Adrenal venous sampling is the procedural standard for identifying patients with primary hyperaldosteronism who may benefit from adrenalectomy. Patients with unilateral aldosterone excess are considered surgical candidates, often referred to as having surgically remediable aldosteronism. Those with bilateral aldosterone excess are typically treated with mineralocorticoid receptor agonists. In this article, the authors present 3 interesting cases that underscore the importance of data analysis. Additionally, they emphasize that primary aldosteronism represents a spectrum of aldosterone production, highlighting the fundamental need for long-term follow-up due to the significant variability in patient responses to treatment.

This study aimed to explore the noninvasive and accurate evaluation methods of primary aldosteronism (PA) classification.

There were 99 patients with aldosterone-producing adenoma (APA) and 61 with idiopathic hyperaldosteronism recruited in this study. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gallium-68 (68Ga)-pentixafor positron emission tomography (PET)/computed tomography (CT) were performed in this cohort. Statistical analysis was used to calculate the diagnostic efficiency of single or double methods.

In steroid profiling detected by LC-MS/MS, the average levels of 6 steroids apart from aldosterone in the APA group were higher than those in the idiopathic hyperaldosteronism group. The differential diagnostic efficiency of 18-oxocortisol (cutoff value at 0.132 ng/mL) was greater than other steroids, with a sensitivity of 75.3% and specificity of 91.2%. As for 68Ga-pentixafor PET/CT, visual analysis showed a sensitivity of 93.7% and specificity of 56.3%. At the optimum maximum standardized uptake value of 8.00, the sensitivity was 69.8%, and the specificity was 93.7%. Taking into account the 18-oxocortisol level and 68Ga-pentixafor PET/CT maximum standardized uptake value, 100% of patients with double positive results were placed in the right APA subtype. If the 18-oxocortisol level with 68Ga-pentixafor PET/CT visual analysis was combined for PA subtyping, the sensitivity of at least 1 positive was 95.2%, and a total of 87.2% of patients could be classified correctly.

The LC-MS/MS and 68Ga-pentixafor PET/CT have great advantages on the subtyping of PA. There was a high accuracy of the combination of the 2 methods, which will contribute to avoid an unnecessary adrenal venous sampling operation before surgery for most patients with PA.

Primary aldosteronism (PA) is the most common secondary hypertension. The best treatment for a lateralized PA is unilateral adrenalectomy. Recent studies explored partial adrenalectomy (pAdx) to reduce the risk of adrenal insufficiency. However, in cases involving multiple aldosterone-producing micronodules/nodules (mAPM/mAPN), pAdx cannot completely remove all origins of excess aldosterone and might not resolve hypertension. CYP11B2 immunohistochemical staining helps HISTALDO (Histopathology of PA) diagnosis, and adrenal specimens were categorized into various groups accordingly. To determine whether pAdx should be considered for lateralized PA, we focused on the success rate of classical (black + grey group) versus non-classical (white group) lateralized PA, and the percentage of co-existing mAPM/mAPN in lateralized PA. The visible tumor in imaging could be either non-functional (incidentaloma; white group), or with concurrent surrounding mAPM/mAPN (grey group) causing hypertension. Among 445 patients who underwent unilateral adrenalectomy, 390 were diagnosed with lateralized PA. There were 63 (30.73%) in the black, 79 (38.54%) in the grey, 63 (30.73%) in the white group. The overall complete clinical success rate was 51.28% in our lateralized PA patients; with 65.08% in the black, 50.63% in the grey, and 26.98% in the white group. The overall partial clinical success rate was 38.54%; with 28.57% in the black, 34.18% in the grey, and 53.97% in the white group. Were pAdx performed, significantly lower success rates would be achieved, especially for lateralized PA patients of the grey and white groups. We speculate that unilateral pAdx is not an appropriate option for the majority of lateralized PA patients. Our results show that unilateral partial adrenalectomy is not a good surgical option for the majority of lateralized PA patients. In clinically lateralized PA patients, no matter which group they are in the HISTALDO classification, they would benefit from unilateral total adrenalectomy.

Background Primary aldosteronism can arise from one or both adrenal glands. Adrenal vein sampling (AVS) is the standard of care for identifying patients with lateralized primary aldosteronism who would benefit from surgery. Variability in AVS lateralization has been primarily attributed to cosyntropin use and lateralization index thresholds. Data regarding intraprotocol variability are lacking. Purpose To assess the rates of intraprotocol lateralization inconsistency during simultaneous AVS. Materials and Methods This retrospective cross-sectional study assessed patients with primary aldosteronism who underwent simultaneous AVS at a single tertiary referral center between January 2015 and December 2023. Six sets of adrenal vein and peripheral vein samples were obtained: three baseline samples obtained after cannulation, 5 minutes apart; and three samples obtained between 5 and 30 minutes after cosyntropin stimulation. Patients with successful cannulation and valid hormonal data at all six time points were included. A lateralization index (computed as the aldosterone-to-cortisol ratio between the two adrenal veins, with the highest number as numerator) of at least 4 was considered indicative of lateralized primary aldosteronism. The proportions of baseline and stimulated AVS sets within which one of three lateralization indexes provided different subtype results were assessed. Linear mixed-effects models were used to estimate the between- and within-patient hormonal and lateralization index variances. Results Of 402 patients (median age, 53 years; IQR, 45-63 years; 233 male) included, 129 patients (32.1%) had at least one lateralization index inconsistency. Of these 402 patients, 89 patients (22.1%) had lateralization inconsistencies within the baseline sets, 53 patients (13.2%) within cosyntropin-stimulated sets, and 13 patients (3.2%) in both baseline and cosyntropin-stimulated sets. The highest outlier prevalence occurred in the first (42 patients; 10.4%) and third (33 patients; 8.2%) baseline samples, with roughly twofold-lower rates in the first (23 patients; 5.7%) and last postcosyntropin stimulation samples (4.2%; 17 patients). The absolute change in baseline and cosyntropin-stimulated lateralization index (maximum-minimum lateralization index within a triplicate) was as high as 152.9 and 327.4, respectively. The highest hormonal variability was noted in the adrenal vein producing less aldosterone. Conclusion Almost a third of patients undergoing AVS in triplicate, both before and after cosyntropin stimulation, had intraprotocol discrepancies in lateralization results, with the highest variability occurring within samples obtained without cosyntropin stimulation. © RSNA, 2025 See also the editorial by Georgiades in this issue.

