Extending the endocrine hypertension spectrum: novel nonclassic apparent mineralocorticoid excess

Endocrine ◽  
2021 ◽  
Author(s):  
Cristian A. Carvajal ◽  
Alejandra Tapia-Castillo ◽  
Carlos E. Fardella
2019 ◽  
Vol 105 (4) ◽  
pp. e924-e936 ◽  
Author(s):  
Cristian A Carvajal ◽  
Alejandra Tapia-Castillo ◽  
Andrea Vecchiola ◽  
Rene Baudrand ◽  
Carlos E Fardella

Abstract Context Arterial hypertension (AHT) is one of the most frequent pathologies in the general population. Subtypes of essential hypertension characterized by low renin levels allowed the identification of 2 different clinical entities: aldosterone-mediated mineralocorticoid receptor (MR) activation and cortisol-mediated MR activation. Evidence Acquisition This review is based upon a search of Pubmed and Google Scholar databases, up to August 2019, for all publications relating to endocrine hypertension, apparent mineralocorticoid excess (AME) and cortisol (F) to cortisone (E) metabolism. Evidence Synthesis The spectrum of cortisol-mediated MR activation includes the classic AME syndrome to milder (nonclassic) forms of AME, the latter with a much higher prevalence (7.1%) than classic AME but different phenotype and genotype. Nonclassic AME (NC-AME) is mainly related to partial 11βHSD2 deficiency associated with genetic variations and epigenetic modifications (first hit) and potential additive actions of endogenous or exogenous inhibitors (ie, glycyrrhetinic acid-like factors [GALFS]) and other factors (ie, age, high sodium intake) (second hit). Subjects with NC-AME are characterized by a high F/E ratio, low E levels, normal to elevated blood pressure, low plasma renin and increased urinary potassium excretion. NC-AME condition should benefit from low-sodium and potassium diet recommendations and monotherapy with MR antagonists. Conclusion NC-AME has a higher prevalence and a milder phenotypical spectrum than AME. NC-AME etiology is associated to a first hit (gene and epigene level) and an additive second hit. NC-AME subjects are candidates to be treated with MR antagonists aimed to improve blood pressure, end-organ damage, and modulate the renin levels.


2019 ◽  
Author(s):  
Marwa Khiari ◽  
Ibtissem Ben Nacef ◽  
Imene Rojbi ◽  
Karima Khiari ◽  
M Jerbi ◽  
...  

Hypertension ◽  
1996 ◽  
Vol 27 (6) ◽  
pp. 1193-1199 ◽  
Author(s):  
Tomoatsu Mune ◽  
Perrin C. White

2016 ◽  
Vol 175 (1) ◽  
pp. 21-28 ◽  
Author(s):  
Vaios Tsiavos ◽  
Athina Markou ◽  
Labrini Papanastasiou ◽  
Theodora Kounadi ◽  
Ioannis I Androulakis ◽  
...  

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.


1979 ◽  
Vol 49 (5) ◽  
pp. 757-764 ◽  
Author(s):  
STANLEY ULICK ◽  
TOSHIKO KODAMA ◽  
PETER GUNCZIER ◽  
GIOVANNI ZANCONATO ◽  
LEYLA C. RAMIREZ ◽  
...  

1996 ◽  
Vol 85 (1) ◽  
pp. 111-113 ◽  
Author(s):  
J Miiller-Berghaus ◽  
J Homoki ◽  
DV Michalk ◽  
U Querfeld

Author(s):  
Huan-huan Ji ◽  
Xue-wen Tang ◽  
Ni Zhang ◽  
Ben-nian Huo ◽  
Ying Liu ◽  
...  

Objective. We aimed to estimate the risk of varied antifungal therapy with azoles causing the syndrome of acquired apparent mineralocorticoid excess (AME) in the real-world practice. Methods. First, we conducted a disproportionality analysis based on data from the FDA Adverse Event Reporting System (FAERS) database to characterize the signal differences of triazoles - related AME. Second, a systematic review was conducted, and to describe clinical features of AME cases reported in clinical practice. Results. In the FAERS database, we identified 27 cases of triazoles - AME, posaconazole [ROR=865.37; 95%CI (464.14; 1613.45)] and itraconazole [ROR=556.21; 95% (303.05; 1020.85)] significantly increased the risk of AME events, while fluconazole, voriconazole and isavuconazole did not affect any of the mineralocorticoid excess targets. 18 studies with 39 cases raised evidence of AME following posaconazole and itraconazole treatment, and another 27 cases were identified by analysis of the description of clinical features in FAERS database. The average age of 66 patients was 55.5 years (6∼87 years). AME mainly occurs in patients with posaconazole concentrations above 3 μg/mL (mean=4.4μg/mL, range 1.8∼9.5μg/mL), and is less likely to occur when levels are below 2 μg/mL (6%). The median time to event onset was 11.5 weeks, and 50% of the adverse events occurred within 3 months for posaconazole. Conclusion. The presented study supports very recent findings that posaconazole and itraconazole but not the other three azole antifungals investigated are associated with AME and the effects were dose-dependent, which allows for a dose de-escalation strategy and for substitution with fluconazole, isavuconazole or voriconazole to resolve the adverse effects.


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