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Sexual Precocity in a 16-Month-Old5 T% E$ \$ A4 a
Boy Induced by Indirect Topical
3 z5 U: o( g, }9 Y! e: HExposure to Testosterone8 `$ j; @( [) ], `; x0 F
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
1 M) G# n; E. W ?) ?, M7 k# iand Kenneth R. Rettig, MD1
/ k4 S8 p4 ]+ q6 e/ q6 jClinical Pediatrics7 x+ N. C+ u! e. U6 p7 C
Volume 46 Number 62 j5 |# E& L# O+ J
July 2007 540-543: ~6 y: R6 j# t; h
© 2007 Sage Publications
# W$ Q g, ]5 T9 n4 K10.1177/00099228062966510 Z; m {. H' Q: U6 t8 B) ~( t
http://clp.sagepub.com, v5 }& b- Y- _' w" t2 v8 {
hosted at( i9 X/ n- X: s" ^* u( R: u
http://online.sagepub.com! q8 `# t% {, T+ I2 r
Precocious puberty in boys, central or peripheral,9 D% k( Q& G* ?5 e! E
is a significant concern for physicians. Central- A% ]9 t' z* S
precocious puberty (CPP), which is mediated( o0 V+ z8 g, Q& Z7 R: h
through the hypothalamic pituitary gonadal axis, has* l2 |8 d' u+ H0 N$ I
a higher incidence of organic central nervous system: B# X# _ _; y/ X) o
lesions in boys.1,2 Virilization in boys, as manifested
, F: L% Z) z" l, x; I( yby enlargement of the penis, development of pubic, Y: g! p& K; C6 ~# q% z# \
hair, and facial acne without enlargement of testi-
& m3 S9 B( _& {; R, j% R: @5 Ycles, suggests peripheral or pseudopuberty.1-3 We$ U. [ X5 g5 V6 _' W% k" X
report a 16-month-old boy who presented with the
+ f( u4 ~% }. b6 `1 D' {enlargement of the phallus and pubic hair develop-, o1 D0 i0 V. r* b& }
ment without testicular enlargement, which was due
6 I5 M" I8 S: mto the unintentional exposure to androgen gel used by/ z& s6 R w- |' D
the father. The family initially concealed this infor-5 S" z- V/ _) O3 d3 i
mation, resulting in an extensive work-up for this9 y( y5 x$ t! s6 N+ Z) ` R5 x6 p- j# d
child. Given the widespread and easy availability of: ^% I. d$ I3 L' C) L& _
testosterone gel and cream, we believe this is proba-
6 H/ d. t9 G- L/ S4 [4 c5 P! _8 ~2 ^bly more common than the rare case report in the0 ~: f& E5 Z5 `. G5 |( f8 |
literature.4
$ D$ u4 X' `( t% J' `( C% @ m" | VPatient Report
0 ]0 ^) S: {. MA 16-month-old white child was referred to the& }4 j) r* w0 e7 \2 \5 D( Y2 d
endocrine clinic by his pediatrician with the concern
) s0 S/ }# ?3 v" N# D& {/ S% Mof early sexual development. His mother noticed2 L* w4 o/ O3 x' C# ]% F, v+ P4 W
light colored pubic hair development when he was' a. l" j) n4 S u
From the 1Division of Pediatric Endocrinology, 2University of
! F: D/ R) ]+ FSouth Alabama Medical Center, Mobile, Alabama.& z# T/ W" X% C* v( q# [, L
Address correspondence to: Samar K. Bhowmick, MD, FACE,
# u' _/ S( U+ z! R w% dProfessor of Pediatrics, University of South Alabama, College of* f/ a- F( r9 a, b3 s0 r
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;7 T ~$ i+ Q \, R0 U
e-mail: [email protected].5 m+ L$ L6 ]9 v
about 6 to 7 months old, which progressively became5 R3 T/ w6 s, N2 W! d7 L/ k
darker. She was also concerned about the enlarge-
. ?' W! P7 x. \& t$ a& Cment of his penis and frequent erections. The child
+ w. [9 X6 b" P( A e, B* ^was the product of a full-term normal delivery, with
3 w0 T+ J5 Q; P+ y+ g0 g/ Ga birth weight of 7 lb 14 oz, and birth length of8 l6 K/ v4 R$ {1 ~( q+ [
20 inches. He was breast-fed throughout the first year& w! c, q9 t2 {- ~3 Q" [
of life and was still receiving breast milk along with
* T2 g V0 Z' f ]7 E2 {solid food. He had no hospitalizations or surgery,1 [' Q0 X0 L, y( q# i ^ H% W
and his psychosocial and psychomotor development
" d# V7 P) F+ U0 k3 i% m1 jwas age appropriate.9 z4 C- E1 y; J9 ~
The family history was remarkable for the father,( C2 G. m- E1 ]8 ?
