Development and Validation of Criteria for Sparing Confirmatory Tests in Diagnosing Primary Aldosteronism

2020 ◽  
Vol 105 (7) ◽  
pp. e2449-e2456 ◽  
Author(s):  
Kanran Wang ◽  
Jinbo Hu ◽  
Jun Yang ◽  
Ying Song ◽  
Peter J Fuller ◽  
...  

Abstract Context The Endocrine Society Guidelines for the diagnosis of primary aldosteronism (PA) suggest that confirmatory tests (CFT) are not required when the following criteria are met: plasma aldosterone concentration (PAC) is >20 ng/dL, plasma renin is below detection levels, and hypokalemia is present. The evidence for the applicability of the guideline criteria is limited. Objective To develop and validate optimized criteria for sparing CFT in the diagnosis of PA. Design and Setting The optimized criteria were developed in a Chinese cohort using the captopril challenge test, verified by saline infusion test (SIT) and fludrocortisone suppression test (FST), and validated in an Australian cohort. Participants Hypertensive patients who completed PA screening and CFT. Main Outcome Measure Diagnostic value of the optimized criteria. Results In the development cohort (518 PA and 266 non-PA), hypokalemia, PAC, and plasma renin concentration (PRC) were selected as diagnostic indicators by multivariate logistic analyses. The combination of PAC >20 ng/dL plus PRC <2.5 μIU/mL plus hypokalemia had much higher sensitivity than the guideline criteria (0.36 vs 0.11). The optimized criteria remained superior when the SIT or FST were used as CFT. Non-PA patients were not misdiagnosed by either criteria, but the percentage of patients in whom CFT could be spared was higher with the optimized criteria. In the validation cohort (125 PA and 81 non-PA), the sensitivity of the optimized criteria was also significantly higher (0.12 vs 0.02). Conclusions Hypertensive patients with PAC >20 ng/dL, PRC <2.5 μIU/mL, plus hypokalemia can be confidently diagnosed with PA without confirmatory tests.

2019 ◽  
Vol 105 (4) ◽  
pp. 1284-1289 ◽  
Author(s):  
Hironobu Umakoshi ◽  
Ryuichi Sakamoto ◽  
Yayoi Matsuda ◽  
Maki Yokomoto-Umakoshi ◽  
Hiromi Nagata ◽  
...  

Abstract Context The current clinical guidelines suggest that confirmatory tests for primary aldosteronism (PA) may be excluded in some of patients who have elevated plasma aldosterone concentration (PAC) under plasma renin suppression. However, this has low-priority evidence and is under debate in use of serum potassium. Objective This study aimed to investigate an appropriate setting for sparing confirmatory tests in PA. Design and Setting A retrospective cross-sectional study in a single referral center. Participants This study included 327 patients who had hypertension under plasma renin suppression and underwent the captopril challenge test (CCT) between January 2007 and April 2019. CCT results were used to diagnose PA. Main Outcome Measure Diagnostic value of PAC and serum potassium in confirmation of PA. Results Of the studied patients, 252 of 327 (77%) were diagnosed with PA. All 61 patients with PAC > 30 ng/dL were diagnosed with PA. In patients with PAC between 20 and 30 ng/dL, 44 of 55 (80%) were diagnosed with PA, while all 26 with PAC between 20 to 30 ng/dL who had spontaneous hypokalemia were diagnosed with PA. The proportion of unilateral PA determined by adrenal vein sampling (AVS) was higher in patients who had PAC > 30 ng/dL or those with spontaneous hypokalemia who had PAC between 20 and 30 ng/dL than those who did not meet the criteria (76% vs. 17%, P < .001). Conclusion Confirmatory tests in PA could be spared in patients who have typical features of PA and these patients had a high probability of unilateral PA on AVS.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Hironobu Umakoshi ◽  
Ryuichi Sakamoto ◽  
Yayoi Matsuda ◽  
Maki Yokomoto-Umakoshi ◽  
Hiromi Nagata ◽  
...  

