Suspicion Of Primary Aldosteronism Research Articles

Aldosterone-to-renin ratio is related to arterial stiffness when the screening criteria of primary aldosteronism are not met

Aldosterone-to-renin ratio (ARR) is a screening tool for primary aldosteronism (PA), but the significance of ARR when the PA criteria are not met remains largely unknown. In this cross-sectional study we investigated the association of ARR with haemodynamic variables in 545 normotensive and never-medicated hypertensive subjects (267 men, 278 women, age range 19–72 years) without suspicion of PA. Supine haemodynamic data was recorded using whole-body impedance cardiography and radial tonometric pulse wave analysis. In sex-adjusted quartiles of ARR, determined as serum aldosterone to plasma renin activity ratio, the mean values were 282, 504, 744 and 1467 pmol/µg of angiotensin I/h, respectively. The only difference in haemodynamic variables between the ARR quartiles was higher pulse wave velocity (PWV) in the highest quartile versus other quartiles (p = 0.004), while no differences in blood pressure (BP), heart rate, wave reflections, cardiac output or systemic vascular resistance were observed between the quartiles. In linear regression analysis with stepwise elimination, ARR was an independent explanatory factor for PWV (β = 0.146, p < 0.001, R2 of the model 0.634). In conclusion, ARR was directly and independently associated with large arterial stiffness in individuals without clinical suspicion of PA. Therefore, ARR could serve as a clinical marker of cardiovascular risk.Trial registration: ClinicalTrails.gov: NCT01742702.

Abstract P232: Dilated Cardiomyopathy With Electrocardiographic Changes And Coronary-Pulmonary Fistula: An Uncommon Presentation Of Primary Aldosteronism In The Covid-19 Era

Primary aldosteronism is the most frequent forms of curable hypertension and elevated aldosterone levels have been associated with endothelial proliferation and pathological remodeling of the heart and arteries; however, coronary arterial abnormalities have never been reported in patients with primary aldosteronism. We report the case of a 53-year-old Caucasian obese man (BMI 37 Kg/m 2 ) with recent history of hypertension, fatigue and subjective dyspnea who was admitted to our hospital after performing an outpatient echocardiography that showed hypertensive and ischemic heart disease in dilated phase (LVEDVI 95 mL/m 2 ; LVEF 43%). His laboratory results showed hypokalemia (3 mmol/L) and an elevated aldosterone-renin ratio [(294 ng/L)/(1μU/mL)]. After case confirmation with saline infusion test, the abdominal CT scan showed a subcentimeter adenoma in the right adrenal gland. Surprisingly we noticed that, after oral potassium correction, the electrocardiogram revealed a symmetrical T-wave inversion and subsequently a coronary angiography detected a coronary artery fistula between the left anterior descending artery and the pulmonary artery in the absence of significant stenosis. In the Italy's CoViD-19 pandemic full spread, we preferred to postpone the diagnosis of the lateralization of aldosterone hypersecretion by adrenal vein sampling and we started a mineralocorticoid receptor antagonist with a clinical follow-up of cardiovascular symptoms for the optimal treatment of coronary artery fistula. After about two months of follow-up, the patient remains asymptomatic with good blood pressure control, normal potassium levels and significant echocardiographic improvement (LVEDVI 67 mL/m 2 ; LVEF 51%). Our case highlights a possible association between hypertensive patients with coronary artery fistulas and primary aldosteronism. We recommend cardiologists and clinicians to maintain a high level of suspicion of primary aldosteronism in these patients.

A prediction model for primary aldosteronism when the salt loading test is inconclusive.

ObjectiveTo develop a prediction model to confirm or exclude primary aldosteronism (PA) in patients with an inconclusive salt loading test (SLT).ContextDiagnosis in patients with a suspicion of PA can be confirmed using an SLT. In case of inconclusive test results the decision about how to manage the patient is usually based on contextual clinical data.DesignWe included a retrospective cohort of 276 patients in the final analysis.MethodsAll patients underwent an SLT between 2005 and 2016 in our university medical center. The SLT was inconclusive (post-infusion aldosterone levels 140–280 pmol/L) in 115 patients. An expert panel then used contextual clinical data to diagnose PA in 45 of them. Together with 101 patients with a positive SLT this resulted in a total of 146 patients with PA. A total of 11 variables were used in a multivariable logistic regression analysis. We assessed internal validity by bootstrapping techniques.ResultsThe following variables were independently associated with PA: more intense potassium supplementation, lower plasma potassium concentration, lower plasma renin concentration before SLT and higher plasma aldosterone concentration after SLT. The resulting prediction model had a sensitivity of 84.4% and a specificity of 94.3% in patients with an inconclusive SLT. The positive and negative predictive values were 90.5 and 90.4%, respectively.ConclusionsWe developed a prediction model for the diagnosis of PA in patients with an inconclusive SLT that results in a diagnosis that was in high agreement with that of an expert panel.

