Prevalence and impact of diabetes and prediabetes on presentation and complications of primary hyperaldosteronism at diagnosis

BACKGROUND Primary hyperaldosteronism(PH)is considered to contribute to increased risk of developing type 2 diabetes mellitus(T2DM)and prediabetes.Both PH and DM are associated with increased risk for hypertension,cardiovascular diseases,and chronic kidney diseases.However,data on prevalence of T2DM and prediabetes in PH,and impact of T2DM and prediabetes on presentation and cardio renal complications in PH at presentation is sparse.AIM To determine the prevalence of T2DM and prediabetes in PH at diagnosis and impact on presentation and complications of PH.METHODS A retrospective cohort study was conducted in tertiary care settings in individuals with confirmed diagnosis of PH at presentation.Demographic variables,clinical presentations,duration and degree of hypertension,complications,laboratory parameters including sodium,potassium levels,plasma aldosterone concentration(PAC),plasma renin activity(PRA),and aldosterone to renin ratio(ARR)and cardio-renal parameters were collected.Comparison was done between three groups:PH with no DM(Group A)or with pre-diabetes(Group B)or with T2DM(Group C).P<0.05 was statistically significant.RESULTS Among 78 individuals with confirmed PH,62%had pre-diabetes or diabetes;with 37%having DM.Mean duration of T2DM was 5.97±4.7 years.The mean levels of glycaemic parameters among the group A vs B vs C individuals were fasting plasma glucose(mg/dL):87.9±6.5,105.4±9.02,130.6±21.1;post prandial plasma glucose(mg/dL):122.7±9.8,154.9±14,196.7±38.0;glycated haemoglobin(%)(5.3±0.2,5.9±0.2,7.5±0.6,P<0.05),respectively.There was no significant difference in the biochemical parameters(PAC,PRA,ARR,sodium,potassium levels),presentation and complications between the groups.Cardio renal parameters or degree and duration of hypertension were comparable between the groups.CONCLUSION Significant prevalence of T2DM and prediabetes in PH at diagnosis does not impact its presentation or complications.Early screening for undetected PH in T2DM and prediabetes subjects with hypertension may prevent complications.

Advances in Medical Treatment of Primary Aldosteronism

Primary aldosteronism(PA)is the most common form of secondary hypertension,with its main manifestations including hypertension and hypokalemia.Early identification of PA is extremely important as PA patients can easily develop cardiovascular complications such as atrial fibrillation,stroke,and myocardial infarction.The past decade has witnessed the rapid advances in the genetics of PA,which has shed new light on PA treatment.While surgery is the first choice for unilateral diseases,bilateral lesions can be treated with mineralocorticoid receptor antagonists(MRAs).The next-generation non-steroidal MRAs are under investigations.New medications including calcium channel blockers,macrophage antibiotics,and aldosterone synthase inhibitors have provided a new perspective for the medical treatment of PA.

Aortic Cell Apoptosis in Rat Primary Aldosteronism Model

This study aimed to determine whether aldosterone could induce vascular cell apoptosis in vivo.Thirty-two male rats were randomly divided into 4 groups:vehicle(control),aldosterone,aldosterone plus eplerenone or hydralazine.They were then implanted with an osmotic mini-pump that infused either aldosterone or the vehicle.Systolic blood pressure(SBP) was measured weekly by the tail-cuff method.After 8 weeks,plasma aldosterone concentration(PAC) and renin activity(PRA) were determined by radioimmunoassay.Aorti...

Primary aldosteronism due to bilateral micronodular hyperplasia and concomitant subclinical Cushing’s syndrome:A case report