Abstract Context: The current clinical guidelines suggest that confirmatory tests for primary aldosteronism (PA) may be excluded in some of patients who have elevated plasma aldosterone concentration (PAC) under plasma renin suppression. However, this has low priority evidence and is under debate in use of serum potassium. Objective: This study aimed to investigate an appropriate setting for sparing confirmatory tests in PA. Design and Setting: A retrospective cross-sectional study in a single referral center. Participants: This study included 327 patients who had hypertension under plasma renin suppression and underwent captopril challenge test (CCT) between January 2007 and April 2019. CCT results were used to diagnose PA. Main outcome measure: Diagnostic value of PAC and serum potassium in confirmation of PA. Results: Of the studied patients, 252 of 327 (77%) were diagnosed with PA. All 61 patients with PAC >30 ng/dl were diagnosed with PA. In patients with PAC between 20 and 30 ng/dl, 44 of 55 (80%) were diagnosed with PA, while all 26 with PAC between 20 to 30 ng/dl who had spontaneous hypokalemia were diagnosed with PA. Areceiver operator curve analysis showed that the sensitivity of diagnosis of PA is 100% in our patients, when PAC set at > 28.8 ng/dl and showed that the sensitivity of diagnosis of PA is 100% in our patients with spontaneous hypokalemia, who had PAC < 30 ng/dl, when PAC was set at > 19.2 ng/dl. While, the prevalence of PA was higher in patients with hypokalemia, who had PAC between 10 and 20 ng/dl than in those with PAC < 10 ng/dl. Collectively, 100 out of 102 (98%) with hypokalemia, who had PAC > 10 ng/dl were diagnosed as PA. The proportion of unilateral PA determined by adrenal vein sampling (AVS) was higher in patients who had PAC >30 ng/dl or those with spontaneous hypokalemia who had PAC between 20 and 30 ng/dl than those who did not meet the criteria (76% vs. 17%, P<0.001). Conclusion: Confirmatory tests in PA could be spared in patients who have typical features of PA and these patients had a high probability of unilateral PA on AVS.


2021 ◽  
Vol 12 ◽  
Author(s):  
Qiao Xiang ◽  
Tao Chen ◽  
Kai Yu ◽  
Yuanmei Li ◽  
Qianrui Li ◽  
...  

ObjectiveThe result interpretation of the captopril challenge test (CCT) for the diagnosis of primary aldosteronism (PA) is not standardized. Superiorities of different indexes in the CCT have not been fully investigated. We aimed to comprehensively evaluate the value and influence factors of different CCT-associated indexes in the diagnosis of PA.MethodsWe enrolled 312, 85, 179 and 97 patients in the groups of PA, essential hypertension (EH), unilateral PA (UPA) and bilateral PA (BPA), respectively. For each single index investigated, we computed diagnostic estimates including the area under the receiver operating characteristic curve (AUC). We performed pre-specified subgroup analyses to explore influence factors. We assessed the diagnostic value of combined indexes in binary logistic regression models.ResultsPost-CCT aldosterone to renin ratio (ARR) (AUC = 0.8771) and plasma aldosterone concentration (PAC) (AUC = 0.8769) showed high value in distinguishing PA from EH, and their combination (AUC = 0.937) was even superior to either alone. The diagnostic efficacy was moderately high for post-CCT aldosterone to angiotensin II ratio (AA2R) (AUC = 0.834) or plasma renin activity (PRA) (AUC = 0.795) but low for the suppression percentage of PAC (AUC = 0.679). Post-CCT PAC had a significantly higher AUC in the UPA than BPA subgroup (AUC = 0.914 vs 0.827, P<0.05).ConclusionWe can take post-CCT ARR and PAC altogether into account to distinguish PA from EH, while caution should be taken to interpret CCT results with the suppression percentage of PAC. Post-CCT PAC may perform better to identify the unilateral than bilateral form of PA.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Jinbo Hu ◽  
Kanran Wang ◽  
Shumin Yang ◽  
Qifu Li

