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Sexual Precocity in a 16-Month-Old
' O g5 n* r* P' D8 ZBoy Induced by Indirect Topical5 K" C: x t) I* n7 G
Exposure to Testosterone
6 w9 z6 \( U% \; J6 L# ASamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
6 D0 y ~ E2 Z5 C; ^and Kenneth R. Rettig, MD1! X# \$ Z [3 z2 I+ r( G: k
Clinical Pediatrics
: m: k& [! Y. `8 t! A! o+ ^" DVolume 46 Number 63 |* J" s& Q2 ~* e) m& Q9 q0 T
July 2007 540-5434 d& z7 q+ K- \0 X
© 2007 Sage Publications
* Q0 Q+ i# P# |# |( D10.1177/0009922806296651
Q3 V1 {1 d" y; d# Qhttp://clp.sagepub.com; w5 l4 Y8 l, a$ e* m8 ^; w
hosted at
1 P, N' q( l: k( B9 _$ e* Ghttp://online.sagepub.com
' v7 U9 n, }( m4 b) ]( APrecocious puberty in boys, central or peripheral,+ ]2 A9 W# H) c- ]
is a significant concern for physicians. Central
# P1 f: i6 T& h! o- l4 eprecocious puberty (CPP), which is mediated
+ N/ m/ a9 g; D( {: Ethrough the hypothalamic pituitary gonadal axis, has3 _9 B+ E% b3 i3 M& j5 @
a higher incidence of organic central nervous system7 t$ H0 V/ M* ^7 U) l% q0 y; U
lesions in boys.1,2 Virilization in boys, as manifested
, |' |" g; j4 N" k! K( d% N) jby enlargement of the penis, development of pubic
/ I, L$ ~5 ^' L5 A2 p8 Whair, and facial acne without enlargement of testi-
" D* X& R, q* r5 L5 W! w8 { H4 q: Qcles, suggests peripheral or pseudopuberty.1-3 We
8 m, n; L! z Creport a 16-month-old boy who presented with the3 D3 G2 O' Y0 l/ p
enlargement of the phallus and pubic hair develop-7 n$ R3 l# v" N
ment without testicular enlargement, which was due; i/ ~' |, ]( [" y) e
to the unintentional exposure to androgen gel used by8 @5 M; R. a3 c8 I R y
the father. The family initially concealed this infor-
[4 F& \1 R( }0 Xmation, resulting in an extensive work-up for this
$ e4 k5 Q3 {+ P, e, u" mchild. Given the widespread and easy availability of! L1 l* p% ^' x
testosterone gel and cream, we believe this is proba-
" r' x% g+ V. f5 v6 Xbly more common than the rare case report in the
9 [2 ?5 n6 v9 v, B% H2 u+ rliterature.47 x( y0 u2 ^& X O1 T
Patient Report
4 `6 C) U" t2 B E3 dA 16-month-old white child was referred to the
/ n) Z8 }6 N8 Z/ oendocrine clinic by his pediatrician with the concern
3 [* i$ N/ E/ ?' k2 q5 s& Yof early sexual development. His mother noticed; h: I, t; q, R3 m. @0 f
light colored pubic hair development when he was
4 `, o/ z- v5 E7 G7 zFrom the 1Division of Pediatric Endocrinology, 2University of
" Z; j4 q6 C! O2 MSouth Alabama Medical Center, Mobile, Alabama.
( l& U/ X+ C! N8 g9 g4 kAddress correspondence to: Samar K. Bhowmick, MD, FACE,+ h. a) _1 P' I
Professor of Pediatrics, University of South Alabama, College of& R9 v. p4 }) C+ E( k. N
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
) u4 t9 k8 L xe-mail: [email protected].( D+ m1 H6 ~- [* S
about 6 to 7 months old, which progressively became' c9 G+ q x) W; g' c( T; L
darker. She was also concerned about the enlarge-' Q0 X" }2 s( A# D t1 l
ment of his penis and frequent erections. The child6 R; w# m! `5 j$ R0 W
was the product of a full-term normal delivery, with
, m; }3 S* Q0 w, Pa birth weight of 7 lb 14 oz, and birth length of
0 q f4 }! w. I4 l0 ?0 _! q6 T20 inches. He was breast-fed throughout the first year
