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Sexual Precocity in a 16-Month-Old& }; [( m l/ h4 G5 _& _3 q
Boy Induced by Indirect Topical
; F+ x3 o# ], P$ j- n% I: |6 @Exposure to Testosterone/ o5 e! {4 g$ g; O& s( S
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,29 q* q! l+ V" E& y8 k2 N. O
and Kenneth R. Rettig, MD1% ~1 ~- t$ @# |8 O: B/ ~
Clinical Pediatrics: j# k5 _( F) X0 a9 x/ p( @- O" N
Volume 46 Number 6
7 M# E# p9 i! T fJuly 2007 540-543
/ {- p6 v' I! R! G" e© 2007 Sage Publications# h" x" D: B# S, r. X
10.1177/0009922806296651! q6 W/ A3 t" r
http://clp.sagepub.com
6 w" W- E% U0 _hosted at
) V6 t2 m- z: R( n4 u9 y9 l: N% w- thttp://online.sagepub.com' b, R* w# Z9 |* T6 I7 I+ t
Precocious puberty in boys, central or peripheral,
% t) F3 k7 n! bis a significant concern for physicians. Central9 ?. w( I% f4 \% Y# U# v
precocious puberty (CPP), which is mediated( J, J q' I2 X: V6 @8 b! ]
through the hypothalamic pituitary gonadal axis, has
6 M. i& |6 @& Ra higher incidence of organic central nervous system: Q: B3 a% X! `9 J8 e- y) r
lesions in boys.1,2 Virilization in boys, as manifested
8 N; t+ k% r2 Bby enlargement of the penis, development of pubic
3 m- I7 M9 O1 b& H) R+ Shair, and facial acne without enlargement of testi-
7 l( w' X$ F+ s) y; W" ~0 q8 O$ u: ccles, suggests peripheral or pseudopuberty.1-3 We3 a: J' d, D% s- t% V' B$ W
report a 16-month-old boy who presented with the8 x* j" @2 O& J' C5 `
enlargement of the phallus and pubic hair develop-
% r2 a" K8 X8 d1 v' ]8 wment without testicular enlargement, which was due! q' o3 o. d/ y- X
to the unintentional exposure to androgen gel used by
! j$ h: E- t. W- ~) V$ p* f1 ~the father. The family initially concealed this infor-6 m4 m, z9 Z+ D0 N: S
mation, resulting in an extensive work-up for this
; c! }* i. |; B* x$ T- V) l& wchild. Given the widespread and easy availability of, e! t/ R: r6 E$ Z) X5 z
testosterone gel and cream, we believe this is proba-3 A; j& F1 t+ e
bly more common than the rare case report in the: o) I: F8 N: [/ f
literature.4
5 ^8 Y+ v, T) ePatient Report
( ^& E u6 w# vA 16-month-old white child was referred to the
; M$ Q7 h6 m! L! y+ ~endocrine clinic by his pediatrician with the concern
, H# P, n# f# h( T2 q8 {of early sexual development. His mother noticed1 Z5 `# g* a/ T$ b) @* L
light colored pubic hair development when he was5 w5 `( q) @( p4 `
From the 1Division of Pediatric Endocrinology, 2University of: E7 m) j$ w( n/ Y. T
South Alabama Medical Center, Mobile, Alabama.0 _* X9 O# s) ~; m1 J" E
Address correspondence to: Samar K. Bhowmick, MD, FACE,
2 Z D+ @4 L4 c, Y4 _8 Q2 }Professor of Pediatrics, University of South Alabama, College of4 O& W6 k+ u; n) E9 A
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
4 n" z3 c& B! E( \! x1 Ge-mail: [email protected].' W; ^0 p7 G V1 J% Q) [3 p
about 6 to 7 months old, which progressively became
. \, F% t7 I% N- ~7 h/ X' H/ n4 Kdarker. She was also concerned about the enlarge-+ Z6 p" G/ q- J; T0 P% D
ment of his penis and frequent erections. The child
" _* @0 ` k7 |: u1 Pwas the product of a full-term normal delivery, with
7 o, S+ j4 Z8 G' [8 s2 xa birth weight of 7 lb 14 oz, and birth length of
4 [ E( p9 V9 I20 inches. He was breast-fed throughout the first year
. w5 U* }. q: B* L9 f$ y% iof life and was still receiving breast milk along with+ s- q: J B5 U: P$ R
solid food. He had no hospitalizations or surgery,
! R/ d- K8 {7 Y+ y& d7 vand his psychosocial and psychomotor development
4 ]/ ^" G$ ?: J: X0 cwas age appropriate.- J! n; `. J. w+ e9 H
The family history was remarkable for the father,
1 g: W }. X8 s/ r7 r( p+ g& P% Cwho was diagnosed with hypothyroidism at age 16,: J! k3 Z& L. r- p5 ]
