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Sexual Precocity in a 16-Month-Old6 k/ d2 z" ?' ~! I6 L( t4 {
Boy Induced by Indirect Topical
8 U) ^$ x6 C( v! L. m' b6 F& JExposure to Testosterone
# ^/ t* X Q+ x" o! ISamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
* U( O( `$ _% W: d# Qand Kenneth R. Rettig, MD1+ x ?' M" Y( q4 z1 F" h
Clinical Pediatrics
! _+ Q/ W$ C( b6 q: o1 A+ TVolume 46 Number 6: ^5 \3 \9 b0 }
July 2007 540-543* Z% _" ]5 _8 P4 U3 s/ a
© 2007 Sage Publications4 g. U7 d% Y; s9 M
10.1177/0009922806296651
U" @: A* i4 x$ ^7 o& zhttp://clp.sagepub.com
( ]; O, K$ c9 ]1 B0 f Z( K- Vhosted at! Q. D, T) p) P" Y7 _: c6 @
http://online.sagepub.com2 ^7 K1 ?. W* i: ?
Precocious puberty in boys, central or peripheral,! N0 e" n6 y9 G& s
is a significant concern for physicians. Central- r# ~+ L: w# k! b
precocious puberty (CPP), which is mediated% F7 ]( f- @+ t; Z6 q
through the hypothalamic pituitary gonadal axis, has
! i4 Z% `/ S' W9 B- Pa higher incidence of organic central nervous system
/ P; K$ J2 \* llesions in boys.1,2 Virilization in boys, as manifested6 Q( |# C( n% Z# ~/ U
by enlargement of the penis, development of pubic
, D% K' q( ^. K& v3 Lhair, and facial acne without enlargement of testi-3 ^9 K4 V" O& t
cles, suggests peripheral or pseudopuberty.1-3 We
& ]+ _, B2 q3 R! p8 @: k) P8 Sreport a 16-month-old boy who presented with the
6 n# E3 O, M* Xenlargement of the phallus and pubic hair develop-7 `/ P/ X, m4 m W8 }' @) O- a
ment without testicular enlargement, which was due
1 ^1 f& c. Q% o& yto the unintentional exposure to androgen gel used by9 I) D+ _ M1 A2 {. ~
the father. The family initially concealed this infor-- Q( t5 ~0 I/ M4 U$ _. C% x9 s* m3 [
mation, resulting in an extensive work-up for this
" M' i8 p0 Q8 f6 e' [child. Given the widespread and easy availability of* X* O: k; Q- N" w8 n0 p" b; V/ m
testosterone gel and cream, we believe this is proba- f5 p5 g* G7 w3 x5 h( t
bly more common than the rare case report in the! E" ^4 w9 b% @) ?8 c
literature.4
' f ?3 |% V7 @0 L) q* Z( p) mPatient Report
* t3 t9 ?6 d+ ~3 ^. v# H6 B' _A 16-month-old white child was referred to the* J2 n- R5 c) o7 ~3 e
endocrine clinic by his pediatrician with the concern
s& ]; ^2 T. A, h; d: b* fof early sexual development. His mother noticed
/ j$ c" _. `' ylight colored pubic hair development when he was1 l+ s) e2 ]4 ?- j! Q" |6 h8 k0 p
From the 1Division of Pediatric Endocrinology, 2University of
: D& @ e( L: V) Y5 d1 `0 \, ISouth Alabama Medical Center, Mobile, Alabama.1 z$ W& A7 l2 u" O' W
Address correspondence to: Samar K. Bhowmick, MD, FACE,$ P* l6 Y+ |% E5 ^) F! D) w
Professor of Pediatrics, University of South Alabama, College of
# f% [9 L9 {- U i) v$ T3 W8 V2 ZMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;" t1 Z$ T2 M- G" ^# N- E
e-mail: [email protected].
9 H( ~0 ~ X% ?% V- _ u1 ^. xabout 6 to 7 months old, which progressively became
' r+ p; ?( R- m* W5 |darker. She was also concerned about the enlarge-
( K T5 d7 _! x# F* S! m, \# oment of his penis and frequent erections. The child" e' p" B# z3 `3 n
was the product of a full-term normal delivery, with
7 [! [6 ?4 d, u( I. da birth weight of 7 lb 14 oz, and birth length of
; y% E! m$ W2 w' ?4 j2 ]6 @20 inches. He was breast-fed throughout the first year
8 ]. T( t, v gof life and was still receiving breast milk along with
R/ d% n" E# R7 ^solid food. He had no hospitalizations or surgery,; u- m* f2 A; ~2 v' h
and his psychosocial and psychomotor development
0 ~, I7 R! S2 Swas age appropriate.