Adrenal vein sampling (AVS) is the standard-of-care for primary aldosteronism (PA) subtyping. Paradoxical bilateral aldosterone suppression (BAS), defined by lower aldosterone/cortisol ratio in both adrenal veins compared to peripheral circulation, has been reported in AVS studies, but the underlying causes remain poorly understood. We aimed to assess the prevalence of BAS in AVS without and with cosyntropin stimulation based on clinical immunoassays, and to probe the BAS results using liquid chromatography mass spectrometry (LC-MS/MS).

We retrospectively assessed the BAS prevalence among patients with confirmed PA who underwent AVS in a referral center between 2015 and 2023. Simultaneous AVS was performed both before and after cosyntropin stimulation. LC-MS/MS quantitation of cortisol and aldosterone was performed in patients with serum available.

Of 402 patients, BAS was observed in 102 (25%): Pre-cosyntropin in 31, post-cosyntropin in 48 (including 10 who did not meet successful catheterization criteria in baseline samples), and both pre- and post- cosyntropin in 23. Paradoxically, AVS indicated lateralized PA in 36% and 43% of patients with BAS based on pre- and post-cosyntropin data, respectively. Using LC-MS/MS, BAS was not present in 42/53 (79%) patients with serum available. Compared to LC-MS/MS, immunoassays overestimated cortisol across the analytical range. In contrast, for aldosterone, immunoassays overestimated low concentrations, but underestimated high concentrations, such as those measured in adrenal veins.

Apparent BAS derives primarily from artifacts in clinical immunoassays. These data caution against assuming that aldosterone suppression indicates contralateral aldosterone lateralization in cases with partial adrenal vein catheterization failure.

To investigate the relationship between plasma aldosterone concentration (PAC) and the prevalence of peripheral artery disease (PAD) in hypertensive patients and to determine any potential threshold effects.

This cross-sectional study analyzed data from 13,157 hypertensive individuals from the People's Hospital of Xinjiang Uygur Autonomous Region, China. PAD was diagnosed based on an ankle-brachial index (ABI) of ≤0.90. A multivariate logistic regression model was utilized to evaluate the association between PAC and PAD, and a generalized additive model (GAM) was employed to explore non-linear relationships.

The fully adjusted logistic regression model revealed a significant positive association between PAC and PAD, with an odds ratio (OR) [95% confidence interval (CI)] of 1.06 (1.04, 1.08) per unit increase in PAC. The GAM identified a critical threshold at 17.00 ng/dl for PAC, above which the prevalence of PAD increased by 9% for each unit increase in PAC, with an OR (95% CI) of 1.09 (1.06, 1.11). Sensitivity and subgroup analyses confirmed the robustness of these findings.

This study establishes a non-linear relationship between PAC and the prevalence of PAD in hypertensive patients, with a critical threshold at 17.00 ng/dl. These findings underscore the importance of aldosterone homeostasis in vascular health and the need for further large-scale, prospective studies to validate these results and explore their clinical implications.

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.

Primary aldosteronism affects 20% of patients with resistant hypertension and may be due to unilateral or bilateral causes. Patients with a unilateral source of aldosterone secretion are potentially curable with adrenalectomy. Adrenal vein sampling (AVS) is the definitive test for subtype differentiation but may not be accessible outside tertiary centers. The goal of this study was to determine whether clinical characteristics can predict a unilateral source of aldosterone on AVS.

Patients with a biochemical diagnosis of primary aldosteronism who underwent AVS between 1998 and 2019 were identified from a prospectively maintained database. Unilateral aldosterone secretion was defined as lateralization index ≥4. Univariate and multivariate logistic regression were used to assess the correlation between clinical characteristics and unilateral aldosterone secretion. A risk score was developed to predict a unilateral source of aldosterone.

Of 461 patients, 61% were male and 39% female. The mean age was 54 ± 11 y, and median duration of hypertension was 10 (interquartile range: 5-20) y. A total of 324 patients had unilateral aldosterone secretion. On multivariate logistic regression analysis, non-Black race, lower body mass index, shorter duration of hypertension, and nonincidental diagnoses were significantly associated with a unilateral source of aldosterone. Neither age nor an adrenal adenoma on imaging was predictive of a unilateral aldosterone source. The clinical risk score had an 86% positive predictive value for a unilateral source of aldosterone.