which was treated with thyroxine. The father’s4 u! S9 a* w% p4 Y4 y
height was 6 feet, and he went through a somewhat
2 H7 c* W0 O0 @& P. o" i) f2 d9 t* Fearly puberty and had stopped growing by age 14.
1 C b2 k/ d2 |6 g z P2 h; J# GThe father denied taking any other medication. The
3 A5 K7 H3 I; u' Y- B" bchild’s mother was in good health. Her menarche
" I* V; l- V: Owas at 11 years of age, and her height was at 5 feet# z! Y& t+ S9 ?, d5 l5 K
5 inches. There was no other family history of pre-
4 Z4 ?7 l! s# Z$ E" v3 Jcocious sexual development in the first-degree rela-; e! G8 C7 i2 J+ j9 U$ I& O/ M
tives. There were no siblings.7 x0 f3 i0 O# z" z% h
Physical Examination3 v# {9 z) k! n5 G: D& G7 L( w
The physical examination revealed a very active,
' a( _+ T+ j/ lplayful, and healthy boy. The vital signs documented' g8 Q* d' }& p
a blood pressure of 85/50 mm Hg, his length was6 ]3 I8 h9 J& t0 [/ b* z
90 cm (>97th percentile), and his weight was 14.4 kg4 O' H. J7 H4 H# \& i
(also >97th percentile). The observed yearly growth9 Z1 v3 U+ A' N3 V
velocity was 30 cm (12 inches). The examination of
1 ^! b3 r- m' Y: w) L' U/ Mthe neck revealed no thyroid enlargement.8 o/ G; j& A O4 N
The genitourinary examination was remarkable for
" m- Q; S6 l; x' M0 Q/ qenlargement of the penis, with a stretched length of6 c& N, J/ n/ o+ k7 e- t6 n
8 cm and a width of 2 cm. The glans penis was very well' m+ {! K$ Z1 U4 ]" q. K3 }( j: ^
developed. The pubic hair was Tanner II, mostly around
% b. x% r0 [" J( M540
8 @ ~0 J& R/ Q% n# Nat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
5 l1 n$ ~+ y! m6 J: {( Tthe base of the phallus and was dark and curled. The% f }7 i& v p
testicular volume was prepubertal at 2 mL each.
! B6 f8 L% b A0 a& }+ D* n6 EThe skin was moist and smooth and somewhat) c4 o. g+ d7 ?
oily. No axillary hair was noted. There were no% e, N6 ]! Q8 I/ z- ~3 m
abnormal skin pigmentations or café-au-lait spots.3 p6 Z4 z( }$ ?
Neurologic evaluation showed deep tendon reflex 2+
7 s d9 U* @# \) T5 |bilateral and symmetrical. There was no suggestion
/ ?) h* Z: C. G$ D; W/ r% xof papilledema.
