Captopril Challenge Test Research Articles

Differences in target organ damage between captopril challenge test-defined definitive-positive and borderline-range groups among patients with primary aldosteronism.

The new Japanese guidelines for primary aldosteronism introduce a category in the judgment of functional confirmatory tests that is called the "borderline range," which is rare in the other international guidelines. The clinical characteristics of this borderline group are not yet understood. To investigate whether this borderline group has any significant differences in terms of target organ damage, we used data from a Japanese nationwide registry (JPAS-II) of individuals with primary aldosteronism or essential hypertension to compare the borderline group with the definitive-positive group and the negative group. We analyzed the cases of 1785 patients based on their captopril-challenge test results. Since the JPAS-II database contains plasma aldosterone concentration values obtained based on both radioimmunoassay (n = 1555) and chemiluminescent enzyme immunoassay (n = 230) principles, we converted these values to their equivalents as if measured by chemiluminescent enzyme immunoassay and conducted all analyses under the simulated condition. Multicovariate-adjusted models revealed significant prevalance odds ratios for chronic kidney disease (2.01, 95% confidence interval: 1.13 to 3.61), electrocardiographic abnormalities (1.66, 95% confidence interval: 1.16 to 2.37). No significant difference was observed between the borderline and negative groups in these assessments (odds ratio [95% confidence interval] for chronic kidney disease: 0.73 [0.26 to 2.02] and electrocardiographic abnormalities: 1.01 [0.60 to 1.70]). We confirmed that the prevalence of target organ damage increases linearly as the aldosterone-to-renin ratio rises following the captopril challenge test. These results provide material to consider regarding the significance of the provisionally established borderline group.

7211 Clinical and Molecular Characterization Of An Aldosterone-Producing Adenoma Harboring Double Somatic Mutations In CTNNB1 and GNA11

Abstract Disclosure: A. Blinder: None. K. Nanba: Grant Recipient; Self; AstraZeneca. A. Udager: None. Y. Hirokawa: None. T. Miura: None. H. Okuno: None. K. Moriyoshi: None. Y. Yamazaki: None. H. Sasano: None. A. Yasoda: None. N. Satoh-Asahara: None. W.E. Rainey: None. T. Tagami: None. Background: Somatic activating mutations in CTNNB1, encoding β-catenin, have been detected in a small subset of aldosterone-producing adenomas (APAs). As a possible pathogenesis, an association of CTNNB1-mutated APA with pregnancy and menopause has been proposed. A recent study reported double somatic mutations in CTNNB1 and GNA11/Q, encoding guanine nucleotide-binding protein subunits alpha-11 and alpha-Q, in APA. However, due to its rare incidence, clinical and molecular features of APA associated with these mutations have not been well characterized. Herein, we report a case of APA harboring somatic CTNNB1 and GNA11 mutations. Clinical Case: A 46-year-old Japanese woman presented with hypertension and hypokalemia. She had two pregnancies in the past but had no history of pregnancy-induced hypertension. She had regular menstrual cycles at presentation. Laboratory testing showed elevated plasma aldosterone concentration with suppressed plasma renin activity. She was diagnosed as having primary aldosteronism based on the results of a captopril challenge test. Adrenal computed tomography revealed a 2 cm right adrenal mass. Adrenal venous sampling indicated excess aldosterone production from the right adrenal gland. She underwent right laparoscopic adrenalectomy. Histologic diagnosis of the resected tumor was adrenocortical adenoma based on the criteria of Weiss. Notably, Ki-67 labeling index was high (6% at hotspots). After surgery, her blood pressure and serum potassium both normalized. According to the primary aldosteronism surgical outcome (PASO) study criteria, PA remained clinically and biochemically cured at follow-up 2.5 years after surgery. Results: Immunohistochemistry (IHC) showed high and diffuse expression of aldosterone synthase (CYP11B2) within the tumor, whereas immunoreactivity of 17α-hydroxylase (CYP17A1) and 11β-hydroxylase (CYP11B1), both required for cortisol biosynthesis, was markedly low. VSNL1, a marker for the zona glomerulosa (ZG) where physiologic aldosterone biosynthesis occurs, was highly expressed within the tumor. CYP11B2 IHC-guided tumor capture followed by targeted next-generation sequencing identified double somatic CTNNB1 (p.D32Y) and GNA11 (p.Q209H) mutations. Quantitative real-time RT-PCR revealed high tumor expression of LHCGR (LH receptor) and GNRHR (GNRH receptor) mRNA levels compared with those in adjacent normal adrenal (148-fold and 56-fold, respectively). Immunofluorescence staining of the tumor revealed the presence of activated β-catenin, consistent with features of the normal ZG. Conclusions: Our study indicates that an APA with double somatic mutations in CTNNB1 and GNA11 has characteristics of the ZG and could occur in adults with no clear association with pregnancy or menopause. Presentation: 6/3/2024

