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Sexual Precocity in a 16-Month-Old
3 m3 G; A% c+ ?8 W- S4 E9 kBoy Induced by Indirect Topical# ^+ v+ b, W( [* e0 k
Exposure to Testosterone1 T9 q1 n6 s3 V5 ^& f
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2- Z9 i6 \ n5 u
and Kenneth R. Rettig, MD1
2 V y, E# B {Clinical Pediatrics
: S4 q, Z; L5 ^( a7 H3 jVolume 46 Number 6
, {4 @& p" {3 H2 l4 fJuly 2007 540-543
: \& E! o/ C9 k1 x* J: n© 2007 Sage Publications
; n3 y) b" g0 W7 Q10.1177/0009922806296651* A& `/ S8 N- {& h: Q
http://clp.sagepub.com
5 L. K l7 H: d) [hosted at
8 J! a8 w) ~- I& m) p z3 Y4 Uhttp://online.sagepub.com" N7 H/ k4 W; F$ b
Precocious puberty in boys, central or peripheral,# V6 P* v/ h5 ?7 |9 l0 @
is a significant concern for physicians. Central) i# o$ p8 S0 S
precocious puberty (CPP), which is mediated! f) \; U- e4 u: E. O
through the hypothalamic pituitary gonadal axis, has
% p0 F+ V/ `4 M5 ^* `# Wa higher incidence of organic central nervous system5 M# _: P8 P& u; h# ~7 O2 i
lesions in boys.1,2 Virilization in boys, as manifested, M7 K: S# A: D- i, t# C
by enlargement of the penis, development of pubic' f/ `& l9 A7 F/ u5 j
hair, and facial acne without enlargement of testi-/ X0 b/ v6 B6 H, F& @
cles, suggests peripheral or pseudopuberty.1-3 We
# y" e* k: z' H1 \# T* j' g N7 f9 E$ Ureport a 16-month-old boy who presented with the
# d8 K! P: K) g! u5 j1 xenlargement of the phallus and pubic hair develop-) X& t) g- j' y" s0 B
ment without testicular enlargement, which was due& Y& u! W% g, z7 D6 h9 A
to the unintentional exposure to androgen gel used by
8 r% v8 A) F; {8 r" Z4 mthe father. The family initially concealed this infor-
% m$ p3 P% q b5 Kmation, resulting in an extensive work-up for this
4 d4 Z4 P+ n, n9 D: A" O& kchild. Given the widespread and easy availability of
/ r) E3 n! p( X% ], Qtestosterone gel and cream, we believe this is proba-
$ \, r4 P( A, ]+ pbly more common than the rare case report in the8 a7 Z; H2 H1 q' O
literature.4! S, Q* b6 z2 p
Patient Report0 B1 q; i) L! p: k+ s
A 16-month-old white child was referred to the( h4 {1 N* T% l, | A, |
endocrine clinic by his pediatrician with the concern
* R% R! X5 \8 a/ Q+ z8 ^$ Iof early sexual development. His mother noticed) |; B3 Y1 q# w- i0 ~3 W& t/ K
light colored pubic hair development when he was
# ?- G( @% _# uFrom the 1Division of Pediatric Endocrinology, 2University of; N0 H) }1 K2 J! N) g
South Alabama Medical Center, Mobile, Alabama.
