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Sexual Precocity in a 16-Month-Old
; t9 W* e- k5 [# \; SBoy Induced by Indirect Topical* y, Q8 F' y" N9 p
Exposure to Testosterone
: P/ b( ^0 h1 nSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
' T# f. e- Q: D) W$ Aand Kenneth R. Rettig, MD1, c8 U# q k* i& H' O, S. P
Clinical Pediatrics
9 D; W9 c& N4 h+ z" T# @' WVolume 46 Number 6
% \9 ]+ x3 V8 B0 j, DJuly 2007 540-543
7 F7 j2 g0 D9 u1 B$ F$ M, N© 2007 Sage Publications
+ H: Q* l- l( _9 l10.1177/0009922806296651
0 s+ b2 U3 i* S. |9 jhttp://clp.sagepub.com
' Y3 I; F3 n2 B Rhosted at
# z( k" u/ U7 d& X# k$ zhttp://online.sagepub.com
# j* A v+ J( |9 F8 F3 v ^5 XPrecocious puberty in boys, central or peripheral,
A) e' H8 W7 O8 p0 C6 n& pis a significant concern for physicians. Central
8 @* ^$ R) I2 N7 E/ T: x% Hprecocious puberty (CPP), which is mediated
* F; ]. @) Q! ~7 n8 O0 u$ Zthrough the hypothalamic pituitary gonadal axis, has8 q7 K% G8 w7 y' }
a higher incidence of organic central nervous system
2 m) e6 n n1 L# o5 O5 [- \/ tlesions in boys.1,2 Virilization in boys, as manifested
2 `9 s, F# N6 a' ?7 eby enlargement of the penis, development of pubic
- o$ [4 v0 j0 e% ?2 N7 B$ Q, Z: `hair, and facial acne without enlargement of testi-2 c: h( T5 {# _
cles, suggests peripheral or pseudopuberty.1-3 We" E1 g% |: e- v! H9 r* N
report a 16-month-old boy who presented with the
& c2 I" A* |: c$ p8 B/ l; `" _% ^enlargement of the phallus and pubic hair develop-
$ \% S. H9 q) h( @& A, q1 G7 @) Yment without testicular enlargement, which was due
% }, I! y! `3 Z+ U% P( X) |to the unintentional exposure to androgen gel used by
' i( |/ c6 e. C! m1 [6 qthe father. The family initially concealed this infor-
7 t, O2 R s* t& `6 Q/ n# wmation, resulting in an extensive work-up for this- T/ c5 W7 `: q' q: t
child. Given the widespread and easy availability of3 T! G- [# B6 {- L# V9 |
testosterone gel and cream, we believe this is proba-
# x% K: s& K+ y$ }bly more common than the rare case report in the7 F4 n$ g0 Q! k8 E! I
literature.4
' z# s% C, C; E- D" k4 V3 xPatient Report
' }6 R8 j& d H' R6 }( `A 16-month-old white child was referred to the* [; |( g }7 R9 r
endocrine clinic by his pediatrician with the concern
6 X* J1 z& H6 }: |: g' q' Rof early sexual development. His mother noticed
. W# D1 _( P# d+ N: @3 d( blight colored pubic hair development when he was
: `, b7 i: Z! U- V$ ], l$ T1 BFrom the 1Division of Pediatric Endocrinology, 2University of
/ g7 Q5 `$ I1 ESouth Alabama Medical Center, Mobile, Alabama.
: N9 }( O- l; _/ eAddress correspondence to: Samar K. Bhowmick, MD, FACE,
' u0 T4 x# S, B9 vProfessor of Pediatrics, University of South Alabama, College of
( x! V" D5 Y- I7 nMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
/ W' _7 ]( i# Le-mail: [email protected].
" {0 ^+ G: T" A, j' F. ~9 c" j$ Habout 6 to 7 months old, which progressively became( M; |) c$ z- v: g' s, Q A
darker. She was also concerned about the enlarge-9 M& Z( _) n( b8 D4 }# h, }9 p
ment of his penis and frequent erections. The child
8 y- V, Y4 S# x4 K8 X. Jwas the product of a full-term normal delivery, with
" Z" L U7 L; }4 s* Z5 U. va birth weight of 7 lb 14 oz, and birth length of
4 K! X% U- l' V/ i% q$ a20 inches. He was breast-fed throughout the first year( d4 R& ^9 x+ G' q
of life and was still receiving breast milk along with$ }+ _7 S! C" F( I* g! k- z, Z% _
solid food. He had no hospitalizations or surgery,) l# `# v5 s; J. v) i
and his psychosocial and psychomotor development, i3 h: D* r/ t* J0 |
was age appropriate.
