The adrenal secretion of androgens was examined in 9 women (ages 19–39 yr) with postadolescent idiopathic acne and compared to age and sex-matched normal controls. Plasma dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), androstenedione (Δ4-A), cortisol, 17-hydroxyprogesterone, 11-deoxycortisol, and testosterone were measured by radioimmunoassay in the basal state and during a 48hr ACTH infusion. The mean plasma and time-integrated plasma levels of the 3 adrenal androgens in patients with acne were 15–25% higher than normal controls, but the groups were not significantly different (p > .05). The plasma testosterone values, on the other hand, were similar in both groups. In addition, cortisol, 11-deoxycortisol and 17-hydroxyprogesterone basal plasma values and responses to ACTH in patients with acne were similar to the normal control values. These findings suggest that adrenal androgen secretion is at most mildly elevated in patients with idiopathic acne and is unlikely to be the sole cause of acne since many patients without acne have similar hormone levels. Increased sensitivity of the sebaceous gland to androgens or increased local metabolism of androgen hormones in the skin to potent androgen metabolites may offer alternative mechanisms for the pathogenesis of this disorder

Chrousos, George P.

Cutler, Gordon B.

Gross, Earl G.

Loriaux, D. Lynn

Peck, Gary L.

Elsevier - Publisher Connector 

0022-202X/ 82/ 7805-0468$02.00/0 
THE JOURNAL OF INVESTIGATIVE DERMATOJ, OGY, 78:468-47 1, 1982 
Copyright © 1982 by The Williams & Wilkins Co. 
Vol. 78, No.6 
Printed in U.S.A. 
Adrenal Function in Women with Idiopathic Acne 
GEORGE P. CHRousos, M.D., GARY L. PEcK, M.D., EARL G. GRoss, M.D., GoRDON B. CuTLER, JR., M.D., 
AND D. LYNN LORIAUX, M.D., PH.D. 
Developmental Endocrinology Branch, National Institute of Ch ild Health and Human. Development, and the Dermatology Branch (G.L.P. 
and E.G. G.), National Cancer Institute, NIH, Bethesda, Maryland, U.S.A. 
The adrenal secretion of androgens was examined in 
9 women (ages 19-39 yr) with postadolescent idiopathic 
acne and compared to age and sex-matched normal con-
trols. Plasma dehydroepiandrosterone (DHA), dehydroe-
piandrosterone sulfate (DHAS), androstenedione (A4 -A), 
cortisol, 17 -hydroxyprogesterone, 11-deoxycortisol, and 
testosterone were measured by radioimmunoassay in 
the basal state and during a 48 hr ACTH infusion. The 
mean plasma and time-integrated plasma levels of the 3 
adrenal androgens in patients with acne were 15-25% 
higher than normal controls, but the groups were not 
significantly different (p > .05). The plasma testosterone 
values, on the other hand, were similar in both groups. 
In addition, cortisol, 11-deoxycortisol and 17-hydroxy-
progesterone basal plasma values and responses to 
ACTH in patients with acne were similar to the normal 
control values. These findings suggest that adrenal an-
drogen secretion is at most mildly elevated in patients 
with idiopathic acne and is unlikely to be the sole cause 
of acne since many patients without acne have similar 
hormone levels. Increased sensitivity of the sebaceous 
gland to androgens or increased local metabolism of 
androgen hormones in the skin to potent androgen me-
tabolites may offer alternative mechanisms for the 
pathogenesis of this disorder. 
Acne is an androgen dependent condition [1). It may be 
present in the newborn (neonatal acne), probably in association 
with the androgen producing fetal adrenal gland or the func-
tioning neonatal testis [2-4]. Later in life, acne usually develops 
around puberty, with facial comedones being seen as early as 
5-8 yr. This coincides with the appearance of the adrenal zona 
reticularis and with increasing adrenal androgen secretion (ad-
renarche) [5,6). Acne is also commonly seen in conditions 