who was diagnosed with hypothyroidism at age 16,5 r1 r# W& K! u# W' H c# ]
which was treated with thyroxine. The father’s
, m7 N: i$ k) y7 I6 xheight was 6 feet, and he went through a somewhat
" Q2 N8 R V( W& V k# D U9 b7 Pearly puberty and had stopped growing by age 14.* O* z4 d2 _ j O
The father denied taking any other medication. The$ w) L. J, p% r1 i) n
child’s mother was in good health. Her menarche& y1 t: s; s0 X
was at 11 years of age, and her height was at 5 feet P/ i9 ~# a9 x6 u6 e- K
5 inches. There was no other family history of pre-! ^8 ]. D V8 F Y2 |& k: f7 `
cocious sexual development in the first-degree rela-( ?$ {' X2 Z9 l1 s9 ^5 X
tives. There were no siblings.
M+ w; i0 L, C" _+ z! MPhysical Examination
, ?1 N t9 T/ xThe physical examination revealed a very active,/ M4 S9 a0 P; t) s7 X! k6 ~, H
playful, and healthy boy. The vital signs documented
5 ?7 ]6 E4 n7 @3 e# t& m0 f% E" [a blood pressure of 85/50 mm Hg, his length was- {9 D( o! J& H8 I$ o' F
90 cm (>97th percentile), and his weight was 14.4 kg
7 `7 o5 R" |6 Z; O/ @* W(also >97th percentile). The observed yearly growth) S9 I7 i8 G+ B% |" r/ P* Z
velocity was 30 cm (12 inches). The examination of7 `# G$ f$ i: @* y: Y/ O. N
the neck revealed no thyroid enlargement.' y3 \+ n% [/ l# d# f& {
The genitourinary examination was remarkable for
; ~. E0 a5 y' o* d& X9 Uenlargement of the penis, with a stretched length of0 E; t) a& v6 O8 e# E
8 cm and a width of 2 cm. The glans penis was very well: [1 t7 ~, u% n A+ o
developed. The pubic hair was Tanner II, mostly around2 G5 `, {2 w+ e8 \3 l
540
' {, }% {8 j' }% q- Cat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from. M Y! @0 L6 ]; [* F3 G P: N
the base of the phallus and was dark and curled. The. `, f" R B. G7 C( t0 N6 j
testicular volume was prepubertal at 2 mL each.
: o8 ?% o8 Z# K! H8 C4 } lThe skin was moist and smooth and somewhat
3 z& Z( t6 q; c" O( b& w4 xoily. No axillary hair was noted. There were no
1 Z @3 W7 a& B* b. b Kabnormal skin pigmentations or café-au-lait spots.6 V0 J6 a) e5 X2 L( }$ K
Neurologic evaluation showed deep tendon reflex 2+1 y3 G* D2 J9 V3 l
bilateral and symmetrical. There was no suggestion0 a d( m* c2 h; m# i6 {- z$ F+ Z4 I
of papilledema.* M- W0 M9 E( `# {5 F' l" x& J
Laboratory Evaluation9 F N# ^- D0 \/ m
The bone age was consistent with 28 months by
( b- f9 @) U2 r& f- L, Gusing the standard of Greulich and Pyle at a chrono-, g! j [7 I. ^3 W7 t
logic age of 16 months (advanced).5 Chromosomal8 G/ h4 l# t1 x& q
karyotype was 46XY. The thyroid function test
+ y8 G7 W, N9 Z+ K& M- t4 |showed a free T4 of 1.69 ng/dL, and thyroid stimu-3 W7 I2 {7 g" d4 F
lating hormone level was 1.3 µIU/mL (both normal).% g7 S9 g3 K/ A: F: w: z/ T' y0 D( m
The concentrations of serum electrolytes, blood: j7 p) J$ W- Q
urea nitrogen, creatinine, and calcium all were
