The role of confirmatory tests in the diagnosis of primary aldosteronism.

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.

Seated Saline Suppression Test Is Comparable With Captopril Challenge Test for the Diagnosis of Primary Aldosteronism: A Prospective Study.

OBJECTIVE: The saline suppression test (SST) and captopril challenge test (CCT) are commonly used confirmatory tests for primary aldosteronism (PA). Seated SST (SSST) has been reported to be superior to recumbent SST. Whether SSST is better than CCT remains unclear. We aimed to compare the diagnostic accuracy of SSST and CCT in a prospective study. METHODS: Hypertensive patients at a high risk of PA were consecutively included. Patients with an aldosterone-renin ratio of ≥1.0 ng/dL/µIU/mL were asked to complete SSST, CCT, and the fludrocortisone suppression test (FST). Using FST as a reference standard (plasma aldosterone concentration [PAC] post FST ≥ 6.0 ng/dL), area under the receiver-operating characteristic curve (AUC), sensitivity, and specificity of SSST and CCT were calculated, and multiple regression analyses were performed to identify potential factors leading to false diagnosis. RESULTS: A total of 196 patients diagnosed with PA and 73 with essential hypertension completed the study. Using PAC post SSST and PAC post CCT to confirm PA, SSST and CCT had comparable AUCs (AUCSSST 0.87 [95% CI 0.82-0.91] vs AUCCCT 0.88 [0.83-0.95], P = .646). When PAC post SSST and post CCT were set at 8.5 and 11 ng/dL, respectively, the sensitivity and specificity of SSST (0.72 [0.65, 0.78] and 0.86 [0.76, 0.93]) and CCT (0.73 [0.67, 0.80] and 0.85 [0.75, 0.92]) were not significantly different. In the multiple regression analyses, 1-SD increment of sodium intake resulted in a 40% lower risk of false diagnosis with SSST. CONCLUSION: SSST and CCT have comparable diagnostic accuracy. Insufficient sodium intake decreases the diagnostic efficiency of SSST but not of CCT. Since CCT is simpler and cheaper, it is preferred over SSST.

Prediction of unilateral hyperaldosteronism on adrenal vein sampling using captopril challenge test in patients with primary aldosteronism.

Captopril challenge test (CCT) is a simple and safe confirmatory test for primary aldosteronism (PA). We investigated the effectiveness of the indices after captopril administration for prediction of unilateral hyperaldosteronism (UHA) on adrenal vein sampling (AVS). We studied 238 patients with PA who had CCT and successful AVS between July 2007 and December 2019 in Sapporo City General Hospital. Receiver operating characteristic (ROC) curve analysis showed that the diagnostic performance for prediction of UHA on AVS in regard to the reduction rate of plasma aldosterone concentration (PAC) after captopril administration was inferior to aldosterone to renin ratio (ARR) and PAC (area under the ROC curve 0.72 vs. 0.84, 0.72 vs. 0.89, respectively, both p < 0.01). Based on the optimal cut-off values in ARR (897 pg/mL/ng/mL/h, sensitivity 64.6%, specificity 93.0%) and PAC (203 pg/mL, sensitivity 73.9%, specificity 93.0%) after captopril administration, the patients were divided into three groups: (1) both positive, (2) one positive, and (3) both negative. The prevalence of UHA on AVS in the three groups were 90.0%, 52.9%, and 7.3%, respectively. In the first group, 31 of 32 patients with unilateral nodular lesion on CT had an ipsilateral unilateral AVS. In conclusion, the combination of post-captopril ARR and PAC is useful for prediction of laterality diagnosis on AVS. AVS is strongly recommended in patients with both positive or one positive results for the optimal cut-off values of post-captopril ARR and PAC and is weakly recommended in patients with both negative results.

Computed tomography combined with confirmatory tests for the diagnosis of aldosterone-producing adenoma.

