Primary Aldosteronism

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Paolo Mulatero - One of the best experts on this subject based on the ideXlab platform.

  • the Primary Aldosteronism surgical outcome score for the prediction of clinical outcomes after adrenalectomy for unilateral Primary Aldosteronism
    Annals of Surgery, 2020
    Co-Authors: Jacopo Burrello, Alessio Burrello, Michael Stowasser, Tetsuo Nishikawa, Marcus Quinkler, Aleksander Prejbisz, Jacques W M Lenders, Fumitoshi Satoh, Paolo Mulatero
    Abstract:

    MINI: Clinical remission after unilateral adrenalectomy to treat unilateral Primary Aldosteronism is achieved in less than half of patients. A linear discriminant model with 6 presurgical predictors of clinical remission was used to build a 25-point prediction score of postsurgical clinical outcomes. The prediction score was integrated into a user-friendly online tool which can be used in a clinical setting to differentiate patients who are likely to be clinically cured after surgery from those who will need continuous surveillance after surgery due to remnant hypertension. OBJECTIVE: To develop a prediction model for clinical outcomes after unilateral adrenalectomy for unilateral Primary Aldosteronism. SUMMARY BACKGROUND DATA: Unilateral Primary Aldosteronism is the most common surgically curable form of endocrine hypertension. Surgical resection of the dominant overactive adrenal in unilateral Primary Aldosteronism results in complete clinical success with resolution of hypertension without antihypertensive medication in less than half of patients with a wide between-center variability. METHODS: A linear discriminant analysis model was built using data of 380 patients treated by adrenalectomy for unilateral Primary Aldosteronism to classify postsurgical clinical outcomes. The total cohort was then randomly divided into training (280 patients) and test (100 patients) datasets to create and validate a score system to predict clinical outcomes. An online tool (Primary Aldosteronism Surgical Outcome predictor) was developed to facilitate the use of the predictive score. RESULTS: Six presurgical factors associated with complete clinical success (known duration of hypertension, sex, antihypertensive medication dosage, body mass index, target organ damage, and size of largest nodule at imaging) were selected based on classification performance in the linear discriminant analysis model. A 25-point predictive score was built with an optimal cut-off of greater than 16 points (accuracy of prediction = 79.2%; specificity = 84.4%; sensitivity = 71.3%) with an area under the curve of 0.839. CONCLUSIONS: The predictive score and the Primary Aldosteronism surgical outcome predictor can be used in a clinical setting to differentiate patients who are likely to be clinically cured after surgery from those who will need continuous surveillance after surgery due to persistent hypertension.

  • genetics prevalence screening and confirmation of Primary Aldosteronism a position statement and consensus of the working group on endocrine hypertension of the european society of hypertension
    Journal of Hypertension, 2020
    Co-Authors: Paolo Mulatero, Gian Paolo Rossi, Tetsuo Nishikawa, Aleksander Prejbisz, Felix Beuschlein, Silvia Monticone, Laurence Amar, Jaap Deinum, Mariachristina Zennaro, Alberto Morganti
    Abstract:

    : Autonomous aldosterone overproduction represents the underlying condition of 5-10% of patients with arterial hypertension and carries a significant burden of mortality and morbidity. The diagnostic algorithm for Primary Aldosteronism is sequentially based on hormonal tests (screening and confirmation tests), followed by lateralization studies (adrenal CT scanning and adrenal venous sampling) to distinguish between unilateral and bilateral disease. Despite the recommendations of the Endocrine Society guideline, Primary Aldosteronism is largely underdiagnosed and undertreated with high between-centre heterogeneity. Experts from the European Society of Hypertension have critically reviewed the available literature and prepared a consensus document constituting two articles to summarize current knowledge on the epidemiology, diagnosis, treatment, and complications of Primary Aldosteronism.

  • the expanding spectrum of Primary Aldosteronism implications for diagnosis pathogenesis and treatment
    Endocrine Reviews, 2018
    Co-Authors: Anand Vaidya, Paolo Mulatero, Rene Baudrand, G Adler
    Abstract:

    Primary Aldosteronism is characterized by aldosterone secretion that is independent of renin and angiotensin II and sodium status. The deleterious effects of Primary Aldosteronism are mediated by excessive activation of the mineralocorticoid receptor that results in the well-known consequences of volume expansion, hypertension, hypokalemia, and metabolic alkalosis, but it also increases the risk for cardiovascular and kidney disease, as well as death. For decades, the approaches to defining, diagnosing, and treating Primary Aldosteronism have been relatively constant and generally focused on detecting and treating the more severe presentations of the disease. However, emerging evidence suggests that the prevalence of Primary Aldosteronism is much greater than previously recognized, and that milder and nonclassical forms of renin-independent aldosterone secretion that impart heightened cardiovascular risk may be common. Public health efforts to prevent aldosterone-mediated end-organ disease will require improved capabilities to diagnose all forms of Primary Aldosteronism while optimizing the treatment approaches such that the excess risk for cardiovascular and kidney disease is adequately mitigated. In this review, we present a physiologic approach to considering the diagnosis, pathogenesis, and treatment of Primary Aldosteronism. We review evidence suggesting that Primary Aldosteronism manifests across a wide spectrum of severity, ranging from mild to overt, that correlates with cardiovascular risk. Furthermore, we review emerging evidence from genetic studies that begin to provide a theoretical explanation for the pathogenesis of Primary Aldosteronism and a link to its phenotypic severity spectrum and prevalence. Finally, we review human studies that provide insights into the optimal approach toward the treatment of Primary Aldosteronism.

