Primary aldosteronism (PA), the most common form of secondary hypertension, can be either surgically cured or treated with targeted pharmacotherapy. PA is frequently undiagnosed and untreated, leading to aldosterone-specific cardiovascular morbidity and nephrotoxicity. Thus, clinicians should perform case detection testing for PA at least once in all patients with hypertension. Confirmatory testing is indicated in most patients with positive case detection testing results. The next step is to determine whether patients with confirmed PA have a disease that can be cured with surgery or whether it should be treated medically; this step is guided by computed tomography scan of the adrenal glands and adrenal venous sampling. With appropriate surgical expertise, laparoscopic unilateral adrenalectomy is safe, efficient and curative in patients with unilateral adrenal disease. In patients who have bilateral aldosterone hypersecretion, the optimal management is a low-sodium diet and lifelong treatment with a mineralocorticoid receptor antagonist administered at a dosage to maintain a high-normal serum potassium concentration without the aid of oral potassium supplements.

Captopril, an orally active angiotensin-converting enzyme (ACE) inhibitor, was effective in the long-term reduction of blood-pressure in 17 patients with essential hypertension. The addition of hydrochlorothiazide produced a further hypotensive effect, and the combined treatment produced satisfactory control of the blood-pressure for eight months. Captopril prevented and reversed the secondary hyperaldosteronism and hypokalaemia induced by simultaneous diuretic administration, thus eliminating the need for potassium supplements. The fall in plasma-angiotensin-II and urinary aldosterone and rise in angiotensin I and plasma-renin provide biochemical evidence that captopril inhibits ACE in vivo. No change in circulating venous bradykinin levels could be detected. The hypotensive action of captopril is not mediated by changes in blood-bradykinin but may involve inhibition of the renin-angiotensin and kallikrein-kinin systems locally within the kidneys or blood vessels.

Glucocorticoid-remediable aldosteronism (GRA), an autosomal dominant disorder, is characterized by hypertension with variable hyperaldosteronism and by high levels of the abnormal adrenal steroids 18-oxocortisol and 18-hydroxycortisol, which are all under control of adrenocorticotropic hormone and suppressible by glucocorticoids. These abnormalities could result from ectopic expression of aldosterone synthase, which is normally expressed only in adrenal glomerulosa, in the adrenal fasciculata. Genes encoding aldosterone synthase and steroid 11 beta-hydroxylase (expressed in both adrenal fasciculata and glomerulosa), which are 95% identical and lie on chromosome 8q (refs 7, 10), are therefore candidate genes for GRA. Here we demonstrate complete linkage of GRA in a large kindred to a gene duplication arising from unequal crossing over, fusing the 5' regulatory region of 11 beta-hydroxylase to the coding sequences of aldosterone synthase (maximum lod score 5.23 for complete linkage, odds ratio of 170,000:1). This mutation can account for all the physiological abnormalities of GRA. Our result represents the demonstration of a mutation causing hypertension in otherwise phenotypically normal animals or humans.

In the 60 years that have passed since the discovery of the mineralocorticoid hormone aldosterone, much has been learned about its synthesis (both adrenal and extra-adrenal), regulation (by renin-angiotensin II, potassium, adrenocorticotrophin, and other factors), and effects (on both epithelial and nonepithelial tissues). Once thought to be rare, primary aldosteronism (PA, in which aldosterone secretion by the adrenal is excessive and autonomous of its principal regulator, angiotensin II) is now known to be the most common specifically treatable and potentially curable form of hypertension, with most patients lacking the clinical feature of hypokalemia, the presence of which was previously considered to be necessary to warrant further efforts towards confirming a diagnosis of PA. This, and the appreciation that aldosterone excess leads to adverse cardiovascular, renal, central nervous, and psychological effects, that are at least partly independent of its effects on blood pressure, have had a profound influence on raising clinical and research interest in PA. Such research on patients with PA has, in turn, furthered knowledge regarding aldosterone synthesis, regulation, and effects. This review summarizes current progress in our understanding of the physiology of aldosterone, and towards defining the causes (including genetic bases), epidemiology, outcomes, and clinical approaches to diagnostic workup (including screening, diagnostic confirmation, and subtype differentiation) and treatment of PA.

