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Introduction: The clinical biochemical characteristics and target organ damage (TOD) in patients with plasma aldosterone concentrations (PAC) ranging from 50 to 100 ng/L after a saline infusion test (SIT) have not been fully studied. Methods: A total of 611 hypertensive patients with an elevated aldosterone-to-renin ratio (ARR) who underwent a supine SIT at Henan Provincial People's Hospital were enrolled. The patients were divided into three groups according to their post-SIT PAC: <50 ng/L (control group), 50–100 ng/L (indeterminate post-SIT results group), and >100 ng/L (PA group). The clinical and biochemical characteristics and TOD of the three groups were compared. The correlation of the post-SIT PAC with left ventricular mass index (LVMI) was assessed via regression analysis. Results: The indeterminate post-SIT results group had the youngest patients and the shortest duration of hypertension. The prevalence of renal impairment (RI) and left ventricular hypertrophy (LVH) was lower than that in the PA group (P<0.05), but there was no statistically significant difference from the control group (P>0.05). After adjustment for confounders, the risk of developing carotid plaque was greater in the indeterminate post-SIT results group than in the control group (OR 1.73, 95% CI: 1.11, 2.69), and the prevalence of RI and LVH tended to increase with increasing post-SIT PAC levels. In multiple regression analyses, LVMI was significantly correlated with post-SIT PAC (P<0.05), but the basal PAC, plasma renin activity, and ARR did not significantly correlate with LVMI (P>0.05). Conclusion: A post-SIT PAC of 50–100 ng/L may be indicative of an early form of PA, and it may serve as an independent predictor of LVH, which could be related to the level of autonomously secreted aldosterone. [ABSTRACT FROM AUTHOR]

Context: Primary aldosteronism (PA) is the most common form of endocrine hypertension. According to the Endocrine Society Practice Guidelines, the diagnosis of PA requires a pathological screening test result and non-suppressible aldosterone levels during confirmatory testing. Sequential testing with more than one confirmatory test may result in discordant test results. Objective and patients: We investigated the association of discordant results of captopril challenge test (CCT) and saline infusion test (SIT) on patient subtype classification by adrenal vein sampling (AVS) and outcome in 111 consecutive patients from the German Conn's Registry. Concordance was defined as non-suppressible aldosterone levels upon both tests, while discordance was defined as conflicting test results. Patients with unilateral disease were offered adrenalectomy (ADX). Biochemical and clinical outcomes were assessed using the PASO criteria. Results: 85 of 111 (77%) patients had concordant results of CCT and SIT. Although baseline characteristics were comparable between patients with concordant and discordant tests, the latter had significantly lower aldosterone levels after testing (CCT: 170 vs. 114pg/ml; SIT: 139 vs. 101pg/ml; p=0.004). In 35% of patients with discordant (n=9) and 46% of concordant test results (n=39), AVS suggested lateralized PA. In 36 of 48 cases ADX was performed. 86% of patients with discordant and 72% with concordant results had complete biochemical success. Conclusion: The use of two confirmatory tests in patients with PA results in discordant results in approximately 23% of cases. Patients having discordant confirmatory test results had a comparable rate of lateralized PA and underwent adrenalectomy with similar long-term outcome. [ABSTRACT FROM AUTHOR]

IntroductionThe clinical biochemical characteristics and target organ damage (TOD) in patients with plasma aldosterone concentrations (PAC) ranging from 50 to 100 ng/L after a saline infusion test (SIT) have not been fully studied.MethodsA total of 611 hypertensive patients with an elevated aldosterone-to-renin ratio (ARR) who underwent a supine SIT at Henan Provincial People’s Hospital were enrolled. The patients were divided into three groups according to their post-SIT PAC: 100 ng/L (PA group). The clinical and biochemical characteristics and TOD of the three groups were compared. The correlation of the post-SIT PAC with left ventricular mass index (LVMI) was assessed via regression analysis.ResultsThe indeterminate post-SIT results group had the youngest patients and the shortest duration of hypertension. The prevalence of renal impairment (RI) and left ventricular hypertrophy (LVH) was lower than that in the PA group (P0.05). After adjustment for confounders, the risk of developing carotid plaque was greater in the indeterminate post-SIT results group than in the control group (OR 1.73, 95% CI: 1.11, 2.69), and the prevalence of RI and LVH tended to increase with increasing post-SIT PAC levels. In multiple regression analyses, LVMI was significantly correlated with post-SIT PAC (P0.05).ConclusionA post-SIT PAC of 50–100 ng/L may be indicative of an early form of PA, and it may serve as an independent predictor of LVH, which could be related to the level of autonomously secreted aldosterone.

