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Sexual Precocity in a 16-Month-Old* D* T! b* \6 p; ^) u* j8 Z
Boy Induced by Indirect Topical
$ Q' c) }7 y& z; eExposure to Testosterone2 i0 K2 @: K" L6 F0 u/ A1 E4 K$ H
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
- [4 N: f7 [! t2 {9 Yand Kenneth R. Rettig, MD1
! y @9 u8 b( ]+ lClinical Pediatrics' [) `, I3 l% R* Q, y
Volume 46 Number 6
a1 }# q. c. C9 cJuly 2007 540-543: e) J$ j/ b- K7 @" _; E$ m
© 2007 Sage Publications
0 v% r" `+ o6 r/ P, }" }10.1177/0009922806296651
1 o6 Y- L5 h2 x' R I1 M% _# @& `+ fhttp://clp.sagepub.com) G3 m9 |6 X" B6 J" \) J+ c! C5 u
hosted at: W% H7 X- x% b- o/ i5 Y6 F; V$ N
http://online.sagepub.com
% V' I. ]/ E* @. oPrecocious puberty in boys, central or peripheral,
2 z- u* H+ `! i( l& p$ z3 ^is a significant concern for physicians. Central
; M7 R7 c8 J$ Fprecocious puberty (CPP), which is mediated. m5 [* w# }* m, K) l! v
through the hypothalamic pituitary gonadal axis, has) u- {! d4 I/ {4 A9 ~
a higher incidence of organic central nervous system a% k/ r5 e9 q7 ]+ e1 h
lesions in boys.1,2 Virilization in boys, as manifested2 R0 s5 R q% r/ z
by enlargement of the penis, development of pubic. F- F; b/ t4 X
hair, and facial acne without enlargement of testi-% [4 X% K: M( O
cles, suggests peripheral or pseudopuberty.1-3 We' j6 q8 d% }* t6 Q
report a 16-month-old boy who presented with the& S, t( ^ ]2 P5 u$ P3 v
enlargement of the phallus and pubic hair develop-) m2 e5 r6 ?" ?$ J8 }; S2 U/ |/ D
ment without testicular enlargement, which was due( Y$ R* ]+ G1 f7 \, q
to the unintentional exposure to androgen gel used by% e4 \2 w+ h8 @( x6 d g4 W' h
the father. The family initially concealed this infor-
# C* j( L8 q1 ~6 }5 d; ], rmation, resulting in an extensive work-up for this
G( K2 M, y& w8 Mchild. Given the widespread and easy availability of' G" o& K* ^$ W9 ?* r. _
testosterone gel and cream, we believe this is proba-
+ ~8 n0 [4 x9 Y, H" H Q' zbly more common than the rare case report in the
# f' k8 p: e vliterature.4
/ q0 ?! m' I/ R6 N- g) KPatient Report4 R* j- S4 o. h- q) i+ g0 Q
A 16-month-old white child was referred to the
+ B: ] Q6 P$ ^, |endocrine clinic by his pediatrician with the concern6 u; u/ y' y3 r: ^' n
of early sexual development. His mother noticed- D6 }8 i( y5 d, I
light colored pubic hair development when he was
) `8 R( V! e0 mFrom the 1Division of Pediatric Endocrinology, 2University of. [* J8 @$ M/ I$ {! B; c) R. h. i. c
South Alabama Medical Center, Mobile, Alabama.- ]; I0 Z( r% e/ |3 A1 ~, v3 p) I
Address correspondence to: Samar K. Bhowmick, MD, FACE,
3 W" ~( M& h& MProfessor of Pediatrics, University of South Alabama, College of$ k, i. P9 X% H+ H* p: p5 [) m
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;: r) Y1 C5 M5 D- d9 |! v; w
e-mail: [email protected].
( N' Q7 Q9 s/ g: ?( _7 ], Eabout 6 to 7 months old, which progressively became6 s/ ?/ B. K- z1 f
darker. She was also concerned about the enlarge-
1 z* t0 S# C* G6 ement of his penis and frequent erections. The child6 p' P3 J: Y8 W& ] |* L
was the product of a full-term normal delivery, with
4 g! N; E) Q8 ~, Q, Ca birth weight of 7 lb 14 oz, and birth length of
5 x y8 D9 g8 h4 D$ D! |7 P7 }20 inches. He was breast-fed throughout the first year
/ H, h6 u* o7 n" Lof life and was still receiving breast milk along with$ J$ w( G' K/ ^1 g: a3 _
solid food. He had no hospitalizations or surgery,
2 @ V# r- A* qand his psychosocial and psychomotor development2 a& e0 z2 \0 f( Y3 V# h
was age appropriate.
