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Background: Hypertension resolution following adrenalectomy in patients with primary aldosteronism (PA) remains a critical clinical challenge. Identifying preoperatively which patients will become normotensive is both a priority and a point of contention. In this narrative review, we explore the controversies and unresolved issues surrounding the prediction of hypertension resolution after adrenalectomy in PA. Methods: A comprehensive literature review was conducted, focusing on studies published between 1954 and 2024 that evaluated all studies that discussed predictive models for hypertension resolution post-adrenalectomy in PA patients. Databases searched included MEDLINE®, Ovid Embase, and Web of Science databases. Results: The review identified several predictors and predictive models of hypertension resolution, including female sex, duration of hypertension, antihypertensive medication, and BMI. However, inconsistencies in study designs and patient populations led to varied conclusions. Conclusions: Although certain predictors and predictive models of hypertension resolution post-adrenalectomy in PA patients are supported by evidence, significant controversies and unresolved issues remain. While the current predictive models provide valuable insights, there is a clear need for further research in this area. Future studies should focus on validating and refining these models. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate a nomogram combining radiomics and pathology features to distinguish between aldosterone-producing adenomas (APAs) and nonfunctional adrenal adenomas (NF-AAs). Methods: Consecutive patients diagnosed with adrenal adenomas via computed tomography (CT) or pathologic analysis between January 2011 and November 2022 were eligible for inclusion in this retrospective study. CT images and hematoxylin & eosin–stained slides were used for annotation and feature extraction. The selected radiomics and pathology features were used to develop a risk model using various machine learning models, and the area under the receiver operating characteristic curve (AUC) was determined to evaluate diagnostic performance. The predicted results from radiomics and pathology features were combined and visualized using a nomogram. Results: A total of 211 patients (APAs, n = 59; NF-AAs, n = 152) were included in this study, with patients randomly divided into either the training set or the testing set at a ratio of 8:2. The ExtraTrees model yielded a sensitivity of 0.818, a specificity of 0.733, and an accuracy of 0.756 (AUC = 0.817; 95% confidence interval [CI]: 0.675–0.958) in the radiomics testing set and a sensitivity of 0.999, a specificity of 0.842, and an accuracy of 0.867 (AUC = 0.905, 95% CI: 0.792–1.000) in the pathology testing set. A nomogram combining radiomics and pathology features demonstrated a strong performance (AUC = 0.912; 95% CI: 0.807–1.000). Conclusion: A nomogram combining radiomics and pathology features demonstrated strong predictive accuracy and discrimination capability. This model may help clinicians to distinguish between APAs and NF-AAs. [ABSTRACT FROM AUTHOR]

Aldosterone-producing adenoma (APA) is a relatively common form of benign adrenal tumor that can cause symptoms including hypertension, hypokalemia, and metabolic alkalosis. We aim to examine the safety and efficacy of laparoscopic adrenalectomy (LA) and percutaneous ablation (PA) as treatments for APA. The Embase, PubMed, Cochrane Library, Wanfang, VIP, and CINK databases were explored for related investigations, after which a meta-analysis was conducted with RevMan v5.3. In total, 4 studies including 102 and 79 APA patients treated via LA and PA, respectively, were included in this analysis, with all of these studies being retrospective in design. Pooled immediate treatment success rates, changes in serum potassium, rates of major complications, rates of minor complications, and rates of hypertensive crisis were similar in LA and PA treatment groups (P = 0.32, 0.24, 0.63, 0.69, and 0.09, respectively). Pooled operative and postoperative hospitalization durations were remarkably lower in PA-treated patients (P < 0.00001 and P = 0.004, respectively). With respect to long-term outcomes, pooled normal blood pressure rates were remarkably higher in the LA group compared with the PA group (P = 0.004), while there were no considerable discrepancies in pooled medication reduction or no response rates between groups (P = 0.20 and 0.56, respectively). Funnel plots did not reveal any evidence of potential publication bias. While PA treatment of patients with APA was related to shorter operative duration and length of postoperative hospitalization, LA treatment of these patients was associated with better long-term patient outcomes. [ABSTRACT FROM AUTHOR]

Background: You Only Look Once version 5 (YOLOv5), a one-stage deep-learning (DL) algorithm for object detection and classification, offers high speed and accuracy for identifying targets. Purpose: To investigate the feasibility of using the YOLOv5 algorithm to non-invasively distinguish between aldosterone-producing adenomas (APAs) and non-functional adrenocortical adenomas (NF-ACAs) on computed tomography (CT) images. Material and Methods: A total of 235 patients who were diagnosed with ACAs between January 2011 and July 2022 were included in this study. Of the 215 patients, 81 (37.7%) had APAs and 134 (62.3%) had NF-ACAs' they were randomly divided into either the training set or the validation set at a ratio of 9:1. Another 20 patients, including 8 (40.0%) with APA and 12 (60.0%) with NF-ACA, were collected for the testing set. Five submodels (YOLOv5n, YOLOv5s, YOLOv5m, YOLOv5l, and YOLOv5x) of YOLOv5 were trained and evaluated on the datasets. Results: In the testing set, the mAP_0.5 value for YOLOv5x (0.988) was higher than the values for YOLOv5n (0.969), YOLOv5s (0.965), YOLOv5m (0.974), and YOLOv5l (0.983). The mAP_0.5:0.95 value for YOLOv5x (0.711) was also higher than the values for YOLOv5n (0.587), YOLOv5s (0.674), YOLOv5m (0.671), and YOLOv5l (0.698) in the testing set. The inference speed of YOLOv5n was 2.4 ms in the testing set, which was the fastest among the five submodels. Conclusion: The YOLOv5 algorithm can accurately and efficiently distinguish between APAs and NF-ACAs on CT images, especially YOLOv5x has the best identification performance. [ABSTRACT FROM AUTHOR]

Background Primary hyperaldosteronism (PA) has been recommended by numerous hypertension guidelines to expand screening, early diagnosis and treatment, as a secondary hypertension disease with the highest incidence, great cardiovascular and cerebrovascular dangers but high cure rate after surgery. However, the diagnosis, classification and clinical outcomes evaluation of these patients are varied and controversial. Captopril challenge test (CCT) is expected to provide whole-course management for PA patients because it is convenient, safe and can be used directly in the community or outpatient clinic. Objective To explore the diagnostic efficacy, classification and biochemical remission assessment of CCT in patients with PA. Methods The study population consisted of 824 patients who completed the cause screening for hypertension and were enrolled in the Department of Endocrinology and Metabolism, West China Hospital, Sichuan University from October 1 th 2020 to December 30 th 2022. After screening, 247 patients with PA and 123 patients with essential hypertension (EH) were enrolled, and PA was classified into aldosterone-producing adenoma (APA, 81 patients), idiopathic hyperaldosteronism (IHA, 55 patients), and uncategorized PA (u-PA, 111 patients). The differences among the four groups were compared and the receiver operating characteristic (ROC) curve analysis showed the diagnostic performance for the prediction of PA. Secondly, the ROC curves of each post-CCT index for APA and IHA respectively were plotted. Finally, according to the postoperative clinical outcomes, the patients with unilateral adrenal resection were divided into three groups: clinical remission, clinical improvement, and no remission group. The difference between the three groups was compared, and the cut-off point of biochemical remission of CCT in APA patients was analyzed. Results The post-CCT plasma aldosterone concentration (PAC) level had the highest diagnostic efficiency for PA (AUC=0.921, 95%CI=0.893-0.950), and the cut-off was 11.7 ng/dL. The sensitivity and specificity respectively was 84.6% and 86.0%. The post-CCT aldosterone to renin ratio (ARR) also had a good diagnostic efficacy for PA (AUC=0.868, 95%CI=0.823-0.923). The cut-off was 2.8 (ng/dL) / (mU/L), and the sensitivity and specificity respectively were 82.2% and 81.0%. The post-CCT PAC>17 ng/dL can assist in the diagnosis of APA subtypes. When post-CCT PAC

Aldosterone-producing adenoma (APA) is one of the main causes of primary aldosteronism (PA). Current researches on its autonomous secretion of aldosterone mainly focus on the detection of somatic driver genetic mutations. However, the specific mechanisms underlying the death and proliferation of adrenal cortical cells and the occurrence and development of adenomas are still unclear. This study aims to review the research progress on the mechanisms of cell death and proliferation of APA by combining previously published studies on genomics, transcriptomics, metabolomics, and epigenetics related to adrenal tissues.

