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Sexual Precocity in a 16-Month-Old
( N" M4 {" e$ _! n+ g+ xBoy Induced by Indirect Topical9 U& o/ G" h9 K5 G
Exposure to Testosterone6 o% U8 V$ c% L. f8 U' o
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
7 c" q% U2 [5 ^4 b' I7 A- oand Kenneth R. Rettig, MD12 M9 f c. ~# G. u! e
Clinical Pediatrics0 `; s9 u! f1 \+ s
Volume 46 Number 6' Y: G+ L) G* b7 l+ H" X
July 2007 540-5434 J x5 V& p' S7 s
© 2007 Sage Publications: N: k$ ] F+ O0 g' W- K$ i( u; [
10.1177/0009922806296651
6 _/ f) f0 s' xhttp://clp.sagepub.com$ J$ |0 Y8 ?6 [8 x7 I
hosted at
3 x- l/ k3 Z: f; O8 ?http://online.sagepub.com/ P5 ]" l- b% Q) r- R# `
Precocious puberty in boys, central or peripheral,
/ Z! E! {0 m$ [' w/ Eis a significant concern for physicians. Central# R: G5 p7 e) L0 E2 J
precocious puberty (CPP), which is mediated
8 v7 g/ n) k# d U: u/ J' Xthrough the hypothalamic pituitary gonadal axis, has
! l9 I8 K" ~/ X) D9 Ba higher incidence of organic central nervous system
6 d' \* ~1 e& }" d0 [+ rlesions in boys.1,2 Virilization in boys, as manifested( k1 F# ^4 |- V4 M) D( S
by enlargement of the penis, development of pubic
1 [3 A- }) R6 U6 U) Bhair, and facial acne without enlargement of testi-
5 E d' W7 f7 [; w0 acles, suggests peripheral or pseudopuberty.1-3 We! G; n0 V) i0 V% F
report a 16-month-old boy who presented with the' `" K) C7 |5 }7 A; k9 A
enlargement of the phallus and pubic hair develop-
. q3 s% I5 O$ Jment without testicular enlargement, which was due- @# s* p5 B! \ x t
to the unintentional exposure to androgen gel used by
; E, f7 o% w0 V; Q) w7 Othe father. The family initially concealed this infor-2 ~) A5 H K) Z. U
mation, resulting in an extensive work-up for this
9 i, m' S! }6 T1 `3 ]9 A# Vchild. Given the widespread and easy availability of
0 G3 S0 u$ ]+ d' v% ptestosterone gel and cream, we believe this is proba-
: C. M1 h( X- lbly more common than the rare case report in the
; K# o% B5 ]9 s& Z% M# g, _' oliterature.45 m$ p+ J8 w7 ?
Patient Report
5 }, T7 |8 J) H* `A 16-month-old white child was referred to the6 G5 T# i9 K n
endocrine clinic by his pediatrician with the concern
- Y0 n# _$ p9 Gof early sexual development. His mother noticed
% [4 H) ~- R* w+ C' flight colored pubic hair development when he was
7 x, _: Y" v" t7 |: n; D- {1 Y( r. xFrom the 1Division of Pediatric Endocrinology, 2University of+ E/ B/ k; C. [7 K- B, F
South Alabama Medical Center, Mobile, Alabama.
; W/ v% L# @2 ^. v8 ^0 e4 XAddress correspondence to: Samar K. Bhowmick, MD, FACE,
* }1 i' M; D- {, ^& V' yProfessor of Pediatrics, University of South Alabama, College of
* r4 e) e- r9 L+ {% W$ eMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297; |) ]% ~7 x1 H: c8 F! U
e-mail: [email protected].& J9 w8 ?. K& h( N
about 6 to 7 months old, which progressively became
, ^2 L$ @5 d* {( n- ydarker. She was also concerned about the enlarge-
* ?, ^- m" @6 ]) n9 M% I6 |. Iment of his penis and frequent erections. The child4 m2 _- g. I, u
was the product of a full-term normal delivery, with
+ Q# J8 ~1 U7 [1 R, t, la birth weight of 7 lb 14 oz, and birth length of1 @( _- Q) L& U: w
20 inches. He was breast-fed throughout the first year2 R9 @' r1 }9 l; Z$ _
of life and was still receiving breast milk along with1 ^# Q3 V' S1 b7 D% C$ Q' Y0 t! A
solid food. He had no hospitalizations or surgery,
5 Z M/ F( ~2 W. `and his psychosocial and psychomotor development
( W) W- S5 s9 i6 P; kwas age appropriate.' O8 ~' |* l) U- i- P
The family history was remarkable for the father,
! M9 k; V' m, U6 ?3 X0 [who was diagnosed with hypothyroidism at age 16,- R$ o7 d. b! o
