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Sexual Precocity in a 16-Month-Old" l+ g( ~! v0 Q+ X7 \9 x! H
Boy Induced by Indirect Topical4 {" Q" S6 B2 I8 Q: W' p1 O! h
Exposure to Testosterone r1 `) H7 m% d) X
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
6 I) x( v q% ?' Y1 Oand Kenneth R. Rettig, MD19 `* }; c C. s& r
Clinical Pediatrics
5 ?: R. r/ r6 VVolume 46 Number 62 B, d1 ^3 o u& ^
July 2007 540-543' }" f8 i0 M K7 ]9 ~# ]9 f: \
© 2007 Sage Publications' A' C. h, b8 j* ^
10.1177/0009922806296651$ g, G; [' C3 }/ J$ ]# L
http://clp.sagepub.com" o: Y( \0 y0 M, @+ }
hosted at2 F# |( `% L' E6 i: R( Y1 u3 x
http://online.sagepub.com
) T1 b0 ^5 Y/ t2 KPrecocious puberty in boys, central or peripheral,2 T8 V9 K1 D7 x
is a significant concern for physicians. Central2 }# n4 @+ I4 m: r4 ]: G# }8 [: Q! Y
precocious puberty (CPP), which is mediated* s6 _4 o+ k* m% |. m- _% G6 C4 {
through the hypothalamic pituitary gonadal axis, has+ m' S2 c l) d8 j
a higher incidence of organic central nervous system) B- G) B A1 B% N
lesions in boys.1,2 Virilization in boys, as manifested0 j5 }) |9 {8 Y) E4 d9 N3 q
by enlargement of the penis, development of pubic
) @" I% c+ G/ b) t; s6 `hair, and facial acne without enlargement of testi-( Y$ k# A/ c/ H8 @& i6 R' u' `1 `
cles, suggests peripheral or pseudopuberty.1-3 We
5 |, B5 O! ~* G5 I$ J2 ]% lreport a 16-month-old boy who presented with the
, v* R1 r" v/ ^6 U+ Z0 menlargement of the phallus and pubic hair develop-
5 m$ a) E! k4 X4 H* p0 nment without testicular enlargement, which was due2 g, k8 t: q1 ^5 p
to the unintentional exposure to androgen gel used by" z& Y$ k1 E1 X# c, n
the father. The family initially concealed this infor-
0 \: v* k+ C$ J3 cmation, resulting in an extensive work-up for this* `9 ]7 l7 [* E, ]- H3 Y3 n Y+ W
child. Given the widespread and easy availability of0 B' b3 A$ a9 @" X* M( A C8 n& x
testosterone gel and cream, we believe this is proba-
' r* b0 O8 B% L4 q/ Kbly more common than the rare case report in the
- q) u, @. v- w. ?3 e0 mliterature.4
4 m; h5 x$ m% u2 k7 D+ W+ r( J$ ?0 OPatient Report, c. z) W- h5 F" |* S2 g
A 16-month-old white child was referred to the" W2 Q N# S# f. p( ^9 k- m
endocrine clinic by his pediatrician with the concern
0 b% ~# `( a0 J; S/ u7 yof early sexual development. His mother noticed
% D% Q+ `6 f) S9 c" Glight colored pubic hair development when he was1 S7 R9 Y- m2 t3 w
From the 1Division of Pediatric Endocrinology, 2University of
6 y' d* E: P9 V6 M3 i) _0 jSouth Alabama Medical Center, Mobile, Alabama.) p4 {- I; r. }& C( q3 ` o! N7 L
Address correspondence to: Samar K. Bhowmick, MD, FACE,
3 h' v- Z* K& O" I! CProfessor of Pediatrics, University of South Alabama, College of
7 F" `0 A5 x% G: ~9 ~6 w# [Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;/ ^! i3 j5 v9 k% |6 t3 ]5 Y
e-mail: [email protected].