Primary aldosteronism (PA) is a common, but frequently overlooked, cause of arterial hypertension and excess cardiovascular events, particularly atrial fibrillation. As timely diagnosis and treatment can provide a cure of hyperaldosteronism and hypertension, even when the latter is resistant to drug treatment, strategies to screen patients for PA early with a simplified diagnostic algorithm are justified. They can be particularly beneficial in some subgroups of hypertensive patients, as those who are at highest cardiovascular risk. However, identification of the surgically curable cases of PA and achievement of optimal results require subtyping with adrenal vein sampling, which, as it is technically challenging and currently performed only in tertiary referral centers, represents the bottleneck in the work-up of PA. Measures aimed at improving the clinical use of adrenal vein sampling and at developing alternative techniques for subtyping, alongside recommendations for drug treatment, including new development in the field, and for follow-up are discussed.

Primary aldosteronism is a common cause of secondary hypertension associated with excess cardiovascular morbidities. Primary aldosteronism is underdiagnosed because it does not have a specific, easily identifiable feature and clinicians can be poorly aware of the disease. The diagnostic investigation is a multistep process of screening, confirmatory testing, and subtype differentiation of unilateral from bilateral forms for therapeutic management. Adrenal venous sampling is key for reliable subtype identification, but can be bypassed in patients with specific characteristics. For unilateral disease, surgery offers the possibility of cure, with total laparoscopic unilateral adrenalectomy being the treatment of choice. Bilateral forms are treated mainly with mineralocorticoid receptor antagonists. The goals of treatment are to normalise both blood pressure and excessive aldosterone production, and the primary aims are to reduce associated comorbidities, improve quality of life, and reduce mortality. Prompt diagnosis of primary aldosteronism and the use of targeted treatment strategies mitigate aldosterone-specific target organ damage and with appropriate patient management outcomes can be excellent. Advances in molecular histopathology challenge the traditional concept of primary aldosteronism as a binary disease, caused by either a unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia. Somatic mutations drive autonomous aldosterone production in most adenomas. Many of these same mutations have been identified in nodular lesions adjacent to an aldosterone-producing adenoma and in patients with bilateral disease. In addition, germline mutations cause rare familial forms of aldosteronism (familial hyperaldosteronism types 1-4). Genetic testing for inherited forms in suspected cases of familial hyperaldosteronism avoids the burdensome diagnostic investigation in positive patients. In this Review, we discuss advances and future management approaches in the diagnosis of primary aldosteronism.

Primary aldosteronism is the most common cause of secondary hypertension in the middle-aged population. A high level of suspicion is required, due to the higher morbidity and mortality associated with damage to target organs (heart, brain, vessels, kidneys) than with essential hypertension. Screening involves 3 phases: detection, confirmation and detection of lateralization if surgery is an option. The choice of treatment will depend on the cause and the patient's wishes and may be either medical (mineralocorticoid receptor antagonists) or surgical (unilateral adrenalectomy). Both treatment options reduce the risk of cardiovascular morbidity and mortality if blood pressure is well controlled.

Background:Primary aldosteronism (PA) is caused by autonomous aldosterone overproduction and characterised by uncontrolled hypertension. There are currently no treatments that target aldosterone synthesis. We evaluated the safety and efficacy of a novel aldosterone synthase inhibitor, dexfadrostat phosphate, in patients with PA. Methods:This multi-centre, randomised, phase 2 trial was conducted between November 2019 and May 2022 (NCT04007406; EudraCT code 2019-000919-85). Adults with PA and an office systolic blood pressure of 145-190 mmHg were included. After a 2-week single-blind placebo run-in period, participants were randomised 1:1:1 to receive oral dexfadrostat phosphate 4, 8, or 12 mg once daily for an 8-week double-blind treatment period, followed by a 2-week single-blind placebo withdrawal period. Randomisation was conducted centrally and stratified by centre and sex. At the beginning and end of the treatment period, 24 h ambulatory systolic blood pressure (aSBP) was recorded. Blood samples were taken every 2 weeks. Primary endpoints were the change in aldosterone-to-renin ratio (ARR) and mean 24 h aSBP from baseline to the end of the treatment period in the combined dose group of all participants receiving any dose of dexfadrostat phosphate. Safety endpoints were the occurrence of treatment-emergent adverse events (TEAEs) and serious adverse events over the entire study in all randomised participants who received at least one dose of dexfadrostat phosphate. Findings:In total, 35 participants received dexfadrostat phosphate and all participants completed the study. Twenty-six participants (74.3%) were male, the mean age was 51.9 years (SD 8.7), and most were White (n = 32, 91.4%). The median ARR and the mean 24 h aSBP significantly decreased from the beginning to the end of the treatment period in the combined dose group (ARR: 15.3 vs 0.6, least-squares mean [LSM] change in log-normal values -2.5, p < 0.0001; aSBP: 142.6 vs 131.9 mmHg, LSM change -10.7 mmHg, p < 0.0001). There were no safety concerns; all TEAEs were mild or moderate and there were no serious TEAEs. Interpretation:Dexfadrostat phosphate corrected the ARR and aSBP and was well tolerated in patients with PA, demonstrating the benefit of pharmacologically targeting the source of hyperaldosteronism. Funding:DAMIAN Pharma AG.