' V* t4 ^" ~6 o& J& D7 `' V \The family history was remarkable for the father,
5 b4 ?* K2 V- B; D ?who was diagnosed with hypothyroidism at age 16,
8 e: G+ z! F9 E7 E, Z9 H6 x7 Jwhich was treated with thyroxine. The father’s. e, \ y2 y7 v; B" U
height was 6 feet, and he went through a somewhat; X0 A$ N( C& T- z- T
early puberty and had stopped growing by age 14.2 i. H( A" s$ p. Y7 y
The father denied taking any other medication. The- p0 @. z" I4 u- o$ W# I4 j$ u
child’s mother was in good health. Her menarche
w9 b+ X* j& S$ c# Iwas at 11 years of age, and her height was at 5 feet0 B' J2 F) u& j! L3 ]6 z, M; [# B+ R
5 inches. There was no other family history of pre-( V- n" s) u3 F; k$ X* j* P5 O, P
cocious sexual development in the first-degree rela-; e0 [! F1 b7 p) H$ r; x2 `* \
tives. There were no siblings.
/ S U' k) o, B- FPhysical Examination
& v0 a) B* M: f( p! b) FThe physical examination revealed a very active,
% r9 S6 k0 C% H- v9 qplayful, and healthy boy. The vital signs documented
; S! _+ c! s: U8 Wa blood pressure of 85/50 mm Hg, his length was0 k. `- {4 i: G% F2 k" A3 X9 W) d
90 cm (>97th percentile), and his weight was 14.4 kg
6 c& z2 ]1 m& V. d2 I' \2 P(also >97th percentile). The observed yearly growth: Y# H" r' n/ |% z9 ~% c4 S
velocity was 30 cm (12 inches). The examination of
1 U- x7 I; E1 d" I% M5 _the neck revealed no thyroid enlargement.
8 j9 t' u0 f0 ~* Q8 n' l: d4 ~The genitourinary examination was remarkable for
! f0 T+ y2 L7 v0 l! F- b3 I8 @enlargement of the penis, with a stretched length of) P& R% N: }7 z2 G7 J: G+ o3 c
8 cm and a width of 2 cm. The glans penis was very well
2 l! w( K! m/ Y" ~2 Rdeveloped. The pubic hair was Tanner II, mostly around' O5 q& `9 X: e
540% {9 X6 r2 M4 h0 ], z" `
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
' A* h0 O. x2 k3 d1 \6 v, mthe base of the phallus and was dark and curled. The
( y% L/ |4 X5 x. m# S" D$ A6 Mtesticular volume was prepubertal at 2 mL each.- M/ ^5 N/ _1 x# D% z/ r
The skin was moist and smooth and somewhat
M/ p9 M1 G% f; K! i9 g+ ?2 Loily. No axillary hair was noted. There were no) Q* i. {3 h4 ^1 j
abnormal skin pigmentations or café-au-lait spots.
- l& k7 ?% J$ k. z$ s, s/ h, a5 _Neurologic evaluation showed deep tendon reflex 2+2 E% g) M5 g1 t7 [ y& I
bilateral and symmetrical. There was no suggestion
& C! n& S$ R. Kof papilledema.; D8 x; y/ p3 {
Laboratory Evaluation5 V. ^: r8 J2 T3 R. _. P7 m! ] _7 ^' A
The bone age was consistent with 28 months by3 t) c( n. X) s" {4 a8 L
using the standard of Greulich and Pyle at a chrono-
2 w* O2 _5 c& [9 Ologic age of 16 months (advanced).5 Chromosomal w+ n: v$ P/ J8 g