  • cardiovascular events and target organ damage in Primary Aldosteronism compared with essential hypertension a systematic review and meta analysis
    The Lancet Diabetes & Endocrinology, 2018
    Co-Authors: Silvia Monticone, Franco Veglio, Tracy Ann Williams, Fabrizio Dascenzo, Claudio Moretti, Fiorenzo Gaita, Paolo Mulatero
    Abstract:

    Summary Background There is conflicting evidence, relying on heterogeneous studies, as to whether aldosterone excess is responsible for an increased risk of cardiovascular and cerebrovascular complications in patients with Primary Aldosteronism. We aimed to assess the association between Primary Aldosteronism and adverse cardiac and cerebrovascular events, target organ damage, diabetes, and metabolic syndrome, compared with the association of essential hypertension and these cardiovascular and end organ events, by integrating results of previous studies. Methods We did a meta-analysis of prospective and retrospective observational studies that compared patients with Primary Aldosteronism and essential hypertension, to analyse the association between Primary Aldosteronism and stroke, coronary artery disease (as co-Primary endpoints), atrial fibrillation and heart failure, target organ damage, metabolic syndrome, and diabetes (as secondary endpoints). We searched MEDLINE and Cochrane Library for articles published up to Feb 28, 2017, with no start date restriction. Eligible studies compared patients with Primary Aldosteronism with patients with essential hypertension (as a control group) and reported on the clinical events or endpoints of interest. We also compared Primary Aldosteronism subtypes, aldosterone-producing adenoma, and bilateral adrenal hyperplasia. Findings We identified 31 studies including 3838 patients with Primary Aldosteronism and 9284 patients with essential hypertension. After a median of 8·8 years (IQR 6·2–10·7) from the diagnosis of hypertension, compared with patients with essential hypertension, patients with Primary Aldosteronism had an increased risk of stroke (odds ratio [OR] 2·58, 95% CI 1·93–3·45), coronary artery disease (1·77, 1·10–2·83), atrial fibrillation (3·52, 2·06–5·99), and heart failure (2·05, 1·11–3·78). These results were consistent for patients with aldosterone-producing adenoma and bilateral adrenal hyperplasia, with no difference between these subgroups. Similarly, Primary Aldosteronism increased the risk of diabetes (OR 1·33, 95% CI 1·01–1·74), metabolic syndrome (1·53, 1·22–1·91), and left ventricular hypertrophy (2·29, 1·65–3·17). Interpretation Diagnosing Primary Aldosteronism in the early stages of disease, with early initiation of specific treatment, is important because affected patients display an increased cardiovascular risk compared with patients with essential hypertension. Funding None.

  • diagnostic accuracy of aldosterone and renin measurement by chemiluminescent immunoassay and radioimmunoassay in Primary Aldosteronism
    Journal of Hypertension, 2016
    Co-Authors: Jacopo Burrello, Fabrizio Buffolo, Giulio Mengozzi, Franco Rabbia, Franco Veglio, Silvia Monticone, Tracy Ann Williams, Manuela Lucchiari, Martina Tetti, Paolo Mulatero
    Abstract:

    Objective:Up to 50% of hypertensive patients should be screened for Primary Aldosteronism, using the aldosterone to renin (or plasma renin activity) ratio [aldosterone to active renin ratio (AARR) and aldosterone to plasma renin activity ratio (ARR), respectively]. Aim of the study was to prospectively compare the diagnostic accuracy of AARR (measured by chemiluminescent immunoassay) and ARR (measured by radioimmunoassay) as screening tests for Primary Aldosteronism and aldosterone assays (measured by chemiluminescence and radioimmunoassay) during confirmatory testing.Methods:One hundred patients were screened for Primary Aldosteronism and 34 underwent confirmatory testing. The cut-offs for ARR and AARR were 30ng/dl/ng/ml/h and 3.7ng/dl/mU/l, respectively. Patients with positive confirmatory test underwent subtype diagnosis.Results:Seventy-five patients were essential hypertensive patients, 15 had idiopathic hyperAldosteronism, five aldosterone-producing adenoma (APA) and five with undefined diagnosis. The AARR displayed a sensitivity of 90% and a specificity of 99%, the ARR had a sensitivity of 100% and a specificity of 73%. Of the two of 20 Primary Aldosteronism patients missed by AARR, none resulted affected by APA. All Primary Aldosteronism patients were correctly diagnosed by chemiluminescence at confirmatory testing. In the total sample of 168 measurements both the correlation for plasma renin activity with renin and for aldosterone in chemiluminescence and radioimmunoassay were highly significant (=0.70, P<0.001 and =0.78, P<0.001, respectively). On receiver operator characteristics curves, the area under the curve for AARR was 0.989 [95% confidence interval (CI) 0.97-1] and 0.934 for ARR (95% CI 0.89-0.98), which were not significantly different.Conclusion:The automated aldosterone and renin chemiluminescent assay is a reliable alternative to the radioimmunometric method, especially for APA detection.

Tracy Ann Williams - One of the best experts on this subject based on the ideXlab platform.