which was treated with thyroxine. The father’s
; w) H$ I* H) \! h- @1 Eheight was 6 feet, and he went through a somewhat
4 Y5 Q1 W# d: c) Z" ^4 Dearly puberty and had stopped growing by age 14.
! q) W- R5 D' t+ k7 ?The father denied taking any other medication. The
) R; n/ R. ]6 N% Uchild’s mother was in good health. Her menarche& T U Q A. f
was at 11 years of age, and her height was at 5 feet
G+ B( |& w& M- Y% h$ [( l5 B4 f5 inches. There was no other family history of pre-# b' t, u0 ?! O3 _
cocious sexual development in the first-degree rela-
9 e' b. x* S5 L# ]) @) gtives. There were no siblings.8 q+ }' I- K, o2 @* N* Q: L$ r
Physical Examination. {9 Q( `7 [, l) ]" g. g, h
The physical examination revealed a very active,
, ^9 U5 W1 u! {: b2 S2 G, vplayful, and healthy boy. The vital signs documented0 ]) a/ G: R! i3 D3 P" x7 x6 A
a blood pressure of 85/50 mm Hg, his length was
+ W, j$ [2 ]$ i+ v" P) X90 cm (>97th percentile), and his weight was 14.4 kg
' O% X& m! i8 V- M(also >97th percentile). The observed yearly growth
' `- p8 I8 L% J" hvelocity was 30 cm (12 inches). The examination of
7 ?3 Q2 r. ] C7 Q$ f: i0 o! Y& w zthe neck revealed no thyroid enlargement.
4 u. O% z9 z2 o, Q. j7 WThe genitourinary examination was remarkable for
+ c% o* Z. {# ?1 }- [2 S2 @" Ienlargement of the penis, with a stretched length of$ p5 {6 r( i- Q4 T; m* c! K
8 cm and a width of 2 cm. The glans penis was very well
. ^0 ?- e; r7 Mdeveloped. The pubic hair was Tanner II, mostly around
9 W/ f6 ]6 T1 K( b* J540- t+ \+ R" \+ h6 `& o
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
2 r5 T7 @5 o7 {1 Q/ Zthe base of the phallus and was dark and curled. The
) N* A1 A {3 f, c' t* ctesticular volume was prepubertal at 2 mL each.) p$ W' s- x$ X R* N- ~- T
The skin was moist and smooth and somewhat
$ I1 G8 M- ?4 d3 Koily. No axillary hair was noted. There were no
: p3 i- r5 H& S, r7 Yabnormal skin pigmentations or café-au-lait spots.; {1 G. J; b: `; k- M6 u E
Neurologic evaluation showed deep tendon reflex 2+
' u& R+ @4 k2 U" Y$ N" mbilateral and symmetrical. There was no suggestion
$ U; j8 ~9 {2 g0 W: Q4 |of papilledema.) ~' l: p6 P$ u7 L. E5 a
Laboratory Evaluation
' a X0 P$ n' y# | S AThe bone age was consistent with 28 months by- \3 }% c0 \% v' O# Z
using the standard of Greulich and Pyle at a chrono-
% L9 G3 ?( P1 i" W8 W% g; B* K: Flogic age of 16 months (advanced).5 Chromosomal" n* ?( a5 X& V4 \; B3 i/ B& q- |
karyotype was 46XY. The thyroid function test p+ u' Z: j& O/ D; e( ~5 J
showed a free T4 of 1.69 ng/dL, and thyroid stimu-2 I' O% }! {, h; U8 j/ u
lating hormone level was 1.3 µIU/mL (both normal)." U( V; R L" u7 a' x
The concentrations of serum electrolytes, blood+ ~- W/ m! x2 K+ [
urea nitrogen, creatinine, and calcium all were- y# ~$ M1 s; v" X
within normal range for his age. The concentration( M: ~5 i, n# z" I( d( F; U
of serum 17-hydroxyprogesterone was 16 ng/dL
9 q% L7 W9 @& J) C, H(normal, 3 to 90 ng/dL), androstenedione was 20
( ~, e0 W: l; w) |" p6 Fng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-9 y# U0 i2 ^! c7 D m
terone was 38 ng/dL (normal, 50 to 760 ng/dL),! K3 k+ I; x# T* e
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
5 z4 {: `. s0 s4 `9 {49ng/dL), 11-desoxycortisol (specific compound S)) e/ y4 ?( d+ s4 }1 m
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-; I, j7 L3 I: b5 m
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total# W; O- q }$ [0 @' ]2 E! z
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),2 k5 }; c0 U) a* k# K8 ^
and β-human chorionic gonadotropin was less than4 W% y/ `* E" t1 C4 W9 K
5 mIU/mL (normal <5 mIU/mL). Serum follicular) W/ O. i" ?) e5 a s+ N
stimulating hormone and leuteinizing hormone
1 O6 Y8 z- m; N$ X$ Xconcentrations were less than 0.05 mIU/mL' y. a' j0 f3 |' K' {
(prepubertal).