2 F+ I( q' b. @8 u4 t! P: S0 bof life and was still receiving breast milk along with: R' Y& ^: f- m6 I+ F$ i" Q# v
solid food. He had no hospitalizations or surgery,
- t! v$ V! |$ Q$ j Mand his psychosocial and psychomotor development
5 F9 ?; e+ U5 Twas age appropriate.
* O1 N$ Z: A3 n4 _9 eThe family history was remarkable for the father,
8 r! H8 ^/ Q+ [ p! F ewho was diagnosed with hypothyroidism at age 16, O' D( ]( ]8 u' w0 s
which was treated with thyroxine. The father’s0 t9 ^: A9 X# n3 \
height was 6 feet, and he went through a somewhat2 G% g- b+ C4 E0 z$ k: u
early puberty and had stopped growing by age 14.5 ?. p0 X" i9 ]# q
The father denied taking any other medication. The* v8 n2 D: A- }& y0 _
child’s mother was in good health. Her menarche
& I4 N u4 n( g nwas at 11 years of age, and her height was at 5 feet
8 k- y/ }8 d; q( o( J: p+ u+ [5 inches. There was no other family history of pre-: p+ [( v5 |. y
cocious sexual development in the first-degree rela-3 Z2 H" m+ |1 Z" ~9 S' A0 C. F- U
tives. There were no siblings.2 A7 ]; l6 u4 @
Physical Examination, f7 e) _, a5 D7 _" k- a# ]8 ~. }
The physical examination revealed a very active,
1 c& e6 y8 F+ m$ V9 Gplayful, and healthy boy. The vital signs documented$ d6 ^! Q) U) }- e, f
a blood pressure of 85/50 mm Hg, his length was K) E; B, U, c! o
90 cm (>97th percentile), and his weight was 14.4 kg
9 a' w8 Q# _$ H0 ]9 n(also >97th percentile). The observed yearly growth
5 q" E. U' Y" g3 }3 L, Svelocity was 30 cm (12 inches). The examination of
) O0 x9 K3 J9 {. P: p: H; u" ethe neck revealed no thyroid enlargement." e, \ ]# W8 M
The genitourinary examination was remarkable for
0 M2 ^0 B, N! W; nenlargement of the penis, with a stretched length of [# Q: `) a: V+ A1 o: m$ I5 @
8 cm and a width of 2 cm. The glans penis was very well
- {$ S/ P0 _: w: c- U G" ~4 M8 gdeveloped. The pubic hair was Tanner II, mostly around
# r6 f" O( N7 K# t3 ]540
$ {0 [4 p9 s% `3 \2 t' }at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
- }0 c9 M; [* pthe base of the phallus and was dark and curled. The" z2 M% Q( K& l' M2 T- [
testicular volume was prepubertal at 2 mL each.+ P. `. M. x# |0 m0 I* i
The skin was moist and smooth and somewhat
) p" x7 E8 f6 U# Coily. No axillary hair was noted. There were no( ?' C9 h& e8 ~4 I
abnormal skin pigmentations or café-au-lait spots.
