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Objective:To analyze the clinical characteristics and prognosis of patients with primary aldosteronism (PA) associated with subclinical Cushing syndrome (SCS).Methods:This retrospective cohort study was conducted at the First Affiliated Hospital of Chongqing Medical University in China. Patients with PA were included between January 2014 and December 2022. According to the results of 1-mg overnight dexamethasone suppression test, the patients were divided into the PA group and PA associated with SCS (PA/SCS) group. The demographic information, hormone levels, and follow-up results were analyzed. Independent sample t-test, chi-square test and Mann-Whitney U test were used for data comparison. Results:A total of 489 PA patients were enrolled in this study, of which 109 had PA/SCS (22.3%). Patients with SCS were on average older (54.4±10.7 vs . 47.4±11.0, P<0.001); had a larger proportion of women (69.7%, 76/109 vs . 57.4%, 218/380; P=0.020); and a longer duration of hypertension [96 (36, 180) vs . 60 (12, 120) months, P=0.001] than patients without SCS. There were 215 and 51 patients in the PA group and PA/SCS group, who completed adrenalectomy and follow-up, respectively. The remission rate of autonomous cortisol secretion in the PA/SCS group was 85.3% (29/34). There was no significant difference in the remission rate of autonomous aldosterone secretion among patients between the PA/SCS and PA group (94.1%, 48/51 vs. 94.4%, 203/215; P=1.000), while the clinical remission rate in the PA/SCS group was lower than that in the PA group (39.2%, 20/51 vs. 61.9%, 133/215; P=0.003). Conclusions:SCS is common in PA patients (22.3%), and the clinical remission rate is low. Screening using the 1-mg overnight dexamethasone suppression test is recommended for all patients with PA.
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Objective:To investigate the distribution of pathological types of unilateral primary aldosteronism, and to explore the clinical characteristics and prognosis of patients with different pathological types.Methods:A total of 241 patients with unilateral primary aldosteronism who underwent adrenal surgery were included in this study. The clinical data and postoperative follow-up data were collected, and the postoperative tissue sections were stained with HE and aldosterone synthase. According to the staining results, pathological types of 241 patients were classified, and the clinical characteristics and surgical prognosis of patients with unilateral primary aldosteronism were compared.Results:According to the international histopathology consensus for unilateral primary aldosteronism, among 241 patients with unilateral primary aldosteronism, 223 were classical(92.5%), 17 were non-classical(7.1%), and 1 was aldosterone producing carcinoma(0.4%). Among classical cases, 189 were aldosterone producing adenoma and 34 were aldosterone producing nodule. In the non-classical cases, 8 cases were multiple aldosterone producing nodule and 9 cases were multiple aldosterone producing nodule. Compared with the classical group, the non-classical group had a longer duration of hypertension(9.0 vs 5.0 years, P=0.062) and a lower baseline plasma aldosterone concentration(273 vs 305 pg/mL, P=0.147), but the difference was not significant. There was no significant difference between the two groups in the proportion of patients who achieved a complete biochemical response after surgery(98% vs 92.3%, P=0.281), but the proportion of patients who achieved a complete clinical response was significantly lower in the non-classical group(23.1% vs 52.9%, P=0.046). Conclusion:The pathological types of unilateral primary aldosteronism are predominantly classical, with aldosterone-producing adenoma being the most common. There were no significant differences in the clinical characteristics and postoperative biochemical remission rates between classical and non-classical patients, but the clinical prognosis of the latter was inferior to the former.