Primary aldosteronism (PA) is the most common cause of secondary hypertension, and a simpler non-invasive method for identification of aldosterone-producing adenoma (APA) is required to improve the standard of medical treatment for PA patients. We retrospectively analyzed the clinical data of hypertensive patients with an aldosterone/renin ratio (ARR) ≥30 (ng/dL)/(ng/mL/h), and surgical and/or adrenal venous sampling (AVS) results served as the gold standard for APA diagnosis. The study aimed to determine whether positive CCT and SIT results plus a unilateral adrenal nodule found by CT allow unambiguous identification of an APA with high diagnostic specificity. Clinical data from 71 APA and 47 non-APA patients were collected, and logistic regression analysis was performed to construct models. Receiver operating characteristic (ROC) curves were used to analyze the efficacy of diagnostic tests. The areas under the ROC curves (AUCs) were similar between the post-SIT plasma aldosterone concentration (PAC) and post-CCT PAC (p > 0.05). The optimal post-SIT and post-CCT PAC cutoff values were 17.2 and 21.2 ng/dL, respectively. Positive CT findings combined with a post-SIT PAC >17.2 ng/dL or post-CCT PAC >21.2 ng/dL provided specificities of 97.8% and 95.7% for predicting APA, respectively. Logistic diagnostic models 1 (M1, CT finding + post-SIT PAC) and 2 (M2, CT finding + post-CCT PAC) were built, which showed equivalent diagnostic value (AUC = 0.959 and 0.932, respectively) (p > 0.05). The models combining CT findings with post-SIT PACs or post-CCT PACs represent an easier method to distinguish APA patients from other hypertensive patients with positive upright ARR results, especially in primary care where AVS may be unavailable.

[The Diagnostic Value of Captopril Challenge Test for Primary Aldosteronism].

OBJECTIVE: To investigate the diagnostic value of different captopril challenge test (CCT) diagnostic criteria for diagnosing primary aldosteronism (PA). METHODS: We collected the clinical data of 184 patients with hypertension retrospectively in West China Hospital of Sichuan University. Receiver operating characteristic (ROC) curves were used to analyze the post-CCT efficacy of aldosterone renin activity ratio (ARR), plasma aldosterone concentration (PAC), plasma renin activity (PRA) and PAC suppression rate for PA diagnosis. RESULTS: This study included 125 cases of primary aldehyde (PA group) and 59 cases of essential hypertension (EH group), and there were 38 normal renin primary hypertension (NREH group) and 21 low renin primary hypertension (LREH group) in EH group. The post-CCT PAC suppression rate (median (P 25, P 75)) of EH and PA group were 0.190 (0.083, 0.351) and 0.125 (0.024, 0.237), respectively. Compared with the NREH group, the basic and post-CCT PRA of LREH group were lower ( P<0.001), and there were no significant differences compared with the PA group ( P>0.05). We found significant overlap of post-CCT PRA and ARR between PA group and LREH group, while the overlap of post-CCT PAC between the two groups was small. In differential diagnosis of PA and EH, the areas under ROC curve of the post-CCT ARR, PAC, PRA and PAC suppression rate were 0.860 (95% confidence interval ( CI): 0.800-0.907), 0.881 (95% CI: 0.825-0.924), 0.771 (95% CI: 0.703-0.831) and 0.632 (95% CI: 0.558-0.701), respectively. There was no significant difference between the first two indexes ( Z=0.443, P=0.658), and both of them were higher than the latter two ( P<0.05). The optimal post-CCT cut-off values for ARR and PAC in differential diagnosis of PA and EH were 19.24 ng·dL -1 with a sensitivity of 78.4% and a specificity of 88.1%, and 32.47 (ng·dL -1)/(ng·mL -1·h -1) with a sensitivity of 84.17% and a specificity of 72.41%. CONCLUSION: Both ARR and PAC have higher diagnostic value than the post-CCT PAC suppression rate, post-CCT PAC is especially suitable as a confirmatory testing criterion of PA.

A combination of captopril challenge test after saline infusion test improves diagnostic accuracy for primary aldosteronism.

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.

Parameters of captopril challenge test can predict results of other confirmatory tests for primary aldosteronism and propose the next test to be done.