BACKGROUND Adrenal incidentaloma(AI)has been frequently encountered in the clinical setting.It has been shown that primary aldosteronism(PA)or subclinical Cushing’s syndrome(SCS)are the representative causative diseases of AI.However,the coexistence of PA and SCS has been reportedly observed.Recently,we encountered a case of AI,in which PA and SCS coexisted,confirmed by histopathological examinations after a laparoscopic adrenalectomy.We believe that there were some clinical implications in the diagnosis of the present case.CASE SUMMARY A 58-year-old man presented with lower right abdominal pain with a blood pressure of 170/100 mmHg.A subsequent computed tomography scan revealed right ureterolithiasis,which was the cause of right abdominal pain,and right AI measuring 22 mm×25 mm.After the disappearance of right abdominal pain,subsequent endocrinological examinations were performed.Aldosterone-related evaluations,including adrenal venous sampling,revealed the presence of bilateral PA.In addition,several cortisol-related evaluations showed the presence of SCS on the right adrenal adenoma.A laparoscopic right adrenalectomy was then performed.The histopathological examination of the resected right adrenal revealed the presence of a cortisol-producing adenoma,while CYP11B2 immunoreactivity was absent in this adenoma.However,in the adjacent nonneoplastic adrenal,multiple CYP11B2-positive adrenocortical micronodules were detected,showing the presence of aldosterone-producing adrenocortical micronodules.CONCLUSION Careful clinical and pathological examination should be performed when a patient harboring AI presents with concomitant SCS and PA.

Adrenal Venous Sampling in Patients with Primary Aldosteronism: Which Is the Best Evaluation Method for Laterality Assessments?

Purpose: The purpose was to investigate the most accurate method of adrenal venous sampling to diagnose unilateral primary aldosteronism (PA) prior to laterality assessment. Materials and Methods: Sixty-four consecutive PA patients were enrolled in this retrospective study. A catheter was placed in the common-trunk-vein (CTV), below the confluence of the inferior-phrenic-vein and the central-adrenal-vein (CAV) and the right-adrenal-vein (RAV). Blood-sampling was performed both pre- and post-adrenocorticotropic hormone stimulation. Lateralized ratio [LR;aldosterone/cortisol ratio (ACR) on high-value side/ACR on low-value side], contralateral ratio (CR;ACR on low-value side/ACR on inferior-vena-cava ratio), and plasma aldosterone concentration (PAC) were evaluated. The diagnostic accuracy of LR, CR and PAC in CTV/ CAV/RAV during pre- and post-ACTH was compared by receiver-operating-characteristic (ROC) analysis. Results: LR-CAV post-ACTH showed the highest detection rate for unilateral adrenal lesions (93.3%;14/15), with a sensitivity of 0.93 and a specificity of 0.84 at a cut-off value of 2.5. CR-post-ACTH had the highest Az value (0.89), with a detection rate of 86.7% (13/14), a sensitivity of 0.98, and a specificity of 0.88 at a cut-off value of 0.8. Conclusion: CR-post-ACTH and LR-CAV-post-ACTH are accurate predictors for laterality assessment in PA.

Comparison of Cardiac Structural Improvement in Patients with Primary Aldosteronism after Surgical Therapy and Drug Therapy: A Meta-Analysis

Background: At present, in clinical practice, patients with primary hyperaldosteronism (PA) are mainly treated by surgery or medical drugs (spironolactone/spironolactone, epridone, etc.). Some studies show that the left ventricular hypertrophy of patients can be significantly improved after treatment. However, at present, the relevant research is very limited, and there is still controversy on the improvement of cardiac structure and function between the two treatment methods. No reliable conclusions have been drawn. Objective: We conducted this meta-analysis to compare the improvement of cardiac structure of patients after surgical treatment and drug treatment, so as to clarify the efficacy of surgical treatment and drug treatment for PA patients. Methods: In order to examine the cardiac color ultrasound data of PA patients receiving surgical treatment and drug therapy (spironolactone, antisterone), randomized or observational studies were searched through Pubmed, Cochrane Library, and Embase. Meta-analysis was then carried out on the comprehensive and individual outcomes. The ROINBS-I scale is utilized to assess the offset risk of study inclusion. Outcomes: A total of nine studies involving 799 patients with PA into meta analysis, according to the results of the surgery in the treatment of patients with PA, left ventricular mass index (LVMI) changes in value (drop range) is significantly higher than drug therapy (Mean difference IV: —2.32, P In 6 studies, after surgical treatment of interventricular septal thickness (IVSD), changes in value (drop range) are also higher than drug therapy (Mean difference IV: —0.35, P In 2 studies, the surgical treatment of plasma aldosterone concentration (PAC) drop degree is superior to drug therapy (Mean difference IV: —12.63, P < 0.05), and blood pressure to improve the degree of surgery and drug treatment has no obvious difference. Conclusions: This meta-analysis result confirmed that after medical and surgical treatment of PA can obviously improve the patient’s blood pressure, and no difference between the two treatments. But for the heart structure improvement, including left ventricular hypertrophy and interventricular septum thickness, surgical treatment effect is significantly better than the medicine treatment, so the adrenalectomy can be used as unilateral PA optimal choice of treatment.

