A new highly sensitive and specific overnight combined screening and diagnostic test for primary aldosteronism

Context Primary aldosteronism (PA) is the most common cause of endocrine hypertension that is diagnosed following a two-step process: an initial screening test, based on the serum aldosterone-to-renin ratio (ARR), followed by a relatively laborious and time-consuming confirmatory test to document autonomous aldosterone (ALD) secretion. Objective The aim of this study is to develop a simple overnight test for the early and definite diagnosis of PA. Patients and methods Totally, 148 hypertensive patients underwent a fludrocortisone–dexamethasone suppression test (FDST) and the new overnight diagnostic test (DCVT) using pharmaceutical RAAS (renin–angiotensin–aldosterone system) blockade with dexamethasone, captopril and valsartan. Results Of the 148 patients, 45 were diagnosed as having PA and they all normalized their elevated blood pressure (BP) after administration of spironolactone or eplerenone. The remaining 103 patients were considered as having essential hypertension and served as controls. Using ROC analysis, the estimated sensitivity and specificity were 91 and 100%, respectively, for the post-FDST ARR, whereas 98% and 89% and 100% and 82% for the post-DCVT ARR and post-DCVT ALD, respectively, with selected cutoffs of 0.32ng/dL/μU/mL and 3ng/dL respectively. However, considering these cutoffs simultaneously, the estimated sensitivity and specificity were 98 and 100% respectively. Applying these cutoffs, the diagnosis of PA was confirmed in 44 (98%) of the 45 patients who were considered to have the disease. Conclusions In this study, a highly sensitive and specific, low-cost, rapid, safe, and easy-to-perform diagnostic test (DCVT) for PA is described, which could be utilized on an outpatient basis potentially substituting conventional laborious testing.

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SAT-543 Human Hair Aldosterone Measurements for Evaluation of Primary Aldosteronism

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1572 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Andrew Paul Demidowich ◽

Jancarlos Camacho ◽

Maria de la Luz Sierra ◽

Elena Belyavskaya ◽

Charalampos Lysikatos ◽

...

Keyword(s):

Primary Aldosteronism ◽

Human Hair ◽

Serum Cortisol ◽

Diagnostic Techniques ◽

Endocrine Hypertension ◽

Serum Aldosterone ◽

Hair Samples ◽

Aldosterone Production ◽

Student’S T ◽

Aldosterone To Renin Ratio

Abstract Background: Primary Aldosteronism (PA) is the most common cause of endocrine hypertension in US. Diagnostic techniques such as a 24 hour urine collection or saline suppression test (SST) can be laborious for both patients and staff. Our group previously showed that human hair cortisol measurements correlated with urine and serum cortisol levels in patients with endogenous cortisol excess. In this study, we explored whether human hair aldosterone correlated with other measures of aldosterone production. Methods: 41 adult subjects were evaluated at the NIH Clinical Center for adrenal disorders. A pencil-width of hair near the occiput was removed, and the 1cm segment closest to the scalp was analyzed by enzyme immunoassay for aldosterone, reported as pg aldosterone/mg dry hair. Not all subjects underwent complete workup for PA. Data were transformed as necessary to maintain assumptions of normality. Student’s t-test and Pearson correlations were used for statistical analysis. Results: Of the evaluated subjects, 18 were diagnosed with PA, 22 subjects did not have PA, and 1 subject was indeterminate. The mean hair weight was 33.0±13.7mg. For hair samples weighing greater than 10mg, hair weight was not correlated with hair aldosterone concentration (p=0.40). There was no difference in measured hair aldosterone between the subjects with and without PA (2.01±1.09 vs. 2.52±2.45 pg/mg; p=0.82). Among all subjects, hair aldosterone did not correlate with serum aldosterone (p=0.92), aldosterone-to-renin ratio (ARR; p=0.94), 24 hour urine aldosterone (Ualdo; p=0.85), or the serum aldosterone at the 4 hour time point of a SST (4hrAldo; p=0.98). Serum aldosterone, ARR, Ualdo, and 4hrAldo all correlated highly amongst each other (all p’s<0.001). Conclusions: Hair aldosterone levels do not correlate with other markers of PA. Further work is needed to understand whether optimization of study conditions could improve the usefulness of hair aldosterone measurements in the evaluation of PA.