$ m% U3 _( b* E: D0 Q- P( Cwithin normal range for his age. The concentration
5 V1 E% H. G/ P3 k1 E" `6 ]8 hof serum 17-hydroxyprogesterone was 16 ng/dL
( Q( o8 C4 h O9 j* N0 @4 Z9 g8 \# g(normal, 3 to 90 ng/dL), androstenedione was 206 b' f/ ]7 b: }9 p% S
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-; v! k; i( I9 X% a- W
terone was 38 ng/dL (normal, 50 to 760 ng/dL),$ N1 r; w8 a, Z+ S
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
! i5 o3 U' r& d49ng/dL), 11-desoxycortisol (specific compound S)0 Z) _( w6 e( D: ~. K
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
o$ O3 u5 l+ m# A- a5 ^tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
* ?" x( }( L F% t, F9 I5 stestosterone was 60 ng/dL (normal <3 to 10 ng/dL),# O6 p' |( k6 K
and β-human chorionic gonadotropin was less than
0 y/ w# K8 u$ h1 E# ]/ j6 B5 mIU/mL (normal <5 mIU/mL). Serum follicular G/ s. \4 c8 m; `' J
stimulating hormone and leuteinizing hormone; @' S: D, L+ V0 ?$ K
concentrations were less than 0.05 mIU/mL
5 M- u6 e# |7 ?0 e2 A0 c(prepubertal).. K& V4 h" w. Q0 H; o9 h
The parents were notified about the laboratory. o3 k% E) U+ c) U* u4 @
results and were informed that all of the tests were) _' [# R) D# K7 G
normal except the testosterone level was high. The
. P9 y- m5 I% x5 ~9 i* qfollow-up visit was arranged within a few weeks to
7 ?8 q( N# m. A" S5 g; E. Aobtain testicular and abdominal sonograms; how-) t: H# Y0 \6 _* l
ever, the family did not return for 4 months.2 C8 k2 l% C) ]7 V; f* a) n
Physical examination at this time revealed that the
- C+ f7 G* ^ v* I" k% J* @child had grown 2.5 cm in 4 months and had gained
, N- ?1 T7 c8 Y& U2 kg of weight. Physical examination remained
0 d% r% L$ R4 T/ G- l$ {unchanged. Surprisingly, the pubic hair almost com-
. r9 Q! }6 H& F; @) m2 E, k Hpletely disappeared except for a few vellous hairs at& o9 S3 v: z5 _2 o; e* z8 f
the base of the phallus. Testicular volume was still 2
9 [9 T$ p5 C. E, E% @' M% x& HmL, and the size of the penis remained unchanged.
( n& j8 T+ Z) B) S0 V, AThe mother also said that the boy was no longer hav-+ ^& i# [1 U5 ]0 E9 D/ O. {, q
ing frequent erections., U4 @2 i5 e2 H$ x3 m, {
Both parents were again questioned about use of
* y' v$ |& b4 F' n2 @any ointment/creams that they may have applied to/ |& ^9 p% c6 b) T& N
the child’s skin. This time the father admitted the
: P% ?8 d( \5 _, E5 B8 T7 K0 }6 JTopical Testosterone Exposure / Bhowmick et al 541- T% @" B, K' g
use of testosterone gel twice daily that he was apply-
+ e* z8 e5 T4 j$ Ging over his own shoulders, chest, and back area for
0 F% q. k" d" N9 pa year. The father also revealed he was embarrassed
6 |; S R0 A5 E3 F: Uto disclose that he was using a testosterone gel pre-* l" h9 z: V* h8 q: d! `5 {
scribed by his family physician for decreased libido4 f; }* |2 g. k& }' v
secondary to depression.
$ g# q: q6 u, _The child slept in the same bed with parents.