Clinical characteristics imperfectly predict subtype differentiation. However, high clinical risk scores have a strong positive predictive value for a unilateral source of aldosterone.

Compared with chemiluminescence immunoassay (CLIA), the quantification of the plasma aldosterone concentration (PAC) via liquid chromatography-tandem mass spectrometry (LC-MS/MS) yields lower values. The extent to which this difference is exacerbated by a reduced glomerular filtration rate (eGFR) is unclear. Therefore, this study aims to assess the impact of renal insufficiency on PAC as measured by CLIA using LC-MS/MS as the reference method.

In subjects with a normal or reduced estimated eGFR, the PAC was measured using both LC-MS/MS and two different CLIA kits (Mindray and Liaison).

In total, 383 patients were included in our study. Among them, 71 subjects had eGFRs > 90 (Group one), 79 had eGFRs range from 60 to 89 (Group two), 108 had eGFR range from 30 to 59 (Group three), 51 had eGFRs range from 15 to 29 (Group four), and 74 had eGFRs < 15 (Group five) ml/min per 1.73 m2. In all the subjects, PAC as measured by CLIA [68.2 (37.1-122.1) pg/ml for Mindray, 109.0 (68.1-170.0) pg/ml for Liaison] were significantly higher than those measured by LC-MS/MS [47.2 (22.9-88.7) pg/ml]. PAC as measured by CLIA was positively correlated with PAC as measured by LC-MS/MS, but the correlation coefficient gradually decreased as eGFR decreased. Between the LC-MS/MS and Liaison CLIA kits, the difference in PAC values increased with reduced eGFR in groups one through five (76.8 %, 69.2 %, 113.2 %, 152.2 %, and 476.2 % for groups one through five, respectively). However, this difference increased only in Group five with the Mindray CLIA kit (46.4 %, 48.1 %, 45.7 %, 45.0 %, and 74.9 % for groups one through five, respectively).

CLIA progressively overestimated PAC as eGFR decreased, particularly with the Liaison method, indicating the need for caution when interpreting these measurements in patients with impaired renal function. In patients with impaired renal function, LC‒MS/MS measurements for PAC are preferable.

Primary aldosteronism is predominantly caused by excessive aldosterone production from the adrenal cortex, and the aldosterone-producing structures could take many forms, like adenomas, nodules, micronodules, and so on. Most studies of primary aldosteronism were limited to the hotspot driver genes responsible for autonomous aldosterone production; however, the panoramic genetic architecture and genomic alterations of aldosterone-producing structures and their adjacent hyperplasia glands remain unknown.

In this study, whole-exome sequencing and transcriptome sequencing (RNA-seq) analyses were performed using functional nodules and matched hyperplasia tissues, which were microdissected guided by aldosterone synthase immunohistochemistry. Phylogenetic trees were constructed based on the shared and unique mutations, gene mutation spectrums, and clonal characteristics.

The rates of mutations represented higher means of functional nodules than hyperplasia samples, and the little mutational overlap was shown between the 2 groups on phylogenetic trees. The mutations of the aldosterone driver gene (KCNJ5 or CACNA1D) were only observed in functional nodules and indicated almost the largest values of cancer cell fraction. Moreover, the functional nodules also harbored some potential variants related to cell proliferation, which were not detected in hyperplasia tissues. Transcriptome analysis suggested that only 25.5% upregulated and 23.3% downregulated genes overlapped between functional nodules and hyperplasia tissues.

This study demonstrated a genetic and transcriptome landscape of aldosterone-producing structures and adjacent hyperplasia glands in primary aldosteronism. The results indicated independent clonal origins on functional nodules and hyperplasia tissues, and little mutual evolutionary relationship was found on their phylogenetic trees.

In this study, we developed and validated machine learning models to predict primary aldosteronism (PA) in hypertensive East-Asian patients, comparing their performance against the traditional saline infusion test. The motivation for this development arises from the need to provide a more efficient and standardized diagnostic approach, because the saline infusion test, although considered a gold standard, is often cumbersome, is time-consuming, and lacks uniform protocols. By offering an alternative diagnostic method, this study seeks to enhance patient care through quicker and potentially more reliable PA detection.

This study sought to both develop and evaluate the performance of machine learning models in detecting PA among hypertensive participants, in comparison to the standard saline loading test.

We used patient data from 3 distinct cohorts: TAIPAI (Taiwan Primary Aldosteronism Investigation), CONPASS (Chongqing Primary Aldosteronism Study), and a South Korean cohort. Random Forest's importance scores, XGBoost, and deep learning techniques are adopted to identify the most predictive features of primary aldosteronism.

We present detailed results of the model's performance, including accuracy, sensitivity, and specificity. The Random Forest model achieved an accuracy of 0.673 (95% CI: 0.640-0.707), significantly outperforming the baseline models.

In our discussion, we address both the strengths and limitations of our study. Although the machine learning models demonstrated superior performance in predicting primary aldosteronism, the generalizability of these findings may be limited to East-Asian hypertensive populations. Future studies are needed to validate these models in diverse demographic settings to enhance their applicability.

The aim of this study is to evaluate performance of aldosterone-to-renin ratio (ARR) before washout of antihypertensive drugs as a screening test for primary aldosteronism (PA).

