Department of Pediatric Endocrinology, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey.
Department of Pediatric Endocrinology and Diabetes, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey.
J Clin Endocrinol Metab. 2021 Aug 18;106(9):e3714-e3724. doi: 10.1210/clinem/dgab225.
Given the rarity of 11β-hydroxylase deficiency (11βOHD), there is a paucity of data about the differences in clinical and biochemical characteristics of classic (C-11βOHD) and nonclassic 11βOHD (NC-11βOHD).
To characterize a multicenter pediatric cohort with 11βOHD.
The clinical and biochemical characteristics were retrospectively retrieved. CYP11B1 gene sequencing was performed. Seventeen plasma steroids were quantified by liquid chromatography-mass spectrometry and compared to that of controls.
102 patients (C-11βOHD, n = 92; NC-11βOHD, n = 10) from 76 families (46,XX; n = 53) had biallelic CYP11B1 mutations (novel 9 out of 30). Five 46,XX patients (10%) were raised as males. Nineteen patients (19%) had initially been misdiagnosed with 21-hydroxylase deficiency. Female adult height was 152 cm [-1.85 SD score (SDS)] and male 160.4 cm (-2.56 SDS).None of the NC-11βOHD girls had ambiguous genitalia (C-11βOHD 100%), and none of the NC-11βOHD patients were hypertensive (C-11βOHD 50%). Compared to NC-11βOHD, C-11βOHD patients were diagnosed earlier (1.33 vs 6.9 years; P < 0.0001), had higher bone age-to-chronological age (P = 0.04) and lower adult height (-2.46 vs -1.32 SDS; P = 0.05). The concentrations of 11-oxygenated androgens and 21-deoxycortisol were low in all patients. The baseline ACTH and stimulated cortisol were normal in NC-11βOHD. Baseline cortisol; cortisone; 11-deoxycortisol; 11-deoxycorticosterone and corticosterone concentrations; and 11-deoxycortisol/cortisol, 11-deoxycorticosterone/cortisol, and androstenedione/cortisol ratios were higher in C-11βOHD than NC-11βOHD patients (P < 0.05). The 11-deoxycortisol/cortisol ratio >2.2, <1.5, and <0.1 had 100% specificity to segregate C-11βOHD, NC-11βOHD, and control groups.
NC-11βOHD can escape from clinical attention due to relatively mild clinical presentation. However, steroid profiles enable the diagnosis, differential diagnosis, and subtyping of 11βOHD.
由于 11β-羟化酶缺乏症（11βOHD）罕见，关于经典（C-11βOHD）和非经典 11βOHD（NC-11βOHD）的临床和生化特征差异的数据很少。
描述一个多中心儿科 11βOHD 患者队列。
回顾性检索临床和生化特征。进行 CYP11B1 基因测序。通过液相色谱-质谱法对 17 种血浆类固醇进行定量，并与对照组进行比较。
来自 76 个家庭（46,XX；n=53）的 102 例患者（C-11βOHD，n=92；NC-11βOHD，n=10）存在双等位基因 CYP11B1 突变（30 个中有 9 个为新突变）。5 名 46,XX 患者（10%）被当作男性抚养长大。19 名患者（19%）最初被误诊为 21-羟化酶缺乏症。女性成年身高为 152cm（-1.85 SDS），男性为 160.4cm（-2.56 SDS）。没有 NC-11βOHD 女孩出现生殖器模糊（C-11βOHD 为 100%），也没有 NC-11βOHD 患者出现高血压（C-11βOHD 为 50%）。与 NC-11βOHD 相比，C-11βOHD 患者的诊断时间更早（1.33 岁 vs 6.9 岁；P<0.0001），骨龄与实际年龄的差值更大（P=0.04），成年身高更低（-2.46 vs -1.32 SDS；P=0.05）。所有患者的 11-氧代雄激素和 21-脱氧皮质醇浓度均较低。NC-11βOHD 患者的基础 ACTH 和刺激皮质醇正常。C-11βOHD 患者的基础皮质醇；皮质酮；11-脱氧皮质醇；11-脱氧皮质酮和皮质醇浓度；11-脱氧皮质醇/皮质醇、11-脱氧皮质酮/皮质醇和雄烯二酮/皮质醇比值均高于 NC-11βOHD 患者（P<0.05）。11-脱氧皮质醇/皮质醇比值>2.2、<1.5 和<0.1 对 C-11βOHD、NC-11βOHD 和对照组具有 100%的特异性。
由于临床表现相对较轻，NC-11βOHD 可能会被临床忽视。然而，类固醇谱能够对 11βOHD 进行诊断、鉴别诊断和亚型分类。