. ?# y# o" b: B6 g6 xNeurologic evaluation showed deep tendon reflex 2+6 Q! V/ s' {; Q$ @8 m
bilateral and symmetrical. There was no suggestion
: T! o3 D+ _$ tof papilledema.8 b, d9 p* B5 |5 M# z4 N2 B
Laboratory Evaluation
; R9 C! ?3 k( Z$ pThe bone age was consistent with 28 months by
) d- H' E0 F( C+ E' Fusing the standard of Greulich and Pyle at a chrono-% u" d; _) S$ H. A
logic age of 16 months (advanced).5 Chromosomal( d. z- _: _+ a$ j, W) W
karyotype was 46XY. The thyroid function test
" Z+ ?' r1 n2 u+ s# Sshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
. w! G$ e! }3 v) f4 j8 slating hormone level was 1.3 µIU/mL (both normal).4 p3 B* b; Q9 k( `
The concentrations of serum electrolytes, blood
6 `4 A3 C3 ^& a( E" B$ V E- xurea nitrogen, creatinine, and calcium all were% ]; O* ~8 z5 @6 q
within normal range for his age. The concentration
" R9 y& Y; j" q. l3 y" Z6 c6 F5 `/ Mof serum 17-hydroxyprogesterone was 16 ng/dL
: h$ F5 g- X; G(normal, 3 to 90 ng/dL), androstenedione was 20
# p5 I7 C8 @8 tng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-4 ^2 n9 I- S2 S. b7 _" b- O
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
6 I# `+ z0 w) j, P" [6 O6 [desoxycorticosterone was 4.3 ng/dL (normal, 7 to' a0 D8 S5 w5 ~2 @
49ng/dL), 11-desoxycortisol (specific compound S)
/ K9 ~7 f+ R4 X" G5 |was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
, I2 a' |9 P, `1 @tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total- }. i9 m k! Z8 E- R' h( v
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
7 X8 O; l# n( _+ _5 x8 wand β-human chorionic gonadotropin was less than8 Z/ N( s/ F5 n) r& ^/ u& N! @1 h
5 mIU/mL (normal <5 mIU/mL). Serum follicular9 C: _# w% r: Z3 D
stimulating hormone and leuteinizing hormone
$ J6 E& @) d/ ]2 U3 cconcentrations were less than 0.05 mIU/mL
: G) ~4 g4 D; @: f- n9 B(prepubertal).* U0 H; m2 j) K6 X
The parents were notified about the laboratory, N& C7 _0 M/ a2 b l" V* q: N
results and were informed that all of the tests were* a) b3 l E) }) v' @* B) I8 L5 i
normal except the testosterone level was high. The
; w+ x+ c, D% z) Ffollow-up visit was arranged within a few weeks to
: m) ^ v. \: o1 O$ aobtain testicular and abdominal sonograms; how-9 a4 i0 w U1 L6 t, X8 ], B( d/ z
ever, the family did not return for 4 months.
# g, P$ v, U: y9 J, W( Y+ ~* APhysical examination at this time revealed that the
9 o, ?2 c o" L3 X3 q9 P5 N( h' Q$ zchild had grown 2.5 cm in 4 months and had gained0 U6 X( j& {0 F0 j
2 kg of weight. Physical examination remained
! Q& V" s) p. ~unchanged. Surprisingly, the pubic hair almost com-
3 e7 [: F2 t4 W! L, X# r8 @pletely disappeared except for a few vellous hairs at
) l& i* O4 Q9 Y- T @# M+ K1 \the base of the phallus. Testicular volume was still 2
( k& Q. Z* j6 y5 amL, and the size of the penis remained unchanged. [4 A. Q/ n* U& x" _; b
The mother also said that the boy was no longer hav-# q* M2 R' t8 F) _+ Y
ing frequent erections.
6 o) r) L' E" ~. Z+ oBoth parents were again questioned about use of. @0 Q( q0 W I4 B+ {+ K' m
any ointment/creams that they may have applied to
V9 M: M" ?. F7 L4 A. cthe child’s skin. This time the father admitted the
) h8 w! w) ]2 l- Z* zTopical Testosterone Exposure / Bhowmick et al 541: G% m3 W- n3 D& w( O0 c) G
use of testosterone gel twice daily that he was apply-
- U, v3 I. P. c/ ~: r' Wing over his own shoulders, chest, and back area for
H; F b! k+ [3 u6 _a year. The father also revealed he was embarrassed, N) f' O% {# r- u5 S3 h4 b
to disclose that he was using a testosterone gel pre-# @4 U4 d6 }: k' e' n# w- P, j
scribed by his family physician for decreased libido+ U6 _# B# c# o# A) p; T
secondary to depression. e9 o m9 n0 ]/ R! q* W; z
The child slept in the same bed with parents.
6 e( N$ P2 s2 G9 B2 ^6 I: }4 M7 |The father would hug the baby and hold him on his( C; e" A' L# [0 l8 U& S- z' S, d
chest for a considerable period of time, causing sig-
+ b4 ]6 k+ G2 q4 {) \* bnificant bare skin contact between baby and father.