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Dietary Sodium Restriction Increases the Risk of Misinterpreting Mild Cases of Primary Aldosteronism

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2016-1963 ◽

2016 ◽

Vol 101 (11) ◽

pp. 3989-3996 ◽

Cited By ~ 26

Author(s):

Rene Baudrand ◽

Francisco J. Guarda ◽

Jasmine Torrey ◽

Gordon Williams ◽

Anand Vaidya

Keyword(s):

Primary Aldosteronism ◽

Sodium Intake ◽

Plasma Renin ◽

Dietary Sodium ◽

Sodium Restriction ◽

Positive Screen ◽

Serum Aldosterone ◽

Optimal Screening ◽

Dietary Sodium Restriction ◽

Aldosterone To Renin Ratio

Context: The aldosterone to renin ratio (ARR) is recommended to screen for primary aldosteronism (PA). Objective: To evaluate whether dietary sodium restriction results in misinterpretation of PA screening. Participants: Untreated hypertensives with ARR more than 20 on a high dietary sodium intake (HS) were also evaluated on a low dietary sodium intake (LS) (n = 241). Positive screening for PA was defined as: plasma renin activity (PRA) less than or equal to 1.0 ng/mL · h with serum aldosterone more than or equal to 6 ng/dL. PA was confirmed by a 24-hour urinary aldosterone excretion more than or equal to 12 mcg with urinary sodium more than 200 mmol. Results: Only 33% (79/241) of participants with an ARR more than 20 had a positive PA screen on HS. On LS, 56% (44/79) of these participants no longer met criteria for positive PA screening. When compared with participants with positive PA screening on both diets, participants with a positive screen on HS but negative on LS exhibited a significantly higher PRA on both diets. Remarkably, of the 48/79 participants who had PA confirmed, 52% had negative PA screening on LS. The distinguishing feature of these participants with “discordant” screening results was a larger rise in PRA on LS resulting in normalization of the ARR and higher Caucasian race prevalence. Conclusions: Sodium restriction is recommended in hypertension; however, it can significantly raise PRA, normalize the ARR, and result in false interpretation of PA screening. Milder phenotypes of PA, where PRA is not as suppressed, are most susceptible to dietary sodium influences on renin and ARR. Optimal screening for PA should occur under conditions of HS.

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Primary aldosteronism as a cause of secondary osteoporosis

Acta Endocrinologica ◽

10.1530/eje-17-0417 ◽

2017 ◽

Vol 177 (5) ◽

pp. 431-437 ◽

Cited By ~ 14

Author(s):

Antonio Stefano Salcuni ◽

Vincenzo Carnevale ◽

Claudia Battista ◽

Serena Palmieri ◽

Cristina Eller-Vainicher ◽

...

Keyword(s):

