Steroid Screening Tools Differentiating Nonclassical Congenital Adrenal Hyperplasia and Polycystic Ovary Syndrome

J Clin Endocrinol Metab. 2020 Aug 1;105(8):dgaa369. doi: 10.1210/clinem/dgaa369.

Abstract

Purpose: To analyze the performance of basal 17OH-progesterone (17OHP) levels versus the basal 17OHP/cortisol ratio in nonclassical congenital adrenal hyperplasia (NCAH) and polycystic ovary syndrome (PCOS) differential diagnosis. Basal 17OHP levels >10 ng/mL have been used to confirm NCAH diagnosis without the adrenocorticotropic hormone (ACTH) test; however, the optimal cutoff value is a matter of debate.

Methods: A cross-sectional study was performed at the endocrinology and gynecological endocrinology outpatient clinics of a tertiary hospital. A total of 361 patients with PCOS (age 25.0 ± 5.3 years) and 113 (age 19.0 ± 13.6 years) patients with NCAH were enrolled. Basal and ACTH-17OHP levels were measured by radioimmunoassay, and CYP21A2 molecular analysis was performed to confirm hormonal NCAH diagnosis. Receiver operating characteristic curve analysis compared basal 17OHP levels and the 17OHP/cortisol ratio between NCAH and PCOS patients.

Results: Basal 17OHP levels were higher in NCAH patients than in those with PCOS (8.85 [4.20-17.30] vs 1.00 [0.70-1.50] ng/mL; P < 0.0001), along with 17OHP/cortisol ratio (0.86 [0.47-1.5]) vs 0.12 [0.07-0.19]; P < 0.0001, respectively). Basal 17OHP levels and the 17OHP/cortisol ratio were strongly correlated in both groups (rho = 0.82; P < 0.0001). Areas under the curves for basal 17OHP levels (0.9528) and the 17OHP/cortisol ratio (0.9455) were not different to discriminate NCAH and PCOS (P > 0.05). Basal 17OHP level >5.4 ng/mL and 17OHP/cortisol ratio >2.90 had 100% specificity to identify NCAH.

Main conclusions: Basal 17OHP levels >5.4 ng/mL can be used to perform differential diagnoses between NCAH and PCOS, dismissing the ACTH test. The basal 17OHP/cortisol ratio was not superior to basal 17OHP levels in this scenario.

Keywords: basal 17OH-progesterone levels; diagnosis screening; nonclassical congenital hyperplasia; polycystic ovary syndrome.

Publication types

  • Observational Study
  • 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 / genetics
  • Adrenocorticotropic Hormone / administration & dosage
  • Adult
  • Biomarkers / blood
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Diagnosis, Differential
  • Diagnostic Techniques, Endocrine*
  • Feasibility Studies
  • Female
  • Genetic Testing
  • Humans
  • Hydrocortisone / blood*
  • Polycystic Ovary Syndrome / blood
  • Polycystic Ovary Syndrome / diagnosis*
  • ROC Curve
  • Reference Values
  • Retrospective Studies
  • Steroid 21-Hydroxylase / genetics
  • Young Adult

Substances

  • Biomarkers
  • 17-alpha-Hydroxyprogesterone
  • Adrenocorticotropic Hormone
  • CYP21A2 protein, human
  • Steroid 21-Hydroxylase
  • Hydrocortisone

Supplementary concepts

  • Congenital adrenal hyperplasia due to 21 hydroxylase deficiency