- @/ w. e+ u9 k$ f. ^0 JThe father also admitted that after the phone call,7 h9 U0 Y& [1 E4 |, [: m3 _
when he learned the testosterone level in the baby5 d. b# \5 s6 O5 l/ H
was high, he then read the product information
) I2 q& L [# U% _packet and concluded that it was most likely the rea-$ `" e! {' _9 s. Z J
son for the child’s virilization. At that time, they7 ^$ ?7 c' b7 N+ ]* a
decided to put the baby in a separate bed, and the& E* W& X+ j& n
father was not hugging him with bare skin and had
: r& D) j( w$ b: abeen using protective clothing. A repeat testosterone
0 d, z7 o* [7 Utest was ordered, but the family did not go to the. t: B( {4 D( f% {8 p
laboratory to obtain the test.' r, n9 `6 U; W
Discussion7 U8 `) `9 l' ?% L6 [6 `- S6 m
Precocious puberty in boys is defined as secondary
; z) r8 j4 ]3 a- C6 ^sexual development before 9 years of age.1,46 P# b) O5 \% b9 X0 ^! U
Precocious puberty is termed as central (true) when W0 q! B7 w) T2 Z
it is caused by the premature activation of hypo-
+ p1 \8 o8 H+ Y7 J1 A6 f; sthalamic pituitary gonadal axis. CPP is more com-' \. k4 @" e7 B# t3 m" [
mon in girls than in boys.1,3 Most boys with CPP5 H/ } ] e! v
may have a central nervous system lesion that is( t+ h$ M S7 E2 Q9 `
responsible for the early activation of the hypothal-
+ L- e; O, }! |: Iamic pituitary gonadal axis.1-3 Thus, greater empha-
. K, R( Z) u( w) z/ Isis has been given to neuroradiologic imaging in/ Q7 x$ ]7 [1 g! t6 O; T0 }2 ~, D
boys with precocious puberty. In addition to viril-" |& g3 E& k: w% K" V0 |# ], Y0 z
ization, the clinical hallmark of CPP is the symmet-
+ d" K j5 C2 P' p) irical testicular growth secondary to stimulation by, W( w. a$ ^0 _- a# h& O7 x7 ~ s& s
gonadotropins.1,32 D% W# a; P9 X* O* ?2 W) S5 O0 }" S
Gonadotropin-independent peripheral preco-
# I8 s0 W9 T! ~# d8 f) ~2 ycious puberty in boys also results from inappropriate. x4 A2 `( r* R& |$ D2 m
androgenic stimulation from either endogenous or
9 d i* e- a8 M! H) {exogenous sources, nonpituitary gonadotropin stim-$ g( R5 F& w2 Z# z, a1 f, _. K& o: ?
ulation, and rare activating mutations.3 Virilizing& b' @" ]1 L4 W- j7 c3 N5 x2 _4 B+ Q
congenital adrenal hyperplasia producing excessive
9 H& P3 q& d1 `" f2 tadrenal androgens is a common cause of precocious
3 D, |( a2 @3 F: a1 }/ _: Z' P' ?4 apuberty in boys.3,4& u. n4 l; W7 K
The most common form of congenital adrenal' C# }- r7 L3 }, A
hyperplasia is the 21-hydroxylase enzyme deficiency.
0 `7 n$ f7 _- }5 e9 MThe 11-β hydroxylase deficiency may also result in& D) F1 c3 W6 x
excessive adrenal androgen production, and rarely, W7 Y1 E# b |
an adrenal tumor may also cause adrenal androgen! X' P A. A5 c1 }# J
excess.1,35 Z4 ?9 |3 l4 l. y3 E7 T Y! x0 c
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from3 S# K) H6 i3 R3 ^$ C
542 Clinical Pediatrics / Vol. 46, No. 6, July 20072 u" I4 `" s7 x! Y4 f
A unique entity of male-limited gonadotropin-: p/ h1 b& _* f. a' U/ N9 m
independent precocious puberty, which is also known4 x. D6 S$ F& K7 F7 M! f* `8 z
as testotoxicosis, may cause precocious puberty at a
* s5 m# b, ]3 _, Zvery young age. The physical findings in these boys; g1 O5 F0 [ W
with this disorder are full pubertal development,2 a2 n% m' C5 w' T9 x5 q1 B
including bilateral testicular growth, similar to boys