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Background Aldosterone-producing adenoma (APA) is a common type of primary aldosteronism. For those with unilateral adrenocortical adenoma, although expert consensus recommends plasma aldosterone-to-renin ratio (ARR) as a screening indicator for APA, the range of ARR cut-off values varies widely due to the lack of unified detection method and diagnostic process. Therefore, there is a clinical need for a reliable and rapid predictive model to assist in identifying APA. Objective To explore the correlation between glomerular filtration rate (GFR) and APA, construct and validate the nomogram prediction model of APA. Methods A total of 493 patients with with pathologic results of unilateral adrenal mass who underwent surgical treatment after evaluation of adrenal endocrine hormones in the first affiliated hospital of Shihezi University from 2012 to 2022 were collected, 155 patients were ultimately included in the APA group and 113 patients in nonfunctioning adrenal adenoma combined with essential hypertension group according to the diagnostic criteria of APA and nonfunctioning adrenal adenoma. The patients' clinical data and biochemical data were collected. The patients were grouped according to GFR quartiles, and the correlation between GFR and APA was analyzed. The risk factors for APA were screened by multivariate Logistic regression analysis and a nomogram prediction model was constructed. Receiver operating characteristic (ROC) curve was used to analyze the discrimination of the prediction model, a consistency index (C-index) was used to evaluate the predictive accuracy of the model, Hosmer Lemeshow test was used to verify the fit of model, and the diagnostic efficacy of the model was evaluated using decision curve and clinical benefit curve. Results The patients were grouped according to GFR quartiles (Q1 to Q4 groups), Q1 group: ≥107.4 mL·min-1· (1.73 m2) -1 (n=67), Q2 group: 99.7-107.3 mL·min-1· (1.73 m2) -1 (n=67), Q3 group: 88.6-99.6 mL·min-1· (1.73 m2) -1 (n=67) and Q4 group: ≤88.5 mL·min-1· (1.73 m2) -1 (n=67), and the proportion of APA in each group was 47.8% (32/67), 53.7% (36/67), 58.2% (39/67) and 71.6% (48/67). Logistic regression trend test suggested that the risk of APA tended to increase as GFR levels decreased (P160 mmHg (OR=5.209, 95%CI=2.531-10.720), hypertension duration≥59 months (OR=4.326, 95%CI=1.950-9.595), blood potassium13.42 ng/dL (OR=8.756, 95%CI=4.320-17.749) were independent risk factors for the occurrence of APA (P

Double somatic mutations in CTNNB1 and GNA11/Q have recently been identified in a small subset of aldosterone-producing adenomas (APAs). As a possible pathogenesis of APA due to these mutations, an association with pregnancy, menopause, or puberty has been proposed. However, because of its rarity, characteristics of APA with these mutations have not been well characterized. A 46-year-old Japanese woman presented with hypertension and hypokalemia. She had two pregnancies in the past but had no history of pregnancy-induced hypertension. She had regular menstrual cycle at presentation and was diagnosed as having primary aldosteronism after endocrinologic examinations. Computed tomography revealed a 2 cm right adrenal mass. Adrenal venous sampling demonstrated excess aldosterone production from the right adrenal gland. She underwent right laparoscopic adrenalectomy. The resected right adrenal tumor was histologically diagnosed as adrenocortical adenoma and subsequent immunohistochemistry (IHC) revealed diffuse immunoreactivity of aldosterone synthase (CYP11B2) and visinin like 1, a marker of the zona glomerulosa (ZG), whereas 11b-hydroxylase, a steroidogenic enzyme for cortisol biosynthesis, was mostly negative. CYP11B2 IHC-guided targeted next-generation sequencing identified somatic CTNNB1 (p.D32Y) and GNA11 (p.Q209H) mutations. Immunofluorescence staining of the tumor also revealed the presence of activated b-catenin, consistent with features of the normal ZG. The expression patterns of steroidogenic enzymes and related proteins indicated ZG features of the tumor cells. PA was clinically and biochemically cured after surgery. In conclusion, our study indicated that CTNNB1 and GNA11-mutated APA has characteristics of the ZG. The disease could occur in adults with no clear association with pregnancy or menopause. [ABSTRACT FROM AUTHOR]

Primary aldosteronism (PA), the most important cause of secondary endocrine hypertension, is hallmarked by excessive aldosterone secretion. There were 2 subtypes of PA--unilateral aldosterone-producing adenoma and bilateral adrenal hyperplasia, which are now outdated. Since conventional adrenal pathological reports only examined hematoxylin and eosin staining, the secretory function of the structural adenoma(s) could not be determined. Several enzymes produce aldosterone-related steroids, and 2 isoforms of 11ß-hydroxylase, namely CYP11B1 and CYP11B2 (aldosterone synthase), are responsible for producing cortisol and aldosterone, respectively. Since the availability of specifically selective antibodies for targeting CYP11B1 and CYP11B2, the diagnosis/nomenclature of PA-related adrenal pathology has been revolutionized by using immunohistochemistry staining for CYP11B2 to identify the aldosterone production site in the human adrenal cortex. The significance of immunohistochemical staining of formalin-fixed paraffin-embedded adrenal tissue sections has become "mandatory" for precisely detecting the lesions responsible for PA. Recently, the histopathology of PA consensus, based on immunochemical findings, was established to define the nomenclature and adrenal histopathological features in unilateral PA. In this study, we further investigate the association between the pathological subtypes and the surgical outcomes of PA as per the criteria of the Primary Aldosteronism Surgery Outcome consensus. Unfortunately, a significant lag is seen in the adaptation of Taiwan's pathologists to the histopathology of PA consensus. Furthermore, a strong push from all urologists across Taiwan and the governmental health care authorities is required to elevate the care level provided to all patients with PA in Taiwan to exceptional. [ABSTRACT FROM AUTHOR]

Unilateral primary aldosteronism is thought to be a surgically curable disease, and unilateral adrenalectomy is the mainstay treatment. The Primary Aldosteronism Surgical Outcome (PASO) consensus was developed to assess clinical and biochemical outcomes to standardize the classification of surgical outcomes. However, fewer than half of patients are cured of hypertension after adrenalectomy; therefore, preoperative patient counseling and evaluation might be necessary. Moreover, current studies show that genetic mutations and histopathology classification are associated with the treatment outcome. The Task Force of Taiwan PA recommends using a specific scoring system, including the PASO score and nomogram-based preoperative score, to predict the clinical outcome before adrenalectomy. Herein, we discuss the associations of current histopathological classification and specific somatic gene mutations with clinical outcomes after surgery. [ABSTRACT FROM AUTHOR]