T! z7 {* {7 |Address correspondence to: Samar K. Bhowmick, MD, FACE,
6 w& K3 _" Z* C, {3 SProfessor of Pediatrics, University of South Alabama, College of
( U8 U; S# P7 n4 S4 _Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;! p, w* a! W% T
e-mail: [email protected]." ^+ ]/ |+ U5 S, G; S9 R8 H: F5 g
about 6 to 7 months old, which progressively became) q, T9 p( c, V, i0 N) }, D7 B
darker. She was also concerned about the enlarge-% `# O, |- ?2 c/ G/ }5 u: l$ k: K
ment of his penis and frequent erections. The child4 E) w/ X+ Y: {& Z- v/ Z9 W
was the product of a full-term normal delivery, with% b/ h' O$ V0 C9 V5 @& o' A
a birth weight of 7 lb 14 oz, and birth length of
: @7 x/ m7 p c# \3 k20 inches. He was breast-fed throughout the first year2 v0 Q$ W+ D9 \) l
of life and was still receiving breast milk along with- S$ x' c* ?2 d% {
solid food. He had no hospitalizations or surgery,9 C# Y; \$ F* U5 h4 R, |3 m
and his psychosocial and psychomotor development
/ V. L# c, u Q* w0 W/ P3 R+ iwas age appropriate.: l' _7 e: a( \4 N# |" T6 a
The family history was remarkable for the father,+ u" S- c K q! ^9 Y/ ]
who was diagnosed with hypothyroidism at age 16,0 c3 Y% _# t2 X# @+ X1 _( t
which was treated with thyroxine. The father’s9 b4 L2 N8 s) A; E
height was 6 feet, and he went through a somewhat
: ` {$ w6 S; o5 ^early puberty and had stopped growing by age 14.; ]% g$ C1 G! W# g1 r+ n% _" r
The father denied taking any other medication. The
4 k! u+ @5 U v3 a9 K7 i. _5 ?child’s mother was in good health. Her menarche
m1 W4 m; ] _- Zwas at 11 years of age, and her height was at 5 feet+ u! C# z) }7 O; h0 m7 Z
5 inches. There was no other family history of pre-
1 i8 U- C8 D$ u- @& Z# b9 O* U% Zcocious sexual development in the first-degree rela-
. P+ J: x% X5 _/ u, ktives. There were no siblings.( {3 v9 w: U: ~. [; `7 t; _
Physical Examination$ h' Y. F$ R# g" O
The physical examination revealed a very active,6 s S# A* K2 r3 ^
playful, and healthy boy. The vital signs documented
" o) P" t4 g3 _/ J& Fa blood pressure of 85/50 mm Hg, his length was
" D! |- W) ?+ O/ I4 Z' p* g5 @90 cm (>97th percentile), and his weight was 14.4 kg
7 T) w4 q: Z/ e' e6 G5 R" @(also >97th percentile). The observed yearly growth
# Z6 O' I( @- v4 m; Z( [velocity was 30 cm (12 inches). The examination of
/ X0 Z# T5 r5 f" A1 d- s! Q% j2 `the neck revealed no thyroid enlargement.
) K# X, A9 f2 s8 U/ a" P# g0 \, T/ M2 mThe genitourinary examination was remarkable for3 e! R8 i2 P- p* @5 x
enlargement of the penis, with a stretched length of1 R6 S5 f3 C& @7 i! ^
8 cm and a width of 2 cm. The glans penis was very well- t/ i+ a+ ~! d3 u& y1 _4 W
developed. The pubic hair was Tanner II, mostly around* n2 z; U, V0 q0 t& U
540
+ p( l4 I: o5 U3 Z9 T' K- `at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from+ ]& N; E; @: A7 ?+ C, @
the base of the phallus and was dark and curled. The: d' Y% s6 @/ q3 U* Q. e
testicular volume was prepubertal at 2 mL each.
0 L% P& m- L3 i" F# c3 m( ZThe skin was moist and smooth and somewhat
0 F4 n1 I: C" \0 H7 S, D2 Poily. No axillary hair was noted. There were no+ o, Y1 J1 t. R7 d$ `, W
abnormal skin pigmentations or café-au-lait spots.
5 r% F; }5 C+ Z+ x4 H8 CNeurologic evaluation showed deep tendon reflex 2+# i* O3 Z! {9 y$ Y" b. A4 Q
bilateral and symmetrical. There was no suggestion
( r# I8 D! U: V" ]/ `/ n5 Fof papilledema.