  • international histopathology consensus for unilateral Primary Aldosteronism
    The Journal of Clinical Endocrinology and Metabolism, 2021
    Co-Authors: Celso E Gomezsanchez, William E Rainey, Tracy Ann Williams, Thomas J Giordano, Alfred Kingyin Lam, Alison Marker, Ozgur Mete, Yuto Yamazaki
    Abstract:

    Objective: Develop a consensus for the nomenclature and definition of adrenal histopathologic features in unilateral Primary Aldosteronism (PA). Context: Unilateral PA is the most common surgically treated form of hypertension. Morphologic examination combined with CYP11B2 (aldosterone synthase) immunostaining reveals diverse histopathologic features of lesions in the resected adrenals. Patients and methods: Surgically removed adrenals (n = 37) from 90 patients operated from 2015 to 2018 in Munich, Germany, were selected to represent the broad histologic spectrum of unilateral PA. Five pathologists (Group 1 from Germany, Italy, and Japan) evaluated the histopathology of hematoxylin-eosin (HE) and CYP11B2 immunostained sections, and a consensus was established to define the identifiable features. The consensus was subsequently used by 6 additional pathologists (Group 2 from Australia, Brazil, Canada, Japan, United Kingdom, United States) for the assessment of all adrenals with disagreement for histopathologic diagnoses among group 1 pathologists. Results: Consensus was achieved to define histopathologic features associated with PA. Use of CYP11B2 immunostaining resulted in a change of the original HE morphology-driven diagnosis in 5 (14%) of 37 cases. Using the consensus criteria, group 2 pathologists agreed for the evaluation of 11 of the 12 cases of disagreement among group 1 pathologists. Conclusion: The HISTALDO (histopathology of Primary Aldosteronism) consensus is useful to standardize nomenclature and achieve consistency among pathologists for the histopathologic diagnosis of unilateral PA. CYP11B2 immunohistochemistry should be incorporated into the routine clinical diagnostic workup to localize the likely source of aldosterone production.

  • cardiovascular events and target organ damage in Primary Aldosteronism compared with essential hypertension a systematic review and meta analysis
    The Lancet Diabetes & Endocrinology, 2018
    Co-Authors: Silvia Monticone, Franco Veglio, Tracy Ann Williams, Fabrizio Dascenzo, Claudio Moretti, Fiorenzo Gaita, Paolo Mulatero
    Abstract:

    Summary Background There is conflicting evidence, relying on heterogeneous studies, as to whether aldosterone excess is responsible for an increased risk of cardiovascular and cerebrovascular complications in patients with Primary Aldosteronism. We aimed to assess the association between Primary Aldosteronism and adverse cardiac and cerebrovascular events, target organ damage, diabetes, and metabolic syndrome, compared with the association of essential hypertension and these cardiovascular and end organ events, by integrating results of previous studies. Methods We did a meta-analysis of prospective and retrospective observational studies that compared patients with Primary Aldosteronism and essential hypertension, to analyse the association between Primary Aldosteronism and stroke, coronary artery disease (as co-Primary endpoints), atrial fibrillation and heart failure, target organ damage, metabolic syndrome, and diabetes (as secondary endpoints). We searched MEDLINE and Cochrane Library for articles published up to Feb 28, 2017, with no start date restriction. Eligible studies compared patients with Primary Aldosteronism with patients with essential hypertension (as a control group) and reported on the clinical events or endpoints of interest. We also compared Primary Aldosteronism subtypes, aldosterone-producing adenoma, and bilateral adrenal hyperplasia. Findings We identified 31 studies including 3838 patients with Primary Aldosteronism and 9284 patients with essential hypertension. After a median of 8·8 years (IQR 6·2–10·7) from the diagnosis of hypertension, compared with patients with essential hypertension, patients with Primary Aldosteronism had an increased risk of stroke (odds ratio [OR] 2·58, 95% CI 1·93–3·45), coronary artery disease (1·77, 1·10–2·83), atrial fibrillation (3·52, 2·06–5·99), and heart failure (2·05, 1·11–3·78). These results were consistent for patients with aldosterone-producing adenoma and bilateral adrenal hyperplasia, with no difference between these subgroups. Similarly, Primary Aldosteronism increased the risk of diabetes (OR 1·33, 95% CI 1·01–1·74), metabolic syndrome (1·53, 1·22–1·91), and left ventricular hypertrophy (2·29, 1·65–3·17). Interpretation Diagnosing Primary Aldosteronism in the early stages of disease, with early initiation of specific treatment, is important because affected patients display an increased cardiovascular risk compared with patients with essential hypertension. Funding None.

  • computed tomography and adrenal venous sampling in the diagnosis of unilateral Primary Aldosteronism
    Hypertension, 2018
    Co-Authors: Leonardo A Sechi, Jacopo Burrello, Rene Baudrand, Tracy Ann Williams, Carlos E Fardella, Joanna Matrozova, Christian Adolf, Stella Bernardi, Felix Beuschlein
    Abstract:

