Screening For Primary Aldosteronism Research Articles

OP.LB01.11] MEASUREMENT OF ANGIOTENSIN II AT EQUILIBRIUM IN THE DIAGNOSTIC WORKUP OF PRIMARY ALDOSTERONISM. IMPACT OF PATIENT POSITIONING AND ACE INHIBITOR TREATMENT

Objective: Primary aldosteronism (PA) is a widely under-diagnosed, potentially curable and specifically treatable cause of hypertension. PA screening involves measuring the aldosterone-to-renin-ratio (ARR), but false negative results can occur in the setting of medications, which block the renin-angiotensin system (RAS). Withdrawing RAS blockers from patients with resistant hypertension is not without cardiovascular risk. A novel diagnostic approach, the aldosterone-to-angiotensin-II-ratio (AA2-Ratio), has the potential for less drug interference and improved reliability in PA screening and confirmation of diagnosis. Design and method: Serum samples from 80 patients undergoing PA confirmation testing were analyzed. Sampling was performed in a recumbent (7 a.m.) and in an upright (10 a.m.) position before and after 4 days of oral administration of fludrocortisone and salt loading. The concentrations of renin, aldosterone and equilibrium Angiotensin-II were determined and ARR and AA2-Ratios were calculated. The interference of ACE-inhibition with the AA2-Ratio was investigated in healthy volunteers receiving 10 mg enalapril daily for 8 days. Results: Renin concentration was undetectable in more than 40% of samples, while equilibrium Angiotensin-II was measurable in 98% of all 320 samples analyzed. Angiotensin-II levels were significantly higher in upright collected samples compared to samples collected in a recumbent position. Comparison of the ARR with the AA2-Ratio revealed a significantly larger diagnostic window for the AA2-Ratio. While the ARR was significantly suppressed by ACE-inhibitor treatment, the AA2-Ratio remained unaffected by ACE-inhibition. Conclusions: The AA2-Ratio may be superior to the ARR in PA screening among hypertensive patients. Equilibrium Angiotensin-II levels show expected responses to posture and appear to outperform renin concentration as a marker for RAS activation in terms of sensitivity, giving a measurable readout even in clinical states characterized by markedly suppressed RAS activity. The stability of the AA2-Ratio in the presence of ACE-inhibition points to a potential use of the AA2-Ratio PA screening in hypertensive patients without ACE-inhibitor discontinuation.

JS ISH-ECCR-4 THE PLASMA ALDOSTERONE / ANGIOTENSIN II RATIO FOR THE SCREENING OF SECONDARY HYPERTENSION

Primary aldosteronism (PA) is severe form of hypertension characterized by a strongly increased aldosterone secretion mediated by adenomas or other forms of adrenal hyper-activity. Once detected, PA can be usually cured by either surgical intervention or by appropriate pharmacologic treatments. The incidence of PA among hypertensive patients varies strongly between different studies, which is in part caused by the complex state-of-the-art testing procedure that is unfortunately far away from being a versatile PA screening tool. Despite strong limitations regarding selectivity and the interference with multiple anti-hypertensive drugs, the antibody-based determination of the aldosterone-renin-ratio (ARR) is widely used in the diagnostic process of PA. However, there is still a strong demand for accurate, reliable and patient friendly PA case detection. The implementation of novel LC-MS/MS based assays for quantification of aldosterone might help to improve the power of the ARR as a diagnostic tool for PA. However, there is a big need for a versatile PA screening test that doesn’t interfere with anti-hypertensive treatments and therefore allows the clear identification of PA patients without complex and risky treatment adaptions being necessary in the course of the diagnostic process. The Aldosterone-to-Angiotensin-II-Ratio (AA2-Ratio) is a novel LC-MS/MS based high-throughput test for PA that combines the molar plasma levels of aldosterone and physiologically active angiotensin II into a single dimension-free diagnostic value. The availability of innovative diagnostic approaches for biochemical analysis of the Renin-Angiotensin-Aldosterone-System paved the way for Angiotensin peptides to be used in clinical routine testing by overcoming pre-analytic issues regarding analyte stability. In addition to overall RAS activity and aldosterone levels, the AA2-Ratio integrates the activity of all plasma enzymes involved in angiotensin II metabolism and accurately estimates of the portion of physiologically active angiotensin II in a patient sample. The performance of the AA2-Ratio is superior to the ARR in terms of the diagnostic window, which can be explained by the much closer functional link between aldosterone and angiotensin II comparing to the molecular distant relationship between aldosterone and renin. It has been shown that the correlation between renin concentration or activity and angiotensin II is poor especially in patients treated with anti-hypertensive drugs. In sharp contrast, the AA2-Ratio does not interfere with first line anti-hypertensive drugs including ACE inhibitors. The AA2-Ratio has the potential to be superior to the ARR in terms of its ability to better reflecting the activity of the true direct circulating regulator of aldosterone (i.e. angiotensin II rather than renin), and being unaffected by antihypertensive medications including ACE inhibitors. Data obtained in proof-of-concept studies proved the AA2-Ratio to be a powerful and cost-effective diagnostic tool for the diagnosis of PA among hypertensive patients. The stability of the AA2-Ratio in the presence of ACE-inhibition points to a potential use of the AA2-Ratio PA screening in hypertensive patients without ACE-inhibitor discontinuation.