Abstract Background The diagnosis of primary aldosteronism (PA) is comprehensive, which includes case-detection testing, case confirmation followed by subtype classification. In certain instances, such as in the setting of spontaneous hypokalemia, suppressed renin activity (PRA) plus plasma aldosterone concentration (PAC) of > 15 ng/dL, one may not proceed with confirmatory tests. However, the quality of evidence behind this approach is very low. This study sought to evaluate the proposed “simplified confirmatory pathway” that can spare confirmatory testing for primary aldosteronism by evaluating the diagnostic performances of the various pre-specified PAC thresholds in combination with findings of suppressed renin and spontaneous hypokalemia. Methods This is a multi-center, retrospective diagnostic accuracy cohort-selected cross-sectional study. A total of 133 participants aged 18 years and above underwent saline infusion test between January 2010 to March 2024. The outcome measures comprise of the diagnostic performances of the different index test combinations (baseline PAC, baseline PRA and presence of spontaneous hypokalemia): sensitivity, specificity, negative predictive value, positive predictive value, positive likelihood ratio, negative likelihood ratio, and diagnostic accuracy. Data analysis was performed using SPSS 29.0.1.0 & MedCalc 20.218. Results Of the 133 patients who underwent saline infusion test, 88 (66.17%) were diagnosed with PA. A PAC of > 25 ng/dL plus PRA < 1.0 ng/dL/hr with spontaneous hypokalemia showed the highest specificity at 100% (95% CI 90.51%, 100.00%) and positive predictive value at 100% (85.18 – 100.00%). The minimum acceptable combination criteria were determined to be a PAC of > 20 ng/dL plus PRA < 0.6 ng/dL/hr, and presence of spontaneous hypokalemia. It has high specificity (94.59%; 95% CI 81.81%, 99.34%), positive predictive value (93.55%, 95% CI 78.49%, 98.29%), and moderate positive likelihood ratio (LR+) (6.39, 95% CI 1.61, 25.38) Conclusion A hypertensive patient with spontaneous hypokalemia and screening findings of PAC > 20 ng/dL and suppressed PRA of < 0.6 ng/ml/hr, may be classified as “overt primary aldosteronism confirmed” and may not need to proceed with dynamic confirmatory testing. Protocol registration number SRCTN34186253

Background: The diagnosis of primary aldosteronism (PA) is comprehensive, which includes case-detection testing, case confirmation followed by subtype classification. In certain instances, such as in the setting of spontaneous hypokalemia, suppressed renin activity (PRA) plus plasma aldosterone concentration (PAC) of > 15 ng/dL, one may not proceed with confirmatory tests. However, the quality of evidence behind this approach is very low. This study sought to evaluate the proposed "simplified confirmatory pathway" that can spare confirmatory testing for primary aldosteronism by evaluating the diagnostic performances of the various pre-specified PAC thresholds in combination with findings of suppressed renin and spontaneous hypokalemia. Methods: This is a multi-center, retrospective diagnostic accuracy cohort-selected cross-sectional study. A total of 133 participants aged 18 years and above underwent saline infusion test between January 2010 to March 2024. The outcome measures comprise of the diagnostic performances of the different index test combinations (baseline PAC, baseline PRA and presence of spontaneous hypokalemia): sensitivity, specificity, negative predictive value, positive predictive value, positive likelihood ratio, negative likelihood ratio, and diagnostic accuracy. Data analysis was performed using SPSS 29.0.1.0 & MedCalc 20.218. Results: Of the 133 patients who underwent saline infusion test, 88 (66.17%) were diagnosed with PA. A PAC of > 25 ng/dL plus PRA < 1.0 ng/dL/hr with spontaneous hypokalemia showed the highest specificity at 100% (95% CI 90.51%, 100.00%) and positive predictive value at 100% (85.18 – 100.00%). The minimum acceptable combination criteria were determined to be a PAC of > 20 ng/dL plus PRA < 0.6 ng/dL/hr, and presence of spontaneous hypokalemia. It has high specificity (94.59%; 95% CI 81.81%, 99.34%), positive predictive value (93.55%, 95% CI 78.49%, 98.29%), and moderate positive likelihood ratio (LR+) (6.39, 95% CI 1.61, 25.38) Conclusion: A hypertensive patient with spontaneous hypokalemia and screening findings of PAC > 20 ng/dL and suppressed PRA of < 0.6 ng/ml/hr, may be classified as "overt primary aldosteronism confirmed" and may not need to proceed with dynamic confirmatory testing. Protocol registration number: SRCTN34186253 [ABSTRACT FROM AUTHOR]