' `7 M: C; f5 T+ i. ^The family history was remarkable for the father,
0 e/ F7 R& L9 B& q( c; G- Jwho was diagnosed with hypothyroidism at age 16,
6 s" V W3 X; O p( P5 V/ S8 jwhich was treated with thyroxine. The father’s
d2 E9 n. N1 `1 Rheight was 6 feet, and he went through a somewhat
. U1 Q- I& L6 t5 s2 _# e) Oearly puberty and had stopped growing by age 14.
8 d9 u) F H" t$ i$ h1 h9 R( jThe father denied taking any other medication. The! C" \8 b* w. D- |' S
child’s mother was in good health. Her menarche
# u- P r. o4 y$ qwas at 11 years of age, and her height was at 5 feet
0 q0 r6 c/ Z7 T/ O5 inches. There was no other family history of pre-
! J% A5 e/ U% Z. @$ P, S9 _cocious sexual development in the first-degree rela-
) I; u0 U. w6 e1 T% i- Q' Ltives. There were no siblings.
* _: {% a. d& W& N" n6 y% cPhysical Examination
1 a! q( b8 E8 V& ~* R$ OThe physical examination revealed a very active,
( [; U( H7 b! w& L$ \playful, and healthy boy. The vital signs documented
9 F" I+ J- n0 a7 Ca blood pressure of 85/50 mm Hg, his length was% C+ y6 h5 d" S @/ D4 `
90 cm (>97th percentile), and his weight was 14.4 kg
( K: p8 [6 D; |% v(also >97th percentile). The observed yearly growth" ~* S6 Y: O# {/ F7 A) f: l
velocity was 30 cm (12 inches). The examination of; ?0 ^- ^ u* P
the neck revealed no thyroid enlargement., E- n4 d4 z! w* g
The genitourinary examination was remarkable for- W! \6 l# {& i R6 Z
enlargement of the penis, with a stretched length of
% z3 X( b1 N+ o/ W! g8 cm and a width of 2 cm. The glans penis was very well
: x$ n- m( f% U. G1 \2 M9 C2 Vdeveloped. The pubic hair was Tanner II, mostly around$ ^; W- @6 x9 L9 _0 N/ C
540+ }- p& Z l3 l; n) R' H9 B
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from9 r! S1 Y, J! K. Y
the base of the phallus and was dark and curled. The, R6 v# M( F- e. l# B
testicular volume was prepubertal at 2 mL each.
1 G2 E. j: A6 B" M* j/ E! {The skin was moist and smooth and somewhat- L7 K, S6 |; C& R' ~
oily. No axillary hair was noted. There were no3 W8 B" r& [/ B# {6 b! M1 O& X
abnormal skin pigmentations or café-au-lait spots.4 V \$ B8 Y X7 v& r/ a
Neurologic evaluation showed deep tendon reflex 2+
5 t: s% N7 ], e/ }: w( E) ?bilateral and symmetrical. There was no suggestion
6 J) H& t2 X7 R7 h1 Nof papilledema.
4 \' A$ h6 T5 J2 b1 I4 NLaboratory Evaluation6 |' P% s" L- T. i5 J: c) S
The bone age was consistent with 28 months by
2 ]' k. }1 v0 {; A6 F: Iusing the standard of Greulich and Pyle at a chrono-3 j7 u8 W% F: x( s
logic age of 16 months (advanced).5 Chromosomal8 P% `. |" `) `- M# {
karyotype was 46XY. The thyroid function test
- K( W: Q! r/ p: mshowed a free T4 of 1.69 ng/dL, and thyroid stimu-8 C$ h/ W& R8 c8 x' b6 A
lating hormone level was 1.3 µIU/mL (both normal).