A clinical case is presented of delayed diagnosis of primary hyperaldosteronism (PHA) due to aldosterone-producing adenoma. Suspicion of PHA arises in case of persistent combination of hypertension with hypokalemia of various severity, a specific neuromuscular syndrome, as well as a high risk of cardiomyopathy, heart failure, and deterioration of kidney function, which are not typical for banal hypertension. Unsatisfactory blood pressure control with a standard combination of pharmacotherapy, an unexpected positive effect of mineralocorticoid receptor antagonists, high blood pressure in young people, as well as a family history of early high blood pressure or stroke at a young age, paroxysmal course of hypertension itself increases the risk of PHA. For a long time, a disease in our patient was considered a banal hypertension, although the diagnostic hypothesis of PHA should appear immediately after severe neuromuscular syndrome, rapid progression of cardiomyopathy and clinically significant heart failure began to dominate in the clinical picture. A 44-year-old female patient came to the attention of rheumatologists with suspicion of inflammatory myopathy due to frequent episodes of muscle weakness whose origin remained unclear. Key complaints of pronounced paroxysmal generalized muscle weakness, especially in the limbs, numbness and paresthesias in the extremities, calf muscle cramps against the background of hypertension were regarded as a neuromuscular syndrome specific to PHA. The PHA hypothesis was supported by the presence of cardiomyopathy, heart failure, clinically significant hypokalemia, and elevated aldosterone level. Computed tomography of the retroperitoneal space confirmed the presence of adrenal adenoma. Unfortunately, with a delay, after 13 years of hypertension, the diagnosis of PHA against the background of aldosterone-producing adenoma was confirmed. Consultation with a surgeon endocrinologist was suggested, as well as administration of eplerenone 50 mg daily in combination with lercanidipine 20 mg daily. Already after 6 weeks of pharmacotherapy, a positive therapeutic effect was obtained regarding the control of hypertension, heart failure, and the severity of neuromuscular syndrome. The differential diagnosis of secondary endocrine hypertension can be successful only with the possession of skills for early clinical detection of endocrine pathology, even in subclinical disease presentation. The diagnosis of PHA makes it possible to offer a patient radical surgical treatment, as well as to choose optimal approaches to pharmacotherapy.

Unilateral primary aldosteronism is thought to be a surgically curable disease, and unilateral adrenalectomy is the mainstay treatment. The Primary Aldosteronism Surgical Outcome (PASO) consensus was developed to assess clinical and biochemical outcomes to standardize the classification of surgical outcomes. However, fewer than half of patients are cured of hypertension after adrenalectomy; therefore, preoperative patient counseling and evaluation might be necessary. Moreover, current studies show that genetic mutations and histopathology classification are associated with the treatment outcome. The Task Force of Taiwan PA recommends using a specific scoring system, including the PASO score and nomogram-based preoperative score, to predict the clinical outcome before adrenalectomy. Herein, we discuss the associations of current histopathological classification and specific somatic gene mutations with clinical outcomes after surgery.

To evaluate the secretory function of adrenal incidentaloma, this study explored the usefulness of a contrast-enhanced computed tomography (CECT)-based radiomics model for distinguishing aldosterone-producing adenoma (APA) from non-functioning adrenal adenoma (NAA). Overall, 68 APA and 60 NAA patients were randomly assigned (8:2 ratio) to either a training or a test cohort. In the training cohort, univariate and least absolute shrinkage and selection operator regression analyses were conducted to select the significant features. A logistic regression machine learning (ML) model was then constructed based on the radiomics score and clinical features. Model effectiveness was evaluated according to the receiver operating characteristic, accuracy, sensitivity, specificity, F1 score, calibration plots, and decision curve analysis. In the test cohort, the area under the curve (AUC) of the Radscore model was 0.869 [95% confidence interval (CI), 0.734–1.000], and the accuracy, sensitivity, specificity, and F1 score were 0.731, 1.000, 0.583, and 0.900, respectively. The Clinic–Radscore model had an AUC of 0.994 [95% CI, 0.978–1.000], and the accuracy, sensitivity, specificity, and F1 score values were 0.962, 0.929, 1.000, and 0.931, respectively. In conclusion, the CECT-based radiomics and clinical radiomics ML model exhibited good diagnostic efficacy in differentiating APAs from NAAs; this non-invasive, cost-effective, and efficient method is important for the management of adrenal incidentaloma. [ABSTRACT FROM AUTHOR]

Context: Adrenal venous sampling (AVS) is the gold standard procedure for subtype diagnosis in patients with primary aldosteronism (PA). Cortisol is usually adopted for the normalization of aldosterone levels in peripheral and adrenal samples. However, asymmetrical cortisol secretion can potentially affect the lateralization index, leading to subtype misdiagnosis. Objective: We aimed to assess the prevalence of asymmetrical cortisol secretion in patients undergoing AVS and whether variations in adrenal vein cortisol might influence AVS interpretations. We then evaluated the use of metanephrines for the normalization of aldosterone levels for lateralization index. Methods: We retrospectively included 101 patients with PA who underwent AVS: 49 patients underwent unstimulated AVS, while 52 patients underwent both unstimulated and cosyntropin-stimulated AVS. Eighty-eight patients had bilateral successful AVS according to metanephrine ratio. We assessed the prevalence of asymmetrical cortisol secretion through the cortisol to metanephrine (C/M) lateralization index (LI). We then evaluated whether the use of aldosterone to metanephrine (A/M) LI can improve the diagnostic accuracy of AVS compared with aldosterone to cortisol (A/C) LI. Results: Asymmetrical cortisol secretion is present in 18% of patients with PA. Diagnosis with A/M LI and A/C LI is discordant in 14% of patients: 9% had a diagnosis of unilateral PA with A/M LI instead of bilateral PA with A/C LI and 5% had a diagnosis of bilateral PA with A/M LI instead of unilateral PA. Conclusion: The assessment of metanephrine levels in AVS is useful for the determination of selectivity and lateralization, allowing an accurate diagnosis, especially in patients with asymmetrical cortisol secretion. [ABSTRACT FROM AUTHOR]

