Adrenocortical hyperresponsivity to adrenocorticotropic hormone: a mechanism favoring the normal production of cortisol in 21-hydroxylase-deficient nonclassic adrenal hyperplasia

Objective: To test the hypothesis that patients with nonclassic adrenal hyp erplasia (NCAH) exhibit a generalized exaggeration in their response to ACT H stimulation that favors the normal production of F. patients with 21-hydr oxylase (21-OH)-deficient NCAH do not demonstrate cortisol (F) deficiency. Design: prospective controlled study. Setting: Tertiary university clinic. Patient(s): Twenty-four untreated patients with NCAH diagnosed by a 17 alph a-hydroxyprogesterone (17-HP) level of >30.3 nmol/L (>10 ng/mL), and 37 age - and body mass-matched healthy eumenorrheic nonhirsute controls. Intervention(s): All study subjects underwent a 60 minute acute stimulation using 0.25 mg of ACTH-(1-24) i.v. Main Outcome Measure(s): Basal and stimulated serum levels of pregnenolone (PREG), 17-hydroxypregnenolone (17-HPREG), dehydroepiandrosterone (DHA), pr ogesterone (P4), 17-HP, androstenedione (A4), 11-deoxycortisol (S), and cor tisol (F). Result(s): The median basal (i.e., Steroid(0)) or ACTH-stimulated (i.e., St eroid(60)) serum levels of PREG, 17-HPREG, DHA, P4, 17-HP, A4 and, most imp ortantly, S were higher in NCAH patients than in controls. In contrast, the levels of F at either 0 minute or 60 minutes of stimulation were similar b etween NCAH and control women. The proportion of NCAH patients with stimula ted steroids levels of >the 95th percentile of controls were as follows: 84 .21% for PREG(60), 87.5% for 17-HPREG(60), 95.8% for DHA(60), 89.5% for P4( 60), 100% for 17-HP60, 91.7% for A4(60), 29.2% for S-60, and 4.1% for F-60. Conclusion(s): A generalized adrenocortical hyperresponsivity to ACTH stimu lation seems to be present in patients with 21-OH-deficient NCAH, with an e xaggerated production of S evident in approximately 30%. The excess product ion of S in these NCAH patients may, in part, account fur their normal F pr oduction. (C)2000 by American Society for Reproductive Medicine.