    Unilateral Primary Aldosteronism is the most common surgically correctable form of endocrine hypertension and is usually differentiated from bilateral forms by adrenal venous sampling (AVS) or computed tomography (CT). Our objective was to compare clinical and biochemical postsurgical outcomes of patients with unilateral Primary Aldosteronism diagnosed by CT or AVS and identify predictors of surgical outcomes. Patient data were obtained from 18 internationally distributed centers and retrospectively analyzed for clinical and biochemical outcomes of adrenalectomy of patients with surgical management based on CT (n=235 patients, diagnosed from 1994-2016) or AVS (526 patients, diagnosed from 1994-2015) using the standardized PASO (Primary Aldosteronism Surgical Outcome) criteria. Biochemical outcomes were highly different according to surgical management approach with a smaller proportion in the CT group achieving complete biochemical success (188 of 235 [80%] patients versus 491 of 526 [93%], <0.001) and a greater proportion with absent biochemical success (29 of 235 [12%] versus 10 of 526 [2%], <0.001). A diagnosis by CT was associated with a decreased likelihood of complete biochemical success compared with AVS (odds ratio, 0.28; 0.16-0.50; <0.001). Clinical outcomes were not significantly different, but the absence of a postsurgical elevated aldosterone-to-renin ratio was a strong marker of complete clinical success (odds ratio, 14.81; 1.76-124.53; =0.013) in the CT but not in the AVS group. In conclusion, patients diagnosed by CT have a decreased likelihood of achieving complete biochemical success compared with a diagnosis by AVS.

  • guidelines for Primary Aldosteronism uptake by Primary care physicians in europe
    Journal of Hypertension, 2016
    Co-Authors: P Mulatero, Jacopo Burrello, Franco Veglio, Silvia Monticone, Tracy Ann Williams, John W Funder
    Abstract:

    Context:Primary Aldosteronism is the most frequent form of secondary hypertension but is still markedly underdiagnosed. In 2008, the Endocrine Society released guidelines for Primary Aldosteronism diagnosis and management; current indications are that they are not being widely followed.Objective:To

  • mass spectrometry based adrenal and peripheral venous steroid profiling for subtyping Primary Aldosteronism
    Clinical Chemistry, 2016
    Co-Authors: Graeme Eisenhofer, Anna Dietz, Martin Bidlingmaier, Tracy Ann Williams, Tanja Dekkers, Mirko Peitzsch, M Treitl, Stefan R Bornstein, Matthias Haase, L C Rump
    Abstract:

    BACKGROUND: Differentiating patients with Primary Aldosteronism caused by aldosterone-producing adenomas (APAs) from those with bilateral adrenal hyperplasia (BAH), which is essential for choice of therapeutic intervention, relies on adrenal venous sampling (AVS)-based measurements of aldosterone and cortisol. We assessed the utility of LC-MS/MS–based steroid profiling to stratify patients with Primary Aldosteronism. METHODS: Fifteen adrenal steroids were measured by LC-MS/MS in peripheral and adrenal venous plasma from AVS studies for 216 patients with Primary Aldosteronism at 3 tertiary referral centers. Ninety patients were diagnosed with BAH and 126 with APAs on the basis of immunoassay-derived adrenal venous aldosterone lateralization ratios. RESULTS: Among 119 patients confirmed to have APAs at follow-up, LC-MS/MS–derived lateralization ratios of aldosterone normalized to cortisol, dehydroepiandrosterone, and androstenedione were all higher (P CONCLUSIONS: LC-MS/MS–based steroid profiling during AVS achieves higher aldosterone lateralization ratios in patients with APAs than immunoassay. LC-MS/MS also enables multiple measures for discriminating unilateral from bilateral aldosterone excess, with potential use of peripheral plasma for subtype classification.

Franco Veglio - One of the best experts on this subject based on the ideXlab platform.

  • mineralocorticoid receptor antagonist effect on aldosterone to renin ratio in patients with Primary Aldosteronism
    The Journal of Clinical Endocrinology and Metabolism, 2021
    Co-Authors: Alessio Pecori, Jacopo Burrello, Fabrizio Buffolo, Giulio Mengozzi, Francesca Rumbolo, Valeria Avataneo, Antonio Davolio, Franco Rabbia, Chiara Bertello, Franco Veglio
    Abstract:

    Purpose We aimed to evaluate the effect of mineralocorticoid receptor antagonists on aldosterone-to-renin ratio in patients with Primary Aldosteronism. Methods We prospectively enrolled 121 patients with confirmed Primary Aldosteronism who started a mineralocorticoid receptor antagonist (canrenone) treatment. Eighteen patients (11 with unilateral and 7 with bilateral Primary Aldosteronism) composed the short-term study cohort and underwent aldosterone, renin and potassium measurement after 2 and 8 weeks of canrenone therapy. The long-term cohort comprised 102 patients (16 with unilateral and 67 with bilateral Primary Aldosteronism, and 19 with undetermined subtype) who underwent hormonal and biochemical re-assessment after 2 to 12 months of canrenone therapy. Results Renin and potassium levels showed a significant increase, and aldosterone-to-renin ratio displayed a significant reduction compared with baseline after both a short and long-term treatment. These effects were progressively more evident with higher doses of canrenone and after longer periods of treatment. We demonstrated that canrenone exerted a deep impact on the diagnostic accuracy of the screening test for Primary Aldosteronism: the rate of false negative tests raised to 16.7%, 38.9%, 54.5% and 72.5% after 2 weeks, 8 weeks, 2-6 months and 7-12 months of mineralocorticoid receptor antagonist treatment, respectively. Conclusions Mineralocorticoid receptor antagonists should be avoided in patients with hypertension before measurement of renin and aldosterone for screening of Primary Aldosteronism.

