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Sexual Precocity in a 16-Month-Old0 a' G1 Y+ d2 ?! ]
Boy Induced by Indirect Topical
/ S, |& p2 c5 FExposure to Testosterone
6 r" k9 x Y& f% y1 }: QSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
& {5 H- `- A) H) g( xand Kenneth R. Rettig, MD1
3 s) e5 t" k( I5 Z" LClinical Pediatrics
. E6 {8 l; ` {' Q8 _. cVolume 46 Number 67 D) D) u$ b6 r k* x9 a6 t- s
July 2007 540-5430 E/ b/ ^! R( [4 y; t5 ]) W
© 2007 Sage Publications X% S9 Q8 c. \5 P
10.1177/0009922806296651& q. T* \3 `$ f$ p8 j8 S# p
http://clp.sagepub.com* S2 j2 i; Q2 m, b# K
hosted at
4 q* M7 c7 z& `7 G3 dhttp://online.sagepub.com
5 \" N( n/ X. Q! P/ X, _& EPrecocious puberty in boys, central or peripheral,8 w0 R) |- o8 ?6 ~% e- j3 _8 A
is a significant concern for physicians. Central8 V) O2 D9 U- F* k0 ^( p+ W& Z+ {
precocious puberty (CPP), which is mediated
. L: Z1 n2 u0 W) w3 jthrough the hypothalamic pituitary gonadal axis, has: s, @! C. p% Q* h. W
a higher incidence of organic central nervous system8 S8 {$ W& Q0 v" q$ v
lesions in boys.1,2 Virilization in boys, as manifested& i: R) Y8 }9 s# g3 |1 W
by enlargement of the penis, development of pubic
( W Z% p: p1 K9 }' W* Lhair, and facial acne without enlargement of testi-3 S; i$ |/ K) k2 C/ q; [& ?
cles, suggests peripheral or pseudopuberty.1-3 We
: ]" p# `0 y& a0 ~report a 16-month-old boy who presented with the
; e- p' @; g: M, p0 c6 A3 _6 nenlargement of the phallus and pubic hair develop-
& {3 ~ `- z+ o" E* Mment without testicular enlargement, which was due0 s' g& S; p# ?4 E( m
to the unintentional exposure to androgen gel used by
( ?9 ~% [6 s" \2 [7 q. E" l5 Jthe father. The family initially concealed this infor-
/ z) o* m1 ?' F) ], S. w# N5 cmation, resulting in an extensive work-up for this
1 \# B9 z) H3 y L8 {$ v, Cchild. Given the widespread and easy availability of! O8 }+ }; _5 x1 b3 B
testosterone gel and cream, we believe this is proba-
+ `+ w9 h2 e) c# Y) I* u0 |1 K, sbly more common than the rare case report in the0 l% A9 u% _; `8 {- [+ e! Q. P7 B% _; M
literature.4
) l& A) c* y, y3 bPatient Report
6 @; D2 ]% i4 Z' V( v/ {" xA 16-month-old white child was referred to the, Y* C4 P7 J" F1 |0 d, p- c- z$ }
endocrine clinic by his pediatrician with the concern1 _% u y. g2 W( m% p
of early sexual development. His mother noticed' f! C0 G& i/ f( h
light colored pubic hair development when he was
- e0 x5 [2 X) RFrom the 1Division of Pediatric Endocrinology, 2University of( N* d7 c2 s/ h" C2 A$ P, r9 f
South Alabama Medical Center, Mobile, Alabama.! C3 w/ o n5 e; h$ ^
Address correspondence to: Samar K. Bhowmick, MD, FACE,1 ^9 m6 i }! g) v
Professor of Pediatrics, University of South Alabama, College of: d0 q. T9 i5 X N
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
+ j1 N$ ?; y* O" L6 }e-mail: [email protected].
