Journal Article

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

Falhammar, Henrik, Cayir, Atilla, Catli, Gonul, Unal, Edip, Abali, Zehra Yavas, Ozbek, Mehmet Nuri, Haklar, Goncagul, Guran, Tulay, Demirbilek, Huseyin, Baris, Tugba, Isik, Emregul, Yaman, Ali, Darendeliler, Feyza, Keskin, Mehmet, Onal, Hasan, Buyukinan, Muammer, Cetin, Tugba, Kara, Cengiz, Ucakturk, Seyit Ahmet, Anik, Ahmet, Bas, Firdevs, Storbeck, Karl-Heinz, Bereket, Abdullah, Yildiz, Melek, Dursun, Fatma, Turan, Serap

2021

Overview

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 nonclassic 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 [−1.85 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. 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.

• Publisher: Oxford University Press
• Subject: Adrenocorticotropic hormone / Androgens / Androstenedione / Biochemical characteristics / Body height / Corticosterone / Cortisol / Differential diagnosis / Hormones / Hydroxylase / Liquid chromatography / Mass spectroscopy / Patients / Pediatrics / Steroid 11β-hydroxylase / Steroid hormones