The diagnosis of nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, based on serum basal or post-ACTH stimulation 17-hydroxyprogesterone, can lead to false-positive diagnosis

Clin Endocrinol (Oxf). 2016 Jan;84(1):23-9. doi: 10.1111/cen.12935. Epub 2015 Oct 9.

Abstract

Objective: As nonclassic congenital adrenal hyperplasia (NCCAH) needs to be taken into account in women with hyperandrogenism, we aimed to assess whether the recommended level of poststimulated 17OHP ≥30 nmol/l confirms NCCAH.

Patients and methods: Forty, consecutive women with biochemical and/or clinical hyperandrogenism (aged 25·4, 18-38) suspected of having NCCAH were recruited to the study. In patients with 17OHP level between 5·1 and 29·9 nmol/l an ACTH stimulation test was performed. In patients with basal or poststimulated 17OHP ≥30 nmol/l, twenty-four-hour urinary steroid profile (USP) analysis was performed and CYP21A2 mutation was assessed. In selected patients with poststimulated 17OHP <30 nmol/l USP was also performed.

Results: The group was divided into two subgroups with basal or poststimulated 17OHP ≥30 nmol/l (group A) and with poststimulated 17OHP <30 nmol/l (group B). Among 40 patients, basal or poststimulated 17OHP ≥30 nmol/l was found in 21, but NCCAH was confirmed by USP followed by genetic testing only in 5 (24%). Four patients were diagnosed as heterozygotes, and in twelve, no CYP21A2 mutation was detected.

Conclusion: The diagnosis of NCCAH based only on serum 17OHP measurements (basal or poststimulated) may lead to false-positive diagnosis when performed by immunoassay with a cut-off value of ≥30 nmol/l. The definitive diagnosis can be established based on USP and/or genetic testing.

MeSH terms

  • 17-alpha-Hydroxyprogesterone / blood*
  • Adolescent
  • Adrenal Cortex Function Tests
  • Adrenal Hyperplasia, Congenital / blood*
  • Adrenal Hyperplasia, Congenital / diagnosis*
  • Adrenal Hyperplasia, Congenital / genetics
  • Adrenocorticotropic Hormone / administration & dosage
  • Adult
  • Female
  • Genetic Testing
  • Humans
  • Hyperandrogenism / blood
  • Hyperandrogenism / diagnosis
  • Mutation
  • Reference Values
  • Sensitivity and Specificity
  • Steroid 21-Hydroxylase / genetics
  • Steroid 21-Hydroxylase / metabolism*
  • Steroids / urine
  • Young Adult

Substances

  • Steroids
  • 17-alpha-Hydroxyprogesterone
  • Adrenocorticotropic Hormone
  • Steroid 21-Hydroxylase