5 J* u( S7 a4 a$ Z& f8 Nabout 6 to 7 months old, which progressively became
7 c, R$ O8 E; x( Qdarker. She was also concerned about the enlarge-% ^" |7 J$ B( C
ment of his penis and frequent erections. The child0 ]. N' _7 _4 g/ j' t! e
was the product of a full-term normal delivery, with
; j4 R* J% K5 Ua birth weight of 7 lb 14 oz, and birth length of
" G; d+ y! v5 L: M20 inches. He was breast-fed throughout the first year( J6 g- d8 `- c; _0 C
of life and was still receiving breast milk along with
x" M1 Y5 b0 csolid food. He had no hospitalizations or surgery,
( W" B/ e6 A) R# G8 c- }( \& land his psychosocial and psychomotor development/ O4 o5 }7 I6 V
was age appropriate.3 n, i: n4 u+ W: s3 R& S
The family history was remarkable for the father,8 s% j& l4 u, ]& j
who was diagnosed with hypothyroidism at age 16,
9 f; X2 u; o/ b, [# N- z/ p* _which was treated with thyroxine. The father’s
0 o8 [7 p7 b- h( Theight was 6 feet, and he went through a somewhat" f8 I+ G3 w* F8 B
early puberty and had stopped growing by age 14.
- Z* t$ z& T* g) wThe father denied taking any other medication. The
4 A8 h% z* X$ x5 E1 b3 q% echild’s mother was in good health. Her menarche) ]3 t E, b) y1 M
was at 11 years of age, and her height was at 5 feet0 t$ @1 Y2 {9 T$ y$ D
5 inches. There was no other family history of pre-: i4 N+ i$ \% P8 A( |( C
cocious sexual development in the first-degree rela-# i6 E0 }) C1 x5 [6 O' \
tives. There were no siblings. ?% U3 X6 g, v6 [; ?, \
Physical Examination
/ D" A- O0 B3 f- SThe physical examination revealed a very active,' X0 K$ D2 H$ j; \- L! D
playful, and healthy boy. The vital signs documented
t l0 I. O# d: I% Ia blood pressure of 85/50 mm Hg, his length was; v! m0 A" z3 R
90 cm (>97th percentile), and his weight was 14.4 kg: ~7 Z: y1 r7 K( L
(also >97th percentile). The observed yearly growth0 E3 G4 X) g& H. V- p- s
velocity was 30 cm (12 inches). The examination of
0 i9 m% u. W7 _5 n6 v4 m* X( rthe neck revealed no thyroid enlargement.
3 f- W$ `8 k! GThe genitourinary examination was remarkable for5 I b( ~8 J1 _1 y3 o
enlargement of the penis, with a stretched length of& j9 {3 Z" U' |' h% r, [
8 cm and a width of 2 cm. The glans penis was very well) S2 s1 ^6 E' C) e
developed. The pubic hair was Tanner II, mostly around' v4 c4 s& }" @6 s, ^
540
/ }$ B: `6 c) R7 A- oat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
. z- j8 g, W6 X/ @: ~. P# t$ ethe base of the phallus and was dark and curled. The+ X' S3 y* G8 W
testicular volume was prepubertal at 2 mL each.
4 I4 e( M* k2 h( d, v3 b: m1 BThe skin was moist and smooth and somewhat
- v3 M; a: h" Z/ c; aoily. No axillary hair was noted. There were no
" S A8 f6 \; _4 `abnormal skin pigmentations or café-au-lait spots.* F9 ^/ C" @+ ^$ Y4 g' W$ Z
Neurologic evaluation showed deep tendon reflex 2+: c/ N; `# G$ i; }" A! ~" s* B( n# v
bilateral and symmetrical. There was no suggestion
. X# n( s- a- i( y8 q$ X$ c. W) sof papilledema., \( l( F' M. f' {3 m
Laboratory Evaluation( t/ R" x! t& @' Q' g
The bone age was consistent with 28 months by& y. v) `, Y, c5 d; U- I3 z
using the standard of Greulich and Pyle at a chrono-" I# H% A( t1 y( `' ~
logic age of 16 months (advanced).5 Chromosomal9 q' y' J0 u4 M
karyotype was 46XY. The thyroid function test5 \2 t8 O W0 b; ] ^+ [
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