BACKGROUND The saline infusion test (SIT) to confirm primary aldosteronism requires infusing 2 L of normal saline over 240 minutes. Previous studies raised concerns regarding increased blood pressure and worsening hypokalemia during SIT. We aimed to evaluate the diagnostic applicability of a SIT that requires 1 L of saline infusion over 120 minutes. METHODS A cross-sectional study, including all patients in a large medical center who underwent SIT from 1 January 2015 to 30 April 2023. Blood samples were drawn for baseline renin and aldosterone (t  = 0) after 2 hours (t  = 120 min) and after 4 hours (t  = 240 min) of saline infusion. We used ROC analysis to evaluate the sensitivity and specificity of various aldosterone cut-off values at t  = 120 to confirm primary aldosteronism. RESULTS The final analysis included 62 patients. A ROC analysis yielded 97% specificity and 90% sensitivity for a plasma aldosterone concentration (PAC) of 397 pmol/L (14 ng/dL) at t  = 120 to confirm primary aldosteronism, and an area under the curve of 0.97 (95% CI [0.93, 1.00], P  < 0.001). Almost half (44%) of the patients did not suppress PAC below 397 pmol/L (14 ng/dL) at t  = 120. Of them, only one (4%) patient suppressed PAC below 276 pmol/L (10 ng/dL) at t  = 240. Mean systolic blood pressure increased from 140.1 ± 21.3 mm Hg at t  = 0 to 147.6 ± 14.5 mm Hg at t  = 240 (P  = 0.011). CONCLUSIONS A PAC of 397 pmol/L (14 ng/dL) at t  = 120 has high sensitivity and specificity for primary aldosteronism confirmation. [ABSTRACT FROM AUTHOR]

ContextPrimary aldosteronism (PA) is the most common form of endocrine hypertension. According to the Endocrine Society Practice Guidelines, the diagnosis of PA requires a pathological screening test result and non-suppressible aldosterone levels during confirmatory testing. Sequential testing with more than one confirmatory test may result in discordant test results.Objective and patientsWe investigated the association of discordant results of captopril challenge test (CCT) and saline infusion test (SIT) on patient subtype classification by adrenal vein sampling (AVS) and outcome in 111 consecutive patients from the German Conn’s Registry. Concordance was defined as non-suppressible aldosterone levels upon both tests, while discordance was defined as conflicting test results. Patients with unilateral disease were offered adrenalectomy (ADX). Biochemical and clinical outcomes were assessed using the PASO criteria.Results85 of 111 (77%) patients had concordant results of CCT and SIT. Although baseline characteristics were comparable between patients with concordant and discordant tests, the latter had significantly lower aldosterone levels after testing (CCT: 170 vs. 114pg/ml; SIT: 139 vs. 101pg/ml; p=0.004). In 35% of patients with discordant (n=9) and 46% of concordant test results (n=39), AVS suggested lateralized PA. In 36 of 48 cases ADX was performed. 86% of patients with discordant and 72% with concordant results had complete biochemical success.ConclusionThe use of two confirmatory tests in patients with PA results in discordant results in approximately 23% of cases. Patients having discordant confirmatory test results had a comparable rate of lateralized PA and underwent adrenalectomy with similar long-term outcome.

Background: To explore the diagnostic accuracy and the optimal cutoff value between the saline infusion test (SIT) and captopril challenge test (CCT) [including the value and suppression of plasma aldosterone concentration (PAC)] for primary aldosteronism (PA) diagnosing. Methods: A total of 318 patients with hypertension were consecutively enrolled, including 126 patients with PA and 192 patients with essential hypertension (EH), in this observational study. The characteristics of patients and laboratory examinations were collected and compared. The comparison between SIT and CCT was carried by drawing the receiver operator characteristic curve (ROC) and calculating the area under the curve (AUC) to explore the diagnostic accuracy and the optimal cutoff value. Results: The average age was 51.59 ± 10.43 in the PA group and 45.72 ± 12.44 in the EH group (p<0.05). The optimal cutoff value was 10.7 ng/dL for post-CCT PAC, 6.8 ng/dL for post-SIT PAC, and 26.9% for suppression of post-CCT PAC. The diagnostic value of post-CCT PAC was the highest with 0.831 for the AUC and 0.552 for the Youden index. The optimal cutoff value for patients who were <50 years old was 11.5 ng/dL for post-CCT PAC and 8.4 ng/dL for post-SIT PAC. The suppression of post-CCT PAC turned to 18.2% for those of age 50 or older. Conclusion: Compared with SIT, CCT had a higher diagnostic value when post-CCT PAC was used as the diagnostic criterion in Chinese people, while the selection of diagnostic thresholds depended on patient age. [ABSTRACT FROM AUTHOR]