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

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. To compare the diagnostic accuracy of the four tests. 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. 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]. 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.

The value of midnight 1 mg dexamethasone suppression test combined with ACTH stimulation test in the diagnosis of primary aldosteronism subtypes

Objective: To explore the value of the midnight 1 mg dexamethasone suppression test combined with adrenocorticotropic hormone (ACTH) stimulation test in the diagnosis of primary aldosteronism (PA) subtypes. Methods: A cross-sectional study. Clinical data of patients diagnosed with PA at the First Medical Center of Chinese PLA General Hospital from January 2020 to September 2022, who completed the midnight 1 mg dexamethasone suppression test combined with ACTH stimulation test, were analysed retrospectively. The clinical characteristics and trial results of patients with aldosterone-producing adenoma (APA) and idiopathic hyper aldosteronism (IHA)were compared. The efficacy of the midnight 1 mg dexamethasone suppression test combined with ACTH stimulation test in distinguishing APA and IHA was evaluated by drawing receiver operating characteristic (ROC) curves, and the cut-off value of the diagnostic indicator was determined with the maximum Youden index. Results: A total of 82 patients with PA were included, including 43 males and 39 females, aged (50.8±11.4) years old. They were divided into APA group (n=49) and IHA group (n=33) based on PA subtype. There was no statistically significant difference in body mass index, systolic and diastolic blood pressure between the two groups (all P>0.05). The blood potassium and orthostatic renin levels in the APA group were lower than those in the IHA group, and the differences were statistically significant (all P<0.001). The orthostatic plasma aldosterone concentration (PAC), orthostatic aldosterone to renin ratio (ARR), PAC before and after captopril challenge test(CCT), ARR after CCT, PAC before and after saline infusion test (SIT), and the proportion of unilateral lesions in the APA group were all higher than those in the IHA group, and the differences were statistically significant (all P<0.001). After the midnight 1 mg dexamethasone suppression test combined with ACTH stimulation test (30, 60, 90, 120 min), the PAC and PAC/cortisol levels in the APA group were significantly higher than those in the IHA group (all P<0.05). The PAC at 90 min showed the highest diagnostic capability according to the area under the ROC(AUC) (0.930,95%CI:0.874-0.986), and the Youden index was the highest at a PAC cut-off value of 39.05 ng/dl(0.766). The sensitivity and specificity for distinguishing APA from IHA were 91.8% and 84.8%, respectively. Conclusions: The midnight 1 mg dexamethasone suppression test with ACTH stimulation test could be useful for differentiating the subtypes of PA. Among them, the PAC and PAC/cortisol at 90 min showed best diagnostic efficacy.