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Objective:To evaluate postoperative biochemical and clinical remission rates in patients with unilateral primary aldosteronism and analyze related influencing factors.Methods:A total of 406 patients of primary aldosteronism with confirmed subtyping, who underwent adrenalectomy and completed follow-up in the Department of Endocrinology of the First Affiliated Hospital of Chongqing Medical University from November 2013 to March 2022 were retrospectively enrolled. Clinical and biochemical data were recorded. Postoperative clinical and biochemical outcomes were assessed according to Primary Aldosteronism Surgery Outcome(PASO) consensus.Results:Complete biochemical success was achieved in 391(96.31%) of 406 primary aldosteronism patients, while partial and absent biochemical success in only 4(0.99%) and 11(2.71%) primary aldosteronism patients; Complete clinical success was seen in 217(53.45%) patients, and partial clinical success in 189(46.55%) patients. Compared to the partial clinical success group, the complete clinical success group was younger, had a greater proportion of women, a smaller body mass index, a shorter duration of hypertension, a smaller daily defined dose value for antihypertensive medication, a higher estimated glomerular filtration rate(eGFR), and a lower proportion of family history of hypertension and diabetes mellitus. Multifactorial logistic regression analysis further showed that gender( OR=2.49, 95% CI 1.42-4.35, P=0.001), body mass index( OR=1.16, 95% CI 1.05-1.28, P=0.003), antihypertensive drug daily defined dose( OR=1.83, 95% CI 1.37-2.44, P<0.001), family history of hypertension( OR=2.16, 95% CI 1.22-3.83, P=0.008), history of diabetes( OR=2.47, 95% CI 1.15-5.29, P=0.021), and eGFR( OR=0.98, 95% CI 0.97-0.99, P=0.001) were independent factors influencing clinical prognosis of primary aldosteronism. Conclusion:The postoperative complete biochemical success is higher in patients with unilateral primary aldosteronism, but only about half of all patients achieve complete clinical success.
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Objective:To investigate the appropriate cut-off for diagnosis of primary aldosteronism (PA) by seated saline suppression test (SSST) based on liquid chromatography with tandem mass spectrometry (LC-MS/MS).Methods:In this cross-sectional study, patients who underwent SSST for suspected PA in the First Affiliated Hospital of Chongqing Medical University from January 2018 to March 2022 were evaluated. Briefly, 300 patients with PA and 119 with essential hypertension (EH) were included. Plasma aldosterone concentration (PAC) after SSST was determined by LC-MS/MS. Primary aldosteronism confirmatory testing (PACT) score was used as the reference standard for diagnosis of PA, and receiver operating characteristic (ROC) curve was used to explore the cut-off value.Results:The average age of the PA group was (50.8±10.5) years, and males accounted for 53.00% ( n=159); the average age of the EH group was (49.4±11.2) years, and males accounted for 26.89% ( n=32). The area under the ROC curve of PAC post-SSST was 0.819 (95% CI 0.775-0.862). When 40 pg/ml (110.8 pmol/L) was selected as the appropriate cut-off for diagnosis of PA, the sensitivity was 83.67% (95% CI 78.88%-87.56%) and specificity was 60.50% (95% CI 51.10%-69.21%). Thus, 95.09% (155/163) of patients with unilateral PA could be identified. Conclusion:PAC after SSST determined by LC-MS/MS has high efficacy for diagnosis of PA, and 40 pg/ml is recommended as the appropriate cut-off value.
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Hemorrhagic transformation (HT) is a serious complication after acute ischemic stroke, leading to increased adverse outcomes and mortality. In recent years, there has been an increasing number of studies in predicting HT occurrence, but most of the existing studies have focused on patients accepted reperfusion therapy, and few studies have predicted spontaneous HT. This article provides a review of epidemiology, risk factors, and available prediction models for prediction of spontaneous HT after acute ischemic stroke.
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The pathogenesis of stroke is complex, with genetic risk factors as one of the main factors. The genetic variants of phosphodiesterase 4D (PDE4D) was significantly associated with the susceptibility to ischemic stroke (IS) in Caucasian population, but its association with the susceptibility to stroke in Chinese population is unclear. This article is intended to review the research on the association between PDE4D genetic variants and stroke susceptibility in Chinese population, aiming to further optimize the relevant research programs and provide reference for the prevention and treatment of stroke in China.
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Humanos , Isquemia Encefálica/genética , Predisposição Genética para Doença , População do Leste Asiático , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Acidente Vascular Cerebral/genética , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
The typical manifestations of primary aldosteronism (PA) are hypertension with or without hypokalemia, high aldosterone, and low renal level. However, PA with normal blood pressure is rare in clinical practice. This article reported the diagnosis and treatment of a patient with subclinical PA, admitted for "adrenal accidental tumor" with normal blood pressure and serum potassium. We summarized and analyzed the clinical characteristics and treatment strategies, in order to provide some reference for clinicians.