Recent studies have explored the association between primary aldosteronism and cardiovascular disease incidence. The association between specific primary aldosteronism treatments and differential improvement in cardiovascular event rates is yet to be established. This study was designed to compare the relative effects of spironolactone therapy and surgical intervention on cardiovascular outcomes among primary aldosteronism patients. This retrospective observational study included 853 primary aldosteronism patients from the First Affiliated Hospital of China Medical University between 2014 and 2022. Patients who had completed abdominal computed tomography (CT) examinations with similar metabolic characteristics and 6-month follow-up analyses were included in this study. These patients were separated into a surgical treatment group (n = 33) and a spironolactone treatment group (n = 51). Demographic data, biochemical analysis results, liver/spleen (L/S) X-ray attenuation ratio, hospitalization frequency, and cardiovascular events were compared between the two groups. The spironolactone group demonstrated significantly improved metabolic characteristics compared to the surgical group, shown by lower BMI, blood pressure, total cholesterol (TC), insulin resistance index (IRI), and reduced non-alcoholic fatty liver disease prevalence. Metabolic parameters did not differ significantly within the surgical treatment group when comparing pre- and postoperative values. The incidence of cardiovascular events was lower in the spironolactone group compared to the surgery group (23/33 vs. 20/51, P < 0.001) despite higher hospitalization rates(37/31 vs. 61/53, P < 0.001). In patients with primary aldosteronism, spironolactone treatment is more effective than surgical intervention in remediating abnormal lipid and glucose metabolism while improving cardiovascular outcomes. Chinese clinical trial registry registration number: ChiCTR2300074574.

Patients with primary aldosteronism have an increased risk of developing cardiovascular disease. The response to mineralocorticoid receptor antagonists varies among individuals, indicating diverse mineralocorticoid receptor activities in these patients. This study explored the factors linked to the efficacy of blood pressure reduction through mineralocorticoid receptor antagonists in patients with primary aldosteronism. We examined the relationship between the reduction in blood pressure and patient characteristics in a group of 41 patients with primary aldosteronism (24 males, mean age 55 ± 13 years, including 34 patients diagnosed with bilateral primary aldosteronism) before and after undergoing treatment with mineralocorticoid receptor antagonists. Significant reductions in office blood pressure were observed 3 and 6 months after treatment initiation. Single correlation analyses showed that the urinary chloride-to-potassium ratio displayed the strongest positive association with blood pressure reduction, surpassing plasma aldosterone concentration, plasma renin activity, and urinary sodium-to-potassium ratio, at 3 and 6 months. Multiple correlation analyses revealed a consistent and independent positive correlation between the urinary chloride-to-potassium ratio and blood pressure reduction at 3 and 6 months. The optimal threshold for the urinary chloride-to-potassium ratio with respect to its ability to lower blood pressure, was determined as 3.18. These results imply that the urinary chloride-to-potassium ratio may be independently associated with the effectiveness of blood pressure reduction facilitated by mineralocorticoid receptor antagonists. Moreover, it could potentially serve as a valuable predictor of the effectiveness of these agents and function as an indicator of endogenous mineralocorticoid receptor activity in patients with primary aldosteronism.

Primary aldosteronism (PA) is the most common cause of secondary hypertension and is associated with increased morbidity and mortality when compared with blood pressure-matched cases of primary hypertension. Current limitations in patient care stem from delayed recognition of the condition, limited access to key diagnostic procedures, and lack of a definitive therapy option for nonsurgical candidates. However, several recent advances have the potential to address these barriers to optimal care. From a diagnostic perspective, machine-learning algorithms have shown promise in the prediction of PA subtypes, while the development of noninvasive alternatives to adrenal vein sampling (including molecular positron emission tomography imaging) has made accurate localization of functioning adrenal nodules possible. In parallel, more selective approaches to targeting the causative aldosterone-producing adrenal adenoma/nodule (APA/APN) have emerged with the advent of partial adrenalectomy or precision ablation. Additionally, the development of novel pharmacological agents may help to mitigate off-target effects of aldosterone and improve clinical efficacy and outcomes. Here, we consider how each of these innovations might change our approach to the patient with PA, to allow more tailored investigation and treatment plans, with corresponding improvement in clinical outcomes and resource utilization, for this highly prevalent disorder.

