Treatment Of Primary Aldosteronism Research Articles

Associations Between Changes in Plasma Renin Activity and Aldosterone Concentrations and Changes in Kidney Function After Treatment for Primary Aldosteronism

IntroductionGreater reduction in estimated glomerular filtration rate (eGFR) after specific treatment for primary aldosteronism (PA) reflects improvement in glomerular hyperfiltration associated with PA and leads to better patient outcomes. However, little is known regarding the mechanisms underlying eGFR reduction after treatment for PA.MethodsWe analyzed data from the nationwide PA registry in Japan. Patients were assigned to adrenalectomy (n = 438) and mineralocorticoid receptor (MR) antagonist (n = 746) groups. We assessed associations between changes in blood pressure (BP), plasma renin activity (PRA) and plasma aldosterone concentrations (PAC), and eGFR before and 6 months after treatment for both groups.ResultsIn a multivariable linear regression, the adjusted β values (95% confidence interval [CI]) for change in eGFR after treatment were −2.76 (−4.29, −1.22) ml/min per 1.73 m2 for PRA (per 3.2 ng/ml per hour), and 1.97 (1.08, 2.85) ml/min per 1.73 m2 for PAC (per 236.1 pg/ml) in the adrenalectomy group; and −0.45 (−0.89, −0.01) ml/min per 1.73 m2 for PRA and −0.72 (−1.62, 0.18) ml/min per 1.73 m2 for PAC in the MR antagonist group. Change in mean arterial pressure after treatment was not significantly associated with change in eGFR in either group. Changes in PRA and PAC but not BP before and 6 months after treatment for PA were associated with greater reductions in eGFR.ConclusionPost-treatment improvements in glomerular hyperfiltration may be attributable to decreased MR activity in the kidneys, but not to reductions in systemic BP.

P0210ASSOCIATIONS BETWEEN CHANGES IN RENIN ACTIVITY AND ALDOSTERONE LEVELS AND CHANGES IN KIDNEY FUNCTION AFTER TREATMENT FOR PRIMARY ALDOSTERONISM: A LARGE MULTICENTER COHORT STUDY IN JAPAN

Abstract Background and Aims Greater reduction in estimated glomerular filtration rate (eGFR) after treatment for primary aldosteronism (PA) reflects improvement of glomerular hyperfiltration associated with PA and leads to better patient outcomes. However, little is known regarding the mechanisms underlying eGFR reduction after treatment for PA. Method We analyzed data from the nationwide PA registry in Japan. Patients were assigned to adrenalectomy (n=419) and mineralocorticoid receptor (MR) antagonist (n=674) groups. We assessed associations between changes in BP, plasma renin activity and aldosterone levels, and eGFR after treatment for both groups. Results Reduction in eGFR after treatment was greater in the surgical compared to MR antagonist treatment group (median -11.0; 95% CI, -12.2 to -9.8 ml/min/1.73 m2 vs. -3.5; 95% CI, -4.3 to -2.7 ml/min/1.73 m2; p <0.001). In a multivariable linear regression, the adjusted betas (95% confidence interval) for change in eGFR after treatment for each standard deviation higher level of plasma renin activity and aldosterone were -2.12 (-4.10, -0.14) and 2.41 (1.20, 3.62) ml/min/1.73 m2, respectively, in the adrenalectomy group, and -0.65 (-1.28, -0.02) and –0.64 (-2.04, 0.76) ml/min/1.73 m2, respectively, in the MR antagonist group. Plasma renin activity Change in mean arterial pressure after treatment was not associated with change in eGFR in either group. Conclusion Changes in plasma renin activity and aldosterone levels but not BP, after treatment for PA were associated with greater reductions in eGFR. Post-treatment improvements in glomerular hyperfiltration may be attributable to suppressed MR activity within the kidneys, not to reductions in systemic blood pressure. It is important for clinicains not only to treat PA, but also to confirm adequate suppressed MR activity after treatment for correction of glomerular hyperfiltration.

SUN-LB92 The Importance of Early Diagnosis and Treatment of Primary Aldosteronism on the Progression of Chronic Kidney Disease, Compared With Essential Hypertension: A Retrospective Cohort Study