9 i e2 ^! t' r( n) m3 iabout 6 to 7 months old, which progressively became
0 P. M7 i7 J2 k8 S: Q0 W: {darker. She was also concerned about the enlarge-
* m" q! g9 X Rment of his penis and frequent erections. The child: a, s+ g6 g& D1 M5 U* P
was the product of a full-term normal delivery, with
, L, A/ U5 a5 z Na birth weight of 7 lb 14 oz, and birth length of; V# ^7 x* P5 N/ O
20 inches. He was breast-fed throughout the first year
- |+ O7 S* p- j. |4 ]! L: K$ B3 Eof life and was still receiving breast milk along with8 e G& o/ |; p" t2 @' Z
solid food. He had no hospitalizations or surgery,& u5 ?" @' g( f% s' K" f4 e
and his psychosocial and psychomotor development H# k# I4 z2 ]4 r
was age appropriate.
. R% W! B$ j* I" v ~5 @$ AThe family history was remarkable for the father,4 f+ H0 M* {3 @: f
who was diagnosed with hypothyroidism at age 16,7 _3 n! g" ?1 ?9 y) @* F
which was treated with thyroxine. The father’s
8 p, Q/ X' `7 Sheight was 6 feet, and he went through a somewhat7 W! e. [ P! o) o7 h
early puberty and had stopped growing by age 14.
/ p9 ^# {! x2 OThe father denied taking any other medication. The4 o8 Y! O0 t( U% l; O6 D
child’s mother was in good health. Her menarche) V- `' o7 ^+ q3 O, `
was at 11 years of age, and her height was at 5 feet: u) y1 d$ }0 D7 \& y3 Z
5 inches. There was no other family history of pre-0 F b+ _1 N; q- s0 ?6 G
cocious sexual development in the first-degree rela-0 F5 ?- P$ @ o% I" ?
tives. There were no siblings.+ f, R. k* ?4 P1 t4 ^- \
Physical Examination4 |3 ~' S9 L K/ |3 ?( m
The physical examination revealed a very active,
4 r7 g/ ~4 r0 ^ oplayful, and healthy boy. The vital signs documented$ n- Y+ C2 G# g( |( p/ E& j
a blood pressure of 85/50 mm Hg, his length was/ g6 F' T6 ~0 w+ x6 K
90 cm (>97th percentile), and his weight was 14.4 kg
. T% q F: A, i(also >97th percentile). The observed yearly growth0 Y) c& L5 F( d. D- L) M/ g* F
velocity was 30 cm (12 inches). The examination of
7 _+ O z- B, N; Tthe neck revealed no thyroid enlargement.
+ U) I3 i7 u6 J' \: Y/ L2 l4 P4 @The genitourinary examination was remarkable for
) ~$ i3 N& k4 K# A9 ?# aenlargement of the penis, with a stretched length of
7 L# P9 S6 O9 @8 cm and a width of 2 cm. The glans penis was very well
; I$ w$ j7 Z# O9 K3 c/ [2 {developed. The pubic hair was Tanner II, mostly around$ O2 l0 Q3 c) ]* Y
5404 O, g: B/ V, K/ u1 V2 V+ h
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from. [6 s* f' b0 K, I" G
the base of the phallus and was dark and curled. The$ B2 B; M: c. @- C4 v
testicular volume was prepubertal at 2 mL each.
5 }( g d. r* rThe skin was moist and smooth and somewhat( a$ p8 ]5 B/ x2 `7 n8 r$ U
oily. No axillary hair was noted. There were no
+ z) s/ F) }# vabnormal skin pigmentations or café-au-lait spots.3 D( t, Y/ ?: i' Q+ B) [
Neurologic evaluation showed deep tendon reflex 2+
8 v, C4 m+ }# m# o4 n8 B/ c: G( o0 Gbilateral and symmetrical. There was no suggestion
! j5 E2 _8 V3 ]- p* Vof papilledema.# ^5 _8 m$ X7 S4 f. t+ l. t
Laboratory Evaluation
. o' y5 B% g; \9 Y. c3 ?. x8 M6 @The bone age was consistent with 28 months by9 Z: v$ ~. E% Z* L0 h# O) G
using the standard of Greulich and Pyle at a chrono-8 ?- M3 u" G! M/ r4 ?
