ACTH stimulation and oral salt loading tests detect biochemical outcome early after primary aldosteronism surgery.

BACKGROUND: In primary aldosteronism (PA), the biochemical outcomes of the Primary Aldosteronism Surgical Outcome study are used to assess aldosterone hypersecretion 6-12 months after surgery. However, few studies have investigated whether the outcomes can be predicted in the early postoperative period. In this retrospective study, we evaluated whether the adrenocorticotropin stimulation test (AST) and oral salt loading test (OST) performed immediately after surgery could predict biochemical outcomes 1 year after surgery. METHODS: We assessed 268 patients with PA who underwent adrenalectomy at our hospital between 2008 and 2020, underwent AST and OST within 15 days of surgery, and were assessed for biochemical outcomes 1 year after surgery. Patients were divided into two groups: biochemical complete success (B-com; n = 219) and incomplete success (B-inc; n = 49). Patients were divided into clinical complete and partial success and absent success groups. The relationships between various AST and OST values and outcomes were analyzed. RESULTS: The B-inc group had significantly higher plasma aldosterone concentration (PAC) and PAC/serum cortisol ratio (PAC/Cort) at baseline and after ACTH loading in AST and 24-hour urine aldosterone in OST than the B-com group. PAC/Cort at 30 min after ACTH loading (area under the curve (AUC) = 0.76) and 24-hour urine aldosterone (AUC = 0.77) were relatively superior predictors of the outcome. Parameters after ACTH loading were better predictors of biochemical and clinical outcomes than baseline. CONCLUSIONS: AST and OST immediately after surgery can predict biochemical and clinical outcomes 1 year after surgery in patients with PA.

Primary and "Pre-Primary" Aldosteronism in Resistant Hypertension: A Practical, Pragmatic, and Prudent Approach in Resource-Limited Milieu.

Introduction Primary aldosteronism (PA), once considered rare, is now recognized as the most common cause of secondary hypertension, accounting for almost a quarter of resistant hypertension (RH) cases. Despite this, PA remains underdiagnosed, with an extremely low percentage of RH patients undergoing screening. Methods In a specialty diabetes-endocrinology clinic, the aldosterone:renin ratio (ARR) was assessed in 115 consecutive RH patients (ages 21-93 years; 47% male; 87% with type 2 diabetes). Fasting blood samples were drawn in a standing position after 30 minutes of walking. Adrenal imaging (CT/MRI) was performed for those with an ARR >20. Results ARR values ranged from 0.4 to 227 (ARR <10 (35%); 11-20 (19%), 21-40 (25%), and >40 (21%)), with corresponding stepwise decreasing plasma renin activity (PRA) (P= 1E-6) and increasing serum aldosterone (SA) (P= 8E-7). Increasing ARR tended to be associated with an increase in serum creatinine (R= 0.23; P= 0.03) and a decrease in estimated glomerular filtration rate (eGFR) (R= -0.24; P= 0.02) and an increase in urine albumin: creatinine ratio. The ARR> 40 group displayed the highest serum creatinine, lowest eGFR, higher urine albumin: creatinine ratio, highest serum sodium, lowest serum potassium, and highest (44%) abnormal adrenal imaging (bilateral hyperplasia diffuse/nodular; solitary adenoma), reflecting a later stage of the pathological spectrum. PA treatment with mineralocorticoid receptor antagonists (MRAs) had a salutary effect. Conclusions Our observations further reinforce that PA is not a binary condition, but exists as a spectrum disorder responsive to MRAs, even in patients with mildly elevated or normal aldosterone levels. Early disease detection/recognition ("renin-independent aldosterone production") can be facilitated by marking "pre-primary" aldosteronism (ARR 11-20), followed by monitoring progression (periodic rescreening) and optimizing treatment, with hopeful mitigation of end-organ damage in RH.

Development of a multivariate model predictive of post-adrenalectomy renal function decline in patients with primary aldosteronism: a large-cohort single-center study.