" h; y* S, ^- S( Z1 K8 }9 Alating hormone level was 1.3 µIU/mL (both normal).2 C) n9 p/ k- ~# a! H( ~
The concentrations of serum electrolytes, blood' A8 _+ {: G: h. p
urea nitrogen, creatinine, and calcium all were
( r7 I3 u! G. `) @! lwithin normal range for his age. The concentration
. D2 K9 b3 \( K' `' yof serum 17-hydroxyprogesterone was 16 ng/dL
# C2 _8 A/ R: P+ T* Y(normal, 3 to 90 ng/dL), androstenedione was 20$ M5 ? Z1 M+ K
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
' p! Z7 x0 S. J6 dterone was 38 ng/dL (normal, 50 to 760 ng/dL),, Q2 {) G$ r. S
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
. {% @0 b, c1 c! A& a5 q5 s/ P: x49ng/dL), 11-desoxycortisol (specific compound S)* z6 y/ b( `" ^+ ^6 s; F
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
' ]* @! V+ D, x+ [9 Z$ Ftisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
+ L) u% m4 E8 P; Z$ X6 l" v, _1 Jtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),+ ^8 I# [* A* c: V. R. [: a
and β-human chorionic gonadotropin was less than: L5 s- E9 z" ]9 M) q; I
5 mIU/mL (normal <5 mIU/mL). Serum follicular6 k. n& C: j+ J4 _# z' c7 r& [
stimulating hormone and leuteinizing hormone( ?0 j2 P3 M9 ~8 U0 \1 q+ G
concentrations were less than 0.05 mIU/mL O# \/ q# t3 r
(prepubertal).6 u; z! r/ F+ M8 D7 Q
The parents were notified about the laboratory
! f( B' R6 X F: Gresults and were informed that all of the tests were
1 r+ Z& ]* R, f" a( snormal except the testosterone level was high. The
/ d+ a$ } e, [, I- M2 dfollow-up visit was arranged within a few weeks to6 b N) O q/ X, d, b& Z. I
obtain testicular and abdominal sonograms; how-
4 _4 }6 ?8 ~( Z) @2 Mever, the family did not return for 4 months.) d0 S& v* I. U; V9 M
Physical examination at this time revealed that the
: w3 f0 i6 K3 k' A, ]# I5 b4 v# Pchild had grown 2.5 cm in 4 months and had gained0 ~* G. P- g: J+ N! b
2 kg of weight. Physical examination remained
: ?; M6 I7 x2 K9 M" R Q- Y' d; ]. }. xunchanged. Surprisingly, the pubic hair almost com-
2 e* A d5 d" \& G( opletely disappeared except for a few vellous hairs at9 V) N6 [1 d* Q9 o2 s
the base of the phallus. Testicular volume was still 2
( W5 C! S# H0 ^% XmL, and the size of the penis remained unchanged.5 z1 h" E v; I/ P" Y
The mother also said that the boy was no longer hav-
' j6 D* I7 Q- n5 N/ I* I# Ging frequent erections.9 s; t3 M2 X" J$ ?1 n. e! [$ y$ i E7 a
Both parents were again questioned about use of
% y2 ~, n7 i: q) y3 p6 J$ f& Pany ointment/creams that they may have applied to
1 I/ n% w1 i* O: A4 ?/ a l1 Zthe child’s skin. This time the father admitted the
: u8 T9 {, j- d# O) s. M! f! e: L6 uTopical Testosterone Exposure / Bhowmick et al 5417 W4 g& I- C) A; f" ^- r. S/ `
use of testosterone gel twice daily that he was apply-
x- R3 [% Z M7 P( ?2 _ing over his own shoulders, chest, and back area for
3 R, B8 R0 J* z3 I: Ia year. The father also revealed he was embarrassed
7 Y' p3 v8 H V8 b# zto disclose that he was using a testosterone gel pre-
% g) M7 z3 P+ e7 [! Xscribed by his family physician for decreased libido
' S3 [! t1 Z2 _9 T3 D% S4 U6 h; ?, ]secondary to depression.6 [* Z. D' B5 D+ z( q9 T
The child slept in the same bed with parents.
3 u( d7 S" h0 P( DThe father would hug the baby and hold him on his
* z3 h) N8 ?: C a3 kchest for a considerable period of time, causing sig-& X# b) l- Z$ Q& b4 } H8 n3 p
nificant bare skin contact between baby and father.