Confirmatory tests for diagnosis of primary aldosteronism (PA) play an important role in sparing patients with a false-positive aldosterone-to-renin ratio (ARR) screening test from undergoing invasive subtyping procedures. We recommend that patients with a positive ARR test should undergo at least one confirmatory test to confirm or exclude the diagnosis of PA before directly proceeding to subtype studies, except for patients with significant PA phenotypes, including spontaneous hypokalemia, plasma aldosterone concentration >20 ng/dL plus plasma renin activity below a detectable level. Although a gold standard confirmatory test has not been identified, we recommend that saline infusion test and captopril challenge test, which were widely used in Taiwan. Patients with PA have been reported to have a higher prevalence of concurrent autonomous cortisol secretion (ACS). ACS is a biochemical condition of mild cortisol overproduction from adrenal lesions, but without the typical clinical features of overt Cushing's syndrome. Concurrent ACS may result in incorrect interpretation of adrenal venous sampling (AVS) and may lead to adrenal insufficiency after adrenalectomy. We recommend screening for ACS in patients with PA scheduled for AVS examinations as well as for adrenalectomy. We recommend the 1-mg overnight dexamethasone suppression test as screening method to detect ACS. [ABSTRACT FROM AUTHOR]

Confirmatory tests for diagnosis of primary aldosteronism (PA) play an important role in sparing patients with a false-positive aldosterone-to-renin ratio (ARR) screening test from undergoing invasive subtyping procedures. We recommend that patients with a positive ARR test should undergo at least one confirmatory test to confirm or exclude the diagnosis of PA before directly proceeding to subtype studies, except for patients with significant PA phenotypes, including spontaneous hypokalemia, plasma aldosterone concentration >20 ng/dL plus plasma renin activity below a detectable level. Although a gold standard confirmatory test has not been identified, we recommend that saline infusion test and captopril challenge test, which were widely used in Taiwan.Patients with PA have been reported to have a higher prevalence of concurrent autonomous cortisol secretion (ACS). ACS is a biochemical condition of mild cortisol overproduction from adrenal lesions, but without the typical clinical features of overt Cushing's syndrome. Concurrent ACS may result in incorrect interpretation of adrenal venous sampling (AVS) and may lead to adrenal insufficiency after adrenalectomy. We recommend screening for ACS in patients with PA scheduled for AVS examinations as well as for adrenalectomy. We recommend the 1-mg overnight dexamethasone suppression test as screening method to detect ACS.

Introduction: Unilateral primary aldosteronism (UPA) and bilateral primary aldosteronism (BPA) are the two subtypes of PA. Discriminating UPA from BPA is of great significance. Although adrenal venous sampling (AVS) is the gold standard for diagnosis, it has shortcomings. Thus, improved methods are needed. Methods: The original data were extracted from the public database “Dryad”. Ten parameters were included to develop prediction models for PA subtype diagnosis using machine learning technology. Moreover, the optimal model was chose and validated in an external dataset. Results: In the modeling dataset, 165 patients (71 UPA, 94 BPA) were included, while in the external dataset, 43 consecutive patients (20 UPA, 23 BPA) were included. The ten parameters utilized in the prediction model include age, sex, systolic and diastolic blood pressure, aldosterone to renin ratio (ARR), serum potassium, ARR after 50 mg captopril challenge test (CCT), primary aldosterone concentration (PAC) after saline infusion test (SIT), PAC reduction rate after SIT, and number of types of antihypertensive agents at diagnosis. The accuracy, sensitivity, specificity, F1 score, and AUC for the optimal model using the random forest classifier were 90.0%, 81.8%, 96.4%, 0.878, and 0.938, respectively, in the testing dataset and 81.4%, 90.0%, 73.9%, 0.818 and 0.887, respectively, in the validating external dataset. The most important variables contributing to the prediction model were PAC after SIT, ARR, and ARR after CCT. Discussion: We developed a machine learning-based predictive model for PA subtype diagnosis based on ten clinical parameters without CT imaging. In the future, artificial intelligence-based prediction models might become a robustprediction tool for PA subtype diagnosis, thereby, might reducing at least some of the requests for CT or AVS and assisting clinical decision-making. [ABSTRACT FROM AUTHOR]