PURPOSE: To develop a multivariate liniear model for predicting long-term (> 3 months) post-adrenalectomy renal function decline in patients with primary aldosteronism (PA). The model aims to help identify patients who may experience a significant decline in renal function after surgery. METHODS: We retrospectively analyzed the clinical data of 357 patients who were diagnosed with PA and underwent adrenalectomy between September 2012 and February 2023. LASSO and multivariate linear regression analyses were used to identify significant risk factors for model construction. The models were further internally validated using bootstrap method. RESULTS: Age (P < 0.001), plasma aldosterone concentration (PAC) measured in the upright-position (PACU, P = 0.066), PAC measured after saline infusion (PACafterNS, P = 0.010), preoperative blood adrenocorticotropic-hormone level (ACTH, P = 0.048), preoperative estimated glomerular filtration rate (eGFR, P < 0.001) and immediate postoperative eGFR (P < 0.001) were finally included in a multivariate model predictive of post-adrenalectomy renal function decline and the coefficients were adjusted by internal validation. The final model is: predicted postoperative long-term (> 3 months) eGFR decline =-70.010 + 0.416*age + 6.343*lg PACU+4.802*lg ACTH + 7.424*lg PACafterNS+0.637*preoperative eGFR-0.438*immediate postoperative eGFR. The predicted values are highly related to the observed values (adjusted R = 0.63). CONCLUSION: The linear model incorporating perioperative clinical variables can accurately predict long-term (> 3 months) post-adrenalectomy renal function decline.

Cutoff Values of Aldosterone and the Aldosterone-Renin Ratio for Predicting Primary Aldosteronism in Patients with Resistant Hypertension: A Real-Life Study.

Primary aldosteronism (PA) is commonly associated with resistant hypertension. Biochemical tests can be clinically useful in the screening and diagnosis of primary aldosteronism. This study aimed to identify the cutoff values of aldosterone levels (A) and the aldosterone-renin ratio (ARR) for an accurate prediction of PA in patients with apparent resistant hypertension in a real-life scenario. This database-based study included a historical cohort of male and female patients with apparent resistant hypertension, aged 18 years or older and surveyed for PA in a specialized center from 2008 to 2018. Aldosterone and plasma renin activity (PRA) or the plasma renin concentration (PRC) were measured in the treated hypertensive patients. The patients with positive screening results were subsequently referred to the endocrinology department for confirmatory tests. The patients with confirmed PA were included in the case group, and the others remained as controls. Receiver-operating characteristic (ROC) curves were used to identify the cutoff points for aldosterone and the ARR, thereby analyzing their sensitivity and specificity for confirmed PA. Among the 3464 patients (59 ± 13 years old, 41% male) who had apparent resistance hypertension screened, PA was confirmed in 276 individuals (8%). A ≥ 16.95 ng/dL (95% CI: 0.908-0.933) had an odds ratio of 6.24 for PA, while A/PRA ≥ 29.88 (95% CI: 0.942-0.984) or an A/PRC ≥ 2.44 (95% CI: 0.978-0.990) had an odds ratio of 216.17 for PA diagnoses. Our findings suggest that a positive PA screening with aldosterone ≥ 17 ng/dL associated with A/PRA ≥ 29.88 or an A/PRC ratio of ≥2.44 should be sufficient to confirm the diagnosis of PA without confirmatory testing.

Role of radiologists in the diagnosis and management of adrenal disorders.

This study aimed to focus on the role of radiologists in the diagnosis and management of adrenal lesions, particularly primary aldosteronism (PA) and secondary hypertension. As hypertension affects more than one-third of the population in Japan, identifying secondary causes such as PA and adrenal lesions is crucial. Establishing a radiological differential diagnosis of adrenal lesions using advanced imaging techniques, such as computed tomography and magnetic resonance imaging, is crucial. Knowledge of the imaging findings of various benign and malignant adrenal lesions, such as adrenocortical adenomas, cortisol-producing lesions, pheochromocytomas, adrenocortical carcinoma, malignant lymphoma, and metastatic tumors, is necessary. Adrenal venous sampling (AVS) plays a crucial role in accurately localizing aldosterone hypersecretion in PA, especially when imaging fails to provide a clear diagnosis. This paper details the technical aspects of AVS, emphasizing catheterization techniques, anatomical considerations, and the importance of preprocedural imaging for successful sampling. Furthermore, we explore segmental adrenal venous sampling (SAVS), a more refined technique that samples specific adrenal tributary veins, offering enhanced diagnostic accuracy, particularly for microadenomas or challenging cases that may be missed with conventional AVS. The methodology for performing SAVS, along with the interpretation criteria for successful sampling and lateralization, is also outlined. Furthermore, radiologists have initiated treatments for unilateral PA, such as radiofrequency ablation, and play an integral role in the management of adrenal lesions. Collaborative approaches across clinical departments are required to enhance patient management in medical care involving the adrenal gland.

Adrenal Vein Sampling for Primary Aldosteronism: Recommendations From the Australian and New Zealand Working Group.