This retrospective analysis included consecutive patients screening for secondary hypertension during a period from January 2017 to May 2022 at the authors' institute. For inclusion in the final analysis, ARR had to be available prior to as well as after discontinuation of antihypertensives. Patients with ARR ≥2.4(ng/dL)/(μIU/mL) after washout proceeded to confirmatory tests. Diagnosis of PA was established based on a positive result of the confirmatory test. The diagnostic accuracy of ARR prior to the washout in predicting PA is shown as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).

The analysis included a total of 1306 patients [median age of 50.2 (41.0-59.0) years, 64.0% male]. Confirmatory tests showed PA in 215(16.5%) patients and essential hypertension (EH) in the remaining 1091(83.5%) patients. In comparison to the second screening test, the first screening test (before washout of antihypertensives) yielded lower plasma aldosterone and higher renin and consequently lower ARR in both the PA and EH groups. At a cutoff of .7(ng/dL)/(μIU/mL), ARR before washout had 96.3% sensitivity, 61.2% specificity, .33 PPV, and .99 NPV. At a lower cutoff of .5(ng/dL)/(μIU/mL), the sensitivity, specificity, PPV, and NPV were 97.7%, 52.0%, .29, and .99, respectively.

ARR prior to washout of antihypertensives is a sensitive screening test for PA. Washout of antihypertensives could be omitted and further investigation for PA is not warranted if ARR is ≤ .7(ng/dL)/(μIU/mL) before washout.

Hypertension remains a significant global health issue, increasingly affecting younger populations due to lifestyle and dietary changes. This case report presents a 28-year-old male diagnosed with primary hyperaldosteronism, a rare but treatable cause of secondary hypertension, presenting as hypertensive urgency. The patient reported persistent headaches and weakness, with an initial blood pressure of 190/120 mmHg and severe hypokalemia. Through a systematic diagnostic approach, including biochemical and imaging assessments, unilateral adrenal hyperplasia was identified as the cause of primary hyperaldosteronism. Targeted treatment, including antihypertensive agents, potassium supplementation, and mineralocorticoid receptor antagonists, led to significant improvements in blood pressure and electrolyte levels. This case underscores the importance of considering secondary hypertension causes in young adults and the potential for positive outcomes with accurate, resource-conscious diagnostic and management strategies.

Resistant and uncontrolled hypertension are common presentations to the nephrology clinic. Many of these patients benefit from evaluation for secondary hypertension in order to optimize antihypertensive therapy and reduce the risks of target organ damage from uncontrolled hypertension. The purpose of this review is to present several cases of difficult-to-control and/or secondary hypertension and to identify optimal approaches to evaluating and managing hypertension in these high-risk patients.

Arterial hypertension in young adults, which includes patients between 19 and 40 years of age, has been increasing in recent years and is associated with a significantly higher risk of target organ damage and short-term mortality. It has been reported that up to 10% of these cases are due to a potentially reversible secondary cause, mainly of endocrine (primary aldosteronism, Cushing's syndrome, and pheochromocytoma/paraganglioma), renal (renovascular hypertension due to fibromuscular dysplasia and renal parenchymal disease), or cardiac (coarctation of the aorta) origin. It is recommended to rule out a secondary cause of high blood pressure (BP) in those patients with early onset of grade 2 or 3 hypertension, acute worsening of previously controlled hypertension, resistant hypertension, hypertensive emergency, severe target organ damage disproportionate to the grade of hypertension, or in the face of clinical or biochemical characteristics suggestive of a secondary cause of hypertension. The 2023 Guideline of the European Society of Hypertension recommends starting pharmacological therapy from grade 1 hypertension (BP ≥140/90 mm Hg), with the aim of achieving BP control of less than 130/80 mm Hg. It is important to highlight that the prevalence of secondary hypertension in these patients could be underestimated, given that there is little evidence available on the management of high BP in young adults, which is why we developed this narrative review on the diagnostic and therapeutic approach to the major secondary causes of arterial hypertension in young adults.

Primary aldosteronism (PA) diagnosis is affected by antihypertensive drugs that are commonly taken by patients with suspected PA. In this study, we developed and validated a diagnostic model for screening PA without drug washout.

We retrospectively analyzed 1095 patients diagnosed with PA or essential hypertension. Patients were randomly grouped into training and validation sets at a 7:3 ratio. Baseline characteristics, plasma aldosterone concentration (PAC), and direct renin concentration (DRC) before and after drug washout were separately recorded, and the aldosterone-to-renin ratio (ARR) was calculated.

PAC and ARR were higher and direct renin concentration was lower in patients with PA than in patients with essential hypertension. Furthermore, the differences in blood potassium and sodium concentrations and hypertension grades between the two groups were significant. Using the abbreviations potassium (P), ARR (A), PAC (P), sodium (S), and hypertension grade 3 (3), the model was named PAPS3. The PAPS3 model had a maximum score of 10, with the cutoff value assigned as 5.5; it showed high sensitivity and specificity for screening PA in patients who exhibit difficulty in tolerating drug washout.

PA screening remains crucial, and standard guidelines should be followed for patients to tolerate washout. The PAPS3 model offers an alternative to minimize risks and enhance diagnostic efficiency in PA for those facing washout challenges. Despite its high accuracy, further validation of this model is warranted through large-scale clinical studies.