associated with hyperandrogenism such as congenital adrenal 
hyperplasia, ovarian tumors, adrenal tumors, Cushing's disease, 
idiopathic hirsutism, and polycystic ovarian disease [7-13]. In 
these conditions plasma testosterone and adrenal androgen 
hormones or their urinary metabolites are usually elevated 
when compared to normal controls [7-13]. In children with a 
strong familial background of idiopathic acne, the androgen 
status has been examined by measuring basal 24 hr urinary 
excretion of testosterone, dehydroepiandrosterone, androster-
one, etiocholanolone, and total 17 -ketosteroids [14,15]. The 
incidence of acne in these children increases as urinary steroid 
excretion rises during adrenarche. Urinary testosterone excre-
tion in the prepubertal children with acne is significantly greater 
than in age-match.ed controls, suggesting that hypersecretion of 
adrenal androgens may contribute to the pathogenesis of this 
disorder. These studies have Jed us to postulate that adrenal 
Manuscript received June 3, 1981; accepted for publication Novem-
ber 15, 1981. 
Reprint requests to: Dr. George P. Chrousos, The National Institutes 
of Health, Bldg. 10, Rm. 10B09, Bethesda, Md 20205. 
Abbreviations: 
DHA: dehydroepiandrosterone 
DHAS: dehydroepiandrosterone sulfate 
THS: tetrahydro-compound S 
hyperandrogenism may also contribute to persistent idiopathic 
acne in adult women. We have tested this hypothesis by mea-
suring plasma androgen levels basally and during maximal 
ach·enal stimulation in women with uncomplicated (not associ-
ated with hirsutism or ovarian dysfunction) idiopathic acne and 
in age-matched controls. 
MAT~RIALS AND METHODS 
Subjects and Protocol 
All subjects, 9 women with acne and 10 age- and sex-matched 
controls, were admitted to the Clinical Center of the National Institutes 
of Health for evaluation. The patients with acne (ages 19-39 yr, mean 
24.3) had never rece ived glucocorticoid therapy and had taken no 
medications for 6 weeks prior to the study except antibiotics. They 
were all menstruating regularly except one that had polymenorrhea. 
There was no hirsutism present in any of them according to the criteria 
of Ferriman and Gallwey [16] (scores <7 on all patients). The normal 
subjects (a~es 19-24 yr, mean 20.5) had no evidence of any illness, 
including acne or hirsutism, by history, physica l examination, and 
routine admission laboratory tests. All were menstruating regularly. 
Both patients and normal control subjects received a standard 48 h1· 
IV ACTH infusion (cosyntropin 80 U/day) [1 7]. Blood samples were 
collected before and during the infusion for steroid measurements. The 
ACTH infusions were administered without regard for the phase of the 
menstrual cycle. There was no significant difference between the pro-
portion of patients and control subjects who received the ACTH 
infusion in the follicular versus the lu teal phase. 
Hormone Assays 
Plasma dehydroepiandrosterone (DHA), dehydroepiandrosterone 
sulfate (DHAS), androstenedione (.1.' -A), cortisol, ll-deoxycortisol and 
17-hydroxyprogesterone were measured by radioim munoas ay as pre-
viously described [18-20]. The detection limits for these assays are 25 
ng/dl. 5 ug/dl, 15 ng/dl, 1 ug/ dl, 40 ng/dl and 7 ng/ dl, respectively. 
Statistical Analysis 
Unless otherwise stated, all data are presented as the mean ± SE. 
Comparisons were made using Student's t-test and the Mann-Whitney 
U test [21]. 
RESULTS 
Cortisol, 11-deoxycortisol and 17 -hydroxyprogesterone values 
in t he basal state and during ACTH were similar in patients 
with acne and normal controls (Fig 1). 
Adrenal anch·ogen levels, including DHA, DHAS and /!:,.4 -A 
were slightly higher in patients with acne at all time points (Fig 
2). However, t-test of the groups at each time point showed that 