In Japan, primary aldosteronism (PA) is diagnosed if any one of the captopril challenge test (CCT), saline infusion test (SIT), furosemide-upright test (FUP), and oral salt-loading test (OST) is positive. The present study aimed to investigate if parameters of CCT, the safest confirmatory test, could predict decisions of other tests and propose the next test to diagnose PA in CCT-negative patients. In a cross-sectional design, 142 patients, who were referred to our hospital for the scrutiny of PA and underwent at least two confirmatory tests, were enrolled. While 123 patients underwent all of the CCT, SIT, and FUP, the OST was successfully done in only six patients and excluded from further analyses. CCT parameters showing correlations of higher degrees with SIT and FUP parameters were selected, and their powers to predict SIT and FUP decisions were investigated by receiver operating characteristic analyses. Proposals of the next test based on the CCT parameters were validated with SIT and FUP decisions in subsets of CCT-negative patients divided by cut-offs of the CCT parameters. The plasma aldosterone concentration and plasma renin activity 60 min after the load of CCT (CCT60-PAC and CCT60-PRA) were selected, and CCT60-PAC ≤59.0 pg/mL and CCT60-PRA ≥1.05 ng/mL/h could predict negativities of SIT and FUP, respectively, with >95% specificities. Based on the validation, the present study suggested the SIT as the next test to be done if the CCT-negative patient belonged to the subset with CCT60-PAC >59.0 pg/mL and CCT60-PRA ≥1.05 ng/mL/h, otherwise the FUP should be selected.

Confirmatory tests for the diagnosis of primary aldosteronism: A systematic review and meta-analysis.

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.

The captopril challenge test for diagnosing primary Aldosteronism in a Chinese population.

BACKGROUND: The Captopril challenge test (CCT) is an easy-conduct confirmatory test for diagnosing primary aldosteronism (PA). Guidelines show that plasma aldosterone is normally suppressed by captopril (> 30%) in primary hypertension (PH) and in healthy people. It is unclear whether this standard is applicable in Chinese subjects. The aim of the present study was to investigate the post-CCT efficacy of plasma aldosterone concentration (PAC) suppression and determine the post-CCT aldosterone renin activity ratio (ARR) and PAC for PA diagnosis. METHODS: We recruited 110 consecutive patients with PA, 163 with primary hypertension (PH), and 40 healthy volunteers (NC). The CCT was conducted in all patients. Total sodium intake was estimated from 24-h urinary excretions. ROC curves were used to analyze the efficiency of different CCT diagnostic criteria for diagnosing PA. RESULTS: In NC and PH patients, PRA was increased and PAC was decreased post-CCT (P < 0.05). The mean degree of PAC decline after CCT was approximately 9.3%, and only 11.7% of the patients with PH showed a greater than 30% suppression of PAC after CCT. In patients with PA, the post-CCT change in PRA and PRC was slight. The post-CCT degree of PAC decline was unrelated to dietary salt intake. The areas under the ROC for the post-CCT ARR, PAC and PAC suppression % were 0.994, 0.754 and 0.606, respectively. The optimal post-CCT cutoff value for ARR for diagnosing PA was 20, which yielded a sensitivity and specificity of 94.0 and 99.4%, respectively. CONCLUSIONS: The PAC suppression percentage after CCT recommended by current clinical guidelines is not applicable when diagnosing Chinese subjects with PA. Compared to post-CCT PAC, post-CCT ARR was a better approach, having an optimal cutoff of 20 when interpreting the results of the CCT in Chinese patients. We found no relationship between high salt intake and low responses of the renin-angiotensin system (RAS) to the CCT.

[Efficacy of Screening and Confirmatory Tests of Primary Aldosteronism in Diagnosing Aldosterone Producing Adenoma].

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.

Saline Infusion Test highly associated with the incidence of cardio- and cerebrovascular events in primary aldosteronism.

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.

[The application of captopril challenge test in the diagnosis of primary aldosteronism].