9 @! r! o" a b1 o2 xThe concentrations of serum electrolytes, blood8 e2 V# O$ V4 a* f1 W/ S
urea nitrogen, creatinine, and calcium all were' }! T% P0 y; K4 q& _
within normal range for his age. The concentration# H2 `5 z5 s1 e: j' ]! C$ h3 C
of serum 17-hydroxyprogesterone was 16 ng/dL
. k' J' t8 O: T3 t* {- {(normal, 3 to 90 ng/dL), androstenedione was 207 }; H% Y. i; e6 Y
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
3 Y" m8 f& M/ h- dterone was 38 ng/dL (normal, 50 to 760 ng/dL),+ @0 y: ?6 b7 ? K
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
% m7 u i& W6 I x49ng/dL), 11-desoxycortisol (specific compound S)
5 K4 z: x/ f( F3 Kwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-2 y5 _( H2 m# R( Y5 w2 a
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total9 v. U" { S; \. J; a
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),% y& n4 e$ M" i: I) p/ o
and β-human chorionic gonadotropin was less than; K, r1 T7 N0 e
5 mIU/mL (normal <5 mIU/mL). Serum follicular+ }+ @" O, G7 \: B1 y. N9 N- ~
stimulating hormone and leuteinizing hormone- N' B5 ]' k. R4 t! z+ K
concentrations were less than 0.05 mIU/mL
) \7 s' _9 j. ?(prepubertal).
/ g. X" h3 V+ l7 \, z) KThe parents were notified about the laboratory, T! w6 Z% U, ^3 u7 ^/ E8 U% X4 F
results and were informed that all of the tests were3 U7 _3 `5 j: ^" Y- u% T
normal except the testosterone level was high. The# n7 W4 J+ r/ z/ s# x% M" s
follow-up visit was arranged within a few weeks to
- y$ a2 {* b" c. F% }obtain testicular and abdominal sonograms; how-
( Y2 b# b1 B, m2 Lever, the family did not return for 4 months.- D( |/ S% Y+ A1 O4 C, c
Physical examination at this time revealed that the
, M! x6 a2 t! [child had grown 2.5 cm in 4 months and had gained
9 O2 p3 {7 B# X) p) k3 K3 }2 kg of weight. Physical examination remained+ e% s% M3 J" s( {7 s1 O1 z' Y
unchanged. Surprisingly, the pubic hair almost com-6 h& N6 J+ n( C! f
pletely disappeared except for a few vellous hairs at4 y4 A: N2 G! Z
the base of the phallus. Testicular volume was still 2
6 ~, x, P( Z- W ?1 \! \/ PmL, and the size of the penis remained unchanged.8 B% l5 f& l+ P- m4 B
The mother also said that the boy was no longer hav-0 E* u. Z$ H b* [
ing frequent erections.8 J& u! r! v( }6 a, I8 i3 D0 I5 I
Both parents were again questioned about use of
# s, K" ~' g/ _2 _* b9 Nany ointment/creams that they may have applied to3 ]* @! Q4 h, ^
the child’s skin. This time the father admitted the0 h5 l! |3 @/ f0 o
Topical Testosterone Exposure / Bhowmick et al 5418 h$ \' h. Y: P5 a) r5 w% m
use of testosterone gel twice daily that he was apply-
) W# ?/ i5 w% Z5 k1 r/ ring over his own shoulders, chest, and back area for
) F/ A8 E! G% e, q" Pa year. The father also revealed he was embarrassed
9 m" {' P5 I8 ?+ N, Q7 Fto disclose that he was using a testosterone gel pre-
9 [' s0 Y9 X0 @$ B$ [, y# Bscribed by his family physician for decreased libido, I0 X) F* D+ o& L
secondary to depression.. w7 y/ u/ }3 S! q( W; i
The child slept in the same bed with parents.& M; u7 n4 \ c- x6 E* W
The father would hug the baby and hold him on his
/ h; u/ f: P6 }7 ^4 S& F% ochest for a considerable period of time, causing sig-
w5 q1 n. ?0 w5 knificant bare skin contact between baby and father.
