title: Significantly higher adrenocorticotropin-stimulated cortisol and 17-hydroxyprogesterone levels in 337 consecutive, premenopausal, caucasian, hirsute patients compared with healthy controls.
abstract: OBJECTIVE
  To investigate whether elevated ACTH-stimulated 17-hydroxyprogesterone (17OHP) levels are caused by CYP21 genetic defects or by a general adrenal hyperresponsiveness in hirsute patients.
  
  
  METHODS
  A total of 337 hirsute patients were evaluated by Ferriman-Gallwey score, serum testosterone, ACTH-stimulated 17OHP, and cortisol during the follicular phase. A cutoff value of 16 nmol/liter for maximum ACTH-stimulated 17OHP (M17OHP) responses was defined as the upper limit of the 95% confidence interval (CI) for the 97.5 percentile in 42 female controls. All patients were offered total screening of the CYP21 gene, and 252 healthy, premenopausal women with regular menses underwent genetic screening.
  
  
  RESULTS
  Patients were divided into idiopathic hirsutism (IH) (n = 180) and polycystic ovary syndrome (PCOS) (n = 157) groups. M17OHP levels were significantly higher in IH [geometric mean value (nmol/liter +/- 2 sd) 12.2 (4.6-32.3)] and PCOS [11.9 (5.3-27.2)] compared with controls [8.5 (5.1-14.2)] (P < 0.001). A similar percentage of IH and PCOS patients had elevated M17OHP (20.5 vs. 20.8%, not significant), and these also had significantly higher 30-min cortisol levels compared with controls (P < 0.05). The prevalence of CYP21 mutations in patients was 8.6% compared with 6.3% in controls (P = 0.38). Ten of 19 carriers had M17OHP levels below the cutoff limit.
  
  
  CONCLUSIONS
  The significantly higher ACTH-stimulated levels of cortisol and 17OHP in hirsute patients indicated adrenal hyperresponsiveness in IH and PCOS. CYP21-carrier status could not explain the observed high prevalence of abnormal ACTH-stimulated 17OHP levels in the hirsute population.
authors.affiliation: Odense University Hospital, Department of Endocrinology, Kløvervaenget 10, 3, 5000 Odense C, Denmark. dorte.glintborg@ouh.fyns-amt.dk
authors.forename: D
authors.initials: D
authors.lastname: Glintborg
authors.forename: A P
authors.initials: AP
authors.lastname: Hermann
authors.forename: K
authors.initials: K
authors.lastname: Brusgaard
authors.forename: J
authors.initials: J
authors.lastname: Hangaard
authors.forename: C
authors.initials: C
authors.lastname: Hagen
authors.forename: M
authors.initials: M
authors.lastname: Andersen
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000097:blood*; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage; D000328:Adult; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006628:Hirsutism / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D011085:Polycystic Ovary Syndrome / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D017697:Premenopause; D015995:Prevalence; D013255:Steroid 21-Hydroxylase / Q000235:genetics*; D044465:White People
chemical_list: D019326:17-alpha-Hydroxyprogesterone; D000324:Adrenocorticotropic Hormone; D013255:Steroid 21-Hydroxylase; D006854:Hydrocortisone