OBJECTIVE:To compare the efficacy (including blood pressure, medication reduction, serum potassium, and clinical success) and safety parameters (including operative time, length of hospital stay, blood loss, hypertension crisis rate, and complication rate) of radiofrequency ablation (RFA) and laparoscopic adrenalectomy (LA) in the treatment of primary aldosteronism (PA). METHODS:Literature search was performed on PubMed, EMBASE, The Cochrane Library (Issue 8, 2023), Web of Science, China National Knowledge Infrastructure, and Wanfang from inception to August 2023. Study selection, data extraction, and risk of bias assessment were performed by two independent reviewers. Quality assessment was conducted using the Newcastle-Ottawa scale. The Stata 12.0 software was used for statistical analyses. Pooled odds ratios (OR) with corresponding 95% confidence interval (CI) were calculated for categorical outcomes, while mean difference (MD) with corresponding 95% CI were calculated for continuous outcomes. RESULTS:A total of 5 studies involving 204 patients (LA, n = 127; and RAF, n = 77) were included. LA had better diastolic blood pressure control than RFA (WMD = 5.19; 95% CI 0.96-9.43); however, the RFA demonstrated better shorter operative time (WMD = - 57.99; 95% CI - 116.54 to 0.57), and shorter length of hospital stay (OR - 1.6; 95% CI - 2.37 to - 0.83) compared to LA. All remaining parameters were comparable between the interventions. CONCLUSION:While grossly comparable in efficacy as treatment options for PA, RFA may allow for shorter operative time and hospital stay, less intraoperative blood loss, and lower hospitalization costs. However, LA has better diastolic blood pressure control. Even so, we still need larger prospective studies, specifically with comparative hypertension response (short and long term) and number of post-procedural antihypertensive medication requirement.

Hypertension leads to multiple comorbidities and increased risk for mortality. Endocrine disorders contribute to the development of hypertension, including primary aldosteronism (PA). This article discusses the evaluation and management of PA.

Background:The effectiveness and side effects between different medical treatments in patients with primary hyperaldosteronism have not been systematically studied. Objective:To analyze the efficacy between different mineralocorticoid receptor antagonists (MRAs) and epithelial sodium channel (ENaC) inhibitors in a network meta-analysis (NMA) framework, while also evaluating adverse events. Design:Systematic review and NMA. Data sources and methods:The systematic review and NMA was reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, MEDLINE, the Cochrane library, and Excerpta Medica database (EMBASE) were searched for randomized controlled trials (RCTs) involving adult patients with primary hyperaldosteronism until 23 June 2023. Studies that compared the efficacy and side effects of different medical treatments of primary hyperaldosteronism were included. The primary outcomes included the effect on blood pressure, serum potassium, and major adverse cardiovascular events. The secondary outcomes were adverse events related to MRAs (hyperkalemia and gynecomastia). Frequentist NMA and pairwise meta-analysis were conducted. Results:A total of 5 RCTs comprising 392 participants were included. Eplerenone, esaxerenone, and amiloride were compared to spironolactone and demonstrated comparable effect on the reduction of systolic blood pressure. In comparison to spironolactone, eplerenone exhibited a less pronounced effect on reducing diastolic blood pressure [-4.63 mmHg; 95% confidence interval (CI): -8.87 to -0.40 mmHg] and correcting serum potassium (-0.2 mg/dL; 95% CI: -0.37 to -0.03 mg/dL). Spironolactone presented a higher risk of gynecomastia compared with eplerenone (relative risk: 4.69; 95% CI: 3.58-6.14). Conclusion:The present NMA indicated that the blood pressure reduction and potassium-correcting effects of the three MRAs may demonstrate marginal differences, with confidence levels in the evidence being very low. Therefore, further research is needed to explore the efficacy of these MRAs, especially regarding their impact on mortality and cardiovascular outcomes. Trial registration:PROSPERO (CRD: 42023446811).