: E/ P& j* `' N/ u7 N& y; s% S1 wThe father also admitted that after the phone call,! }7 f7 t9 a+ S) f2 w6 t6 q5 X
when he learned the testosterone level in the baby, H9 o- `" V% c+ V9 z% r
was high, he then read the product information- k' i, ~; ^* p9 o) @& c9 q
packet and concluded that it was most likely the rea-- p0 w, ?' i' Q7 n# c' H! K* f4 Y
son for the child’s virilization. At that time, they
9 l% S$ Y! s5 L9 `6 Gdecided to put the baby in a separate bed, and the
$ B6 @. d, l3 [7 G4 U' Q: Q" ~, w6 V# Nfather was not hugging him with bare skin and had. q% U! r2 s9 @- H. }. p( o
been using protective clothing. A repeat testosterone% [, V* H. H' {0 {- j$ F6 v
test was ordered, but the family did not go to the' E1 m" i1 O( m2 f" a0 O! j9 J+ ?
laboratory to obtain the test.. J4 o. f. Q1 C! V0 |& j/ J- q" Y/ M
Discussion) M+ ?4 N3 X- H, G- f* B8 m
Precocious puberty in boys is defined as secondary
+ E8 h' ?( r% L0 C5 Dsexual development before 9 years of age.1,4
+ w7 [4 j( e. T4 w3 j% G2 WPrecocious puberty is termed as central (true) when$ W: C" Q/ ^: D0 x
it is caused by the premature activation of hypo-
- r0 B8 H* ^3 ]/ f! e/ s* Uthalamic pituitary gonadal axis. CPP is more com-1 v9 t' Z0 B( r+ m$ M
mon in girls than in boys.1,3 Most boys with CPP$ I9 [# I! Z- C+ d4 v
may have a central nervous system lesion that is, _* B6 F- U' M$ s4 u3 f& A2 C
responsible for the early activation of the hypothal-/ Y6 y( N6 p7 a% Z1 r
amic pituitary gonadal axis.1-3 Thus, greater empha-7 S' \6 r) T/ _" J1 U4 G L2 D z
sis has been given to neuroradiologic imaging in
: u$ {8 m( }" p: R5 A. Jboys with precocious puberty. In addition to viril-1 ~$ e; o2 ]( ^$ H( b, Q
ization, the clinical hallmark of CPP is the symmet-$ n) ~" e, K) P
rical testicular growth secondary to stimulation by
; ~) X. a3 I0 j' i1 C: N2 Tgonadotropins.1,37 n8 J* s E; k) t+ i
Gonadotropin-independent peripheral preco-0 \* i6 d' {( N( l
cious puberty in boys also results from inappropriate- r/ S# a* U5 k- A: _
androgenic stimulation from either endogenous or
0 u3 N0 [7 p+ W: _' _' Y& u0 zexogenous sources, nonpituitary gonadotropin stim-$ @ l4 T9 f6 T# M9 s1 v T
ulation, and rare activating mutations.3 Virilizing
' W' O$ q# Z% D) ^% t& I: U0 ccongenital adrenal hyperplasia producing excessive2 d& F. n9 H0 E, E: k( u) a6 M
adrenal androgens is a common cause of precocious2 l _" E/ x/ } S( b# i3 w
puberty in boys.3,4. h! s/ o4 I e" Z$ u
The most common form of congenital adrenal
1 G7 O% h7 Y* W) ^9 A0 B6 s# Xhyperplasia is the 21-hydroxylase enzyme deficiency.9 R, v$ k1 q7 n. k& |6 p) ?* I6 w
The 11-β hydroxylase deficiency may also result in! A( _+ [2 O9 h' l' s: x1 x
excessive adrenal androgen production, and rarely,
$ U, P1 x! h( _3 X8 san adrenal tumor may also cause adrenal androgen
$ T7 C% w6 p& i* t' W8 v" gexcess.1,3