Long-term follow-up studies on primary aldosteronism (PA) are lacking. We aim to review results of diagnostic procedures and histopathology for patients diagnosed during 2012–2016 in Iceland, compare unilateral (UD) and bilateral disease (BD) and assess treatment response. Thirty-two patients aged 28–88 were diagnosed and treated according to guidelines. The majority had BD. Everyone needed potassium supplementation at case detection. We saw a reduction in systolic blood pressure (p <.001, both groups), antihypertensive agents (p =.002 UD and p =.04 BD) and potassium supplementation (p <.001, both groups). Similar treatment response was seen in both subgroups. Ratio of hypokalemia and number of cases indicates severe PA underdiagnosis in Iceland. [ABSTRACT FROM AUTHOR]

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]

Abstract Background Satisfactory tools to preclude low-risk patients from intensive diagnostic testing for primary aldosteronism (PA) are lacking. Therefore, we aimed to develop a decision tool to determine which patients with difficult-to-control hypertension have a low probability of PA, thereby limiting the exposure to invasive testing while at the same time increasing the efficiency of testing in the remaining patients. Methods Data from consecutive patients with difficult-to-control hypertension, analysed through a standardized diagnostic protocol between January 2010 and October 2017 (n = 824), were included in this cross-sectional study. PA was diagnosed by a combined approach: 1) elevated aldosterone-to-renin ratio (> 5.0 pmol/fmol/s), confirmed with 2) non-suppressible aldosterone after standardized saline infusion (≥280 pmol/L). Multivariable logistic regression analyses including seven pre-specified clinical variables (age, systolic blood pressure, serum potassium, potassium supplementation, serum sodium, eGFR and HbA1c) was performed. After correction for optimism, test reliability, discriminative performance and test characteristics were determined. Results PA was diagnosed in 40 (4.9%) of 824 patients. Predicted probabilities of PA agreed well with observed frequencies and the c-statistic was 0.77 (95% confidence interval (95%CI) 0.70–0.83). Predicted probability cut-off values of 1.0–2.5% prevented unnecessary testing in 8–32% of the patients with difficult-to-control hypertension, carrying sensitivities of 0.98 (95%CI 0.96–0.99) and 0.92 (0.83–0.97), and negative predictive values of 0.99 (0.98–1.00) and 0.99 (0.97–0.99). Conclusions With a decision tool, based on seven easy-to-measure clinical variables, patients with a low probability of PA can be reliably selected and a considerable proportion of patients with difficult-to-control hypertension can be spared intensive diagnostic testing.

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.

Context Urinary aldosterone levels (Uald) are widely measured in the oral sodium-loading test to confirm primary aldosteronism (PA), but reliable studies on their diagnostic value are limited. This may be due to the difficulty in collecting urine with reliable accuracy, keeping oral sodium intake constant between patients. Therefore, we focused on 24-hour Uald after intravenous saline infusion in a hospitalized setting, which provides a reliable sodium load in consistent amounts. Objective Comparing plasma aldosterone concentrations (PAC) and Uald after saline infusion in the sitting position, to evaluate the accuracy in determining PA subtypes and the correlation of both measurements. Design and Setting This was a retrospective cross-sectional study in a single referral center. Patients Of 53 patients without renal dysfunction who were diagnosed with PA and underwent adrenal venous sampling, 16 and 37 were diagnosed with unilateral and bilateral PA, respectively. Main Outcome Measures Uald collected for 24 hours and PAC after saline infusion. Results The area under the receiver operating characteristic curve for diagnosing unilateral PA was not significantly different between Uald and PAC after saline infusion (0.921 and 0.958, respectively; P  = 0.370). The predicted optimal cutoff value of Uald was 16.5 μg/day (sensitivity, 87.5%; specificity, 100%), and that of PAC after saline infusion was 19.3 ng/dL (sensitivity, 87.5%; specificity, 97.3%). In studied patients with PA, Uald was positively correlated with PAC after saline infusion (r  = 0.617; P  < 0.001). Conclusions We reassessed Uald in PA patients under sufficient sodium loading and demonstrated the correlation between Uald and PAC after saline infusion. [ABSTRACT FROM AUTHOR]