karyotype was 46XY. The thyroid function test
5 {( k/ i2 C* p- Sshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
5 G* @& e2 ?! v" h# }lating hormone level was 1.3 µIU/mL (both normal).
: ~9 I+ c. i& S: ^( j- ^The concentrations of serum electrolytes, blood- K7 `; _5 d. B6 q. S9 q
urea nitrogen, creatinine, and calcium all were
2 C4 G$ y" u! P& wwithin normal range for his age. The concentration3 H1 E8 i7 W9 o7 ^
of serum 17-hydroxyprogesterone was 16 ng/dL) F. ]( r; z7 q
(normal, 3 to 90 ng/dL), androstenedione was 208 r$ O6 d- k P" o- a
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
% g' a$ _ c6 z" eterone was 38 ng/dL (normal, 50 to 760 ng/dL),/ I' p+ n& P6 A B$ @7 y) \
desoxycorticosterone was 4.3 ng/dL (normal, 7 to( i" z8 V2 H7 }$ Y
49ng/dL), 11-desoxycortisol (specific compound S)( I9 y! Z+ A+ r! S7 Q- m+ y$ k
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
K) M3 c* [ h8 qtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total5 F- p4 \' a. K" f9 w! i/ T6 Q
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),0 z" A7 M* U/ B! m
and β-human chorionic gonadotropin was less than( l9 i7 o& p' P5 g) l% N3 t& X
5 mIU/mL (normal <5 mIU/mL). Serum follicular: G t. E$ m2 g6 u3 W" c
stimulating hormone and leuteinizing hormone% j; A. q. u: w' r. v7 D3 f
concentrations were less than 0.05 mIU/mL$ ?6 G9 F- K* M: o* s! |
(prepubertal).
! H! J# g$ I; P" AThe parents were notified about the laboratory: ]+ y3 W- _7 s
results and were informed that all of the tests were' j0 \" v" \& O$ P
normal except the testosterone level was high. The
# o( A1 F( h9 J! Qfollow-up visit was arranged within a few weeks to
4 a0 x# L1 q6 @obtain testicular and abdominal sonograms; how-
$ l$ h$ M5 W4 B, j2 j0 aever, the family did not return for 4 months.
7 L$ E; G: u" h/ v B; h2 qPhysical examination at this time revealed that the: Y- f, b0 J4 c6 r' E; ~+ ?
child had grown 2.5 cm in 4 months and had gained- I! a" Y7 ~9 e. f. n' l. @
2 kg of weight. Physical examination remained" B# j3 H1 ]! o3 }, k) G
unchanged. Surprisingly, the pubic hair almost com-
4 b- o# g( L z a' G4 ]' u, ypletely disappeared except for a few vellous hairs at
* C9 h- B& J# T$ Q- z5 [3 nthe base of the phallus. Testicular volume was still 2/ s- O% L6 t* ^ M, H9 p |6 C
mL, and the size of the penis remained unchanged.5 B% L6 M3 l+ ]; L) k; x: Z! y5 e
The mother also said that the boy was no longer hav-0 `( l, L9 m& i X
ing frequent erections.
$ x9 P9 f, N) r2 n/ ?/ T% o; R8 eBoth parents were again questioned about use of
* q2 _6 R1 o' Y; G/ \8 R& P7 u8 }any ointment/creams that they may have applied to; B E1 k0 C% l" G
the child’s skin. This time the father admitted the9 \6 ]& A# R( b
Topical Testosterone Exposure / Bhowmick et al 541* P1 a) g. \( d( k0 t) ?- S, B
use of testosterone gel twice daily that he was apply-
6 ]& q4 o3 i! K8 _6 ]3 ting over his own shoulders, chest, and back area for
/ l( |9 K* J' u8 Sa year. The father also revealed he was embarrassed7 @8 H: G" T! R