Objective: To evaluate the value of captopril challenge test (CCT) in the diagnosis of primary aldosteronism (PA). Methods: A total of 674 patients [(45.0±13.7) years, men 341, women 333] admitted to Peking Union Medical College Hospital from 2000 to 2015 were analyzed. Among them, 222 subjects were with essential hypertension (EH), 28 were with pheochromocytoma (PHEO), 246 were with idiopathic hyperaldosteronism (IHA) and 178 were with aldosterone producing adenoma (APA). All patients received CCT. 24 h urine sodium was measured in partial patients. Plasma renin activity (PRA), aldosterone (ALD) were detected. Results: Compared with EH [PRA: before 0.5(0.2, 0.9) µg·L(-1)·h(-1,) after 0.8(0.4, 1.5) µg·L(-1)·h(-1;) ALD: before (393±122) pmol/L, after (360±97) pmol/L] and PHEO [PRA: before 0.3(0.1, 0.9) µg·L(-1)·h(-1,) after 0.4(0.1, 1.6) µg·L(-1)·h(-1;) ALD: before (396±108) pmol/L, after (374±114) pmol/L], lower levels of PRA and higher levels of ALD before and after CCT were observed in PA patients [PRA: before 0.1 (0.1, 0.2) µg·L(-1)·h(-1,) after 0.1 (0.1, 0.2) µg·L(-1)·h(-1;) ALD: before (468±216) pmol/L; after (457±199) pmol/L]. After CCT, the suppression rate of ALD [2.8% (-8.8%, 15.4%) vs 6.6% (-4.3%, 17.6%)] and increasing rate of PRA [0(0, 50%) vs 50%(0, 200%)] in PA patients were lower than those in EH patients. The ALD/PRA ratio (ARR) were higher in PA than that in EH or PHEO patients. In the EH subjects, ALD levels of seated posture were higher than those of recumbent posture both before and after receiving captopril, but with no changes in ARR after CCT. No significant differences in ALD and ARR (before and after receiving captopril) were observed between seated and recumbent position in the PA group. The ARR after CCT tended to decrease in EH subjects with elevated urine-sodium compared with those with normal urine-sodium. No changes could be viewed in ALD and PRA levels between normal urine-sodium and elevated urine-sodium groups among APA, IHA and EH patients either before or after CCT. Among patients with APA, the ALD levels before CCT and the ARR after CCT were lower in the patients with AngiotensionⅡ(AngⅡ) reactive than those without. A ROC curve analysis suggested that the optimal cutoff value was 46.2 (ALD unit: ng/dl; PRA unit: µg·L(-1)·h(-1)) for ARR after challenge in diagnosing PA, with the sensitivity of 88.7% and specificity of 84.8%. Conclusions: ARR after 25 mg captopril had high sensitivity and specificity in diagnosis of PA with the cutoff of 46.2. Seated CCT could replace recumbent CCT as a more confirmatory test. The PRA increasing rate should be taken into consideration when diagnosis of PA.

Captopril challenge test: an underutilized test in the diagnosis of primary aldosteronism.

Primary aldosteronism (PA) is the most common cause of endocrine hypertension and is often underdiagnosed. This condition is associated with increased cardiovascular morbidity and mortality in comparison to age and blood pressure matched individuals with essential hypertension (EH). The diagnostic pathway for PA consists of three phases: screening, confirmatory testing, and subtyping. The lack of specificity in the screening step, which relies on the aldosterone to renin ratio, necessitates confirmatory testing. The Endocrine Society's clinical practice guideline suggests four confirmatory tests, including the fludrocortisone suppression test (FST), saline suppression test (SST), captopril challenge test (CCT), and oral sodium loading test (SLT). There is no universally accepted choice of confirmatory test, with practices varying among centers. The SST and FST are commonly used, but they can be resource-intensive, carry risks such as volume overload or hypokalemia, and are contraindicated in severe/uncontrolled HTN as well as in cardiac and renal impairment. In contrast, CCT is a safe and inexpensive alternative that can be performed in an outpatient setting and can be applied when other tests are contraindicated. Despite its simplicity and convenience, the variability in captopril dose, testing posture, and diagnostic threshold limit its widespread use. This narrative review evaluates the diagnostic accuracy of the CCT across different populations, addresses controversies in its usage, and proposes recommendations for its use in the diagnosis of PA. Furthermore, suggestions for future research aimed at promoting the wider utilization of the CCT as a simpler, safer, and more cost-effective diagnostic test are discussed.

