Clinical, Biochemical, and Genetic Characteristics of "Nonclassic" Apparent Mineralocorticoid Excess Syndrome

Tapia-Castillo A.; Baudrand R.; Vaidya A.; Campino C.; Allende F.; Valdivia C.; Vecchiola A.; Lagos C.F.; Fuentes C.A.; solari s.; Martínez-Aguayo A.; García H.; Carvajal C.A.; Fardella C.E.


Context: Classical apparent mineralocorticoid excess (AME) is a rare recessive disorder, caused by severe 11 beta-hydroxysteroid dehydrogenase type 2 enzyme (11 beta-FISD2) 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 11 beta-FISD2 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 11 beta-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.

Más información

Título según WOS: Clinical, Biochemical, and Genetic Characteristics of "Nonclassic" Apparent Mineralocorticoid Excess Syndrome
Título según SCOPUS: Clinical, Biochemical, and Genetic Characteristics of "nonclassic"" Apparent Mineralocorticoid Excess Syndrome"
Volumen: 104
Número: 2
Fecha de publicación: 2018
Página de inicio: 595
Página final: 603
Idioma: English