Hiperaldosteronismo primario

Primary hyperaldosteronism (PHA) is the most frequent cause of secondary hypertension (HT). Furthermore, it is associated with greater cardiometabolic and mortality risk than the observed in patients with essential HT. It is recommended to screen for PHA by determining the aldosterone-to-renin ratio in patients with severe and/or resistant HT, HT with hypokalemia, HT and adrenal incidentaloma, HT and a first-degree family history of PHA, and in HT associated with atrial fibrillation that cannot be explained by other causes. If a pathological aldosterone-to-renin ratio is confirmed, dynamic tests should be performed to establish a confirmatory diagnosis; these are usually a saline infusion test or captopril challenge test. These tests can be omitted in patients with overt PHA (plasma aldosterone greater than 20 ng/dl, suppressed renin, and hypokalemia). The last step in the diagnosis is the localization study, being the computed tomography (CT) scan of the adrenal glands the initial test of choice. Nevertheless, in most patients in whom adrenal surgery is considered, adrenal vein sampling (AVS) will be necessary to establish PHA laterality. AVS is not considered necessary in cases of suspected aldosterone-producing adrenocortical carcinoma and/or PHA in patients younger than 35 years with a clear unilateral lesion on a CT/magnetic resonance imaging (MRI) test. The treatment of PHA depends on the results of the localization study: the treatment of choice is a unilateral adrenalectomy in unilateral forms and mineralocorticoid receptor antagonists in bilateral forms.

COMPARISON OF SALINE INFUSION TEST AND CAPTOPRIL CHALLENGE TEST IN THE DIAGNOSIS OF PRIMARY ALDOSTERONISM IN DIFFERENT AGE GROUPS

Objective: To explore the diagnostic accuracy and the optimal cut-off value between the saline infusion test (SIT) and captopril challenge test (CCT) (including the value and suppression of plasma aldosterone concentration (PAC)) for PA diagnosing. Design and method: A total of 318 patients with hypertension were consecutive enrolled including 126 patients with PA and 192 patients with essential hypertension (EH). The characteristics of patients and laboratory examinations were collected and compared. The comparison between SIT and CCT was carried by drawing receiver operator characteristic curve (ROC) and calculating area under the curve (AUC) to explore the diagnostic accuracy and the optimal cut-off value. Results: The average age was 51.59±10.43 in PA group and 45.72±12.44 in EA group (P&lt;0.05). The optimal cut-off 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 cut-off value for patients who were less than 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 50 years old or more than 50 years old. Conclusions: Compared with SIT, CCT presented a higher diagnostic value when post-CCT PAC was used as the diagnostic criteria among Chinese people, while the selection of diagnostic thresholds depended on patients at different age stages.

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 plasma aldosterone measured by chemiluminescence immunoassay and liquid chromatography-tandem mass spectrometry in screening test for primary aldosteronism

BackgroundWhether chemiluminescence immunoassay (CLIA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for plasma aldosterone concentration (PAC) measurement can be used interchangeably in primary aldosteronism (PA) screening is still controversial. The purpose of this study was to compare CLIA to LC-MS/MS for PAC measurement in PA screening. MethodsAll participants underwent aldosterone-to-renin ratio (ARR) testing. PA was diagnosed by captopril challenge test or saline infusion test. PAC in screening test was measured with CLIA and LC-MS/MS. Plasma direct renin concentration in screening and confirmatory test was measured with CLIA. The concordance between CLIA and LC-MS/MS for PAC measurement in PA screening was analyzed. ResultsTwenty-one healthy volunteers, 61 patients with essential hypertension (EH) and 43 PA patients were enrolled. Median PAC by CLIA was 84.7 % higher than that by LC-MS/MS in screening test (P < 0.001). A positive correlation of PAC was observed between the two assays (Pearson r coefficient 0.770, P < 0.001). When ARR was used in differentiating PA from EH, there was no difference in the area under the receiver operating characteristic curve between CLIA and LC-MS/MS for PAC measurement (0.968 vs 0.950, P = 0.249). ConclusionCLIA and LC-MS/MS for PAC measurement exhibited high and comparable efficacy in PA screening. CLIA is a reliable and feasible alternative in PA screening test.

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.

Impact of the transition from radioimmunoassay (RIA) to chemiluminescent enzyme immunoassay (CLEIA) for the measurement of plasma aldosterone concentration (PAC) on the diagnosis of primary aldosteronism (PA) via retrospective analyses in Okinawa, Japan.