Investigating the cut-off values of captopril challenge test for primary aldosteronism using the novel chemiluminescent enzyme immunoassay method: a retrospective cohort study.

The measurement evolution enabled more accurate evaluation of aldosterone production in hypertensive patients. However, the cut-off values for novel assays have been not sufficiently validated. The present study was undertaken to validate the novel chemiluminescent enzyme immunoassay for aldosterone in conjunction with other methods. Moreover, we also aimed to establish a new cut-off value for primary aldosteronism in the captopril challenge test using the novel assay. First, we collected 390 plasma samples, in which aldosterone levels measured using liquid chromatography-mass spectrometry ranged between 0.18 and 1346 ng/dL. The novel chemiluminescent enzyme immunoassay showed identical correlation of plasma aldosterone with liquid chromatography-mass spectrometry, in contrast to conventional radioimmunoassay. Further, we enrolled 299 and 39 patients with primary aldosteronism and essential hypertension, respectively. Plasma aldosterone concentrations measured using the novel assay were lower than those measured by radioimmunoassay, which resulted in decreased aldosterone-to-renin ratios. Subsequently, positive results of the captopril challenge test based on radioimmunoassay turned into "negative" based on the novel assay in 45% patients with primary aldosteronism, using the conventional cut-off value (aldosterone-to-renin activity ratio > 20 ng/dL per ng/mL/h). Receiver operating characteristic curve analysis demonstrated that aldosterone-to-renin activity ratios > 8.2 ng/dL per ng/mL/h in the novel assay was compatible with the conventional diagnosis (sensitivity, 0.874; specificity, 0.980). Our study indicates the great measurement accuracy of the novel chemiluminescent enzyme immunoassay for aldosterone, and the importance of measurement-adjusted cut-offs in the diagnosis of primary aldosteronism.

Comparison of saline infusion test and captopril challenge test in the diagnosis of Chinese with primary aldosteronism in different age groups.

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.

Comparison of four confirmatory tests for the diagnosis of primary aldosteronism: Bayesian analysis in the absence of a gold standard.

BACKGROUND: Captopril challenge test (CCT), seated saline infusion test (SSIT), oral sodium loading test (OSLT) and fludrocortisone suppression test (FST) are widely used diagnostic tests for primary aldosteronism (PA). These tests differ in terms of safety and complexity. Whether the simpler tests (CCT and SSIT) are comparable in diagnostic performance to the more complex ones (FST and OSLT) is unclear. PURPOSE: To compare the diagnostic accuracy of the four tests. METHODS: This is a retrospective study of hypertensive patients who were screened for PA and completed at least one confirmatory test. The patients were divided into two cohorts: one including those who completed one to three tests was used for the estimation of sensitivity and specificity. The other including those who completed four tests was used for the comparison of accuracy. Bayesian method was used to obtain the sensitivity, specificity, and Youden index of each test. RESULTS: The study included 1011 hypertensive patients. Among them, 895 patients completed one to three tests (including 889 CCT, 605 FST, 611 SSIT and 69 OSLT), and 116 patients completed four tests. SSIT had the highest sensitivity of 0.82(95% CI 0.78-0.86) but the lowest specificity of 0.76(0.70-0.80). OSLT had the lowest sensitivity of 0.65(0.56-0.75) but the highest specificity of 0.91(0.82-0.96). The sensitivity and specificity were 0.78 (95% CI, 0.75-0.82), 0.82 (95% CI, 0.78-0.85), for CCT, and 0.77 (95% CI, 0.73-0.81), 0.87 (95% CI, 0.82-0.91) for FST, respectively. The Youden index was not significantly different among the four tests[0.60(0.55-0.65) for CCT; 0.58(0.51-0.64) for SSIT; (0.64(0.57-0.69) for FST; 0.56(0.43-0.67) for OSLT]. CONCLUSION: The accuracy of simpler tests is comparable to the more complex ones. Considering the safety and simplicity of CCT, it may be a reasonable first choice when confirming the diagnosis of PA.

