Department of Endocrinology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
Center for Genetics and Genomics, School of Medicine, Clínica Alemana-Universidad del Desarrollo, Lo Barnechea, Chile.
J Clin Endocrinol Metab. 2019 Feb 1;104(2):595-603. doi: 10.1210/jc.2018-01197.
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.
To evaluate nonclassic AME (NC-AME) due to partial 11β-HSD2 insufficiency and its association with hypertension, mineralocorticoid receptor (MR) activation, and inflammatory parameters.
Cross-sectional study.
Primary care cohort.
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.
NC-AME.
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/Ls vs 0.64 ± 0.47 ng/Ls, 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.
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.
经典显性醛固酮过多症（AME）是一种罕见的隐性疾病，由严重的 11β-羟化类固醇脱氢酶 2 型（11β-HSD2）缺乏引起。AME 表现为低肾素性儿科高血压、低钾血症和高皮质醇/皮质酮（F/E）比值。
评估由于部分 11β-HSD2 不足引起的非典型 AME（NC-AME）及其与高血压、盐皮质激素受体（MR）激活和炎症参数的关系。
横断面研究。
初级保健队列。
我们招募了 127 名青少年和成年人。排除了继发性高血压患者。我们测量了临床、生化、肾脏、血管和炎症变量。对所有受试者进行 HSD11B2 基因测序。
NC-AME。
血清 F/E 比值与收缩压（BP）、微量白蛋白尿和高敏 C 反应蛋白（hs-CRP）呈正相关。血清皮质酮与 MR 激活参数相关，即使在调整年龄、体重指数和性别后也是如此：皮质酮较低与钾排泄量较高（部分 r = -0.29，P = 0.002）和血浆肾素活性（PRA）较低（部分 r = 0.29，P = 0.001）相关。同样，我们在 127 名受试者中有 9 名（7.1%）发现 F/E 比值较高（第一四分位数）和皮质酮较低（最后四分位数），提示 NC-AME。这些受试者的收缩压较高，为 141.4±25.7mmHg 比 127.3±18.1mmHg，P=0.03；PRA 较低，为 0.36±0.19ng/Ls 比 0.64±0.47ng/Ls，P<0.0001；钾排泄量、微量白蛋白尿、hs-CRP 和纤溶酶原激活物抑制剂较高。我们只在 9 名 NC-AME 患者中发现了 HSD11B2 基因的杂合突变。
这些发现提示在初级保健队列中存在 11β-HSD2 部分不足的谱，其表型和基因型均不典型 AME。NC-AME 可能代表 MR 激活和心血管风险的表型，提示这些患者可使用 MR 拮抗剂治疗。