logic age of 16 months (advanced).5 Chromosomal
: [+ N1 { S) g |- O) Xkaryotype was 46XY. The thyroid function test. D/ g/ p/ z& n" z
showed a free T4 of 1.69 ng/dL, and thyroid stimu-+ \ V/ V5 P! R- ]' k& G1 k
lating hormone level was 1.3 µIU/mL (both normal).5 U# U3 X- R; s5 ^0 E' x9 Z% [% u
The concentrations of serum electrolytes, blood
( i6 F4 |# }- T) @* D9 lurea nitrogen, creatinine, and calcium all were
* K9 H6 E6 D5 H, h N5 Fwithin normal range for his age. The concentration. z j2 |* X+ ]& t
of serum 17-hydroxyprogesterone was 16 ng/dL
; _/ [/ d% f, s2 d- x# \, j(normal, 3 to 90 ng/dL), androstenedione was 20
. h1 Q; _; w/ W) a( G, Gng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
& [9 Z; d/ \$ h6 b/ J: Zterone was 38 ng/dL (normal, 50 to 760 ng/dL),
) P \5 G5 j- _( wdesoxycorticosterone was 4.3 ng/dL (normal, 7 to# n7 R2 {: } v$ O
49ng/dL), 11-desoxycortisol (specific compound S)
. E: R9 i' ~7 z( w1 i# n pwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
+ @5 X* W( a* Z0 U4 h; K. E) Q5 T0 ftisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total7 G1 j6 c- T& I! j3 G) S
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
9 b) G5 l2 ]) _1 ^3 X# J% \) x) Fand β-human chorionic gonadotropin was less than8 @# V A# {8 h# P5 O
5 mIU/mL (normal <5 mIU/mL). Serum follicular
, H' j9 U8 [9 s; y; Q2 ^: kstimulating hormone and leuteinizing hormone4 B# C$ J3 z8 N* a
concentrations were less than 0.05 mIU/mL8 o3 O1 I- p5 c. V. w% g) q
(prepubertal).
1 e1 P8 l9 ]5 b$ g9 Y8 C6 rThe parents were notified about the laboratory Q' p* b/ p8 S/ e1 u
results and were informed that all of the tests were
* E; V$ g3 F5 J6 B) Qnormal except the testosterone level was high. The9 P- `' d8 c! r
follow-up visit was arranged within a few weeks to
" l4 T2 U" y. ~) Z8 lobtain testicular and abdominal sonograms; how-
6 o: N# f1 [ ?3 S* Zever, the family did not return for 4 months.+ ~5 p3 |4 g. ~+ F
Physical examination at this time revealed that the; O. X+ U5 N7 @. U' R" ]
child had grown 2.5 cm in 4 months and had gained
+ n! T8 G9 ^& V: u2 f2 kg of weight. Physical examination remained
/ |! j5 `9 R0 @unchanged. Surprisingly, the pubic hair almost com-7 A4 z s! m9 j. H2 [" C: I Z
pletely disappeared except for a few vellous hairs at
6 i7 {6 a* {& u9 z6 P! athe base of the phallus. Testicular volume was still 2) N7 N& D/ D6 w& H& R# v3 l
mL, and the size of the penis remained unchanged.) N* ?) k( b" W% A
The mother also said that the boy was no longer hav-
9 L3 a0 k1 U X8 R& k w8 Xing frequent erections.
3 J" a8 k$ `/ i% T" } x WBoth parents were again questioned about use of
! T/ Y8 w. e0 g6 a: ^3 N( N; many ointment/creams that they may have applied to1 [* M/ |. R( _7 ]( S
the child’s skin. This time the father admitted the
* L4 s9 `$ w M+ V, |" H/ g4 rTopical Testosterone Exposure / Bhowmick et al 541
* z) q+ K: c1 j+ N9 h: w- wuse of testosterone gel twice daily that he was apply-
9 T# ~" k% [& W5 \ing over his own shoulders, chest, and back area for" M& Z# t( ]2 y8 x6 i! }9 o
a year. The father also revealed he was embarrassed K) w$ D7 ~5 h* y
to disclose that he was using a testosterone gel pre-
! F- U# Y& K% D2 xscribed by his family physician for decreased libido3 b# i0 w- R! h- ?
secondary to depression.