  • prevalence of hypokalemia and Primary Aldosteronism in 5100 patients referred to a tertiary hypertension unit
    Hypertension, 2020
    Co-Authors: Jacopo Burrello, Fabrizio Buffolo, Franco Rabbia, Franco Veglio, Silvia Monticone, Martina Tetti, Isabel Losano, Giovanni Cavaglia, Michele Covella, Barbara Pasini
    Abstract:

    Primary Aldosteronism (PA) was considered a rare disorder almost always associated with hypokalemia. The widespread screening of patients with hypertension unveiled an increased prevalence of PA wi...

  • cardiovascular events and target organ damage in Primary Aldosteronism compared with essential hypertension a systematic review and meta analysis
    The Lancet Diabetes & Endocrinology, 2018
    Co-Authors: Silvia Monticone, Franco Veglio, Tracy Ann Williams, Fabrizio Dascenzo, Claudio Moretti, Fiorenzo Gaita, Paolo Mulatero
    Abstract:

    Summary Background There is conflicting evidence, relying on heterogeneous studies, as to whether aldosterone excess is responsible for an increased risk of cardiovascular and cerebrovascular complications in patients with Primary Aldosteronism. We aimed to assess the association between Primary Aldosteronism and adverse cardiac and cerebrovascular events, target organ damage, diabetes, and metabolic syndrome, compared with the association of essential hypertension and these cardiovascular and end organ events, by integrating results of previous studies. Methods We did a meta-analysis of prospective and retrospective observational studies that compared patients with Primary Aldosteronism and essential hypertension, to analyse the association between Primary Aldosteronism and stroke, coronary artery disease (as co-Primary endpoints), atrial fibrillation and heart failure, target organ damage, metabolic syndrome, and diabetes (as secondary endpoints). We searched MEDLINE and Cochrane Library for articles published up to Feb 28, 2017, with no start date restriction. Eligible studies compared patients with Primary Aldosteronism with patients with essential hypertension (as a control group) and reported on the clinical events or endpoints of interest. We also compared Primary Aldosteronism subtypes, aldosterone-producing adenoma, and bilateral adrenal hyperplasia. Findings We identified 31 studies including 3838 patients with Primary Aldosteronism and 9284 patients with essential hypertension. After a median of 8·8 years (IQR 6·2–10·7) from the diagnosis of hypertension, compared with patients with essential hypertension, patients with Primary Aldosteronism had an increased risk of stroke (odds ratio [OR] 2·58, 95% CI 1·93–3·45), coronary artery disease (1·77, 1·10–2·83), atrial fibrillation (3·52, 2·06–5·99), and heart failure (2·05, 1·11–3·78). These results were consistent for patients with aldosterone-producing adenoma and bilateral adrenal hyperplasia, with no difference between these subgroups. Similarly, Primary Aldosteronism increased the risk of diabetes (OR 1·33, 95% CI 1·01–1·74), metabolic syndrome (1·53, 1·22–1·91), and left ventricular hypertrophy (2·29, 1·65–3·17). Interpretation Diagnosing Primary Aldosteronism in the early stages of disease, with early initiation of specific treatment, is important because affected patients display an increased cardiovascular risk compared with patients with essential hypertension. Funding None.

  • guidelines for Primary Aldosteronism uptake by Primary care physicians in europe
    Journal of Hypertension, 2016
    Co-Authors: P Mulatero, Jacopo Burrello, Franco Veglio, Silvia Monticone, Tracy Ann Williams, John W Funder
    Abstract:

    Context:Primary Aldosteronism is the most frequent form of secondary hypertension but is still markedly underdiagnosed. In 2008, the Endocrine Society released guidelines for Primary Aldosteronism diagnosis and management; current indications are that they are not being widely followed.Objective:To

  • diagnostic accuracy of aldosterone and renin measurement by chemiluminescent immunoassay and radioimmunoassay in Primary Aldosteronism
    Journal of Hypertension, 2016
    Co-Authors: Jacopo Burrello, Fabrizio Buffolo, Giulio Mengozzi, Franco Rabbia, Franco Veglio, Silvia Monticone, Tracy Ann Williams, Manuela Lucchiari, Martina Tetti, Paolo Mulatero
    Abstract:

    Objective:Up to 50% of hypertensive patients should be screened for Primary Aldosteronism, using the aldosterone to renin (or plasma renin activity) ratio [aldosterone to active renin ratio (AARR) and aldosterone to plasma renin activity ratio (ARR), respectively]. Aim of the study was to prospectively compare the diagnostic accuracy of AARR (measured by chemiluminescent immunoassay) and ARR (measured by radioimmunoassay) as screening tests for Primary Aldosteronism and aldosterone assays (measured by chemiluminescence and radioimmunoassay) during confirmatory testing.Methods:One hundred patients were screened for Primary Aldosteronism and 34 underwent confirmatory testing. The cut-offs for ARR and AARR were 30ng/dl/ng/ml/h and 3.7ng/dl/mU/l, respectively. Patients with positive confirmatory test underwent subtype diagnosis.Results:Seventy-five patients were essential hypertensive patients, 15 had idiopathic hyperAldosteronism, five aldosterone-producing adenoma (APA) and five with undefined diagnosis. The AARR displayed a sensitivity of 90% and a specificity of 99%, the ARR had a sensitivity of 100% and a specificity of 73%. Of the two of 20 Primary Aldosteronism patients missed by AARR, none resulted affected by APA. All Primary Aldosteronism patients were correctly diagnosed by chemiluminescence at confirmatory testing. In the total sample of 168 measurements both the correlation for plasma renin activity with renin and for aldosterone in chemiluminescence and radioimmunoassay were highly significant (=0.70, P<0.001 and =0.78, P<0.001, respectively). On receiver operator characteristics curves, the area under the curve for AARR was 0.989 [95% confidence interval (CI) 0.97-1] and 0.934 for ARR (95% CI 0.89-0.98), which were not significantly different.Conclusion:The automated aldosterone and renin chemiluminescent assay is a reliable alternative to the radioimmunometric method, especially for APA detection.