1 N' x& ?/ w, v! o+ a) bat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from0 H( Z1 h1 ?5 D3 b2 b% |3 n
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
4 o5 B* o- K% U$ mA unique entity of male-limited gonadotropin-
! S- D& L/ x$ H/ sindependent precocious puberty, which is also known: n% Z8 e+ E2 S. [7 G9 s5 l
as testotoxicosis, may cause precocious puberty at a, q3 v' c" ~+ [) U% v/ M
very young age. The physical findings in these boys
1 N) U! Z/ F, Twith this disorder are full pubertal development,% z1 b N8 U& W% j& V# I/ [" L- x
including bilateral testicular growth, similar to boys
% H* n6 F$ L( o! Q+ y$ K6 {with CPP. The gonadotropin levels in this disorder
# ?3 w3 ^/ R: S9 o- gare suppressed to prepubertal levels and do not show
9 \- U5 j2 C8 W( T- E4 W3 X$ rpubertal response of gonadotropin after gonadotropin-
1 W% B$ M" Y- V' R! n* j7 v" Oreleasing hormone stimulation. This is a sex-linked
2 j9 \7 s+ Y9 ]2 }autosomal dominant disorder that affects only
0 \, T3 y9 y+ _7 S& w( b5 s/ Pmales; therefore, other male members of the family4 P" [& Q, P& x$ T
may have similar precocious puberty.3
. E, Z1 O- G6 F& R8 Q6 l3 [ X4 oIn our patient, physical examination was incon-
) j' Q" w% w; i. \; {! x. Z) q1 j gsistent with true precocious puberty since his testi-
- T) p$ z. B6 L) Bcles were prepubertal in size. However, testotoxicosis
' F5 G6 Z% `7 Xwas in the differential diagnosis because his father6 w! Y, r) O$ c; I( H1 \( A4 T" S
started puberty somewhat early, and occasionally,4 z$ `/ v5 C" f; v' J" q
testicular enlargement is not that evident in the
$ ?* |# p1 N, J% g$ `# abeginning of this process.1 In the absence of a neg-
6 t; B+ G( C# o; b5 Zative initial history of androgen exposure, our
; x& _. V8 x2 N; N. }biggest concern was virilizing adrenal hyperplasia,
" ?! ]2 E) S' z! ?. J( S( M* seither 21-hydroxylase deficiency or 11-β hydroxylase
" O& [9 N) ^ }9 wdeficiency. Those diagnoses were excluded by find-
, a: [- p; V8 Oing the normal level of adrenal steroids./ ]* n) z% \6 L) y
The diagnosis of exogenous androgens was strongly
1 v) R! ^) n3 _1 p0 Z5 v* Isuspected in a follow-up visit after 4 months because
% a' ?+ b* M, z% H0 n0 y$ nthe physical examination revealed the complete disap-! W0 I! R r, z) C; j4 u% ^8 z- U% a
pearance of pubic hair, normal growth velocity, and: b, b$ c' n- @7 s, P0 m6 R
decreased erections. The father admitted using a testos-
. U8 S$ Y' f) hterone gel, which he concealed at first visit. He was
, i3 c y/ h* M3 l4 }using it rather frequently, twice a day. The Physicians’
' ?# L0 k# F5 u! _! \* F: YDesk Reference, or package insert of this product, gel or4 U. E0 y! U/ c0 d, V
cream, cautions about dermal testosterone transfer to1 P) C) ]& _5 \: H
unprotected females through direct skin exposure.3 B0 I3 m. U% ^# }/ K. E U6 X$ M