: h0 M9 c3 \; L% W3 o' n# {/ R" _The child slept in the same bed with parents.* f/ q' e) _2 y* J4 q0 p
The father would hug the baby and hold him on his# q( m5 l& t+ A8 p
chest for a considerable period of time, causing sig-: k3 E3 l+ h/ K" M" [6 o
nificant bare skin contact between baby and father. S5 v: Q) _$ Z o% ^' Q- Z, P
The father also admitted that after the phone call,* Q/ v$ n# O3 m8 r6 c
when he learned the testosterone level in the baby+ P. }8 f# ^. k1 V' Y2 T6 w
was high, he then read the product information- u7 G( z5 Z- ]0 H) m6 ^1 z
packet and concluded that it was most likely the rea-* h3 A9 G: r' m. m; G
son for the child’s virilization. At that time, they% f, K9 Z6 [: b) Q, c, u
decided to put the baby in a separate bed, and the
1 G$ N" E# w* Z& ^father was not hugging him with bare skin and had
8 N# x3 j# e j$ H0 obeen using protective clothing. A repeat testosterone0 d% w) f# s1 Z: e' J+ G9 @
test was ordered, but the family did not go to the
* e' }: L7 B+ _+ K9 C3 a6 \$ Ilaboratory to obtain the test.2 Y" G2 r" A1 X1 `, J
Discussion
( W# c Z: t {5 ?! n: V IPrecocious puberty in boys is defined as secondary
- f1 o$ c: A# X$ h" _/ G8 usexual development before 9 years of age.1,4
6 e4 T" x$ o! Z0 S: qPrecocious puberty is termed as central (true) when
2 X6 y" o( t% d1 V. [/ ]: r, I4 \it is caused by the premature activation of hypo-
. C1 _4 h! w3 L9 p1 A' h: ithalamic pituitary gonadal axis. CPP is more com-
' J! T3 B$ f9 l( u6 D, E5 \mon in girls than in boys.1,3 Most boys with CPP' Q" m+ Y$ H* S' Z A' e
may have a central nervous system lesion that is
& H3 P9 \ k$ q1 C% u! [responsible for the early activation of the hypothal-
' E) x k. m5 L1 E' c9 Eamic pituitary gonadal axis.1-3 Thus, greater empha-
0 o' I( b7 V3 ^( i. Asis has been given to neuroradiologic imaging in9 `8 G' Q) r& h7 R
boys with precocious puberty. In addition to viril-
4 h4 S A n5 r: {9 [! nization, the clinical hallmark of CPP is the symmet-8 b" b6 h+ t5 o' ]
rical testicular growth secondary to stimulation by
" t! F) S0 A5 i1 e" F+ l! {gonadotropins.1,3& i/ m& _' M; _1 m* ^
Gonadotropin-independent peripheral preco-
* {8 E5 c) v7 g' X, O' Mcious puberty in boys also results from inappropriate; f/ M3 ?! Q' i# o$ \7 r5 A6 x
androgenic stimulation from either endogenous or% f' K# c, c) z5 b3 y) _& |
exogenous sources, nonpituitary gonadotropin stim-
6 E# H1 P: h# |2 [ulation, and rare activating mutations.3 Virilizing5 H, w0 z( I4 x! e% ^
congenital adrenal hyperplasia producing excessive
5 C8 R/ X- ?4 L3 T! G2 V* Fadrenal androgens is a common cause of precocious
/ z2 Z$ a1 Q4 w- [puberty in boys.3,45 v+ c6 q0 D( B$ P, Z
The most common form of congenital adrenal
3 s* g6 p, h- z. R4 Z- Y# X6 @hyperplasia is the 21-hydroxylase enzyme deficiency.