Captopril challenge test in the diagnosis of primary aldosteronism: consistency between 1- and 2- h sampling.

Objective: To examine the consistency of plasma aldosterone concentration at 1 and 2 h in the captopril challenge test (CCT) and to explore the possibility of replacing 2-h aldosterone concentration with 1-h aldosterone concentration for diagnosis of primary aldosteronism (PA). Methods: This retrospective analysis included a total of 204 hypertensive patients suspected of having PA. Subjects received oral captopril challenge at 50 mg (25 mg if the systolic blood pressure was <120 mmHg), and plasma aldosterone concentration and direct renin concentration were measured at 1 and 2 h afterward (chemiluminescence immunoassay Liaison® DiaSorin, Italy). Sensitivity and specificity were used to reflect the diagnostic performance of 1-h aldosterone concentration using 2-h aldosterone concentration (11 ng/dl as the cutoff) as the reference. A receiver operating characteristic curve analysis was also conducted. Results: Among the 204 included patients [median age of 57.0 (48.0-61.0) years, 54.4% men], a diagnosis of PA was established in 94 patients. Aldosterone concentration in the patients with essential hypertension was 8.40 (interquartile range 7.05-11.00) ng/dl at 1 h and 7.65 (5.98-9.30) ng/dl at 2 h (P < 0.001). In patients with PA, aldosterone concentration was 16.80 (12.58-20.50) ng/dl at 1 h and 15.55 (12.60-20.85) ng/dl at 2 h (P > 0.999). At a cutoff of 11 ng/dl, the sensitivity and specificity of using 1-h aldosterone concentration to diagnose PA were 87.2% and 78.2%, respectively. A higher cutoff of 12.5 ng/ml increased specificity to 90.0% but decreased sensitivity to 75.5%. A lower cutoff of 9.3 ng/ml increased sensitivity to 97.9% but decreased specificity to 65.4%. Conclusions: When diagnosing PA with CCT, 1-h aldosterone concentration could not be used to replace 2-h aldosterone concentration.

A new machine learning-based prediction model for subtype diagnosis in primary aldosteronism.

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 robust prediction tool for PA subtype diagnosis, thereby, might reducing at least some of the requests for CT or AVS and assisting clinical decision-making.

The Value of Different Single or Combined Indexes of the Captopril Challenge Test in the Diagnosis of Primary Aldosteronism.

Objective: The 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. Methods: We 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. Results: Post-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). Conclusion: We 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.

The value of the post-captopril aldosterone/renin ratio for the diagnosis of primary aldosteronism and the influential factors: A meta-analysis.

OBJECTIVE: The procedure for the captopril challenge test (CCT) in diagnosing primary aldosteronism (PA) is not standardized. We performed a meta-analysis to evaluate the controversial diagnostic value and influential factors of the post-captopril aldosterone/renin ratio (ARR). METHODS: We searched literature in databases for eligible studies (until October 1, 2020). We extracted information regarding study and patient characteristics, CCT methods, outcome data. We pooled studies using the random-effect model. We performed meta-regression and six pre-specified subgroup analyses to explore heterogeneity. RESULTS: Nineteen studies involving 4568 subjects were included. The pooled sensitivity and specificity were 0.825 (95% CI 0.804-0.844) and 0.919 (95% CI 0.908-0.928). The area under the summary receiver operating characteristic curve was 0.9487 (95% CI 0.9207-0.9767). Meta-regression revealed that heterogeneity might derive from time interval (p = 0.0117) and study population (p = 0.0033). Subgroup analyses showed significant differences between the subgroups stratified by the dose, posture, study region, time interval, cut-off value and study population for sensitivity and/or specificity (p < 0.05). CONCLUSION: Post-captopril ARR is comparably valuable for diagnosing PA at cut-offs from 12.0 to 50.0. Conducting the CCT in the supine position with 25 mg of captopril may attain greater sensitivity. Conducting the CCT in the seated position with 50 mg of captopril may attain greater specificity. A 90-min time interval may perform best in both the sensitivity and specificity.