, \, e8 L4 u( {/ yThe family history was remarkable for the father,
6 z' w, q Y# P3 S; m" X4 z- A, }who was diagnosed with hypothyroidism at age 16,
# b, g% F9 v K" @1 z9 V+ \which was treated with thyroxine. The father’s( Q) V2 z2 H- n9 Z7 h- w3 O' |: k
height was 6 feet, and he went through a somewhat
) T0 }+ T5 F+ [5 j/ E) Cearly puberty and had stopped growing by age 14.
" y& G. H* c/ oThe father denied taking any other medication. The0 J# o! G, S+ g( A) _
child’s mother was in good health. Her menarche* T! A/ V1 Y" S3 ^& i u- L
was at 11 years of age, and her height was at 5 feet( P7 F) n7 n" R
5 inches. There was no other family history of pre-7 }2 V7 t% S2 C+ b' v+ v/ x6 G
cocious sexual development in the first-degree rela-
6 E& M" z' h5 }" I' otives. There were no siblings.. P% k& i0 c2 g. o G- o5 R/ P% K' j
Physical Examination
$ r' H$ F' ^% q0 N* J W! aThe physical examination revealed a very active,6 ~5 b3 ?4 y1 }; ~9 M) M
playful, and healthy boy. The vital signs documented( M2 G. D; z# g. P% _, c
a blood pressure of 85/50 mm Hg, his length was4 R: P& g8 q _$ m# s: Q
90 cm (>97th percentile), and his weight was 14.4 kg% v' y' [' A! O1 M/ ~8 {; ^
(also >97th percentile). The observed yearly growth
8 J+ e! {$ p. M& ~& L& O+ C' wvelocity was 30 cm (12 inches). The examination of1 w) K7 p; o0 V* d$ p* q! Q& c
the neck revealed no thyroid enlargement.
9 y9 |# e# G0 Z; ~The genitourinary examination was remarkable for! c( n! a0 Z! `
enlargement of the penis, with a stretched length of9 E3 P6 [5 |6 R
8 cm and a width of 2 cm. The glans penis was very well4 }4 [0 ]& r1 l8 \
developed. The pubic hair was Tanner II, mostly around
4 V: @( \1 }/ z. {540
, C. V y8 Z7 h x' A: \" e, Q' iat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from! j' y# f0 c, E! b4 V; \& R
the base of the phallus and was dark and curled. The
4 m. I# k; c1 m( N: C+ n) ytesticular volume was prepubertal at 2 mL each.: Q6 E4 q o7 A- V
The skin was moist and smooth and somewhat
6 m) A. H, J# q$ h/ z; goily. No axillary hair was noted. There were no
4 t( C% K* l0 N Z6 y9 {abnormal skin pigmentations or café-au-lait spots.
0 E. ?5 ~" q7 S+ H' ^$ ~8 fNeurologic evaluation showed deep tendon reflex 2+& Y+ ^+ E6 y% H# V3 n" j
bilateral and symmetrical. There was no suggestion
6 B" K7 H5 |9 y- F' S, w8 u3 Yof papilledema.
- c' L' j; e" yLaboratory Evaluation
5 d6 ]0 h" Z: m6 p7 {The bone age was consistent with 28 months by
9 \+ x6 V9 o( musing the standard of Greulich and Pyle at a chrono-" q) N( j3 o9 M- d- ?. \
logic age of 16 months (advanced).5 Chromosomal
/ v+ x3 r/ P* k" v4 U" O0 lkaryotype was 46XY. The thyroid function test$ |! `1 G4 J z5 \ T5 o
showed a free T4 of 1.69 ng/dL, and thyroid stimu-% `( |0 n$ }8 Y& Q
lating hormone level was 1.3 µIU/mL (both normal).