" z: I5 w2 G) T+ Jwith CPP. The gonadotropin levels in this disorder
[" y) M/ p( vare suppressed to prepubertal levels and do not show
! v8 x0 Y. R& e' U# }1 opubertal response of gonadotropin after gonadotropin-
9 K9 y. \! J" M: ~# Treleasing hormone stimulation. This is a sex-linked$ h9 A6 q' I5 u' o
autosomal dominant disorder that affects only5 K2 [, M& U/ I8 ]& I
males; therefore, other male members of the family
5 i% ]/ f5 }- B- y2 c% bmay have similar precocious puberty.3
: J; [$ `8 s4 l% y' M2 bIn our patient, physical examination was incon-$ j( Y/ I3 b2 Y g1 z( V, P
sistent with true precocious puberty since his testi-" C" N# X0 e/ d! i; W Z8 A7 m) a- g4 V
cles were prepubertal in size. However, testotoxicosis
3 d/ D6 ]) ^; p, ?was in the differential diagnosis because his father+ a7 N* k& a6 U0 A. ^" E0 @
started puberty somewhat early, and occasionally,& r# r- J7 H9 U& w0 o& x
testicular enlargement is not that evident in the
1 \ G$ l) Q2 V+ A' M2 {# zbeginning of this process.1 In the absence of a neg-
% \3 C2 e+ V' _4 q0 }# _& M! _ative initial history of androgen exposure, our' X5 l' C% s% y9 l+ i
biggest concern was virilizing adrenal hyperplasia,
, A! z! B' V/ k% G }- heither 21-hydroxylase deficiency or 11-β hydroxylase
: }6 ~- n8 u, X* T0 Wdeficiency. Those diagnoses were excluded by find-( ]0 p9 _$ c3 W
ing the normal level of adrenal steroids.
, K+ f8 z$ A0 X" w2 A# sThe diagnosis of exogenous androgens was strongly* ]9 e2 G: r$ v/ |
suspected in a follow-up visit after 4 months because
" ]2 Y5 h- N: K/ f) i( r" f: hthe physical examination revealed the complete disap-
0 ]; }: h/ K, n3 u, Wpearance of pubic hair, normal growth velocity, and
8 V. V& C; e9 O+ b2 ^* Fdecreased erections. The father admitted using a testos-, g* n+ n3 d; x
terone gel, which he concealed at first visit. He was
: j* i, q8 B! I& r. l% E( e- b1 susing it rather frequently, twice a day. The Physicians’5 v; S2 _$ w: c3 X( e% [% |& u; {
Desk Reference, or package insert of this product, gel or6 b0 o1 Z/ A8 `9 z' `
cream, cautions about dermal testosterone transfer to
\: g! @4 N, W- y# xunprotected females through direct skin exposure.
w# p2 K4 ?9 H i, nSerum testosterone level was found to be 2 times the
( a/ o* Z: c& v$ K. u, {8 }: M/ _baseline value in those females who were exposed to
3 t7 R& x3 U2 G8 a" {1 `even 15 minutes of direct skin contact with their male
3 h7 j% h# _: cpartners.6 However, when a shirt covered the applica-3 G$ R5 b& M, N5 v, y, M$ n
tion site, this testosterone transfer was prevented.
- {- Q8 v, k& W1 o; c( Q4 V' N4 |Our patient’s testosterone level was 60 ng/mL,# `7 A5 g7 h2 K9 I% u9 N2 w
which was clearly high. Some studies suggest that+ ^4 ^1 _+ q8 v* Z! H# X9 T
dermal conversion of testosterone to dihydrotestos-
9 r; K) L6 `9 ?0 @7 {( aterone, which is a more potent metabolite, is more9 n3 K ?4 C$ k- ~# B5 J0 J+ |
active in young children exposed to testosterone
: D$ u2 {9 z$ V4 T8 f* sexogenously7; however, we did not measure a dihy-! G$ M. B+ F' H) g" W4 I
drotestosterone level in our patient. In addition to
0 {3 w0 _9 e' Q4 |0 s9 [/ s! cvirilization, exposure to exogenous testosterone in
1 m8 o3 N# E2 m% } ^children results in an increase in growth velocity and9 F7 S! B% ^$ e. F
advanced bone age, as seen in our patient.