In Japan, the traditional method for measuring plasma aldosterone concentration (PAC) was radioimmunoassay (RIA), which had several challenges, including poor traceability of certified reference materials and reduced detection sensitivity at low concentrations. To overcome these issues, a chemiluminescent enzyme immunoassay (CLEIA) for PAC measurement was introduced in April 2021 and the Japan Endocrine Society published new guidelines for primary aldosteronism (PA). This study aimed to evaluate the impact of the transition from RIA to CLEIA for PAC measurement on PA diagnosis. Data from 190 patients admitted to the Second Department of Internal Medicine, University of the Ryukyus Hospital, between April 2012 and March 2021 were analyzed. Patients who were diagnosed with PA underwent adrenal venous sampling. The PAC measured by RIA (PAC(RIA)) was converted to the estimated PAC measured by CLEIA (ePAC(CLEIA)) using a conversion formula. The present study evaluated the discordance rates in diagnoses based on screening (SC), captopril challenge test (CCT), saline infusion test (SIT), and diagnosis of PA between results judged by PAC(RIA) according to the previous guidelines and those judged by ePAC(CLEIA) according to the new guidelines. The results revealed discordant diagnosis rates of 6.4% for SC and 10.1% for CCT, with no discordance for SIT. The discordant diagnosis rate for PA was 3.7%. Our study reveals the challenges in establishing appropriate diagnostic criteria for PA using PAC(CLEIA) and highlights the demand for further research on provisionally positive categories.

Long-Term Follow-Up of Patients With Elevated Aldosterone-to-Renin Ratio but Negative Confirmatory Test: The Progression of Primary Aldosteronism Phenotypes.

About 10% of patients with arterial hypertension have a positive screening test for primary aldosteronism (PA) and 50% to 70% of them have a negative confirmatory test: the appropriate follow-up of these patients is currently unknown. We investigated the incidence of PA in patients with previous negative confirmatory testing, after at least a 2-year follow-up. One hundred eighty-four patients with a previously elevated aldosterone-to-renin ratio followed by a negative confirmatory test were recruited in 2 hypertension centers (Torino and Munich). We repeated the screening test for PA and, if positive, the confirmatory test (seated saline infusion test or captopril challenge test). Primary end point of the study was the incidence of newly diagnosed overt PA, as defined by a positive confirmatory test. After a mean follow-up of 5 years, 20% of patients developed overt PA. When subtype diagnosis was offered systematically, one-third of patients displayed unilateral PA. Patients who developed PA showed worsening of blood pressure control and a higher rate of cardiac organ damage, despite similar implementation of antihypertensive therapy, compared with patients without PA. A mild progression of autonomous aldosterone secretion was evident even in patients without confirmed PA but with relatively stable control of blood pressure levels over time. About one-fifth of patients with a negative confirmatory test develop overt PA over time. A clinical follow-up of patients with a negative confirmatory test is advisable, along with the repetition of PA investigation, primarily in patients with worsening of blood pressure control.

Efficacy of Oral Furosemide Test for Primary Aldosteronism Diagnosis.

Confirmatory tests represent a fundamental step in primary aldosteronism (PA) diagnosis, but they are laborious and often require a hospital environment due to the risks involved. To evaluate the efficacy of oral furosemide as a new confirmatory test for PA diagnosis. We prospectively evaluated the diagnostic performance of 80 mg of oral furosemide in 64 patients with PA and 22 with primary hypertension (controls). Direct renin concentration (DRC) was measured before, and 2 hours and 3 hours after the oral furosemide. In addition, the oral furosemide test was compared with 2 other confirmatory tests: the furosemide upright test (FUT) and saline infusion test (SIT) or captopril challenge test (CCT) in all patients with PA. The cut-off of 7.6 µU/mL for DRC at 2 hours after oral furosemide had a sensitivity of 92%, specificity of 82%, and accuracy of 90% for PA diagnosis. In 5 out of 6 controls with low-renin hypertension, which might represent a PA spectrum, renin remained suppressed. Excluding these 6 controls with low-renin hypertension, the DRC cut-off of 10 µU/mL at 2 hours after oral furosemide had a sensitivity of 95.3%, specificity of 93.7% and accuracy of 95% for PA diagnosis. DRC after 3 hours of oral furosemide did not improve diagnostic performance. Using the cut-off of 10 µU/mL, the oral furosemide test and the FUT were concordant in 62 out of 64 (97%) patients with PA. Only 4 out of 64 cases with PA (6.4%) ended the oral furosemide test with potassium <3.5 mEq/L. Hypotension was not evidenced in any patient with PA during the test. The oral furosemide test was safe, well-tolerated and represents an effective strategy for PA investigation.