• Accurate aldosterone measurements are important for primary aldosteronism diagnosis. • Immunoassay interference can lead to misdiagnosis and wrongful treatment. • Immunoassay interferences can be patient specific and problematic to recognise. • Mass spectrometry provides for accuracy of plasma aldosterone measurements. • Improved measurement methods may improve recognition of primary aldosteronism. Diagnosis of primary aldosteronism (PA) involves a multistep process reliant on the accuracy of aldosterone measurements at each step. We report on immunoassay interference leading to a wrongful diagnosis and indication for surgical intervention. A 38-year old hypertensive male with a 1.4 cm left adrenal mass was diagnosed with PA based on an elevated aldosterone:renin ratio and a positive saline infusion test. Adrenal venous sampling (AVS) indicated left-sided aldosterone hypersecretion, supporting a decision to remove the left adrenal. The patient was also enrolled in a study to evaluate mass spectrometry-based steroid profiling, which indicated plasma aldosterone concentrations measured in five different peripheral samples averaging only 11% those of the immunoassay. Mass spectrometric measurements did not support left-sided adrenal aldosterone hypersecretion. Two independent laboratories confirmed differences in measurements by immunoassay and mass spectrometry. Lowered concentrations measured by the immunoassay that matched those by mass spectrometry were achieved after sample purification to remove macromolecules, confirming immunoassay interference. Although our patient may represent an isolated case of immunoassay interference leading to misdiagnosis of PA, unnecessary AVS and potentially wrongful removal of an adrenal, it is also possible that such inaccuracies may impact the diagnostic process and treatment for other patients. [ABSTRACT FROM AUTHOR]

Background: Satisfactory tools to preclude low-risk patients from intensive diagnostic testing for primary aldosteronism (PA) are lacking. Therefore, we aimed to develop a decision tool to determine which patients with difficult-to-control hypertension have a low probability of PA, thereby limiting the exposure to invasive testing while at the same time increasing the efficiency of testing in the remaining patients. Methods: Data from consecutive patients with difficult-to-control hypertension, analysed through a standardized diagnostic protocol between January 2010 and October 2017 (n = 824), were included in this cross-sectional study. PA was diagnosed by a combined approach: 1) elevated aldosterone-to-renin ratio (> 5.0 pmol/fmol/s), confirmed with 2) non-suppressible aldosterone after standardized saline infusion (≥280 pmol/L). Multivariable logistic regression analyses including seven pre-specified clinical variables (age, systolic blood pressure, serum potassium, potassium supplementation, serum sodium, eGFR and HbA1c) was performed. After correction for optimism, test reliability, discriminative performance and test characteristics were determined. Results: PA was diagnosed in 40 (4.9%) of 824 patients. Predicted probabilities of PA agreed well with observed frequencies and the c-statistic was 0.77 (95% confidence interval (95%CI) 0.70–0.83). Predicted probability cut-off values of 1.0–2.5% prevented unnecessary testing in 8–32% of the patients with difficult-to-control hypertension, carrying sensitivities of 0.98 (95%CI 0.96–0.99) and 0.92 (0.83–0.97), and negative predictive values of 0.99 (0.98–1.00) and 0.99 (0.97–0.99). Conclusions: With a decision tool, based on seven easy-to-measure clinical variables, patients with a low probability of PA can be reliably selected and a considerable proportion of patients with difficult-to-control hypertension can be spared intensive diagnostic testing. [ABSTRACT FROM AUTHOR]

Introduction: Adrenal venous sampling is useful for discriminating unilateral and bilateral hypersecretion in patients with primary aldosteronism, but it is relatively invasive. To determine the site of hypersecretion more non-invasively, we evaluated predictors of unilateral hypersecretion.Materials and Methods: We evaluated the baseline characteristics and the results of confirmatory tests of 123 patients with primary aldosteronism who underwent adrenal venous sampling.Results: Unilateral hypersecretion was identified in 22.0%. The plasma aldosterone concentration and aldosterone-renin ratio were significantly higher and serum potassium concentration and plasma renin activity were significantly lower in patients with unilateral hypersecretion. Plasma aldosterone concentrations after captopril challenge test, saline infusion test and rapid adrenocorticotropic hormone stimulation test were significantly higher among patients with unilateral hypersecretion. The plasma aldosterone concentration reduction ratio in saline infusion test and plasma aldosterone concentration elevation ratio during rapid adrenocorticotropic hormone stimulation test were significantly higher in patients with unilateral hypersecretion. However, areas under the curve for these parameters were not superior to the values after confirmatory tests.Conclusions: The plasma aldosterone concentration values after captopril challenge test, saline infusion test and rapid adrenocorticotropic hormone stimulation test were useful for identifying patients with unilateral hypersecretion. However, value changes or ratios during confirmatory tests are less useful for this aim. [ABSTRACT FROM AUTHOR]