6 u* N$ k; m+ ]0 c' B4 ~: BLaboratory Evaluation& e* t. d1 L' r/ F
The bone age was consistent with 28 months by
# a/ x( a2 z% \" m' Y8 W7 Iusing the standard of Greulich and Pyle at a chrono-" x1 D9 Y8 N* L3 Y: Q+ v9 _
logic age of 16 months (advanced).5 Chromosomal$ y$ _: [' [4 k+ A. Z
karyotype was 46XY. The thyroid function test
0 Q6 e1 u! c/ {. r h) h/ l; v5 y/ R' ashowed a free T4 of 1.69 ng/dL, and thyroid stimu-- t% z- u" b d# k0 W- D1 i8 D
lating hormone level was 1.3 µIU/mL (both normal).' P5 E; O# Z9 E1 g! O9 {( f& G" a7 ]
The concentrations of serum electrolytes, blood4 ]5 j4 e D8 d; `, m
urea nitrogen, creatinine, and calcium all were
( }2 w, |1 q9 `/ Awithin normal range for his age. The concentration6 {# p+ Y- Y# A3 n$ k
of serum 17-hydroxyprogesterone was 16 ng/dL+ M, D' [+ S" K# \# U1 |3 V
(normal, 3 to 90 ng/dL), androstenedione was 20% d- n$ ^/ v. F m
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
d6 H% z/ ?& U% dterone was 38 ng/dL (normal, 50 to 760 ng/dL),
& V( r* q( I" |desoxycorticosterone was 4.3 ng/dL (normal, 7 to2 \' k) W& n; S, T
49ng/dL), 11-desoxycortisol (specific compound S)5 ?) `% {: }6 `% j) i1 x# [
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-4 r6 R, F8 ~1 w3 a2 s0 u: t
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total* w8 {, f: u5 ], C, I5 Z$ }
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),- \4 y$ P, p/ l
and β-human chorionic gonadotropin was less than
7 {2 ]% ~9 X7 i5 mIU/mL (normal <5 mIU/mL). Serum follicular* o* K4 {- s2 @* b
stimulating hormone and leuteinizing hormone' B2 o2 Q y4 j# S' w
concentrations were less than 0.05 mIU/mL
3 |: j3 P4 ~$ s$ e: X; |(prepubertal).; u0 v' ]; X( G" r: j1 O: V
The parents were notified about the laboratory4 \, l' [7 H* R, G, {+ B
results and were informed that all of the tests were6 I6 ]; s ], g+ e" b/ }: J
normal except the testosterone level was high. The! g+ H4 Z/ W1 a @# Z
follow-up visit was arranged within a few weeks to# V4 K2 \5 d. ?
obtain testicular and abdominal sonograms; how-
' C7 I# L' I. ]1 ?, J2 _* bever, the family did not return for 4 months.# N* n4 d$ f& e# ^! Q9 a# w
Physical examination at this time revealed that the) C- w5 k, T J2 z3 e
child had grown 2.5 cm in 4 months and had gained
) h9 f+ x9 n# {2 c/ E: c. d2 kg of weight. Physical examination remained
u: c7 h- V8 k* E }7 M$ yunchanged. Surprisingly, the pubic hair almost com-) j9 \" q4 v8 l) p0 K* h
pletely disappeared except for a few vellous hairs at
* c% J* B5 N' i1 Tthe base of the phallus. Testicular volume was still 2
) B$ p! M$ U2 G, r2 nmL, and the size of the penis remained unchanged.4 Y! {% L2 w5 E. K9 g
The mother also said that the boy was no longer hav-! y2 q. M9 O" B7 z
ing frequent erections.
$ k8 e3 w( i$ y8 nBoth parents were again questioned about use of, [7 o" N( Q) T$ d2 Q# E" D: `
any ointment/creams that they may have applied to
2 \5 p; I2 @0 H% q% G* g! fthe child’s skin. This time the father admitted the
4 A) O8 W0 i) X& h \$ aTopical Testosterone Exposure / Bhowmick et al 5410 v2 t' v( M8 G/ q% a/ w6 R
use of testosterone gel twice daily that he was apply-
$ Z; v5 z, Q% t! Z" ^) \% i. [/ Bing over his own shoulders, chest, and back area for. j, D/ z; B/ ?( T6 y9 y
a year. The father also revealed he was embarrassed+ L3 \+ l6 r m3 z. b4 v
to disclose that he was using a testosterone gel pre-7 X& q9 A1 _6 m8 k; q* T
scribed by his family physician for decreased libido9 e) c& s6 l1 G
secondary to depression./ c- F6 h# G: j$ |) h V
The child slept in the same bed with parents.
. {+ i' A8 T1 y9 ~+ r1 lThe father would hug the baby and hold him on his0 [( t0 }% i Z$ h$ Q- u* K
chest for a considerable period of time, causing sig-
/ w2 I2 u2 b, |3 M+ y* Qnificant bare skin contact between baby and father.