Case detection and diagnosis of primary aldosteronism - The consensus of Taiwan Society of Aldosteronism.

Even though the increasing clinical recognition of primary aldosteronism (PA) as a public health issue, its heightened risk profiles and the availability of targeted surgical/medical treatment being more understood, consensus in its diagnosis and management based on medical evidence, while recognizing the constraints of our real-world clinical practice in Taiwan, has not been reached. The Taiwan Society of Aldosteronism (TSA) Task Force acknowledges the above-mentioned issues and reached this Taiwan PA consensus at its inaugural meeting, in order to provide updated information of internationally acceptable standards, and also to incorporate our local disease characteristics into the management of PA. When there is suspicion of PA, a plasma aldosterone to renin ratio (ARR) should be obtained initially. Patients with abnormal ARR will undergo confirmatory laboratory and image tests. Subtype classification with adrenal venous sampling (AVS) or NP-59 nuclear imaging, if AVS not available, to lateralize PA is recommended when patients are considered for adrenalectomy. The strengths and weaknesses of the currently available identification methods are discussed, focusing especially on result interpretation. With this consensus we hope to raise more awareness of PA among medical professionals and hypertensive patients in Taiwan, and to facilitate reconciliation of better detection, identification and treatment of patients with PA.

Primary Aldosteronism in a Patient Who Exhibited Heart Failure

Primary aldosteronism (PA) is a common cause of secondary hypertension due to unilateral adrenocortical adenoma (APA) or idiopathic hyperplasia. There is increased awareness of the possible cardiac sequelae of aldosterone excess, including cardiac hypertrophy, fibrosis, and vascular endothelium injury. A 54-year-old woman was referred for rest and nighttime worsening dyspnea and palpitations. One year earlier she was admitted to another hospital with the same symptoms and discharged with a diagnosis of idiopathic dilated cardiomiopathy. At admission, physical examination revealed a body mass index of 21 kg ⁄m and blood pressure (BP) of 210 ⁄105 mm Hg. Chest auscultation revealed mild expiratory wheezes and rales in both lower lobes. Electrocardiography showed signs of left ventricular (LV) overloading and hypertrophy. Laboratory analysis showed severe hypokalemia (1.8 mEq ⁄L; normal range 3.5–5 mEq ⁄L) and metabolic alkalosis (pH 7.51; partial pressure of carbon dioxide 41 mm Hg; partial pressure of oxygen 86 mm Hg; HCO 3 32.6 mmol ⁄L; excess bases 10 mmol ⁄L) (Table I). Chest radiography revealed an enlarged cardiac silhouette, congested pulmonary hilum, and bilateral pleural effusion (Figure 1A). Echocardiography showed an increase in LV end-diastolic diameter (58 mm) and left atrial volume (46 mm) and a signficant decrease in global LV performance (ejection fraction [EF] 30%) (Table II). The 24hour ambulatory BP monitoring (ABPM) revealed severe systo-diastolic hypertension without physiological nocturnal fall (nondipper pattern). Subsequent investigation showed suppressed plasma renin activity (PRA) (0.08 ng ⁄mL ⁄h; normal range 0.2–2.7 ng ⁄mL ⁄h), high plasma aldosterone (PAC 16.17 ng ⁄dL; normal range 7.5–15 ng ⁄dL), and PAC ⁄ PRA ratio (202.17 ng ⁄dL: ng ⁄ml ⁄h; normal value<30 ng ⁄dL: ng ⁄mL ⁄h). Because of suspicion of PA, we performed a captopril test. After 60 minutes of captopril 50 mg, the PAC ⁄PRA ratio was still elevated (529.93 ng ⁄dL: ng ⁄mL ⁄h). Magnetic resonance imaging of the superior abdomen demonstrated a 20-mm nodule in the left adrenal gland (Figure 2). The patient underwent laparoscopy adrenalectomy, and histopathology revealed an APA. Subsequently, her BP was normalized at 140 ⁄90 mm Hg with amlodipine, ramipril, and serum potassium. After 6 months of follow-up, BP was 110 ⁄80 mm Hg, with normal serum potassium. Chest radiography showed resolution of congestive heart pulmonary imaging with a decreased cardiac silhouette (Figure 1B). Repeat echocardiography demonstrated a significant improvement in LV hypertrophy and EF (50%). Recently, the Primary Aldosteronism Prevalence in Italy Study (PAPY) reported a PA prevalence of 11.2% in patients with new-onset hypertension. The potential comorbidity and prevention of excessive cardiovascular events and organ damage led to development of accurate strategies for diagnosis of PA. PA patients display an unfavorable cardiovascular profile, suggesting a role of aldosterone beyond its well-known hypertensive effects. TABLE I. Laboratory Data and Blood Gas Analysis