to disclose that he was using a testosterone gel pre-2 F$ \; J! E; [
scribed by his family physician for decreased libido
m7 [% e* O9 u+ Nsecondary to depression.! G9 ]& K2 [7 Q4 @& I' O
The child slept in the same bed with parents.! w; v' a5 I$ P3 C
The father would hug the baby and hold him on his' {7 g! h+ e6 X+ m. x
chest for a considerable period of time, causing sig-
2 L" H8 r2 c6 ^# lnificant bare skin contact between baby and father.
. o" D) j/ o" n% V2 P' SThe father also admitted that after the phone call,
$ x0 T' u6 u& L% X$ u1 ywhen he learned the testosterone level in the baby9 {: g+ S/ N6 g/ c7 H# @, i
was high, he then read the product information; W b) o0 W8 j/ L( H' \; t
packet and concluded that it was most likely the rea-
! q) o+ [9 \; k7 `# P7 q m9 ason for the child’s virilization. At that time, they4 z* ?! H0 e# ^
decided to put the baby in a separate bed, and the5 Z: D/ q5 ?9 ^
father was not hugging him with bare skin and had
) o' Y5 E1 y J. rbeen using protective clothing. A repeat testosterone" `+ n% f6 L1 [; C9 k. v5 D
test was ordered, but the family did not go to the8 c! T$ N* I5 q/ o0 j# S
laboratory to obtain the test.: Q5 _. w3 l! N
Discussion I3 U0 ]* I7 N6 g/ V
Precocious puberty in boys is defined as secondary! j6 y, {6 i" B6 z, S- A& p1 C
sexual development before 9 years of age.1,46 v+ O0 G0 Z/ f' K; o3 F
Precocious puberty is termed as central (true) when
m+ _3 K8 y9 J6 L9 kit is caused by the premature activation of hypo-
! i0 v2 l. Q8 \( A, A! m& \5 O/ v: sthalamic pituitary gonadal axis. CPP is more com-" ]2 a! V4 {9 E7 X
mon in girls than in boys.1,3 Most boys with CPP
( s4 t$ ~9 ^0 Imay have a central nervous system lesion that is" t3 N) o! N: v' W
responsible for the early activation of the hypothal-
% [) d$ ~6 V( B: ?- r4 E. t" Kamic pituitary gonadal axis.1-3 Thus, greater empha-3 U* c% k' F8 j
sis has been given to neuroradiologic imaging in
: g# ]' }( S" U* Q" f0 f/ Pboys with precocious puberty. In addition to viril-. U1 ]% y1 |2 N I! b) m( M
ization, the clinical hallmark of CPP is the symmet-
9 c% `* Y- a% I: B3 ` o& ?: t0 Drical testicular growth secondary to stimulation by# c. l8 n5 h: M! [ |) g1 _
gonadotropins.1,3( K+ E4 N4 h. i" X% ~( f0 T: V3 `' K
Gonadotropin-independent peripheral preco-) Y& @$ |$ k$ F6 Z0 a7 }/ K, R
cious puberty in boys also results from inappropriate
$ ^# a" L8 Z5 ?" `8 Sandrogenic stimulation from either endogenous or
7 g. d( |+ y- |* H$ g% t/ ^/ z g0 \exogenous sources, nonpituitary gonadotropin stim-
3 m+ V+ v% q, a4 a/ oulation, and rare activating mutations.3 Virilizing
3 m8 ]* o; \1 d" F G. l: Scongenital adrenal hyperplasia producing excessive
& v" D( c3 M5 a& T9 eadrenal androgens is a common cause of precocious* \6 c& S7 g, U5 h# R' N t, J
puberty in boys.3,4
; g0 n6 a4 P1 ]1 v2 x. @The most common form of congenital adrenal
4 t6 _/ L2 N7 P6 a5 J2 L' `hyperplasia is the 21-hydroxylase enzyme deficiency./ s! m/ v- @ {7 Q/ n
The 11-β hydroxylase deficiency may also result in" ^+ u' E0 t {# Q7 y
excessive adrenal androgen production, and rarely,, c2 A/ ^: f+ p1 m! `3 b
an adrenal tumor may also cause adrenal androgen4 k" p; p9 b* u; {* U) \
excess.1,33 B/ W5 q- r# k0 ^- Y1 N, a
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from" m# h( ?6 N3 b! D
542 Clinical Pediatrics / Vol. 46, No. 6, July 20073 g! x. N+ G \: d
A unique entity of male-limited gonadotropin-
3 M, ^0 v! G4 j1 a, V2 N7 Y/ Sindependent precocious puberty, which is also known9 \" r( F/ q9 F
