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.


METHODS
Prospective controlled study.


METHODS
Tertiary university clinic.


METHODS
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.


METHODS
All study subjects underwent a 60 minute acute stimulation using 0.25 mg of ACTH-(1-24) i.v.


METHODS
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).


RESULTS
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).


CONCLUSIONS
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.
Huerta
R
R
Department of Obstetrics and Gynecology, The University of Alabama, Birmingham 35294-7333, USA.
Dewailly
D
D
Decanter
C
C
Knochenhauer
E S
ES
Boots
L R
LR
Azziz
R
R
D006907:17-alpha-Hydroxypregnenolone / Q000097:blood; D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism; D000312:Adrenal Hyperplasia, Congenital / Q000188:drug therapy* / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000328:Adult; D000735:Androstenedione / Q000097:blood; D016022:Case-Control Studies; D003350:Cortodoxone / Q000097:blood; D003687:Dehydroepiandrosterone / Q000097:blood; D005260:Female; D006628:Hirsutism / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D011284:Pregnenolone / Q000097:blood; D011374:Progesterone / Q000097:blood; D011446:Prospective Studies; D013255:Steroid 21-Hydroxylase / Q000187:drug effects* / Q000235:genetics
D006907:17-alpha-Hydroxypregnenolone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D011374:Progesterone; D011284:Pregnenolone; D000324:Adrenocorticotropic Hormone; D013255:Steroid 21-Hydroxylase; D003350:Cortodoxone; D006854:Hydrocortisone