A clinical case is presented of delayed diagnosis of primary hyperaldosteronism (PHA) due to aldosterone-producing adenoma. Suspicion of PHA arises in case of persistent combination of hypertension with hypokalemia of various severity, a specific neuromuscular syndrome, as well as a high risk of cardiomyopathy, heart failure, and deterioration of kidney function, which are not typical for banal hypertension. Unsatisfactory blood pressure control with a standard combination of pharmacotherapy, an unexpected positive effect of mineralocorticoid receptor antagonists, high blood pressure in young people, as well as a family history of early high blood pressure or stroke at a young age, paroxysmal course of hypertension itself increases the risk of PHA. For a long time, a disease in our patient was considered a banal hypertension, although the diagnostic hypothesis of PHA should appear immediately after severe neuromuscular syndrome, rapid progression of cardiomyopathy and clinically significant heart failure began to dominate in the clinical picture. A 44-year-old female patient came to the attention of rheumatologists with suspicion of inflammatory myopathy due to frequent episodes of muscle weakness whose origin remained unclear. Key complaints of pronounced paroxysmal generalized muscle weakness, especially in the limbs, numbness and paresthesias in the extremities, calf muscle cramps against the background of hypertension were regarded as a neuromuscular syndrome specific to PHA. The PHA hypothesis was supported by the presence of cardiomyopathy, heart failure, clinically significant hypokalemia, and elevated aldosterone level. Computed tomography of the retroperitoneal space confirmed the presence of adrenal adenoma. Unfortunately, with a delay, after 13 years of hypertension, the diagnosis of PHA against the background of aldosterone-producing adenoma was confirmed. Consultation with a surgeon endocrinologist was suggested, as well as administration of eplerenone 50 mg daily in combination with lercanidipine 20 mg daily. Already after 6 weeks of pharmacotherapy, a positive therapeutic effect was obtained regarding the control of hypertension, heart failure, and the severity of neuromuscular syndrome. The differential diagnosis of secondary endocrine hypertension can be successful only with the possession of skills for early clinical detection of endocrine pathology, even in subclinical disease presentation. The diagnosis of PHA makes it possible to offer a patient radical surgical treatment, as well as to choose optimal approaches to pharmacotherapy. [ABSTRACT FROM AUTHOR]

Complete resolution of hypertension (CRH) after adrenalectomy for primary aldosteronism is far from a certainty. Although several prognostic models have been proposed to predict outcome after adrenalectomy, studies have not clarified which of the available models can be used reliably in clinical practice. To identify, describe and appraise all prognostic models developed to predict CRH, and meta‐analyse their predictive performances. We searched MEDLINE, Embase and Web of Science for development and validation studies of prognostic models. After selection, we extracted descriptive statistics and aggregated area under the receiver operator curve (AUC) using meta‐analysis. From 25 eligible studies, we identified 12 prognostic models used for predicting CRH after total adrenalectomy in primary aldosteronism. We report the results for 3 models that had available data from at least 3 external validation studies: the primary aldosteronism surgical outcome (PASO) score (AUC: 0.81; 95% confidence interval [CI]: 0.74‒0.86; 95% predictive interval [PI]: 0.04‒1.00), Utsumi nomogram (AUC: 0.79; 95% CI: 0.72‒0.85; 95% PI: 0.03‒1.00) and the aldosteronoma resolution score (ARS) model (AUC: 0.77; 95% CI: 0.74‒0.80; 95% PI: 0.59‒0.86 for all studies and AUC: 0.80; 95% CI: 0.75‒0.85; 95% PI: 0.57‒0.93 for the studies with the same adrenal vein sampling‐guided adrenalectomy rate compared to the models meta‐analysed). The PASO score, Utsumi nomogram and ARS model showed comparable discrimination performance to predict CRH in primary aldosteronism. Unlike the ARS model, the number of external validation studies for the PASO score and the Utsumi nomogram was relatively low to draw definite conclusions. [ABSTRACT FROM AUTHOR]

Laparoscopic adrenalectomy is currently the standard treatment modality for unilateral aldosteroneproducing adenoma (APA); however, a less-invasive treatment is needed for its treatment. A new bipolar ablation system that poses a lower risk of complications has been recently developed. This study aimed to evaluate the safety and performance of a novel bipolar radiofrequency ablation (RFA) system for the treatment of APAs. Ablations were performed in an ex vivo study using bovine adrenal glands [group A: n = 6, single-probe; group B: n = 6, two probes, interprobe distance (ID) = 12 mm; group C: n = 6, two probes, ID = 20 mm]. The in vivo study was conducted in groups A and B (n = 2 each) using porcine adrenal glands. For the ex vivo study, the mean vertical diameter (Dv) of the coagulative necrosis area and the mean transverse diameter (Dt) values were 11.99 mm and 10.96 mm for group A, 12.66 mm and 10.0 mm for group B, and 23.37 mm and 22.10 mm for group C, respectively. For the in vivo study, the mean Dv and Dt values were 12.23 mm and 9.03 mm for group A, and 16.38 mm and 9.52 mm for group B, respectively. No heat-induced damage to the adjacent organs was observed. To our best knowledge, this is the first study to evaluate the performance of the bipolar system in RFA of the adrenal gland. RFA using the new bipolar ablation system is safe and produces a sufficient coagulation area to treat APAs. [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate the predicting value of existing models for idiopathic hyperaldosteronism (IHA) in the Chinese population. METHODS In this cross-sectional study, 387 patients with primary aldosteronism (PA) in the First Affiliated Hospital of Chongqing Medical University from January 2013 to March 2021 were evaluated. Briefly, 275 patients with unilateral PA and 112 with IHA were included. Patients with PA were subtyped according to adrenal venous sampling or postoperative remission situation. Based on the subtype, the diagnostic value of 7 IHA prediction models was evaluated using the receiver operating characteristic (ROC) curve and sensitivity and specificity analysis. RESULTS Among the 7 IHA prediction models, the Kobayashi2018 score and Xiao model were verified to have high diagnostic efficiency, with an area under the ROC curve (AUC) of 0.88 and 0.92, respectively. The AUC of the other 5 models ranged from 0.51 to 0.80. The recommended cutoffs of the model were further verified. Kobayashi2018 score (≥8 points) and Umakoshi model (normal serum K+ with negative adrenal computed tomography) were found to have relatively high sensitivity (38% and 36%, respectively) when high specificity (≥95%) was achieved. CONCLUSION Considering simplicity, feasibility, generalizability, and accuracy, the Kobayashi2018 score or Umakoshi model is recommended to predict IHA in the Chinese population. [ABSTRACT FROM AUTHOR]

The mechanism behind the higher incidence of aldosterone-producing adenoma (APA) in women compared to men is not yet understood. In this study, we utilized single-cell RNA sequencing (scRNA-seq) to investigate the immune cell infiltration and adrenal cell characteristics in APA. Our findings revealed a high presence of immune cells in the tumor microenvironment, with macrophages and T lymphocytes being the most prevalent. Comparison of infiltrating cells between males and females showed that female CD8+T cells had stronger cytotoxic and inflammation-related functions, while female myeloid cells had more enrichment in inflammatory pathways. Additionally, we found that female adrenal cells had greater upregulation of immune-related and antigen presentation pathways. Furthermore, our analysis revealed that zona glomerulosa (ZG) cells had a higher capability for aldosterone synthesis. These results provide a deeper understanding of the APA microenvironment in patients of different sexes and offer new insights into the onset of APA.