OS 35-04 THE AA2-RATIO

Objective: Primary aldosteronism (PA) is form of hypertension characterized by production of aldosterone by the adrenal that is excessive and relatively autonomous of the renin-angiotensin system. Once detected, unilateral PA can be usually cured by surgical removal of the affected adrenal, while bilateral PA can be specifically treated by medications, which antagonize aldosterone action. Clinical guidelines of Endocrine Societies in Europe and the US recommend screening for PA among most hypertensive patients. The incidence of PA among hypertensive patients varies from 5–30% between different studies. This may be due, at least in part, to variability in screening approaches and assay performance. Design and Method: There is an urgent need for a versatile PA screening approach that doesn’t require withdrawal of potentially interfering medications and therefore allows the clear identification of PA patients without potentially complex and risky treatment amendments being necessary during the course of the diagnostic process. The Aldosterone-to-Angiotensin-II-Ratio (AA2-Ratio) is a novel LC-MS/MS based high-throughput test for PA that combines the plasma levels of aldosterone and physiologically active angiotensin II into a diagnostic ratio. Results: The AA2-Ratio has the potential to be superior to the ARR in terms of its ability to discriminate between PA and other forms of hypertension, accuracy in measuring aldosterone, better reflecting the activity of the true direct circulating regulator of aldosterone (i.e. angiotensin II rather than renin), and being less affected by antihypertensive medications including ACE inhibitors. First data obtained in a proof-of-concept study investigating PA positive and negative patients proved the AA2-Ratio to be a powerful and cost-effective diagnostic tool for the diagnosis of PA among hypertensives. Conclusions: The availability of novel diagnostic approaches for the Renin-Angiotensin-Aldosterone-System (Equilibrium Analysis) might pave the way for Angiotensin peptides to be used in clinical routine testing by solving pre-analytic problems of analyte stability.

Diagnosing and Managing Primary Aldosteronism in Hypertensive Patients: a Case-Based Approach

Primary aldosteronism with a prevalence of 8% of hypertension and 20% of pharmacologically resistant hypertension is the most common secondary cause of hypertension. Yet, the diagnosis is missed in the vast majority of patients. Current clinical practice guidelines recommend screening for primary aldosteronism in patients with sustained elevation of blood pressure (BP) ≥150/100mmHg if possible prior to initiation of antihypertensive therapy, and in patients with resistant hypertension, spontaneous or diuretic-induced hypokalemia, adrenal incidentaloma, obstructive sleep apnea, a family history of early onset of hypertension or cerebrovascular accident <age 40, and first-degree relatives of patients with primary aldosteronism. Clinical and laboratory methods of screening, confirmatory testing, subtype classification, and medical and surgical management are systematically reviewed and illustrated with a clinical case.

Hyperaldosteronism and cardiovascular risk in patients with autosomal dominant polycystic kidney disease.

