To determine the adrenal contribution to elevated plasma
androgens in 31 young hyperandrogenemic women with
acne and/or
hirsutism, we compared their responses to
ACTH with those of 14 normal women. Each subject was given a low dose (10 micrograms/m2) of synthetic ACTH-(1-24) (
Cortrosyn) after administration of 1.5 mg
dexamethasone the night before the test. Thirty and 60 min responses of plasma
17 alpha-hydroxypregnenolone (17-Preg),
17 alpha-hydroxyprogesterone, (17-prog),
dehydroepiandrosterone (
DHEA),
androstenedione,
11-deoxycortisol, and
cortisol were measured. Eighteen (58%) patients had increased responses of at least one 17-ketosteroid or adrenal
androgen precursor. All patients had
cortisol responses within the range of those of the 14 normal subjects. Nine patients (29%) had evidence of
steroid biosynthetic
enzyme deficiencies, either mild
congenital adrenal hyperplasia or the heterozygote state; after
ACTH, 4 of these patients had elevated 17-prog in the range of values in heterozygote carriers of
21-hydroxylase deficiency, 2 had elevated levels of
11-deoxycortisol compatible with
11 beta-hydroxylase deficiency, and 3 had elevated levels of 17-Preg and
DHEA, suggestive of
3 beta-hydroxysteroid dehydrogenase deficiency. Another 9 subjects (29%) had 17-ketosteroid (
DHEA and/or
androstenedione) hyperresponsiveness to
ACTH with associated elevated 17-Preg responses. As a group, their patterns suggested relatively deficient
3 beta-hydroxysteroid dehydrogenase and relatively hyperactive C
lyase without impairment of
cortisol secretion. This pattern resembles exaggerated adrenarche, and we postulate that these 9 patients have
hyperplasia of the zona reticularis. Neither basal levels of plasma
androgens (free
testosterone and
DHEA sulfate) nor menstrual history predicted which patients would have abnormal
ACTH responses. Although 5 of 11 (45%) patients with
acne alone had abnormal responses to
ACTH, 10 of 14 patients with
acne and
hirsutism (71%) had abnormal responses to
ACTH. We conclude that an adrenal contribution is found in about half of hyperandrogenemic women with
acne and/or
hirsutism. This adrenal
androgen hyperresponsiveness is heterogeneous. Some patients may have mild forms of
congenital adrenal hyperplasia. However, functional androgenic hyperresponsiveness to
ACTH, which resembles an exaggeration of adrenarche, is the most common abnormality found. Such findings may provide an explanation for the clinical observation of exacerbations of
acne with stress.