Primary aldosteronism (PA) is a major cause of secondary hypertension. Aldosterone-producing adenoma (APA) is a subtype of PA, and adrenalectomy is the gold-standard treatment. Recently, a high prevalence of the KCNJ5 gene mutation has been reported in APA, particularly in Japan. Herein, we present 2 extremely rare cases of PA recurrence more than 10 years after adrenalectomy for APA. In the first case, a 52-year-old woman was examined for hypertension 22 years after total adrenalectomy of the right adrenal gland. Recurrent PA was diagnosed based on high aldosterone-renin-ratio (ARR), identification of left adrenal gland tumor by computed tomography (CT), and a confirmatory test. In the second case, a 65-year-old man was examined for hypertension 17 years after total adrenalectomy of the left adrenal gland. He had maintained his blood pressure using medication since the onset of hypertension 4 years after the surgery. A year later, a high ARR was observed. PA recurrence was determined by a right adrenal gland tumor noted on CT and a confirmatory test. Somatic mutations in KCNJ5 were detected in the resected tissues in both cases. We recommend careful follow-ups after adrenalectomy in APA cases, especially in those with a KCNJ5 gene mutation. [ABSTRACT FROM AUTHOR]

Aldosterone‐producing adenoma (APA) is a common cause of secondary hypertension. This study aimed to explore the lncRNA‐miRNA‐mRNA competitive endogenous RNA (ceRNA) network to uncover molecular mechanism underlying APA. The mRNA and lncRNA expression data of APA and adjacent adrenal gland (AAG) from GSE60044, GSE64957 and GSE101894 were obtained from the Gene Expression Omnibus (GEO) database to analyse differentially expressed genes (DEGs) and lncRNAs (DElncs). Hub genes were identified by robust rank aggregation (RRA) and protein–protein interaction (PPI) network analysis. The miRcode and miRWalk network tools were used to construct the ceRNA network. 1526 upregulated and 1512 downregulated DEGs were identified, which are mainly enriched in extracellular matrix and Ca2+‐related GO terms. In the KEGG pathway analysis, Ca2+ signalling and the aldosterone synthesis and secretion pathways were enriched. ceRNA network included 2 lncRNAs, 9 miRNAs, and 13 mRNAs. The lncRNAs are MEG3 and LINC00115. The mRNAs included CCND1, TP53, GPRC5B, BMI1, COMMD3‐BMI1, ADAMTS15, STAT3, MMP2, SCN2B, CXCL12, HGF, FOS, and THBS1. Overall, this study conducted a ceRNA regulatory network analysis and identified that 2 lncRNAs and 13 mRNAs may contribute to the development of APA. These findings may provide novel diagnostic and intervention targets for APA. [ABSTRACT FROM AUTHOR]

Primary aldosteronism (PA) is the most frequent form of secondary endocrine hypertension, which is characterized by excessive aldosterone secretion and suppressed renin. The currently recommended diagnostic algorithm is very clear, and the plasma aldosterone-to-renin ratio (ARR) is considered the first-line screening test. However, this indicator is influenced by many factors, some of which may cause false-negative results, consequently leading to underdiagnosed PA. Here, we report the rare case of a 38-year-old man who presented with bilateral accessory renal arteries and aldosterone-producing adenoma but had a negative ARR test result. [ABSTRACT FROM AUTHOR]

Context: There are inconsistent results and insufficient evidence as to whether an association exists between the size and aldosteroneproducing ability of aldosterone-producing adenomas. Objective: We further investigated this possible association retrospectively. Methods: A total of 142 cases of primary aldosteronism diagnosed as unilateral by adrenal venous sampling at 2 referral centers between 2009 and 2019 were included. We classified these individuals into small and large tumor groups using a diameter of 14 mm as a cutoff. This size was the median diameter of the tumor on the affected side of the adrenal gland. We compared plasma aldosterone concentration (PAC), plasma renin activity (PRA), PAC to PRA ratio, PAC from a saline infusion test (SIT), urinary aldosterone secretion (uAld), and serum potassium as indices of aldosterone-producing ability between the 2 groups. In some cases, we conducted histopathological evaluations and detection of the KCNJ5 mutation. Results: PAC, PAC to PRA ratio, PAC from SIT, and uAld were higher and serum potassium was lower in the large tumor group. PAC, PAC from SIT, uAld, and serum potassium significantly correlated with tumor diameter. PRA was not associated with tumor diameter. Clear cell-dominant cases were more common in the large tumor group, while cases showing a strong expression of CYP11B2 were not significantly different between the groups. KCNJ5 mutations tended to be more common in the large tumor group. Conclusion: The higher aldosterone-producing ability in larger adenomas can be used to infer the responsible lesion and disease type. [ABSTRACT FROM AUTHOR]

Background: Patients with primary aldosteronism (PA) exhibit a high prevalence of diabetes mellitus (DM). However, the relationship between visceral adipose tissue (VAT) and new-onset diabetes mellitus (NODM) in PA patients remains unclear., Objectives: To explore the association between VAT and the risk of NODM in PA patients., Design: This is a prospective cohort study spanning 10 years (2010-2020)., Methods: A total of 342 PA patients were enrolled prospectively. Abdominal adiposity indexes, including VAT area, VAT ratio, subcutaneous adipose tissue (SAT) area, and SAT ratio, were measured using a computed tomography-based software at diagnosis., Results: Of 342 PA patients (46.2% male, mean age 50.8 ± 11.2 years), 35 (10.2%) developed NODM over a mean follow-up of 7.4 years. A positive nonlinear association between NODM risk and Log (VAT ratio) ⩾ -0.72 was observed (high-VAT group). High VAT (odds ratio (OR), 6.09; p  = 0.005), older age (OR, 1.09; p  < 0.001), higher body mass index (OR, 1.24; p  < 0.001), higher waist-to-hip ratio (OR, 1.11, p  < 0.001), lower baseline aldosterone (OR, 0.99, p  = 0.011), higher diastolic blood pressure (OR, 1.05, p  = 0.012), and lower systolic blood pressure (OR, 0.98, p  = 0.045) as risk factors for high VAT. Adrenalectomy did not significantly associate with reduced NODM risk (OR, 0.49; p  = 0.292)., Conclusion: Our findings highlight that 10.2% of PA patients develop NODM over a mean follow-up of 7.4 years, with high VAT increasing the risk. Baseline VAT is a key determinant of NODM development in PA patients, regardless of targeted treatments., (© The Author(s), 2024.)

Hai Cai,1,&ast; Shao-Ming Chen,2,&ast; Zhi-Bin Ke,1,&ast; Hang Chen,1,&ast; Jun-Ming Zhu,1 Ting-Ting Lin,1 Fei Huang,3,4 Yong Wei,1 Qing-Shui Zheng,1 Xue-Yi Xue,1 Xiong-Lin Sun,1 Ning Xu1,3 1Department of Urology, Urology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 2Department of Nuclear Medicine, First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 3Fujian Key Laboratory of Precision Medicine for Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 4Central Lab, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Xu; Xiong-Lin Sun Tel +86-059187981687Email drxun@fjmu.edu.cn; sunxionglin@fjmu.edu.cnObjective: To develop and validate hub genes involving in the development and progression of primary aldosteronism (PA) and adrenal aldosterone-producing adenoma (APA).Materials and Methods: A total of four datasets of gene expression profiles related to APA were downloaded from GEO datasets. GSE60042 and GSE8514 were used to identify DEGs. Weighted gene co-expression network analysis (WGCNA) and protein–protein interaction (PPI) network module analysis were conducted. GO and KEGG enrichment analysis was performed. GSE10927 and GSE33371 were used for further external validation.Results: We identified a total of 892 DEGs from GSE60042 and 1167 DEGs from GSE8514. WGCNA analysis demonstrated that the blue module (255 genes) and turquoise module (303 genes) were significantly correlated with APA. PPI networks were then constructed. GO term enrichment analysis suggested that cellular divalent inorganic cation homeostasis, calcium ion homeostasis, collagen-containing extracellular matrix, transport vesicle and metal ion transmembrane transporter activity were the vital annotations. KEGG pathway analysis found that these genes were significantly enriched in neuroactive ligand−receptor interaction, calcium signaling pathway. Finally, we identified a total of 11 candidate genes involving in the development and progression of APA and PA. Besides, two independent datasets (GSE10927 and GSE33371) were used for external validation, and there were seven hub genes successfully verified, including C3, GRM3, AVPR1A, WFS1, PTGFR, NTSR2, and JUN.Conclusion: These newly identified genes could contribute to the understanding of potential mechanism in APA and PA and might be promising targets for the treatment of APA and PA.Keywords: aldosterone-producing adenoma, bioinformatics, primary aldosteronism, gene expression omnibus datasets