<META NAME=“author” CONTENT=“Windows 사용자”>Introduction: Primary aldosteronism(PA) has few clinical phenotypes and features, compared with other endocrine hypertension(HTN). Even though hypokalemia is a typical sign of PA, most of PA reveals normal potassium concentration. For that reason, PA is likely to undetected and underestimated and it may account for larger proportion of total HTN than we expected. However, it has known that PA has higher risk of renal complications than essential hypertension(EH) and has been controversy which treatment between medication and operation is better for renal protection of PA. Methods: We retrospectively reviewed the medial records of patients with PA and EH of a single medical center from January, 2009 to December, 2019. PA patients were divided into medical and surgical treatment groups. EH patients were distinguished from one that satisfied with case detection test, called non-confirmed PA. We excluded cases with other secondary HTN and baseline eGFR < 60 mL/min/1.73m2. Results: Patients with PA(N=66) and patients with EH(N=514) were selected for analysis. Each baseline mean eGFR of patients with PA and EH indicated 91.2 ± 74.5 and 87.1 ± 19.7 mL/min/1.73m2 and statistically insignificant differences(P = 0.1688) as well as baseline SBP(P = 0.5403) and DBP(P = 0.8691). However, in spite of treatment of PA and controlled BP, mean eGFR of PA patients was lower than one of EH patients and its difference was statistically significant showing 66.5 ± 14.2 and 94.6 ± 195.9 mL/min/1.73m2 (P < .0001) at 2~ 5 years, 52.4 ± 17.9 and 77.6 ± 20.6 mL/min/1.73m2 (P < 0.0004) at 6~10 years. Baseline mean eGFR of PA with normokalemia and hypokalemia respectively were 77.7 ± 11.6 and 98.9 ± 92.5 mL/min/1.73m2 (P = 0.0269). Baseline mean eGFR of non-confirmed PA and EH were 82.5 ± 13.2 and 88.4 ± 21.1 mL/min/1.73m2 (P = 0.0240). Although baseline mean eGFR of PA with surgical treatment was better than one with medical treatment, it was reversal after 2~5 years indicating mean eGFR of PA patients treated with operation, 62.9 ± 16.1 mL/min/1.73m2 and one treated with spironolactone, 70.5 ± 12.6 mL/min/1.73m2 (P = 0.0010). Conclusions: This study support PA has worse effects on renal function than EH. PA is frequently unsuspected and undiagnosed because it hardly shows symptoms and signs. Many cases do not reveal main characteristics such as uncontrolled HTN and hypokalemia, so that patients with PA maybe have longstanding exposure to risk of CKD. Therefore it is necessary to do case detection test and rule out PA in initial hypertensive patients. In addition, more longitudinal study and research should be performed to decide personalized and adequate treatments for PA patients.

OR34-04 Efficiency of Adrenal Venous Sampling in the Treatment Choice of Primary Aldosteronism (AVSTAT Study)

BACKGROUND: Adrenal venous sampling (AVS) is strongly recommended for a subtype diagnosis of primary aldosteronism (PA) if adrenalectomy (ADX) is desired by the patient. Given various issues related to AVS such as technical demand, invasive nature, expensive cost and radiation exposure, AVS is expected to lead efficiently to the subtype diagnosis and ADX. Aim: Primary objective was to assess the performance of AVS to determine treatment of PA by investigating the ratio of unilateral disease and rate of ADX following AVS in patients with unilateral disease. Methods: Sixteen major referral centers in ENS@T (n=10) and Japan (n=6) participated in the study. Study period was from 2006 to 2018. Data on total number of PA patients, AVS (total number and number of successful procedures), number of patients with unilateral diseases, and number of patients that underwent ADX were collected by a questionnaire-based survey. In addition, reasons for not proceeding to ADX in patients with a unilateral diagnosis were investigated. The diagnosis of PA was based on the positive case detection and at least one positive result in confirmatory testing. Results: Total number of confirmed PA patients and conducted AVS showed a dramatic increase during the past decade (PA: 1061 pts/ 2006–2011 to 3718 pts/ 2012–2018; AVS: 720/ 2006–2011 to 2448/ 2012–2018). Success rate of AVS was improved from 79.0% (2006–2011) to 92.5% (2012–2018). Both rate of unilateral PA and ADX of successful procedures decreased from 42.7% (2006–2011) to 37.3% (2012–2018) and from 40.8% (2006–2011) to 34.9% (2012–2018), respectively. Of the patients with successful AVS, bilateral disease was diagnosed in 63.5% (1812/2854 pts). Of the unilateral PA patients, 11.9% (125/ 1054 pts) were not subjected to ADX. The rate of the patients not subjected to ADX was significantly higher in Japan than in ENS@T centers both in patients with successful AVS (75.8% vs. 53.4%) and with unilateral disease (19.9% vs. 8.6%). Clinical decision against ADX in unilateral disease was made by the physicians in 33.3%, the patients in 33.3%, and both in 33.3%. Medical factors for Dr.’s decision against ADX in unilateral disease included good blood pressure control, normokalemia, comorbidities (e.g. DM, CKD), non-lateralized CT findings (e.g. no tumor, contralateral tumor), and discordant results among different criteria of AVS.Conclusions: High prevalence of bilateral disease and change of treatment policy after implementation affected the efficiency of AVS as an essential diagnostic procedure prior to ADX. Development of non-invasive procedures to exclude bilateral PA and more strict indication of AVS are warranted.