?, _( [5 h! Y( v* p+ TThe father also admitted that after the phone call,
# _5 y/ ~" r- q* p* @when he learned the testosterone level in the baby& ^6 U$ v% B8 t: N
was high, he then read the product information
: J7 {! z( y7 ]( g- l) I' d0 g/ qpacket and concluded that it was most likely the rea-7 Q, u+ E3 f; i* M
son for the child’s virilization. At that time, they
2 T! r- k* s. _3 `decided to put the baby in a separate bed, and the) L S1 | N: [! a) k
father was not hugging him with bare skin and had/ p e- J4 t+ }5 A
been using protective clothing. A repeat testosterone+ l) C* S7 P, B7 J0 o- x
test was ordered, but the family did not go to the
! W3 O5 t, O1 i; s# P; ulaboratory to obtain the test.- u2 M0 I2 P3 ^1 x4 _, j l
Discussion
7 ?; W. `8 b# g" |Precocious puberty in boys is defined as secondary
9 Q* V- d) }6 n, F# xsexual development before 9 years of age.1,4
: K/ S/ \+ V" Y9 { y& P1 VPrecocious puberty is termed as central (true) when
- z+ w' H5 `4 }1 m( ]) zit is caused by the premature activation of hypo-- K; Y' Z7 K3 P N
thalamic pituitary gonadal axis. CPP is more com-
7 h. k* v& ^; Umon in girls than in boys.1,3 Most boys with CPP
4 s# m2 ^3 F: H/ \4 Zmay have a central nervous system lesion that is7 e) L) k U! m; ?; M
responsible for the early activation of the hypothal-/ P+ O( f4 _/ ?' S) R
amic pituitary gonadal axis.1-3 Thus, greater empha-8 T" x4 o: i+ x; \+ M4 M& @9 M
sis has been given to neuroradiologic imaging in2 N. `- P0 j! h, g* m
boys with precocious puberty. In addition to viril-
; Q) R4 n c' {! cization, the clinical hallmark of CPP is the symmet-
, W0 @3 A8 u0 C$ J) X; {rical testicular growth secondary to stimulation by
# K8 h: Y, O! K) |" X; W+ c# Zgonadotropins.1,3
$ u( K- k+ j+ p) G1 oGonadotropin-independent peripheral preco-
% O& M6 f* U- D4 P# B# y+ Pcious puberty in boys also results from inappropriate
- n6 A! ~7 G4 E$ q/ J( n. `- U4 Zandrogenic stimulation from either endogenous or. s% {! ]" ?6 W) P6 p+ G
exogenous sources, nonpituitary gonadotropin stim-0 T& ]$ J: j5 [2 h/ p6 p2 y1 C
ulation, and rare activating mutations.3 Virilizing6 D9 m1 `( x* U7 L8 M$ |' k
congenital adrenal hyperplasia producing excessive1 A$ B& E d" \6 f9 t8 ?
adrenal androgens is a common cause of precocious
3 X2 t% r7 F( n: R+ Kpuberty in boys.3,4
. s& Z+ q y- A# Q3 j2 @% pThe most common form of congenital adrenal
6 R$ G9 ]& `' r: {$ Ghyperplasia is the 21-hydroxylase enzyme deficiency.
- G' Y* j3 g1 G2 p# B7 E; H5 j: IThe 11-β hydroxylase deficiency may also result in1 J8 _" J3 b) x/ \# f/ E K6 c2 W
excessive adrenal androgen production, and rarely,
6 v: Y; ?% }1 Y2 M1 I3 ?6 E( e: d+ Oan adrenal tumor may also cause adrenal androgen
: b) n, z; `$ M7 Rexcess.1,3! _0 T: a4 n) q$ N {4 {* ]4 }
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from+ m$ ]+ d: o( Y( }
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007- M: F1 d+ h) P; O
A unique entity of male-limited gonadotropin-# J( \4 s0 O: K6 A
independent precocious puberty, which is also known
. H0 _' }2 X5 o: C4 ?9 O) _as testotoxicosis, may cause precocious puberty at a
. u% M h$ O( |0 p* qvery young age. The physical findings in these boys
: ]* M' `1 j: o: _* N4 Y& ?with this disorder are full pubertal development,
7 a8 I! m b) K! p8 Xincluding bilateral testicular growth, similar to boys- m2 d( I# K" ~! c4 D: A9 B
with CPP. The gonadotropin levels in this disorder
1 j6 [; I' F8 L uare suppressed to prepubertal levels and do not show! X/ Y1 J+ ~. z+ O
pubertal response of gonadotropin after gonadotropin-
# O; l/ i( q1 S( c xreleasing hormone stimulation. This is a sex-linked, b: v+ L2 o" y7 m* W2 t. X
autosomal dominant disorder that affects only1 `9 j3 G- d) d- F* J4 Y
males; therefore, other male members of the family
8 n# u5 d9 u3 s4 f7 rmay have similar precocious puberty.3
3 u. [" J* C ?7 oIn our patient, physical examination was incon-+ m" [6 K7 O5 a3 L& ?