the groups were not significantly different. 
Plasma testosterone values were similar in acne patients and 
normal controls, both basally and dUl·ing ACTH stimulation 
(Fig 2, bottom panel). 
To compare adrenal steroid responses between acne patients 
and controls over the entire infusion, we calculated the time-
integrated steroid response to ACTH for each patient (a1·ea 
under the curves, as presented in Fig 1 and 2) and compared 
the means of the 2 groups (Fig 3) using Student's t-test. None 
of these comparisons were significant (p > 0.05) although the 
DHA, DHAS and tJ.4-A values were 22, 15 and 25% higher in 
patients with acne. Furthermore, no significant differences were 
found when we compared the two groups using the nonpara-
metic Mann-Whitney U test (p > 0.05). However, in 5 of 9 
468 
June 1982 ADRENAL FUNCTION IN WOMEN WITH IDIOPATHIC ACNE 469 
60 
20 
~ 
800 
0> 
.E 
-' 600 0 
(J) 
i= 
r:r 
0 
u 400 >-X 
0 
UJ 
'? 200 
~ 
0> 
.E 
UJ 
z 
300 
0 
cr: 
UJ 
1-
(J) 
UJ 200 (.!) 
0 
a: 
a... 
>-X 
.(£ 100 a 
>-
:::z: 
~ 
eACNE (N = 91 
o NORMAL (N = 101 
• 
I 
I 
0 4 8 24 
TIME( h) 
30 36 48 
FIG 1. P lasma cortisol, 11-deoxycortisol and 17-hydl·oxyprogester-
one during ACTH infusion in 9 patients with acne (e--e) and 10 
normal controls (0 --0 ). 
patients with acne (ages 19-25) the time-integrated tl.'' -A values 
were above the 95% confidence limits for normals suggesting 
that examining a larger patient sample might show significant ly 
although only slightly elevated plasma levels of 6.''-androstene-
dione. 
There was no correlation between the severity of acne as 
evaluated by the number of skin lesions and basal or time-
integrated plasma androgen hormone values (data not shown). 
DISCUSSION 
These studies demonstrate that circulating adrenal andro-
gens, testosterone and cortisol, both basally and after prolonged 
adrenal stimulation, are not significantly different between 
women with persistent acne and age-matched controls. Thus, 
although acne is an androgen dependent condition, its expres-
sion in women does not appear to be substantially related to 
increased circulating androgen levels. 
Mild (late onset) congeni tal adrenal hyperplasia can be dif-
ficult to diagnose, and may require ACTH stimulation with 
measurement of plasma 17 -hydroxyprogesterone or 11-deoxy-
3000 
~ 
Ol 
.s 2000 
<( 
I 
Cl 
-ACNE (N = 9l 
o-NORMAL (N = 101 ~ /~1 
J/~ 
_.__~ ... ~' 
..._. 1---------t -
1000 
500 
~ 400 Ol 
3-
(f) 300 <( 
I 
Cl 200 
l--------1 
l--'~~ / ..--v 
~-·---------
• 
100 
0 
1000 
~ 800 
Ol 
.s 600 
<( 
..;. 
400 <l 
200 
0 
~ 100 
Ol 
.s 80 
UJ 
z 
0 60 
a: 
UJ 
I- 40 (f) 
0 
I-
(f) 20 UJ 
I-
0 
0 4 8 24 30 36 48 
TIME (h) 
FIG 2. P lasma DHA, DHAS, 6'-A and testosterone during ACTH 
infusion in 9 patients with acne (e--e) and 10 normal controls 
(0 --0 ). 
cortisol, or their urinary metabolites pregnanetriol and THS, to 
establish a diagnosis [22,23]. No patient in the acne group met 
the requirements for 21 or 11-hydroxylase deficiency. In con-
trast, in another study patients with severe, refractory, nodu-
locystic acne, had increased ACTH-stimulated urinary preg-
nanetriol and tetrahydro-compound S(THS) but normal 17-
ketosteroids [8]. No mention of associated hirsutism and ovar-
ian dysfunction (menstrual irregularities and infertility) was 
made. The same author later reported a group of women who 
had acne but who had presented to a gynecologist with a chief 
complaint other than acne. T hese patients also had increased 
ACTH-stimulated urinary pregnanetriol and THS [9]. This 
latter group clearly differs from our patient population, who 
presented to a dermatologist (G.L.P. and E.G.G.) with the sole 
complaint of acne. We suspect that this difference in patient 
selection may contribute to the different findings of our studies. 
