Fludrocortisone Suppression Test Research Articles

6636 Primary Hyperaldosteronism Leading to Aldosterone Deficiency

Abstract Disclosure: N.G. Haverstick: None. J.R. Anthony: None. Primary Hyperaldosteronism is a disease process that is often missed, and under checked due to poor screening tools. The disease presents with a common problem, uncontrolled hypertension. It also presents with hypokalemia, fatigue and headaches. It can easily be masked with blood pressure medications, CKD, and pain medications. After treatment there are some rare reports of patients developing hypoaldosteronism. Some risk factors are age >50, duration of hypertension >10 years, pre-existing renal impairment and adrenal adenoma size >2 cm. The patient will present with the opposite: hyperkalemia and hypotension. This is due to the atrophy of the previously healthy gland. Usually this resolves within a year. However in our patient she has continued to require long standing mineralocorticoid replacement therapy. This case highlights the importance of early recognition of hyperaldosteronism. A 63 year-old-female with a medical history of hypertension and diabetes mellitus is being followed for 30+ years of uncontrolled hypertension. Patient has been on multiple agents and blood pressure remained elevated after trying triamterene/hctz, metoprolol, irbesartan, amlodipine. After changing her PCP, there was further investigation into the cause. Leading differentials were Primary Hyperaldosteronism vs Renal Artery Stenosis vs Primary Hypertension. She also had multiple labs with her Potassium below 3 mEq/l. Additional labs were obtained and her Aldosterone level 209 ng/dl and Renin <0.167 ng/mL/hr. The patient was referred to Endocrinology who performed a fludrocortisone suppression test, which did not suppress the levels. A CT scan of the abdomen was performed that showed a 1.3 cm right adrenal mass typical with adrenal adenoma. The patient had an adrenalectomy surgery in February 2022. The patient recovered well, however now developed hypotension off medication, and had consistent hyperkalemia with K > 5.5 mEq/l. The patient had now developed aldosterone deficiency. This was due to the long standing hyperaldosteronism that had caused her left adrenal gland to atrophy after 30 years. The patient was started on Fludrocortisone 0.1 mg daily and a low potassium diet. She has remained off any blood pressure medications since her right adrenalectomy. She has continued to require the mineralocorticoid replacement to date. The diagnostic work-up for primary aldosteronism involves screening, confirmatory testing, and localization studies to distinguish unilateral pathology which may be amenable to adrenalectomy from bilateral adrenal hyperplasia. Through literature review, one theory is that chronic suppression of renin may cause atrophy of the zona glomerulosa cells and hypoaldosteronism. Throughout the case report we emphasize on the importance of early diagnostic screening of secondary hypertension as well as the complications from adrenalectomy. Presentation: 6/2/2024

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.

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.

Exclusion Tests in Unilateral Primary Aldosteronism (ExcluPA) Study.

Determining the diagnostic accuracy of "exclusion" tests for primary aldosteronism (PA) compared to the aldosterone to renin ratio (ARR) is fundamental to avoid invasive subtyping in false-positive patients at screening. To assess the accuracy of exclusion tests for PA using the diagnosis of unilateral PA as reference. PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched for studies published from January 1, 1970, to December 31, 2021, meeting tight quality criteria. Data were extracted following the PRISMA methodology. We performed a two-stage meta-analysis that entailed an exploratory and a validation phase based on a "golden" or "gold" diagnostic standard, respectively. Pooled specificity, negative likelihood ratio, diagnostic odds ratio, and summary area under the ROC curve (sAUROC) were calculated to analyze the accuracy of exclusion tests. A meta-analysis of 31 datasets comprising a total of 4242 patients fulfilling the predefined inclusion criteria found that pooled accuracy estimates (sAUROC) did not differ between the ARR (0.95; 95% CI, 0.92-0.98), the captopril challenge test (CCT) (0.92; 95% CI, 0.88-0.97), and the saline infusion test (SIT) (0.96; 95% CI, 0.94-0.99). Solid information could not be obtained for the fludrocortisone suppression test and the furosemide upright test, which were assessed in only 1 study each. The apparently high diagnostic accuracy of the CCT and the SIT was due to the selection of patients with an elevated ARR and thus a high pretest probability of unilateral PA; however, neither test furnished a diagnostic gain over the ARR. Therefore, the systematic use of these exclusion tests in clinical practice is not justified by available evidence.