as testotoxicosis, may cause precocious puberty at a
) p" e* }0 z nvery young age. The physical findings in these boys
' B+ y9 Q1 G5 j1 m! A' @1 gwith this disorder are full pubertal development,
" k' P4 G9 F8 d7 E. V. uincluding bilateral testicular growth, similar to boys( d c3 Y0 b5 C1 J
with CPP. The gonadotropin levels in this disorder
& @$ |: T" Y( G Qare suppressed to prepubertal levels and do not show$ \8 _9 l( E X4 S( i% G2 Q) N
pubertal response of gonadotropin after gonadotropin-# a: V* e% v- g8 D( X* N; h- s0 j
releasing hormone stimulation. This is a sex-linked
% k, F! N+ U2 }autosomal dominant disorder that affects only. ~5 j6 f' U9 _8 F
males; therefore, other male members of the family
o) M6 V# r6 v b' X2 _8 |7 \may have similar precocious puberty.3
; f4 l3 G. E& q# K3 E! CIn our patient, physical examination was incon-( m5 n, g# g( k/ W
sistent with true precocious puberty since his testi-
5 z% E' x9 i6 f( xcles were prepubertal in size. However, testotoxicosis
+ p$ e& u) C0 g. Y+ Vwas in the differential diagnosis because his father! [ W' D: b- e R" |% J; b$ }6 }
started puberty somewhat early, and occasionally,2 L( X. n4 L, U7 o& a6 L$ h
testicular enlargement is not that evident in the
" p5 b3 W. [7 o: f g# j8 r& jbeginning of this process.1 In the absence of a neg-
9 @0 V! @5 @1 o! G% E2 J0 f1 vative initial history of androgen exposure, our
. o; v# X4 Y% a, Nbiggest concern was virilizing adrenal hyperplasia,
8 o& L2 S, _2 H2 meither 21-hydroxylase deficiency or 11-β hydroxylase
! |/ e; z0 K6 v4 X5 udeficiency. Those diagnoses were excluded by find-2 N. q8 Z4 e( ]% n" `& z
ing the normal level of adrenal steroids.+ [, n# g3 L- J4 C. I- }9 p
The diagnosis of exogenous androgens was strongly
1 `1 y! G/ q, s4 i; ususpected in a follow-up visit after 4 months because
9 c3 v, S% ~6 ^0 Z+ Qthe physical examination revealed the complete disap-6 ?* X C/ G" I
pearance of pubic hair, normal growth velocity, and
8 V9 C1 l% W) s( ?' D: ~decreased erections. The father admitted using a testos-
' @( e8 e$ p- Z3 n, e0 f6 @terone gel, which he concealed at first visit. He was7 D0 ]: p- q) ^2 V
using it rather frequently, twice a day. The Physicians’
3 G# r1 n* [" _8 i5 bDesk Reference, or package insert of this product, gel or
* O' |0 d9 q. S \0 mcream, cautions about dermal testosterone transfer to( J& g5 F% m8 ]1 E G% g7 h8 L& ~
unprotected females through direct skin exposure.2 ^% `; @9 |6 b4 c% e; [
Serum testosterone level was found to be 2 times the9 ^, E) ~( `- X l8 ~, I9 F
baseline value in those females who were exposed to0 F. u3 n7 B, H, H+ S- \
even 15 minutes of direct skin contact with their male8 x, o& Y2 t! E6 v, r
partners.6 However, when a shirt covered the applica-( A# B2 l% e$ y c+ `" R+ ]) H
tion site, this testosterone transfer was prevented.
! E2 h+ S7 n1 M, GOur patient’s testosterone level was 60 ng/mL,
2 F" L0 L% }& ?% Y' H( H. P0 ywhich was clearly high. Some studies suggest that- ~5 f& ?, a1 ]/ }1 b" m. [
dermal conversion of testosterone to dihydrotestos-
; P1 s# g! @; \5 Nterone, which is a more potent metabolite, is more" F2 z/ h: Z) ^" @5 {9 Y
active in young children exposed to testosterone* ^: C1 w! z# f+ h% ]
exogenously7; however, we did not measure a dihy-
6 M% q* E2 Z; Q6 p4 U N1 I7 p1 Adrotestosterone level in our patient. In addition to' n& G) q, [: `3 I3 n3 r
virilization, exposure to exogenous testosterone in
+ M# F; N7 v$ F5 v; r9 Ychildren results in an increase in growth velocity and
" t$ d5 o: B2 o" b* Uadvanced bone age, as seen in our patient.