Nicotine-induced adrenal beta-arrestin1 upregulation mediates tobacco-related hyperaldosteronism leading to cardiac dysfunction

BACKGROUND Tobacco-related products,containing the highly addictive nicotine together with numerous other harmful toxicants and carcinogens,have been clearly associated with coronary artery disease,heart failure,stroke,and other heart diseases.Among the mechanisms by which nicotine contributes to heart disease is elevation of the renin-angiotensin-aldosterone system(RAAS)activity.Nicotine,and its major metabolite in humans cotinine,have been reported to induce RAAS activation,resulting in aldosterone elevation in smokers.Aldosterone has various direct and indirect adverse cardiac effects.It is produced by the adrenal cortex in response to angiotensin II(AngII)activating AngII type 1 receptors.RAAS activity increases in chronic smokers,causing raised aldosterone levels(nicotine exposure causes the same in rats).AngII receptors exert their cellular effects via either G proteins or the twoβarrestins(βarrestin1 and-2).AIM Since adrenal?arrestin1 is essential for adrenal aldosterone production and nicotine/cotinine elevate circulating aldosterone levels in humans,we hypothesized that nicotine activates adrenal?arrestin1,which contributes to RAAS activation and heart disease development.METHODS We studied human adrenocortical zona glomerulosa H295R cells and found that nicotine and cotinine upregulateβarrestin1 mRNA and protein levels,thereby enhancing AngII-dependent aldosterone synthesis and secretion.RESULTS In contrast,siRNA-mediatedβarrestin1 knockdown reversed the effects of nicotine on AngII-induced aldosterone production in H295 R cells.Importantly,nicotine promotes hyperaldosteronism via adrenalβarrestin1,thereby precipitating cardiac dysfunction,also in vivo,since nicotine-exposed experimental rats with adrenal-specificβarrestin1 knockdown display lower circulating aldosterone levels and better cardiac function than nicotine-exposed control animals with normal adrenalβarrestin1 expression.CONCLUSION Adrenalβarrestin1 upregulation is one of the mechanisms by which tobacco compounds,like nicotine,promote cardio-toxic hyperaldosteronism in vitro and in vivo.Thus,adrenalβarrestin1 represents a novel therapeutic target for tobaccorelated heart disease prevention or mitigation.

New advances in the diagnosis of primary aldosteronism

Primary aldosteronism (PA) is a common form of endocrine hypertension. The diagnostic process of PA includes a screening test, confirmatory test, and subtype classification. In this review, we have summarized the latest advances in the diagnosis of PA with regard to screening and confirmatory tests and provided some recommendations to improve clinical practice.

Diagnostic value of aldosterone to renin ratio calculated by plasma renin activity or plasma renin concentration in primary aldosteronism: a meta-analysis