Ambulatory fludrocortisone suppression test in the diagnosis of primary aldosteronism: Safety, accuracy and cost-effectiveness.

The aims of this study were to explore if the ambulatory fludrocortisone suppression test (FST) wassafe, accurateand cost-effective. The diagnosis of primary aldosteronism (PA) remains time-consuming and complex. The FSTis used to confirm PA, but it is an in-patient test due to potentially serious complications such as hypokalemia. In Stockholm, FST has been performed since 2005 as an ambulatory procedure. This is a retrospective study including all patients investigated with FST in four hospitals in Stockholm, Sweden, during 2005-2019. In total, 156 cases of ambulatory FST (FSTamb) and 15 cases of in-patient FST (FSTin) were included. FSTamb and FSTin were compared regarding health costs, clinical characteristicsand laboratory results. No difference was found in the outcomes of FSTamb and FSTin. No severe complications were reported in FSTamb patients. No difference was found in the median value for plasma potassium on Day 5 between the two groups. Only three patients (1.9%) in the FSTamb had to repeat the test due to incomplete intake of medications. FSTamb and FSTin were equally accurate. The cost of performing FSTamb was at least 50% lower compared with FSTin ($2400 vs. $5200 per patient). The time needed for FSTamb was 60 min of physician's time and 150 min of nurse's time which were lower than the 5 days in FSTin. Ambulatory FST is safe and accurate and can be performed with significantly less healthcare costs compared to FSTin.

Performance of Confirmatory Tests for Diagnosing Primary Aldosteronism: a Systematic Review and Meta-Analysis.

Background:Confirmatory tests are recommended for diagnosing primary aldosteronism, but the supporting evidence is unclear.Methods:We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials. Studies evaluating any guideline-recommended confirmatory test (ie, saline infusion test, salt loading test, fludrocortisone suppression test, and captopril challenge test), compared with a reference standard were included. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the risk of bias. Meta-analyses were conducted using hierarchical summary receiver operating characteristic models.Results:Fifty-five studies were included, comprising 26 studies (3654 participants) for the recumbent saline infusion test, 4 studies (633 participants) for the seated saline infusion test, 2 studies (99 participants) for the salt loading test, 7 studies (386 participants) for the fludrocortisone suppression test, and 25 studies (2585 participants) for the captopril challenge test. Risk of bias was high, affecting more than half of studies, and across all domains. Studies with case-control sampling overestimated accuracy by 7-fold (relative diagnostic odds ratio, 7.26 [95% CI, 2.46–21.43]) and partial verification or use of inconsistent reference standards overestimated accuracy by 5-fold (5.12 [95% CI, 1.48–17.77]). There were large variations in how confirmatory tests were conducted, interpreted, and verified. Under most scenarios, confirmatory testing resulted in an excess of missed cases. The certainty of evidence underlying each test (Grading of Recommendations, Assessment, Development, and Evaluations) was very low.Conclusions:Recommendations for confirmatory testing in patients with abnormal screening tests and high probability features of primary aldosteronism are based on very low-quality evidence and their routine use should be reconsidered.

Re-evaluation of the diagnostic value and optimal cutoff point of captopril challenge test in diagnosis of primary aldosteronism

Objective: The aim of the present study was to re-evaluate the diagnostic value and optimal cutoff point of captopril challenge test (CCT) in diagnosis of primary aldosteronism (PA). Methods: This is a retrospective study. All patients with a high risk for PA underwent screening test, and then proceeded to CCT and fludrocortisone suppression test (FST) on different days. The FST was used as a reference standard for PA. The plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) were measured with an automated chemiluminescence immunoassay. Random number method was performed in the patients with unilateral primary aldosteronism (UPA), in order to make the proportion of the analyzed UPA in PA was 35%. Receiver operating characteristic (ROC) analyses were performed to compare diagnostic accuracy. Results: A total of 543 patients with 400 PA patients and 143 essential hypertension (EH) patients were enrolled. The diagnostic value of post-CCT PAC was significantly higher than that of the post-CCT plasma aldosterone-renin ratio (ARR), and that of the PAC suppression percentage, respectively. The area under the ROC curve (AUCROC) was 0.86 (0.83, 0.89) for PAC, 0.78 (0.74, 0.82) for ARR, and 0.62 (0.56, 0.67) for the PAC suppression percentage (all P<0.01), respectively. The optimal cutoff point of post-CCT PAC for PA was 110 ng/L, in which the sensitivity and specificity were 73.25% and 79.02%, respectively. The diagnostic efficiency of post-CCT PAC was not improved either in combination with PAC suppression percentage or in combination with post-CCT ARR. Conclusions: CCT is a useful test for the confirmation of PA. PAC level of 110 ng/L at 2 h after 50 mg of captopril is recommended as an optimal cutoff point for the diagnosis of PA.

