A prospective study of the prevalence of nonclassical congenital adrenal hyperplasia among women presenting with hyperandrogenic symptoms and signs

J Clin Endocrinol Metab. 2008 Feb;93(2):527-33. doi: 10.1210/jc.2007-2053. Epub 2007 Nov 13.


Context: The diagnosis of the polycystic ovary syndrome requires the exclusion of nonclassical congenital adrenal hyperplasia (NCAH).

Objective: Our objective was to evaluate the actual prevalences of 21-hydroxylase and 11beta-hydroxylase deficiencies among women presenting with hyperandrogenic complaints.

Settings: This study was performed at an academic hospital.

Patients: A total of 270 consecutive unselected women presenting with hyperandrogenic symptoms were prospectively recruited.

Interventions: Basal and ACTH-stimulated 11-deoxycortisol and 17-hydroxyprogesterone concentrations were measured.

Main outcome measures: The prevalences of 21-hydroxylase and 11beta-hydroxylase deficiencies were calculated, and the diagnostic performance of basal serum 17-hydroxyprogesterone levels for the screening of NCAH was evaluated by receiver operating characteristic curve analysis.

Results: Six of the 270 patients had 21-hydroxylase-deficient NCAH that was confirmed by CYP21 genotyping, whereas no patient was diagnosed with 11beta-hydroxylase deficiency, for an overall NCAH prevalence of 2.2% (95% confidence limits 0.5-3.9%). According to receiver operating characteristic analysis, a single basal serum 17-hydroxyprogesterone determination has a 0.97 (95% confidence interval: 0.934-1.008) chance of detecting NCAH in hyperandrogenic women. In our experience, the most appropriate cutoff value for the detection of NCAH is a 17-hydroxyprogesterone above 1.7 ng/ml, showing a 100% sensitivity and a 88.6% specificity. Five of the six 21-hydroxylase-deficient NCAH patients carried a severe CYP21 allele requiring genetic counseling and highlighting the importance of excluding this disorder among hyperandrogenic patients.

Conclusions: The prevalence of NCAH among hyperandrogenic patients from Spain is 2.2%. Basal serum 17-hydroxyprogesterone measurements have an excellent diagnostic performance, yet the cutoff value should be established in each laboratory to avoid false-negative results.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 17-alpha-Hydroxyprogesterone / blood
  • Adolescent
  • Adrenal Hyperplasia, Congenital / blood
  • Adrenal Hyperplasia, Congenital / diagnosis
  • Adrenal Hyperplasia, Congenital / enzymology
  • Adrenal Hyperplasia, Congenital / epidemiology*
  • Adult
  • Cortodoxone / blood
  • Diagnosis, Differential
  • Female
  • Humans
  • Hyperandrogenism / blood
  • Hyperandrogenism / diagnosis
  • Hyperandrogenism / enzymology
  • Hyperandrogenism / epidemiology*
  • Polycystic Ovary Syndrome / blood
  • Polycystic Ovary Syndrome / diagnosis
  • Polycystic Ovary Syndrome / enzymology
  • Polycystic Ovary Syndrome / epidemiology
  • Prevalence
  • Prospective Studies
  • ROC Curve
  • Sensitivity and Specificity
  • Spain / epidemiology
  • Steroid 11-beta-Hydroxylase / metabolism
  • Steroid 21-Hydroxylase / metabolism


  • 17-alpha-Hydroxyprogesterone
  • Steroid 21-Hydroxylase
  • Steroid 11-beta-Hydroxylase
  • Cortodoxone