Background:Since the diagnostic value of aldosterone to renin ratio(ARR)calculated by plasma renin concentration(PRC)or plasma renin activity(PRA)is still inconclusive,we conducted a meta-analysis by systematically reviewing relevant literature to explore the difference in the diagnostic efficacy of ARR calculated by PRC or PRA,so as to provide guidance for clinical diagnosis.Methods:We searched PubMed,Embase,and Cochrane Library from the establishment of the database to March 2021.We included studies that report the true positive,false positive,true negative,and false negative values for the diagnosis of primary aldosteronism,and we excluded duplicate publications,research without full text,incomplete information,or inability to conduct data extraction,animal experiments,reviews,and systematic reviews.STATA 15.1 was used to analyze the data.Results:The pooled results showed that ARR(plasma aldosterone concentration[PAC]/PRC)had a sensitivity of 0.82(95%confidence interval[CI]:0.78-0.86),a specificity of 0.94(95%CI:0.92-0.95),a positive-likelihood ratio(LR)of 12.77(95%CI:7.04-23.73),a negative LR of 0.11(95%CI:0.07-0.17),and symmetric area under the curve(SAUC)of 0.982,respectively.Furthermore,the diagnostic odds ratio(DOR)of ARR(PAC/PRC)was 180.21.Additionally,the pooled results showed that ARR(PAC/PRA)had a sensitivity of 0.91(95%CI:0.86-0.95),a specificity of 0.91(95%CI:0.90-0.93),a positive LR of 7.30(95%CI:2.99-17.99),a negative LR of 0.10(95%CI:0.04-0.26),and SAUC of 0.976,respectively.The DOR of ARR(PAC/PRA)was 155.52.Additionally,we conducted a subgroup analysis for the different thresholds(<35 or≥35)of PAC/PRC.The results showed that the DOR of the cut-off≥35 groups was higher than the cut-off<35 groups(DOR=340.15,95%CI:38.32-3019.66;DOR=116.40,95%CI=23.28-581.92).Conclusions:The research results suggest that the determination of ARR(PAC/PRC)and ARR(PAC/PRA)was all effective screening tools for PA.The diagnostic accuracy and diagnostic value of ARR(PAC/PRC)are higher than ARR(PAC/PRA).In addition,within a certain range,the higher the threshold,the better the diagnostic value.

Diagnostic evaluation of plasma aldosterone concentration to plasma renin activity ratio in primary aldosteronism

Using the plasma aldosterone concentration to plasma renin activity ratio(PAC/PRA ratio)as the screening test of choice for primary aldosteronism in hypertensive patients,we studied the clinical character-istics and the diagnostic value of PAC/PRA ratio in primary aldosteronism.The plasma aldosterone concen-tration(PAC)and plasma renin activity(PRA)levels were measured by radioimmunoassay in 902 hypertensive patients from out-patient clinics or hospitals.One hundred and twenty-six suspected primary aldosteronism patients whose PAC/PRA ratio was>25 ng/dL/ng/mL/hr had a lamellar computed tomography(CT)scan in the adrenal gland and follow-up visits.The proportion of primary aldosteronism in hypertensive patients was 14%(126/902).There were 54 patients with unilateral or bilateral hyperplasia and 25 patients with adenoma according to the CT scan.39%(49/126)of the patients with primary aldosteronism had hypokalemia.Twenty-five patients received surgical treatment.The efficacy and cure rates were 100%(25/25)and 48%(12/25),respect-ively.The effective rate of aldactone and the single-drug cure rate were 89%(48/54)and 24%(13/54),respectively.Primary aldosteronism affects over 10%of hypertensive patients in China.The PAC/PRA ratio can be considered as a routine screening test in hypertensives,especially resistant hypertensive patients and a high PAC/PRA ratio is an invaluable index in primary aldosteronism diagnosis.

Atractylenolide-I covalently binds to CYP11B2,selectively inhibits aldosterone synthesis, and improves hyperaldosteronism

Hyperaldosteronism is a common disease that is closely related to endocrine hypertension and other cardiovascular diseases. Cytochrome P450 11 B2(CYP11 B2), an important enzyme in aldosterone(ALD) synthesis, is a promising target for the treatment of hyperaldosteronism. However, selective inhibitors targeting CYP11 B2 are still lacking due to the high similarity with CYP11 B1. In this study,atractylenolide-I(AT-I) was found to significantly reduce the production of ALD but had no effect on cortisol synthesis, which is catalyzed by CYP11 B1. Chemical biology studies revealed that due to the presence of Ala320, AT-I is selectively bound to the catalytic pocket of CYP11 B2, and the C8/C9 double bond of AT-I can be epoxidized, which then undergoes nucleophilic addition with the sulfhydryl group of Cys450 in CYP11 B2. The covalent binding of AT-I disrupts the interaction between heme and CYP11 B2 and inactivates CYP11 B2, leading to the suppression of ALD synthesis;AT-I shows a significant therapeutic effect for improving hyperaldosteronism.

Application and evaluation of postural stimulation test and captopril challenge test in diagnosis of primary aldosteronism

Methods One hundred and twenty-eight patients with essential hypertension and 71 patients with primary aldosteronism were included in this study.The efficacy of different diagnostic indices of postural stimulation test(PST)with captopril challenge test(CCT)were compared by constructing receiver operating characteristic curve.

