On the origin of the elevated 17-hydroxyprogesterone levels after adrenal stimulation in hyperandrogenism.
Hyperandrogenic women appear to demonstrate an exaggerated 17-hydroxyprogesterone (17-HP) response to adrenal stimulation which is not due to the marked 21-hydroxylase deficiency of late-onset adrenal hyperplasia (LOAH). Furthermore, in hyperandrogenism the ovary also appears to secrete excessive amounts of 17-HP. It is not clear to what extent the elevated 17-HP levels after ACTH stimulation are due to extraadrenal production of the steroid. This investigation was undertaken to assess the adrenal contribution to the elevated 17-HP levels after ACTH stimulation observed in non-LOAH hyperandrogenism. One hundred and sixty consecutive unselected women with hirsutism and/or hyperandrogenic oligomenorrhea formed the clinical population. Excluded were 4 women with LOAH and all patients with hyperprolactinemia. For the purpose of investigating the relationship between adrenal response and clinical symptoms, hyperandrogenic patients were divided into 3 subgroups: hirsute only (n = 23), hirsute oligomenorrheic (n = 84), and oligomenorrheic only (n = 24). Subclassification for an additional 29 patients (18%) with hyperandrogenemia was not possible, since their symptomatology was not clearly stated in the record. However, these individuals were included in the patient group as a whole. Controls consisted of 21 healthy, regularly menstruating, nonhirsute female volunteers. Both patients and controls underwent acute adrenal stimulation with 1 mg ACTH-(1-24), and serum was obtained before and 30 min after ACTH administration. Hyperandrogenic patients had higher mean basal total testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHS), 17-HP, and LH/FSH levels, but not cortisol (F), compared to normal subjects (P less than 0.02). Oligomenorrheic only women had higher mean A and progesterone (P) levels than other hyperandrogenic patients (P less than 0.02). No correlation was noted between body mass index (BMI) and the levels of DHS, P, or A, while a weak positive association was noted between the BMI and the mean T (r = 0.31; P less than 0.002) and a weak negative correlation between the mean F and BMI (r = -0.21; P less than 0.05). The mean 17-HP level 30 min after ACTH administration (17-HP30) was significantly higher in hyperandrogenic women than in normal subjects whether analyzed in separate subgroups or together and was due to the higher basal 17-HP levels. Basal 17-HP correlated with the circulating levels of T, A, and P, steroids largely of ovarian origin. Alternatively, the net increment in 17-HP from 0-30 min after ACTH (delta 17-HP30) was not significantly higher in hyperandrogenic women than normal subjects and did not correlate with the basal levels of T, A, and P. Neither the basal level of 17-HP nor its response to ACTH correlated with circulating DHS levels.(ABSTRACT TRUNCATED AT 400 WORDS)
Azziz
R
R
Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Rafi
A
A
Smith
B R
BR
Bradley
E L
EL
Zacur
H A
HA
D019326:17-alpha-Hydroxyprogesterone; D000302:Adrenal Cortex / Q000187:drug effects* / Q000502:physiology; D000312:Adrenal Hyperplasia, Congenital / Q000378:metabolism*; D000328:Adult; D000728:Androgens / Q000378:metabolism*; D000735:Androstenedione / Q000378:metabolism; D003366:Cosyntropin; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000378:metabolism; D019314:Dehydroepiandrosterone Sulfate; D005260:Female; D006801:Humans; D006908:Hydroxyprogesterones / Q000378:metabolism*; D008875:Middle Aged; D011085:Polycystic Ovary Syndrome / Q000378:metabolism; D011863:Radioimmunoassay; D013739:Testosterone / Q000378:metabolism
D000728:Androgens; D006908:Hydroxyprogesterones; D003366:Cosyntropin; D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D019326:17-alpha-Hydroxyprogesterone