Gynecologic disorders such as menstrual irregularity or hirsu-
tism freq uently are associated with high ciJ'culating androgen 
levels and acne as a related consequence of hyperandrogenism. 
470 CHROUSOS ET AL 
200 
100 
0'------'----'---'-<.....C....<...a..-
6 30 
CORTISOL lmg/dl·h) 
3 15 
0 '--...J...._--L-.....1....<:--<-.L.a.__ 0 L.._J.______JL.._.JLL.L.L.JL--
50 
25 
1 1-DEOXYCORTISOL 
!,..gl dl · h) 
0 '----'----'---'-''--<-<:....£L..-
20 
10 
17-HYDROXYPRO-
GESTERONE 
(flg/dl·h) 
CONTROL ACNE 
50 
25 
0 L._..l__L.._..LL..<'-L-LlL-
6 
3 
TESTOSTERONE 
l,..g;dl"h) 
CONTROL ACNE 
FIG 3. Comparison of time-integrated plasma steroid hormone val-
ues between patients with acne (shaded bars, mean ± SE, N = 9) and 
normal control subjects (open bars, N = 10). T he time-in tegrated va lue 
for each patient was calculated from the area under the cuJ"Ve of steroid 
concentration vs. time for the 48 hr ACTH infusion. 
T hus, although attenuated 21-hydroxylase and 11-hydroxylase 
deficiencies have been reported in. this setting [8,9], we did not 
encounter these disorders in our patients with uncomplicated 
acne. 
T he various circulating androgens act on the sebaceous gland 
to stimulate sebum production either directly, as hormones, or 
as pro hormones, which undergo local metabolism to form active 
metaboli tes. H uman skin has been shown to convert testoster-
one to Sa-dihydrotestosterone (DHT) and other Sa-reduced 
steroids both in vivo and in vitro [24-27]. The sebaceous gland 
itself has a high s·£~-red u ctase activity when tested in vitro by 
a micromethod [28]. On the other hand, circulating ~·-andro­
stenedione is converted peripherally to testosterone [29]. De-
hydroepiandrosterone may be converted peripherally to ~"­
androstenediol [30], which itself may have intrinsic androgenic 
activity [31], and then to testosterone. However, there is lit tle 
knowledge of the extent to which these conversions occur in 
the normal and abnormal sebaceous gland, and of their impor-
tance relative to plasma uptake as a sow·ce of local testosterone. 
T hus, our observation that circulating testosterone, DHA, 
DHAS and ~4-A in patients with acne were not significantly 
Vol. 78, No. 6 
different from normal controls does not invalidate the hypoth-
esis that altered local metabolism of these hormones may 
contribute to the pathogenesis of acne. In fact, increased Sex-
red uctase activity has been observed in the skin of patients 
with acne [32,33], as well as in other andxogen dependent 
conditions, such as male pattern baldness and idiopathic hir-
sutism [34,35]. In addition, increased sensitivity of the seba-
ceous gland to androgens represents another potential but 
unproven mechanism for the pathogenesis of this disorder. 
We are grateful to Mr. Mark Sauer for developing computer 
programs that allowed the analysis of these data. We also thank 
Ms. Rebecca Raymond for typing the manuscript with h er 
customary precision and the personnel of the 12E ward, NIH 
Clinical Center , for their assistance in performing the tests. 
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Announcement 
The Annual Clinically Oriented Symposium of the European Society for Dermatologic;:1l Research 
(E.S.D.R.) will be held in Amsterdam, The Netherlands, J anuary 31, to February 1, 1983. The theme of 
this meeting will be: "Brain and Skin." Abstracts should be submitted in English, typed double-spaced on 
A4-sized paper (five copies). The deadline for submission is October 1, 1982. Correspondence: Professor 
Rudi H. Cormane, M .D., Department of Dermatology, Academic Medical Center, Meibergdreef 9, NL-
1105 AZ Amsterdam-Zuid-Oost, The Netherlands. 


Adrenal Function in Women with Idiopathic Acne 

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