This article discusses the genetic mutations associated with familial and non-familial primary aldosteronism, a condition characterized by excessive production of the hormone aldosterone. The authors highlight the role of mutations in the KCNJ5 gene, specifically in the selectivity filter of the Kir3.4 channel, in the development of aldosterone-producing adenomas and familial hyperaldosteronism type III. They also mention other germline mutations outside the selectivity filter that have been implicated in different disease states. Further research is needed to fully understand the role of these mutations in various forms of primary aldosteronism. [Extracted from the article]

Context: Due to its rare incidence, molecular features of primary aldosteronism (PA) in young adults are largely unknown. Recently developed targeted mutational analysis identifed aldosterone-driver somatic mutations in aldosterone-producing lesions, including aldosterone-producing adenomas (APAs), aldosterone-producing nodules (APNs), and aldosterone-producing micronodules, formerly known as aldosterone-producing cell clusters. Objective: To investigate histologic and genetic characteristics of lateralized PA in young adults. Methods: Formalin-fxed, paraffn-embedded adrenal tissue sections from 74 young patients with lateralized PA (<35 years old) were used for this study. Immunohistochemistry (IHC) for aldosterone synthase (CYP11B2) was performed to defne the histopathologic diagnosis. Somatic mutations in aldosterone-producing lesions were further determined by CYP11B2 IHC-guided DNA sequencing. Results: Based on the CYP11B2 IHC results, histopathologic classifcation was made as follows: 48 APAs, 20 APNs, 2 multiple aldosteroneproducing nodules (MAPN), 1 double APN, 1 APA with MAPN, and 2 nonfunctioning adenomas (NFAs). Of 45 APAs with successful sequencing, 43 (96%) had somatic mutations, with KCNJ5 mutations being the most common genetic cause of young-onset APA (35/45, 78%). Of 18 APNs with successful sequencing, all of them harbored somatic mutations, with CACNA1D mutations being the most frequent genetic alteration in young-onset APN (8/18, 44%). Multiple CYP11B2-expressing lesions in patients with MAPN showed several aldosterone-driver mutations. No somatic mutations were identifed in NFAs. Conclusion: APA is the most common histologic feature of lateralized PA in young adults. Somatic KCNJ5 mutations are common in APAs, whereas CACNA1D mutations are often seen in APNs in this young PA population. [ABSTRACT FROM AUTHOR]

Purpose of the Review: Primary aldosteronism (PA) is the leading cause of secondary hypertension, accounting for over 10% of patients with high blood pressure. It is characterized by autonomous production of aldosterone from the adrenal glands leading to low-renin levels. The two most common forms arise from bilateral adrenocortical hyperplasia (BAH) and aldosterone-producing adenoma (APA). We discuss recent discoveries in the genetics of PA. Recent Findings: Most APAs harbor variants in the KCNJ5, CACNA1D, ATP1A1, ATP2B3, and CTNNB1 genes. With the exception of β-catenin (CTNNB1), all other causative genes encode ion channels; pathogenic variants found in PA lead to altered ion transportation, cell membrane depolarization, and consequently aldosterone overproduction. Some of these genes are found mutated in the germline state (CYP11B2, CLCN2, KCNJ5, CACNA1H, and CACNA1D), leading then to familial hyperaldosteronism, and often BAH rather than single APAs. Summary: Several genetic defects in the germline or somatic state have been identified in PA. Understanding how these molecular abnormalities lead to excess aldosterone contributes significantly to the elucidation of the pathophysiology of low-renin hypertension. It may also lead to new and more effective therapies for this disease acting at the molecular level. [ABSTRACT FROM AUTHOR]

Context The association between primary aldosteronism and obesity, especially its sex difference, remains unknown. Objective To assess the association for each subtype of primary aldosteronism with obesity parameters including visceral adipose tissue and differences between sexes. Methods In this case-control study, 4 normotensive controls were selected for each case with primary aldosteronism. Multivariable conditional logistic regression models were used to estimate the association between each type of primary aldosteronism and obesity indicators. We used a random forest to identify which visceral or subcutaneous tissue areas had a closer association with disease status. Results The study subjects included 42 aldosterone-producing adenoma cases (22 women) and 68 idiopathic hyperaldosteronism cases (42 women). In multivariable conditional logistic regressions, aldosterone-producing adenoma was significantly associated with body mass index only in men (odds ratio [OR] [95% CI)], 4.62 [1.98-10.80] per 2.89 kg/m2) but not in women (OR [95% CI], 1.09 [0.69-1.72] per 3.93 kg/m2) compared with the matched controls, whereas idiopathic hyperaldosteronism was associated with body mass index in both men (OR [95% CI], 3.96 [2.03-7.73] per 3.75 kg/m2) and women (OR [95% CI], 2.65 [1.77-3.96] per 3.85 kg/m2) compared with the matched controls. In random forests, visceral adipose tissue areas were the better predictor of both aldosterone-producing adenoma and idiopathic hyperaldosteronism than subcutaneous adipose tissue. Conclusions Aldosterone-producing adenoma cases were obese among men, but not among women. Idiopathic hyperaldosteronism cases were obese among both men and women. Visceral adipose tissue may contribute to the pathophysiology of primary aldosteronism. [ABSTRACT FROM AUTHOR]

This report presents a case of left adrenal aldosterone-producing adenoma (APA) diagnosed by segmental adrenal venous sampling in a patient with primary aldosteronism and a rare venous anomaly in which the left inferior phrenic vein (LIPV) and adrenal central vein entered the left renal vein separately. The outflow of tumor blood into the LIPV and the specimen from the LIPV that showed much higher aldosterone level than that from the adrenal central vein and tributaries were useful for proving the aldosterone hypersecretion from the APA. Sampling from the LIPV could be of diagnostic value for left APA.

Abstract The aim of this study was to explore the long‐term clinical results of Renal denervation (RDN) from the adventitia of the renal artery plus unilateral laparoscopic adrenalectomy to treat patients with resistant hypertension caused by unilateral aldosterone‐producing adenoma (APA). Sixty patients with resistant hypertension caused by APA who were treated at Henan Provincial People's Hospital from December 2016 to March 2018 were selected and randomly assigned to undergo RDN from the adventitia of the renal artery plus adrenalectomy (RDN group, n = 30) or adrenalectomy alone (control group, n = 30). Office blood pressure (BP), antihypertensive medication usage and other laboratory characteristics were followed every 6 months through 36 months. Follow‐up data were available at 36 months for 23 of 30 subjects in the RDN group and for 21 of 30 subjects who were in the control group. At 36 months postprocedure, the reduction in the RDN group was 42.2 ± 21.6 mmHg and that in the control group was 29.8 ± 13.5 mmHg (p = .029 between the groups). During the follow‐up to 36 months postprocedure, no patients in either the RDN group or the control group died due to surgical complications, and the RDN group had no procedural complications, including renal artery dissection, perforation, and renal artery stenosis. There was no change in the mean eGFR of the two groups, and no serious adverse events were reported. In conclusion, RDN from the adventitia of the renal artery plus unilateral laparoscopic adrenalectomy resulted in sustained lowering of BP at 3 years in a selected population of subjects with resistant hypertension caused by unilateral APA without serious safety concerns.