; f% c, V( z/ ] Z G& [. f1 tThe concentrations of serum electrolytes, blood
: }; z# g' C v0 ~urea nitrogen, creatinine, and calcium all were
# R5 U9 m: C" P& owithin normal range for his age. The concentration
z7 ]6 j b2 N! a2 t2 N% e& F' lof serum 17-hydroxyprogesterone was 16 ng/dL) b$ i" a3 I2 f4 J
(normal, 3 to 90 ng/dL), androstenedione was 20& Y$ f- n0 k5 k( q$ B: X0 v
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
3 D* m$ |9 n" x8 W: y# Qterone was 38 ng/dL (normal, 50 to 760 ng/dL),
% c8 v$ y/ S9 e. O( ~! r0 i$ T& y- Y( Zdesoxycorticosterone was 4.3 ng/dL (normal, 7 to
' D* x2 o1 C8 f) r49ng/dL), 11-desoxycortisol (specific compound S)
8 w, o2 e4 t! V5 D, j3 d0 owas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor- \/ h& R9 _( d" B" L- r5 f
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
2 o z" x! G M( t# l) ~% M4 Qtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),* N3 ?0 p) d0 G! d6 M! {4 x% r
and β-human chorionic gonadotropin was less than) C" T$ w3 E: @" g: c
5 mIU/mL (normal <5 mIU/mL). Serum follicular# Q% O9 A* p- v* k2 d! N
stimulating hormone and leuteinizing hormone4 R) S3 {3 O3 Z2 C# Y
concentrations were less than 0.05 mIU/mL9 n; K9 c* s8 A: ~/ a# J+ W3 |
(prepubertal).8 J/ G' V" P0 @& @7 r
The parents were notified about the laboratory
5 Q V. G# Q( h0 e9 N4 n/ C7 vresults and were informed that all of the tests were, _8 g. B6 a/ N' X' n
normal except the testosterone level was high. The
N3 ~% E- V3 n" x0 kfollow-up visit was arranged within a few weeks to6 w: c8 @' |+ i8 P. `
obtain testicular and abdominal sonograms; how-# J: r5 K* s6 Y+ M
ever, the family did not return for 4 months.; D! s2 x) ]) f8 h
Physical examination at this time revealed that the# {* l: w6 S9 G
child had grown 2.5 cm in 4 months and had gained# m7 u7 ]6 v0 i+ v$ I# g
2 kg of weight. Physical examination remained
6 }0 z3 |5 ?3 q& |6 g8 H' wunchanged. Surprisingly, the pubic hair almost com-8 U" }9 d, S" w1 {" T4 i
pletely disappeared except for a few vellous hairs at
8 G M7 t8 ?, [+ W* N2 Wthe base of the phallus. Testicular volume was still 2
" |- T6 _ Z' i* ]8 SmL, and the size of the penis remained unchanged.
6 v, r' w) R& `* |4 w# ^0 CThe mother also said that the boy was no longer hav-
0 a3 ^0 V- H* ~! }9 Ning frequent erections.; O) R5 N- n4 {. m* f
Both parents were again questioned about use of5 x- x! A' p/ ^& l1 q
any ointment/creams that they may have applied to
% Z; x; x* @' p0 hthe child’s skin. This time the father admitted the
: |. K) b' Y; NTopical Testosterone Exposure / Bhowmick et al 5414 O0 I' P) ?5 U" s: R& }8 _) ^
use of testosterone gel twice daily that he was apply-) P9 j, H$ t/ j
ing over his own shoulders, chest, and back area for
6 o4 W# G* q% B7 J3 G4 g: `a year. The father also revealed he was embarrassed# z5 H' Z1 G! z, M
to disclose that he was using a testosterone gel pre-
% P; Y* j1 Y3 K5 ]scribed by his family physician for decreased libido' }' X* f/ {$ N
secondary to depression.
% J4 r, b% n% T8 s7 H$ @The child slept in the same bed with parents., z, Z8 w- P3 [) K" p" z% S4 j% p
The father would hug the baby and hold him on his$ ? C# F! X" M2 G
chest for a considerable period of time, causing sig-
, m5 W& |* t6 s9 s+ Q; {. c! J9 Dnificant bare skin contact between baby and father.