2 ?5 [. a' t4 w; U% @' [8 y7 d! zLaboratory Evaluation" R+ v* O( q; }5 G1 M
The bone age was consistent with 28 months by. x, r3 S Z/ o) r( L U- a
using the standard of Greulich and Pyle at a chrono-0 _) \% \2 I# {. Z( E
logic age of 16 months (advanced).5 Chromosomal
+ q b# U M+ ]8 _0 o0 u9 h$ w5 G' Ykaryotype was 46XY. The thyroid function test7 Y% ?/ m0 v- J( e4 o$ A
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
+ \/ r& Y: Z/ y( plating hormone level was 1.3 µIU/mL (both normal).0 [3 R' U v1 H/ g7 [# q" j+ }
The concentrations of serum electrolytes, blood' ^6 I6 d4 _5 C/ G0 ~* W0 Z1 Y# W
urea nitrogen, creatinine, and calcium all were
8 H5 _4 b; `$ \ k. _+ x6 K8 K. Dwithin normal range for his age. The concentration7 E2 v; `5 d- y4 m/ X! C
of serum 17-hydroxyprogesterone was 16 ng/dL
6 c. ] B: a2 s O(normal, 3 to 90 ng/dL), androstenedione was 205 _# R7 Y, Q( p4 Y" ~
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-1 ]. V% J/ p8 H
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
& ]3 c' d% `6 v+ p. ydesoxycorticosterone was 4.3 ng/dL (normal, 7 to
3 j0 c+ B1 k4 ^: K. B49ng/dL), 11-desoxycortisol (specific compound S)) F+ w; p0 b" B
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
4 w+ h; e; A$ L1 n9 s; Ntisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
0 f `, y" r. E8 R! t, dtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
! k8 W6 I. V2 f0 @3 _and β-human chorionic gonadotropin was less than5 l) T; h i3 N# d( `. F" y) B
5 mIU/mL (normal <5 mIU/mL). Serum follicular
# V% i+ A3 a" h0 o$ d% `6 mstimulating hormone and leuteinizing hormone% ?& n1 w5 \ p6 q
concentrations were less than 0.05 mIU/mL' ]5 U0 B( }. v2 @& X" A
(prepubertal)." W" Z0 ^$ ]! D% U: s" z# J; ~
The parents were notified about the laboratory
V+ _4 J1 m8 X1 uresults and were informed that all of the tests were, T1 g. Q8 g# q1 i4 _" ?1 S
normal except the testosterone level was high. The, q' j& W6 |) P, _% u% T$ g* c
follow-up visit was arranged within a few weeks to4 {. \1 p0 m/ x" w
obtain testicular and abdominal sonograms; how-
$ e1 n( F( o: I( z9 }3 iever, the family did not return for 4 months.% I0 R8 i% z$ T
Physical examination at this time revealed that the% i) H4 P8 `+ T; U$ J
child had grown 2.5 cm in 4 months and had gained g X. u, E$ O! z# f
2 kg of weight. Physical examination remained
6 W. G" ?2 D3 r" N" F" T% F5 u5 dunchanged. Surprisingly, the pubic hair almost com-% ~" V- F1 ~9 t$ |
pletely disappeared except for a few vellous hairs at
; @( @# `9 C; d+ M$ R" ethe base of the phallus. Testicular volume was still 2
; \) @$ ]% q* Q. w* E [: j" hmL, and the size of the penis remained unchanged.0 F1 H$ \* T" \, d* a
The mother also said that the boy was no longer hav-& u# S) a" i) q: q. T
ing frequent erections.1 i; a) E) e! a8 \- k7 l3 H5 |8 {: \
Both parents were again questioned about use of7 n) i9 o' Y6 E) x; H4 z' h# d
any ointment/creams that they may have applied to6 r8 |' w: v( W+ b& D
the child’s skin. This time the father admitted the
2 D: o& R4 P% F! D4 R1 ?2 y% |Topical Testosterone Exposure / Bhowmick et al 541
2 y' m' U+ T# ause of testosterone gel twice daily that he was apply-
' m; b0 m! A5 Zing over his own shoulders, chest, and back area for
5 i: E0 g+ ?8 h5 wa year. The father also revealed he was embarrassed( I8 W- u* e; F; D. g5 l, q8 l! S
to disclose that he was using a testosterone gel pre-
* K7 r# R! F. ?2 r' O% n4 Y# [scribed by his family physician for decreased libido' L+ X h4 n+ B& U; @/ l0 [* M0 X
secondary to depression.