) y/ D! q% s+ @$ M' i7 d9 SThe father would hug the baby and hold him on his1 @! a" [9 Q, x+ Q
chest for a considerable period of time, causing sig-
: i: \/ @4 q. F% i) Rnificant bare skin contact between baby and father.0 A! f- V* l8 H M! ~2 [) \
The father also admitted that after the phone call,
^' P0 y: s" e! T A& t) Dwhen he learned the testosterone level in the baby
7 F. F4 h) T8 S" ^& w# Swas high, he then read the product information( m( L+ M% L; ?6 X2 ]+ H* m
packet and concluded that it was most likely the rea-
- K4 b6 C* a+ e5 Ison for the child’s virilization. At that time, they9 {1 l! ~6 J8 P) U K
decided to put the baby in a separate bed, and the
6 n) V" e# r$ X' u8 Hfather was not hugging him with bare skin and had/ a- s: l4 ~0 B4 G
been using protective clothing. A repeat testosterone
% N |. F- _# u/ C) a- S7 b8 j" itest was ordered, but the family did not go to the
1 ^! A0 ]# ]7 C$ n. [7 N' P1 l) Xlaboratory to obtain the test.# y- D7 L: }5 l, ]0 P* S2 r# M- S
Discussion9 i6 Z7 H7 M- p
Precocious puberty in boys is defined as secondary) G: [, J9 t# _/ G/ \' e- S
sexual development before 9 years of age.1,4
6 `# O9 k, c& i- _1 F }% Y/ |Precocious puberty is termed as central (true) when
. v$ ?% J3 M3 Bit is caused by the premature activation of hypo-: B% R7 A, S' C+ c
thalamic pituitary gonadal axis. CPP is more com-9 Y1 V8 D; X. R2 y E- ~: }
mon in girls than in boys.1,3 Most boys with CPP
3 Y) c6 L. P, t& F7 t0 Bmay have a central nervous system lesion that is
5 ^% i2 n4 O! U4 C6 A# Yresponsible for the early activation of the hypothal-0 I, ?+ `( v v( k" Q5 J7 a9 A9 g
amic pituitary gonadal axis.1-3 Thus, greater empha-
9 D' {: H5 f6 y/ c5 @9 _sis has been given to neuroradiologic imaging in
# G; S7 s6 q8 y x' O; g" jboys with precocious puberty. In addition to viril-
: F o# |& a1 m+ _: |; mization, the clinical hallmark of CPP is the symmet-
0 Y( s2 C% ~5 Grical testicular growth secondary to stimulation by% m- B8 L5 K, [
gonadotropins.1,3
2 ~, `* ~ V. v. ^: pGonadotropin-independent peripheral preco-
, P# j* I9 J7 }' p5 Mcious puberty in boys also results from inappropriate
/ e$ W0 e: e; o7 w# I- O5 `androgenic stimulation from either endogenous or# H3 g1 k$ p4 B' }/ g) W/ g
exogenous sources, nonpituitary gonadotropin stim-
: {: O" b& ~* I1 {: `4 v. l6 Rulation, and rare activating mutations.3 Virilizing
* @6 Q! X5 J4 c0 ?9 n; Acongenital adrenal hyperplasia producing excessive
/ u0 M H& f; X# y) B. o0 u8 K0 Gadrenal androgens is a common cause of precocious
2 _% y" m5 \. a$ Q- K3 A Ppuberty in boys.3,4' m" s3 _- i2 a
The most common form of congenital adrenal
2 `1 f# u1 I" m% Y+ f9 dhyperplasia is the 21-hydroxylase enzyme deficiency.8 N3 m) X4 x: H$ w3 g
The 11-β hydroxylase deficiency may also result in
% ~+ A) S; {+ x2 zexcessive adrenal androgen production, and rarely,
7 T6 R$ i( x' K6 ], @2 t1 Tan adrenal tumor may also cause adrenal androgen2 [7 ~* u5 C+ |: I2 J% J
excess.1,3
8 L0 Q m" ?; A% Q, i' \! H8 E8 oat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