Significance of Adrenocorticotropin Stimulation Test in the Diagnosis of an Aldosterone-Producing Adenoma

Adrenal venous sampling is the "gold standard" test in the diagnosis of an aldosterone-producing adenoma (APA) among patients with primary aldosteronism (PA) but is available only in specialized medical centers. Meanwhile, an APA is reported to be generally more sensitive to ACTH than idiopathic hyperaldosteronism. The aim was to evaluate the diagnostic accuracy of the ACTH stimulation test in the diagnosis of an APA among those with suspicion of PA. Fifty-nine patients admitted to Kyoto University Hospital on suspicion of PA were included in the study. ACTH stimulation tests with 1-mg dexamethasone suppression were performed. Plasma aldosterone concentrations (PAC) were examined every 30 min after ACTH stimulation. Receiver-operated characteristics curve analysis was used to evaluate the diagnostic accuracy. PAC after ACTH stimulations were significantly higher in patients with an APA than in patients with idiopathic hyperaldosteronism or non-PA. Receiver-operated characteristics curve analyses showed that the PAC after ACTH stimulation was effective for the diagnosis of an APA among patients suspected of PA. The diagnostic accuracy was highest at 90 min after ACTH injection, with the optimal cutoff value greater than 37.9 ng/dl corresponding with sensitivity and specificity of 91.3 and 80.6% for the diagnosis of an APA. Our study indicates that the ACTH stimulation test is useful in the diagnosis of an APA among patients suspected of PA. This test can be used to select patients who are highly suspected of an APA and definitely require adrenal venous sampling.

LEVELS OF THE CORTISOL, CORTISONE AND THEIR METABOLITES AS A MARKERS OF APPARENT MINERALOCORTICOID EXCESS (AME) – CASE PRESENTATION: PP.18.200

Among the causes of secondary hypertension are a group of disorders with a Mendelian inheritance pattern. Apparent mineralocorticoid excess (AME) is an autosomal recessive disease caused by deficiency of the enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2). 11beta-HSD2 is responsible for conversion of cortisol (F) to inactive cortisone (E). In AME deficiency of 11beta-HSD2 allows the unmetabolized cortisol to bind to the mineralocorticoid receptor inducing sodium retention, hypokalemia, suppression of plasma renin activity (PRA) and hypertension. F and E are metabolized in the liver - the reaction is catalyzed by alfa-reductase obtaining allo-tetrahydrocortisol (allo-THF) and allo-tetrahydrocortisone (allo-THE). For beta-reductase followed the products are: tetrahydrocortisol (THF) and tetrahydrocortisone (THE). The balance between 11beta-HSD1 and 11beta-HSD2 activity can be demonstrated by measuring the ratio of reduced metabolites of F and E in urine as well as by determining of urinary free cortisol (UFF) and cortisone (UFE). Plasma F/E ratio is another valuable parameter in estimation of the coordinated activity of two isoforms of 11beta-hydroxysteroid dehydrogenase. Case presentation: 67 years old white men with the five years history of hypertension was admitted to the hospital with the suspicion of primary aldosteronism. Lab tests: unprovoked low plasma potassium (3.3 mmol/l), decreased serum aldosterone level (11.64 pg/ml) and normal PRA (1.30 ng/ml/h). Left ventricular hypertrophy was found in echocardiography, but in ultrasound suprarenal glands were normal. F, E and their metabolites, after extraction from human plasma and urine and after pre-column derivatization, were determined using high performance liquid chromatography methods. The following results were obtain: serum F/E - 13.12; UFF/UFE in urine – 1.48; (THF+allo-THF)/(THE+allo-THE) in urine - 1,70. Patient's hormone levels were significantly different in compare with levels obtain in control group (healthy volunteers, n = 14) – 3.97 ± 1.43; 0.42 ± 0.16 and 0.79 ± 0.19 respectively. The presented data show the screening tool in the assessment of abnormalities of 11beta-hydroxysteroid dehydrogenase activity, but the final diagnosis should be confirm by molecular analysis of the gene.