Primary Aldosteronism ◽

Urinary Calcium ◽

Calcium Excretion ◽

Outpatient Basis ◽

Mineral Density ◽

Mean Values ◽

Metabolic Bone ◽

Confirmatory Tests ◽

Aldosterone To Renin Ratio ◽

Serum Pth

Objective Patients with primary aldosteronism (PA) have a high prevalence of osteoporosis (OP) and fractures (Fx). We evaluated the presence of PA in patients admitted to our metabolic bone disease outpatient clinic. Design Study conducted on an in- and outpatient basis in a referral Italian endocrinology unit. Methods A total of 2632 patients were evaluated. 2310 were excluded because they were taking drugs known to affect bone or mineralocorticoids metabolism or were diagnosed to have a secondary cause of osteoporosis. The remaining 322 subjects (304 females, 18 males) took part in the study. Bone mineral density (BMD) and thoracic and lumbar spine vertebral morphometry were performed by dual X-ray absorptiometry. All patients were screened for PA with aldosterone-to-renin ratio. In those who had positive results, confirmatory tests were performed. Results Among 322 subjects, 213 were osteoporotics and 109 were not. PA was diagnosed in eleven out of 213 osteoporotic patients (5.2%) and one out of 109 non-osteoporotic subjects (0.9%, P = 0.066). PA was observed in the 26.1% of patients with the concomitant presence of osteoporosis, hypertension and hypercalciuria. Compared with patients without PA, patients with PA had mean values of urinary calcium excretion, 4.8 ± 2.5 mmol/day vs 7.6 ± 3.2 mmol/day, P < 0.001 and serum PTH levels, 5.4 pmol/L vs 7.3 pmol/L, P < 0.01, significantly higher. Conclusions PA should be considered among the causes of secondary OP.

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Progress in Primary Aldosteronism 2019: New Players on the Block?

Hormone and Metabolic Research ◽

10.1055/a-1156-9926 ◽

2020 ◽

Vol 52 (06) ◽

pp. 345-346 ◽

Cited By ~ 2

Author(s):

Martin Reincke ◽

Felix Beuschlein ◽

Tracy Ann Williams

Keyword(s):

Resistant Hypertension ◽

Primary Aldosteronism ◽

Retrospective Cohort ◽

Plasma Renin ◽

Epidemiological Data ◽

Screening Rate ◽

Aldosterone Secretion ◽

Endocrine Hypertension ◽

High Prevalence ◽

Aldosterone To Renin Ratio

Primary aldosteronism (PA) is characterized by hypertension caused by inappropriately high adrenal aldosterone secretion, consecutively low plasma renin, and an elevated aldosterone to renin ratio. It is nowadays the universally accepted main cause of endocrine hypertension. According to the most recent epidemiological data, PA is present in 5.8% of unselected hypertensives in primary care, 6–12% of hypertensives treated in hypertension centers, and up to 30% in subjects with resistant hypertension 1. Despite this high prevalence, a recent survey demonstrated that screening for PA is not universally followed. Renin and aldosterone measurements, the basis for PA screening, are currently performed by only 7% of general practitioners in Italy and 8% in Germany 2. Accordingly, the prevalence of PA was low with 1% among hypertensives in Italy and 2% in Germany. In a retrospective cohort study of 4660 patients with resistant hypertension in California the screening rate for PA was 2.1% 3. Based on these data, it is clear that we still miss the majority of PA cases, despite advances in diagnosis and therapy.

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Determination of adrenal hypersecretion in primary Aldosteronism without aldosterone-production adenomas

BMC Endocrine Disorders ◽

10.1186/s12902-021-00770-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Fang Sun ◽

Yangning Hong ◽

Hexuan Zhang ◽

Xiaoli Liu ◽

Zhigang Zhao ◽

...

Keyword(s):

Primary Aldosteronism ◽

Metabolic Diseases ◽

Heart Diseases ◽

Confirmatory Test ◽

Plasma Aldosterone Concentration ◽

Aldosterone Production ◽

Confirmatory Tests ◽

Biochemical Evaluation ◽

Aldosterone To Renin Ratio

Abstract Background Primary aldosteronism (PA) is highly prevalent in hypertensive population. Adrenal vein sampling (AVS) is the only procedure to assess adrenal aldosterone hypersecretion in PA. PA patients without aldosterone-producing adenomas (APA) frequently have unilateral aldosterone hypersecretion (UAH). These patients could bear inappropriate adrenalectomy without AVS. This study aims to identify which clinical characteristics should be recommended to perform AVS in these PA patients. Methods This study was performed from January 2018 to July 2019 at a center for hypertension and metabolic diseases. Adrenal computed tomography (CT) scan, biochemical evaluation, and AVS were performed. Results Total 141 patients were included in this study. Aldosterone to renin ratio (ARR) after confirmatory test is highly associated with adrenal laterality. The specificity of ARR > 10 (ng/dL)/(mU/L) after confirmatory test is 100%. After confirmatory test, patients with ARR > 10 (ng/dL)/(mU/L) had higher plasma aldosterone concentration and incidences of ischemic heart diseases and renal damage(p < 0.05). Conclusions After confirmatory tests, ARR > 10 (ng/dL)/(mU/L) indicates adrenal laterality, with increasingly cardiorenal damage in PA patients without APA. Thus, AVS should be recommended in these patients before surgery. Trial registration NCT03398785, Date of Registration: December 24, 2017.