Adrenal vein sampling (AVS) is the current recommended procedure for identifying unilateral subtypes of primary aldosteronism (PA), which are amenable to surgery with the potential for cure. AVS is a technically challenging procedure usually undertaken by interventional radiologists at tertiary centres. However, there are numerous variations in AVS protocols relating to patient preparation, sampling techniques and interpretation which may impact the success of AVS and patient care. To reduce practice variations, improve the success rates of AVS and optimise patient outcomes, we established an Australian and New Zealand AVS Working Group and developed evidence-based expert consensus recommendations for the preparation, performance and interpretation of AVS. These recommendations can be used by all healthcare professionals in a multidisciplinary team who look after the diagnosis and management of PA.

Severe hydronephrosis complicated with primary aldosteronism: a case report and review of the literature.

BACKGROUND: Primary aldosteronism is characterized by high plasma aldosterone and low renin. The plasma aldosterone-to-renin ratio is recommended for screening. Severe hydronephrosis leads to renal parenchymal ischemia, resulting in increased renin secretion. Since nonsuppression of renin may cause a negative result in the aldosterone-to-renin ratio test, severe hydronephrosis and primary aldosteronism occurring simultaneously in a patient are challenging to diagnose. CASE PRESENTATION: A 54-year-old Chinese man of Han ethnicity was diagnosed with hypertension and severe hypokalemia (minimum 1.57 mmol/L) 13 years prior, and was also diagnosed with severe hydronephrosis due to congenital ureteral stenosis on the left side. His clinical features suggested primary aldosteronism, but the aldosterone-to-renin ratio result of the patient was negative every time he underwent the primary aldosteronism screening test. No further treatment for primary aldosteronism was performed, which led the patient to suffer from severe hypokalemia, such that he was taking 12-15 g/day potassium chloride orally to keep his blood potassium between 3.0 and 3.5 mmol/L (reference value, 3.5-5.5 mmol/L) for 13 years, and the patient needed to be hospitalized in the intensive care unit for rescue several times. At admission, although the aldosterone-to-renin ratio result of the patient was negative, we still did the saline stress test and captopril inhibition test, and the results showed that the plasma aldosterone level was not lower after the test than before the test. Adrenal enhanced computed tomography suggested an adenoma in the left adrenal gland, and the results of adrenal vein sampling suggested that the left side was the dominant side. Therefore, laparoscopic total resection of the left adrenal gland was performed, and 2 weeks later, the patient developed short-term renal function impairment and hyperkalemia, but his renal function and blood potassium returned to normal after treatment that included fluid rehydration. The patient's biochemical test results and clinical symptoms were completely normal after 1 year. CONCLUSION: We suggest that for patients with a high suspicion of primary aldosteronism in the clinic, comprehensive analysis must be performed in combination with clinical characteristic assessments, such as severe hydronephrosis, if renin is within the normal range or if the aldosterone-to-renin ratio result is negative at screening and diagnostic tests, and adrenal vein sampling should be performed if necessary. It can help avoid misdiagnoses and contribute to the treatment of patients with severe hydronephrosis and primary aldosteronism.

Primary Aldosteronism Influences Cardiac Structure, Function, and Disease Risk: Evidence From Mendelian Randomization Analysis.

Although observational studies have linked primary aldosteronism (PA) with cardiovascular diseases (CVDs), the causality remains uncertain. In this study, we aimed to investigate whether PA is causally associated with CVD risk and cardiac magnetic resonance (CMR) parameters using the Mendelian randomization (MR) method. Independent and genome-wide significant single nucleotide polymorphisms for PA were extracted from genome-wide association study (GWAS) summary statistics. Genetic associations with the CVDs and CMR parameters were obtained from recent large-scale GWASs or genetic consortia. Inverse-variance weighted (IVW) method was utilized for the preliminary estimates, and multiple sensitivity analyses (including weighted median, Cochran's Q test, MR-Egger, MR-PRESSO, and leave-one-out analysis) were conducted to verify the robustness of the results. The MR analyses using the IVW method showed that genetically predicated PA was significantly associated with atrial fibrillation (OR = 1.046, 95% CI: 1.029-1.062, padj < 0.001), myocardial infarction (OR = 1.029, 95% CI: 1.005-1.053, padj = 0.027), heart failure (OR = 1.023, 95% CI: 1.004-1.042, padj = 0.027), any stroke (OR = 1.062, 95% CI: 1.031-1.095, padj < 0.001), any ischemic stroke (OR = 1.058, 95% CI: 1.022-1.095, padj = 0.004), and small vessel stroke (OR = 1.116, 95% CI: 1.041-1.196, padj = 0.004). Notably, PA also had a causal effect on adverse cardiac remodeling, including larger ventricular and atrial volumes, higher ventricular stroke volume, and reduced left atrial emptying fraction. Our findings support a causal role of PA in higher cardiovascular disease risk and adverse cardiac remodeling. Given the diagnostic delay and disease burden in PA, more attention should be paid to the screening and treatment of PA to reduce the incidence of cardiovascular outcomes.