We report a case of a ruptured triple hormone-secreting adrenal mass with hyperaldosteronism, hypercortisolism, and elevated normetanephrine levels, diagnosed as adrenal cortical carcinoma (ACC) by histology. A 53-year-old male patient who initially presented with abdominal pain was referred to our hospital for angiocoagulation of an adrenal mass rupture. Abdominal computed tomography revealed a heterogeneous 19×11×15 cm right adrenal mass with invasion into the right lobe of the liver, inferior vena cava, retrocaval lymph nodes, and aortocaval lymph nodes. Angiocoagulation was performed. Laboratory evaluation revealed excess cortisol via a positive 1-mg overnight dexamethasone suppression test, primary hyperaldosteronism via a positive saline infusion test, and plasma normetanephrine levels three times higher than normal. An adrenal mass biopsy was performed for pathological confirmation to commence palliative chemotherapy because surgical management was not deemed appropriate considering the extent of the tumor. Pathological examination revealed stage T4N1M1 ACC. The patient started the first cycle of adjuvant mitotane therapy along with adjuvant treatment with doxorubicin, cisplatin, and etoposide, and was discharged. Clinical cases of dual cortisol- and aldosterone-secreting ACCs or ACCs presenting as pheochromocytomas have occasionally been reported; however, both are rare. Moreover, to the best of our knowledge, a triple hormone-secreting ACC has not yet been reported. Here, we report a rare case and its management. This case report underscores the necessity of performing comprehensive clinical and biochemical hormone evaluations in patients with adrenal masses because ACC can present with multiple hormone elevations.

Congenital adrenal hyperplasia (CAH) is an uncommon genetic disorder which affects cortisol production in the adrenal glands. It is usually treated with glucocorticoids. We present a case of non-classical CAH caused by the partial deficiency of 11 beta-hydroxylase (11βOH) which was treated with aldosterone antagonist (eplerenone) monotherapy.

An adolescent male was diagnosed with 11 beta-hydroxylase deficiency (11βOHD) at 13 years of age when he presented with hypertension, fatigue and headaches. He was initially treated with glucocorticoids, but requested an alternative therapy. Eplerenone was commenced at 25 mg with subsequent dose increases to 100 mg daily. His hypertension was controlled on this regimen, achieving a 24 h average blood pressure of 124/81 mmHg.

CAH caused by 11βOHD is a known cause of hypertension. It is usually managed with glucocorticoids, and antihypertensives are added if blood pressure remains uncontrolled. In this case, glucocorticoid therapy was not tolerated and treatment with aldosterone antagonist monotherapy was effective in controlling his hypertension.

The diagnosis of primary aldosteronism (PA) is critical for determining treatment strategies. The aim of the present study was to investigate the clinical value of preoperative adrenal venous sampling (AVS) for determining the benefit of PA surgery. Patients diagnosed with PA at Liaocheng People's Hospital (Liaocheng, China) between January 2015 and December 2020 were selected and divided into two groups: Group A underwent adrenal computed tomography (CT) only, whereas Group B underwent adrenal CT and successful AVS. Subsequently, the improvement rate of adrenal CT and adrenal CT + AVS in the treatment of PA was compared. A total of 164 patients were included, with an average age of 46.69±13.64 years. There were 62 patients in Group A and 102 in Group B. Among the patients diagnosed with unilateral lesions on adrenal CT scan, 82.61% of patients in group A and 87.72% in group B showed improvement; however, the difference was not significant (χ2=0.534, P=0.465). Among the patients diagnosed with bilateral lesions on adrenal CT images, 62.50% of patients in Group A and 91.11% of patients in Group B showed improvement (P=0.019). In conclusion, unilateral adrenal lesions detected by CT did not benefit significantly from surgical decision-making after AVS. AVS should be advised for all patients with bilateral adrenal PA who are willing to undergo adrenal surgery, which is conducive to correct lateral segmentation and improve treatment choices.

Primary aldosteronism is a form of low-renin hypertension characterized by dysregulated aldosterone production.

To investigate the contributions of renin-independent aldosteronism and ACTH-mediated aldosteronism in individuals with a low-renin phenotype representing the entire continuum of blood pressure.

Human physiology study of 348 participants with a low-renin phenotype with severe and/or resistant hypertension, hypertension with hypokalemia, elevated blood pressure and stage I/II hypertension, and normal blood pressure.

4 international centers.

The saline suppression test (SST) to quantify the magnitude of renin-independent aldosteronism; dexamethasone suppression and ACTH-stimulation tests to quantify the magnitude of ACTH-mediated aldosteronism; adrenal venous sampling to determine lateralization.

There was a continuum of nonsuppressible and renin-independent aldosterone production following SST that paralleled the magnitude of the blood pressure continuum and transcended conventional diagnostic thresholds. In parallel, there was a full continuum of ACTH-mediated aldosteronism wherein post-SST aldosterone levels were strongly correlated with ACTH-stimulated aldosterone production (r = 0.75, P < .0001) and nonsuppressible aldosterone production postdexamethasone (r = 0.40, P < .0001). Beyond participants who met the criteria for primary aldosteronism (post-SST aldosterone of ≥10 ng/dL or ≥277 pmol/L), the continuum of nonsuppressible and renin-independent aldosterone production persisted below this diagnostic threshold, wherein 15% still had lateralizing aldosteronism amenable to surgical adrenalectomy and the remainder were treated with mineralocorticoid receptor antagonists.

In the context of a low-renin phenotype, there is a continuum of primary aldosteronism and dysregulated aldosterone production that is prominently influenced by ACTH. A large proportion of individuals with low renin may benefit from aldosterone-directed therapy.