/ |& q/ u7 z8 k& j2 e% B0 JThe father also admitted that after the phone call,. i3 P) u/ r4 \9 z
when he learned the testosterone level in the baby
$ W! [* @ x/ D4 swas high, he then read the product information- D1 }' t6 c2 U' V# J! {
packet and concluded that it was most likely the rea-! {) t$ N# P# ~& a6 E
son for the child’s virilization. At that time, they6 l: W$ N" \+ b+ @% P" `& q4 j
decided to put the baby in a separate bed, and the
8 b4 P i; x# J) S& T d( @) {father was not hugging him with bare skin and had9 A/ L+ }7 p C/ E
been using protective clothing. A repeat testosterone. L: K# I# @* X7 Y. W* N
test was ordered, but the family did not go to the0 M9 }9 j% x. l- n( P
laboratory to obtain the test.
; S% T: h6 _; g- d% V Z! `Discussion: a5 B% x- k- s1 v2 o% D
Precocious puberty in boys is defined as secondary; r6 @: L; V, I3 {6 l: B' S
sexual development before 9 years of age.1,4
+ v2 \% @/ d7 g7 q2 CPrecocious puberty is termed as central (true) when
. g' C8 s! J9 S7 d5 |' ~& Yit is caused by the premature activation of hypo-
m$ h3 l1 p2 K% `- J# r0 rthalamic pituitary gonadal axis. CPP is more com-' q& L3 L) f9 W1 d3 G, I
mon in girls than in boys.1,3 Most boys with CPP( f# K7 w+ [$ H: Y7 `0 H1 C% k
may have a central nervous system lesion that is
# M" |4 G1 t# Y+ Bresponsible for the early activation of the hypothal-
7 T I* P1 w) f1 Eamic pituitary gonadal axis.1-3 Thus, greater empha-' p' f% R5 @/ C& b5 c5 }
sis has been given to neuroradiologic imaging in! E3 E5 L0 M8 J
boys with precocious puberty. In addition to viril-* d, ]) ?: ^2 r8 b g U
ization, the clinical hallmark of CPP is the symmet-2 r( b, m% @# E3 `! K
rical testicular growth secondary to stimulation by( N) Q% X4 k7 i. T$ K( K
gonadotropins.1,3( `3 k' e( k; g( d% k" ~
Gonadotropin-independent peripheral preco-
$ g$ B7 ?6 G& g% Ncious puberty in boys also results from inappropriate
' j; T9 Y. T$ [- m/ Nandrogenic stimulation from either endogenous or# Z5 z0 D! u2 F+ \ X( t; y4 E
exogenous sources, nonpituitary gonadotropin stim-
* I/ b( P& @* julation, and rare activating mutations.3 Virilizing, }7 @6 b' z6 T" o4 S
congenital adrenal hyperplasia producing excessive- `) v* V( O% d6 t0 E
adrenal androgens is a common cause of precocious
6 ]8 y& d3 E, B( u* {, hpuberty in boys.3,4 r8 V1 f- V, s% l6 S1 P! \
The most common form of congenital adrenal
7 J. {5 B3 W+ ~' ahyperplasia is the 21-hydroxylase enzyme deficiency.
( M$ _0 U# l5 o: l; @% I! ~The 11-β hydroxylase deficiency may also result in
2 w3 m/ b4 ^4 eexcessive adrenal androgen production, and rarely, [% d& Z0 t! k! L
an adrenal tumor may also cause adrenal androgen
1 ]( J' E' g" B. f/ @! W( qexcess.1,32 H2 D. T, n: H) A, m- c4 L* ?- F+ j* T9 t
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
+ _' V. Z, K) ~" p/ [; Y542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
. b; B7 H* b4 T b1 ^: P2 f) hA unique entity of male-limited gonadotropin-
& H* N$ [1 Z+ P3 o4 Vindependent precocious puberty, which is also known- `/ S. y8 R7 i7 }
as testotoxicosis, may cause precocious puberty at a
1 Z# Z6 D& J# j& H% [very young age. The physical findings in these boys6 {7 e) M2 B3 ~5 W* J; N
with this disorder are full pubertal development,
$ g' q7 L E/ fincluding bilateral testicular growth, similar to boys