SAT-564 Effectiveness of Treatment with Mineralocorticoid Receptor Antagonistsin Primary Aldosteronism

Background: Medical treatment with mineralocorticoid receptor antagonists (MRAs) is preferred for patients with primary aldosteronism (PA) who are not surgical candidates. Adequate mineralocorticoid receptor blockade, as suggested by renin elevation above suppression levels, has been associated with lower rates of cardiovascular and renal complications as compared with PA with sustained renin suppression. Objectives: To assess the timeline and rates of achieving target renin levels in patients with PA and low renin hypertension treated with MRAs. Patients and Methods: We conducted a retrospective cohort study of adult patients with hypertension who were treated with MRAs in an academic center between 2003-2019. Of these, we included patients who had suppressed renin at baseline, and repeated renin measurement(s) during MRAs therapy. Renin suppression was defined as plasma renin activity (PRA) 1.0 ng/mL/h or direct renin concentration (DRC) 8.0 pg/mL. We excluded patients with adrenal cancer, end-stage renal disease, exogenous glucocorticoids, and critically ill. Mann-Whitney test, Wilcoxon signed rank test, Chi-Square test and multiple logistic regression analysis were employed, as appropriate. Results: So far, 89 patients (45 men), median age 56 (range, 19-84), have been included. Of these, 46% had confirmed PA; 25% had positive PA screening, but no confirmatory tests; and 29% had other forms of low-renin hypertension. On average, patients were on 2.9 1.6 antihypertensive agents; 62% of patients were prescribed beta blockers, and 38% were on K+ supplements. Overall, renin (PRA in 69 cases, and DRC in 20 cases) increased after MRA treatment (from 0.40 [0.10, 0.60] ng/mL/h to 1.10 [0.60, 2.23] ng/mL/h; and from 2.1 [2.1, 3.7] pg/mL to 5.7 [2.9, 16.7] pg/mL, respectively, p<0.0001 for both). The cumulative proportions of patients in whom renin reached target levels during MRA treatment were: 25% at 2 weeks; 38.9% at 1 month; 34.2% at 3 months; 39.5% at 6 months; and 47.2% at 1 year. Age, sex, race, blood pressure, use of beta blockers, renal function, serum K+ and aldosterone concentrations were similar between patients with target vs. suppressed renin. Multiple logistic regression analysis suggested that after adjusting for age and sex, higher MRA dose and higher BMI were associated with higher likelihood of achieving target renin during MRA therapy (odds ratio (95%CI): 1.021 (1.001-1.041) and 1.097 (1.008-1.193), respectively, p<0.05 for both); conversely, beta blockers use tended to be less often associated with target renin (odds ratio, 0.37 (0.13-1.008), p=0.052). Conclusion: Although raising renin above suppression levels is important for reducing the cardiovascular risk associated with PA, this goal is achieved in less than half of patients, even after one year of treatment with MRAs, in an academic setting. Strategies for optimizing PA treatment are critically needed.

Preoperative non-stimulated adrenal venous sampling index for predicting outcomes of adrenalectomy for unilateral primary aldosteronism

The aim of this study was to predict outcomes of adrenalectomy for unilateral primary aldosteronism (PA) using non-stimulated adrenal venous sampling (AVS) indices and the standardized Primary Aldosteronism Surgical Outcome (PASO) criteria. Patients with unilateral PA who underwent adrenalectomy based on non-stimulated AVS and had follow-up data regarding surgical outcomes between 2011 and 2016 were enrolled. Demographic data and non-stimulated AVS indices, including lateralization index (LI) and contralateral suppression, were collected for analysis. This study included 54 patients who underwent adrenalectomy. Clinical and biochemical outcomes were evaluated in all patients and in 52 (96.3%) patients, respectively. Complete clinical and biochemical success was achieved in 31 (57.4%) of 54 patients and 42 (80.8%) of 52 patients, respectively. An LI>4 was significantly associated with complete clinical and biochemical success (OR=4.30, 95% CI 1.18-15.68, p=0.03, and OR=7.55, 95% CI 1.28-44.47, p=0.03, respectively). Contralateral suppression was an independent predictor of complete biochemical success (OR=17.27, 95% CI 1.95-153.21, p=0.01). Non-stimulated AVS indices including LI and contralateral suppression are reliable preoperative determinants for predicting the outcomes of adrenalectomy in patients with unilateral PA. Our findings provide more evidence and confidence to clinicians when applying non-stimulated AVS to determine PA treatment.

