Clinical, hormonal, ovarian, and genetic aspects of 46,XX patients with congenital adrenal hyperplasia due to CYP17A1 defects

Objective: To perform a clinical, biochemical, and molecular evaluation of patients with CYP17A1 defects, including ovarian imaging. Design: Retrospective study. Setting: Tertiary care center. Patient(s): Sixteen patients with congenital adrenal hyperplasia due to CYP17A1 defects with a median chronological age of 20 years and belonging to 10 unrelated families. Intervention(s): None. Main Outcome Measure(s): Clinical and biochemical parameters, molecular diagnosis, ovarian imaging, and therapeutic management. Result(s): Seventy-one percent of patients presented with primary amenorrhea, 500/0 had no breast development, and pubic hair was absent or sparse in all patients; 880/o had high blood pressure at diagnosis. Basal LH and P levels were high, and androgen levels were low in all patients. Ultrasound revealed ovarian enlargement in 68.70/0 and ovarian macrocysts in 62.50/0 of patients before treatment; three patients had a previous surgical correction of ovarian torsion or rupture. Molecular analysis revealed inactivating CYP17A1 mutations in all patients. The most prevalent mutation was p.W406R, and one patient bore a novel p.G478S/ p.1223Nfs*10 compound heterozygous mutation. Treatment with dexamethasone, estrogen, and P resulted in reduction of ovarian volume. Conclusion (s): Amenorrhea, absent/sparse pubic hair, hypertension, and ovarian macrocysts, whichincrease the risk of ovarian torsion, are important elements in the diagnosis of 46,XX patients with CYP17A1 defects. High basal P levels in patients with hypergonadotropic hypogoriadisiri point to the diagnosis of CYP17A1 defects. Fertility can be achieved in these patients with novel reproductive techniques. (Fertil Steil(R) 2016;105:1612-9. (C) 2016 by American Society for Reproductive Medicine.)