Abstract Abstract Background: Confirmatory tests of primary aldosteronism (PA), including saline infusion test (SIT), captopril challenge test (CCT) and fludrocortisone suppression test (FST), are recommended by the Endocrine Society Clinical Practice Guideline. In order to simplifying diagnostic process, a criterion for skipping confirmatory tests was established by the guideline, while the evidence is lacking. Objective: To validate and optimize the guideline criterion for skipping confirmatory tests. Design: Prospective diagnostic study. Setting: Chongqing, China. Measurements: A total of 501 patients with high risk of PA were retrospectively enrolled. All of them completed at least two confirmatory tests (CCT, SIT, and FST). The guideline criterion is: history of spontaneous hypokalemia, plasma renin concentration (PRC) below detection levels and plasma aldosterone (PAC)>20ng/dl (550pmol/L). An optimized criterion (history of spontaneous hypokalemia, PRC <2.5 uIU/ml and PAC>20 ng/dl) was established based on the guideline criterion. Parameters such as sensitivity, specificity and area under the receiver-operator characteristic curves (AUC) were calculated to compare the diagnostic value of these two criteria. Results: Using SIT, CCT and FST (cutoffs: PAC post-SIT 10 ng·dl-1; PAC post-CCT 11 ng·dl-1; PAC post-FST 6 ng·dl-1) for PA diagnosis, the specificity of the guideline criterion was 1.00 (0.98–1.00), 1.00(0.98–1.00) and 1.00(0.97–1.00) respectively, while the sensitivity was 0.12 (0.09–0.17), 0.12(0.08–0.16) and 0.09(0.06–0.12) respectively. Compared to the guideline criterion, the sensitivity of the optimized criterion was significantly improved [SIT: 0.42 (0.36–0.49); CCT: 0.41 (0.35–0.48); FST: 0.30 (0.25–0.34), all the P values < 0.001 when compared to the guideline criterion]. However, the specificity of the optimized criterion was similar to the guideline criterion (all the P values>0.05). Limitation: This study was carried out in a single center. Conclusions: The guideline criterion shows high specificity but low sensitivity for direct diagnosis of PA. The optimized criterion has greatly improved the sensitivity and may be more suitable for skipping confirmatory tests of PA.


2019 ◽  
Vol 51 (03) ◽  
pp. 172-177 ◽  
Author(s):  
Maud Vivien ◽  
Emilie Deberles ◽  
Remy Morello ◽  
Aimi Haddouche ◽  
David Guenet ◽  
...  

AbstractThe diagnostic workup for primary aldosteronism includes a screening step using the aldosterone-to-renin ratio (ARR) and a confirmatory step based on dynamic testing of aldosterone secretion autonomy. International guidelines suggest that precise clinical and biochemical conditions may allow the bypassing of the confirmatory step, however, data which validate hormone thresholds defining such conditions are lacking. At our tertiary center, we retrospectively examined a cohort of 173 hypertensive patients screened for PA by the ARR, of whom 120 had positive screening and passed a saline infusion test (SIT) or a captopril challenge test (CCT). Fifty-nine had PA, including 34 Conn adenomas and 25 with idiopathic aldosteronism (IA). Using a threshold of 160 pmol/l, post-SIT plasma aldosterone concentration (PAC) identified PA with 86.4% sensitivity, 94.7% specificity, and a negative predictive value of 92.3%. Of those subjects with a high ARR and a PAC above 550 pmol/l, 93% had a positive SIT, while 100% of subjects with a high ARR, but a PAC under 240 pmol/l had a negative SIT. Our results thus validate the biochemical conditions defined in the French and US guidelines for bypassing the confirmatory step in the workup for PA diagnosis.


2012 ◽  
Vol 13 (3) ◽  
pp. 367-371 ◽  
Author(s):  
Janusz Myśliwiec ◽  
Łukasz żukowski ◽  
Anna Grodzka ◽  
Agata Piłaszewicz ◽  
Szymon Drągowski ◽  
...  