2 A% ] P- O" [( i, @8 g& O' a542 Clinical Pediatrics / Vol. 46, No. 6, July 20074 D- D3 h0 B* n- o' u
A unique entity of male-limited gonadotropin-2 F- }6 j* r) P9 q
independent precocious puberty, which is also known
! j% v$ h+ Q( x# J% ]" W0 fas testotoxicosis, may cause precocious puberty at a. g$ p" M7 `/ h1 w$ Z
very young age. The physical findings in these boys
8 b5 \1 }; @; R3 Awith this disorder are full pubertal development,
- l. w- r: t, l" c1 R: u3 ~including bilateral testicular growth, similar to boys8 `( _+ J5 o. H. d. F. d
with CPP. The gonadotropin levels in this disorder! X5 U/ j, W7 S2 u) o8 L# F
are suppressed to prepubertal levels and do not show; R/ H+ y4 |& _2 y* Q1 A
pubertal response of gonadotropin after gonadotropin-
! [3 N# S" ]/ d. P1 J+ Ireleasing hormone stimulation. This is a sex-linked
+ @! G8 ]' _; ^; a2 O, sautosomal dominant disorder that affects only
2 i! g$ V; T7 M4 f* \& P9 emales; therefore, other male members of the family5 D! [* k/ n1 D$ W* d$ x4 `5 B
may have similar precocious puberty.34 b6 |% C- e$ m# F- ~
In our patient, physical examination was incon-
% y; R. i7 ?3 ?* r' H) ?& F4 Esistent with true precocious puberty since his testi-
s: Y/ B5 j5 i7 fcles were prepubertal in size. However, testotoxicosis+ ?4 M3 U, T* V, D ?9 V
was in the differential diagnosis because his father) i) L& C0 y, @1 A
started puberty somewhat early, and occasionally,
$ j0 `: G0 M% Ntesticular enlargement is not that evident in the
k- ~. n' H) y3 _4 G% O0 dbeginning of this process.1 In the absence of a neg-+ w" m/ b4 k) N* \2 E
ative initial history of androgen exposure, our6 R( r* K, L |; u1 F% n, P
biggest concern was virilizing adrenal hyperplasia,
, P# A0 Y/ A9 O$ Meither 21-hydroxylase deficiency or 11-β hydroxylase
$ |. B4 B" [- V# ydeficiency. Those diagnoses were excluded by find-
5 X# l; Z. ~ @7 v5 z j; {$ c9 Ling the normal level of adrenal steroids.
$ |! N# c ? t- ?The diagnosis of exogenous androgens was strongly
. X0 J; n6 |, G! s4 fsuspected in a follow-up visit after 4 months because
) `6 u; _3 S- @) ~8 x0 dthe physical examination revealed the complete disap-
* r% X) \! Q8 c9 ^5 e/ Tpearance of pubic hair, normal growth velocity, and
$ ]& R; s, m7 H7 @# R$ ndecreased erections. The father admitted using a testos-5 H6 \2 _. L- Z% A
terone gel, which he concealed at first visit. He was
! g/ H/ B6 t& O! Jusing it rather frequently, twice a day. The Physicians’, z% y$ S# g' o0 d9 n) b9 ?
Desk Reference, or package insert of this product, gel or
, m# H$ L5 Y! v7 u, \, g8 p0 pcream, cautions about dermal testosterone transfer to
* L: e$ `& ~; m0 T+ ^unprotected females through direct skin exposure.. y: W% e5 C. ]5 {' `# p0 ]
Serum testosterone level was found to be 2 times the
9 [& K3 L& }% W. R* w1 kbaseline value in those females who were exposed to) r' J. ^ ]. t
even 15 minutes of direct skin contact with their male
! o) \9 f$ O& A* k5 B; Wpartners.6 However, when a shirt covered the applica-7 E' O" G6 [/ e; T$ ]
tion site, this testosterone transfer was prevented.
