Clinical, Biochemical, and Genetic Characteristics of “Nonclassic” Apparent Mineralocorticoid Excess Syndrome
Date
2019
Type:
Article
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ORCID:
Journal Title
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Volume Title
Publisher
Oxford University Press
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Abstract
Context
Classical apparent mineralocorticoid excess (AME) is a rare recessive disorder, caused by severe 11β-hydroxysteroid dehydrogenase type 2 enzyme (11β-HSD2) deficiency. AME manifests as low-renin pediatric hypertension, hypokalemia and high cortisol/cortisone (F/E) ratio.
Objective
To evaluate nonclassic AME (NC-AME) due to partial 11β-HSD2 insufficiency and its association with hypertension, mineralocorticoid receptor (MR) activation, and inflammatory parameters.
Design
Cross-sectional study.
Setting
Primary care cohort.
Participants
We recruited 127 adolescents and adults. Subjects with secondary hypertension were excluded. We measured clinical, biochemical, renal, vascular, and inflammatory variables. Sequencing of HSD11B2 gene was performed in all subjects.
Main Outcome Measure
NC-AME.
Results
Serum F/E ratio was positively associated with systolic blood pressure (BP), microalbuminuria, and high-sensitivity C-reactive protein (hs-CRP). Serum cortisone correlated with MR activation parameters even when adjusted for age, body mass index, and sex: lower cortisone with higher potassium excretion (partial r = −0.29, P = 0.002) and with lower plasma renin activity (PRA) (partial r = 0.29, P = 0.001). Consistently, we identified 9 in 127 subjects (7.1%) with high F/E ratios (first quartile) and low cortisone (last quartile), suggestive of NC-AME. These subjects had higher systolic BP, 141.4 ± 25.7 mm Hg vs 127.3 ± 18.1 mm Hg, P = 0.03; lower PRA, 0.36 ± 0.19 ng/L*s vs 0.64 ± 0.47 ng/L*s, P < 0.0001; and greater potassium excretion, microalbuminuria, hs-CRP, and plasminogen activator inhibitor. We only found in 2 out of 9 subjects with NC-AME heterozygous mutations in the HSD11B2 gene.
Conclusions
These findings suggest a spectrum of partial 11β-HSD2 insufficiency in a primary care cohort without the classic phenotype and genotype of AME. NC-AME may represent a phenotype of MR activation and cardiovascular risk, suggesting that these subjects could be treated with MR antagonists.
Description
Centro de Genética y Genómica(CGG)
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Citation
Alejandra Tapia-Castillo, Rene Baudrand, Anand Vaidya, Carmen Campino, Fidel Allende, Carolina Valdivia, Andrea Vecchiola, Carlos F Lagos, Cristóbal A Fuentes, Sandra Solari, Alejandro Martínez-Aguayo, Hernán García, Cristian A Carvajal, Carlos E Fardella, Clinical, Biochemical, and Genetic Characteristics of “Nonclassic” Apparent Mineralocorticoid Excess Syndrome, The Journal of Clinical Endocrinology & Metabolism, Volume 104, Issue 2, February 2019, Pages 595–603, https://doi.org/10.1210/jc.2018-01197
Keywords
Apparent mineralocorticoid excess (AME), Hypertension, Mineralocorticoid receptor (MR), Inflammatory parameter