On the origin of the elevated 17-hydroxyprogesterone levels after adrenal stimulation in hyperandrogenism

Ricardo Azziz, Ashi Rafi, Beverly R. Smith, Edwin L. Bradley, Howard A. Zacur

Research output: Contribution to journalArticle

Abstract

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-(l-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 < 0.02). Oligomenorrheic only women had higher mean A and progesterone (P) levels than other hyperandrogenic patients (P < 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 < 0.002) and a weak negative correlation between the mean F and BMI (r = -0.21; P < 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 (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. Furthermore, neither the basal F level nor its response to stimulation correlated with the 17-HP response, although a weak negative correlation was noted between the post-ACTH level of F and 17-HP30(r = -0.20; P < 0.04) or 17- HP0–30 (r = -0.21; P < 0.04). Our data suggest that in non- LOAH hyperandrogenic women the elevated 17-HP levels observed after adrenal stimulation most likely represent a normal 17-HP adrenocortical response superimposed on an elevated circulating 17-HP level of nonadrenal origin. Furthermore, measurements of steroid increments after adrenal stimulation, rather than the absolute level, may more accurately reflect adrenal output.

Original languageEnglish (US)
Pages (from-to)431-436
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume70
Issue number2
DOIs
StatePublished - Feb 1990

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Fingerprint Dive into the research topics of 'On the origin of the elevated 17-hydroxyprogesterone levels after adrenal stimulation in hyperandrogenism'. Together they form a unique fingerprint.

Cite this