Context: The saline infusion test (SIT) is a common confirmatory test for primary aldosteronism (PA). According to the guideline, a postinfusion plasma aldosterone concentration (PAC) of 5‐10 ng/dL is considered indeterminate, and recommendations for diagnostic strategies are currently limited in this situation. Objective: To explore whether an addition of the captopril challenge test (CCT) could improve the diagnostic accuracy in patients with indeterminate SIT. Methods: A total of 280 hypertensive patients with high risk of PA completed this study. Subjects were defined as SIT indeterminate based on their PAC post‐SIT. These patients then underwent the CCT where PACs post‐CCT >11 ng/dL were considered positive. Using fludrocortisone suppression test (FST) as the reference standard, diagnostic parameters including area under the receiver‐operator characteristic curves (AUC), sensitivity and specificity were calculated. Results: There were 65 subjects (23.2%) diagnosed as PA indeterminate after SIT. With the addition of CCT, true‐positive numbers increased from 134 to 147, and false‐negative numbers decreased from 27 to 14. Compared to SIT alone, a combination of SIT and CCT showed a higher AUC (0.91 [0.87,0.94] vs 0.87 [0.83,0.91], P =.041) and an increased sensitivity for the diagnosis of PA (0.91 [0.86,0.95] vs 0.83 [0.76,0.89], P =.028), while the specificity remained similar. In the subgroup with indeterminate SIT results, using PAC post‐CCT resulted in a 36% higher AUC than using PAC post‐SIT alone for the diagnosis of PA. Conclusion: For patients under investigation for possible PA who have indeterminate SIT results, an addition of CCT improves the diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Summary: Objective: Saline infusion test (SIT), captopril challenge test (CCT), fludrocortisone suppression test (FST) and oral sodium loading test (SLT) are recommended by the Endocrine Society's Clinical Practice Guidelines to diagnose primary aldosteronism, but which one is the best remains controversial. We aimed to summarize the available comparative data and evaluate the diagnostic accuracy of these four tests. Design: We searched PubMed, Embase and the Cochrane Library for relevant studies published between January 1980 and January 2018. Patients: Eligible studies reported on the accuracy of one or more of the four confirmatory tests in patients suspected of PA. Measurements: Two reviewers independently conducted the data extraction of all selected studies, which consisted of study characteristics and data to estimate the summary receiver operating characteristic (SROC) curve and the corresponding summary area under the curve (SAUC), pooled sensitivity and specificity, diagnostic odds ratios (DOR) with 95% confidence interval (CI). Results: We identified 26 articles including 3686 patients. Fifteen articles evaluated the diagnostic accuracy of CCT, 10 of SIT, 1 of FST and none of SLT. For CCT, the SAUC was 0.9207, and the pooled sensitivity and specificity were 0.87 (95% CI: 0.84‐0.89) and 0.84 (95% CI: 0.81‐0.86), respectively. For SIT, the SAUC was 0.9232, and the pooled sensitivity and specificity were 0.85 (95% CI: 0.82‐0.87) and 0.87 (95% CI: 0.85‐0.89), respectively. For FST, the pooled sensitivity and specificity were 0.87 (95% CI: 0.66‐0.97) and 0.95 (95% CI: 0.82‐0.99), respectively. Overall, we found no significant differences in the diagnostic accuracy of CCT and SIT. Conclusions: CCT and SIT exhibit high and comparable accuracy for diagnosing PA. CCT may be a more feasible alternative as it is safe and much easier to perform. [ABSTRACT FROM AUTHOR]

Anal manometry, rectal capacity measurement, and the saline-infusion test were performed in 350 patients, 178 of whom had fecal incontinence and 172 of whom were continent. Anal manometry was also performed in 80 control subjects, whose results were compared with the patients. Women and older patients exhibited lower pressures. Compared with continent patients, incontinent patients had lower anal sphincter pressures at rest and during squeeze, a smaller rectal capacity, and leaked earlier and more with the saline infusion test. Differentiation between incontinent and continent patients was not possible with a single test because there was complete overlap. The maximum squeeze pressure showed the best discrimination. Combining the three tests did not show better discrimination than any individual test. Anal pressure and rectal capacity below the normal range only were found in very few incontinent patients. The authors' study demonstrates that no prediction can be made about continence with anorectal function tests. Therefore, in the individual patient, an abnormal result in one test must be interpreted with caution and only in relationship with other tests, especially when therapeutic surgery is considered. [ABSTRACT FROM AUTHOR]