Diagnostic and therapeutic approaches to a case of pregnancy complicated by bilateral adrenocortical adenomas with primary aldosteronism and Cushing's syndrome.

Aldosterone/cortisol co-secreting adenomas (A/CPA) are a rare type of primary aldosteronism(PA), and cases of aldosterone/cortisol co-secreting adenomas during pregnancy are extremely rare, with no reported cases to date. The unique physiological state of pregnancy increases cortisol secretion through the hypothalamic-pituitary-adrenal (HPA) axis and leads to elevated levels of all components of the renin-angiotensin-aldosterone system (RAAS). This can cause overlapping symptoms with abnormal cortisol and aldosterone secretion, making diagnosis very challenging. This case involves a 29-year-old woman who developed hypercortisolism at 33 weeks of pregnancy. Despite receiving treatment for her symptoms and having a successful delivery, she continued to experience hypertension and hypokalaemia after giving birth. Eventually, she was diagnosed with ACTH-independent Cushing's syndrome and primary aldosteronism due to independent cortisol and aldosterone secretion from bilateral adrenal adenomas. Following a thorough diagnosis, classification, treatment, and follow-up, the patient achieved a clinical cure while preserving normal adrenal function. Further investigation revealed that both diseases were caused by KCNJ5 and PRKACA mutations found in the bilateral adrenal adenomas.

Arterial Stiffness Associated with Long-Term Major Adverse Cardiac Events in Patients of Primary Aldosteronism.

CONTEX: As a novel parameter for risk prediction, artery stifiness may hold promise in refining risk assessment strategies, guiding therapeutic interventions, and ultimately improving cardiovascular outcomes in patients with primary aldosteronism (PA). OBJECTIVE AND METHODS: To investigate the correlation between brachial-ankle pulse wave velocity (baPWV), an indicator of arterial stiffness, and the occurrence of major adverse cardiovascular events (MACEs) in patients with PA under a primary prevention design. RESULTS: Among the 830 patients included in the final analysis, 113 (13.6%) developed inciden t MACEs over a median follow-up period of 5.8 years, with a crude rate of 23.2 per 1000 person-years. Multivariable Cox proportional hazards analyses revealed that baPWV was an independent risk factor for incident MACEs, with an adjusted hazard ratio of 1.01 (P = 0.028). The generalized additive model identified a cut-off value of 2000 cm/s for baPWV, which was independently associated with incident MACEs, with a hazard ratio of 1.72 (P = 0.045). Subgroup analyses revealed that PA patients who were mineralocorticoid receptor antagonist (MRA) users and had high baPWV had a significantly higher risk of incident MACEs (HR = 3.34; P < 0.001), while the risk was not significant in patients who underwent adrenalectomy (P = 0.062). Furthermore, the addition of baPWV to the cardiovascular Framingham risk score significantly improved the category-free net reclassification index (0.308, P < 0.001). CONCLUSIONS: Our study found that 13.6% of patients with PA developed MACEs after a median follow-up of 5.8 years. Our findings highlight the potential utility of baPWV as a tool for risk stratification in PA patients in primary prevention, whereas adrenalectomy appears to mitigate this risk irrespective of baPWV. The measurement of baPWV could be a valuable addition to hypertension screening programs for primary prevention, providing additional predictive information for the potential occurrence of MACEs.

A comparative study of postadrenalectomy hyperuricemia and renal impairment in patients with unilateral primary aldosteronism: does histopathology subtype matter?