COMPARISON OF PARTIAL SEATED SALINE INFUSION TEST AND SEATED SALINE INFUSION TEST FOR THE DIAGNOSIS OF PRIMARY ALDOSTERONISM

Objective: Seated saline infusion test (SSIT) has proved to be much more sensitive to recumbent saline infusion test (RSIT) in confirmation of primary aldosteronism (PA), highly specific, much cheaper and less complicated than fludrocortisone suppression testing (FST). However, SSIT requires the subjects to keep sitting position for 4.5 h, which is not comfortable for all patients, especially for the elderly. The purpose of this study was to explore the diagnostic consistency between more free and comfortable partial seated saline infusion test (PSSIT) and SSIT. Design and method: The current study involved 89 hypertensive patients who had positive results in the screening test and underwent both PSSIT and SSST for the confirmation of PA. For SSIT, patients remained sitting posture for 4.5 hours (0.5 h before the basal measurement of PAC at 9am local time and during the whole process of saline infusion). For PSSIT, patients remained sitting posture for 0.5 h before the measurement of basal PAC and 0.5 h before the completion of saline infusion, for the rest of the time in the process of infusion, subjects were permitted to adopted more free and comfortable posture. Two liters of 0.9% NaCl was administered intravenously over 4 h during SSIT or PSSIT. The diagnostic consistency between PSSIT and SSIT was analyzed. Results: The plasma aldosterone concentration (PAC) after PSSIT was significantly lower than that of SSIT (6.06 vs 7.07ng/dL, P &lt; 0.001). Eight patients (9%) who had post-PSSIT PAC less than 10ng/dl had post-SSIT PAC greater than 10ng/dl. The two saline infusion tests had lower correlation coefficient (r = 0.246, P = 0.02) and intra group correlation coefficient (ICC = 0.194, P = 0.015). ROC analysis predicted optimal cut-off aldosterone levels of 5.385 ng/dl for PSSIT with high sensitivity (80%) but low specificity (50%) when use 6 ng/dl for SSIT according to the Endocrine Society Guideline. Conclusions: The optimal cut-off values of PAC for PSSIT were lower than that of SSIT with high sensitivity but low specificity, which need to be noted in clinical application.

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

ObjectiveThe 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. MethodsHypertensive 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. ResultsA 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. ConclusionSSST 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.

The Cl-/HCO3- exchanger pendrin is downregulated during oral co-administration of exogenous mineralocorticoid and KCl in patients with primary aldosteronism.

In primary aldosteronism (PA), the occurrence of K+ loss and hypertension suggest alterations in renal tubular transport, but the molecular basis of these alterations in humans is unclear. In this study, urinary extracellular vesicles (uEVs) isolated from patients undergoing fludrocortisone suppression testing (FST, as a means of confirming or excluding PA) were analyzed using mass spectrometry-based proteomics to determine the combined effects of an aldosterone analogue, NaCl and KCl supplementation on renal tubular protein abundance. Of quantified proteins, the Cl-/HCO3- exchanger pendrin decreased by a median 37% [-15, 57] (P < 0.01) and the potassium channel ROMK increased by a median 31% [-10, 85] (P < 0.01) during FST among 10 PA subjects. The trends remained, but to a lesser degree, in two subjects cured of PA by unilateral adrenalectomy. In PA subjects, plasma K+ increased from median 3.6 to 4.2 mM (P < 0.01) and 24 h urine K+ from 101 to 202 mmol (P < 0.01), while 24 h urine Na+/K+ decreased from 2.3 to 0.8 (P < 0.01). At baseline, pendrin negatively correlated with plasma K+ (P < 0.05) and positively correlated with plasma aldosterone (P < 0.01). There were no clear correlations between Δ pendrin (Δ = D4-D0) and changes in blood or urine variables, and no correlations between ROMK in any of the blood or urine variables either at baseline or during FST. We conclude that oral co-administration of mineralocorticoid and KCl in PA patients is associated with reduced pendrin and enhanced ROMK in uEVs. Pendrin reduction during FST suggests that the suppressive effects of oral KCl may outweigh pendrin upregulation by mineralocorticoids.