Purpose: Adrenal venous sampling (AVS) performed to distinguish unilateral and bilateral primary aldosteronism (PA) is invasive and poorly standardized. This study aimed to identify non-invasive characteristics that can select the patients with unilateral PA who could bypass AVS before surgery. Methods: A single-center study collected a total of 450 patients with PA. Development and validation cohorts included 242 and 208 patients. The AVS was successful in 150 and 138 patients from the cohorts, and the unilateral PA was found in 96 and 94 patients, respectively. Clinical factors independently associated with lateralized AVS in multivariable logistic regression were used to construct a unilateral PA prediction score (SCORE). Results: The proposed SCORE was calculated as a sum of the prevalence of adrenal nodule on computed tomography (2 points) and plasma/serum aldosterone concentration ≥ 165 ng/L after the saline infusion test (SIT) (1 point). Importantly, the SCORE = 3 points identified 48% of unilateral PA patients with a specificity of 100% in the development cohort. The zero rate of false-positive classifications was preserved with the same cut-off value in the validation cohort. Conclusions: AVS could be omitted before surgery in patients with typical Conn´s adenoma provided the aldosterone concentration ≥ 165 ng/L after the SIT. [ABSTRACT FROM AUTHOR]

Objectives: This study compared cardiac function, morphology, and tissue characteristics between two common subtypes of primary aldosteronism (PA) using a 3T MR scanner. Design: A retrospective, single-center, observational study. Methods: We retrospectively reviewed 143 consecutive patients with PA, who underwent both adrenal venous sampling and cardiac magnetic resonance. We acquired cine, late gadolinium enhancement, and pre- and postcontrast myocardial T1-mapping images. Results: PA was diagnosed as unilateral aldosterone-producing adenoma (APA) in 70 patients and bilateral hyperaldosteronism (BHA) in 73. The APA group showed significantly higher plasma aldosterone concentration (PAC) and aldosterone to renin rate (ARR) than the BHA group. After controlling for age, sex, antihypertensive drugs, systolic and diastolic blood pressure, and disease duration, the parameters independently associated with APA were: left ventricular end-diastolic volume index (EDVI: adjusted odds ratio (aOR) = 1.06 (95% CI: 1.030–1.096), P < 0.01), end-systolic volume index (ESVI: 1.06 (1.017–1.113), P < 0.01), stroke index (SI: 1.07 (1.020–1.121), P < 0.01), cardiac index (CI: 1.001 (1.000–1.001), P < 0.01), and native T1 (1.01 (1.000–1.019), P = 0.038). Weak positive correlations were found between PAC and EDVI (R = 0.28, P < 0.01), ESVI (0.26, P < 0.01), and SI (0.18, P = 0.03); and between ARR and EDVI (0.25, P < 0.01), ESVI (0.24, P < 0.01), and native T1 (0.17, P = 0.047). Conclusions: APA is associated with greater LV volumetric parameters and higher native T1 values, suggesting a higher risk of volume overload and myocardial damage.

Context: Aldosterone-producing adenomas (APAs) are a common cause of primary aldosteronism (PA). Despite the discovery of somatic mutations in APA and the characterization of multiple factors regulating adrenal differentiation and function, the sequence of events leading to APA formation remains to be determined. Objective: We investigated the role of Wnt/β-catenin and adrenocorticotropin signaling, as well as elements of paracrine regulation of aldosterone biosynthesis in adrenals with APA and their relationship to intratumoral heterogeneity and mutational status. Methods: We analyzed the expression of aldosterone-synthase (CYP11B2), CYP17A1, β-catenin, melanocortin type 2 receptor (MC2R), phosphorlyated cAMP response element-binding protein (pCREB), tryptase, S100, CD34 by multiplex immunofluorescence, and immunohistochemistry-guided reverse transcription–quantitative polymerase chain reaction. Eleven adrenals with APA and 1 with micronodular hyperplasia from patients with PA were analyzed. Main outcome measures included localization of CYP11B2, CYP17A1, β-catenin, MC2R, pCREB, tryptase, S100, CD34 in APA and aldosterone-producing cell clusters (APCCs). Results: Immunofluorescence revealed abundant mast cells and a dense vascular network in APA, independent of mutational status. Within APA, mast cells were localized in areas expressing CYP11B2 and were rarely colocalized with nerve fibers, suggesting that their degranulation is not controlled by innervation. In these same areas, ß-catenin was activated, suggesting a zona glomerulosa cell identity. In heterogeneous APA with KCNJ5 mutations, MC2R and vascular endothelial growth factor A expression was higher in areas expressing CYP11B2. A similar pattern was observed in APCC, with high expression of CYP11B2, activated β-catenin, and numerous mast cells. Conclusion: Our results suggest that aldosterone-producing structures in adrenals with APA share common molecular characteristics and cellular environment, despite different mutation status, suggesting common developmental mechanisms. [ABSTRACT FROM AUTHOR]

Context: Adrenal vein sampling (AVS) represents the current diagnostic gold standard for differentiation between unilateral and bilateral primary aldosteronism (PA). Postural stimulation testing (PST) has been used to provide additional diagnostic information. Objective: This work aimed to evaluate the diagnostic utility of PST in the differential diagnosis of PA. Methods: This cohort study was conducted at a single tertiary reference center. We analyzed 106 PST performed between 2008 and 2020. Diagnosis of PA and cause of PA were determined according to the Endocrine Society Clinical Practice Guideline, taking into account results of saline infusion testing, AVS, preoperative imaging, and outcome after medical or surgical treatment. The suggested cutoffs for the diagnosis of unilateral PA were revisited and optimized for high specificity using receiver operating characteristics (ROC) analysis. Results: A total of 106 patients had confirmed PA (unilateral PA: n = 55, bilateral PA: n = 29, AVS unsuccessful/declined by patients: n = 22). Based on decreased aldosterone plasma concentration of 28% or more after 4 hours in the upright position, the PST showed a sensitivity of 36.4% at a specificity of 100% to identify unilateral disease (area under the curve [AUC] = 0.72; 95% CI, 0.62-0.83; P = .001). In patients with valid testing (drop of cortisol of 10% or more after 4 hours, n = 53) the sensitivity of PST rose to 51.4% at a specificity of 100% (AUC = 0.77; 95% CI, 0.65-0.90; P = .001). Conclusion: The high specificity of 100% for the detection of unilateral PA in patients with decreased aldosterone by at least 28% after 4 hours makes PST a simple, noninvasive contribution to subtype differentiation in PA. [ABSTRACT FROM AUTHOR]

Aldosterone-producing adenoma (APA), the main cause of endocrine hypertension, has recently been reported to be associated with other diseases, such as metabolic syndrome, but the detailed mechanism underlying this association remains unclear. Here, we used untargeted metabolomics and compared the abundance of serum metabolites between essential hypertension (EHT) and APA patients, as well as the serum metabolites of APA patients before and after adrenalectomy. Our results revealed 44 differential metabolites between APA and EHT patients and 39 differential metabolites between pre- and postoperative APA patients. Several metabolites involved in cardiovascular disease, obesity, and diabetes were dysregulated in APA patients compared to EHT patients, including arachidonic acid metabolites [e.g., 5(S)-HpETE and 12-HETE], amino acids (e.g., L-carnitine, taurine, and L-arginine), nucleotide metabolites (e.g., hypoxanthine) and cholesterol 3-sulfate. Importantly, the levels of hypoxanthine and cholesterol 3-sulfate, two metabolites that promote the development of atherosclerotic lesions and obesity, were originally increased in APA patients, but those elevated levels were reversed by adrenalectomy. Conversely, levels of L-carnitine and (3-carboxypropyl) trimethylammonium cation, two metabolites participating in lipid metabolism, were decreased in APA patients but increased postoperatively. We conclude that APA might participate in cardiovascular and metabolic diseases by regulating serum metabolites.