BACKGROUND: Primary aldosteronism (PA), which is present in 5-18% of hypertensive patients, is a leading cause of secondary hypertension. Adrenalectomy is often recommended for patients with unilateral primary aldosteronism (uPA), yielding good long-term outcomes. PA patients without hyperuricemia and chronic renal failure before adrenalectomy were enrolled in this cohort study. Serum uric acid (SUA) and renal filtration were measured one year post-adrenalectomy. Their relationships with pathologic features, histopathological subtype (classical or nonclassical (HISTALDO consensus)), and vessel stiffness were explored. The aim of this cohort study is to evaluate the correlation between post-adrenalectomy serum uric acid (SUA) levels and estimated glomerular filtration rate (eGFR) with the pathologic features delineated by the HISTALDO consensus. Additionally, the study seeks to assess the impact of these biochemical markers on peripheral vessel stiffness and brachial-ankle pulse wave velocity (baPWV) at a one-year follow-up visit. METHODS: This prospective cohort study included patients (N = 100) diagnosed with uPA who underwent adrenalectomy from Jan 1, 2007 to Dec 31, 2022. RESULTS: At follow-up, elevated SUA, hyperuricemia, and a > 25% eGFR decrease were significantly more common in the classical than the nonclassical group. The incidence of postoperative hyperuricemia, herein referred to as post-adrenalectomy hyperuricemia (PAHU), was 29% (29/100) overall, 34.8% (23/66) in the classical group and 17.6% (6/34) in the nonclassical group. The incidence of eGFR reduction > 25% was 33% (33/100), 43.9% (29/66), and 11.8% (4/34), respectively. baPWV decreased more in the classical group than the nonclassical group. CONCLUSION: For PA patients with PAHU and/or renal impairment, we suggest monitoring SUA, pH, urine uric acid, and urine crystals and performing a KUB study and peripheral vascular and renal sonography (on which pure uric acid stones in the KUB are radiolucent) to determine whether drug intervention is required for cases of asymptomatic PAHU, especially patients in male gender, classical histopathology, or renal impairment.

Cost-effectiveness analysis of segmental adrenal venous sampling with radiofrequency ablation for primary aldosteronism in Japan.

PURPOSE: The purpose of this study was to evaluate the cost-effectiveness of comprehensive treatment strategy, including segmental adrenal venous sampling (sAVS) and radiofrequency ablation (RFA), versus medication-only strategy for primary aldosteronism. MATERIALS AND METHODS: A Markov decision model was developed to compare the cost-effectiveness of a comprehensive treatment strategy and a medication-only strategy for 50-year-old men and women with stage I-III hypertension. The comprehensive treatment strategy included aldosterone/renin ratio measurement, two loading tests, computed tomography, sAVS, drugs, surgery, and RFA. We built a model with a yearly cycle over 32- and 38-year time horizons for men and women, respectively, and four health states: hypertension, heart failure, stroke, and death. The incremental cost-effectiveness ratio (ICER), expressed as Japanese yen per quality-adjusted life-years (QALYs), was estimated, and strategy preference was determined on the basis of 5 million Japanese yen per QALY societal willingness-to-pay threshold. RESULTS: The ICERs of the comprehensive treatment strategy over the medication-only strategy were 201,482 and 3,399 JPY per QALY for men and women, respectively. The resultant ICER was less than the 5 million JPY societal willingness-to-pay threshold. Deterministic sensitivity analysis and probabilistic sensitivity analysis revealed that the results varied with the input values, but the comprehensive strategy was likely to be more cost-effective than the medication-only strategy. CONCLUSION: This cost-effectiveness study revealed that a comprehensive treatment strategy including sAVS and RFA was favorable compared with the medication-only strategy for managing stage I-III hypertension in 50-year-old men and women, with acceptable willingness-to-pay thresholds. This cost-effectiveness study revealed that a comprehensive treatment strategy for primary aldosteronism that included segmental adrenal sampling and radiofrequency ablation was favorable compared with the medication-only strategy for managing stage I-III hypertension in 50-year-old men and women, with acceptable willingness-to-pay thresholds.

Usefulness of the Upright Posture Test in the Diagnosis of Primary Aldosteronism.

Objective: To assess the usefulness of the upright posture stimulation test (UPT) in the confirmation of primary aldosteronism (PA) in patients in whom saline tests (ST) were inconclusive. Methods: One hundred eighty-seven adult patients with possible PA were retrospectively included and compared to 25 control subjects. Blood samples were obtained after a 1-hour supine posture and during 2 hours of ambulation. An increase in plasma aldosterone concentration (PAC) ≥ 50% with a suppressed renin (≤10.1 ng/L; ≤1 ng/mL/hour) and a cortisol increase ≤50% were considered abnormal. Results: PA patients had higher basal PAC and lower basal direct renin concentration (DRC) (P < .0001) and a higher maximal PAC (P = .0025) and lower maximal DRC (DRCmax) (P < .0001) during UPT compared to controls. PA was confirmed in 145 patients (77.5%), based on either oral/IV ST or UPT. DRCmax ≤12 ng/L during UPT was a predictor of PA (receiver operating characteristic curve sensitivity 93.8%, specificity 88%), and 95.6% of PA patients increased PAC ≥50% on UPT (median 222.2%), while renin remained suppressed. All 41 PA patients with false-negative IV ST (PAC < 162 pmol/L) and 88.9% with borderline response (162-240 pmol/L) had a DRCmax ≤12, while, respectively, 97.6% and 100% increased aldosterone by ≥50%. Similar responses to UPT were found in lateralized (28/63) and bilateral PA source (35/63). PA diagnosis increased from 23.6% to 88.8% using UPT results instead of IV ST and were confirmed at pathology and clinical outcome after adrenalectomy (n = 22). Conclusion: UPT can be useful to confirm PA, particularly in patients with suspected false-negative ST.