Objective: Accurate assessment and localization of aldosterone-producing adenomas (APAs) are essential for the treatment of primary aldosteronism (PA). Although adrenal venous sampling (AVS) is the standard method of reference for subtype diagnosis in PA, controversy exists concerning the criteria for its interpretation. This study aims to determine better indicators that can reliably predict subtypes of PA., Method: Retrospective, single-cohort analysis including 209 patients with PA who were subjected to AVS. Eighty-two patients whose plasma aldosterone concentrations (PAC) were normalized after surgery were histopathologically or genetically diagnosed with APA. The accuracy of image findings was compared to AVS results. Receiver operating characteristic (ROC) curve analysis between the operated and the no-apparent laterality groups was performed using AVS parameters and loading test for diagnosis of PA., Result: Agreement between image findings and AVS results was 56.3%. ROC curve analysis revealed that the lateralization index (LI) after adrenocorticotropin stimulation cutoff was 2.40, with 98.8% sensitivity and 97.1% specificity. The contralateral suppression index (CSI) cutoff value was 1.19, with 98.0% sensitivity and 93.9% specificity. All patients over the LI and CSI cutoff values exhibited unilateral subtypes. Among the loading test, the best classification accuracy was achieved using the PAC reduction rate after a saline infusion test (SIT) >33.8%, which yielded 87.2% sensitivity or a PAC after a SIT <87.9 pg/mL with 86.2% specificity for predicting bilateral PA., Conclusion: The combined criteria of the PAC reduction rate and PAC after the SIT can determine which subset of patients with APA who should be performed AVS for validation., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To assess the efficacy of screening and confirmatory tests of primary aldosteronism (PA) in diagnosing aldosterone producing adenoma (APA)., Methods: Clinical data of 167 hypertensive patients were retrospectively reviewed,including 93 patients with APA and 74 patients with essential hypertension (EH). The area under curves ( AUC ) of receiver operating characteristic (ROC) curves were compared among the five indicators: supine plasma aldosterone concentration (PAC),absolute PAC values and PAC drop rates post saline infusion test (SIT) and captopril challenge test (CCT)., Results: APA patients had higher supine PAC,higher percentage of third degree hypertension,and lower serum potassium level than EH patients ( P <0.05). Compared with EH patients,APA patients had lower PAC change rates,post posture change and SIT ( P <0.05),but similar post CCT ( P >0.05). The AUC of supine PAC reached 0.975. Higher AUC was found in absolute PAC values post SIT compared with PAC droop rates (0.984 vs. 0.680, P <0.001). Similar results were also found with CCT (0.949 vs. 0.538, P <0.001). A cut-off of supine aldosterone renin ratio (ARR) >30 and supine PAC>17.8 ng/dL had 96.8% sensitivity and 90.5% specificity. A cut-off of 14.59 ng/dL PAC post SIT had 90.2% sensitivity and 97.3% specificity. A cut-off of 19.11 ng/dL PAC post CCT had 88.8% sensitivity and 95.9% specificity., Conclusion: Screening tests using supine ARR>30 plus supine PAC>17.83 ng/dL are preferred with high sensitivity and specificity. The absolute values of PAC post SIT and CCT are recommended for confirming APA., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Primary aldosteronism (PA) is caused by excess secretion of aldosterone and is an independent risk factor for cardio-cerebro-vascular (CCV) events. The goal of treatment of PA should include prevention of CCV events. A definitive diagnosis of PA is established by confirmatory tests [saline infusion test (SIT), furosemide upright test (FUT) and captopril challenge test (CCT)]. However, there is no information on whether the hormone levels measured by these confirmatory tests are associated with CCV events. The aim of this retrospective study was to elucidate the relationship between the results of the above confirmatory tests and prevalence of CCV disease in patients with PA. The study subjects were 292 PA patients who were assessed for past history of CCV events at the time of diagnosis of PA. CCV events were significantly higher in patients with positive than negative SIT (12.8% vs. 3.3%, p=0.04). There were no differences in the incidences of CCV events between patients with positive and negative CCT and FUT (CCT: 11.0% vs. 3.9%, p=0.13, FUT: 6.1% vs. 5.7%, p=0.93). Our results demonstrated a higher incidence of CCV disease in PA SIT-positive patients compared to those with negative test. SIT is a potentially useful test not only for the diagnosis of PA but also assessment of the risk of CCV events.