FRI138 Diagnostic Accuracy Of Plasma Renin Activity Measured By Radioimmunoassay And LC-MS/MS For The Screening Of Primary Aldosteronism

Abstract Disclosure: A. Hong: None. J. Yoon: None. J. Park: None. W. Choi: None. H. Kim: None. H. Kang: None. Background: Plasma aldosteronism (PA) is screened based on the levels of aldosterone-to-renin ratio (ARR) and/or plasma aldosterone concentration. However, false positive cases are often observed due to low levels of plasma renin activity (PRA). Here, we aimed to compare diagnostic accuracy of PRA measured by radioimmunoassay (RIA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the screening of PA. Materials and Methods: We retrospectively included 67 patients in whom PRA was measured using both RIA and LC-MS/MS due to adrenal incidentaloma or suspected secondary hypertension in a tertiary referral center. Patients with ARR≥20 underwent saline infusion test (SIT) and/or captopril challenge test (CCT) for the confirmation of PA. Results: The mean PRA was 3.1±7.5 ng/mL/hr by RIA and 3.0±6.3 ng/mL/hr by LC-MS/MS (P=0.284). The mean ARR was 53.7±137.4 by RIA and 41.2±129.9 by LC-MS/MS. The correlation coefficient between RIA and LC-MS/MS was 0.992 in patients with ARR&amp;lt;20 (n=38) (P&amp;lt;0.001) and 0.595 in patients with ARR ≥20 (n=29) (P=0.001). In patients who underwent confirmative test (CCT or SIT), false-positivity rate was 77.8% (7/9) based on RIA and 66.7% (6/9) based on LC-MS/MS. Conclusion: PRA measured using LC-MS/MS showed a significant positive correlation with PRA using RIA, particularly at ARR&amp;lt;20. ARR calculated by both methods for PRA revealed similar false-positives. Further studies are needed to validate diagnostic accuracy between the two methods of PRA for PA screening. Presentation: Friday, June 16, 2023

Abstract P100: Paradoxical Increase In Post-Captopril Aldosterone

Hypertension remains one of the strongest risk factors for cardiovascular disease. Primary aldosteronism, the most common form of secondary hypertension, can be confirmed using the captopril challenge test. This study aims to investigate a subset of patients who exhibit a paradoxical increase in aldosterone levels after the administration of captopril, despite the expected decrease in aldosterone production. A retrospective design was employed to evaluate patients who exhibited atypical captopril suppression test results. The cohort consisted of 120 patients who underwent the captopril suppression test as part of their diagnostic evaluation for resistant hypertension. Demographic data and clinical parameters were collected for each patient.Among the patients who tested positive on the captopril suppression test based on a post-aldosterone level criterion of &gt;12 mg/dL, one-third exhibited an increase equal to or greater than 50% in aldosterone levels (9 out of 27).We proposed different theories to explain this phenomenon. Intraindividual variability, which has been previously reported with a laboratory coefficient of variation between 2.7% and 4.4%, was ruled out using a cut-off ≥ 50%. Another possibility is the presence of extraadrenal aldosterone production independent of the regulation provided by captopril or ATII. This could be attributed to unrecognized compensation of aldosterone production by extra-adrenal tissues in response to a decrease in adrenal aldosterone levels. Additionally, conditions such as preeclampsia, post-transplant acute rejection, autoimmune diseases, lupus, and primary hyperaldosteronism have been associated with increased aldosterone production by zona glomerulosa cells due to the presence of activating antibodies.There are certain limitations to this study. Other biochemical tests were not performed, and the sample size was relatively small, making it challenging to draw definitive conclusions. In conclusion, this study aims to contribute to our understanding of the pathogenesis of primary aldosteronism. The findings highlight the utility of the captopril suppression test as a biochemical confirmation test for the diagnosis of primary aldosteronism and resistant hypertension.