A New Disease Severity Score for Measuring Treatment Response to Adrenalectomy in Patients With Primary Aldosteronism.

OBJECTIVE: Cure after adrenalectomy for primary aldosteronism has been reported in only 15% to 40% of patients, with no disease severity score available to measure response objectively. Furthermore, the criteria used to define cure are outdated. This study aims to determine the rate of cure based on the current definition of normal blood pressure and develop a disease severity score to measure clinical improvement after adrenalectomy for primary aldosteronism. METHODS: This was a retrospective single-center study that included patients who underwent adrenalectomy for primary aldosteronism between 2000 and 2023. Blood pressure, a defined daily dose of antihypertensives, and potassium supplementation were incorporated into a new Primary Aldosteronism Disease Severity Score (PADSS), which was calculated with preoperative and 6-month postoperative parameters. RESULTS: The study included 201 patients. Adrenalectomy was guided by adrenal venous sampling in 86.1% of patients. The cure rate per the new definition of normal blood pressure was 7.5% (n = 15). The median PADSS was 16.3 (13.6-19.9) preoperatively and decreased to 10 (4.5-13.3) postoperatively. An improvement of the PADSS was observed in 90% (n = 180) of patients at 6 months of adrenalectomy. The median rate of improvement in PADSS was 33.3% (13.8% to 56.6%). CONCLUSIONS: Although complete cure rates are low after adrenalectomy in primary aldosteronism, especially based on the new definition of normal blood pressure, a clinical improvement is seen in the vast majority of patients postoperatively. The newly introduced PADSS can be used to assess the clinical benefit achieved with adrenalectomy.

Bilateral superselective adrenal artery embolization for bilateral primary aldosteronism: a novel approach in an efficacy and safety proof-of-principle trial.

Superselective adrenal artery embolization (SAAE) offers a novel approach for treating primary aldosteronism (PA). In this study, we aimed to assess the efficacy and safety of SAAE for the treatment of PA based on the lateralization results obtained from adrenal vein sampling (AVS).In this prospective study, we enrolled 40 patients with PA who underwent SAAE. The patients were categorized into two groups, unilateral PA and bilateral PA, based on AVS results. Clinical parameters and biochemical markers were assessed at 3 and 12 months postoperatively. The primary outcomes were changes in blood pressure and defined daily dose (DDD) of antihypertensive medications compared to baseline. Thirty-eight patients achieved technical success, with favorable clinical and biochemical efficacy rates. At three months postoperatively, the clinical efficacy rates were 79.2% and 78.6% for the UPA and BPA groups, respectively. At 12 months, the rates were 83.3% and 71.4%, respectively. Both groups exhibited a significant decrease in average blood pressure at 3 and 12 months compared with baseline (P < 0.001), and there was also a notable reduction in DDD (P < 0.05). At three months, the biochemical efficacy rates were 61.9% and 58.3% in the UPA and BPA groups, respectively. Due to loss to follow-up, biochemical indicators were not assessed at 12 months postoperatively. No severe adverse reactions occurred during or after SAAE. Patients with both UPA and BPA can benefit from SAAE. The superiority of bilateral adrenal artery embolization in the treatment of BPA over unilateral adrenal artery embolization requires further investigation.

Typing diagnostic value of 68Ga-pentixafor PET/CT for patients with primary aldosteronism and unilateral nodules.

