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 hyperplasia (NCAH) exhibit a generalized exaggeration in their response to ACTH stimulation that favors the normal production of F. Patients with 21-hydroxylase (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 alpha-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), progesterone (P4), 17-HP, androstenedione (A4), 11-deoxycortisol (S), and cortisol (F).

RESULT(S): The median basal (i.e., Steroid(0)) or ACTH-stimulated (i. e., Steroid(60)) serum levels of PREG, 17-HPREG, DHA, P4, 17-HP, A4 and, most importantly, 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 between NCAH and control women. The proportion of NCAH patients with stimulated 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-HP(60), 91.7% for A4(60), 29.2% for S(60), and 4. 1% for F(60).

CONCLUSION(S): A generalized adrenocortical hyperresponsivity to ACTH stimulation seems to be present in patients with 21-OH-deficient NCAH, with an exaggerated production of S evident in approximately 30%. The excess production of S in these NCAH patients may, in part, account for their normal F production.