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

OBJECTIVE:Superselective adrenal arterial embolization (SAAE) is a potential alternative treatment for patients with unilateral primary aldosteronism (PA) who refuse unilateral adrenalectomy. Therefore, we aimed to establish a scoring model to differentiate between hypertensive remission after SAAE. METHODS:This prospective cohort study involved 240 patients who underwent SAAE for unilateral PA. Patients were randomly divided into a model training set and a validation set at a ratio of 7:3. The clinical outcome was a response to hypertension remission, defined as complete, partial, or absent success at 6 months after SAAE. Multivariate logistic regression was performed to identify independent parameters and develop a nomogram to predict clinical outcomes after SAAE. The discrimination, calibration efficacy, and clinical utility of the predictive model were assessed. RESULTS:Five independent predictors were identified: female sex, duration of hypertension, defined daily dose of antihypertensive medication, diabetes, and target organ damage. The above five independent predictors were put into a predictive model that was presented as a nomogram. Using bootstrapping for internal validation, the C-statistic for the predictive model was 0.866 (95% confidence interval [CI]: 0.834 to 0.898). In the validation cohort, the area under the curve (AUC) of the nomogram for predicting hypertension remission after SAAE was 0.809. CONCLUSION:The present model is the first nomogram-based score that specifically predicts hypertension remission after SAAE in patients with unilateral PA using conventional parameters. This is an effective risk stratification tool that can be used by clinicians for timely and tailored preoperative risk discussions.

In patients with primary hyperaldosteronism (PA), adrenal vein sampling (AVS) can identify patients suitable for unilateral adrenalectomy. However, in AVS with an indeterminate aldosterone-to-cortisol lateralization (ACL) ratio of 3.0-4.0, clinical guidance is unclear. The authors screened all patients undergoing AVS at the Cleveland Clinic from October 2010 to January 2021 and identified 18 patients with indeterminate ACL results. Ten underwent adrenalectomy and eight continued medical management. The surgical group was younger (58.5 vs. 68 years, p = .17), and more likely to have a unilateral imaging adrenal abnormality (90% vs. 38%, p = .043) and a lower contralateral suppression index (0.63 vs. 1.1, p = .14). Post-treatment, the surgical group had a significant reduction in diastolic blood pressure (-5.5 mmHg, p = .043) and aldosterone (4.40 vs. 35.80 ng/mL, p = .035) and required fewer anti-hypertensive medications (2 vs. 3, p = .015). These findings may support the benefit of adrenalectomy in a select group of patients with indeterminate ACL.

An increased risk of target organ damage (TOD) has been reported in patients with primary aldosteronism (PA). However, there is relatively little related research on the correlation between the degree of TOD and those with and without PA in newly diagnosed hypertensive patients. The aim of this study was to assess the association between PA and TOD among patients with newly diagnosed hypertension. Newly diagnosed hypertensive patients were consecutively recruited from January 2015 to June 2020 at the University of Hong Kong-Shenzhen Hospital. Patients were stratified into those with and without PA. Data for left ventricular mass index (LVMI), carotid intima-media thickness (CIMT) and plaque, and microalbuminuria were systematically collected. A total of 1044 patients with newly diagnosed hypertension were recruited, 57 (5.5%) of whom were diagnosed with PA. Patients with PA had lower blood pressure, serum lipids, body mass index, and plasma renin activity and a higher incidence of hypokalemia than those without PA. In contrast, the prevalence of left ventricular hypertrophy, increased CIMT, and microalbuminuria was higher in patients with PA than in those without PA. Multivariable regression analysis demonstrated that PA was independently associated with increased LVMI, CIMT and microalbuminuria. Among patients with newly diagnosed hypertension, those with PA had more severe TOD, including a higher LVMI, CIMT and microalbuminuria, than those without PA. These findings emphasize the need for screening TOD in newly diagnosed hypertension due to underlying PA.