0 z* f$ o: a5 s7 T( D+ jThe parents were notified about the laboratory
& f$ |) m. a+ y$ Qresults and were informed that all of the tests were
% z. Y4 ]0 L9 ^! y M* s! S# L- hnormal except the testosterone level was high. The
# i* i! d, [$ ^follow-up visit was arranged within a few weeks to; I; W( z* w, E1 @
obtain testicular and abdominal sonograms; how-
: k" [# W7 p. b7 D3 x8 Tever, the family did not return for 4 months.% v1 E/ S+ Q0 g1 n6 D/ M1 s. S4 }
Physical examination at this time revealed that the9 v+ y$ _0 j* S; E8 p/ z: w
child had grown 2.5 cm in 4 months and had gained7 T8 k7 {/ I0 n* j9 k }& F
2 kg of weight. Physical examination remained
9 Y" t% }" W. Z2 ?9 A1 Kunchanged. Surprisingly, the pubic hair almost com-
: z$ R8 m* z+ t: A8 spletely disappeared except for a few vellous hairs at
- p9 I6 [% J% T' w2 Y" O2 @the base of the phallus. Testicular volume was still 27 t1 k+ s2 m' b9 P0 F* g9 [
mL, and the size of the penis remained unchanged.8 Q2 M q0 e9 ^! B7 x2 N
The mother also said that the boy was no longer hav-
/ ?! U3 @, O/ v: bing frequent erections.
8 Q9 J+ k: p0 A$ V0 S5 S( ^Both parents were again questioned about use of
/ M& y1 \/ Y9 N' Pany ointment/creams that they may have applied to- r% ]* a- T1 P" N/ l
the child’s skin. This time the father admitted the
' i6 E' U' G/ X6 E4 GTopical Testosterone Exposure / Bhowmick et al 5412 ?+ E w* F F
use of testosterone gel twice daily that he was apply-
' E/ i! T, G) fing over his own shoulders, chest, and back area for
' o' g* c( S; a3 }/ H1 wa year. The father also revealed he was embarrassed
3 u, z- F8 K3 h/ e4 ]! ]to disclose that he was using a testosterone gel pre-
, G- ?3 N+ O! Y' Y; |1 I6 B( L6 Q8 iscribed by his family physician for decreased libido
) K% ?% I" O0 Esecondary to depression.. ~8 p- Z7 w2 W+ n+ ]( D5 C9 t
The child slept in the same bed with parents. U( f: j$ ]# e% `+ M+ [7 G: z
The father would hug the baby and hold him on his2 s, Z1 t$ ]3 r. B! D
chest for a considerable period of time, causing sig-
s2 e2 g, }; c8 E% r7 gnificant bare skin contact between baby and father.1 A+ L8 d9 C% { ]5 [3 T
The father also admitted that after the phone call,) @ P! h: }8 w+ F" \
when he learned the testosterone level in the baby
D/ i$ I% v7 {. C; W9 w* x$ xwas high, he then read the product information3 _$ a# f5 D, D. i, a) I+ D. d. W
packet and concluded that it was most likely the rea-
: c: q+ G3 a o( C9 Bson for the child’s virilization. At that time, they6 Q% f" F; ]0 ~3 |3 g
decided to put the baby in a separate bed, and the
* T5 d' S! K) ~: [father was not hugging him with bare skin and had
& G, K M$ c# u% V5 cbeen using protective clothing. A repeat testosterone; q1 H! _6 L* R# P