Diagnosis and Treatment of Primary Aldosteronism in West China Hospital of Sichuan University from 2009 to 2018

To summary the clinical diagnosis and treatment of primary aldosteronism (PA) in West China Hospital (WCH) of Sichuan University during 2009-2018. This study enrolled the patients diagnosed as PA and admitted in WCH of Sichuan University from January 2009 to December 2018. The information of the patients including epidemiological and clinical data, diagnosis and treatment as well as therapeutic outcomes were collected and analyzed. A total of 853 patients with 1 248 diagnostic cases were included in the analysis, and the diagnosis cases of PA increased year by year from 2009 to 2018. Most patients (74.33%) were confirmed the diagnosis in the Department of Endocrinology and Metabolism and then admitted to the hospital. PA was more frequent in female than in male, with a ratio of female to male about 1.34∶1. Hypertension was the most common chief complaint, in contrast, the proportion of fatigue and/or numbness as the symptoms of hypokalemia was declining. More and more patients were diagnosed because of imaging examination founding adrenal incidentoma. After 2016, more and more patients were diagnosed by recumbent saline suppression test and captopril challenge test, and the number of adrenal venous sampling to classify PA subtypes was increasing to help choosing different treatment options. The proportion of surgical treatment decreased year by year, and more and more patients adopted medical treatment or transferred to surgery with combined treatment instead of simple operation. During the past 10 years, remarkable progress was made in the diagnosis and treatment of PA. Hypertension was the most important clinical manifestation of PA, so the screening of PA in hypertensive patients should be strengthened. Adrenal incidentaloma has become prevalent manifestation of PA with an increasing trend, which needs more attention in clinical practice.

Diabetes Mellitus Itself Increases Cardio-Cerebrovascular Risk and Renal Complications in Primary Aldosteronism.

The prevalence of diabetes mellitus (DM) in patients with primary aldosteronism (PA) is higher than in those with essential hypertension and the general population. Although DM is a common major risk factor for cardio-cerebrovascular (CCV) diseases and renal complications, details of its effects in PA have not been demonstrated. The aim of this study was to determine the effects of coexistent DM on the risk of CCV events and progression of renal complications in PA patients. A multi-institutional, cross-sectional study was conducted. PA patients experienced between January 2006 and October 2016 and with available data of CCV events and DM were enrolled from the Japan PA registry of the Japan Primary Aldosteronism Study/Japan Rare Intractable Adrenal Diseases Study (n = 2524). CCV events and renal complications were compared between a DM group and a non-DM group by logistic and liner-regression analysis. DM significantly increased the odds ratio (OR) of CCV events (OR 1.59, 95% CI: 1.05-2.41) and that of proteinuria (OR 2.25, 95% CI: 1.59-3.16). DM correlated significantly with declines in estimated glomerular filtration rate (β = .05, P = .02). This the first report to demonstrate the presence of DM as an independent risk factor for CCV events and renal complications, even in PA patients. Management of DM should be considered in addition to the specific treatment of PA.

Salt Appetite and its Effects on Cardiovascular Risk in Primary Aldosteronism.

First described in 1955 by Jerome W. Conn, primary aldosteronism (PA) today is well established as a relevant cause of secondary hypertension and accounts for about 5-10 % of hypertensives. The importance of considering PA is based on its deleterious target organ damage far beyond the effect of elevated blood pressure and on PA being a potentially curable form of hypertension. Aside the established contributory role of high dietary salt intake to arterial hypertension and cardiovascular disease, high salt intake is mandatory for aldosterone-mediated deleterious effects on target-organ damage in patients with primary aldosteronism. Consequently, counselling patients on the need to reduce salt intake represents a major component in the treatment of PA to minimize cardiovascular damage. Unfortunately, in PA patients salt intake is high and far beyond the target values of 5 g per day, recommended by the World Health Organization. Insufficient patient motivation for lifestyle interventions can be further complicated by enhancing effects of aldosterone on salt appetite, via central and gustatory pathways. In this context, treatment for PA by adrenalectomy results in a spontaneous decrease in dietary salt intake and might therefore provide further reduction of cardiovascular risk in PA than specific medical treatment alone. Furthermore, there is evidence from clinical studies that even after sufficient treatment of PA dietary salt intake remains a relevant prognostic factor for cardiovascular risk. This review will focus on the synergistic benefits derived from both blockade of aldosterone-mediated effects and reduction in dietary salt intake on cardiovascular risk.

Primary Aldosteronism Decreases Insulin Secretion and Increases Insulin Clearance in Humans.