Screening and diagnosis of primary aldosteronism

Primary aldosteronism (PA) is the most common cause of mineralocorticoid hypertension. Different studies using the plasma aldosterone concentration (PAC)–plasma renin activity ratio (ARR ratio) for the screening of patients with hypertension, have shown a marked increase in the detection rate of PA. PA is commonly caused by an adrenal adenoma (APA) or idiopathic bilateral adrenal hyperplasia of the adrenal zona glomerulosa (IHA) and, in rare cases, by the inherited condition of glucocorticoid-remediable aldosteronism (GRA). The early diagnosis of PA is important, not only because the forms caused by adrenal adenoma are surgically curable, but also because correlation between the duration of PA and the development of cardiovascular complications has been reported. Patients with resistant and/or severe hypertension, patients with hypokalemia, those with a family history of hypertension and stroke at an early age, or patients with an adrenal incidentaloma should be screened for PA using the ARR ratio. Suspicion of PA owing to a pathological ratio requires confirmatory testing, including fludrocortisone suppression test, saline infusion and captopril challenge. Adrenal gland imaging is important in subtype differentiation (APA vs IHA), but adrenal venous sampling is the gold standard and should be used when other tests prove inconclusive. Genetic testing has facilitated detection of GRA.

Screening for primary aldosteronism

Normokalaemic manifestation of primary aldosteronism is a frequent cause of secondary hypertension. It occurs in approximately 5-12% of all patients with hypertension, primarily patients with severe and uncontrolled blood pressure. Main causes are bilateral adrenal hyperplasia (2/3 of cases) and aldosterone-producing adenoma (1/3 of cases). Screening is performed by measurement of the aldosterone/renin ratio, which is raised in affected patients. Suspicion of primary aldosteronism due to a pathological ratio requires confirmatory testing e.g. by saline infusion test or fludrocortisone suppression test. If the diagnosis is confirmed, the underlying cause of aldosterone excess needs to be identified because therapy differs. First, adrenal imaging (CT/MRI) is performed, which is followed by postural testing in cases with a unilateral lesion. Concordant results confirm the diagnosis of an aldosterone-producing adenoma and allow treatment to proceed to adrenalectomy. In cases of equivocal results or normal/bilaterally enlarged adrenal glands on imaging, adrenal venous sampling must be performed for subtype differentiation.

Gammagrafía suprarrenal cortical con frenación y supresión de la frenación con dexametasona en el estudio del hiperaldosteronismo primario

To evaluate the diagnostic performance and efficacy of adrenal scintigraphy in primary aldosteronism following the protocol that combines adrenal suppression scintigraphy plus non-suppression study. 20 patients referred to our service with the suspicion of primary aldosteronism were studied by combined scintigraphy. Thirteen men and 7 women, mean age of 52 years, aged from 31 to 73 years, were included. Uptake of free iodine by the thyroid was inhibited by oral Lugol 5 % administration. Dexamethasone 4 mg per day was administered from day 7 to the third day of detection, when administration was stopped. Adrenal scintigraphy was performed after intravenous injection of I-131-norcolesterol (37 MBq). Images were taken at 24 and/or 48 hours and on the third day. Afterwards, dexamethasone administration was stopped and late images on 5th and/or 7th days were obtained. The scintigraphic result was confirmed with the final clinical evaluation (FCE) of the patient. 11 patients presented pathological studies, 9 adenomas (8TP + 1FP) and 2 bilateral adrenal hyperplasia (2TP); 7 normal scintigraphies (6TN and 1 non-conclusive FCE) and 2 non-conclusive scintigraphies (1 incidentaloma and 1 non-conclusive FCE). Normal adrenal glands were visualized in all cases on the 5th and/or 7th day scintigraphy. The study of adrenal functionalism by the combined protocol of adrenal suppression study plus later non-suppression study made it possible to identify with high precision primary aldosteronism and to confirm the function of normal adrenal glands.

Plasma aldosterone-plasma renin activity ratio. A simple test to identify patients with primary aldosteronism.

Thirty-two patients with hypertension and recurrent hypokalaemia were investigated on the suspicion of primary aldosteronism. On the basis of unsuppressible aldosterone secretion upon oral mineralocorticoid administration in 16 patients, a surgical exploration was made revealing a typical aldosteronoma in 12 of them, macronodular hyperplasia in two, micronodular hyperplasia in one, and micronodular hyperplasia together with a phaeochromocytoma in one patient. The remaining 16 patients with normal aldosterone suppressibility were considered to have primary hypertension. The discriminatory power of various biochemical tests related to the renin-angiotensin-aldosterone axis was analyzed in retrospect. The only parameter allowing a separation of patients with biochemically and surgically confirmed primary aldosteronism from the other group was the plasma aldosterone-plasma renin activity ratio. The present study therefore confirms the diagnostic value of this ratio for identifying patients with primary aldosteronism.