9 [, y q6 n. ?) d% V/ t+ Z% JThe child slept in the same bed with parents.$ X& ]; \8 o5 C$ y$ N# [
The father would hug the baby and hold him on his
0 {' b) t: h2 d7 G3 ichest for a considerable period of time, causing sig-$ i, i6 x0 ^4 w# H
nificant bare skin contact between baby and father./ ~% o) A8 p: U; x k6 ^
The father also admitted that after the phone call,
( [. G0 S2 w+ |5 |5 h. Y9 O4 jwhen he learned the testosterone level in the baby
1 w7 p. B# M$ l* lwas high, he then read the product information9 p1 l# @' w# Q: U/ i, w
packet and concluded that it was most likely the rea-! x3 B' I$ ~, Q7 |2 Z
son for the child’s virilization. At that time, they! ~: ^. h1 ^, K- G& U
decided to put the baby in a separate bed, and the
8 q/ m3 b+ k9 a, L, F& Kfather was not hugging him with bare skin and had
2 A, ^' q0 G; ^been using protective clothing. A repeat testosterone
) w0 x! `% }, u0 @test was ordered, but the family did not go to the$ i, ~/ G% o: g4 B* p" M
laboratory to obtain the test.
4 y( m, |: w; a3 G: T1 aDiscussion0 D6 E, A4 ^. j. o5 L2 V
Precocious puberty in boys is defined as secondary
[2 O! r" g5 z+ O( k# xsexual development before 9 years of age.1,4
2 Q h3 p8 w8 g' s) M; @$ BPrecocious puberty is termed as central (true) when9 {1 H' z$ }% K& n. _
it is caused by the premature activation of hypo-
. V* v3 }: S1 ?+ d4 |/ ?2 e7 C9 Sthalamic pituitary gonadal axis. CPP is more com-2 R' u& W6 N( R! a* F. H
mon in girls than in boys.1,3 Most boys with CPP2 H o0 d8 Z G- T& A! h9 O2 H
may have a central nervous system lesion that is# S+ w8 }1 `+ e- I
responsible for the early activation of the hypothal-" l% h0 h" S, G( ~1 u" v
amic pituitary gonadal axis.1-3 Thus, greater empha-
- n2 l/ y4 ]# m3 e esis has been given to neuroradiologic imaging in
. P) J9 N8 Q5 L/ kboys with precocious puberty. In addition to viril-
7 ^9 M* b; B0 `# cization, the clinical hallmark of CPP is the symmet-3 `: f6 K0 Q) X0 e$ y
rical testicular growth secondary to stimulation by
5 m! l- }. z" |) ~; N. V; I9 ogonadotropins.1,3. P1 y5 ]' J1 s
Gonadotropin-independent peripheral preco-
- o/ V0 N+ h" w. N' Vcious puberty in boys also results from inappropriate
0 _" A, ^5 ]5 f) X) v5 Landrogenic stimulation from either endogenous or* h# a7 q" o' m2 B6 I$ N
exogenous sources, nonpituitary gonadotropin stim-, ?4 L% o! K/ M* F0 b# D5 I
ulation, and rare activating mutations.3 Virilizing
# Z/ R+ i/ i% |5 [( s. ]congenital adrenal hyperplasia producing excessive
% K& s& N; Q0 H7 z# Kadrenal androgens is a common cause of precocious7 C% l" C k6 C7 h. I9 Z
puberty in boys.3,4
9 ]( V5 t1 T" b+ UThe most common form of congenital adrenal, Q' k/ X( t1 x' |# ^" s1 l
hyperplasia is the 21-hydroxylase enzyme deficiency.