William F Young - One of the best experts on this subject based on the ideXlab platform.

  • Primary Aldosteronism renaissance of a syndrome
    Clinical Endocrinology, 2007
    Co-Authors: William F Young
    Abstract:

    Great strides have been made in our understanding of the pathophysiology of Primary Aldosteronism syndrome since Conn's description of the clinical presentation of a patient with an aldosterone-producing adenoma (APA) more than 50 years ago. It is now recognized that the APA is just one of the seven subtypes of Primary Aldosteronism. APA and bilateral idiopathic hyperAldosteronism (IHA) are the most common subtypes of Primary Aldosteronism. Although most clinicians had thought Primary Aldosteronism to be a rare form of hypertension for more than three decades, it is now recognized to be the most common form of secondary hypertension. Using the plasma aldosterone to plasma renin activity ratio as a case-finding test, followed by aldosterone suppression confirmatory testing, has resulted in much higher prevalence estimates of 5-13% of all patients with hypertension. In addition, there has been a new recognition of the aldosterone-specific cardiovascular morbidity and mortality associated with aldosterone excess. Although thought to be daunting and complex in the past, the diagnostic approach to Primary Aldosteronism is straightforward and can be considered in three phases: case-finding tests, confirmatory tests and subtype evaluation tests. Patients with hypertension and hypokalaemia (regardless of presumed cause), treatment-resistant hypertension (three antihypertensive drugs and poor control), severe hypertension (>or= 160 mmHg systolic or >or= 100 mmHg diastolic), hypertension and an incidental adrenal mass, onset of hypertension at a young age or patients being evaluated for other forms of secondary hypertension should undergo screening for Primary Aldosteronism. In patients with suspected Primary Aldosteronism, screening can be accomplished by measuring a morning (preferably between 0800 and 1000 h) ambulatory paired random plasma aldosterone concentration (PAC) and plasma renin activity (PRA). An increased PAC:PRA ratio is not diagnostic by itself, and Primary Aldosteronism must be confirmed by demonstrating inappropriate aldosterone secretion. Aldosterone suppression testing can be performed with orally administered sodium chloride and measurement of urinary aldosterone or with intravenous sodium chloride loading and measurement of PAC. Unilateral adrenalectomy in patients with APA or unilateral adrenal hyperplasia results in normalization of hypokalaemia in all these patients; hypertension is improved in all and is cured in approximately 30-60% of them. In bilateral adrenal forms of Primary Aldosteronism, unilateral or bilateral adrenalectomy seldom corrects the hypertension and they should be treated medically with a mineralocorticoid receptor antagonist.

  • Primary Aldosteronism diagnostic and treatment strategies
    Nature Reviews Nephrology, 2006
    Co-Authors: Cecilia Mattsson, William F Young
    Abstract:

    Primary Aldosteronism is found in about one-tenth of people with hypertension. Following diagnosis, effective treatment is based on identification of the specific subtype of this condition. Of the various causes underlying Primary Aldosteronism, bilateral idiopathic hyperplasia and aldosterone-producing adenoma are the most common. In this Review, the authors describe the optimal approaches to detection and management of subtypes of aldosterone hypersecretion. Primary Aldosteronism is caused by bilateral idiopathic hyperplasia in approximately two-thirds of cases and aldosterone-producing adenoma in one-third. Most patients with Primary Aldosteronism are normokalemic. In the clinical setting of normokalemic hypertension, patients who have resistant hypertension and hypertensive patients with a family history atypical for polygenic hypertension should be tested for Primary Aldosteronism. The ratio of plasma aldosterone concentration to plasma renin activity has been generally accepted as a first-line case-finding test. If a patient has an increased ratio, autonomous aldosterone production must be confirmed with an aldosterone suppression test. Once Primary Aldosteronism is confirmed, the subtype needs to be determined to guide treatment. The initial test in subtype evaluation is CT imaging of the adrenal glands. If surgical treatment is considered, adrenal vein sampling is the most accurate method for distinguishing between unilateral and bilateral adrenal aldosterone production. Optimal treatment for aldosterone-producing adenoma or unilateral hyperplasia is unilateral laparoscopic adrenalectomy. The idiopathic bilateral hyperplasia and glucocorticoid-remediable Aldosteronism subtypes should be treated pharmacologically. All patients treated pharmacologically should receive a mineralocorticoid receptor antagonist, a drug type that has been shown to block the toxic effects of aldosterone on nonepithelial tissues.