Primary aldosteronism is a frequent cause of resistant hypertension and is associated with an increased risk of developing diabetes mellitus. Aldosterone impairs insulin secretion in isolated islets, and insulin secretion is increased in aldosterone synthase-deficient mice. We hypothesized that treatment for primary aldosteronism increases insulin secretion and insulin sensitivity in humans. We conducted a prospective cohort study in patients with primary aldosteronism, with assessment of glucose metabolism before and 3 to 12 months after treatment. Participants underwent treatment for primary aldosteronism with adrenalectomy or a mineralocorticoid receptor antagonist at the discretion of their treating physician. We assessed insulin secretion and insulin sensitivity by hyperglycemic and hyperinsulinemic-euglycemic clamps, respectively, on 2 study days after a 5-day standardized diet. After treatment, the C-peptide and insulin response during the hyperglycemic clamp increased compared with pretreatment (ΔC-peptide at 90-120 minutes +530.5±384.1 pmol/L, P=0.004; Δinsulin 90-120 minutes +183.0±122.6, P=0.004). During hyperinsulinemic-euglycemic clamps, insulin sensitivity decreased after treatment (insulin sensitivity index 30.7±6.2 versus 18.5±4.7 nmol·kg-1·min-1·pmol-1·L; P=0.02). Insulin clearance decreased after treatment (872.8±207.6 versus 632.3±178.6 mL/min; P=0.03), and disposition index was unchanged. We conclude that the insulin response to glucose increases and insulin clearance decreases after treatment for primary aldosteronism, and these effects were not due to alterations in creatinine clearance or plasma cortisol. These studies may provide further insight into the mechanism of increased diabetes mellitus risk in primary aldosteronism.

Patients With Primary Aldosteronism Respond to Unilateral Adrenalectomy With Long-Term Reduction in Salt Intake.

ContextHigh dietary salt intake is known to aggravate arterial hypertension. This effect could be of particular relevance in the setting of primary aldosteronism (PA), which is associated with cardiovascular damage independent of blood pressure levels. The aim of this study was to determine the impact of therapy on salt intake in PA patients.Patients and MethodsA total of 148 consecutive PA patients (66 with unilateral and 82 with bilateral PA) from the database of the German Conn’s Registry were included. Salt intake was quantified by 24-hour urinary sodium excretion before and after initiation of PA treatment.Study designObservational longitudinal cohort study.SettingTertiary care hospital.ResultsAt baseline, unilateral PA patients had a significantly higher urinary sodium excretion than patients with bilateral disease (205 vs 178 mmol/d, P = 0.047). Higher urinary sodium excretion correlated with an increased cardiovascular risk profile including proteinuria, impaired lipid, and glucose metabolism and was associated with higher daily doses of antihypertensive drugs to achieve blood pressure control. In unilateral disease, urinary sodium excretion dropped spontaneously to 176 mmol/d (P = 0.012) 1 year after unilateral adrenalectomy and remained low at 3 years of follow-up (174 mmol/d). In contrast, treatment with mineralocorticoid receptor antagonists (MRA) in bilateral PA patients was not associated with a significant change in urinary sodium excretion at follow-up (179 mmol/d vs 183 mmol/d).ConclusionPA patients consuming a high-salt diet, estimated based on urinary sodium excretion, respond to adrenalectomy with a significant reduction of salt intake, in contrast to MRA treatment.

Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) as an alternative to left sided adrenalectomy in the treatment of primary aldosteronism

Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) as an alternative to left sided adrenalectomy in the treatment of primary aldosteronism

Treatment of Primary Aldosteronism with mTORC1 Inhibitors

CONTEXT Mammalian target of rapamycin complex 1 (mTORC1) activity is often increased in the adrenal cortex of patients with primary aldosteronism (PA), and mTORC1 inhibition decreases aldosterone production in adrenocortical cells, suggesting the mTORC1 pathway as a target for treatment of PA. OBJECTIVE To investigate the effect of mTORC1 inhibition on adrenal steroid hormones and hemodynamic parameters in mice and in patients with PA. DESIGN (i) Plasma aldosterone, corticosterone, and angiotensin II (Ang II) were measured in mice treated for 24 hours with vehicle or rapamycin. (ii) Plasma aldosterone levels after a saline infusion test, plasma renin, and 24-hour urine steroid hormone metabolome and hemodynamic parameters were measured during an open-label study in 12 patients with PA, before and after 2 weeks of treatment with everolimus and after a 2-week washout. MAIN OUTCOME MEASURES (i) Change in plasma aldosterone levels. (ii) Change in other steroid hormones, renin, Ang II, and hemodynamic parameters. RESULTS Treatment of mice with rapamycin significantly decreased plasma aldosterone levels (P = 0.007). Overall, treatment of PA patients with everolimus significantly decreased blood pressure (P < 0.05) and increased renin levels (P = 0.001) but did not decrease aldosterone levels significantly. However, prominent reduction of aldosterone levels upon everolimus treatment was observed in four patients. CONCLUSION In mice, mTORC1 inhibition was associated with reduced plasma aldosterone levels. In patients with PA, mTORC1 inhibition was associated with improved blood pressure and renin suppression. In addition, mTORC1 inhibition appeared to reduce plasma aldosterone in a subset of patients.

