Melek Yildiz1,2, Emregul Isik3, Zehra Yavas Abali4, Mehmet Keskin5, Mehmet Nuri Ozbek6, Firdevs Bas2, Seyit Ahmet Ucakturk7, Muammer Buyukinan8, Hasan Onal1, Cengiz Kara9, Karl-Heinz Storbeck10, Feyza Darendeliler2, Atilla Cayir11, Edip Unal6, Ahmet Anik12, Huseyin Demirbilek13, Tugba Cetin14, Fatma Dursun15, Gonul Catli16, Serap Turan4, Henrik Falhammar17, Tugba Baris18, Ali Yaman19, Goncagul Haklar19, Abdullah Bereket4, Tulay Guran4. 1. Department of Pediatric Endocrinology, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey. 2. Department of Pediatric Endocrinology and Diabetes, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey. 3. Clinics of Pediatric Endocrinology, Gaziantep Children's Hospital, Gaziantep, Turkey. 4. Department of Pediatric Endocrinology and Diabetes, Marmara University, Faculty of Medicine, Istanbul, Turkey. 5. Department of Pediatric Endocrinology and Diabetes, Gaziantep University, School of Medicine, Gaziantep, Turkey. 6. Department of Pediatric Endocrinology and Diabetes, SBU Diyarbakir Gazi Yasargil Education and Research Hospital, Diyarbakir, Turkey. 7. Department of Pediatric Endocrinology, Ankara City Hospital, Children's Hospital, Ankara, Turkey. 8. Department of Pediatric Endocrinology, Konya Training and Research Hospital, Konya, Turkey. 9. Department of Pediatrics, Division of Pediatric Endocrinology, Altinbas University, Faculty of Medicine, Istanbul, Turkey. 10. Department of Biochemistry, Stellenbosch University, Stellenbosch, South Africa. 11. Department of Pediatric Endocrinology and Diabetes, Erzurum Training and Research Hospital, Erzurum, Turkey. 12. Department of Pediatric Endocrinology and Diabetes, Adnan Menderes University, School of Medicine, Aydin, Turkey. 13. Department of Pediatric Endocrinology and Diabetes, Hacettepe University, School of Medicine, Ankara, Turkey. 14. Department of Pediatric Endocrinology, Sanliurfa Training and Research Hospital, Sanliurfa, Turkey. 15. Department of Pediatric Endocrinology and Diabetes, Istanbul University of Health Science, Umraniye Training and Research Hospital, Istanbul, Turkey. 16. Department of Pediatric Endocrinology, Izmir Katip Celebi University, School of Medicine, Izmir, Turkey. 17. Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. 18. Gelisim Genetik Tani Merkezi, Istanbul, Turkey. 19. Department of Biochemistry, Marmara University, Faculty of Medicine, Istanbul, Turkey.
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.
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.
Authors: Dong Ho Lee; Sung Hye Kong; Han Na Jang; Chang Ho Ahn; Seung Gyun Lim; Young Ah Lee; Sang Wan Kim; Jung Hee Kim Journal: Arch Osteoporos Date: 2022-03-08 Impact factor: 2.617
Authors: Gabriela P Finkielstain; Ana Vieites; Ignacio Bergadá; Rodolfo A Rey Journal: Front Endocrinol (Lausanne) Date: 2021-12-20 Impact factor: 5.555