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- Title
Clinical, Biochemical, and Genetic Characteristics of "Nonclassic" Apparent Mineralocorticoid Excess Syndrome.
- Authors
Tapia-Castillo, Alejandra; Baudrand, Rene; Vaidya, Anand; Campino, Carmen; Allende, Fidel; Valdivia, Carolina; Vecchiola, Andrea; Lagos, Carlos; Fuentes, Cristóbal; Solari, Sandra; Martínez-Aguayo, Alejandro; García, Hernán; Carvajal, Cristian A; Fardella, Carlos; Lagos, Carlos F; Fuentes, Cristóbal A; Fardella, Carlos E
- Abstract
<bold>Context: </bold>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.<bold>Objective: </bold>To evaluate nonclassic AME (NC-AME) due to partial 11β-HSD2 insufficiency and its association with hypertension, mineralocorticoid receptor (MR) activation, and inflammatory parameters.<bold>Design: </bold>Cross-sectional study.<bold>Setting: </bold>Primary care cohort.<bold>Participants: </bold>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.<bold>Main Outcome Measure: </bold>NC-AME.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Publication
Journal of Clinical Endocrinology & Metabolism, 2018, pN.PAG
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2018-01197