BACKGROUND:Primary aldosteronism (PA) has been broadly dichotomized into unilateral and bilateral forms. Adrenal vein sampling (AVS) lateralization indices (LI) ≥2 to 4 are the standard-of-care to recommend unilateral adrenalectomy for presumed unilateral PA. We aimed to assess the rates and characteristics of residual PA after AVS-guided adrenalectomy. METHODS:We conducted an international, retrospective, cohort study of patients with PA from 7 referral centers who underwent unilateral adrenalectomy based on LI≥4 on baseline and/or cosyntropin-stimulated AVS. Aldosterone synthase (CYP11B2) immunohistochemistry and next generation sequencing were performed on available formalin-fixed paraffin-embedded adrenal tissue. RESULTS:The cohort included 283 patients who underwent AVS-guided adrenalectomy, followed for a median of 326 days postoperatively. Lack of PA cure was observed in 16% of consecutive patients, and in 22 patients with lateralized PA on both baseline and cosyntropin-stimulated AVS. Among patients with residual PA postoperatively, 73% had multiple CYP11B2 positive areas within the resected adrenal tissue (versus 23% in those cured), wherein mutations were most prevalent (63% versus 33% in those cured). In adjusted regression models, independent predictors of postoperative residual PA included Black versus White race (odds ratio, 5.10 [95% CI, 1.45-17.86]), AVS lateralization only at baseline (odds ratio, 8.93 [95% CI 3.00-26.32] versus both at baseline and after cosyntropin stimulation), and CT-AVS disagreement (odds ratio, 2.75 [95% CI, 1.20-6.31]). CONCLUSIONS:Multifocal, asymmetrical bilateral PA is relatively common, and it cannot be excluded by robust AVS lateralization. Long-term postoperative monitoring should be routinely pursued, to identify residual PA and afford timely initiation of targeted medical therapy.

INTRODUCTION:Primary aldosteronism (PA) is associated with several cardiometabolic comorbidities. Specific treatment by mineralocorticoid receptor antagonists (MRA) or adrenalectomy has been reported to reduce the cardiometabolic risk. However, the cardiovascular benefit could depend on plasma renin levels in patients on MRA. AIM:To compare the development of cardiovascular, renal and metabolic complications between medically treated patients with PA and those who underwent adrenalectomy, taking the renin status during MRA treatment into account. METHODS:A multicenter retrospective study (SPAIN-ALDO Register) of patients with PA treated at 35 Spanish tertiary hospitals. Patients on MRA were divided into two groups based on renin suppression (n = 90) or non-suppression (n = 70). Both groups were also compared to unilateral PA patients (n = 275) who achieved biochemical cure with adrenalectomy. RESULTS:Adrenalectomized patients were younger, had higher plasma aldosterone concentration, and lower potassium levels than MRA group. Patients on MRA had similar baseline characteristics when stratified into treatment groups with suppressed and unsuppressed renin. 97 (55.1%) of 176 patients without comorbidities at diagnosis, developed at least one comorbidity during follow-up (median 12 months vs. 12.5 months' follow-up after starting MRA and surgery, respectively). Surgery group had a lower risk of developing new cardiovascular events (HR 0.40 [95% CI 0.18-0.90]) than MRA group. Surgical treatment improved glycemic and blood pressure control, increased serum potassium levels, and required fewer antihypertensive drugs than medical treatment. However, there were no differences in the cardiometabolic profile or the incidence of new comorbidities between the groups with suppressed and unsuppressed renin levels (HR 0.95 [95% CI 0.52-1.73]). CONCLUSION:Cardiovascular, renal, and metabolic events were comparable in MRA patients with unsuppressed and suppressed renin. Effective surgical treatment of PA was associated with a decreased incidence of new cardiovascular events when compared to MRA therapy.

Primary aldosteronism (PA) is an endocrinopathy characterized by dysregulated aldosterone production that occurs despite suppression of renin and angiotensin II, and that is non-suppressible by volume and sodium loading. The effectiveness of surgical adrenalectomy for patients with lateralizing PA is characterized by the attenuation of excess aldosterone production leading to blood pressure reduction, correction of hypokalemia, and increases in renin-biomarkers that collectively indicate a reversal of PA pathophysiology and restoration of normal physiology. Even though the vast majority of patients with PA will ultimately be treated medically rather than surgically, there is a lack of guidance on how to optimize medical therapy and on key metrics of success. Herein, we review the evidence justifying approaches to medical management of PA and biomarkers that reflect endocrine principles of restoring normal physiology. We review the current arsenal of medical therapies, including dietary sodium restriction, steroidal and nonsteroidal mineralocorticoid receptor antagonists, epithelial sodium channel inhibitors, and aldosterone synthase inhibitors. It is crucial that clinicians recognize that multimodal medical treatment for PA can be highly effective at reducing the risk for adverse cardiovascular and kidney outcomes when titrated with intention. The key biomarkers reflective of optimized medical therapy are unsurprisingly similar to the physiologic expectations following surgical adrenalectomy: control of blood pressure with the fewest number of antihypertensive agents, normalization of serum potassium without supplementation, and a rise in renin. Pragmatic approaches to achieve these objectives while mitigating adverse effects are reviewed.