! r& x& Q) \3 k1 L4 `The 11-β hydroxylase deficiency may also result in+ n2 o" D. @' K# \& `( V" Y6 E
excessive adrenal androgen production, and rarely,: w8 }+ A' a; Z* v# K
an adrenal tumor may also cause adrenal androgen
- K; W" r. N4 |" F: H5 V+ _excess.1,3
- \4 D m& [; o0 ^- i* N8 E) I3 aat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
+ f I5 M1 B7 k- {4 X. l542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
8 j% ^# ?/ w3 M5 sA unique entity of male-limited gonadotropin-9 H; [& y$ V: s, g' o* |
independent precocious puberty, which is also known
) X" g M! ]4 ras testotoxicosis, may cause precocious puberty at a6 {, w$ c4 S/ c5 R
very young age. The physical findings in these boys; g0 Q( A4 J1 i( R( I9 K
with this disorder are full pubertal development,
x7 w# t0 [7 Y+ t+ y& Y" Kincluding bilateral testicular growth, similar to boys+ m% |+ q9 ]3 I8 n9 p' k
with CPP. The gonadotropin levels in this disorder
V8 \* J8 u# H1 J8 vare suppressed to prepubertal levels and do not show/ q* g# C% m/ w- c
pubertal response of gonadotropin after gonadotropin-
. t9 H8 m. j% d; s- ~5 \5 creleasing hormone stimulation. This is a sex-linked
: F% I- W6 v& }0 b v& pautosomal dominant disorder that affects only
- g% s5 z# a I4 r( V# {males; therefore, other male members of the family; z' ^5 ]" y" n' Y' i6 T F) c
may have similar precocious puberty.39 F" @7 \# I6 }1 k
In our patient, physical examination was incon-
6 h5 [, A9 ?0 K: [sistent with true precocious puberty since his testi-
4 w+ ?/ a$ K/ _. e' U" rcles were prepubertal in size. However, testotoxicosis- W/ J$ F- s! u: m- s7 S; U
was in the differential diagnosis because his father
" Q6 Y4 G6 R) l* L: U: ], wstarted puberty somewhat early, and occasionally,1 {" V3 J" @3 E& ], t
testicular enlargement is not that evident in the% t) Q9 ^6 }# U3 {2 p
beginning of this process.1 In the absence of a neg-
% [7 r6 _6 F2 w1 u& }; Eative initial history of androgen exposure, our$ I" k% A$ K4 }+ m8 [1 R0 I, S
biggest concern was virilizing adrenal hyperplasia,
8 R# [$ s2 U- f0 s8 {- f2 Ieither 21-hydroxylase deficiency or 11-β hydroxylase
' _( L% X2 Q2 S! ^, Z% Udeficiency. Those diagnoses were excluded by find-5 E1 c5 R- u @4 h, @6 ?0 {( S( ]
ing the normal level of adrenal steroids. k, Z3 D, z5 `6 z6 A2 f9 T* n
The diagnosis of exogenous androgens was strongly L# W1 `* i/ k- @
suspected in a follow-up visit after 4 months because
/ j( G, d9 x+ Ythe physical examination revealed the complete disap-9 b. z$ v3 d* n% @) c0 ~
pearance of pubic hair, normal growth velocity, and8 a/ }: L- E% k' T" @
decreased erections. The father admitted using a testos-6 b- y/ e. j, j1 R
terone gel, which he concealed at first visit. He was, b, y9 g/ X$ @( e" a
using it rather frequently, twice a day. The Physicians’1 G% f( E% y5 h1 K
Desk Reference, or package insert of this product, gel or4 ^2 F2 s, F! G+ [3 N
cream, cautions about dermal testosterone transfer to6 I' d- F" ?2 H0 w: n# S
unprotected females through direct skin exposure." M1 z) A* P$ ^3 n, F$ G7 w
Serum testosterone level was found to be 2 times the6 z9 H, [ ^6 V+ b
baseline value in those females who were exposed to
5 _2 o) u3 T! p. Z) q: L9 jeven 15 minutes of direct skin contact with their male
: X2 T1 D. Z2 Q/ t, K9 Rpartners.6 However, when a shirt covered the applica-* a1 p* P/ \0 g
tion site, this testosterone transfer was prevented. g9 O% d+ M& P3 Z
Our patient’s testosterone level was 60 ng/mL,
* F, X4 u1 V2 P: J( ~which was clearly high. Some studies suggest that0 l4 g4 W) J/ _9 \3 @
dermal conversion of testosterone to dihydrotestos-
6 F$ ]: a: C7 qterone, which is a more potent metabolite, is more+ J! E# |+ F0 ]9 c
active in young children exposed to testosterone
4 b) u# I3 f4 c* \2 K/ Y' yexogenously7; however, we did not measure a dihy-
4 ]- U0 D/ A. W% a3 _3 sdrotestosterone level in our patient. In addition to, @& b! A* `# T+ `
virilization, exposure to exogenous testosterone in# g6 a/ ]6 L2 H5 o9 Y! f
children results in an increase in growth velocity and8 K& W' V' f8 \, H k0 z
advanced bone age, as seen in our patient.
