Publications

The Primary Aldosteronism Foundation maintains a list of salient publications. Topics range from pathogenesis to the implications of excess aldosterone. We regularly update the list with new topics, and new articles are added as they become public.

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Abstract/Summary:

Fatty liver disease is one of the most common forms of chronic liver disease. The renin-angiotensin-aldosterone system has been implicated in the pathogenesis of fatty liver. The objective of the study was to determine the relationship between fatty liver and aldosterone in a large cohort study using the original Jackson Heart Study cohort which enrolled African American participants from the Jackson, Mississippi, metropolitan area in Hinds, Madison, and Rankin Counties. The study population consisted of 2507 Jackson Heart Study participants (1625 women and 882 men) who had liver attenuation measured per computed tomography scans, had aldosterone measurements, and were not taking angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or mineralocorticoid receptor antagonists. Univariate regression analysis demonstrated a statistically significant correlation between aldosterone levels and liver attenuation. Each doubling of aldosterone was associated with 1.08 Hounsfield unit decrease (95% confidence interval, 1.47 to −0.69, P < 0.001). A multivariable model adjusted for body mass index, age, alcohol intake, and homeostatic model assessment of insulin resistance determined that the association was statistically significant only for women. Our data demonstrate a positive association between aldosterone levels and fatty liver in African American women.

Authors: Aditi Kumar, Chad Blackshear, Jose S. Subauste, Nazanene H. Esfandiari, Elif Arioglu Oral, Angela R. Subauste
Keywords: fatty liver, African American, women
DOI Number: 10.1210/js.2017-00055
Publication Year: 2017

Abstract/Summary:

Primary aldosteronism (PA) is the most common type of secondary hypertension, and it is associated with a higher rate of cardiovascular complications. KCNJ5 somatic mutations have recently been identified in aldosterone-producing adenoma (APA), however their influence on vascular remodeling and injury is still unclear. The aim of this study was to investigate the association between KCNJ5 somatic mutation status and vascular status. We enrolled 179 APA patients who had undergone adrenalectomy from a prospectively maintained database, of whom 99 had KCNJ5 somatic mutations. Preoperative clinical, biochemical and imaging data of abdominal CT, including abdominal aortic calcification (AAC) score, aortic diameter and wall thickness at levels of superior (SMA) and inferior (IMA) mesenteric arteries were analyzed. After propensity score matching for age, sex, body mass index, triglycerides and low-density lipoprotein, there were 48 patients in each KCNJ5 (+) and KCNJ5 (-) group. Mutation carriers had a lower AAC score (217.3 ± 562.2 vs. 605.6 ± 1359.1, P=0.018), higher aortic wall thickness (SMA level: 2.2 ± 0.6 mm vs. 1.8 ± 0.6 mm, P=0.006; IMA level: 2.4 ± 0.6 mm vs. 1.8 ± 0.7 mm, P<0.001) than non-carriers. In multivariate analysis, KCNJ5 mutations were independently associated with AAC score (P=0.014) and aortic wall thickness (SMA level: P<0.001; IMA level: P=0.004). After adrenalectomy, mutation carriers had less aortic wall thickness progression than non-carriers (Δthickness SMA: -0.1 ± 0.8 mm vs. 0.9 ± 0.6 mm, P=0.024; IMA: -0.1 ± 0.6 mm vs. 0.8 ± 0.7 mm, P=0.04). KCNJ5 mutation carriers had less calcification burden of the aorta, thickened aortic wall, and less wall thickness progression than non-carriers.

Authors: Bo-Ching Lee, Victor Jing-Wei Kang, Chien-Ting Pan, Jia-Zheng Huang, Yu-Li Lin, Yi-Yao Chang, Cheng-Hsuan Tsai, Chia-Hung Chou, Zheng-Wei Chen, Che-Wei Liao, Yu-Wei Chiu, Vin-Cent Wu, Chi-Sheng Hung, Chin-Chen Chang, Yen-Hung Lin
Keywords: KCNJ5, mutation, aldosterone-producing adenoma, APA, aortic wall
DOI Number: 10.3389/fendo.2022.830130
Publication Year: 2022

Abstract/Summary:

Primary aldosteronism (PA) is the most common and potentially curable endocrine cause of secondary hypertension, and carries a worse prognosis than essential hypertension. Despite the high prevalence of hypertension in patients with chronic kidney disease (CKD), the screening rates for primary aldosteronism in CKD are unknown. In this study, we retrospectively reviewed medical records of 1627 adults who presented to the nephrology clinics of 2 tertiary hospitals in Melbourne, Australia, between 2014 and 2019. In addition to assessing the pattern of screening, we also evaluated patient-specific factors associated with the decision to test for primary aldosteronism. Patients were excluded from the final analysis if they did not have CKD, had an organ transplant, had end stage renal failure, or had insufficient data or follow-up. Of the 600 patients included in the analysis, 234 (39%) had an indication for screening for primary aldosteronism based on recommendations made by the Endocrine Society. However, only 33 (14%) were tested. They were younger, had a higher mean systolic blood pressure, better renal function, and lower mean serum potassium than those who were indicated but not screened. Of the 33 screened patients, an elevated aldosterone-to-renin ratio was noted in 8 patients and a diagnosis of primary aldosteronism was made in 4 patients. The screening rate for primary aldosteronism is low in a CKD population, especially in patients who are older, have a lower eGFR and normal serum potassium. The consequences of undiagnosed primary aldosteronism in this select population may be substantial due to the cardiovascular and renal sequelae associated with untreated disease.