" L4 ^6 e9 n4 O* H5 A+ ?with CPP. The gonadotropin levels in this disorder
. ~/ q8 d1 ` o9 ^7 qare suppressed to prepubertal levels and do not show
3 N% g7 ~+ B, epubertal response of gonadotropin after gonadotropin- ^# |! A5 O: O/ \1 m5 Z
releasing hormone stimulation. This is a sex-linked
) y- Q S; W0 K0 K' F0 H8 r o0 Fautosomal dominant disorder that affects only
4 i3 F; n' x! amales; therefore, other male members of the family- _" p; i6 C- T+ P' j4 ~
may have similar precocious puberty.3
. R( S) P# A R6 G2 C0 e1 |+ q7 F) UIn our patient, physical examination was incon-
( y/ _" |4 D bsistent with true precocious puberty since his testi-6 f3 e0 B. o+ x0 Z
cles were prepubertal in size. However, testotoxicosis
8 e2 J/ D# X. q# H; X0 }6 [8 Pwas in the differential diagnosis because his father
$ ^* Y l' S# a) istarted puberty somewhat early, and occasionally,- n( i" G6 ~. I# Z) A# Z) t5 j
testicular enlargement is not that evident in the
/ ?2 ~+ v6 A" ^ O6 Xbeginning of this process.1 In the absence of a neg-
e/ `5 D4 f% ]: K# ?ative initial history of androgen exposure, our
. K. A0 i( o6 I& p! ?7 ]1 ebiggest concern was virilizing adrenal hyperplasia,
& W: F0 E* H" c; Z' Z. Feither 21-hydroxylase deficiency or 11-β hydroxylase
) J- b V( w w4 A, Odeficiency. Those diagnoses were excluded by find-$ N: B `$ C* I/ [7 Y
ing the normal level of adrenal steroids.- f9 o9 n5 t% t1 k1 _6 b5 S8 J
The diagnosis of exogenous androgens was strongly
5 P+ h( b# w+ M8 F7 x: jsuspected in a follow-up visit after 4 months because
$ |5 ?2 }' S# ^9 }the physical examination revealed the complete disap-
+ ^# V4 C( k- S8 T9 O% B) Qpearance of pubic hair, normal growth velocity, and+ Q, r( w$ e* a5 x% x ?" c& v
decreased erections. The father admitted using a testos-' U7 a) g+ T. G' Z" Q# u7 H. Z9 H0 O
terone gel, which he concealed at first visit. He was
) j& |( S- e, D" l( W2 m& [using it rather frequently, twice a day. The Physicians’2 ]$ ~2 c" U" m+ j2 l
Desk Reference, or package insert of this product, gel or$ Y/ b3 _3 m( E+ n( M2 B& g
cream, cautions about dermal testosterone transfer to
3 C3 S( n% l2 b$ V# Nunprotected females through direct skin exposure.) i. w; {8 k+ c9 M4 E; e
Serum testosterone level was found to be 2 times the
; c4 r7 E2 ~! ~! `! V! Rbaseline value in those females who were exposed to
, N3 V) G2 ]( J \) w; x+ q8 Ueven 15 minutes of direct skin contact with their male
& u5 C/ V/ g4 _( R% y( jpartners.6 However, when a shirt covered the applica-
* l% s$ h4 O r! D( ktion site, this testosterone transfer was prevented.
8 S% K8 e+ I6 \! C1 POur patient’s testosterone level was 60 ng/mL," N+ X5 l1 Q3 f: y
which was clearly high. Some studies suggest that2 a- g* B# a/ \' L
dermal conversion of testosterone to dihydrotestos-
8 ]; m9 p5 Q. c+ G% g6 Uterone, which is a more potent metabolite, is more
8 [6 Z3 C1 c/ }; a3 @' o$ Gactive in young children exposed to testosterone
4 @* a$ |8 E% O( Yexogenously7; however, we did not measure a dihy-
% T7 _1 l( X! B: [8 Udrotestosterone level in our patient. In addition to( s/ F/ g% |1 { y$ t
virilization, exposure to exogenous testosterone in; R( J+ X6 P& X% G
children results in an increase in growth velocity and
/ } f o+ u1 o9 \# V7 `) W1 Vadvanced bone age, as seen in our patient.