PURPOSE: Our goal was to compare the lateralization of 68Ga-pentixafor PET/CT with adrenal vein sampling (AVS) in primary aldosteronism (PA) patients with unilateral lesions. METHODS: We retrospectively enrolled 61 patients with PA and all patients showed unilateral nodular lesions on CT and underwent 68Ga-Pentixafor PET/CT. The general clinical data, imaging and AVS results were collected. The diagnostic efficiency of 68Ga-Pentixafor PET/CT imaging in PA patients was calculated by visual and semi-quantitative analysis to compare the consistency with AVS, and the correlation between CXCR4 express and 68Ga-Pentixafor uptake was performed. RESULTS: The study included 42 unilateral PA (UPA) and 19 bilateral PA (BPA). The area under curve (AUC) of 68Ga-Pentixafor PET/CT to diagnosis UPA with 10 min maximum standardized uptake value (SUVmax) > 8.17 was 0.82 ([0.70-0.90], P < 0.001), and the sensitivity and specificity were 0.64 and 0.90, respectively. The maximal AUC of 68Ga-pentixafor PET/CT for the diagnosis UPA in patients with nodules with a diameter ≥1 cm was 0.87 ([0.73-0.95],P both <0.001,[10 min SUVmax=8.17 and 10 min mean standardized uptake value (SUVmean)=5.57]), and the sensitivity and specificity were 0.73 and 0.93, respectively. Unilateral adrenalectomy and significant CXCR4 expression were present in 32 UPA, including 27 aldosterone-producing adenoma and 5 idiopathic adrenal hyperplasia. Additionally, 68Ga-pentixafor uptake in adrenal lesions was significantly correlated with CXCR4 expression, and statistical differences in 68Ga-pentixafor uptake among IRS subgroups. CONCLUSIONS: 68Ga-Pentixafor PET/CT can be helpful for subtyping diagnosis of PA patients with unilateral adrenal nodular, showing significant potential in non-invasive PA classification.

Endothelial epoxyeicosatrienoic acid release is intact in aldosterone excess.

BACKGROUND AND AIMS: Endothelial dysfunction (ED) is considered to be a major driver of the increased incidence of cardiovascular disease in primary aldosteronism (PA). The functionality of the epoxyeicosatrienoic acid (EET) pathway, involving the release of beneficial endothelium-derived lipid mediators, in PA is unknown. Evidence suggests this pathway to be disturbed in various models of experimental hypertension. We therefore assessed EET production in primary human coronary artery endothelial cells exposed to aldosterone excess and measured circulating EET in patients with PA. METHODS: We used qPCR to investigate changes in the expression levels of essential genes for the synthesis and degradation of EET, calcium imaging to address the functional impact on overall endothelial function, as well as mass spectrometry to determine endothelial synthetic capacity to release EET upon stimulation. RNA-seq was performed to gain further mechanistic insights. Eicosanoid concentrations in patient's plasma were also determined by mass spectrometry. RESULTS: Aldosterone, while eliciting proinflammatory VCAM1 expression and disturbed calcium response to acetylcholine, did not negatively affect stimulated release of endothelial EET. Likewise, no differences were observed in eicosanoid concentrations in plasma from patients with PA when compared to essential hypertensive controls. However, an inhibitor of soluble epoxide hydrolase abrogated aldosterone-mediated VCAM1 induction and led to a normalized endothelial calcium response probably by restoring expression of CHRNE. CONCLUSION: EET release appears intact despite aldosterone excess. Epoxide hydrolase inhibition may revert aldosterone-induced functional changes in endothelial cells. These findings indicate a potential new therapeutic principle to address ED, which should be explored in future preclinical and clinical trials.

[131I]6ß-Iodomethyl-19-norcholesterol SPECT/CT for the Lateralization of Mineralocorticoid Overproduction in Primary Aldosteronism.

Primary: aldosteronism is a frequent cause of secondary hypertension. With access to specialized care, an increasing number of patients with aldosteronism are being identified. Primary aldosteronism is treatable by adrenal surgery if aldosterone excess originates from one of the two, and not from both, adrenals. Bilateral hyperplasia requires lifelong mineralocorticoid receptor antagonist treatment. Up till now, adrenal venous sampling (AVS) has been widely used to distinguish between one-sided and two-sided aldosterone overproduction and patient selection for surgery. AVS is an invasive technique, and the unsuccessful sampling of the right adrenal vein during AVS often prevents side comparison, making the AVS procedure useless. Molecular imaging using [131I]6ß-iodomethyl-19-norcholesterol with SPECT CT imaging (SPECT/CT) may be a potential alternative. METHODS: In 42 consecutive patients with confirmed primary aldosteronism, molecular imaging has been performed. After dexamethasone suppression of the non-affected adrenal tissue, 37 MBq [131I]6ß-iodomethyl-19-norcholesterol was injected i.v., and SPECT/CT images were taken 7 days later. Based on the visual evaluation of the images by two nuclear medicine specialists, patients with one-sided tracer accumulation underwent adrenalectomy. To identify a SPECT/CT parameter that best characterizes the side difference, the maximum counts and the mean counts of spherical VOIs were analyzed. RESULTS: Of the 42 patients, 24 had one-sided aldosterone overproduction by SPECT/CT. After surgical removal of the involved adrenal, all 24 patients with SPECT/CT-identified unilateral aldosteronism achieved biochemical cure, defined as a normalized potassium level combined with an aldosterone-to-renin ratio ≤ 30. To identify the best measurable parameter of SPECT/CT side difference, the mean counts and maximum counts of a series of spherical VOIs of different diameters were analyzed. The ratio of the mean counts of 3 cm spherical VOIs of the right and left adrenal regions (lateralization index) was the best discriminator; a ratio of ≥1.29 was characteristic of one-sided disease, without overlap between the one-sided and two-sided patient groups. CONCLUSIONS: [131I]6ß-iodomethyl-19-norcholesterol SPECT/CT with a count-based image interpretation and side-ratio calculation may be an equipollent non-invasive substitute for adrenal venous sampling in the lateralization of mineralocorticoid overproduction. It reliably identifies unilateral disease and facilitates patients' selection for surgical intervention. If confirmed by others, this functional imaging may replace AVS when lateralization is required for management decisions in primary aldosteronism.