sistent with true precocious puberty since his testi-- y- B3 c3 ~0 ]- z7 w+ {
cles were prepubertal in size. However, testotoxicosis! X; ~) |4 p* ]! K" c
was in the differential diagnosis because his father
, M" W' b( i3 K+ P- h+ `1 xstarted puberty somewhat early, and occasionally,6 I* g s6 n5 h; L0 e3 W' I* m6 j) S
testicular enlargement is not that evident in the
5 d9 u; l9 ^3 w; C6 t# B* s' D- {beginning of this process.1 In the absence of a neg-8 `) b: [, j& P, S& A
ative initial history of androgen exposure, our
0 T8 K8 }- U1 t p9 N- T/ u1 Mbiggest concern was virilizing adrenal hyperplasia,
( U) ?0 B, b6 r* o$ Peither 21-hydroxylase deficiency or 11-β hydroxylase2 D, \ b) B' w3 h+ {1 p
deficiency. Those diagnoses were excluded by find-
6 j" _( X0 I2 e: Xing the normal level of adrenal steroids.
: H& J7 v6 m7 y' v3 eThe diagnosis of exogenous androgens was strongly0 s4 e' N$ f* c: V& U' _+ J
suspected in a follow-up visit after 4 months because
" c/ a4 O! f5 t3 P4 l# Ethe physical examination revealed the complete disap-& V7 t' X0 @7 J/ q" J; q
pearance of pubic hair, normal growth velocity, and
# v# w( @" {% R# Q; Odecreased erections. The father admitted using a testos-
5 I8 ~" E3 {8 m' Q3 U6 o0 v6 [* [terone gel, which he concealed at first visit. He was
' j% y3 D2 Y3 A8 I4 Rusing it rather frequently, twice a day. The Physicians’/ c# F( [$ @1 S( C. A: w
Desk Reference, or package insert of this product, gel or
# I0 ^. Q& C$ W: bcream, cautions about dermal testosterone transfer to
r# i: I# ^/ q' | gunprotected females through direct skin exposure.1 V3 M9 q* i* h$ S' ]. \' u* [
Serum testosterone level was found to be 2 times the6 N1 h& i9 |8 Q% u o$ H2 p( g& }
baseline value in those females who were exposed to
! V6 m- C; W2 Reven 15 minutes of direct skin contact with their male
% [$ ?$ a/ R3 P- {. bpartners.6 However, when a shirt covered the applica-
! }2 O* p2 H: @! c5 `/ H8 X l3 Etion site, this testosterone transfer was prevented.! s# `* S$ y; |6 E
Our patient’s testosterone level was 60 ng/mL,
* Y* L/ @- `+ ^3 \' E* Q7 J' @which was clearly high. Some studies suggest that0 ]2 \% l" k" j {+ u
dermal conversion of testosterone to dihydrotestos-
! F) E" B+ O- D0 Tterone, which is a more potent metabolite, is more6 ^! ^7 j; g& k: p& v
active in young children exposed to testosterone
- J: x' V* I, dexogenously7; however, we did not measure a dihy-. r' a; o( @9 v# h) W" C
drotestosterone level in our patient. In addition to
; b7 L3 c7 d! c0 ?virilization, exposure to exogenous testosterone in
" y. P* g( A5 `children results in an increase in growth velocity and
) O7 @' o; ?$ f. i+ }1 Eadvanced bone age, as seen in our patient.. U- W" T7 Q& [/ |6 C4 I
The long-term effect of androgen exposure during
; B0 \* w+ P: B; o1 f2 ~* m1 ] l+ }early childhood on pubertal development and final' \& a9 S6 k, O: ~: o. W {& x
adult height are not fully known and always remain# ^9 K! F3 _; N7 ^ E
a concern. Children treated with short-term testos-' ?. z: Y) f% }" E/ W7 R& E* F
terone injection or topical androgen may exhibit some
% t+ E% F. `- c4 Z4 Y; Gacceleration of the skeletal maturation; however, after
. P9 o+ Q# Y3 Q/ I- Icessation of treatment, the rate of bone maturation! S+ m$ Y: l" T4 Q