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

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. To develop and validate optimized criteria for sparing CFT in the diagnosis of PA. 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. Hypertensive patients who completed PA screening and CFT. Diagnostic value of the optimized criteria. 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). Hypertensive patients with PAC >20 ng/dL, PRC <2.5 μIU/mL, plus hypokalemia can be confidently diagnosed with PA without confirmatory tests.

MON-207 Validating and Optimizing the Guideline Criterion for Skipping Confirmatory Tests of Primary Aldosteronism

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.

MON-221 Seated Saline Suppression Testing Is Comparable to Captopril Challenge Test for the Diagnosis of Primary Aldosteronism: A Prospective Study

:Objective: Saline suppression testing (SST) and captopril challenge test (CCT) are commonly used confirmatory tests for primary aldosteronism (PA). Seated SST (SSST) is reported to be superior to recumbent SST (RSST). Whether SSST is better than CCT remains unclear. Therefore we conducted a prospective study to compare the diagnostic accuracy of SSST and CCT.Methods: Hypertensive patients with high risk of PA were consecutively included. Patients with aldosterone-renin ratio≥1.0 ng•dl-1/μIU•ml-1 were asked to complete SSST, CCT and fludrocortisone suppression test (FST). Using FST as the reference standard (plasma aldosterone concentration [PAC] post-FST ≥6.0 ng•dl-1), area under the receiver-operator characteristic curves (AUC), sensitivity and specificity of SSST and CCT were calculated, and multiple regression analyses were conducted to identify potential factors for false diagnosis.Results: A total of 183 patients diagnosed as PA and 48 as essential hypertension completed the study. Using PAC post-SSST and PAC post-CCT to confirm PA, SSST and CCT had comparable AUCs (AUCSSST 0.83 [0.78,0.88] vs. AUCCCT 0.86 [0.81,0.90], P=0.308). Setting PAC post-SSST and post-CCT at 8.5 ng•dl-1 and 11 ng•dl-1, respectively, the sensitivity and specificity of SSST [0.71 (95%CI 0.64 to 0.77) and 0.82(0.68,0.90)] and CCT [0.73(0.66,0.79) and 0.80(0.66,0.89)] were not significantly different. In the multiple regression analyses, 1SD increment of sodium intake resulted in 40% lower risk of false diagnosis in SSST.Conclusions: SSST and CCT have comparable diagnostic accuracy. Insufficient sodium intake decreases the diagnostic efficiency of SSST but not CCT. Since the CCT is simpler and cheaper, it is preferable to the SSST.

Update and Research Progress in the Diagnosis of Primary Aldosteronism

Primary aldosteronism (PA) is the most common cause of secondary hypertension. The diagnosis procedure of PA includes screening, confirmatory diagnosis and subtype classification. International and national guidelines recommended plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio (ARR) to detect possible cases of PA, and one or more tests (fludrocortisone suppression test, saline infusion test, oral sodium loading test, or captopril challenge test) to confirm ARR positive patients. Adrenal venous sampling (AVS) is also recommended as the best method to distinguish unilateral and bilateral adrenal disease when surgical treatment is feasible and desired by the patient. However, many studies find that each of the above diagnostic method has shortcomings. Recently, more and more studies are attempting to explore new methods with higher diagnostic efficiency and more conveniences, including new screening tests, new confirmatory diagnostic tests, new imaging and pathological histology methods. In our studies, the regression model, which included upright PAC, upright PRA, and lowest potassium, is superior to ARR for PA screening; the blood potassium and the ratio of blood potassium to blood sodium after the saline infusion test are not suitable for PA subtyping. This article will review the advances and progress in PA diagnosis.

Measurement of Equilibrium Angiotensin II in the Diagnosis of Primary Aldosteronism.