Introduction: Assessment of the renin-angiotensin-aldosterone system has been recently granted a much greater role in the evaluation of patients with arterial hypertension. There is no single test efficient in selection of patients for second-step etiological investigation. Methods: Altogether, 198 consecutive patients − 119 women (60%) and 79 men (40%) – hospitalized in years 2009–2011 at the Clinical Department of Endocrinology Medical University of Bialystok were diagnosed with primary aldosteronism. In each patient, plasma renin activity and plasma aldosterone concentration (basic and after 2 l NaCl infusion) were evaluated. Results: The percentage of patients with plasma aldosterone concentration ≥15 ng/ml was 53 and the percentage of patients with plasma renin activity ≤0.1 ng/ml/h was 20. The percentage of patients screened for primary aldosteronism in which the aldosterone:renin ratio exceeded consecutive cut-offs of 20, 30, 40 and 50 were respectively 57, 45, 34 and 29. Among 15 patients in which plasma aldosterone concentration after infusion of 2 l of saline was ≥6.5 ng/dl (8.6%), 13 (6.6%) were diagnosed with primary aldosteronism. Conclusion: The obligatory use of tests confirming autonomy of aldosterone secretion in patients screened for primary aldosteronism seems cost-effective in limiting the number of patients for further diagnosis.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Zhixin Xu ◽  
Jun Yang ◽  
Jinbo Hu ◽  
Ying Song ◽  
Ting Luo ◽  
...  

Abstract Abstract Background 44.7% adults in China have hypertension but the prevalence of primary aldosteronism (PA) in Chinese hypertensives is unknown. Objective We prospectively investigated the prevalence of PA in newly diagnosed hypertensives and tested the hypothesis that these PA patients have less severe cardiovascular complications and better outcomes when compared to those diagnosed after established (or prolonged) hypertension. Method In a community health center, consecutive hypertensive patients with an aldosterone-renin ratio≥2 (ng∙dL−1/mIU∙L−1) and plasma aldosterone concentration >10ng/dL underwent captopril challenge test and/or saline infusion test for confirmation. Adrenal CT scan and adrenal vein sampling were used for subtyping. PA patients were followed up for one year and clinical outcomes were compared with PA patients from an established hypertensive cohort. Results 1020 newly diagnosed hypertensive patients were screened over 16 months. Forty were diagnosed with PA, 948 with non-PA, resulting in a prevalence of 4.0%. Thirty-two patients were diagnosed as “possible PA” due to positive screening but failure to complete the confirmatory test. Compared to non-PA, PA patients more frequently displayed microalbuminuria (P=0.031), but the incidence of cardiovascular events was not different (P=0.927). For patients treated with surgery, complete clinical success rate was 85.7%, 28% higher than that of PA patients diagnosed after prolonged hypertension. For patients treated with medication, blood pressure control rate was 79.3%, 30% higher than that of PA patients diagnosed after prolonged hypertension. Conclusions The prevalence of PA in patients with newly diagnosed hypertension in China was at least 4.0%. PA screening in newly diagnosed hypertensive patients can lead to better clinical outcomes.


2020 ◽  
Vol 105 (5) ◽  
pp. e1990-e1998 ◽  
Author(s):  
Junji Kawashima ◽  
Eiichi Araki ◽  
Mitsuhide Naruse ◽  
Isao Kurihara ◽  
Katsutoshi Takahashi ◽  
...  

Abstract Context Previous studies have proposed cutoff value of baseline plasma aldosterone concentration (bPAC) under renin suppression that could diagnose primary aldosteronism (PA) without confirmatory testing. However, those studies are limited by selection bias due to a small number of patients and a single-center study design. Objective This study aimed to determine cutoff value of bPAC and baseline plasma renin activity (bPRA) for predicting positive results in confirmatory tests for PA. Design The multi-institutional, retrospective, cohort study was conducted using the PA registry in Japan (JPAS/JRAS). We compared bPAC in patients with PA who showed positive and negative captopril challenge test (CCT) or saline infusion test (SIT) results. Patients Patients with PA who underwent CCT (n = 2256) and/or SIT (n = 1184) were studied. Main outcome measures The main outcomes were cutoff value of bPAC (ng/dL) and bPRA (ng/mL/h) for predicting positive CCT and/or SIT results. Results In patients with renin suppression (bPRA ≤ 0.3), the cutoff value of bPAC that would give 100% specificity for predicting a positive SIT result was lower than that for predicting a positive CCT result (30.85 vs 56.35, respectively). Specificities of bPAC cutoff values ≥ 30.85 for predicting positive SIT and CCT results remained high (100.0% and 97.0%, respectively) in patients with bPRA ≤ 0.6. However, the specificities of bPAC cutoff values ≥ 30.85 for predicting positive SIT and CCT results decreased when patients with bPRA > 0.6 were included. Conclusion Confirmatory testing could be omitted in patients with bPAC ≥ 30.85 in the presence of bPRA ≤ 0.6.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Linqiang Ma ◽  
Ying Song ◽  
Mei Mei ◽  
Wenwen He ◽  
Jinbo Hu ◽  
...  