Steroid Profiling and Immunohistochemistry for Subtyping and Outcome Prediction in Primary Aldosteronism-a Review.

Steroid profiling and immunohistochemistry are both promising new tools used to improve diagnostic accuracy in the work-up of primary aldosteronism (PA) and to predict treatment outcomes. Herein, we review the recent literature and present an outlook to the future of diagnostics and therapeutic decision-making in patients with PA. PA is the most common endocrine cause of arterial hypertension and unilateral forms of the disease are potentially curable by surgical resection of the overactive adrenal. Recent studies have shown that adrenal steroid profiling by liquid chromatography-tandem mass spectrometry (LC-MS/MS) can be helpful for subtyping unilateral and bilateral forms of PA, classifying patients with a unilateral aldosterone-producing adenoma (APA) according to the presence of driver mutations of aldosterone production in APAs, and potentially predicting the outcomes of surgical treatment for unilateral PA. Following adrenalectomy, immunohistochemistry of aldosterone synthase (CYP11B2) in resected adrenals is a new tool to analyze "functional" histopathology and may be an indicator of biochemical outcomes after surgery. Biochemical and clinical outcomes of therapy in PA vary widely among patients. Peripheral venous steroid profiling at baseline could improve diagnostic accuracy and help in surgical decision-making in cases of a suspected APA; results of "functional" histopathology could help determine which patients are likely to need close post-surgical follow-up for persistent aldosteronism.

Abstract P2024: Treatment of Primary Hyperaldosteronism Increases Plasma Epoxyeicosatrienoic Acids

Epoxyeicosatrienoic acids (EETs) are lipid signaling molecules formed from arachidonic acid by the action of CYP450s. EETs cause vasodilation, exert anti-inflammatory effects, and enhance insulin secretion and sensitivity. 14,15-DHET has been reported to be increased in patients with hyperaldosteronism, but the effects of aldosteronism on EETs and sEH activity are unknown. We tested the hypothesis that treatment of hyperaldosteronism would alter EET concentrations. We studied 9 patients with biochemically confirmed hyperaldosteronism before and after unilateral adrenalectomy (6) or treatment with a mineralocorticoid (MR) antagonist. Aldosterone decreased significantly from 20.4±15.2 to 6.2±3.7 ng/mL following treatment, but cortisol did not change. Circulating total EET concentrations increased from 11.9±5.9 to 18.5±12.6 nM with treatment of primary hyperaldosteronism. Among the regioisomers of EETs, 14,15-EET significantly increased after treatment, whereas 11,12-EET and 8,9 EET did not change significantly ( Figure ; • adrenalectomy, ○ MR antagonist). EET concentrations increased in patients treated with an MR antagonist as well as those treated by surgical resection. Total DHET concentrations and specific regioisomers of DHET did not change significantly with treatment. Circulating total EETs (r=-0.52, p =0.026), 14,15-EET (-0.56, p =0.015) and 11,12-EET (r=-0.48, p =0.042) correlated inversely with aldosterone. We report for the first time that circulating EET concentrations increase following treatment of primary hyperaldosteronism.

SYSTEMATIC HORMONAL SCREENING OF INCIDENTALLY DISCOVERED ADRENAL TUMORS YIELDS A HIGH DETECTION OF HYPERALDOSTERONISM

Objective: The detection of adrenal incidentalomas is increasing. Current European guidelines suggest that all adrenal incidentalomas (AI) should be screened for excess cortisol and cathecolamines, but excess aldosterone only in the presence of hypertension and/or hypokalemia. Consistently, the reported prevalence of primary aldosteronism (PA), in AI is only 2–6%. The spectrum of primary aldosteronism has expanded to patients with mild hypertension and normokalemia, or even normotensives. Interestingly, even so-called “non-functioning” AI have been associated with future risk of hypertension. Screening by hypertensive status and diagnosis based on strict PA criteria suggest that current biochemical study is incomplete and/or insensitive to detect mild cases. To evaluate whether a systematic protocolized study can improve the detection of PA in adrenal incidentalomas.Design and method: We recruited a cohort of 226 adults with an adrenal incidentaloma, evaluated in our endocrinology clinic. We measured in all patients (hypertensives and normotensives) plasma aldosterone and renin with a protocolized approach: measurement in seated position, with unrestricted sodium intake, during follicular phase in premenopausal women and performing washout of confounding medications in selected cases. We defined a positive PA screening with suppressed renin in the setting of plasma aldosterone >6 ng/dL and aldosterone-renin ratio >20. We defined confirmed PA with either a positive confirmatory test or achievement of clinical and biochemical success criteria for PA treatment with adrenal surgery or aldosterone antagonists, as published by PASO study group. Results: Considering all subjects with AI, 17.25% (39/226) had a positive screening for PA and confirmed in 11% (25/226). These subjects had female predominance 68%, mean age 54 years, mean adenoma size 20 mm and did not differ from subjects with AI. Also, among confirmed cases 25% (5/25) were normotensive and 8% (2/25) had hypokalemia. Conclusions: Our study suggests that an important proportion of patients with PA are not currently being detected by usual clinical care of adrenal incidentalomas. Our protocolized study, including normotensive subjects and sensitive thresholds, improves diagnosis of milder cases. Since PA is associated with significant cardiovascular morbidity, earlier detection of the complete spectrum of this disease is clinically relevant.