test was ordered, but the family did not go to the
* `3 N3 u6 O: L( \0 t$ Q; E; nlaboratory to obtain the test.' M6 Z/ |* D1 \
Discussion
1 j( u. n s# `4 d+ q8 M0 YPrecocious puberty in boys is defined as secondary, a& k+ j3 @& O1 }0 ?2 C2 H5 D
sexual development before 9 years of age.1,4
9 J/ C: y0 B- @& i/ M* dPrecocious puberty is termed as central (true) when
X- h7 C- Z0 Eit is caused by the premature activation of hypo-
+ U) a, Y4 f/ X5 W2 M. Z$ x1 y- \thalamic pituitary gonadal axis. CPP is more com- a# C/ r, c& s4 P! G/ x# r
mon in girls than in boys.1,3 Most boys with CPP
* V) e4 Q4 n0 emay have a central nervous system lesion that is9 }. ~( L g; j1 q$ Z
responsible for the early activation of the hypothal-; J$ _: _5 Y- m9 v( _) [8 T3 x
amic pituitary gonadal axis.1-3 Thus, greater empha-
( a* W; j- F7 q* Psis has been given to neuroradiologic imaging in
+ } m1 C7 y. W! r. q6 p& } Lboys with precocious puberty. In addition to viril-
2 _( Q# i9 W# u5 w3 Vization, the clinical hallmark of CPP is the symmet-
; C, `6 D$ E: J; e0 l+ `rical testicular growth secondary to stimulation by; Z/ g: I/ Z6 Y9 ^/ L& E
gonadotropins.1,3
& A1 s" R+ T, p0 F6 U3 ]+ h* x; ZGonadotropin-independent peripheral preco-1 d2 X e) ^ |4 `2 l4 X9 U
cious puberty in boys also results from inappropriate( a- [7 b5 E* u/ D5 E
androgenic stimulation from either endogenous or& a; x6 N; [6 v* |" \' f! j, I
exogenous sources, nonpituitary gonadotropin stim-
: ]* [/ {! T0 \- S# L( D& F- _ulation, and rare activating mutations.3 Virilizing d+ T ]2 a3 s4 x, _5 E: J5 q: H8 p6 o
congenital adrenal hyperplasia producing excessive7 N: L# i( G- c/ a7 k
adrenal androgens is a common cause of precocious
6 _' i9 U5 W& E" Y I: A& upuberty in boys.3,44 \4 `: L X0 ?5 J6 b* R
The most common form of congenital adrenal8 x! r/ { P# t1 [3 |
hyperplasia is the 21-hydroxylase enzyme deficiency.2 v1 a! p# @" T( j7 y
The 11-β hydroxylase deficiency may also result in' J; t& t. B# `! T, c7 y% L
excessive adrenal androgen production, and rarely,- ^! k E6 O/ a) g* @8 z
an adrenal tumor may also cause adrenal androgen0 i( z9 h0 ~, e8 q
excess.1,3; |* J1 R3 x4 r6 B8 s. p9 F
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
1 n; u3 o, t6 V9 O4 n* R: E: _2 r542 Clinical Pediatrics / Vol. 46, No. 6, July 20070 p& j, r7 S* B$ q' T! D4 }
A unique entity of male-limited gonadotropin-
, Q/ |( z _& D& h; G2 r3 l/ T3 [independent precocious puberty, which is also known
, Q8 w7 R2 e0 Q* ^as testotoxicosis, may cause precocious puberty at a
3 t6 G# } ? Q+ {9 M9 c% Dvery young age. The physical findings in these boys
2 ^. t8 f) f" _) h. H3 m# h, }' wwith this disorder are full pubertal development,5 o9 K3 L* A( b+ H