+ y* e- y* f3 E* q2 Y+ H8 d MThe long-term effect of androgen exposure during
5 P" K. v& n+ P* ^early childhood on pubertal development and final
/ o! P! o5 j: p4 J6 U7 jadult height are not fully known and always remain0 d9 b g3 [- z
a concern. Children treated with short-term testos-
& |9 u6 r+ y; d$ T" M, Y' |: cterone injection or topical androgen may exhibit some
/ h7 w. Q2 P: M7 nacceleration of the skeletal maturation; however, after
' d3 `- E o, p. Qcessation of treatment, the rate of bone maturation9 ^. Y. `: P6 } h1 p3 z8 G
decelerates and gradually returns to normal.8,9
2 {' L6 k3 e' [# q! M% \: `There are conflicting reports and controversy% S( O1 p. y3 s: ^" @
over the effect of early androgen exposure on adult
0 G% o' _7 r$ \) u s# S7 F) o8 qpenile length.10,11 Some reports suggest subnormal
# l: l- ]$ T; E: E; o3 d' }adult penile length, apparently because of downreg-. i5 c( ^1 {$ P& {) R
ulation of androgen receptor number.10,12 However,
: O" A' T1 h. ]2 X1 E+ i" ^7 zSutherland et al13 did not find a correlation between; m0 x) f4 p6 X2 y; i+ b6 H1 D
childhood testosterone exposure and reduced adult, |$ O; C* k& ~ n- s- x
penile length in clinical studies.
! e) n. u/ b. y4 O; [# }Nonetheless, we do not believe our patient is
/ M* V$ N2 O7 o! T6 wgoing to experience any of the untoward effects from6 |0 Z7 n; n( y1 l t# w
testosterone exposure as mentioned earlier because
, s; f, h9 F G* X. b; h/ v; @& ythe exposure was not for a prolonged period of time.
7 m7 n0 f% R4 A1 {Although the bone age was advanced at the time of( L; [( [8 c0 ]- s' U
diagnosis, the child had a normal growth velocity at
l: C* m4 j! mthe follow-up visit. It is hoped that his final adult% x8 M" S P+ i
height will not be affected.& R K% ?, s8 Y6 s+ R3 T7 {* M
Although rarely reported, the widespread avail-
" U# Y/ G' P8 L4 a2 k( mability of androgen products in our society may
! o; `. ]% j. f' t( |8 {indeed cause more virilization in male or female0 H h _- N; j \
children than one would realize. Exposure to andro-
6 \8 Q" X% n! p" y9 H- Xgen products must be considered and specific ques-, m/ O& z+ T; L# A* Z- H' O! o* h w
tioning about the use of a testosterone product or
; ]7 M& \- b% |% u- y h+ |5 Hgel should be asked of the family members during
4 U( g" y5 \0 H( O0 Q+ h1 g* Zthe evaluation of any children who present with vir-" |3 K# B1 H4 M5 i# x5 s4 Y
ilization or peripheral precocious puberty. The diag-* F9 S4 T$ `& T
nosis can be established by just a few tests and by
- j# S3 V; W, x5 Q u8 Aappropriate history. The inability to obtain such a
+ U/ Y- Z1 j. x0 L/ @history, or failure to ask the specific questions, may/ I3 {% n3 m6 u2 L& u5 f
result in extensive, unnecessary, and expensive
% \+ ^5 h; q: U+ i& l! V; oinvestigation. The primary care physician should be
" v: a: ?2 u: N+ e! {1 L+ P. }# W, Maware of this fact, because most of these children1 X' X+ ?1 z x7 u- B& ?8 g) u
may initially present in their practice. The Physicians’2 b& ^1 x( ]& m* p6 ]. n
Desk Reference and package insert should also put a7 S- h1 O. ?& ~
warning about the virilizing effect on a male or
- a0 z7 w* f! X4 qfemale child who might come in contact with some-
, i6 ]7 l/ J/ C* ?one using any of these products.
5 C/ ]& V' ?! HReferences$ W$ q5 e) m, ^9 v+ R1 o) ]
1. Styne DM. The testes: disorder of sexual differentiation% I8 ^& J% _2 I% k. Y
and puberty in the male. In: Sperling MA, ed. Pediatric
! I/ W! y+ H# k5 ^0 w1 `Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
5 ~1 Z! P W3 w0 W4 z4 E5 B2002: 565-628.
- N |" j/ L3 Y+ i" ?. ]/ `4 z2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious! W) _3 Q9 F1 E9 i% {) m
puberty in children with tumours of the suprasellar pineal |
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