Aim. This retrospective study is aimed at investigating whether aldosterone-renin ratio (ARR) cutoffs calculated by the plasma aldosterone concentration (PAC)/plasma renin concentration (PRC) should be set differently in patients of different ages. Methods. 521 hypertensive patients were screened for primary aldosteronism (PA) by the PAC/PRC. 174 patients diagnosed with PA and 311 patients with essential hypertension (EH) were included in the final analysis. Subjects were subdivided into four age groups: <40, 40–49, 50–59, and ≥60 years old. Results. The accuracy of the ARR varied greatly among the different age groups. An ARR of 3.7 (ng/dl)/(μIU/ml) had a sensitivity of 100% and a specificity of 80% in patients ≥ 60 years old. With this cutoff, the sensitivities in patients < 40, 40–49, and 50–59 years old were 74%, 82%, and 87%, respectively, and the specificities were 94%, 95%, and 94%, respectively. To achieve a sensitivity higher than 90%, the ARR cutoff needed to be lowered to 2.0 (ng/dl)/(μIU/ml) for patients 40–49 and 50–59 years old, resulting in sensitivities of 90% and 95%, respectively, and specificities of 80% and 84%, respectively. To achieve a sensitivity higher than 90%, the ARR cutoff needed to be lowered to 1.0 (ng/dl)/(μIU/ml) for patients < 40 years old, resulting in a sensitivity of 90% and a specificity of 82%. Conclusions. An ARR of 3.7 (ng/dl)/(μIU/ml) is optimal for patients ≥ 60 years; for patients 40–59 years, the optimal ARR cutoff is 2.0; for those younger than 40 years, an ARR of 1.0 may be more reasonable.


PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0253807
Author(s):  
Naohisa Tamura ◽  
Erika Watanabe ◽  
Rumi Shirakawa ◽  
Eiji Nakatani ◽  
Kanako Yamada ◽  
...  

Determining values of plasma renin activity (PRA) or plasma active renin concentration (ARC), plasma aldosterone concentration (PAC), and aldosterone-to-renin ratio (ARR) is essential to diagnose primary aldosteronism (PA), but it takes several days with conventional radioimmunoassays (RIAs). Chemiluminescent enzyme immunoassays for PAC and ARC using the Accuraseed® immunoanalyzer facilitated the determination, but relations between Accuraseed® immunoanalyzer-based and RIA-based values in samples of PA confirmatory tests and adrenal venous sampling remained to be elucidated. We addressed this issue in the present study. This is a prospective, cross-sectional study. ARC and PAC values were measured by the Accuraseed® immunoanalyzer in samples, in which PRA and PAC values had been measured by the PRA-FR® RIA and SPAC®-S Aldosterone kits, respectively. The relations between Accuraseed® immunoanalyzer-based and RIA-based values were investigated with regression analyses. The optimal cutoff of Accuraseed® immunoanalyzer-based ARR for PA screening was determined by the receiver operating characteristic analysis. After log-log transformations, linear relations with high coefficients of determination were observed between Accuraseed® immunoanalyzer-based and RIA-based data of renin and aldosterone. Following the PA guidelines of Japan Endocrine Society, Accuraseed® immunoanalyzer-based cutoffs were calculated from the regression equations: the basal PAC for PA screening >12 ng/dL, PAC for the saline infusion test >8.2 ng/dL, ARC for the furosemide-upright test <15 pg/mL, and ARR for the captopril challenge test >3.09 ng/dL per pg/mL. The optimal cutoff of Accuraseed® immunoanalyzer-based ARR for PA screening was >2.43 ng/dL over pg/mL not to overlook bilateral PA patients. The present study provided conversion formulas between Accuraseed® immunoanalyzer-based and RIA-based values of renin, aldosterone, and ARR, not only in basal samples but also in samples of PA confirmatory tests and adrenal venous sampling. Although validation studies are awaited, the present study will become priming water of harmonization of renin and aldosterone immunoassays.


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