; O& P( G. N5 U) Y8 C: Z; a9 v2 }Our patient’s testosterone level was 60 ng/mL,
/ Q7 ~/ |5 f& [+ `/ fwhich was clearly high. Some studies suggest that
+ W( B6 U9 p9 @$ D. ~, jdermal conversion of testosterone to dihydrotestos- O" g% x, h, }3 L+ V% A
terone, which is a more potent metabolite, is more
3 }6 U% W I; d: G- tactive in young children exposed to testosterone
6 F" R$ r& t5 h' K* kexogenously7; however, we did not measure a dihy-$ U! g( s& I. ?% F( V
drotestosterone level in our patient. In addition to0 ^# n- B& F$ |% Z/ x
virilization, exposure to exogenous testosterone in
0 l0 x2 R- `2 E9 rchildren results in an increase in growth velocity and% s/ c( d$ |$ E7 s. A" U! z4 o Z
advanced bone age, as seen in our patient.5 j1 a* F# l+ b- x7 \6 y
The long-term effect of androgen exposure during
$ d/ P% q* Z2 Y2 C9 I% m" Kearly childhood on pubertal development and final
6 t# L. }- O9 I0 ]; N: Uadult height are not fully known and always remain7 p/ `+ C8 z7 U$ @. y4 A4 V+ u" p
a concern. Children treated with short-term testos-
5 u3 h+ y1 y5 Y; C; Iterone injection or topical androgen may exhibit some
. }7 E, ^8 ~$ e4 u9 L3 Gacceleration of the skeletal maturation; however, after1 ]% F3 V& B" E- p- y' E4 t9 v5 x
cessation of treatment, the rate of bone maturation
6 v2 _! A, q( m' h0 Cdecelerates and gradually returns to normal.8,9
- ~# @4 R7 } ]# m* bThere are conflicting reports and controversy
5 V& J3 J4 _/ R2 ?" A! ^over the effect of early androgen exposure on adult
: o' y+ u' k1 V B Kpenile length.10,11 Some reports suggest subnormal
# A- E) o* Q4 R( l# Tadult penile length, apparently because of downreg-. E+ f$ u6 J N7 ?) [
ulation of androgen receptor number.10,12 However,
; H% t% _: K0 f; r! H( zSutherland et al13 did not find a correlation between
7 N9 P8 E0 M2 H, J! S/ cchildhood testosterone exposure and reduced adult
: w) d/ T1 T6 Z% ^ _penile length in clinical studies. p6 N/ ?' p. y5 v
Nonetheless, we do not believe our patient is0 V5 y n: M# r& j: ?* @
going to experience any of the untoward effects from
) L- q1 `5 A: A1 }6 v# I! Otestosterone exposure as mentioned earlier because
0 |8 F+ q" ~7 V, t' U" ]! {the exposure was not for a prolonged period of time.
/ d7 K: @" T5 `$ b1 cAlthough the bone age was advanced at the time of& |6 M' ~' B: m3 z3 \ d8 d
diagnosis, the child had a normal growth velocity at: W( `& R. T& @) |
the follow-up visit. It is hoped that his final adult
: S0 V, D! E' M5 u: ]* {height will not be affected.: ]9 K+ p; ^" T6 w' }7 q$ S8 w' `, v: Y: y
Although rarely reported, the widespread avail-
, y7 \$ J7 t/ Y4 j! `ability of androgen products in our society may+ S/ o" B" x+ e% e
indeed cause more virilization in male or female& V8 |7 t; @2 `# r& a' ]
children than one would realize. Exposure to andro-: H/ A, z( J4 N: A* k8 c& e# b
gen products must be considered and specific ques-
) p6 @4 { Z# i# rtioning about the use of a testosterone product or/ Z: X( w& c4 j0 {% {
gel should be asked of the family members during
^0 ?" [: h' Kthe evaluation of any children who present with vir-% z7 {$ H* V5 e, H
ilization or peripheral precocious puberty. The diag-, y. n8 X5 e ?$ s/ v4 p- _' r+ | J
nosis can be established by just a few tests and by
9 P- {9 ~5 i$ Y+ x3 F. o) O Oappropriate history. The inability to obtain such a- Z4 d9 K# j5 C
history, or failure to ask the specific questions, may' t5 z* d( u& M7 [9 l
result in extensive, unnecessary, and expensive3 a* }5 V% i: g8 [' u* f) P
investigation. The primary care physician should be
0 w: C# i1 {' V( X* b6 Eaware of this fact, because most of these children% r9 k# |9 l7 M# g5 E. B, m; ]/ y' k
may initially present in their practice. The Physicians’. [/ ?) [, ]$ t
Desk Reference and package insert should also put a
6 @: Z0 t. R. O' {warning about the virilizing effect on a male or
7 K8 h! A- F' G! Q, ~female child who might come in contact with some-
8 ]) G6 \. i" J Y& V7 L1 B& Qone using any of these products.
$ ^9 f* O [. c7 i4 c0 a# jReferences+ [8 c U8 `% h9 m: S
1. Styne DM. The testes: disorder of sexual differentiation" |+ {) j% ^, x, V5 o: `
and puberty in the male. In: Sperling MA, ed. Pediatric
( _; i0 V. x$ `8 d1 x& f3 QEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;, g4 Y W7 E/ | U! o/ p
2002: 565-628.8 N0 s) e, t# N8 B5 _6 e4 _4 K
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
" j i0 d G9 V- k8 q9 J+ mpuberty in children with tumours of the suprasellar pineal |
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