Hypertension is commonly associated with autosomal dominant polycystic kidney disease (ADPKD), often discovered before the onset of renal failure, albeit the pathogenetic mechanisms are not well elucidated. Hyperaldosteronism in ADPKD may contribute to the development of insulin resistance and endothelial dysfunction, and progression of cardiorenal disease. The aim of study was to evaluate the prevalence of primary aldosteronism (PA) in ADPKD patients and identify some surrogate biomarkers of cardiovascular risk.We have enrolled 27 hypertensive ADPKD patients with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min, evaluating the renin–angiotensin–aldosterone system (RAAS), inflammatory indexes, nutritional status, homocysteine (Hcy), homeostasis model assessment-insulin resistance (HOMA-IR), mineral metabolism, microalbuminuria, and surrogate markers of atherosclerosis [carotid intima media thickness (cIMT), ankle/brachial index (ABI), flow mediated dilation (FMD), renal resistive index (RRI) and left ventricular mass index (LVMI)]. Furthermore, we have carried out the morpho-functional magnetic resonance imaging (MRI) with high-field 3 T Magnetom Avanto.We have divided patients into group A, with normal plasma aldosterone concentration (PAC) and group B with PA, present in 9 (33%) of overall ADPKD patients. Respect to group A, group B showed a significant higher mean value of LVMI, HOMA-IR and Hcy (P = 0.001, P = 0.004, P = 0.018; respectively), and a lower value of FMD and 25-hydroxyvitamin D (25-OH-VitD) (P = 0.037, P = 0.019; respectively) with a higher prevalence of non-dipper pattern at Ambulatory Blood Pressure Monitoring (ABPM) (65% vs 40%, P < 0.05) at an early stage of the disease.In this study, we showed a high prevalence of PA in ADPKD patients, associated to higher LVMI, HOMA-IR, Hcy, lower FMD, and 25-OH-VitD, considered as surrogate markers of atherosclerosis, compared to ADPKD patients with normal PAC values. Our results indicate a higher overall cardiovascular risk in ADPKD patients with inappropriate aldosterone secretion, and a screening for PA in all patients with ADPKD is recommended.

Aldosterone/direct renin concentration ratio as a screening test for primary aldosteronism: A meta-analysis.

Objective:The accuracy of aldosterone/direct renin concentration ratio (ADRR) as a screening test in patients with primary aldosteronism (PA) varies widely across the studies. Therefore, we conducted a meta-analysis to assess the accuracy of ADRR.Methods:A literature search was performed in PubMed, Embase, and the Cochrane library published between April 1971–February 2016. Studies focusing on the accuracy of ADRR for PA screening were included. Two authors independently extracted information regarding patient characteristics, antihypertensives status, true positives, true negatives, false positives, and false negatives. The random-effects model was used for statistical analysis. Heterogeneity was explored by subgroup analysis and meta-regression.Results:Nine studies involving 974 patients were included. The overall sensitivity, specificity, area under the curve, and diagnostic odds ratio of ADRR were 0.89 (95% confidence interval (CI) 0.84–0.93), 0.96 (95% CI 0.95–0.98), 0.985 and 324 respectively, with substantial heterogeneity. Meta-regression showed that antihypertensive status affects the ADRR and may account for the heterogeneity (p=0.03). Subgroup analysis of patients who discontinued the antihypertensives revealed a sensitivity of 0.99 (95% CI, 0.95–1.00) and a specificity of 0.98 (95% CI, 0.96–0.99).Conclusions:This study demonstrates the efficacy of ADRR as a screening test for PA. However, as antihypertensive drugs can interfere with the interpretation of ADRR, it is recommended to interrupt therapy or at least replace with analogues that do not significantly affect the ADRR value.

SFE/SFHTA/AFCE consensus on primary aldosteronism, part 1: Epidemiology of PA, who should be screened for sporadic PA?

Depending on the study, the prevalence of primary aldosteronism (PA) in patients with hypertension varies from 6 to 18%. Prevalence is higher in each of the following conditions, any one of which requires screening for PA: severe hypertension (systolic blood pressure [BP]≥180mmHg and/or diastolic BP≥110mmHg); resistant hypertension (systolic BP≥140mmHg and/or diastolic BP≥90mmHg despite adherence to a tritherapy including a thiazide diuretic); hypertension associated with hypokalemia (either spontaneous or associated with a diuretic); Hypertension or hypokalemia associated with adrenal incidentaloma. It should be borne in mind that PA can induce hypertension without hypokalemia or, less frequently, hypokalemia without hypertension. Finally, as cardiovascular and renal morbidity in PA is greater than in essential hypertension of equivalent level, screening for PA is indicated when cardiovascular or renal morbidity is more severe than predicted from BP level.

