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

Fertil Steril. 2016 Jun;105(6):1612-9. doi: 10.1016/j.fertnstert.2016.02.008. Epub 2016 Feb 23.

Abstract

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, 50% had no breast development, and pubic hair was absent or sparse in all patients; 88% 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 68.7% and ovarian macrocysts in 62.5% 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.I223Nfs*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 hypogonadism point to the diagnosis of CYP17A1 defects. Fertility can be achieved in these patients with novel reproductive techniques.

Keywords: CYP17A1; P450c17 activity deficiency; congenital adrenal hyperplasia; hypergonadotropic hypogonadism; ovarian cysts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 46, XX Disorders of Sex Development / blood
  • 46, XX Disorders of Sex Development / diagnosis
  • 46, XX Disorders of Sex Development / genetics*
  • Adolescent
  • Adrenal Cortex Hormones* / blood
  • Adrenal Hyperplasia, Congenital / blood
  • Adrenal Hyperplasia, Congenital / diagnosis
  • Adrenal Hyperplasia, Congenital / genetics*
  • Adult
  • Child
  • Female
  • Humans
  • Ovarian Diseases / blood
  • Ovarian Diseases / diagnosis
  • Ovarian Diseases / genetics*
  • Pedigree
  • Retrospective Studies
  • Steroid 17-alpha-Hydroxylase / genetics*
  • Young Adult

Substances

  • Adrenal Cortex Hormones
  • CYP17A1 protein, human
  • Steroid 17-alpha-Hydroxylase