Serum testosterone level was found to be 2 times the, W) v; K! F- t' e: L
baseline value in those females who were exposed to
, @' L$ y# J# z* x; Y. Yeven 15 minutes of direct skin contact with their male
5 v3 i9 {* _, _& `7 u6 upartners.6 However, when a shirt covered the applica-
8 T9 F' g' H, k# @ F5 S* y gtion site, this testosterone transfer was prevented.
* ` Z4 r& E3 P, cOur patient’s testosterone level was 60 ng/mL,
8 _; h& A+ Q! K% Q- ~ @which was clearly high. Some studies suggest that
! \$ F4 j7 E2 y% G3 Rdermal conversion of testosterone to dihydrotestos-
- I* g! X# [% }( A3 L* f( |# ^terone, which is a more potent metabolite, is more
9 c# V' o8 D; |" Vactive in young children exposed to testosterone) Y$ B, w) t W' o* N3 l
exogenously7; however, we did not measure a dihy-: x* P) H& w( T# U
drotestosterone level in our patient. In addition to
& D7 `" t& Q9 U6 ~. o/ fvirilization, exposure to exogenous testosterone in5 N* r) v* k1 D3 d
children results in an increase in growth velocity and) \4 W2 |; D4 n; B. P) b. ]
advanced bone age, as seen in our patient.! |/ _3 M& I$ @& {' s5 Y9 u
The long-term effect of androgen exposure during) Q: _% M" T& Q2 }* ]6 {2 s! k
early childhood on pubertal development and final) e$ J: u3 W+ k* _% h7 {8 ]) D
adult height are not fully known and always remain7 u- E- j; e* F6 H8 _! g
a concern. Children treated with short-term testos-
4 \: {) `$ x7 _2 I6 v4 Bterone injection or topical androgen may exhibit some: q5 C2 p3 H1 g/ _* B
acceleration of the skeletal maturation; however, after
7 \/ C2 Q c8 {) ^6 ^% Q0 |cessation of treatment, the rate of bone maturation$ r; d6 s, }, {7 Z/ @
decelerates and gradually returns to normal.8,9
( [! ~! h- F5 {( \$ l. NThere are conflicting reports and controversy, Z' e# S9 A# p3 j3 n- t
over the effect of early androgen exposure on adult
' C# U8 F. o; L8 tpenile length.10,11 Some reports suggest subnormal
$ Q/ M, @' B fadult penile length, apparently because of downreg-
% ~+ n& Q& [, [. s7 e& `* x6 lulation of androgen receptor number.10,12 However,
( l0 f f {3 kSutherland et al13 did not find a correlation between
1 N; ?( x3 F5 s& ^& j4 d! H' ochildhood testosterone exposure and reduced adult
% o# h. ~6 Y; P5 R1 t3 |penile length in clinical studies.
9 o5 ^( H; B [3 ~ K* U4 XNonetheless, we do not believe our patient is
! @7 f6 G \: f1 n/ `( s+ n8 Fgoing to experience any of the untoward effects from
2 v9 `1 B0 r- E x; Jtestosterone exposure as mentioned earlier because
6 M, q# I. d" z8 ]. M$ \0 x5 jthe exposure was not for a prolonged period of time.
- H" j6 s$ w) K: M" z/ a4 {Although the bone age was advanced at the time of* y6 ?" l8 v1 w5 V! Q; v" ?5 K
diagnosis, the child had a normal growth velocity at M6 X( M* g7 i) }/ z( _) P8 A
the follow-up visit. It is hoped that his final adult
/ M* p3 J' s5 r. H6 {- S. cheight will not be affected.
4 Q o1 ?/ U, M, F, VAlthough rarely reported, the widespread avail-3 P6 k! R$ V& S+ [! j* F3 S" V
ability of androgen products in our society may" i3 y' D T( q4 f
indeed cause more virilization in male or female
& Q5 D+ l% D8 n' q) J+ r9 hchildren than one would realize. Exposure to andro-0 K% @ E2 l% ^) u) ?2 u2 Z0 c
gen products must be considered and specific ques-
0 _ s' x5 J6 Etioning about the use of a testosterone product or
/ W* C/ O3 {+ Ygel should be asked of the family members during
0 G0 }- z4 h; C. E. Kthe evaluation of any children who present with vir-3 b' P# R& u7 R" L$ X: z) e. G6 P; t2 p
ilization or peripheral precocious puberty. The diag-
. O8 |1 O2 B" R5 R$ vnosis can be established by just a few tests and by% ? i; t M A* `; p
appropriate history. The inability to obtain such a
: M& V- y7 Z3 i) [ N2 ghistory, or failure to ask the specific questions, may7 d+ u# N3 ~7 T0 t
result in extensive, unnecessary, and expensive5 w7 K5 U& K. y+ T
investigation. The primary care physician should be
( ?/ `: {' d! Yaware of this fact, because most of these children
- i; O g* x6 C7 o+ O& gmay initially present in their practice. The Physicians’
3 a( B# L/ _* }Desk Reference and package insert should also put a
3 x2 X9 s7 c; p7 E% u' m4 N, _. b Qwarning about the virilizing effect on a male or0 [+ I& N; l# X- i6 l% }
female child who might come in contact with some-
! M5 Z5 G9 [2 T, Eone using any of these products.
6 Y* t9 ~& D& d3 S9 T+ S1 b- HReferences3 F: i7 j! t) d2 {/ m/ A
1. Styne DM. The testes: disorder of sexual differentiation
5 N! a+ P- k6 j+ E9 vand puberty in the male. In: Sperling MA, ed. Pediatric, }, R) `3 _5 ]) y
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;' N, [8 G1 k# ?" I, z; f- o+ M
2002: 565-628.; s4 R9 e+ q2 i- h/ m
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
, R2 T( t% `+ tpuberty in children with tumours of the suprasellar pineal |
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