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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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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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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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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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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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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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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: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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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 compare the detection efficiency of the ratio of plasma aldosterone concentration 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 patients 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 value of CYP11B2 immunohistochemistry in the histopathological diagnosis of primary aldosteronism(PA) among Chinese population.@*Methods@#Ninety-six cases of unilateral PA patients were retrospectively enrolled, and with 15 cases of non-hyperfunctioning adenoma, and 15 cases of cortisol producing adenoma as control. CYP11B2 immunohistochemistry was performed in the tumor sections of these patients and was analysed by semi-quantified method. The positive rate of CYP11B2 in tumor specimen of all cases enrolled was calculated and PA patients were subtypely classified based on their histopathological features and CYP11B2 expressions.@*Results@#The immune-positive rate of CYP11B2 in the PA group was 91.7% (88/96), with the control group being 6.7% (2/30, P<0.001). Subgroup analysis revealed that the immune-positive rate of CYP11B2 in the aldosterone producing adenoma group and unilateral hyperplasia group were 91.8% (78/85) and 90.9% (10/11), respectively. Based upon histopathological feature and CYP11B2 immunohistochemistry, PA patients were further subtypely classified as aldosterone producing adenoma (85/96), unilateral diffuse adrenocortical hyperplasia (7/96), unilateral mono-adrenocortical micronodules (1/96), unilateral multiple adrenocortical micronodules (1/96), and unilateral multiple aldosterone-producing cell clusters (multiple APCCs, 2/96).@*Conclusion@#CYP11B2 immunohistochemistry may serve as an useful tool for the histopathological diagnosis of 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.
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Objective To compare the imported (Diasorin,Italy) and domestic (Mindray,Shenzhen) chemiluminescent systems used in the measurement of plasma aldosterone and renin concentrations;To establish the reference interval of plasma aldosterone and renin concentrations in healthy adults.Methods With the assay instrument and its kits from Italy Diasorin as the reference system,the concentrations of plasma aldosterone and renin were measured by the two systems,in 143 healthy adults,72 patients with hypertension (16 patients with primary aldosteronism) and to establish the medical reference range (P2.5-P97.5) of them.Results The plasma aldosterone (r=0.914,P＜0.01) and renin(r=0.977,P＜0.01)concentrations detected by the two systems were positively correlated.Distribution of plasma aldosterone and renin was skewed in healthy adults.The reference interval was 30.8-344.6 pg/ml for aldosterone and 2.4-90.0 μIU/ml for renin by the imported chemiluminescent system.The reference interval was 29.4-473.3 pg/ml for aldosterone and 3.6-98.3 μIU/ml for renin by the domestic chemiluminescent detection system.Conclusion The two systems are closely correlated in measuring plasma aldosterone and renin concentrations.
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More and more cases of aldosterone-and cortisol-producing adenoma (A/CPA) have been reported in recent years.In order to further understand the clinical characteristics of patients with A/CPA,we report 2 cases of A/CPA treated in our hospital,and analyzes them in combination with domestic reports.We recommend that clinicians routinely perform Low Dose Dexamethasone Suppression Test on every primary aldosteronism patient prior to adrenal vein sampling (AVS) or adrenal adenoma surgery to rule out the possibility of Cushing's syndrome so as to avoid the wrong judgment of AVS results and avoid adrenal hypofunction or adrenal crisis after operation.
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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 assess the diagnostic value of saline infusion test ( SIT) and its optimal cutoff in the diagnosis of primary aldosteronism ( PA ), and to analyze whether the dietary salt intake affects the SIT accuracy. Methods This is a prospective study. All 236 patients with a high risk for PA underwent the screening test, SIT and the fludrocortisone suppression test (FST) in separate days. The diagnosis of PA was established according to the FST criteria. According to the 24 h urinary sodium level, the patients were divided into low salt, normal salt, and high salt groups respectively, and the effect of salt intake on SIT was analyzed. Receiver operating characteristic (ROC) analysis was performed to compare the diagnostic accuracies. Results Finally, in 236 patients with high risk for PA, 134 patients with PA and 102 patients with essential hypertension ( EH) were diagnosed. Using post-test plasma aldosterone concentration (PAC) for diagnosis, the area under the ROC curve (AUCROC) of the SIT was 0.974 (0.957, 0.991), which was significantly higher than that of the post-test plasma aldosterone to renin ratio (ARR) [0.900 ( 0. 862, 0. 938)] and that of the PAC suppression percentage [ 0. 752 ( 0. 690, 0. 813)] ( both P<0.01). Considering both sensitivity and specificity, an optimal cutoff of PAC post-SIT was set at 8 ng/dl, resulting in a sensitivity of 88. 1% and a specificity of 95. 1%. The PAC post-SIT, whether in PA or EH patients, had no statistically significant differences among low salt, normal salt, and high salt groups (P>0.05). Conclusion SIT is reliable for the diagnosis of PA. PAC post-SIT more than 8.0 ng/dl is recommended to confirm PA.
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Prevalence of primary aldosteronism (PA) ranges from 5%to 10%in hypertensive patients. The diagnostic process of PA includes screening, confirmation, and subtype classification. In this manuscript, the recently published data from China regarding to screening and confirmatory tests were summarized, and some important instructions of screening and confirmatory tests were emphasized for improving clinical practice.
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Primary aldosteronism is a common cause of endocrine hypertension. Aldosterone-producing adenoma and bilateral idiopathic hyperplasia are the two major subtypes of primary aldosteronism. Unilateral adrenal hyperplasia as one of the rare subtypes was seldom reported. Herein, we present in detail a patient with unilateral adrenal hyperplasia difficult to be subtyped. By discussing several key points of the diagnosis and treatment process, some useful experiences and information are provided for the clinicians.