Primary aldosteronism (PA) is the most frequent cause of secondary hypertension and is associated with a higher cardiometabolic risk than essential hypertension. The aim of this consensus is to provide practical clinical recommendations for its surgical and medical treatment, pathology study and biochemical and clinical follow-up, as well as for the approach in special situations like advanced age, pregnancy and chronic kidney disease, from a multidisciplinary perspective, in a nominal group consensus approach of experts from the Spanish Society of Endocrinology and Nutrition (SEEN), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN), Spanish Society of Internal Medicine (SEMI), Spanish Radiology Society (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Society of Laboratory Medicine (SEQC(ML)), Spanish Society of Anatomic-Pathology and Spanish Association of Surgeons (AEC).

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.

Simple and practical tools for screening high-risk new-onset diabetes after percutaneous coronary intervention (PCI) (NODAP) are urgently needed to improve post-PCI prognosis. We aimed to evaluate the risk factors for NODAP and develop an online prediction tool using conventional variables based on a multicenter database. China evidence-based Chinese medicine database consisted of 249, 987 patients from 4 hospitals in mainland China. Patients ≥ 18 years with implanted coronary stents for acute coronary syndromes and did not have diabetes before PCI were enrolled in this study. According to the occurrence of new-onset diabetes mellitus after PCI, the patients were divided into NODAP and Non-NODAP. After least absolute shrinkage and selection operator regression and logistic regression, the model features were selected and then the nomogram was developed and plotted. Model performance was evaluated by the receiver operating characteristic curve, calibration curve, Hosmer-Lemeshow test and decision curve analysis. The nomogram was also externally validated at a different hospital. Subsequently, we developed an online visualization tool and a corresponding risk stratification system to predict the risk of developing NODAP after PCI based on the model. A total of 2698 patients after PCI (1255 NODAP and 1443 non-NODAP) were included in the final analysis based on the multicenter database. Five predictors were identified after screening: fasting plasma glucose, low-density lipoprotein cholesterol, hypertension, family history of diabetes and use of diuretics. And then we developed a web-based nomogram ( https://mr.cscps.com.cn/wscoringtool/index.html ) incorporating the above conventional factors for predicting patients at high risk for NODAP. The nomogram showed good discrimination, calibration and clinical utility and could accurately stratify patients into different NODAP risks. We developed a simple and practical web-based nomogram based on multicenter database to screen for NODAP risk, which can assist clinicians in accurately identifying patients at high risk of NODAP and developing post-PCI management strategies to improved patient prognosis.

Aldosterone secretion in primary aldosteronism (PA) is often regulated by adrenocorticotropic hormone (ACTH) in addition to its autonomous secretion. However, the clinical characteristics and risk of cardiovascular and cerebrovascular (CCV) events in PA patients with aldosterone responsiveness to ACTH stimulation remain unclear. This study aimed to investigate the prevalence of CCV events in PA patients with high aldosterone responsiveness to ACTH stimulation. A retrospective cross-sectional study was conducted as part of the Japan Primary Aldosteronism Study/Japan Rare Intractable Adrenal Disease project. PA patients with adrenal venous sampling (AVS) between January 2006 and March 2019 were enrolled. The ACTH-stimulated plasma aldosterone concentration (PAC) of the inferior vena cava during AVS was used to evaluate aldosterone responsiveness to ACTH. We analyzed the relationship between responsiveness and previous CCV events. Logistic regression analysis demonstrated that the ΔPAC (the difference between the PAC measurements before and after ACTH stimulation) significantly increased the odds of previous CCV events in PA patients after adjusting for classical CCV event risk factors, baseline PAC and duration of hypertension (relative PAC: odds ratio [OR], 2.896; 95% confidence interval [CI], 0.989-8.482; ΔPAC: OR, 2.344; 95% CI, 1.149-4.780; ACTH-stimulated PAC: OR, 2.098; 95% CI, 0.694-6.339). This study clearly demonstrated that aldosterone responsiveness to ACTH is closely related to previous CCV events. The responsiveness of the PAC to ACTH could be useful in predicting CCV event risk.Registration Number in UMIN-CTR is UMIN000032525.

To evaluate whether the clinical, biochemical and radiological features of patients with primary aldosteronism (PA) can predict both main subtypes of PA.

A retrospective multicenter study of PA patients followed in 27 Spanish tertiary hospitals (SPAIN-ALDO Register). Only patients with confirmed unilateral or bilateral PA based on adrenal venous sampling (AVS) and/or postsurgical biochemical cure after adrenalectomy were included. Supervised regression techniques were used for model development.

328 patients [270 unilateral PA (UPA), 58 bilateral PA (BPA)] were included. The area under the curve (AUC) for aldosterone/potassium ratio and aldosterone responses following saline infusion test were 0.602 [95%CI 0.520 to 0.684] and 0.574 [95% CI 0.446-0.701], respectively, to differentiate UPA from BPA. The AUC was 0.825 [95% 0.764-0.886] when the prediction model with seven parameters - comorbidities (dyslipidemia, cerebrovascular disease, sleep apnea syndrome [SAS]), systolic blood pressure (SBP), plasma aldosterone levels (PAC), hypokalemia and unilateral adrenal nodule >1 cm and normal contralateral adrenal gland on CT/MRI - was used. In patients without comorbidities, hypokalemia, SBP > 160 mmHg, PAC > 40 ng/dL, and unilateral adrenal lesions were associated with a likelihood of having a UPA of 98.5%. The chance of BPA was higher in individuals with comorbidities, SBP < 140 mmHg, normokalemia, low PAC levels, and no adrenal tumors on the CT/MRI (91.5%).