including bilateral testicular growth, similar to boys8 T7 @( K# N7 X2 i. y# M
with CPP. The gonadotropin levels in this disorder6 I- D$ O% t8 ]' w$ x& q2 f
are suppressed to prepubertal levels and do not show
: R1 D& J; ]6 f+ ]1 bpubertal response of gonadotropin after gonadotropin-: E. d; L; I. ^3 Y1 D
releasing hormone stimulation. This is a sex-linked
2 Q1 J* r7 X! f) H# A3 }! yautosomal dominant disorder that affects only+ h+ u! @# a9 X! W
males; therefore, other male members of the family
2 z; |: S# v) I! @may have similar precocious puberty.3: d! I& l1 N7 v! r1 r
In our patient, physical examination was incon-0 }( f2 ]8 H# W3 }9 T" L) W& E1 u4 v# k% c
sistent with true precocious puberty since his testi-. m9 U/ q/ q1 d4 O7 v; f
cles were prepubertal in size. However, testotoxicosis
% m$ a6 N8 r7 i& A: {/ qwas in the differential diagnosis because his father) |/ H5 b5 r. _
started puberty somewhat early, and occasionally,
) \3 e( o; i+ M/ q) b' n: \) k7 ~testicular enlargement is not that evident in the2 n9 q) {3 D0 ~' ~+ r5 W$ _- p4 K
beginning of this process.1 In the absence of a neg-
6 F8 L, d$ c* [$ M0 q+ ?+ ]' q# m' |ative initial history of androgen exposure, our& x! Z {; ~7 z7 o" K& d0 b
biggest concern was virilizing adrenal hyperplasia,/ o. G: h- n' t0 J: g* e* {, d, z
either 21-hydroxylase deficiency or 11-β hydroxylase
$ u/ {( v) }8 P2 o" }( t! w3 _7 n- Zdeficiency. Those diagnoses were excluded by find-
$ T2 q6 k0 ]# ?ing the normal level of adrenal steroids.
' @; t# m& J: w# Q+ d; E. h& d/ p0 EThe diagnosis of exogenous androgens was strongly
; n3 Z ]. _/ x* |9 A9 ysuspected in a follow-up visit after 4 months because& b! a1 Z1 N: G& Y: x% B1 M4 b$ i! j
the physical examination revealed the complete disap-
9 I% S+ u2 r; m. D' Q9 gpearance of pubic hair, normal growth velocity, and- _! u' H' e0 \
decreased erections. The father admitted using a testos-
9 \6 O6 r0 h4 s6 L' T4 |' A4 n% Uterone gel, which he concealed at first visit. He was
* N" `$ g2 v( f: f( gusing it rather frequently, twice a day. The Physicians’
+ R+ l- q0 N5 z$ {$ I( YDesk Reference, or package insert of this product, gel or: @1 l- r3 q3 ]( g% J+ Z
cream, cautions about dermal testosterone transfer to
o( R) t4 d. B/ t; c* ~4 H* punprotected females through direct skin exposure.
1 G/ ^* Z' e: o" g1 W0 n3 @$ I& P. ASerum testosterone level was found to be 2 times the) R5 _' N2 E0 A: R7 k
baseline value in those females who were exposed to* D5 f0 B$ [; {
even 15 minutes of direct skin contact with their male' V6 Z2 L8 X. z6 d
partners.6 However, when a shirt covered the applica-
- f! V/ W) }. K4 ption site, this testosterone transfer was prevented.
