ESPE Abstracts (2014) 82 P-D-2-2-282

Adrenals & HP Axis (1)

Steroid 11β-Hydroxylase Deficiency Due to CYP11B1 Mutations in Females with Hyperandrogenemia

Christos Shammasa, Stefania Byroua, Alexia AP Phedonosa, Stella Nicolaoub, Meropi Toumbac, Nicos Skordisa,d, Vassos Neocleousa & Leonidas A Phylactoua

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aThe Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus; bMakarios III Hospital, Nicosia, Cyprus; cIasis Hospital, Paphos, Cyprus; dSt George’s, University of London Medical School at the University of Nicosia, Nicosia, Cyprus


Background: More than >90% of cases of congenital adrenal hyperplasia (CAH) are caused by 21-hydroxylase deficiency, steroid 11β-hydroxylase deficiency accounts for 5–8% of cases.

Objective and hypotheses: To seek evidence on the prevalence of CYP11B1 mutations in prepubertal girls, adolescents and adult females with clinical signs of hyperandrogenemia.

Method: The study included 31 girls with premature adrenarche (PA) of whom 15 were identified heterozygotes for CYP21A2 gene mutation and 25 adolescents and adult females with polycystic ovary syndrome (PCOS), of whom seven were heterozygotes for CYP21A2. The diagnosis of PCOS was based on the Rotterdam Criteria. Direct DNA sequencing was used to identify mutations in CYP11B1.

Results: In the group of girls, who presented early with PA, 48.4% were heterozygotes and 51.6% had no identifiable mutations in CYP21A2. On the contrary, in the group of females with late onset hyperandrogenemia, the presence of one mutation was detected in 28%, whereas 72% carried no mutation. In the total group of 31 girls, who presented early with PA, 16 had no identifiable mutation both in CYP21A2 or CYP11B1, 14 were identified as heterozygotes in CYP21A2 only and one girl was identified with digenic inheritance in CYP21A2 (p.Qln318stop) and the CYP11B1 (p.Arg43Gln). In the group of 25 females with late onset hyperandrogenemia (PCOS), 17 had no identifiable mutation, seven were identified as heterozygotes in CYP21A2 and one was identified in heterozygosity with the missense p.Arg43Gln in CYP11B1. No mutants were identified in the 3′ and 5′ untranslated region (UTR) of the CYP21A2 and CYP11B1 genes.

Conclusion: The carrier status for CYP21A2 may be an important factor in the variable phenotype of hyperandrogenism and a contributing factor for the early manifestation of the disease. Furthermore non-classic 11β-hydroxylase deficiency is a rare disorder and it is not a significant factor of hyperandrogenemia in females with PA and PCOS.

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