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Persistent Hyperkalemia Post-Adrenalectomy for Aldosterone-Producing Adenoma

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.298 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A147-A148

Author(s):

Marisa Khatijah Borhan ◽

Florence Hui Sieng Tan

Keyword(s):

Risk Factors ◽

Hospital Admission ◽

Primary Aldosteronism ◽

Clinical Risk Factors ◽

Confirmatory Test ◽

Clinical Risk ◽

Serum Aldosterone ◽

Adequate Hydration ◽

Low Potassium ◽

Aldosterone Producing Adenoma

Abstract Background:Post-operative hypoaldosteronism due to chronic suppression of the renin-aldosterone axis of the contralateral gland can be complicated with hyperkalemia. We describe a case of persistent hyperkalemia post adrenalectomy for aldosterone-producing adenoma. Clinical Case: A 47-year-old male was first diagnosed with hypertension in 2011. He was investigated for secondary hypertension after hospital admission in 2019 for hypertensive urgency and symptomatic hypokalemia (potassium, K 1.9–2.3 mmol/L, n = 3.5–5.0). Subsequent laboratory investigation revealed elevated serum aldosterone (3565 pmol/L, n < 103) with an aldosterone renin ratio of 115 (n < 35). A confirmatory test with saline loading showed an unsuppressed serum aldosterone level of 1840 pmol/L. Adrenal CT reported a 4.1-cm, heterogeneous left adrenal lesion. A diagnosis of primary aldosteronism was made, and he underwent laparoscopic left adrenalectomy in July 2020. Histopathology examination was consistent with adrenal cortical adenoma. Both potassium supplementation and spironolactone were stopped immediately postoperatively. Two weeks later, he developed symptomatic hyperkalemia (K 6.0 mmol/L), requiring hospital admission, and started on potassium binder. Throughout clinic follow-ups, potassium remained high (K 5.4–6.1 mmol/L), despite low potassium diet and potassium binder. His case was co-managed with the nephrology team and given a trial of frusemide and sodium bicarbonate to normalize his potassium. However, after 4 months, he remained hyperkalemic. Repeated serum aldosterone was not elevated (<103 pmol/L). He was then started on fludrocortisone and finally managed to achieve serum potassium normalisation (K 4.1–4.5 mmol/L). Conclusion: This case highlights the importance of monitoring potassium levels in all patients after adrenalectomy, particularly those with clinical risk factors. Retrospective studies by Park et al and Fischer et al reported that a long duration of hypertension, impaired preoperative renal function, older age, and large adenoma size represent risks for developing hyperkalemia postoperatively, whereas the use of mineralocorticoid receptor antagonists preoperatively does not prevent hyperkalemia. Treatment includes a low potassium diet, a high sodium diet, adequate hydration, potassium binder, frusemide, and fludrocortisone. In some cases, hyperkalemia may be prolonged, necessitating long-term fludrocortisone therapy, up to 11–46 months². References: 1. Park KS, Kim JH, Ku EJ, et al. Clinical risk factors of postoperative hyperkalemia after adrenalectomy in patients with aldosterone-producing adenoma. Eur J Endocrinol. 2015 Jun;172(6):725–31. 2. Fischer E, Hanslik G, Pallauf A, et al. Prolonged zona glomerulosa insufficiency causing hyperkalemia in primary aldosteronism after adrenalectomy. J Clin Endocrinol Metab. 2012 Nov;97(11):3965–73.