Hyperaldosteronism: Screening and Diagnostic Tests.

Primary aldosteronism (PA) is the most common secondary cause of hypertension, accounting for 10% of hypertensives and 20% of those with drug-resistant hypertension. Aldosterone excess is associated with the development of adverse cardiovascular, renal and metabolic effects that are partly independent of its effect on blood pressure. Guidelines recommended wider screening for PA in an effort to maximize detection of patients who may benefit from optimal, specific management. All patient groups with increased prevalence of PA, including hypertensive patients with type 2 diabetes mellitus and those with obstructive sleep apnea, should be carefully screened for PA. Screening with aldosterone-to-renin ratio (ARR) is the most practical and informative initial test. Subsequent confirmatory tests are: (1) oral salt loading; (2) saline infusion; (3) captopril challenge and (4) fludrocortisone suppression test. Confirmation of PA can avoid that patients with a false positive ARR would inappropriately undergo costly and harmful lateralization procedures. If confirmatory testing is positive, further investigations are directed toward determining the subtype of PA, as the treatment differs for each subtype.

Evaluation of the ratio of plasma aldosterone to rennin concentration measured by an automated chemiluminescent immunoassay in screening for primary aldosteronism

To investigate the optimal cutoff of plasma aldosterone to rennin concentration ratio (ARR) determined by an automated chemiluminescent immunoassay for primary aldosteronism (PA) screening. A total of 154 hypertensive patients and 83 healthy volunteers were recruited in the study. Blood for aldosterone and rennin were collected from patients in the supine position and from patients and healthy volunteers after 2-hour upright posture. Plasma aldosterone concentration(PAC) and plasma rennin concentration(PRC) were determined with the automated chemiluminescent immunoassay. The diagnoses of PA were made based on clinical manifestations, confirmatory tests and pathologic results. A ROC curve analysis was performed to determine the optimal ARR cutoffs for PA. Fifty-three patients were diagnosed with PA, 85 were with essential hypertension and 16 were with other types of endocrine hypertension. In hypertensive patients, the areas under the ROC curves (AUCROC) of ARR were 0.962 (95%CI 0.933-0.990, P<0.01) in the supine position and 0.980 (95%CI 0.962-0.998, P<0.01) after 2-hour upright posture, respectively. The AUCROC of ARR was higher than that of either PAC or PRC in the same position. The highest Youden's index of ARR in the upright posture was 0.85 with the cutoff value of 119.1 pmol/mU [4.3 (ng/dl)/(mU/L)] (sensitivity 94%, specificity 91%). ARR in the upright position by the automated chemiluminescent immunoassay provides a high efficiency screening test for PA. The optimal cutoff of ARR is 119.1 pmol/mU.

Sodium Infusion Test for Diagnosis of Primary Aldosteronism in Chinese Population.

The plasma aldosterone concentration (PAC) is less than 5 ng/dL after saline infusion test (SIT) in essential hypertension (EH) and healthy people. It is unclear if the same standard is applicable for Chinese subjects. We assessed the serum aldosterone response after SIT in subjects with primary aldosteronism (PA), EH, and healthy volunteers (normal control, NC), and to investigate the optimal aldosterone level of post-SIT for the diagnosis of PA. The study included 120 hypertensive patients who conform to the PA screening criteria and 21 healthy volunteers. All subjects underwent SIT. PAC was measured in all subjects before and after SIT. The total sodium intake was estimated from 2 timed 24-hour urinary excretion. The area under the receiver-operator characteristic curves was higher than under the diagonal (0.967, 95% confidence interval [CI]: 0.94-0.993). The best cutoff value for PAC after SIT for diagnosis of PA was 11.45 ng/dL, with sensitivity and specificity of 88.2% and 95.4%, respectively. The PAC of post-SIT was more than 10 ng/dL in most PA patients, whereas it was greater than 5 ng/dL in both EH and NC except for 1 at 4.93 ng/dL. Serum aldosterone level was unrelated to dietary salt intake. The optimal post-SIT aldosterone cutoff value for identifying PA was 11.45 ng/dL in Chinese patients. However, the PAC higher than 5 ng/dL after SIT was found in a majority of EH and healthy subjects. The cutoff value of aldosterone post-SIT is higher than the current clinical recommendations and practice guidelines of The Endocrine Society. We found no relationship between high salt intake and lower responses of renin aldosterone system to high loading with saline infusion.