Many medications (including most antihypertensives) and physiological factors affect the aldosterone/renin ratio (ARR) when screening for primary aldosteronism (PA). We sought to validate a novel equilibrium angiotensin II (eqAngII) assay and compare correlations between the aldosterone/angiotensin II ratio (AA2R) and the current ARR under conditions affecting the renin-angiotensin system. Among 78 patients recruited, PA was excluded in 22 and confirmed in 56 by fludrocortisone suppression testing (FST). Peripheral levels of eqAngII, plasma renin activity (PRA) and direct renin concentration (DRC) were measured. EqAngII showed good consistency with DRC and PRA independent of PA diagnosis, posture, and fludrocortisone administration. EqAngII showed close (P < 0.01) correlations with DRC (r = 0.691) and PRA (r = 0.754) during FST. DRC and PRA were below their assays' functional sensitivity in 43.9% and 15.1%, respectively, of the total 312 samples compared with only 7.4% for eqAngII (P < 0.01). Bland-Altman analysis revealed an overestimation of PRA and DRC compared with eqAngII in a subset of samples with low renin levels. The AA2R showed not only consistent changes with the ARR but also close (P < 0.01) correlations with the ARR, whether renin was measured by DRC (r = 0.878) or PRA (r = 0.880). Dynamic changes of eqAngII and the AA2R show good consistency and close correlations with renin and the ARR. The eqAngII assay shows better sensitivity than DRC and PRA assays, especially at low concentrations. Whether the AA2R can reduce the impact of some factors that influence the diagnostic power of the ARR warrants further study.

Diagnosis of Primary Aldosteronism by Seated Saline Suppression Test—Variability Between Immunoassay and HPLC-MS/MS

In primary aldosteronism (PA), excessive, autonomous secretion of aldosterone is not suppressed by salt loading or fludrocortisone. For seated saline suppression testing (SSST), the recommended diagnostic cutoff 4-hour plasma aldosterone concentration (PAC) measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS is 162 pmol/L. Most diagnostic laboratories, however, use immunoassays to measure PAC. The cutoff for SSST using immunoassay is not known. We hypothesized that the cutoff is different between the assays. We analyzed 80 of the 87 SSST tests that were performed during our recent study defining the HPLC-MS/MS cutoff. PA was confirmed in 65 by positive fludrocortisone suppression testing (FST) and/or lateralization on adrenal venous sampling and excluded in 15 by negative FST. PAC was measured by a chemiluminescence immunoassay (PACIA) in the SSST samples using the DiaSorin Liaison XL analyzer, and receiver operating characteristics (ROC) analysis was performed to identify the PACIA cutoff. ROC revealed good performance (area under the curve = 0.893; P < .001) of 4-hour postsaline PACIA for diagnosis of PA and an optimal diagnostic cutoff of 171 pmol/L, with sensitivity and specificity of 95.4% and 80.0%, respectively. A higher cutoff of 217 pmol/L improved specificity (86.7%) with lower sensitivity (86.2%). PACIA measurements strongly correlated with PAC measured by HPLC-MS (r = 0.94, P < .001). A higher diagnostic cutoff for SSST should be employed when PAC is measured by immunoassay rather than HPLC-MS/MS. The results suggest that (i) PA can be excluded if 4-hour PACIA is less than 171 pmol/L, and (ii) PA is highly likely if the PACIA is greater than 217 pmol/L by chemiluminescence immunoassay. A gray zone exists between the cutoffs of 171 and 217 pmol/L, likely reflecting a lower specificity of immunoassay.

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

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. We searched PubMed, Embase and the Cochrane Library for relevant studies published between January 1980 and January 2018. Eligible studies reported on the accuracy of one or more of the four confirmatory tests in patients suspected of PA. 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). 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. 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.

A1728 Measurement of aldosterone

Objectives: To compare aldosterone assay by RIA with LC-MS/MS and to evaluate the performance of proposed LC-MS/MS-specific cut-offs for primary aldosteronism (PA) screening and confirmatory testing. Methods: Peripheral aldosterone concentration (PAC) was tested by both methods among 52 patients during fludrocortisone suppression testing (FST). Direct renin concentration (DRC) was measured by CLIA. The proposed PACLC-MS/MS cut-offs for the aldosterone/renin ratio (ARR) and FST were derived from the regression equation obtained from our previous in-house comparison between two assays. Results: The obtained equation was PACLC-MS/MS = 0.79 × PACRIA-28.1 (R2 = 0.87, n = 200). In this study, median PACLC-MS/MS was 29.3% lower (p < 0.05) than PACRIA. A positive correlation (Spearman coefficient 0.92, p < 0.01) and linear relationship (p < 0.01, R2 = 0.81, n = 208) were observed between the two assays, with a positive bias of 34.5% (95% limits of agreement: −34.2% to 103.3%) for RIA. Forty-one patients showed conclusive FSTs (37 consistent and 4 inconsistent by two assays) A good agreement (Kappa coefficient 0.74, p < 0.01) and no differences were observed between the current FST day 4 upright PACRIA cut-off of 165 pmol/L and the proposed PACLC-MS/MS cut-off of 130 pmol/L. Among the 37 patients with consistent FSTs, no differences were observed in sensitivity (89.7% vs 93.1%) and specificity (87.5% for both) between the current ARRRIA cut-off of 70 and the proposed ARRLC-MS/MS cut-off of 55. Conclusion: Adjustment of the current cut-off for PA diagnostic testing is necessary if PACLC-MS/MS is measured. Our preliminary results revealed that the proposed cut-offs of 55 for the ARR (PACLC-MS/MS/DRC) and 130 pmol/L for FST day 4 upright PACLC-MS/MS perform as well as the current RIA threshold values.