  • role for adrenal venous sampling in Primary Aldosteronism
    Surgery, 2004
    Co-Authors: William F Young, David R Farley, Geoffrey B Thompson, Clive S Grant, Anthony W Stanson, Jon A Van Heerden
    Abstract:

    Background The aim of this study was to determine the effect of adrenal venous sampling (AVS) on the management of patients with Primary Aldosteronism. Methods From September 1990 through October 2003, 203 patients with Primary Aldosteronism (mean age, 53 years; range, 17-80; 163 men) were selected prospectively for AVS on the basis of degree of aldosterone excess, age, desire for surgical treatment, and computed tomographic (CT) findings. Results Both adrenal veins were catheterized in 194 patients (95.6%). Notable among the 110 patients (56.7%) with unilateral aldosterone hypersecretion were 24 (41.4%) of 58 patients with normal adrenal CT findings, 24 (51.1%) of 47 with unilateral micronodule (≤10 mm) apparent on CT (7 had unilateral aldosterone hypersecretion from the contralateral adrenal), 21 (65.6%) of 32 with unilateral macronodule (>10 mm) apparent on CT (1 had unilateral aldosterone hypersecretion from the contralateral adrenal), 16 (48.5%) of 33 with bilateral micronodules, and 2 (33%) of 6 with bilateral macronodules. Conclusions On the basis of CT findings alone, 42 patients (21.7%) would have been incorrectly excluded as candidates for adrenalectomy, and 48 (24.7%) might have had unnecessary or inappropriate adrenalectomy. AVS is an essential diagnostic step in most patients to distinguish between unilateral and bilateral adrenal aldosterone hypersecretion.

  • minireview Primary Aldosteronism changing concepts in diagnosis and treatment
    Endocrinology, 2003
    Co-Authors: William F Young
    Abstract:

    Primary Aldosteronism affects 5-13% of patients with hypertension. Patients with hypertension and hypokalemia and most patients with treatment-resistant hypertension should undergo screening for Primary Aldosteronism with a plasma aldosterone concentration to plasma renin activity ratio. A high plasma aldosterone concentration to plasma renin activity ratio is a positive screening test result, a finding that warrants confirmatory testing. For those patients that want to pursue a surgical cure, the accurate distinction between the subtypes (unilateral vs. bilateral adrenal disease) of Primary Aldosteronism is a critical step. The subtype evaluation may require one or more tests, the first of which is imaging the adrenal glands with computed tomography, followed by selective use of adrenal venous sampling. Because of the deleterious cardiovascular effects of aldosterone, normalization of circulating aldosterone or aldosterone receptor blockade should be part of the management plan for all patients with Primary Aldosteronism. Unilateral laparoscopic adrenalectomy is an excellent treatment option for patients with unilateral aldosterone-producing adenoma. Bilateral idiopathic hyperAldosteronism should be treated medically. In addition, aldosterone-producing adenoma patients may be treated medically if the medical treatment includes mineralocorticoid receptor blockade.

  • Primary Aldosteronism factors associated with normalization of blood pressure after surgery
    Annals of Internal Medicine, 2001
    Co-Authors: Anna M Sawka, David R Farley, Geoffrey B Thompson, William F Young, Clive S Grant, Cynthia L Leibson, Jon A Van Heerden
    Abstract:

    Resolution of hypertension after adrenalectomy for Primary Aldosteronism is independently associated with a lack of family history of hypertension and preoperative use of two or fewer antihypertens...

Jacopo Burrello - One of the best experts on this subject based on the ideXlab platform.

  • mineralocorticoid receptor antagonist effect on aldosterone to renin ratio in patients with Primary Aldosteronism
    The Journal of Clinical Endocrinology and Metabolism, 2021
    Co-Authors: Alessio Pecori, Jacopo Burrello, Fabrizio Buffolo, Giulio Mengozzi, Francesca Rumbolo, Valeria Avataneo, Antonio Davolio, Franco Rabbia, Chiara Bertello, Franco Veglio
    Abstract:

    Purpose We aimed to evaluate the effect of mineralocorticoid receptor antagonists on aldosterone-to-renin ratio in patients with Primary Aldosteronism. Methods We prospectively enrolled 121 patients with confirmed Primary Aldosteronism who started a mineralocorticoid receptor antagonist (canrenone) treatment. Eighteen patients (11 with unilateral and 7 with bilateral Primary Aldosteronism) composed the short-term study cohort and underwent aldosterone, renin and potassium measurement after 2 and 8 weeks of canrenone therapy. The long-term cohort comprised 102 patients (16 with unilateral and 67 with bilateral Primary Aldosteronism, and 19 with undetermined subtype) who underwent hormonal and biochemical re-assessment after 2 to 12 months of canrenone therapy. Results Renin and potassium levels showed a significant increase, and aldosterone-to-renin ratio displayed a significant reduction compared with baseline after both a short and long-term treatment. These effects were progressively more evident with higher doses of canrenone and after longer periods of treatment. We demonstrated that canrenone exerted a deep impact on the diagnostic accuracy of the screening test for Primary Aldosteronism: the rate of false negative tests raised to 16.7%, 38.9%, 54.5% and 72.5% after 2 weeks, 8 weeks, 2-6 months and 7-12 months of mineralocorticoid receptor antagonist treatment, respectively. Conclusions Mineralocorticoid receptor antagonists should be avoided in patients with hypertension before measurement of renin and aldosterone for screening of Primary Aldosteronism.