β-Blocker withdrawal is preferable for accurate interpretation of the aldosterone-renin ratio in chronically treated hypertension.

To evaluate the effects of β-adrenoreceptor antagonists (β-blockers) on the aldosterone-renin ratio (ARR) in the context of antihypertensive polypharmacy in chronic hypertension. To determine the optimal duration of β-blocker withdrawal required to normalize the ARR. A prospective, longitudinal study design was employed investigating two groups whom either remained on or withdrew from β-blocker therapy. Hypertensive individuals taking β-blockers and a combination of thiazide diuretics, α1-blockers, calcium channel antagonists and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker were recruited and followed over 10-12 weeks. β-Blockers were withdrawn at the first visit. Blood pressure (BP) was measured at each visit and blood drawn serially for measurement of plasma renin activity (PRA), direct renin concentration (DRC) and aldosterone. BP was optimized by maximizing non-renin-suppressing antihypertensives. Main outcomes were ARR, DRC, PRA and aldosterone. Plasma renin activity was calculated from angiotensin I measured using radioimmunoassay (RIA), DRC was measured using chemiluminescent immunoassay assay, and aldosterone was measured using both RIA and Chemilluminescence Assay (CIL). False-positive ARR for primary aldosteronism (PA) occurred in 31% of patients taking β-blockers. ARR returned to normal following β-blocker withdrawal resulting from an increase in the DRC and PRA without affecting aldosterone. The optimum time for β-blocker withdrawal was 2 weeks when using DRC and 3 weeks for PRA. β-Blocker withdrawal did not adversely affect blood pressure. Raised ARR consequent to β-blocker therapy causes false-positive screening for PA. Where β-blockers can be safely withdrawn, this effect is reversed within 2-3 weeks depending on whether DRC or PRA is used to calculate ARR.

Abstract MP12: The AA2-Ratio: A Novel Screening Test for Primary Aldosteronism in Hypertensive Patients

Primary aldosteronism (PA) is severe form of hypertension characterized by a strongly increased aldosterone secretion mediated by adenomas or other forms of adrenal hyper-activity. Once detected, PA can be usually cured by either surgical intervention or by appropriate pharmacologic treatments. This is also reflected in clinical guidelines of Endocrine Societies in Europe and the US, suggesting extensive PA screening activities among resistant hypertensive patients. The incidence of PA among hypertensive patients varies strongly between different studies, which is in part caused by the complex state-of-the-art testing procedure that unfortunately is far away from being a versatile PA screening tool. Despite strong limitations regarding selectivity, sensitivity and the interference with multiple anti-hypertensive drugs, the aldosterone-renin-ratio (ARR) is widely used for PA case detection. However, there is still a strong demand for accurate and reliable and patient friendly PA case detection. The use of novel and more accurate technologies for quantification of aldosterone and renin activity might help to improve the power of the ARR as a diagnostic tool for PA. However, there is a big need for a versatile PA screening assay that doesn’t interfere with anti-hypertensive treatments and therefore allows the clear identification of PA patients without complex corrections and adaptions being necessary and without increasing the patient’s cardiovascular risk in the course of the diagnostic process. The Aldosterone-to-Angiotensin-II-Ratio (AA2-Ratio) is a novel mass-spectrometry based high-throughput test for PA that combines the plasma levels of aldosterone and physiologically active angiotensin II into a diagnostic ratio. The test performance is superior to the ARR in terms of the diagnostic window and method accuracy. The AA2-Ratio does not interfere with standard anti-hypertensive drugs including ACE inhibitors. First data obtained in a proof-of-concept study investigating PA positive and negative patients proved the AA2-Ratio to be a powerful and cost-effective diagnostic tool for the diagnosis of PA in clinical practice.