: a# Q( h/ l J7 J! N8 UOur patient’s testosterone level was 60 ng/mL,
- {5 O ^; e( ?8 }# owhich was clearly high. Some studies suggest that/ ^& P* |7 {) ~1 S! u
dermal conversion of testosterone to dihydrotestos-: N6 E- W6 @1 c: [
terone, which is a more potent metabolite, is more
+ z4 e- q; s6 M$ \active in young children exposed to testosterone+ I2 f! Q/ r5 O% x) L# I0 Z
exogenously7; however, we did not measure a dihy-3 n$ N$ f2 L9 ^, i8 O/ k. h# H3 D
drotestosterone level in our patient. In addition to& X2 h3 s& ?& r. E X) C# [
virilization, exposure to exogenous testosterone in9 q6 o' `8 a5 P& K& Z
children results in an increase in growth velocity and
# \* F. y2 a# s5 ^# \0 W2 M0 Fadvanced bone age, as seen in our patient.& T; o. k5 |/ l$ b) _
The long-term effect of androgen exposure during
/ @: g0 r5 |/ ~" _early childhood on pubertal development and final- X7 Z& K- Q$ |! `+ B3 ?) g: M C
adult height are not fully known and always remain9 S: L# D2 A/ p7 v1 n! Y
a concern. Children treated with short-term testos-; G+ {; L4 L& ^7 f1 I$ l* M3 l
terone injection or topical androgen may exhibit some
$ P1 S7 N1 E r3 eacceleration of the skeletal maturation; however, after
1 S/ c0 {, j* P ccessation of treatment, the rate of bone maturation6 c5 c9 n9 K5 I+ D
decelerates and gradually returns to normal.8,9
( c& M0 I" j) e. b. e9 bThere are conflicting reports and controversy
* `& S V8 ?% `% H0 ]4 ?over the effect of early androgen exposure on adult. m4 q5 R' u3 {" @5 N
penile length.10,11 Some reports suggest subnormal
% {6 n& }. {$ b) Madult penile length, apparently because of downreg-
9 T+ S2 ^0 X5 a/ V- u: v# R3 Oulation of androgen receptor number.10,12 However,
. f+ v$ I0 g" E" }6 R$ `Sutherland et al13 did not find a correlation between
5 u C/ a5 b: a7 V% \1 f# y% ?childhood testosterone exposure and reduced adult5 [4 K- _2 f) b) I! k3 ?4 S
penile length in clinical studies.
6 C9 q7 A& c/ x3 k6 \% |) K0 JNonetheless, we do not believe our patient is, ]+ U& Z/ Q! y0 E
going to experience any of the untoward effects from! q' z5 r% \5 `' D4 ^
testosterone exposure as mentioned earlier because; t0 K% S& i0 E0 ~3 o
the exposure was not for a prolonged period of time.* t, C& M" ~% A8 ]
Although the bone age was advanced at the time of. |3 ^$ C" s% z0 u
diagnosis, the child had a normal growth velocity at; |( |6 \% M, b( C$ h* O% X2 M
the follow-up visit. It is hoped that his final adult
% Z/ P! Q! c, p& Aheight will not be affected.
9 Y' k) ]4 @3 r' d3 k+ Q5 m5 OAlthough rarely reported, the widespread avail-. R) t& |* q+ R
ability of androgen products in our society may" c2 L2 R, D3 T( a
indeed cause more virilization in male or female
! }/ l0 z0 q' D' l! t- |children than one would realize. Exposure to andro-
( y) w+ u, g8 C1 c' Hgen products must be considered and specific ques-% S: T- v/ R" S$ e! q
tioning about the use of a testosterone product or
$ F! m/ A0 X5 e0 sgel should be asked of the family members during7 p5 }' @3 K# u8 N9 g3 K- B, S
the evaluation of any children who present with vir-
! T4 l& E, I: uilization or peripheral precocious puberty. The diag-
- e2 k& G9 v! i/ b. r8 |* ]) j% v6 _nosis can be established by just a few tests and by
4 G! t* M3 x6 V# \, w% bappropriate history. The inability to obtain such a
9 s. q. m: r- u6 L/ y# z, w- D. {history, or failure to ask the specific questions, may- g- {+ m" X( ?" ~1 y
result in extensive, unnecessary, and expensive( ]5 b7 ?8 _+ M# U" k
investigation. The primary care physician should be
1 W$ e2 s( v1 M7 taware of this fact, because most of these children
9 M) w; `, D! r7 f2 I: U$ y$ Dmay initially present in their practice. The Physicians’
3 M* l# S3 e( I( k2 r: t. RDesk Reference and package insert should also put a0 I3 h; O( y3 x n/ @6 r6 c
warning about the virilizing effect on a male or' P6 M$ s, E) ^$ @9 h& @
female child who might come in contact with some-
2 _& o$ \$ \ ?6 ^one using any of these products.
1 C4 R* ~' B5 P% Q' P, QReferences
3 A+ C/ C0 @' o) K! [. S7 _1. Styne DM. The testes: disorder of sexual differentiation
) u! Z* M: n* I3 tand puberty in the male. In: Sperling MA, ed. Pediatric3 C. ]" \$ }5 w' D8 M# F) s7 j3 q
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;9 B0 W* A4 N3 ^# i
2002: 565-628.
* { m& N$ v! ?0 n2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
+ U. D% Q( h$ x4 Tpuberty in children with tumours of the suprasellar pineal |
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