2445-PUB: Impact of Primary Aldosteronism on Renal Function in Type 2 Diabetes Patients

Primary aldosteronism (PA) is associated with higher renal damage than essential hypertension (HT). In particular, the prevalence of chronic kidney disease increases after treatment for PA, as actual renal damage may be underestimated in untreated PA due to glomerular hyperfiltration. Previous studies have indicated the role of the renin-angiotensin-aldosterone system in renal dysfunction in type 2 diabetes (T2DM) patients, but whether PA causes additional renal function damage in T2DM is unclear. The aim of this study was to investigate this issue. A retrospective review of all T2DM outpatients who visited our high-volume center for PA in the FY 2017 was carried out. We segregated patients that underwent PA treatment (PA group) and those without PA (non-PA group). Treatment for PA was defined as adrenalectomy or the use of aldosterone receptor antagonists (MRAs). Untreated PA was excluded, since renal damage might be underestimated in these patients. We compared the renal function between these two groups. There were 83 patients in the PA group and 1580 patients in the non-PA group. In the PA group, 21 patients underwent adrenalectomy, 60 patients underwent MRA treatment, and 2 patients underwent both. Compared to the non-PA group, patients in the PA group were younger (62 [55-69] vs. 66 [55-75] years, p=0.014), and had a higher BMI (25.9 [23.8-27.8] vs. 24.8 [21.7-28.1] kg/m2, p=0.019) and lower HbA1c (6.8 [6.5-7.1] vs. 7.3 [6.7-8.0]%, p&amp;lt;0.001). In the renal function evaluation, the PA group had significantly lower eGFR (66.3 [52.4-78.2] vs. 70.5 [56.0-85.6] ml/min/1.73 m2, p=0.047) than the non-PA group. Multiple regression analysis revealed that PA was a factor for decreased eGFR, independent from age, sex, BMI, HbA1c, and HT (p=0.007). PA induced a 3.3 (95% CI: 0.90-5.7)-ml/min/1.73 m2 decrease in eGFR, equivalent to 3.8 years of aging. Our results show that PA was a risk factor for renal dysfunction independent from HT in T2DM patients. To prevent the progression of renal failure, PA should not be overlooked. Disclosure S. Katsuragawa: None. Y. Tsurutani: Research Support; Self; Astellas Pharma Inc. T. Takiguchi: None. J. Saito: None. T. Nishikawa: None.

Roentgenoendovascular destruction of adrenal glands in the management of primary aldosteronism

Background. In the XXI century, interventional radiology is developing rapidly in the surgical treatment for endocrine pathology of adrenal glands. Until the introduction of aldosterone to renin ratio calculation as a screening test by K. Hiramatsu in 1981, primary aldosteronism was thought to be a rare pathology. Further study of the disease obtained new data on its prevalence – from 5 to 10 % among patients with hypertension and more than 20 % of patients with refractory hypertension. In Ukraine, the prevalence of primary aldosteronism among patients with refractory arterial hypertension is 1.2 %. The aim of the study was to evaluate the effectiveness of roentgenoendovascular destruction of adrenal glands (REDAG) in patients with primary aldosteronism (PA). Materials and methods. During the period from 2014 to July2018, a total of 132 patients with adrenal pathology were examined and treated at the Clinic of Hospital Surgery of ZSMU. Operative treatment for primary aldosteronism was performed in 38 patients, including 15 patients who underwent REDAG. There were 10 (66.7 %) women and 5 (33.3 %) men. The average age was 49.4 ± 14.9 years. According to CT (MRT), anatomy of adrenal neoplasms had the following localization: left-sided – in 11 (73.3 %) patients, right-sided – in 1 (6.7 %), bilateral – in 3 (20 %). The mean volume of adrenal neoplasms was 9.0 (6.3–10.0) mm. Diagnostics was performed according to the clinical practical recommendations for the diagnosis and treatment of PA (Clinical Practical Guideline – The Management of Primary Aldosteronism, 2016). Roentgenoendovascular surgery in patients with PA included destruction of the right adrenal gland in 3 (20 %) cases, of the left – in 12 (80 %). The results of the operative treatment were evaluated according to the standard criteria and clinical biochemical criteria of PASO (Primary Aldosteronism Surgical Outcomes) including the echocardiographic data. Results. The duration of the REDAG was 36.6 ± 6 minutes. Conversions, postoperative complications, lethal outcomes were avoided. The length of hospital stay was 9 (7–12) days. Comparative analysis of surgical treatment results showed a statistically significant decrease in systolic and diastolic blood pressure, aldosterone levels (P < 0.05). The control CT performed after treatment identified adrenal adenomas in the contralateral glands in 2 (13.3 %) patients. However, the follow-up clinical and laboratory diagnostics did not reveal its hormonal activity. According to PASO criteria, the complete biochemical effect was achieved in 73.3 %, complete clinical - in 66.7 %, partial biochemical effect – in 20 %, partial clinical effect – in 26.6 % of patients, failure of biochemical and clinical effects – in 6.7 %. Conclusions. Interventional methods of surgical treatment for adrenal pathology represent a complete alternative to endoscopic methods of surgical treatment in case i f it is clinically indicated. REDAG for primary aldosteronism demonstrates the statistically significant efficacy of symptomatic arterial hypertension treatment: complete biochemical effect in 73.3 %, complete clinical – 66.7%, partial biochemical effect – 20 %, partial clinical effect – 26.6 % of patients.