$ l' H5 ]# Q( a7 dThe long-term effect of androgen exposure during
9 |) n; ?% S- R& Y- R# K/ x) nearly childhood on pubertal development and final
& c1 T" r/ \; s" B$ h8 ?( }6 `; \adult height are not fully known and always remain
3 I& @! a7 S& P3 q+ La concern. Children treated with short-term testos-1 v' ]' l! ~' s7 N
terone injection or topical androgen may exhibit some
& u9 q% i$ L7 Macceleration of the skeletal maturation; however, after
& s5 l9 ^0 o; @cessation of treatment, the rate of bone maturation
+ \1 m) l/ z) W6 Rdecelerates and gradually returns to normal.8,9
8 D$ G( a: g3 J* U) E: R5 I$ jThere are conflicting reports and controversy
$ R7 O2 A1 y# L/ Aover the effect of early androgen exposure on adult/ O, C6 d/ F% M- l: O2 u
penile length.10,11 Some reports suggest subnormal
8 S4 h& J& {1 u! }7 dadult penile length, apparently because of downreg-& q1 U. l+ b( `/ v* O; B
ulation of androgen receptor number.10,12 However,
3 x8 L6 F2 K, a+ M gSutherland et al13 did not find a correlation between
( a2 \8 }' C+ c% W' Uchildhood testosterone exposure and reduced adult2 c9 w) f @$ m* ]2 b" Q" |) Y
penile length in clinical studies.
Z! y$ k% A' O3 P N+ ONonetheless, we do not believe our patient is4 |% H* O7 O. Z9 S. j ^9 ^9 l% l
going to experience any of the untoward effects from+ y( V+ t& m4 W! |
testosterone exposure as mentioned earlier because3 P" O( \( E% O2 i$ y
the exposure was not for a prolonged period of time.) m7 R& M9 o o
Although the bone age was advanced at the time of
& ^; b. M& ]& w" {0 U- Ediagnosis, the child had a normal growth velocity at
5 [2 [' K' j& Athe follow-up visit. It is hoped that his final adult. x! J1 h0 [; I, G( _ r: p
height will not be affected.
9 C `3 i# M ^* a( a2 j8 WAlthough rarely reported, the widespread avail-
3 R) p* u7 r# M0 o( L( X/ Y1 r4 Tability of androgen products in our society may
' ~. F- J: `8 L4 [indeed cause more virilization in male or female' l- [! f' m7 @( h5 ]: {, S3 Q
children than one would realize. Exposure to andro-( G7 E+ C, A8 C( |) }: Q
gen products must be considered and specific ques-4 K3 x0 V: F' Q6 T- ?4 u
tioning about the use of a testosterone product or
8 |$ p D; x+ W5 @gel should be asked of the family members during. ~* |5 y5 Y7 |+ ^" |: ?4 N! l3 O# r
the evaluation of any children who present with vir-; u1 R* }% Y6 v% b$ w) B1 X; g& ?
ilization or peripheral precocious puberty. The diag-3 h- z/ O) u8 X2 Z2 R+ v$ w
nosis can be established by just a few tests and by4 p9 x, m2 S8 H3 }* {. I
appropriate history. The inability to obtain such a+ Z J3 i5 D9 r, [6 f/ B
history, or failure to ask the specific questions, may9 O7 _5 G& }' f1 h- R) w
result in extensive, unnecessary, and expensive9 n+ f; O1 p9 X$ _' `
investigation. The primary care physician should be
* V v3 N3 w+ H" _/ E; |. A4 Y7 Q( Faware of this fact, because most of these children6 j9 O8 }5 h. f2 U& k% j3 M
may initially present in their practice. The Physicians’
8 Z! K0 _. w- Y7 d/ D/ QDesk Reference and package insert should also put a$ Q* B8 m8 h6 }! B( P H
warning about the virilizing effect on a male or
1 b3 h2 v6 h6 x' Q% M( N H: j6 o$ Gfemale child who might come in contact with some-
! s+ y! c. o3 p& Gone using any of these products.! R2 G" P1 ^% X2 l9 O
References* l1 ~( c8 k2 d4 K$ O; u; D- ^
1. Styne DM. The testes: disorder of sexual differentiation
0 y l- ]! O: u2 P2 b* i2 j( a6 W" aand puberty in the male. In: Sperling MA, ed. Pediatric
3 T( ~0 A7 p; v4 dEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;9 n; W8 }2 ^% x8 `% q6 |: q
2002: 565-628.2 V4 q3 O& }+ q: @
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious5 Y* L- { f2 | H1 g5 a; r
puberty in children with tumours of the suprasellar pineal |
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