Abstract 135: Activated Intrarenal Renin Angiotensin System Contributes to the Development of Chronic Kidney Disease in Primary Aldosteronism

Background: Patients with primary aldosteronism (PA) have higher prevalence of albuminuria than those with essential hypertension (EH). We have shown that about 15% in PA patients had chronic kidney disease (CKD). Hence, the active screening of PA is important to prevent CKD. Urinary angiotensinogen (UAGT) has been reported as the earliest predictor of nephropathy in patients with type 1 diabetes (DM). UAGT indicates the intrarenal renin angiotensin systems (RAS) activation which plays an important role in the development of CKD. This study aimed to confirm the existence of activated intrarenal RAS by measuring UAGT in patients with PA. Methods: Consecutive 58 patients of aldosteronoma (APA) participated. No patients had CKD defined as eGFR &lt;60 ml/min/1.73m 2 or urinary albumin (UA) ≥30 mg/g cre and DM defined as HbA1c ≥6.5% or taking treatments. As control subjects, 59 EH patients were included. All APA patients were treated by sufficient dose of mineralocorticoid receptor (MR) antagonists (MRA) until the day of adrenalectomy. Urine samples were collected on 10g salt diet between baseline and after MRA treatment. UAGT (ng/g cre) was measured and the value was transformed by logarithm. Results: Age, sex distribution, blood pressure, duration of hypertension, eGFR, and UA were similar between two groups at baseline. However, UAGT was significantly higher in APA than in EH (Fig). In multivariate analysis, only plasma aldosterone was significantly related with UAGT in APA (t=3.572, p=0.0007). UAGT was significantly decreased after MRA treatment (Fig). Conclusion: Intrarenal RAS is activated by aldosterone/MR in patients of PA, which might contribute to the development of CKD.

Primary Aldosteronism: Seismic Shifts

Jerome Conn, the father of primary aldosteronism (PA), proposed that the syndrome may account for approximately 20% of patients with blood pressure (BP) elevation. For decades thereafter, conventional wisdom considered PA a rare (1%) and relatively benign form of hypertension,whichwenowknowisnotthecase.Thefirst seismic shift came with the introduction of screening for PA by the aldosterone-to-renin ratio (ARR); on this basis, followed by confirmatory/exclusion testing, it is now rec

Screening for primary aldosteronism in an argentinian population: a multicenter prospective study.

Primary aldosteronism (PA) is characterized by the autonomous overproduction of aldosterone. Its prevalence has increased since the use of the aldosterone (ALD)/plasma renin activity (PRA) ratio (ARR). The objective of this study is to determine ARR and ARC (ALD/plasma renin concentration ratio) cut-off values (COV) and their diagnostic concordance (DC%) in the screening for PA in an Argentinian population.Design multicenter prospective study. We studied 353 subjects (104 controls and 249 hypertensive patients). Serum aldosterone, PRA and ARR were determined. In 220 randomly selected subjects, 160 hypertensive patients and 60 controls, plasma renin concentration (PRC) was simultaneously measured and ARC was determined. According to the 95th percentile of controls, we determined a COV of 36 for ARR and 2.39 for ARC, with ALD ≥ 15 ng/dL. In 31/249 hypertensive patients, ARR was ≥ 36. PA diagnosis was established in 8/31 patients (23/31 patients did not complete confirmatory tests). DC% between ARR and ARC was calculated. A significant correlation between ARR and ARC (r = 0.742; p < 0.0001) was found only with PRA > 0.3 ng/mL/h and PRC > 5 pg/mL. DC% for ARR and ARC above or below 36 and 2.39 was 79.1%, respectively. This first Argentinian multicenter study determined a COV of 36 for ARR and 2.39 for ARC. Applying an ARR ≥ 36 in the hypertensive group, we confirmed PA in a higher percentage of patients than the previously reported one in our population. As for ARC, further studies are needed for its clinical application, since DC% is acceptable only for medium range renin values.

Genetic and potential autoimmune triggers of primary aldosteronism.