Primary hyperaldosteronism in Acute Central Serous Chorioretinopathy: a real need for screening?

Central Serous Chorioretinopathy (CSCR) is a prevalent ocular disease classified in the pachychoroidal spectrum with an elevated morbidity. Although the pathogenesis is yet unclear, mineralocorticoid-mediated pathways seem to be implicated. Primary hyperaldosteronism (PA) is a relatively frequent, albeit underdiagnosed, cause of hypertension, and has a specific therapy. A previous study assessed the prevalence of CSCR-like signs in a cohort of patients diagnosed with PA and found signs in seven out of thirteen PA patients. The present study aims to study the contrary, screening for PA in a cohort of acute CSCR patients. Between March 2017 and September 2018 all patients with acute CSCR were systematically referred to Endocrinology Department after complete ophthalmic evaluation was performed with visual acuity, spectral domain optical coherence tomography, fundus autofluorescence, fluorescein and indocyanine green angiography. The method applied for detection of PA was the 2-h 25mg captopril challenge test (CCT). Of the nineteen patients screened, two of them had a CCT positive for PA (2-h plasma aldosterone/renin ratio > 50 and/or an aldosterone level of 130pg/ml or higher), and were treated with mineralocorticoid receptor antagonists (MRA). No ophthalmic pattern was identified in them in terms of time to resolution, recurrences or features of the acute episode. The only differential feature in the fundus of PA patients was pathological arteriovenous crossings (AVC) as well as elevated BP levels. a high incidence of PA was found among acute CSCR patients. This preliminary study suggests a need for screening for PA in hypertensive CSCR patients in real clinical practice.

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

To examine the consistency of plasma aldosterone concentration at 1 and 2h 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). 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 2h 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. 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 1h and 7.65 (5.98-9.30) ng/dl at 2h (P < 0.001). In patients with PA, aldosterone concentration was 16.80 (12.58-20.50) ng/dl at 1h and 15.55 (12.60-20.85) ng/dl at 2h (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%. When diagnosing PA with CCT, 1-h aldosterone concentration could not be used to replace 2-h aldosterone concentration.

Renin-independent aldosteronism and chronic kidney disease in diabetes: Observational and Mendelian randomization analyses

BackgroundRenin-independent aldosteronism (RIA) describes the spectrum of autonomous aldosterone secretion from mild to overt. We aimed to explore whether RIA is causally associated with chronic kidney disease (CKD) in patients with diabetes. MethodsWe cross-sectionally included 1027, 402 and 39,709 patients with any type of diabetes from cohorts of EIMDS, CONPASS and UK Biobank, respectively. In EIMDS, we defined RIA and renin-dependent aldosteronism based on plasma aldosterone and renin concentrations. We performed captopril challenge test to confirm renin-dependent or independent aldosteronism in CONPASS. In UK Biobank, we generated genetic instruments for RIA based on the genome-wide association studies (GWAS). We extracted the corresponding single nucleotide polymorphisms (SNPs) information from the GWAS data of CKD in diabetes. We harmonized the SNP-RIA and SNP-CKD data to conduct the two-sample Mendelian randomization analyses. FindingsIn EIMDS and CONPASS, when compared to subjects with normal aldosterone concentration or renin-dependent aldosteronism, participants with RIA had a lower estimated glomerular filtration rate, a higher prevalence of CKD, and a higher multivariate-adjusted odds ratio (OR) of CKD (OR 2.62 [95%CI 1.09–6.32] in EIMDS, and 4.31 [1.39–13.35] in CONPASS). The two-sample Mendelian randomization analysis indicated that RIA was significantly associated with a higher risk of CKD (inverse variance weighted OR 1.10 [95 % CI 1.05–1.14]), with no evidence of significant heterogeneity or substantial directional pleiotropy. InterpretationAmong patients with diabetes, renin-independent aldosteronism is causally associated with a higher risk of CKD. Targeted treatment of autonomous aldosterone secretion may benefit renal function in diabetes.