' [0 C4 ~, L+ d7 r! a) C& r4 s# Z# aThe long-term effect of androgen exposure during
* z( Y. R. Q" P/ Hearly childhood on pubertal development and final
" I% ?" ~: |& \+ v# Zadult height are not fully known and always remain
! D; ~2 E. @: S( Sa concern. Children treated with short-term testos-% Y% f5 j: U2 ^) f- m
terone injection or topical androgen may exhibit some; p8 b% t) r9 M; G6 r$ t2 G% Q
acceleration of the skeletal maturation; however, after3 M. a4 G( f& p; i, k
cessation of treatment, the rate of bone maturation
3 x; y1 ?) z1 sdecelerates and gradually returns to normal.8,9
) K8 @! }3 w3 Q% ^" o& Y- w3 }There are conflicting reports and controversy) v( p) L$ m" s/ }, t
over the effect of early androgen exposure on adult
7 Z D% ?4 ^$ t) Q4 @2 n; Lpenile length.10,11 Some reports suggest subnormal
1 d. S7 p5 j" ?7 B! Z6 l8 k& Wadult penile length, apparently because of downreg- _, |4 [; X8 {* k0 P5 R
ulation of androgen receptor number.10,12 However,
. h& |, A7 F7 Q! B1 PSutherland et al13 did not find a correlation between- A0 E1 u0 ?9 a3 ^8 A' `
childhood testosterone exposure and reduced adult
5 d+ W2 L% z& |4 G) Xpenile length in clinical studies.
6 r- y# r: Y8 ]7 U; j6 \1 F1 S6 fNonetheless, we do not believe our patient is
' O1 T7 _7 X& t, E- ngoing to experience any of the untoward effects from
9 @4 m; B6 B$ J' Z* A, Itestosterone exposure as mentioned earlier because$ B( m" w* J* L# ^
the exposure was not for a prolonged period of time.3 \6 S# L6 I% e- m+ i$ E f4 R8 e
Although the bone age was advanced at the time of: T! g) ^5 E( r, q9 E' H
diagnosis, the child had a normal growth velocity at
% {* [; L8 Y5 D3 Athe follow-up visit. It is hoped that his final adult
5 b' J2 _# n6 u/ U, Theight will not be affected.) l. H1 {6 U. e% w
Although rarely reported, the widespread avail-
' D, J3 W6 T9 `" b, \0 @/ V+ }ability of androgen products in our society may
, m/ E9 S& w9 X* ^5 D+ _6 Z! G3 l+ Y# pindeed cause more virilization in male or female. i- R, o6 i9 }. O1 i& E& a; Z1 i
children than one would realize. Exposure to andro-. B( T% k9 a$ L$ B* P6 C+ H* d0 G# V
gen products must be considered and specific ques-
7 p# J0 K) `' t! gtioning about the use of a testosterone product or
6 q8 R- W6 h- u: Q! f% tgel should be asked of the family members during% _# z/ \% G; \8 V* R
the evaluation of any children who present with vir-& [. p& R% U# I# u
ilization or peripheral precocious puberty. The diag-
- ]2 K9 R7 I: e: k, Znosis can be established by just a few tests and by2 ?6 e7 u4 y( V/ j. Z- X, k
appropriate history. The inability to obtain such a
) H" i+ e1 N; r E5 Zhistory, or failure to ask the specific questions, may5 T4 j, m! Y5 u, E% y1 G5 ]. m
result in extensive, unnecessary, and expensive S( D$ l7 l C& M- S
investigation. The primary care physician should be/ J5 a7 b& p) \- m
aware of this fact, because most of these children
- l; k& n$ |, l3 j) l Q' @may initially present in their practice. The Physicians’' W2 u/ X( g8 J- r6 S) M0 ]
Desk Reference and package insert should also put a8 q3 p9 N+ i6 ] Q
warning about the virilizing effect on a male or- p- W5 [' z* h3 E! E N+ F" L
female child who might come in contact with some-
; W9 D, R2 J+ D8 p2 U% ~+ ~one using any of these products." Q/ i# y! \8 _. o, L& s
References
: {# J7 U: H4 G4 K! ~1. Styne DM. The testes: disorder of sexual differentiation
: L7 T- N& k5 eand puberty in the male. In: Sperling MA, ed. Pediatric4 B f9 t- g% W4 ], x9 ?
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;! P/ k2 M: }( t. _8 y# x+ [
2002: 565-628.- m! ?0 U3 a$ t* m* ]" r) I/ U
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
5 e& N, k2 V. [( Xpuberty in children with tumours of the suprasellar pineal |
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