A7813 Variations in abundance of urinary exosomal renal sodium transporters in response to mineralocorticoid administration and oral salt loading and in relation to baseline plasma aldosterone and potassium

Objectives: To quantify changes in abundance of sodium transporters [Na-Cl cotransporter (NCC), its phosphorylated form (pNCC), Na-K-Cl cotransporter (NKCC2) and epithelial sodium channel g-subunit (g-ENaC)] and prostasin in urinary exosomes in response to mineralocorticoid administration and oral salt loading, and explore associations with plasma aldosterone (aldo) and K+, in patients undergoing fludrocortisone suppression testing (FST).Methods: Baseline (D0) and day 4 (D4) morning urine samples were collected from 13 patients, including 10 with hypertension and raised aldo/renin ratio undergoing FST to confirm or exclude primary aldosteronism (PA; confirmed in 9) and 3 cured of PA by unilateral adrenalectomy. Urinary exosomes were isolated by ultracentrifugation and analysed by immunoblotting.Results: Increases in abundance of NCC (1.48 fold, p = 0.03) and pNCC (1.52 fold, p = 0.04) and trends towards increases in prostasin (p = 0.07), NKCC2 (p = 0.09) and cleaved g-ENaC (p = 0.11) were observed among the 13 subjects after 4 days FST. Abundance of cleaved g-ENaC rose significantly (p = 0.02) in the 10 non-operated subjects. Among the 13 subjects, D0 aldo and K+ did not correlate significantly with abundance of the target proteins, although D0 pNCC showed a trend towards positive correlation with aldo (p = 0.09). In the 10 non-operated subjects, D0 pNCC showed a negative correlation with plasma K+ that almost reached significance (p = 0.06).Conclusion: FST is associated with significant increases in NCC and pNCC and trends towards increases in ENaC, prostasin and NKCC2. The negative correlation between baseline plasma K+ and abundance of pNCC observed in adrenal-intact subjects suggests a possible role for K+ in the regulation of tubular salt handling and blood pressure.

Diagnosis of primary aldosteronism in the hypertension specialist centers in Italy: a national survey.

Primary aldosteronism (PA) is the most common endocrine cause of resistant hypertension. Individuals with PA are at increased cardiovascular risk, and an appropriate management and treatment would ideally reduce such risk. Screening and diagnosis of PA requires a specific diagnostic test whichis considered time- and cost-consuming and, as a result, is underperformed in clinical practice. An online survey reviewing available diagnostic procedures, laboratory testing, and clinical protocols for screening and confirmation of PA diagnosis was conducted among clinical lead of Reference andExcellence centers of the Italian Hypertension Society. A total of 102 questionnaires were sent and 62 centers participated in the survey. Assessment of the plasma renin (plasma renin activity/direct renin concentration) and plasma aldosterone concentration (PAC) was available in all centers. Captopril challenge test (CCT) and saline infusion test (SIT) were available in 60% and 61% of the centers, respectively. Fludrocortisone suppression test was available in 32% of the units. Adrenal vein sampling was accessible in 32% of the centers. We found discrepancies in cutoff levels of aldosterone-to-renin ratio (ARR) and PAC after SIT. Other discrepancies involved the duration of the wash-out period before ARR testing and dosage of captopril administered during CCT. In conclusion, although all centers are sufficiently equipped to perform PA screening, often patients should be referred to other centers to confirm the diagnosis of PA. A greater uniformity across centers to define precise cutoffs for screening and confirmatory testing for the diagnosis of PA would be of utility.