Bilateral adrenal artery embolization for the treatment of idiopathic hyperaldosteronism: A proof-of-principle single center study.

Unilateral adrenal artery embolization (AAE) has emerged as an alternative treatment for patients with primary aldosteronism due to aldosterone-producing adenomas or idiopathic hyperaldosteronism with bilateral adrenal hyperplasia. This study aimed to investigate the effectiveness and safety of bilateral AAE in idiopathic hyperaldosteronism. We enrolled a total of 58 patients with idiopathic hyperaldosteronism who underwent successful bilateral AAE, and 55 of them completed 6-month follow-up. Bilateral AAE significantly lowered blood pressure of patients with IHA at 1, 3, and 6 months (all P < 0.01). Six months after the procedure, office, home, and 24-hour ambulatory blood pressure decreased by 20.3/13.5, 18.4/12.6, and 13.7/9.9 mmHg, respectively. Among them, 92.7%, 90.9%, and 89.1% had significant or moderate improvement in blood pressure control at 1, 3, and 6 months after the procedure. Bilateral AAE substantially decreased plasma aldosterone levels, reversed plasma renin suppression, decreased aldosterone-to-renin ratio, and corrected hypokalemia. Importantly, the procedure did not significantly change serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels, and the cortisol and ACTH circadian rhythms remained intact three months after the procedure. Additionally, 16 patients underwent ACTH stimulation tests three months post-procedure and all of them had normal results except for one with a decreased response due to exogenous steroid therapy. Flank pain was the most common side effect which happened in 96.4% of the patients and resolved within 48 h. There were no long-term side effects in the 6 months. The present study provides evidence that bilateral AAE is an effective and safe alternative treatment for patients with IHA. Changes in office and 24h ambulatory blood pressure at 1, 3, and 6 months after bilateral adrenal artery embolization in patients with idiopathic hyperaldosteronism.

Suppressed Renin Status Is a Risk Factor for Cardiocerebrovascular Events in Bilateral Primary Aldosteronism Treated With Mineralocorticoid Receptor Antagonists.

OBJECTIVE: Mineralocorticoid receptor antagonists are the recommended medical therapy for bilateral primary aldosteronism (BPA). Patients with BPA have higher risk of cardiocerebrovascular disease (CCVD) than those with essential hypertension. There is no consensus on the criteria to assess the effectiveness of medical therapy for BPA. This study aimed to investigate the incidence of and risk factors for CCVD after medical therapy of BPA. METHODS: We conducted a retrospective cohort study including 240 patients with BPA treated with mineralocorticoid receptor antagonists. The posttreatment plasma renin activity (PRA) was defined as unsuppressed (PRA, ≥1 ng/mL/h); otherwise, it was defined as suppressed. We analyzed the association of posttreatment PRA status with CCVD outcomes. RESULTS: Of patients with BPA, 7.1% (17/240) developed CCVD at a median follow-up of 5.0 (range, 2.96-7.66) years. Moreover, 57.1% of patients had a PRA of ≥1 ng/mL/h after treatment. Patients with a PRA of <1 ng/mL/h had a higher incidence of CCVD (12.6% vs 2.9%, P < .05) and were at higher risk than those with a PRA of ≥1 ng/mL/h (hazard ratio, 4.50 [95% CI, 1.47-13.83; P < .05]; adjusted hazard ratio, 3.98 [95% CI, 1.22-13.02; P < .05]). CONCLUSION: Patients with BPA who receive pharmacologic treatment have a high incidence of CCVD. PRA may be an indicator that mineralocorticoids are being adequately antagonized.