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Performance of the Aldosterone-to-Renin Ratio as a Screening Test for Primary Aldosteronism: A Systematic Review and Meta-Analysis

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab348 ◽

2021 ◽

Author(s):

Annie Hung ◽

Sumaiya Ahmed ◽

Ankur Gupta ◽

Alexandra Davis ◽

Gregory A Kline ◽

...

Keyword(s):

Sensitivity And Specificity ◽

Primary Aldosteronism ◽

Screening Test ◽

Diagnostic Performance ◽

Clinical Decision Making ◽

Meta Analysis ◽

Risk Of Bias ◽

Reference Standard ◽

Confirmatory Testing ◽

Aldosterone To Renin Ratio

Abstract Context The aldosterone-to-renin ratio (ARR) is the guideline-recommended screening test for primary aldosteronism. However, there is limited data in regard to the diagnostic performance of the ARR. Objective To evaluate the sensitivity and specificity of the ARR as a screening test for primary aldosteronism. Data Sources We searched MEDLINE, Embase, and Cochrane until February 2020. Study Selection Observational studies assessing ARR diagnostic performance as a screening test for primary aldosteronism were selected. To limit verification bias, only studies where dynamic confirmatory testing was implemented as a reference standard regardless of the ARR result were included. Data Extraction Study-level data was extracted and risk of bias and applicability were assessed using the QUADAS-2 tool. Data Synthesis Ten studies, involving a total of 4,110 participants, were included. Potential risk of bias related to patient selection was common and present in half of the included studies. The population base, ARR positivity threshold, laboratory assay, and reference standard for confirmatory testing varied substantially between studies. The reported ARR sensitivity and specificity varied widely with sensitivity ranging from 10-100% and specificity ranging from 70-100%. Notably, four of the ten studies reported an ARR sensitivity of <50% suggesting a limited ability of the ARR to adequately identify patients with primary aldosteronism. Conclusions ARR performance varied widely based on patient population and diagnostic criteria, especially with respect to sensitivity. Therefore, no single ARR threshold for interpretation could be recommended. Limitations in accuracy and reliability of the ARR must be recognized in order to appropriately inform clinical decision-making.

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Prevalence of primary aldosteronism among bulgarian hypertensive patients

Open Medicine ◽

10.2478/s11536-010-0005-x ◽

2010 ◽

Vol 5 (3) ◽

pp. 399-405 ◽

Cited By ~ 1

Author(s):

Joanna Matrozova ◽

Sabina Zacharieva ◽

Georgi Kirilov ◽

Mihail Boyanov

Keyword(s):

Primary Aldosteronism ◽

Final Diagnosis ◽

Hypertensive Patients ◽

Hypertensive Population ◽

Endocrine Hypertension ◽

High Prevalence ◽

Aldosterone Producing Adenoma ◽

Aldosterone To Renin Ratio ◽

Adrenal Ct ◽

Captopril Test

AbstractPrimary aldosteronism (PA) has long been considered a rare disease, but a higher prevalence was suggested recently. The aim of this study was to evaluate the prevalence of PA in a group of Bulgarian hypertensive patients, including patients with adrenal incidentalomas (AI). The aldosterone to renin ratio (ARR)>750 was used as a positive screening test and the Captopril test was performed to confirm the diagnosis. Adrenal CT scan was used to differentiate between the main subtypes of PA- aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA). The diagnosis of APA was retrospectively confirmed after surgery. After excluding other forms of endocrine hypertension, except PA, we investigated a total of 472 consecutive hypertensive patients, among them 96 patients with AI. Final diagnosis of PA was reached in 38 patients (8.05%) in the entire hypertensive population and in 12 patients (12.5%) among hypertensive patients with AI. In the group of PA, 15 patients (39.5%) were diagnosed with APA and 23 patients (60.5%) had an IHA. Among all patients with PA 21 (55.3 %) presented with hypokalemia. Our findings of a relatively high prevalence of PA support an early diagnosis of this potentially curable disease, especially in hypertensive patients with AI.

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