+ w0 j# I- p( c B& S: M/ A( NThe father also admitted that after the phone call," q3 u3 E+ x+ v6 s: t' B4 ^3 L/ b% r
when he learned the testosterone level in the baby
! n6 f3 O6 J: T" K& z( lwas high, he then read the product information6 V2 f4 T6 ~9 B" W- Y# i6 R
packet and concluded that it was most likely the rea-; o$ c" A+ h0 P- t8 u( L4 M7 h
son for the child’s virilization. At that time, they
8 S7 h( y$ k! v) S5 c1 Jdecided to put the baby in a separate bed, and the- Z- J- l- e% Y( \& }
father was not hugging him with bare skin and had. x! @3 C9 `7 m6 `# | r6 l
been using protective clothing. A repeat testosterone
8 l0 [/ g; l! x' P5 ?2 z1 t5 mtest was ordered, but the family did not go to the
4 X& ]# F: @9 I6 E; e$ K3 ]* Vlaboratory to obtain the test.
8 ]$ Z( t- w8 o. m* s1 xDiscussion7 W) m6 |/ z& t2 R u
Precocious puberty in boys is defined as secondary& b/ o t, f6 \, E
sexual development before 9 years of age.1,4
0 ^! b* t" Q+ T I: O$ B1 s" `( _Precocious puberty is termed as central (true) when
9 b+ `7 B9 q j' _, X" s. f2 \it is caused by the premature activation of hypo-3 S- l; B1 v/ o. a6 q2 l1 ^9 R
thalamic pituitary gonadal axis. CPP is more com-
5 b& n% k# w, g, c, F# z" _0 g4 jmon in girls than in boys.1,3 Most boys with CPP F7 z; S: s, A+ j0 I( [
may have a central nervous system lesion that is% U1 K; ~9 M' w
responsible for the early activation of the hypothal-! d4 J3 [, e0 A' I
amic pituitary gonadal axis.1-3 Thus, greater empha-
; ~( O; `/ P K5 M" x* d0 c: y2 qsis has been given to neuroradiologic imaging in
5 _$ x& K' n* D4 \7 Nboys with precocious puberty. In addition to viril-
, v" g! G" }6 l+ s8 fization, the clinical hallmark of CPP is the symmet-
: ]; b1 ~2 T% F0 O$ t+ _rical testicular growth secondary to stimulation by' r/ n# ?+ p, U' K+ w/ [
gonadotropins.1,30 W# \$ x, P5 I5 U) p u d1 a M
Gonadotropin-independent peripheral preco-
' m ?, _0 F+ acious puberty in boys also results from inappropriate
# t) f( ?$ f! j: {& tandrogenic stimulation from either endogenous or/ F8 m, v" u4 Y( a! `5 i8 E, J
exogenous sources, nonpituitary gonadotropin stim-0 ]; r$ V) D+ l
ulation, and rare activating mutations.3 Virilizing
2 c! @9 l$ p3 `8 j5 R! _" Z7 gcongenital adrenal hyperplasia producing excessive, |& H- P. |$ n
adrenal androgens is a common cause of precocious
5 a* d4 R; x. @/ I( e& Gpuberty in boys.3,40 N. a! H y# ?$ L8 T
The most common form of congenital adrenal# ]" d2 V" @! g
hyperplasia is the 21-hydroxylase enzyme deficiency.