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Objective:To analyze the distribution characteristics of plasma renin concentration (PRC) in patients with aldosterone-producing adenoma (APA) and its impact on diagnosis.Methods:In this retrospective case series, clinical data from 200 patients with APA (80 men and 120 women; mean age 45.6 years) in the First Affiliated Hospital of Chongqing Medical University from November 2013 to January 2022 were evaluated. PRC was determined by automated chemiluminescence immunoassay. The distribution characteristics of PRC were analyzed, and 8.2 mU/L was used as the low renin cutoff to evaluate whether renin was suppressed.Results:The median PRC was 1.6 mU/L (range, 0.4-41.5 mU/L). There were 116 patients with APA with PRC of ≤2 mU/L, 41 patients with 2<PRC≤4 mU/L. PRC was not suppressed (PRC>8.2 mU/L) in 8.0% (16/200) of the patients with APA. And PRC was not suppressed in 2.5% (5/200) of the patients with APA, resulting in a primary aldosteronism negative screening outcome.Conclusions:Although most patients with APA have low PRC, there are a small number (8%) of patients whose PRC has not been fully suppressed, which can lead to missed diagnoses during primary aldosteronism screening. While primary aldosteronism is highly suspected, further investigations are required to determine the diagnosis, even if PRC is not fully suppressed at screening.
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Primary aldosteronism (PA) is a kind of disease caused by excessive aldosterone secretion from the adrenal cortex, the reason of which include bilateral adrenal hyperplasia, aldosteronoma, unilateral adrenal hyperplasia, etc. Surgical treatment is the first choice for unilateral adrenal lesions. In this article, we report a patient who underwent left adrenal surgery but did not achieve the expected results. This case suggests that clinicians need to further improve the level of diagnosis and treatment of primary aldosteronism, especially the surgical methods.
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Unilateral primary aldosteronism (UPA) is a common form of PA that is surgically curable by adrenalectomy of the overactive gland. Pathological evaluation of resected adrenals is crucial in the diagnosis of UPA, and its subsequent treatment and follow-up as well. Histomorphological evaluation is the basis for the pathological diagnosis of UPA, and the wide use of aldosterone synthase immunohistochemical staining in recent years has greatly improved the pathological diagnosis of UPA. However, there is a lack of standardized nomenclature and diagnostic criteria. Therefore, consensus on the histopathologic diagnosis of UPA were developed by an international group of pathologists led by Tracy Ann Williams, and published in J Clin Endocrinol Metab, 2021. This article will elaborates on the key points in the consensus to advance the understanding and overall improve clinical mangement of UPA.
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Primary aldosteronism(PA) is one of the most common secondary hypertension, the pathogenesis is still not fully understood. Aldosterone synthase(CYP11B2) was thought to be continuously expressed in the zona glomerulosa of the adrenal cortex. In recent years, it is found that there were discontinuous CYP11B2 positive cell clusters in adrenal cortex via immunohistochemical staining, and proposed the concept of aldosterone-producing cell clusters(APCC). Thenceforwarding a growing body of studies suggest that there may be a potential causal link between APCC and PA. This article summarizes the latest studies on APCC and provide an update on the potential role of APCC in the pathogenesis of PA.