A combination of high PAC, SBP > 160 mmHg, low serum potassium, a unilateral adrenal nodule>1 cm and no comorbidities could predict a UPA with a 98.5% accuracy.

Adrenal venous sampling (AVS) is the primary method for differentiating between primary aldosterone (PA) subtypes. The aim of study is to develop prediction models for subtyping of patients with PA using computed tomography (CT) radiomics and clinicobiochemical characteristics associated with PA.

This study retrospectively enrolled 158 patients with PA who underwent AVS between January 2014 and March 2021. Neural network machine learning models were developed using a two-stage analysis of triple-phase abdominal CT and clinicobiochemical characteristics. In the first stage, the models were constructed to classify unilateral or bilateral PA; in the second stage, they were designed to determine the predominant side in patients with unilateral PA. The final proposed model combined the best-performing models from both stages. The model's performance was evaluated using repeated stratified five-fold cross-validation. We employed paired t-tests to compare its performance with the conventional imaging evaluations made by radiologists, which categorize patients as either having bilateral PA or unilateral PA on one side.

In the first stage, the integrated model that combines CT radiomic and clinicobiochemical characteristics exhibited the highest performance, surpassing both the radiomic-alone and clinicobiochemical-alone models. It achieved an accuracy and F1 score of 80.6% ± 3.0% and 74.8% ± 5.2% (area under the receiver operating curve [AUC] = 0.778 ± 0.050). In the second stage, the accuracy and F1 score of the radiomic-based model were 88% ± 4.9% and 81.9% ± 6.2% (AUC=0.831 ± 0.087). The proposed model achieved an accuracy and F1 score of 77.5% ± 3.9% and 70.5% ± 7.1% (AUC=0.771 ± 0.046) in subtype diagnosis and lateralization, surpassing the accuracy and F1 score achieved by radiologists' evaluation (p < .05).

The proposed machine learning model can predict the subtypes and lateralization of PA. It yields superior results compared to conventional imaging evaluation and has potential to supplement the diagnostic process in PA.

The prevalence of unilateral primary aldosteronism (UPA) with cortisol co-secretion varies geographically.

To investigate the prevalence and clinical characteristics of UPA with cortisol co-secretion in a Chinese population.

Retrospective cohort study.

We recruited 580 patients with UPA who underwent cosyntropin stimulation test (CST) after the 1-mg dexamethasone suppression test (DST) and retrospectively analyzed the clinical characteristics and postoperative outcomes of UPA with and without cortisol co-secretion.

UPA with cortisol co-secretion (1 mg DST>1.8 ug/dL) was identified in 65 of 580 (11.2%) patients. These patients were characterized by older age, longer duration of hypertension, higher concentration of plasma aldosterone and midnight cortisol, lower adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS), larger tumor diameter, and more history of diabetes mellitus. Cortisol and aldosterone levels were higher and DHEAS level was lower in UPA with cortisol co-secretion at 0-120 min after CST. Among 342 UPA patients with KCNJ5 gene sequencing and follow-up results, the complete clinical success rate was lower in UPA with cortisol co-secretion (33.3% vs. 56.4%, P<0.05); the complete biochemical success rate and KCNJ5 mutation did not differ between the two groups. Age, tumor size, and ACTH were independent predictors of UPA with cortisol co-secretion. Sex, BMI, duration of hypertension, KCNJ5 mutation, and cortisol co-secretion were independent predictors for complete clinical success in UPA after surgery.

UPA with cortisol co-secretion is not uncommon in China, but the clinical features were distinctly different from those without co-secretion. Cortisol co-secretion is an independent risk factor for incomplete clinical success after surgery in UPA.

The prevalence of patients with primary aldosteronism (PA) is about 5%-15% in hypertensive patients, and it is common cause of secondary hypertension in clinical practice. Two major causes of PA are noted, namely bilateral adrenal hyperplasia and aldosterone-producing adenoma, and the general diagnosis is based on three steps: (1) screening, (2) confirmatory testing, and (3) subtype differentiation (Figure 1). The recommendation for screening patients is at an increased risk of PA, here we focus on which patients should be screened for PA, not only according to well-established guidelines but for potential patients with PA. We recommend screening for 1) patients with resistant or persistent hypertension, 2) hypertensive patients with hypokalemia (spontaneous or drug-induced), 3) young hypertensive patients (age <40 years), and 4) all hypertensive patients with a history of PA in first-degree relatives. Moreover, we suggest screening for 1) hypertensive patients themselves or first-degree relatives with early target organ damage, such as stroke and other diseases, 2) all hypertensive patients with a concurrent adrenal incidentaloma, 3) hypertensive patients with obstructive sleep apnea, 4) hypertensive patients with atrial fibrillation unexplained by structural heart defects and/or other conditions resulting in the arrhythmia, 5) hypertensive patients with anxiety and other psychosomatic symptoms, and 6) hypertensive patients without other comorbidities to maintain cost-effectiveness.

To summarize the available data on the prevalence, clinical repercussion, and diagnosis of primary aldosteronism (PA) and to discuss the SPAIN-ALDO registry's findings, which is the largest PA patient registry in Spain.

A comprehensive review of the literature focused on the prevalence, clinical presentation and diagnosis of PA was performed.