Association of KCNJ5 gene missense mutations with aldosterone-producing adenoma and primary hyperaldosteronism

Objective To detect the KCNJ5 gene variations in aldosterone-producing adenoma (APA) with primary hyperaldosteronism (PA) ,and to investigate the association of the KCNJ5 gene missense mutations with APA and PA.Methods A total of 46 APA tumors and their clinical characteristics were collected from Hypertension Center of the People’s Hospital of Xinjiang Uygur Autonomous Region,and all the tumors were confirmed by pathology.

The Beneficial Effect of Renin-Angiotensin-Aldosterone System Blockade in Treatment of Hypertension, Resistant to Conventional Antihypertensives, in Patients on Maintenance Hemodialysis

Background: Hypertension (HTN) is present in up to 90% of end stage kidney disease (ESRD) patients irrespective of the etiology of their kidney disease. Moreover, it is an important modifiable risk factor for progression to ESRD and its overall cardiovascular morbidity and mortality. Objective: to evaluate, prospectively, the role of Renin-Angiotensin-Aldosterone System blockade (RAAS) in HTN, resistant to 3 conventional antihypertensives, in patients on maintenance hemodialysis (MHD). Patients and methods: A total of 52 such patients were treated with Ramipril and 5 with Losartan after intolerable cough/shortness of breath following Ramipril-use. None of the patients had fluid depletion, renal artery stenosis and primary endocrinopathy. The study group was compared to a matched control group of MHD patients with normal blood pressure following 3 drugs-combination therapies. Results: All patients, with resistant HTN, had significant activation of RAAS system prior to treatment compared to inactive one in the control group. In those with resistant HTN, control of HTN, was established within 2 weeks of therapy and was associated with suppression of the RAAS. Such therapy was associated with minor side effects. Conclusion: Our study has shown that RAAS blockade is safe and effective in controlling such resistant HTN in MHD patients.

MicroRNA-155 mediates endogenous angiotensin II type 1 receptor regulation:implications for innovative type 2 diabetes mellitus management

Type 2 diabetes mellitus(T2DM)is a lifelong condition and a threat to human health.Thorough understanding of its pathogenesis is acutely needed in order to devise innovative,preventative,and potentially curative pharmacological interventions.MicroRNAs(miRNA),are small,non-coding,one-stranded RNA molecules,that can target and silence around 60%of all human genes through translational repression.MiR-155 is an ancient,evolutionarily well-conserved miRNA,with distinct expression profiles and multifunctionality,and a target repertoire of over 241 genes involved in numerous physiological and pathological processes including hematopoietic lineage differentiation,immunity,inflammation,viral infections,cancer,cardiovascular conditions,and particularly diabetes mellitus.MiR-155 Levels are progressively reduced in aging,obesity,sarcopenia,and T2DM.Thus,the loss of coordinated repression of multiple miR-155 targets acting as negative regulators,such as C/EBPβ,HDAC4,and SOCS1 impacts insulin signaling,deteriorating glucose homeostasis,and causing insulin resistance(IR).Moreover,deranged regulation of the renin angiotensin aldosterone system(RAAS)through loss of Angiotensin II Type 1 receptor downregulation,and negated repression of ETS-1,results in unopposed detrimental Angiotensin II effects,further promoting IR.Finally,loss of BACH1 and SOCS1 repression abolishes cytoprotective,anti-oxidant,anti-apoptotic,and anti-inflam matory cellular pathways,and promotesβ-cell loss.In contrast to RAAS inhibitor treatments that further decrease already reduced miR-155 Levels,strategies to increase an ailing miR-155 production in T2DM,e.g.,the use of metformin,mineralocorticoid receptor blockers(spironolactone,eplerenone,finerenone),and verapamil,alone or in various combinations,represent current treatment options.In the future,direct tissue delivery of miRNA analogs is likely.