Standardized diagnosis and treatment of primary aldosteronism from a surgeon's perspective

Primary aldosteronism (PA) is a subtype of adrenal diseases in urological department, which is the most common cause of secondary hypertension. In recent years, great improvements and achievements have been made in the field of diagnosis and treatment of adrenal hypertension in China, however, there are some insufficiencies in the process of screening, diagnosis, function diagnosis and treatment. Because of the disease complexity and different levels of health care among China, it’s necessary for urological doctors to learn about the standarization of diagnosis and treatment of PA. This review gives emphasize on the common problems during the process of diagnosis and treatment of PA. We highlight the principle in standarization of diagnosis and treatment of PA by discussing epidemiology, screening, multidisciplinary team building, adrenal venous sampling and treatment strategy, hoping to improve clinical practice of adrenal hypertension in China. Key words: Primary aldosteronism; Adrenal gland; Hypertension

MON-LB062 A Preemptive Strike at Suspected Primary Aldosteronism in a Medically Underserved Patient

INTRODUCTION: Empiric treatment for primary aldosteronism (PA) and deferring confirmatory biochemical testing may be considered in a medically-underserved patient with high clinical suspicion for PA. CASE: A 29-year-old uninsured male with untreated hypertension, inadequate access to outpatient care, and frequent emergency department (ED) visits presented to the ED with a two-day history of headaches, blurry vision, chest pain, and shortness of breath. He denied muscle cramps, prescription medication use, illicit drug use, or family history of hypertension. His physical exam showed a blood pressure (BP) of 280/140 mmHg, otherwise normal vital signs, and normal cardiopulmonary and neurologic exams. Initial lab studies revealed a low serum potassium (2.2 mEq/L) and elevated serum creatinine (1.4 mg/dL). ECG and serial troponin measurements ruled out acute MI. He was diagnosed with hypertensive emergency with acute kidney injury (AKI) and treated in an ICU setting with potassium repletion and continuous esmolol and nicardipine infusions. With suspicion for PA, morning serum samples for aldosterone and plasma renin activity measurement were collected. The patient was transitioned onto maximum doses of three antihypertensive agents and required continued potassium repletion. Though his AKI resolved his BP remained elevated and, on hospital day #4, he voiced a desire to be discharged at a time his lab evaluation for PA was still pending. With high concern for PA, he was prescribed spironolactone with subsequent improvement in BP and serum potassium. He was discharged with follow up in a local clinic for the uninsured, and his lab evaluation later returned confirming high suspicion for PA. Confirmatory biochemical testing for PA was deferred, CT imaging showed a 2.3 cm right adrenal adenoma, and arrangements were made for right adrenalectomy. CONCLUSIONS: PA is an often underrecognized cause of secondary hypertension that carries significant morbidity. Treatment-resistant hypertension and spontaneous hypokalemia are cardinal features in PA that should prompt a diagnostic evaluation for it. This can be costly, time-consuming, and challenging, however. Medications, hypokalemia, and AKI can result in falsely elevated or suppressed results of biochemical tests used for PA case detection. Further, consensus guidelines indicate confirmatory testing—often to include adrenal venous sampling—should be pursued for many patients for whom PA is suspected based on biochemical case detection results. A patient-centered approach to the evaluation and treatment of PA is essential for medically-underserved patients for whom high clinical suspicion for this diagnosis exists. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.