Clinical and Hormonal Profiles Correlate With Molecular Characteristics in Patients With 11 beta-Hydroxylase Deficiency

Background Given the rarity of 11 beta-hydroxylase deficiency (11 beta OHD), there is a paucity of data about the differences in clinical and biochemical characteristics of classic (C-11 beta OHD) and nonclassic 11 beta OHD (NC-11 beta OHD). Objective To characterize a multicenter pediatric cohort with 11 beta OHD. 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-11 beta OHD, n = 92; NC-11 beta OHD, 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-11 beta OHD girls had ambiguous genitalia (C-11 beta OHD 100%), and none of the NC-11 beta OHD patients were hypertensive (C-11 beta OHD 50%). Compared to NC-11 beta OHD, C-11 beta OHD 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-11 beta OHD. 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-11 beta OHD than NC-11 beta OHD patients (P < 0.05). The 11-deoxycortisol/cortisol ratio >2.2, <1.5, and <0.1 had 100% specificity to segregate C-11 beta OHD, NC-11 beta OHD, and control groups. Conclusion NC-11 beta OHD can escape from clinical attention due to relatively mild clinical presentation. However, steroid profiles enable the diagnosis, differential diagnosis, and subtyping of 11 beta OHD.

Automated summary

This study characterized a multicenter pediatric cohort with 11 beta-hydroxylase deficiency (11 beta OHD) and found that nonclassic 11 beta OHD (NC-11 beta OHD) may escape clinical attention due to relatively mild clinical presentation. However, steroid profiles enable the diagnosis, differential diagnosis, and subtyping of 11 beta OHD.