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Objective:The aim of the present study was to re-evaluate the diagnostic value and optimal cutoff point of captopril challenge test (CCT) in diagnosis of primary aldosteronism (PA).Methods:This is a retrospective study. All patients with a high risk for PA underwent screening test, and then proceeded to CCT and fludrocortisone suppression test (FST) on different days. The FST was used as a reference standard for PA. The plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) were measured with an automated chemiluminescence immunoassay. Random number method was performed in the patients with unilateral primary aldosteronism (UPA), in order to make the proportion of the analyzed UPA in PA was 35%. Receiver operating characteristic (ROC) analyses were performed to compare diagnostic accuracy.Results:A total of 543 patients with 400 PA patients and 143 essential hypertension (EH) patients were enrolled. The diagnostic value of post-CCT PAC was significantly higher than that of the post-CCT plasma aldosterone-renin ratio (ARR), and that of the PAC suppression percentage, respectively. The area under the ROC curve (AUC ROC) was 0.86 (0.83, 0.89) for PAC, 0.78 (0.74, 0.82) for ARR, and 0.62 (0.56, 0.67) for the PAC suppression percentage (all P<0.01), respectively. The optimal cutoff point of post-CCT PAC for PA was 110 ng/L, in which the sensitivity and specificity were 73.25% and 79.02%, respectively. The diagnostic efficiency of post-CCT PAC was not improved either in combination with PAC suppression percentage or in combination with post-CCT ARR. Conclusions:CCT is a useful test for the confirmation of PA. PAC level of 110 ng/L at 2 h after 50 mg of captopril is recommended as an optimal cutoff point for the diagnosis of PA.
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Stroke is a common disease with high incidence worldwide. Ischemic stroke (IS) is a major subtype of stroke. IS, a complex polygenic disease, is affected by a variety of environmental and genetic factors. Therefore, understanding the genetic risk factors for IS is an important step to clarify the pathogenesis, optimize the prevention strategy and determine new therapeutic targets of IS. Two genome wide association studies (GWASs) in 2012 and 2015 showed that there were risk loci on chromosome 6p21.1 associated with IS, but the results of subsequent replication studies were controversial. Moreover, the exploration of biological function and molecular mechanism of genetic variants on chromosome 6p21.1 affecting IS susceptibility is in the initial stage. This paper reviews the studies on the correlation between genetic variation in chromosome 6P21.1 region and IS susceptibility, in order to further clarify its mechanism in IS and provide theoretical basis for prevention and treatment of IS.
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Objective:To investigated the clinical, biochemical, and immunohistological characteristics of patients with aldosterone producing adenoma(APA)and different gene mutations.Methods:The clinical and biochemical data of 206 patients with APA who received unilateral adrenalectomy were collected. Sanger sequencing was used to identify the mutation in the hot-point of KCNJ5 and other genes. The tumor samples were stained by 11β-hydroxylase(CYP11B1)and aldosterone synthase(CYP11B2), which was quantified by McCarty′s H-score system.Results:The gene mutations were identified in 166 out of 206(80.6%)patients with APA, of which 158 cases were KCNJ5 mutation, 2 ATP1A1 mutation, 5 ATP2B3 mutation, and 1 CTNNB1 mutation. Age, duration of hypertension, and serum potassium in APA patients with genetic mutant were significantly lower than those without genetic mutation( P<0.05) while the proportion of female, systolic blood pressure, diastolic blood pressure, aldosterone/renin ratio(ARR), and plasma aldosterone concentration(PAC)post saline infusion test(SIT)were significantly higher( P<0.05). Subgroup analysis showed that age, duration of hypertension, systolic blood pressure, and proportion of left ventricular hypertrophy in APA patients with ATP1A1 and ATP2B3 mutations were significantly higher than those with KCNJ5 mutation( P<0.05)while the PAC post SIT and tumor diameter were significantly lower( P<0.05). The positive rates of CYP11B2 in APA with different mutations were not significantly different. The H-score of CYP11B1 was significantly higher [160.0(127.5, 193.5) vs 80.0(27.5, 152.3), P=0.020] and the H-score of CYP11B2 was significantly lower [155.0(123.0, 190.0) vs 240.0(140.0, 270.0), P<0.01] in APA with KCNJ5 mutation compared with those with ATPase mutation. Conclusion:The types of genetic mutation are closely correlated with the clinical, biochemical, and immunohistological phenotypes in patients with APA.