Hypertension is a major life-threatening disease of high morbidity and mortality, which affects between 10% to 40% of the general population in an age-dependent manner. The pathogenesis of essential hypertension is multifactorial, with various underlying contributory mechanisms. Primary aldosteronism (PA) is the leading cause of secondary hypertension that affects 4.3% of patients in the general hypertensive population and 9.5% of patients referred to hypertension units.1 The 2 predominant causes of the constitutive aldosterone secretion that define PA is either aldosterone-producing adenomas (APA) or bilateral adrenal hyperplasia (BAH, also called idiopathic hyperaldosteronism). Exome sequencing has unraveled the pathogenetic basis of around half of APA, but the underlying cause of the aldosterone excess in BAH remains an enigma. The diagnosis of PA is made by a multistep process, recommended by the Endocrine Society guidelines,2 that ends with the invasive protocol of adrenal venous sampling. Once diagnosed, it is imperative to distinguish the surgically correctable forms (APA) from those that should be treated pharmacologically with mineralocorticoid receptor antagonists (BAH). With the application of wider screening for PA, >70% of cases of aldosterone excess have been defined as caused by BAH, with APA making up most of the remainder. APA and BAH are sporadic forms of PA, but 3 rarer familial forms of PA also exist called familial hyperaldosteronism (FH) types I, II, and III, described in more detail below. Three familial forms of PA with distinct clinical characteristics have been described.3,4 FH type I or glucocorticoid remediable aldosteronism is caused by a hybrid gene resulting from the unequal crossing-over between the adjacent genes CYP11B1 and CYP11B2 .5,6 Only few families (≈50) have been identified worldwide. FH type II seems to be inherited as an autosomal dominant trait. A locus has been mapped on chromosome 7p22 …

PP.09.22

Objective: Screening test is the first and crucial step of case detection for primary aldosteronism (PA), aldosterone/renin ratio (ARR) is currently regarded as the most reliable and available screening test for PA, however, the falling accuracy of ARR with increasing age has posed crucial challenge for PA screening among older-aged population.Design and method: To clarify potential effects of age on screening for PA, 216 subjects with PA and 657 subjects with non-PA were recruited and subdivided into four age groups (less than or equal to 39, 40–49, 50–59 and greater than or equal to 60 years). we respectively compared the level and tendency of PRA, PAC and ARR between different age groups and examined the accuracy as well as the best cutoff value of ARR as screening test for PA in each age group. Results: As expected, plasma renin activity (PRA) lowered more than plasma aldosterone concentration (PAC) and led to gradually elevated ARR with increasing age in the non-PA group (P < 0.001), whereas this phenomenon was unconspicuous in PA group. The best cutoff values of ARR for PA screening were elevated in subjects aged 50–59 years (28.0) and over 60 years (25.0) compared to subjects under 50 years (20.4), while the area under the receiver operating characteristic curves (AUCs), sensitivity, specificity, Youden's index (YI) and positive likelihood ratio (LR) of ARR were declined with increasing age, especially in patients over 60 years (AUC = 0.863, sensitivity = 95.2%, specificity = 69.0%, YI = 0.643 and LR = 3.1). The AUCs of PAC increased with increasing age and even slightly surpassed that of ARR in patients over 60 years (AUCPAC = 0.884). Conclusions: Our data suggest that the criteria of ARR for PA screening in patients over 50 years may need setting higher than in patients under 50 years; the falling accuracy of ARR with increasing age, especially in patients over 60 years, could be improved by taking into account the absolute value of the PAC when applicable by the center.

9B.07

Objective: The aldosterone to renin ratio(ARR)is currently the most reliable available means of screening for Primary aldosteronism. It could be measured in the supine, seating or upright positions. The Endocrine Society and recent French guidelines recommended screening primary aldosteronism by the measurement of ARR in the seating position. The aim of this work is to study the influence of postural changes on ARR in patients with suspected secondary hypertension & to evaluate sensitivity and specificity of seated ARR compared to supine and upright ARR.Design and method: 43 patients were prospectively hospitalized for secondary hypertension exploration (age 51 ± 16,5; SBP/DBP:139 ± 12/85 ± 9mmHg, number of antihypertensive drugs:2 ± 1). After a conventional washout of drugs interfering with renin angiotensin aldosterone system, plasma aldosterone concentration was measured by RIA method(Normal values: 40–175ng/l)and direct renin concentration(DRC)with CLIA method (Normal values: 4,2–59.7 μUI/l). Aldosterone and renin samples were collected in the morning, at bed after an overnight supine position, then out of bed after 1 hour of upright position and finally 2 hours later after 15 minutes in seating position. When DRC was <5 μUI/l it was counted 5 μUI/l as recommended. Results: Referring to ARR cut-off value of 23pg/μUI, the sensitivity of seated ARR was 50% with a specificity of 96.5%. The negative predictive value was 80% and the positive predictive value was 87.5%. Compared to these results, a cut-off value of 19pg/μUI improved sensitivity to 85.7% with a specificity of 89.6%. Negative predictive value and positive predictive value were 92.8%and80% respectively. Seated ARR mean value(17 ± 15pg/μUI/l) was lower than supine and upright ARR, respectively measured at 23 ± 20pg/μUI and 24 ± 20pg/μUI. This could be explained by an overall increase in DRC at seating compared to the supine position with a mean increase by factor 2.2 (53 μUI/l vs 24 μUI/l), whereas at the same time, aldosterone just slightly increased by a factor 1.05(235ng/l vs 223ng/l). Seated ARR correlated to supine and upright ARR with correlation coefficients (r)of 0.89 and 0.93 respectively (p < 0,0001). Conclusions: Current recommended measurement of ARR in the seating position is fairly correlated to ARR in supine and upright positions. However, even if the recommended cut-off value of 23pg/μUI offers a good specificity, a suggested cut-off value of 19pg/μUI increases the discriminating power of this test.