Background: Distinguishing unilateral aldosterone-producing adenomas (APA) from idiopathic hyperaldosteronism (IHA), nonfunctional adrenal adenoma (NFA), and pheochromocytoma (PHEO) within primary aldosteronism (PA) presents a significant challenge. Studies have demonstrated high levels of chemokine receptor (CXCR) 4 expression in APA, thereby validating the use of 68 Ga-labeled CXCR4 PET/CT for detecting APA. This study evaluates the efficacy of [ 18 F]AlF-NOTA-pentixather PET/CT in distinguishing APA from other PA types. Methods: In the initial experiment, a comparative analysis was conducted to evaluate the diagnostic efficacy of [ 18 F]AlF-NOTA-T140 PET/CT and [ 18 F]AlF-NOTA-pentixather PET/CT for APA in 3 patients with PA. Based on the preliminary findings, [ 18 F]AlF-NOTA-pentixather PET/CT was subsequently performed on 45 patients with suspected PA and 5 controls. Lesions exhibiting higher tracer uptake than normal adrenal glands were considered positive and referred for adrenalectomy. Prior to surgery, adrenal venous sampling (AVS) was performed in 71.1% of patients to assess laterality. Postoperative follow-up was conducted in 91.1% of patients. The semi-quantitative analysis involved assessing maximum standardized uptake value (SUVmax), LLR (lesion-to-liver ratio), and lesion-to-contralateral ratio (LCR). Correlations were made between PET/CT findings, histopathology results, outcomes, and AVS. Results: In terms of diagnosing APA, [ 18 F]AlF-NOTA-pentixather PET/CT demonstrated a sensitivity of 100%, specificity of 91.7%, and accuracy of 95.8%. The mean SUVmax for APAs (25.62 ± 12.71, n = 24) was significantly higher compared to non-APA cases (7.24 ± 3.27, n = 24, P < 0.0001). An optimal SUVmax threshold of 11.60 accurately predicted the presence of APA with a sensitivity of 95.8%, specificity of 96.0%, and accuracy of 93.9%. A cutoff value for LCR at 1.38 provided 95.8% sensitivity and 92.0% specificity, while an LLR cutoff at 5.28 yielded a sensitivity rate of 91.7% and a specificity rate of 92.0%. Positive findings on PET/CT scans were completely consistent with AVS results. All patients with positive lesions derived significant benefits from surgical intervention. Conclusion: [ 18 F]AlF-NOTA-pentixather PET/CT seems to be highly related to AVS and could be a noninvasive method for diagnosing APA in patients with PA., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Introduction Primary aldosteronism is characterized by the autonomous excretion of aldosterone, which may induce bone mineral disorders. Methods A total of 96 patients with primary aldosteronism were analyzed to identify differences in the regulation of serum calcium/phosphate balance between patients with unilateral and bilateral aldosterone hypersecretion and to determine whether or not adrenalectomy or mineralocorticoid receptor blockers affected such differences. Results Serum phosphate concentrations were significantly lower in patients with unilateral aldosterone hypersecretion than in patients with bilateral aldosterone hypersecretion (2.96±0.45 vs. 3.36±0.55 mg/dL, p<0.05), and recovered after adrenalectomy (2.96±0.45 vs. 3.49±0.32 mg/dL, p<0.01). In patients with bilateral aldosterone hypersecretion, the baseline serum phosphate levels were significantly lower in responders to mineralocorticoid receptor blocker treatment, defined as post-treatment plasma renin activity ≥1 ng/mL/h, than in non-responders. In responders, these levels tended to recover after treatment. A weak negative correlation between the plasma aldosterone concentration (PAC) and serum phosphate was observed, but there were no associations between the PAC and serum calcium concentration or between the aldosterone renin ratio and serum calcium and phosphate concentrations. Conclusion The effects on calcium/phosphate homeostasis may differ according to the primary aldosteronism subtype.

Many cases of primary aldosteronism (PA) in patients who developed hypokalemia-induced rhabdomyolysis and underwent adrenalectomy for aldosterone-producing adenoma (APA) have been reported; however, the immunohistopathological and molecular features remain unknown. We herein report the case of a 28-year-old woman with PA who presented with hypokalemia-induced rhabdomyolysis and underwent adrenalectomy for unilateral APA. An immunohistochemical analysis revealed that most adenoma cells were positive for steroidogenic enzymes, including CYP11B2. A genetic analysis revealed a somatic mutation in the KCNJ5. These findings suggest a strong aldosterone production capacity in our patient's adenoma, which was presumably related to her severe hyperaldosteronism and the resultant hypokalemia-induced rhabdomyolysis.

The new clinical prediction score (SCORE) has been recently proposed for primary aldosteronism (PA) subtyping prior to adrenal vein sampling (AVS). This study aimed to compare that SCORE with previously published scores and their validation using a cohort of patients at our center who had had positive SIT confirming PA and had been diagnosed with either bilateral PA according to AVS or unilateral PA if biochemically cured after an adrenalectomy. Final diagnoses were used to evaluate the diagnostic performance of the proposed clinical prediction tools. Only Kamemura’s model (with a maximum score of 4 points) and Kobayashi’s score (with a maximum score of 12 points) reached 100% reliability for prediction of bilateral PA; however, with sensitivity of only 3%. On the other hand, the values of SCORE = 3 (with sensitivity of 48%), the SPACE score ≥18 (with sensitivity of 35%), the Kobayashi’s score ≤2 (with sensitivity of 28%), and the Kocjan’s score = 3 (with sensitivity of 28%) were able to predict unilateral PA with 100% probability. Furthermore, Umakoshi’s and Young’s models both reached 100% reliability for a unilateral PA with score = 4 and both predictive factors together respectively; however, the sensitivity was lower compared with previous models; 4% and 14%, respectively. None of the clinical prediction tools applied to our cohort predicted unilateral and bilateral subtypes together with the expected high diagnostic performance, and therefore can only be used for precisely defined cases.

A 29-year-old female patient diagnosed with primary aldosteronism (PA) in 2004 underwent complete adrenalectomy for left aldosterone-producing adenoma (APA) confirmed by hematoxylin and eosin (HE) and CYP11B2 staining. Her hypokalemia was corrected, and her blood pressure (BP) normalized and maintained without medication for 10 years. In 2014, her BP became elevated again, and a recurrence of PA with an adenoma on the right adrenal gland was discovered by computed tomography scan. She underwent partial right adrenalectomy in 2018 due to unsatisfactory BP control with medication and gradually enlarging adenoma. The resected adrenal tissue contained a CYP11B2 staining positive APA. Her BP was then controlled by two drugs. Sanger sequencing of DNA extracted from tissue slices revealed that both left and right adenomas carried the same aldosterone-driver KCNJ5 gene mutation, but with different nucleotide changes. We suggest that patients who undergo adrenalectomy for APA should be followed up for life.