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Objective:Aimed to investigate the value of adrenocorticotropic hormone (ACTH) stimulation in adrenal venous blood sampling (AVS).Methods:Patients who diagnosed as primary aldosteronism (PA) and completed successful bilateral cannulation judged by selection index (SI) for routine and(or) ACTH stimulation AVS were enrolled. The lateralization index(LI) was calculated to compare the effect of ACTH stimulation on AVS cannulation success rate and lateralization judgment.Results:A total of 73 patients with PA were enrolled in the study, of whom 28 were confirmed as aldosterone producing adenoma (APA) after unilateral adrenalectomy. Cortisol and aldosterone in peripheral and adrenal veins were significantly increased after ACTH stimulation. The left SI was increased from 6.5(3.0-13.6) to 26.8 (16.9-40.3) ( P<0.01) and the right SI from 20.8(4.8-34.8) to 57.6(35.7-80.9) ( P<0.01) after ACTH stimulation. There was no significant difference on LI before and after ACTH stimulation [7.7(2.3-19.6) vs 5.6(1.9-14.6), P=0.14]. The success rates of left and right adrenal cannulation were increased by 15% and 10% respectively after ACTH stimulation. For 57 patients who were determined in successful cannulation by both routine and ACTH stimulation AVS, 27 patients were determined to have lateralization by both AVS methods, 21 patients were determined to have bilateralization, and the consistency of lateralization by both AVS methods was 84%(48/57). Among the 28 patients who were confirmed to be APA after unilateral adrenalectomy, the correct rate of lateralization by both AVS methods was 89% (25/28). Conclusion:ACTH stimulation is able to improve the success rate of bilateral adrenal vein cannulation, and is helpful to judge AVS results. For patients with successful cannulation, there is no significant difference in lateralization judgment for routine and ACTH stimulation AVS.
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To investigate the renal venous and spermatic venous sampling in assisting the diagnosis of reninoma. The case of reninoma was retrospectively reviewed together with the literature review of reninoma diagnosed with renal venous and spermatic venous sampling. A young patient with hypertension and headache was admitted to our hospital. Laboratory test showed high plasma renin concentration (>500 mIU/L), and enhanced computed tomography(CT) in the upper abdomen showed a mass in left inferior renal pole. The concentration of renin in the left spermatic vein was significantly higher than that in renal veins and branches, and peripheral vein, which was considered the left reninoma possibility. The left renal mass was resected surgically and pathologic exam revealed reninoma. The renin level and the blood pressure recoveried normal after operation.The literature reported that the positive rate of renal vein segmental blood collection for locating renin tumor was only 8.3%-64%. The possible reason was that reninoma usually located in the renal cortex, and the tumor blood might be collected by renal capsule vein instead of renal vein. In fact, the renal capsule vein intersects with the lateral division of the spermatic vein, but there have been no reports about the localization of reninoma by spermatic vein sampling. Since renin secreted by reninoma may go into the spermatic vein through renal capsule vein, it should be noted that spermatic venous blood should be collected simultaneously in renal vein sampling when locating reninoma.
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An article entitled "Adrenal incidentalomas are tied to increased risk of diabetes: findings from a prospective study" published in JCEM in April 2020, was hereby translated into Chinese after obtaining the copyright [Giuseppe R, et al. J Clin Endocrinol Metab, 2020, 105(4): dgz284]. This is a prospective study to explore the frequency of adrenal incidentalomas and their association with comorbid diseases. It recruited 601 patients who underwent abdominal CT scan in the radiology department at a public hospital. Those with any history or doubt of adrenal diseases or malignancy were considered as non-eligible. In 7.3% of the patients, adrenal incidentalomas were serendipitously found. The patients with an adrenal incidentaloma were with higher body mass index( P=0.009) and higher waist circumference( P=0.007) and were more frequently diabetic(31.8% vs 14.2%, P=0.003 8). Multivariate regression analysis showed that diabetes was significantly associated with the presence of adrenal incidentalomas( P=0.003). Autonomous cortisol secretion was observed in 50% of patients(plasma cortisol≥50 nmol/L after 1 mg dexamethasone). This is the first study showing that the frequency of adrenal incidentalomas is 7.3% in a prospective radiological series avoiding ascertainment bias and adrenal incidentalomas are tied to increased risk of type 2 diabetes.