Endocrine hypertension:An overview on the current etiopathogenesis and management options

Endocrine causes of secondary hypertension include primary aldosteronism,pheochromocytoma,cushing's syndrome,hyperparathyroidism and hypo-and hyperthyroidism.They comprise 5%-10% of the causes of secondary hypertension.Primary hyperaldosteronism,the most common of the endocrine cause of hypertension often presents with resistant or difficult to control hypertension associated with either normo-or hypokalemia.Pheochromocytoma,a great mimicker of many conditions,is associated with high morbidity and mortality if left untreated.A complete history including pertinent family history,physical examination along with a high index of suspicion with focused biochemical and radiological evaluation is important to diagnose and effectively treat these conditions.The cost effective targeted genetic screening for current known mutations associated with pheochromocytoma are important for early diagnosis and management in family members.The current review focuses on the most recent evidence regarding causes,clinical features,methods of diagnosis,and management of these conditions.A multidisciplinary approach involving internists,endocrinologists and surgeons is recommended in optimal management of these conditions.

Aldosteronoma causing Conn’s syndrome: a case report and literature review

We report a case of primary aldosteronism caused by bilateral solitary aldosteronomas occurring 6 months apart, the diagnosis being confirmed by clinical features. Multiple aldos-terone-producing adenomas can be unilateral or bilateral. If bilateral, most of them are found simultaneously. Bilateral solitary aldosterono-mas occurring at separate times are rarely re-ported and the pathogenesis is still elusive. We believe, from this case, the postoperative fol-low-up in patients with primary aldosteronism is mandatory.

Sex difference in the prevalence of metabolic syndrome and its relationship to BMI and age

Objective:To investigate the prevalence of metabolic syndrome (MetS) in primary aldosteronism(PA) patients with different genders and relationship between body mass index(BMI), age and MetS. Methods:This study included 168 PA patients who were hospitalized in hypertension treatment center of Xinjiang Uygur Autonomous Region People' Hospital, including 94 male patients and 74 female patients and the backgrounds and biochemical parameters of two groups were compared. Based on this, the relationship between BMI, age and MetS were also analyzed. Results:The prevalence of MetS was significantly higher in male patients with PA than female patients with PA(83.0% vs 58.1%,P<0.001). Compared to PA patients without MetS, PA patients with MetS had a higher level of BMI and greater prevalence of obesity (P<0.05). According to the BMI stratification analysis, we found the prevalence of MetS was higher in obese groups than non-obese groups (P<0.05). Moreover, the obese male patients with PA had higher prevalence of every component of MetS and prevalence of MetS with 5 metabolic factors compared to the non-obese group (P<0.05);while the obese female patients with PA only had higher prevalence of abdominal obesity compared to the non-obese group (P<0.001). Among the patients classified by age, the both prevalence of MetS was higher in male than female, and there was no male:female ratio inverted in patients with PA after menopause. Conclusions:The prevalence of MetS in male patients with PA was higher than female patients with PA. In addition, the obese groups had the higher prevalence of MetS than non-obese groups.

肾上腺醛固酮瘤和嗜铬细胞瘤的多层螺旋CT诊断

醛固酮瘤（aldosterone-producing adenoma,APA）和嗜铬细胞瘤（pheochromocytoma）是肾上腺最常见的肿瘤。虽然肿瘤的组织来源不同,但临床上都以继发性高血压为主要临床表现,鉴别诊断依靠实验室检查和影像学技术[1]。随着CT技术的发展,尤其是多层螺旋CT（multi-slice computed tomography,MSCT）的普及应用,CT较B超诊断肾上腺醛固酮瘤与嗜铬细胞瘤的优势更突出。

Coexistence of the Hypersecretion of Catecholamine,Adrenal Cortical Nodular Hyperplasia,and Nephrotic-Range Proteinuria of Focal Segmental Scleronephrosis:Is It Fat-Induced Hypertension?

Two patients had a long history of hypertension and one of them also had a nephrotic-range proteinuria secondary to focal segmental scleronephrosis which had been diagnosed by kidney biopsy. They presented with uncontrolled hypertension. Laboratory examination suggested hypersecretion of catecholamines by the left adrenal glands in both patients and primary aldosteronism in one of them. A computed tomography scan revealed small nodules on left adrenal gland in both patients. Patients underwent laparoscopic left adrenalectomy. After surgery, blood pressure was normalized and proteinuria was resolved. Most interestingly, prominent adipocytes infiltrated were detected in the adrenal cortex and were associated with the presence of lymphocytes, which suggested that adipocytes might have a role in the pathogenesis of these diseases in our patients.