Optimal application of captopril challenge test in the diagnosis of primary aldosteronism

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Pitfalls in the diagnosis and treatment of a hypertensive patient with unilateral primary aldosteronism and contralateral pheochromocytoma: a case report

BackgroundPrimary aldosteronism (PA) is a common cause of secondary hypertension, whereas pheochromocytoma is a rare cause of it. Thus, concomitant PA and pheochromocytoma is a very rare condition.Case presentationA 52-year-old woman was admitted to our hospital with suspected PA based on the presence of hypertension, spontaneous hypokalemia, and a high aldosterone-to-renin ratio. She had no catecholamine excess symptoms other than hypertension. Abdominal computed tomography (CT) showed a right lipid-rich adrenal mass and a left lipid-poor adrenal mass. PA was diagnosed by the captopril challenge test. The 24-h urinary fractionated metanephrines were slightly elevated. Adrenal vein sampling (AVS) confirmed that the right adrenal gland was responsible for aldosterone hypersecretion. Medical therapy with eplerenone was started because the patient refused surgery. Five years later, she requested surgery for PA. The second AVS confirmed right unilateral hyperaldosteronism, as expected. Repeated abdominal CT showed the enlargement of the left adrenal mass. The 24-h urinary fractionated metanephrines had risen to the diagnostic level. 123I- metaiodobenzylguanidine (MIBG) scintigraphy showed a marked tracer uptake in the left adrenal mass with no metastatic lesion. After preoperative management with α-blockade, laparoscopic left partial adrenalectomy was performed. Immunohistochemical examination of the tumor showed chromogranin A positivity leading to the diagnosis of left pheochromocytoma.ConclusionsWe report an extremely rare case of concomitant unilateral PA and contralateral pheochromocytoma. When diagnosing unilateral PA by AVS, especially in cases with a lipid-poor adrenal mass, clinicians should rule out the possibility of the presence of pheochromocytoma before proceeding to undergo unilateral adrenalectomy. Although there is no standard treatment for this rare condition, it is essential to select personalized treatment from the perspective of conserving the adrenal gland.

Impact of a change to a novel chemiluminescent immunoassay for measuring plasma aldosterone on the diagnosis of primary aldosteronism.

In Japan, the standard method for measuring plasma aldosterone concentration (PAC) for primary aldosteronism (PA) diagnosis was changed from radioimmunoassay (RIA) to a novel chemiluminescent enzyme immunoassay (CLEIA). The purpose of this study is to simulate the possible impact of the change on PA diagnosis. This retrospective study assessed 2,289 PA patients. PACs measured by conventional RIA were transformed to estimated PACs (CLEIA) as follows: RIA (pg/mL) = 1.174 × CLEIA (pg/mL) + 42.3. We applied the estimated PAC (CLEIA) to the conventional cut-off of aldosterone-to-renin activity ratio ≥200 for screening and captopril challenge test (CCT) and PAC ≥60 pg/mL for saline infusion test (SIT). Application of the estimated PAC to screening and confirmatory tests decreased the number of PA diagnoses by 36% (743/2,065) on CCT and 52% (578/1,104) on SIT (discrepant cases). Among the discrepant cases, 87% (548/628) of CCT and 87% (452/522) of SIT were bilateral on adrenal venous sampling (AVS). Surgically treatable aldosterone-producing adenomas (APAs) were observed in 6% (36/579) and 5% (23/472) of discrepant cases on CCT and SIT, respectively; most were characterized by hypokalemia and/or adrenal nodule on CT imaging. Application of the PAC measured by the novel CLEIA to conventional cut-offs decreases the number of PA diagnoses. Although most discrepant cases were bilateral on AVS, there are some APA cases that were characterized by hypokalemia and/or adrenal tumor on CT. Further studies which evaluate PACs measured by both RIA and CLEIA for each patient are needed to identify new cut-offs for PAC measured by CLEIA.