aldosterone-to-renin ratio. The baseline mean baPWV was also significantly higher in the PA patients with ACS. After multivariable regression analysis, the presence of ACS was a significant predictor of worse baseline mean baPWV (β: 235.745, 95% CI: 59.602-411.888, P = 0.010). In addition, the PA patients with ACS had worse vascular fibrosis (fibrosis area: 25.6 ± 8.4%) compared to those without ACS (fibrosis area: 19.8 ± 7.7%, P = 0.020). After 1 year of PA treatment, baPWV significantly improved in both groups. The presence of ACS in PA patients is associated with worse arterial stiffness and vascular remodeling.

Phenotype-genotype correlation in aldosterone-producing adenomas characterized by intracellular cholesterol metabolism

Aldosterone-producing adenoma (APA) is histologically composed of clear and compact tumor cells. KCNJ5- mutated APAs were reported to be associated with higher plasma aldosterone concentration and more abundant clear tumor cells containing lipid droplets than non-KCNJ5- mutated APAs. However, the association among cholesterol uptake and/or synthesis, cellular morphology and genotypes has remained unknown. Therefore, in order to explore these differences, 52 APA cases (KCNJ5 mt: n = 33, non-KCNJ5 mt: n = 19; ATP1A1: n = 3, ATP2B3: n = 3, CACNA1D: n = 5, CTNNB1: n = 1, tumors without any mutation above: n = 7), zona glomerulosa (ZG) tissue adjacent to APA and 10 non-pathological adrenal glands (NAs) were examined for quantitative histopathological analysis of tumor morphology and immunohistochemical analysis of cholesterol receptors (SR-B1, LDL-R), cholesterol metabolic enzymes (ACAT1, ACAT2, HSL, DHCR24, StAR), and the enzymes required for steroid synthesis (CYP11A1, CYP17A, 3βHSD, CYP11B1, CYP11B2). Gas chromatography-mass spectrometry (GC-MS) analysis was further performed to profile cholesterol precursors and metabolites in 21 APA cases (KCNJ5 mt: n = 16, non-KCNJ5 mt: n = 5) and 14 adrenal cortex of adjacent adrenal tissues. Results demonstrated that both SR-B1 and DHCR24 were significantly lower in the ZG than in fasciculata or reticularis of NAs but LDL-R was not significantly different among them in immunohistochemical analysis. SR-B1 and DHCR24 were both significantly higher in APAs than in ZG tissue adjacent to APA. In GC-MS analysis, most cholesterol precursors and metabolites, except for lanosterol, and their metabolic ratios (= concentration of cholesterol/ precursor) were higher in APAs than in the adjacent adrenal cortex tissue. LDL-R, ACAT1/2, HSL, DHCR24 were all significantly lower in clear than in compact tumor cells of APA. LDL-R was significantly lower and cholesterol/lanosterol ratio was significantly higher in KCNJ5- mutated than non-KCNJ5- mutated APAs. We demonstrated SR-B1 mediated selective uptake of cholesterol ester and de novo cholesterol synthesis were both enhanced in APAs. In addition, cholesterol uptake and metabolism were different between clear and compact tumor cells. KCNJ5- mutated APAs were predominantly composed of clear tumor cells containing abundant cholesteryl ester but less activated LDL-R mediated uptake and increased de novo synthesis. Those findings above indicated their more pronounced functional deviation from the normal ZG cells in terms of their steroidogenic and intracellular cholesterol metabolism.

Higher Plasma Aldosterone Concentrations Are Associated With Elevated Risk of Aortic Dissection and Aneurysm: a Case-Control Study

Animal models demonstrate circulating aldosterone leads to aortic dissection and aneurysm, whereas data from humans are lacking. Therefore, we aimed to examine the associations of plasma aldosterone concentrations (PAC) with aortic dissection and aneurysm. We identified patients with aortic dissection and aneurysm with assessed PAC before disease onset from hospital-based electronic database and set as case group. Simultaneously, age and gender-matched cohort with PAC measurement whereas without aortic dissection and aneurysm were selected as control group using ratio of 1:4. Multi-variable logistic regression analysis was used to assess the relationship of PAC with aortic dissection and aneurysm. Totally, 133 cases and 531 controls (all hypertensive) were enrolled between 2004 and 2021, with 77.9% men, mean age of 55.5 years and PAC of 13.9 ng/dL. Case group showed significantly higher PAC(14.51 versus 13.65 ng/dL, P=0.012) than did control group. In logistic regression analysis, higher PAC exhibited 1.68-fold higher odds (95% CI, 1.14-2.48, P=0.008) for presence of aortic dissection and aneurysm, significant in adjusted model (odds ratio, 1.69 [95% CI, 1.11-2.57], P=0.015). In stratified analysis, the association between the two was observed in women of all ages and in men with coronary artery disease. Sensitivity analysis by excluding those under interfering agents at PAC measurement and those with primary aldosteronism did not change the relationship of the two. Higher PAC is associated with the increased odd for aortic dissection and aneurysm in patients with hypertension, even in the absence of primary aldosteronism, implying that PAC might be a target for prevention.