8 C) J' Z9 U f) hThe long-term effect of androgen exposure during" b2 N8 }0 i6 E& [* r/ T
early childhood on pubertal development and final; ^7 I9 j7 ^; w0 P( Q" T5 {) y' C
adult height are not fully known and always remain$ X3 |/ f8 g0 }/ Q% p4 N9 }
a concern. Children treated with short-term testos-$ F, S) y, X4 c# R8 r5 X
terone injection or topical androgen may exhibit some: a# C2 Z" h9 u/ U
acceleration of the skeletal maturation; however, after
+ z. H6 p/ `- V% S: M Xcessation of treatment, the rate of bone maturation' c. v8 j- T- g" @' K
decelerates and gradually returns to normal.8,9/ X- ^$ b, T% Z8 \' i' L
There are conflicting reports and controversy
/ ]! P: B) z1 N y+ C2 @+ D: G* gover the effect of early androgen exposure on adult' m+ o, N/ v% c7 ^( ?" q
penile length.10,11 Some reports suggest subnormal6 ^/ {( e! h6 T
adult penile length, apparently because of downreg-
6 R* t8 i4 n/ W" Z& }' nulation of androgen receptor number.10,12 However,
9 | F; i1 A% P( U+ `Sutherland et al13 did not find a correlation between
" x+ z' x: a) g8 C0 c/ `, k' _childhood testosterone exposure and reduced adult
; d0 J" }6 W6 |$ w* B. b" k5 zpenile length in clinical studies.1 I `/ z4 o( U, m# s1 h" d" B$ M/ a
Nonetheless, we do not believe our patient is% Z( e& F) S* ^
going to experience any of the untoward effects from; P, G' e8 M* X3 {
testosterone exposure as mentioned earlier because
/ g' d7 G7 D$ P1 ^1 D: Gthe exposure was not for a prolonged period of time.3 a9 F9 F }0 P( Q9 ]3 V
Although the bone age was advanced at the time of
R& ~% {' b" [$ ~diagnosis, the child had a normal growth velocity at
% e$ Z; \, d, y% g5 Othe follow-up visit. It is hoped that his final adult
7 B- ~3 i: t7 m) X6 Pheight will not be affected.' I, }, [7 N6 `, B" h$ ^* x5 C# i
Although rarely reported, the widespread avail-0 i9 x- s/ k% o1 G, D o# b
ability of androgen products in our society may
- ^4 H6 r: J- i' \3 l( d# Uindeed cause more virilization in male or female4 B* T3 n7 ]; u5 o/ v
children than one would realize. Exposure to andro-; ^- h7 O: K4 k5 s$ n, A
gen products must be considered and specific ques-
! F- T9 _. ^% L3 {% y% t$ z% f$ Jtioning about the use of a testosterone product or+ s- R/ D# r& C' Y
gel should be asked of the family members during
I/ d" ] S' s) athe evaluation of any children who present with vir-
& ~/ G I3 I( C! h- k* Filization or peripheral precocious puberty. The diag-
; J1 q5 l, ?1 x0 ?( [6 z* }nosis can be established by just a few tests and by+ O* h- l) u2 S L
appropriate history. The inability to obtain such a7 V/ v$ e3 Q- B3 S5 M; P! X
history, or failure to ask the specific questions, may
2 R5 N0 k3 e8 c, hresult in extensive, unnecessary, and expensive* o/ _" V' R7 P- A4 @( Y% F8 X! U% U6 A
investigation. The primary care physician should be
: P, S7 W; |% K1 ]1 ^aware of this fact, because most of these children4 M, E3 U" U$ g( O, V0 K7 Q$ F3 J% {# h
may initially present in their practice. The Physicians’6 P0 K1 O( ^9 I: x; \
Desk Reference and package insert should also put a
+ s1 i% {6 X# r! O2 k7 Pwarning about the virilizing effect on a male or4 @. e- _. s, D, W
female child who might come in contact with some-5 n8 C4 q1 l6 h# ?% z( R
one using any of these products.2 b" w8 f0 ?6 {- D. y Y
References
2 z: {& r! M$ u! q1. Styne DM. The testes: disorder of sexual differentiation4 [+ B% g7 Q7 o2 X
and puberty in the male. In: Sperling MA, ed. Pediatric3 @0 Z! V N$ |3 @! N2 [7 i
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;7 I k" i. e* W6 e
2002: 565-628.0 T. |; ~- C+ a/ i" t1 p) X
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious1 H% z; ^ }2 ]$ ?4 I
puberty in children with tumours of the suprasellar pineal |
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