decelerates and gradually returns to normal.8,9
/ N$ [0 Q5 G8 ~& wThere are conflicting reports and controversy3 Z5 o2 g$ M4 `/ |8 r" `4 L
over the effect of early androgen exposure on adult
# H( D5 z' K2 z+ Q/ H2 a3 A \penile length.10,11 Some reports suggest subnormal9 \6 P( X7 x5 f# v1 \; n; ~: X
adult penile length, apparently because of downreg-8 L* s6 g! w' g4 X
ulation of androgen receptor number.10,12 However,$ K5 x# r* X9 |7 [) v9 R/ K
Sutherland et al13 did not find a correlation between
4 j0 o2 P! [) b7 p1 [childhood testosterone exposure and reduced adult
1 `7 _8 `5 t, V- ipenile length in clinical studies.4 Y$ }9 I ~2 s" J
Nonetheless, we do not believe our patient is
& I5 X& Z9 o* F) t9 \going to experience any of the untoward effects from1 Q9 g# E ~6 d3 s, ~" l+ ]# Y0 J6 M7 i
testosterone exposure as mentioned earlier because0 w V. z& [) l8 x3 Y
the exposure was not for a prolonged period of time.+ P' q! Z% b1 |, Q
Although the bone age was advanced at the time of( {+ B/ f# @* O2 `0 z0 a
diagnosis, the child had a normal growth velocity at
9 i6 M+ y: c+ A7 S- L* t. t6 Ythe follow-up visit. It is hoped that his final adult
, p5 F( @3 |, \. Oheight will not be affected./ u: Y+ @5 }0 w, |0 ^
Although rarely reported, the widespread avail-4 Z, p( ^5 V2 c* K6 s4 k0 C- k
ability of androgen products in our society may
8 c: B# M+ ~0 q5 f% c! n4 Qindeed cause more virilization in male or female+ f0 m; a3 y0 d% D+ A. b+ r9 C1 v
children than one would realize. Exposure to andro-' F2 q, a0 d' P6 d
gen products must be considered and specific ques-2 X( E; P, a0 u ]8 {' h
tioning about the use of a testosterone product or; [. {! M& K* b# T t4 h
gel should be asked of the family members during
9 D. Z9 D$ z( n$ P1 n1 cthe evaluation of any children who present with vir-
. p8 E5 }3 L8 A' z2 W! H7 `ilization or peripheral precocious puberty. The diag-8 ?/ `3 G; W& [& p
nosis can be established by just a few tests and by
: c+ \* V2 ~# Z! c) {appropriate history. The inability to obtain such a, X* \* B' m5 i7 g1 T/ _
history, or failure to ask the specific questions, may& _" T0 y% r5 o7 _1 W4 g4 s
result in extensive, unnecessary, and expensive/ L7 t- Y: B+ j2 u% y( H
investigation. The primary care physician should be
4 t) s9 \( O h! a$ Yaware of this fact, because most of these children5 J* O9 O' ~: S0 _; ^% T0 c, ~: `
may initially present in their practice. The Physicians’$ S/ C4 }" ~) S0 E; b( G! M
Desk Reference and package insert should also put a
$ Z( A, i. O) M: c$ q" Cwarning about the virilizing effect on a male or8 _' ]! Z. ^7 m, Y2 r# o4 B, Q
female child who might come in contact with some-
( @4 I: Z6 y# V" }7 u9 bone using any of these products.
7 P: k1 ? M) H. s! dReferences
7 I5 h2 ?' [" P. c% Z: n1. Styne DM. The testes: disorder of sexual differentiation
* Y/ i1 A" X9 z/ d! land puberty in the male. In: Sperling MA, ed. Pediatric
@+ }# ^+ o0 V+ d+ GEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;. s K% z' p u3 g9 m
2002: 565-628.
. Q( E2 f$ Z7 A, Z* B( D. Y9 \, K2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
! p& \+ ]5 R2 G0 P; w6 epuberty in children with tumours of the suprasellar pineal |
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