Authors: Karanjeet Chauhan, Eitan Schachna, Renata Libianto, Jessica Ryan, Holly Hutton, Peter J. Fuller, Scott Wilson, Peter G. Kerr, Jun Yang
Keywords: chronic kidney disease
DOI Number: 10.1007/s40620-022-01267-3
Publication Year: 2022

Abstract/Summary:

Primary aldosteronism is one of the most frequent causes of secondary arterial hypertension, and whether primary aldosteronism is associated with masked hypertension is unknown. We describe a 64-year-old man with a history of hypothyroidism, recurring hypokalemia, and normal home and office blood pressure values. Ambulatory blood pressure monitoring revealed masked hypertension with strikingly high systolic blood pressure variability and typical hypertension-mediated organ damage. The patient required gradual escalation of antihypertensive medication to four drugs. During the diagnostic process we identified primary aldosteronism, cobalamin deficiency, severe obstructive sleep apnea, and low baroreflex sensitivity (1.63 ms/mmHg). Following unilateral adrenalectomy, cobalamin supplementation and continuous positive airway pressure, we observed a spectacular improvement in the patient’s blood pressure control, baroreflex sensitivity (4.82 ms/mmHg) and quality of life. We report an unusual case of both masked arterial hypertension and primary aldosteronism. Elevated blood pressure values were masked in home and office measurements by coexisting hypotension which resulted most probably from deteriorated baroreflex sensitivity. Baroreflex sensitivity increased following treatment, including unilateral adrenalectomy. Hypertension can be masked by coexisting baroreceptor dysfunction which may derive from structural but also functional reversible changes.

Authors: Joanna Kanarek-Kucner, Beata Graff, Vlasta Bari, Rufus Barraclough, Krzysztof Narkiewicz, Michał Hoffmann
Keywords: masked hypertension, baroreceptor dysfunction
DOI Number: 10.1080/08037051.2021.2003699
Publication Year: 2021

Abstract/Summary:

The goal of the study was to assess the identification of primary aldosteronism (PA) in newly diagnosed, treatment-naïve patients with hypertension by screening in primary care. General practices were surveyed in the South Eastern Melbourne Primary Health Network with at least three general practitioners and general practices elsewhere in Victoria that had referred patients to the Endocrine Hypertension Clinic at Monash Health, 2017‒2020. Participants included adults (18–80 years) with newly diagnosed hypertension (measurements of systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg on at least two occasions) and not taking antihypertensive medications were screened for PA by assessing their aldosterone-to-renin ratio (ARR). Participants with two ARR values exceeding 70 pmol/mU underwent saline suppression testing at the Endocrine Hypertension Service (Monash Health) to confirm the diagnosis of PA. Sixty-two of 247 screened participants had elevated ARR values on screening (25%); for 35 people (14%; 95% CI, 10–19%), PA was confirmed by saline suppression testing. Baseline characteristics (mean age, sex distribution, median baseline blood pressure levels, and serum potassium concentration) were similar for people with or without PA. PA was diagnosed in 14% of patients with newly diagnosed hypertension screened by GPs, indicating a potential role for GPs in the early detection of an important form of secondary hypertension for which specific therapies are available.

Authors: Renata Libianto, Grant M Russell, Michael Stowasser, Stella M Gwini, Peta Nuttall, Jimmy Shen, Morag J Young, Peter J Fuller, Jun Yang
Keywords: primary care, screening
DOI Number: 10.5694/mja2.51438
Publication Year: 2022

Abstract/Summary:

The goal of the study was to review the validity and applicability of clinical guidelines on the management of primary aldosteronism and to list their discrepancies to allow health-care providers and guideline developers to make informed decisions. Primary aldosteronism management guidelines, including specialist, subgroup, general guidelines written in English, were obtained from electronic databases. Appraisers independently extracted the data, and used the Appraisal Guidelines Research and Evaluation II (AGREE-II) tool and the Institute of Medicine (IOM) criteria to independently evaluate the methodological quality of the guidelines. Then, the appraisers used the Guideline Implementability Appraisal (GLIA) tool to assess the implementation of the guidelines that complied with AGREE-II and IOM. In addition, we further compared the discrepancies in the primary aldosteronism management recommendations. We have identified 12 guidelines published between 2006 and 2016. Only the Endocrine Society and the Canadian Hypertension Education Program guidelines of them were of good methodological quality according the AGREE-II and IOM instrument, but with still much room for improvement. Neither of these two was rated as easily implementable according to the GLIA tool. Discrepant recommendations were identified at all management steps (screening, confirmation, classification, treatment and follow-up). The guidelines quality was mostly poor, and the higher quality guidelines also needed improvement prior to their implementation. Meanwhile, significant differences existed in the recommendation for the same clinical problem. Therefore, future guideline development should be performed in strict accordance with the AGREE-II, IOM and GLIA criteria to improve the diagnosis and treatment of primary aldosteronism.

Authors: Wu Jueli, Tian Wenqing, Zhang Lu, Zhang Jiao, Zhou Bo
Keywords: guidelines
DOI Number: 10.1097/HJH.0000000000002046
Publication Year: 2019

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Primary Aldosteronism Foundation

The Primary Aldosteronism Foundation is a registered 501(c)(3) public charity. Donations are tax deductible in the US.

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