Effect of postural changes on aldosterone to plasma renin ratio in patients with suspected secondary hypertension

AimsTo study the influence of postural changes on aldosterone to renin ratio (ARR) in patients with suspected secondary hypertension and to evaluate the sensitivity and specificity of the recommended seated ARR compared to supine and upright ARR for primary aldosteronism screening. MethodsFifty-three hypertensive patients were prospectively hospitalized for secondary hypertension exploration (age: 51±12, 66% males). After withdrawal of drugs interfering with renin angiotensin system, plasma aldosterone and direct renin concentration were measured in the morning, at bed after an overnight supine position, then out of bed after 1hour of upright position and finally 2hours later after 15minutes of seating. Minimal renin value was set at 5μUI/mL. ResultsReferring to ARR cut-off of 23pg/μUI, the sensitivity of seated ARR was 57.1% and specificity was 92.3%. The negative and positive predictive values were 95.1% and 45.2% respectively. Compared to these results, a cut-off of 19 improved sensitivity to 85.7% with a specificity of 89.7%. Negative and positive predictive values were 98.3% and 41.1% respectively. Seated ARR mean value was lower than supine and upright ARR mean values, due to an overall increase in renin at seating compared to the supine position by factor 1.9 while aldosterone just slightly increased by factor 1.2. Seated ARR correlated to supine and upright ARR: correlation coefficients (r) 0.90 and 0.93 respectively (P<0.001). ConclusionsCurrent recommended measurement of ARR in the seating position is fairly correlated to supine and upright ARR. A suggested cut-off value of 19 instead of 23pg/μUI increased the discriminating power of this test.

PP.09.14

Objective: Primary aldosteronism (PA) is a potentially curable form of secondary arterial hypertension provided there is unilateral aldosterone overproduction. Adrenal venous sampling (AVS) enables to identify the PA patients who can profit from unilateral adrenalectomy. The aim of the study was to analyse the AVS experience in our centre. Design and method: The data of the patients who were referred for AVS were enrolled in the study. All AVS procedures were performed according to the routine standardised protocol used in our centre. An infusion of cosyntrophin was administered 30 minutes before and during the procedure. Samples were taken step by step from both adrenal veins, and the inferior vena cava. Adrenal samples were considered adequate if the cortisol concentration was at least 5-fold greater than that of the inferior vena cava. The lateralization of aldosterone secretion was confirmed when cortisol-corrected aldosterone concentration from the affected gland was at least 4-fold higher than that of the contralateral side. The procedural success, the frequency of lateralisation of aldosterone secretion, and the complication rate were the main analysed parameters. Results: In the period 2005–2014, the AVS was performed in 184 patients. After repeating the procedure in 17 (9.2%), the adequate adrenal samples were obtained in 170 (92.4%) of patients. The lateralization of aldosterone secretion was identified in 72 (42.3%) cases where the AVS was successful. One periprocedural complication was noted. An adrenal hematoma developed as a consequence of adrenal vein injury. This adverse event resolved without a negative sequel. Conclusions: Provided the procedure is initially unsuccessful, repeating the AVS increases the success rate not augmenting the risk of complications. The rather high number of cases with proven lateralization of aldosterone secretion could be attributed to the selection of patients who have a high probability of surgically correctable form of PA when initiating the PA screening.