PA is the most common cause of secondary arterial hypertension. In addition, PA patients have a higher cardio-metabolic risk than patients with essential arterial hypertension matched by age, sex, and blood pressure levels. However, despite its high prevalence and associated metabolic and cardiovascular complications, PA remains largely under-recognized, with less than 2% of people in at-risk populations ever tested. The diagnostic investigation is a multistep process, including screening, confirmatory testing, and subtype differentiation of unilateral from bilateral PA forms. Data from the SPAIN-ALDO registry have shed light on the cardiometabolic impact of PA and about the limitations in the PA diagnosis of these patients in Spain.

The most common cause of secondary hypertension is PA. One of the most challenging aspects of the diagnosis is the differentiation between unilateral and bilateral PA because adrenal venous sampling is a difficult procedure that should be performed in experienced centers. Data from the SPAIN-ALDO registry have provided important information on the nationwide management of this pathology.

Adrenal venous sampling (AVS) is a crucial method for the lateralization of primary aldosteronism (PA). It is advised to halt the use of the patient's antihypertensive medications and correct hypokalemia prior to undergoing AVS. Hospitals equipped to conduct AVS should establish their own diagnostic criteria based on current guidelines. If the patient's antihypertensive medications cannot be discontinued, AVS can be performed as long as the serum renin level is suppressed. The Task Force of Taiwan PA recommends using a combination of adrenocorticotropic hormone stimulation, quick cortisol assay, and C-arm cone-beam computed tomography to maximize the success of AVS and minimize errors by using the simultaneous sampling technique. If AVS is not successful, an NP-59 (131 I-6-β-iodomethyl-19-norcholesterol) scan can be used as an alternative method to lateralize PA. We depicted the details of the lateralization procedures (mainly AVS, and alternatively NP-59) and their tips and tricks for confirmed PA patients who would consider to undergo surgical treatment (unilateral adrenalectomy) if the subtyping shows unilateral disease.

Primary aldosteronism (PA) leads to kidney function deterioration after treatment, but the effects of the estimated glomerular filtration rate (eGFR) dip following adrenalectomy and its long-term implications are unclear.

This study aims to examine eGFR dip in patients with unilateral PA (uPA) after adrenalectomy and clarify their long-term prognosis.

This multicenter prospective population-based cohort study, enrolled patients with uPA who underwent adrenalectomy. Patients were divided into 4 groups based on their eGFR dip ratio. Outcomes investigated included mortality, cardiovascular composite events, and major adverse kidney events (MAKEs).

Among 445 enrolled patients, those with an eGFR dip ratio worse than -30% (n = 74, 16.6%) were older, had higher blood pressure, higher aldosterone concentration, and lower serum potassium levels. During 5.0 ± 3.6 years of follow-up, 2.9% died, 14.6% had cardiovascular composite events, and 17.3% had MAKEs. The group with eGFR dip worse than -30% had a higher risk of MAKEs (P < .001), but no significant differences in mortality (P = .295) or new-onset cardiovascular composite outcomes (P = .373) were found. Multivariate analysis revealed that patients with an eGFR dip ratio worse than -30% were significantly associated with older age (odds ratio [OR], 1.04), preoperative eGFR (OR, 1.02), hypokalemia (OR, 0.45), preoperative systolic blood pressure (OR, 1.03), and plasma aldosterone concentration (OR, 0.99).

Within 5 years post adrenalectomy, 17.3% of patients had reduced kidney function. Notably, individuals with an eGFR dip ratio worse than -30% faced higher MAKE risks, underscoring the need to monitor kidney function in PA patients after surgery.

Primary aldosteronism (PA), a significant and curable cause of secondary hypertension, is seen in 5-10% of hypertensive patients, with its prevalence contingent upon the severity of the hypertension. The principal aetiologies of PA include bilateral idiopathic hypertrophy (BIH) and aldosterone-producing adenomas (APAs), while the less frequent causes include unilateral hyperplasia, familial hyperaldosteronism (FH) types I-IV, aldosterone-producing carcinoma, and ectopic aldosterone synthesis. This condition, characterised by excessive aldosterone secretion, leads to augmented sodium and water reabsorption alongside potassium loss, culminating in distinct clinical hallmarks: elevated aldosterone levels, suppressed renin levels, and hypertension. Notably, hypokalaemia is present in only 28% of patients with PA and is not a primary indicator. The association of PA with an escalated cardiovascular risk profile, independent of blood pressure levels, is notable. Patients with PA exhibit a heightened incidence of cardiovascular events compared to counterparts with essential hypertension, matched for age, sex, and blood pressure levels. Despite its prevalence, PA remains frequently undiagnosed, underscoring the imperative for enhanced screening protocols. The diagnostic process for PA entails a tripartite assessment: the aldosterone/renin ratio (ARR) as the initial screening tool, followed by confirmatory and subtyping tests. A positive ARR necessitates confirmatory testing to rule out false positives. Subtyping, achieved through computed tomography and adrenal vein sampling, aims to distinguish between unilateral and bilateral PA forms, guiding targeted therapeutic strategies. New radionuclide imaging may facilitate and accelerate such subtyping and localisation. For unilateral adrenal adenoma or hyperplasia, surgical intervention is optimal, whereas bilateral idiopathic hyperplasia warrants treatment with mineralocorticoid antagonists (MRAs). This review amalgamates established and emerging insights into the management of 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.