) ]4 t% G% m' D( x- wThe 11-β hydroxylase deficiency may also result in( K" M5 \) T8 a
excessive adrenal androgen production, and rarely,+ x/ T3 u: ^8 @9 @7 u1 f
an adrenal tumor may also cause adrenal androgen
8 j3 @! i9 B8 F) G7 [excess.1,3
8 E& M, G+ W# p' j5 mat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
8 m' g' H- L+ C8 z" }& G- p542 Clinical Pediatrics / Vol. 46, No. 6, July 2007% b! ]2 b+ S; u! I
A unique entity of male-limited gonadotropin-, _9 W1 }2 M. O6 J9 N
independent precocious puberty, which is also known
5 ?9 w# {1 V& G, J) c/ W; {as testotoxicosis, may cause precocious puberty at a, V P. `5 I( A9 b( @3 @8 m, C
very young age. The physical findings in these boys" m9 N& o4 I+ L
with this disorder are full pubertal development,% ]! [: ^% t1 k( i
including bilateral testicular growth, similar to boys
) n8 k5 Y# | N+ p5 z9 Iwith CPP. The gonadotropin levels in this disorder& k' ]7 R, Q, h$ ]9 I" l) y ]1 B
are suppressed to prepubertal levels and do not show) A! v+ }* o7 v' r
pubertal response of gonadotropin after gonadotropin-
' Y: C5 S; K7 d4 ~* g8 X+ v" Xreleasing hormone stimulation. This is a sex-linked" u1 e2 D$ g3 C7 x- ^4 q/ P- ~2 d4 y
autosomal dominant disorder that affects only- Z5 G1 [$ |2 U( B- y) _- z
males; therefore, other male members of the family* j& a1 f9 U0 F$ i; }( }
may have similar precocious puberty.3$ d/ e# Q, ? _" z3 R: G
In our patient, physical examination was incon-. m3 z/ V2 D2 S9 Y9 L
sistent with true precocious puberty since his testi-: ^7 z+ q- e: N/ `% u$ W
cles were prepubertal in size. However, testotoxicosis7 S" j( j8 w) m* Y3 |
was in the differential diagnosis because his father
# r8 T& Z, v- d( V1 D2 p' i. c" w5 `; _started puberty somewhat early, and occasionally,' h' A- f/ A* Y" g
testicular enlargement is not that evident in the( Q* E: N9 B+ p& g9 @, l
beginning of this process.1 In the absence of a neg-( l# E* @+ _2 `% G) g
ative initial history of androgen exposure, our/ @5 @/ C1 g+ S5 n4 l3 |5 G/ T. v9 ?
biggest concern was virilizing adrenal hyperplasia,
/ t2 d2 b/ ?9 B9 ^either 21-hydroxylase deficiency or 11-β hydroxylase
5 }1 P. l" V: o4 B4 cdeficiency. Those diagnoses were excluded by find-
2 v5 R+ r& `* g7 ~ing the normal level of adrenal steroids.7 p' [; I3 r) l: V$ h9 n
The diagnosis of exogenous androgens was strongly- U2 r/ G# }* S0 J2 D
suspected in a follow-up visit after 4 months because, C) K1 V/ f( _% P( F7 ?
the physical examination revealed the complete disap-2 n/ B8 p) v$ g0 X3 u
pearance of pubic hair, normal growth velocity, and# Y g) }6 R, P5 y( a
decreased erections. The father admitted using a testos-
6 H5 x# _/ U& Q0 T) h o& Lterone gel, which he concealed at first visit. He was2 u0 U" p! D5 ~3 L
using it rather frequently, twice a day. The Physicians’1 l# f- _: G+ p3 e" g* V" M
Desk Reference, or package insert of this product, gel or* |' j5 D; v! q) l. d' g
cream, cautions about dermal testosterone transfer to3 u- N" q T' H/ H0 q% k
unprotected females through direct skin exposure.; E" {- J1 s$ J B7 q
Serum testosterone level was found to be 2 times the z$ s! L0 E$ k. X
baseline value in those females who were exposed to) e, f* q2 B5 Z/ h
even 15 minutes of direct skin contact with their male3 V$ I* f; \1 I6 U0 m
partners.6 However, when a shirt covered the applica-' I2 v! r, V5 J, b" J: E
tion site, this testosterone transfer was prevented.
6 l* x4 O" w/ d7 nOur patient’s testosterone level was 60 ng/mL,
; l. {6 C" G/ b' s, Twhich was clearly high. Some studies suggest that
0 F2 _7 J& ?6 t$ |dermal conversion of testosterone to dihydrotestos-% R$ l7 z: x3 o R( D, L
terone, which is a more potent metabolite, is more3 ?$ w$ o) N! k" t; I* y4 O
active in young children exposed to testosterone- O+ u% |( X. K3 |; a
exogenously7; however, we did not measure a dihy-% g3 F) I1 J4 e" F/ n
drotestosterone level in our patient. In addition to
1 m7 `6 X |# w8 Tvirilization, exposure to exogenous testosterone in: `- ?* K0 x7 F8 s4 ?