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Objective:To explore the proportion of obstructive sleep apnea (OSA) in primary aldosteronism (PA) in Chinese population and compare the clinical characteristics between PA patients with OSA and those without.Methods:A total of 96 patients diagnosed with PA from September 2015 to November 2018 were recruited in this study. OSA was screened by cardio-respiratory polygraphy. According to the apnea hypopnea index (AHI), the patients were divided into PA with OSA group (AHI ≥5 times) and PA without OSA group (AHI<5 times).Results:Among all patients (96), 69 (71.9%) were with OSA, among them 22 patients (22.9%) were with mild OSA, 17 patients (17.7%) were with moderate OSA and 30 patients (31.3%) were with severe OSA. Compared with the patients without OSA, the patients with OSA were elder, and had higher levels of body mass index (BMI), waist circumference (WC), hip circumference (HC), creatinine (CR) and glycosylated haemoglobin (HbA1c) ( P<0.05), but lower concentrations of plasma aldosterone (PAC), supine aldosterone renin concentration ratio(ARR) and the PAC after the diagnosis test ( P<0.05). Spearman correlation analyses showed that BMI, WC, HC, CR and HbA1c were positively correlated with AHI ( P<0.05), while high-density lipoproteincholesterol (HDL-C), supine-PAC and saline infusion test(SIT)-post PAC were negatively correlated with AHI ( P<0.05). Conclusions:The proportion of OSA in PA patients is relatively high (71.9%). Metabolic abnormalities are more common in PA patients with OSA, indicating that screening for OSA should be carried out routinely in PA patients.
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Objective To compare the detection efficiency of the ratio of plasma aldosterone concentra-tion to renin concentration (ARR) measured by imported and domestic chemiluminescent immunoassay kits for screening primary aldosteronism (PA). Methods A total of 164 patients with essential hypertension and 64 pa-tients with PA were recruited in this study. Plasma aldosterone concentration (PAC) and renin concentration (PRC) were measured concurrently by imported chemiluminescent immunoassay kit(Diasorin, Italy) and domestic kit (Mindray, Shenzhen, China), and then ARR were calculated. A ROC curve analysis was performed to compare the screening efficacy of the two kits and the optimal ARR cut-offs for PA screening were recommended according to Youden's index. Results The areas under the ROC curves (AUCROC) of ARR were 0.937 (95% CI 0.897-0.965, P<0.0001) detected by imported kit and 0.942 (95% CI 0.903-0.968, P<0.0001) detected by domestic kit. The difference of AUCROC of ARR detected by two kits was 0.00457 (95% CI -0.0210-0.0302, P<0.7263).The highest Youden's indexes of ARR were 0.749 (detected by imported kit) with the cut-off value of 12.8(pg/ml)/(μIU/ml)(sensitivity 96.87%, specificity 78.05%) and 0.756 (detected by domestic kit) with the cut-off value of 12.5 (pg/ml)/(μIU/ml)(sensitivity 89.06%, specificity 86.59%). Conclusions There was no significant difference between domestic and imported chemiluminescent immunoassays in the screening efficiency of ARR for PA.
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Objective@#To evaluate the consistency of different methods for detecting aldosterone concentration in blood and to establish a reference interval of serum aldosterone concentration by liquid chromatography-tandem mass spectrometry(LC-MS/MS).@*Methods@#Concentrations of blood aldosterone were measured by LC-MS/MS, chemiluminescent assays (Diasorin, Domestic A and B systems) and radioimmunoassay (RIA) in 138 healthy adults, 67 patients with essential hypertension and 23 patients with primary aldosteronism.@*Results@#Aldosterone concentrations measured by various methods were quiet different(P<0.01). Spearman correlation analysis showed that the correlation coefficient were 0.776(P<0.01) between CLIA (Diasorin) and LC-MS/MS, 0.805(P<0.01) between CLIA (Domestic A) and LC-MS/MS, 0.058(P>0.05) between CLIA(Domestic B) and LC-MS/MS, 0.338(P<0.01) as well as between RIA and LC-MS/MS. Bland-Altman analysis for the measurements showed poor consistency among methods for aldosterone concentrations. The reference interval was 15.2-222.2 pg/ml for serum aldosterone concentrations by LC-MS/MS.@*Conclusions@#There are significant differences of blood aldosterone concentrations determined by different methods. Clinically, a specified reference interval might be needed while using different methods.