  • the Primary Aldosteronism surgical outcome score for the prediction of clinical outcomes after adrenalectomy for unilateral Primary Aldosteronism
    Annals of Surgery, 2020
    Co-Authors: Jacopo Burrello, Alessio Burrello, Michael Stowasser, Tetsuo Nishikawa, Marcus Quinkler, Aleksander Prejbisz, Jacques W M Lenders, Fumitoshi Satoh, Paolo Mulatero
    Abstract:

    MINI: Clinical remission after unilateral adrenalectomy to treat unilateral Primary Aldosteronism is achieved in less than half of patients. A linear discriminant model with 6 presurgical predictors of clinical remission was used to build a 25-point prediction score of postsurgical clinical outcomes. The prediction score was integrated into a user-friendly online tool which can be used in a clinical setting to differentiate patients who are likely to be clinically cured after surgery from those who will need continuous surveillance after surgery due to remnant hypertension. OBJECTIVE: To develop a prediction model for clinical outcomes after unilateral adrenalectomy for unilateral Primary Aldosteronism. SUMMARY BACKGROUND DATA: Unilateral Primary Aldosteronism is the most common surgically curable form of endocrine hypertension. Surgical resection of the dominant overactive adrenal in unilateral Primary Aldosteronism results in complete clinical success with resolution of hypertension without antihypertensive medication in less than half of patients with a wide between-center variability. METHODS: A linear discriminant analysis model was built using data of 380 patients treated by adrenalectomy for unilateral Primary Aldosteronism to classify postsurgical clinical outcomes. The total cohort was then randomly divided into training (280 patients) and test (100 patients) datasets to create and validate a score system to predict clinical outcomes. An online tool (Primary Aldosteronism Surgical Outcome predictor) was developed to facilitate the use of the predictive score. RESULTS: Six presurgical factors associated with complete clinical success (known duration of hypertension, sex, antihypertensive medication dosage, body mass index, target organ damage, and size of largest nodule at imaging) were selected based on classification performance in the linear discriminant analysis model. A 25-point predictive score was built with an optimal cut-off of greater than 16 points (accuracy of prediction = 79.2%; specificity = 84.4%; sensitivity = 71.3%) with an area under the curve of 0.839. CONCLUSIONS: The predictive score and the Primary Aldosteronism surgical outcome predictor can be used in a clinical setting to differentiate patients who are likely to be clinically cured after surgery from those who will need continuous surveillance after surgery due to persistent hypertension.

  • prevalence of hypokalemia and Primary Aldosteronism in 5100 patients referred to a tertiary hypertension unit
    Hypertension, 2020
    Co-Authors: Jacopo Burrello, Fabrizio Buffolo, Franco Rabbia, Franco Veglio, Silvia Monticone, Martina Tetti, Isabel Losano, Giovanni Cavaglia, Michele Covella, Barbara Pasini
    Abstract:

    Primary Aldosteronism (PA) was considered a rare disorder almost always associated with hypokalemia. The widespread screening of patients with hypertension unveiled an increased prevalence of PA wi...

  • computed tomography and adrenal venous sampling in the diagnosis of unilateral Primary Aldosteronism
    Hypertension, 2018
    Co-Authors: Leonardo A Sechi, Jacopo Burrello, Rene Baudrand, Tracy Ann Williams, Carlos E Fardella, Joanna Matrozova, Christian Adolf, Stella Bernardi, Felix Beuschlein
    Abstract:

    Unilateral Primary Aldosteronism is the most common surgically correctable form of endocrine hypertension and is usually differentiated from bilateral forms by adrenal venous sampling (AVS) or computed tomography (CT). Our objective was to compare clinical and biochemical postsurgical outcomes of patients with unilateral Primary Aldosteronism diagnosed by CT or AVS and identify predictors of surgical outcomes. Patient data were obtained from 18 internationally distributed centers and retrospectively analyzed for clinical and biochemical outcomes of adrenalectomy of patients with surgical management based on CT (n=235 patients, diagnosed from 1994-2016) or AVS (526 patients, diagnosed from 1994-2015) using the standardized PASO (Primary Aldosteronism Surgical Outcome) criteria. Biochemical outcomes were highly different according to surgical management approach with a smaller proportion in the CT group achieving complete biochemical success (188 of 235 [80%] patients versus 491 of 526 [93%], <0.001) and a greater proportion with absent biochemical success (29 of 235 [12%] versus 10 of 526 [2%], <0.001). A diagnosis by CT was associated with a decreased likelihood of complete biochemical success compared with AVS (odds ratio, 0.28; 0.16-0.50; <0.001). Clinical outcomes were not significantly different, but the absence of a postsurgical elevated aldosterone-to-renin ratio was a strong marker of complete clinical success (odds ratio, 14.81; 1.76-124.53; =0.013) in the CT but not in the AVS group. In conclusion, patients diagnosed by CT have a decreased likelihood of achieving complete biochemical success compared with a diagnosis by AVS.

  • guidelines for Primary Aldosteronism uptake by Primary care physicians in europe
    Journal of Hypertension, 2016
    Co-Authors: P Mulatero, Jacopo Burrello, Franco Veglio, Silvia Monticone, Tracy Ann Williams, John W Funder
    Abstract:

    Context:Primary Aldosteronism is the most frequent form of secondary hypertension but is still markedly underdiagnosed. In 2008, the Endocrine Society released guidelines for Primary Aldosteronism diagnosis and management; current indications are that they are not being widely followed.Objective:To

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