* Y; W, O4 y% [, |# ]& O# m3 q9 FThe 11-β hydroxylase deficiency may also result in
0 I* e ^/ H5 q& T; nexcessive adrenal androgen production, and rarely,
9 O( Q: X! P% @ l3 san adrenal tumor may also cause adrenal androgen
4 x4 z% [) x0 [- D2 G# z# hexcess.1,37 o% z& `- S3 c' e6 D7 r8 |
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from( m4 M+ F" Q* \$ v: E
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
) }% l0 ^' s& \% @ q( h$ UA unique entity of male-limited gonadotropin-
/ J# u/ M: Y, o( l0 b+ Sindependent precocious puberty, which is also known/ k* d2 f0 J+ e& V' p9 v% `: {
as testotoxicosis, may cause precocious puberty at a
7 w: n9 u1 B @6 Avery young age. The physical findings in these boys$ h7 A. L# w* f3 X( ?- r7 Z
with this disorder are full pubertal development,; d& S( V( q2 v' |: w
including bilateral testicular growth, similar to boys
7 Y! o. ~8 c' F) w2 B/ [! mwith CPP. The gonadotropin levels in this disorder" H. k" O0 z' C5 x4 l) U) Y' _+ ^) ?4 U: `
are suppressed to prepubertal levels and do not show" _: m) f: n' h% `' E9 t( C/ u
pubertal response of gonadotropin after gonadotropin-
5 N( D7 c. i8 F2 Zreleasing hormone stimulation. This is a sex-linked
2 B1 k, y1 F4 P% u/ |autosomal dominant disorder that affects only
/ m2 [! K/ Y/ u8 S* E0 |8 X/ Emales; therefore, other male members of the family) ~ c, f8 |! B: p2 R! g
may have similar precocious puberty.3! G3 ^; w2 b0 H
In our patient, physical examination was incon-
- C0 s" B/ }& s( E& Ssistent with true precocious puberty since his testi-
( ^, {4 Z8 d; H: vcles were prepubertal in size. However, testotoxicosis
7 m5 t+ _% N c; R8 i9 I# @was in the differential diagnosis because his father
6 Y9 S! j* }+ n* n j# P: O, Ustarted puberty somewhat early, and occasionally,% O w5 e8 @* l
testicular enlargement is not that evident in the
. [! U0 v, W7 E& {3 f" fbeginning of this process.1 In the absence of a neg-
: C+ K+ B/ W% @0 f. rative initial history of androgen exposure, our5 N2 c+ s8 ?+ d4 } Z0 d0 v% W
biggest concern was virilizing adrenal hyperplasia,! \' e, O" k, p& }1 x/ j
either 21-hydroxylase deficiency or 11-β hydroxylase
8 q' U- {! f+ M$ zdeficiency. Those diagnoses were excluded by find-( q$ t4 e. ~7 Y# o3 c
ing the normal level of adrenal steroids.4 Q. @0 V7 D% \% b
The diagnosis of exogenous androgens was strongly
9 o, t: F2 t% u. K' S6 ~% Ysuspected in a follow-up visit after 4 months because
' n2 p2 \; p% e; h7 }the physical examination revealed the complete disap-4 u1 D/ q/ W) [6 _9 \0 W& c
pearance of pubic hair, normal growth velocity, and- Y0 R* y) s& w d% s" a- g0 G2 l
decreased erections. The father admitted using a testos-% t0 O. X1 }4 s( _3 D5 z
terone gel, which he concealed at first visit. He was4 J# c9 u0 B. C- n* p6 A% P/ E# A( j
using it rather frequently, twice a day. The Physicians’
. f% s( U _+ s" T" }! f4 }: dDesk Reference, or package insert of this product, gel or! b7 S5 c& D) x% @
cream, cautions about dermal testosterone transfer to: m! ]- q. X, t# X
unprotected females through direct skin exposure.
) `( b0 w: L. f6 ZSerum testosterone level was found to be 2 times the3 d* q. {' g) M0 [2 S
baseline value in those females who were exposed to8 L) P5 H0 k( e: y
even 15 minutes of direct skin contact with their male
+ B" ]0 m4 q+ `4 ~9 {partners.6 However, when a shirt covered the applica-
) ^5 K9 w5 P- z1 z4 q( K; ttion site, this testosterone transfer was prevented.7 l* u3 @) y8 j: n1 a2 T
Our patient’s testosterone level was 60 ng/mL,) @' q3 D1 j1 \- N$ T7 E
which was clearly high. Some studies suggest that1 V7 [, k9 n2 [. i( y2 d
dermal conversion of testosterone to dihydrotestos-, d; V3 z0 B: ^5 Q
terone, which is a more potent metabolite, is more2 _8 k, V0 `# u9 t, }8 n
active in young children exposed to testosterone
8 D: J, G. D8 t {exogenously7; however, we did not measure a dihy-( B* _* _" N f4 h( F1 d1 z! l4 \
drotestosterone level in our patient. In addition to- `+ U2 [/ k; n! r2 E* W
virilization, exposure to exogenous testosterone in
4 `& z) j9 E& w" \+ xchildren results in an increase in growth velocity and
S/ X/ b/ B t0 _* e0 d% Madvanced bone age, as seen in our patient.