children results in an increase in growth velocity and
6 b' U8 a+ ?* R8 L0 @* V3 g6 Qadvanced bone age, as seen in our patient.# t- |( g8 A1 y0 {: z
The long-term effect of androgen exposure during) |& ?' f. C. ~4 B# h: B
early childhood on pubertal development and final: {3 K: ~6 ?7 `& W
adult height are not fully known and always remain
- Z `* `& y4 G3 Ea concern. Children treated with short-term testos-& F& Z/ ^( I h1 J0 i
terone injection or topical androgen may exhibit some
, C, ?9 n7 Q. a. Qacceleration of the skeletal maturation; however, after* \, y, p( {" t( O
cessation of treatment, the rate of bone maturation
: g; v. h& `# D! j v8 ndecelerates and gradually returns to normal.8,90 V+ b& ] ?1 Q( k1 Y3 s
There are conflicting reports and controversy- R0 p# y$ g1 s$ n% N- u
over the effect of early androgen exposure on adult' n+ s1 t( _2 z( i- o7 ?
penile length.10,11 Some reports suggest subnormal
! O# O9 F! {. b$ Hadult penile length, apparently because of downreg-
. I/ d8 _9 K# H& D( aulation of androgen receptor number.10,12 However,
, B: I! b m: t& M3 ^6 b8 Y" fSutherland et al13 did not find a correlation between0 ]6 W5 d8 w( [/ f* U* Z2 j% d0 @' K
childhood testosterone exposure and reduced adult9 f8 O8 j3 x( w8 ^. c7 p2 ^3 g2 [
penile length in clinical studies.; a1 \( k7 v0 R% P2 \( u! `4 Y
Nonetheless, we do not believe our patient is
( P6 I0 M+ V7 f: }9 p( ^$ Lgoing to experience any of the untoward effects from
1 u) D3 S7 P) L( T' F Ptestosterone exposure as mentioned earlier because
, \! @9 w* D! g9 j! |4 x% M+ k5 mthe exposure was not for a prolonged period of time.
: J9 I& V0 O5 g/ u) pAlthough the bone age was advanced at the time of' `6 ] E3 Q( I3 ~4 r/ ]% I8 k
diagnosis, the child had a normal growth velocity at
6 ^4 h8 _7 l3 B5 R# V- j, dthe follow-up visit. It is hoped that his final adult
7 `* y2 q# e* v+ sheight will not be affected.
# m* x$ ?, ?8 ^3 o N9 _8 CAlthough rarely reported, the widespread avail-
; [9 ~0 w" Y( l$ nability of androgen products in our society may
7 ?8 b8 }& R9 R8 W. r. z: D Cindeed cause more virilization in male or female ^+ x c0 [. o& \! O
children than one would realize. Exposure to andro-
: `0 ]/ i! i; b) x3 u6 s2 ogen products must be considered and specific ques-
& r: Q$ \/ {; R2 ctioning about the use of a testosterone product or# ]3 i, _, c. F+ |
gel should be asked of the family members during: I; i$ W8 R; g6 O
the evaluation of any children who present with vir-4 O3 z% t6 c. ]+ ^9 \
ilization or peripheral precocious puberty. The diag-
0 d" |5 Q& ^2 P( D! t0 Onosis can be established by just a few tests and by6 r) H% b% V0 ~
appropriate history. The inability to obtain such a5 T4 ~' c$ a/ | Z, ] l% S' H7 }
history, or failure to ask the specific questions, may2 F2 W' A9 D0 u4 ?" F; u- S! U6 V
result in extensive, unnecessary, and expensive$ O8 H5 O0 X& F
investigation. The primary care physician should be
* A, C/ W5 W/ n `aware of this fact, because most of these children
+ C- H0 \7 Y+ Nmay initially present in their practice. The Physicians’3 m9 {( z, b) e9 G4 J# W& n
Desk Reference and package insert should also put a) [8 q' h- O6 p" ]( w# z2 ]
warning about the virilizing effect on a male or. n9 p, ]( p; {8 d2 }7 a/ ~. A2 D
female child who might come in contact with some-9 ]3 C1 `% E6 `' D, ]
one using any of these products.
0 g) l O1 T: |References! N/ ]5 O1 ]2 a" {
1. Styne DM. The testes: disorder of sexual differentiation
/ E# z9 q; U w" p+ |" Land puberty in the male. In: Sperling MA, ed. Pediatric
2 k/ \+ X4 L( K3 |+ BEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;# A5 M$ |: s0 T
2002: 565-628.3 j7 w3 W( G0 n' P3 q: d1 k
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious/ ]0 A3 O9 Q7 y7 k9 l R
puberty in children with tumours of the suprasellar pineal |
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