Abstract
Background
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 non-classic 11βOHD (NC-11βOHD).
Objective
To characterize a multicenter pediatric cohort with 11βOHD.
Method
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.
Results
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 (-1.85SDS) and male 160.4 cm (-2.56SDS).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. -1.32SDS, 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.
Conclusion
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.