( Z. U1 C% M. {& X bThe long-term effect of androgen exposure during0 n2 x2 G8 N( O7 c) i& |0 H
early childhood on pubertal development and final% \$ M* D1 B- L: Y( A2 C
adult height are not fully known and always remain
$ w3 K& x/ b5 l0 E+ Ca concern. Children treated with short-term testos-
! b9 ~! J6 w( P: J0 p1 nterone injection or topical androgen may exhibit some
1 \+ d" C' k. g+ oacceleration of the skeletal maturation; however, after
& Y" C9 t. ?: S8 Y0 O( J9 Bcessation of treatment, the rate of bone maturation
* M2 L: |8 L% E. u& v2 d9 _decelerates and gradually returns to normal.8,95 c+ I) W# g/ H) n0 l
There are conflicting reports and controversy2 W, U+ s) P4 ^
over the effect of early androgen exposure on adult, x5 D# a J7 R+ @0 @; ^& X
penile length.10,11 Some reports suggest subnormal' y/ \0 z4 b. q( p
adult penile length, apparently because of downreg-# B2 h! W1 C5 ^# P4 W7 i1 q
ulation of androgen receptor number.10,12 However,
: S. ?5 `- c5 b5 ~* [8 tSutherland et al13 did not find a correlation between
% i- s# n( i$ K+ z9 s: @childhood testosterone exposure and reduced adult% ^3 p b; z1 E: m2 |
penile length in clinical studies.8 a5 f9 P4 Q( b+ @
Nonetheless, we do not believe our patient is4 q5 ~# K, u/ \
going to experience any of the untoward effects from2 U. n3 @# K, {/ {" v; ~& {$ b
testosterone exposure as mentioned earlier because% b) \. t3 l2 g) m& h G$ s* B
the exposure was not for a prolonged period of time.
( T5 p! f9 y" ^Although the bone age was advanced at the time of
) d# b8 C3 a/ O1 U' Y1 H+ U& I v) Cdiagnosis, the child had a normal growth velocity at
. E+ Z/ i8 Q, l& j+ ]5 x& |the follow-up visit. It is hoped that his final adult
" Z6 A& C* _ q1 Dheight will not be affected.
% _5 m" U; Q4 h; d) J. sAlthough rarely reported, the widespread avail-
N4 @% l( X! s* B; K4 wability of androgen products in our society may0 a; l. |# l5 F, }- B
indeed cause more virilization in male or female$ K+ _. v4 O- O/ H. J
children than one would realize. Exposure to andro-
7 U2 ^0 W$ g8 V) R9 ~3 G6 Vgen products must be considered and specific ques-# T4 U1 v$ A6 y) W; p8 [. ~6 G0 T
tioning about the use of a testosterone product or
, a$ C" I& _' X* e/ W; F3 Egel should be asked of the family members during4 }# e* k, J+ Y" m& V1 ]# `1 g2 J
the evaluation of any children who present with vir-. M. N0 p& S( M" ?# ~
ilization or peripheral precocious puberty. The diag-: M7 B- }8 u6 O0 K
nosis can be established by just a few tests and by
7 B/ m. s% }+ i1 `" o) f# Z: s* Iappropriate history. The inability to obtain such a3 | j( E4 z1 o) c8 ?" K
history, or failure to ask the specific questions, may% a3 R4 i/ V1 a2 W
result in extensive, unnecessary, and expensive
5 y0 c( D/ y7 ginvestigation. The primary care physician should be
V+ U, N+ c" Naware of this fact, because most of these children- E2 H" W& }2 z4 w) \. x: F! W
may initially present in their practice. The Physicians’
6 L" N) {8 L0 y1 f5 s4 O' vDesk Reference and package insert should also put a C+ I/ ]5 K t$ Z X: l$ G! m
warning about the virilizing effect on a male or
" Y$ s/ P- z4 b' J7 Mfemale child who might come in contact with some-- K3 z( ?% h E q5 E+ V
one using any of these products.
2 [7 A0 Q ~9 j) N0 I/ iReferences' V- [6 K# l4 V4 A
1. Styne DM. The testes: disorder of sexual differentiation
" y( ?6 L; Q2 b6 E! K6 eand puberty in the male. In: Sperling MA, ed. Pediatric" x9 B) F3 |2 J! {( x: p* e
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
0 N7 L5 X! z! G E) Z9 B* b O `2002: 565-628.
7 j p! Z3 d* d E/ K& X2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
0 Q4 [, h6 h ^puberty in children with tumours of the suprasellar pineal |
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