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Sexual Precocity in a 16-Month-Old
, `' S# r+ x2 U/ N% A" `: k# z2 N! ~Boy Induced by Indirect Topical
( p" X& T5 |% g" `/ JExposure to Testosterone
' h" K% P9 q6 h4 I. m P& bSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,26 Y$ x9 d# i1 Z
and Kenneth R. Rettig, MD1
9 w# m( i8 E1 q% pClinical Pediatrics: z/ @' M7 e" D( I5 |! F" v' ~+ ~
Volume 46 Number 6
* y9 u0 E! u A7 f/ V, Q9 }July 2007 540-543
6 w3 V3 v6 {' V" T) `) e© 2007 Sage Publications
1 T" w" ?( }( u* `4 Y/ z" M2 J10.1177/0009922806296651
: @' F6 x4 _: b8 khttp://clp.sagepub.com
5 y0 o+ r m! ?6 B# Lhosted at$ j+ d- M) C6 j6 m0 E s, ~9 m
http://online.sagepub.com! I% u8 A3 Q# k( c. `
Precocious puberty in boys, central or peripheral,) G7 k! U. ?' z' P6 N
is a significant concern for physicians. Central
0 D, T/ @8 ^! q" I, Rprecocious puberty (CPP), which is mediated' x- Y) ~3 f4 @
through the hypothalamic pituitary gonadal axis, has) J( j5 p- _4 ~3 w; B0 F( p: Y
a higher incidence of organic central nervous system* |. }; {' O1 Q
lesions in boys.1,2 Virilization in boys, as manifested* @) u3 i$ A- H. \; k$ ~ D: u# Z
by enlargement of the penis, development of pubic
/ w! t' _; x- f8 A2 phair, and facial acne without enlargement of testi-
$ p$ B$ ~1 `) |, @+ Q& Wcles, suggests peripheral or pseudopuberty.1-3 We I# u9 D3 ]3 A9 D" a
report a 16-month-old boy who presented with the
6 {* o: o e* }enlargement of the phallus and pubic hair develop-* s/ ?6 j. k( \. A1 n' Z
ment without testicular enlargement, which was due+ w# z( z |" m
to the unintentional exposure to androgen gel used by
9 b- i. R3 Q, n- l5 ~the father. The family initially concealed this infor-
" q. M3 h @0 P; V `% g( E1 O9 jmation, resulting in an extensive work-up for this8 |8 [( Z" r' B8 u
child. Given the widespread and easy availability of
1 u( C: h1 {( x* X% ^testosterone gel and cream, we believe this is proba- ~, k% [5 l& `0 M$ k4 t+ h6 j
bly more common than the rare case report in the
5 ^+ p0 W& ]* d- Z+ S3 ]' jliterature.4% [9 e* L& s, w1 \% T+ O
Patient Report6 s9 z$ ~3 s; {6 B+ H# I
A 16-month-old white child was referred to the
' D" J: {1 r. a. rendocrine clinic by his pediatrician with the concern
) w, Y J$ B2 {" y( pof early sexual development. His mother noticed7 D- _. s5 R1 ~. F+ H
light colored pubic hair development when he was Q7 \: w6 P& t4 D+ Y( P. K; w
From the 1Division of Pediatric Endocrinology, 2University of
0 p- l8 q1 ]' ^, K% YSouth Alabama Medical Center, Mobile, Alabama.
$ u: f/ L$ n {5 ~' c" R+ w4 sAddress correspondence to: Samar K. Bhowmick, MD, FACE,
. q6 T! f' X6 S9 oProfessor of Pediatrics, University of South Alabama, College of
5 r9 C0 J% K% Q3 |# Z7 I. R; sMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
Z# Z! i- s @8 w: e) s) Re-mail: [email protected].' n+ ^1 u4 V2 z" z) ?3 y5 N: p& |/ G
about 6 to 7 months old, which progressively became
) K/ b) p1 h/ R- Q" Odarker. She was also concerned about the enlarge-) H0 D x+ Z* x3 e! X% F
ment of his penis and frequent erections. The child+ C& s! T' o( ?
was the product of a full-term normal delivery, with9 p8 `- N9 H: X! [
a birth weight of 7 lb 14 oz, and birth length of
# Q" H# |/ w1 R7 p+ p20 inches. He was breast-fed throughout the first year) h% \5 x. h) w
of life and was still receiving breast milk along with
* a0 G1 t, V# C* P( n6 fsolid food. He had no hospitalizations or surgery,
4 O' @% J1 g, Z1 C3 @2 Q7 Rand his psychosocial and psychomotor development2 A% C/ N3 w/ v3 J1 `
was age appropriate.
4 x4 r2 y: B# Y3 GThe family history was remarkable for the father,, P0 ?# C( P0 v/ d' }$ C
who was diagnosed with hypothyroidism at age 16,/ p2 {/ W3 n0 M2 _6 B1 p- g
which was treated with thyroxine. The father’s
3 ~" X9 H/ p. S( l& B+ u6 Wheight was 6 feet, and he went through a somewhat
9 ?. j5 V" G: B! Y% m7 U( Z$ Pearly puberty and had stopped growing by age 14.
|$ G+ W; K% [( Z( WThe father denied taking any other medication. The
1 s# m5 J0 ]1 Y7 Z2 e8 N! C8 c4 e) nchild’s mother was in good health. Her menarche
8 ^2 R x( _* W1 X% |2 e, Twas at 11 years of age, and her height was at 5 feet
/ K6 q1 H! ^8 w B4 z* b5 inches. There was no other family history of pre-2 k# c- i% ^% o" v
cocious sexual development in the first-degree rela-! g5 \* ]) q4 u0 ~& E
tives. There were no siblings.# i" @/ Y% P8 b# H
Physical Examination, K% Y5 [8 F' X$ [# I2 w
The physical examination revealed a very active,
$ ]3 J/ y! o" p& Z; Tplayful, and healthy boy. The vital signs documented! E: d8 U: p( n+ U9 A
a blood pressure of 85/50 mm Hg, his length was3 t% s/ |* N3 q! q( w2 R5 i
90 cm (>97th percentile), and his weight was 14.4 kg
' ^( x, [9 I1 d, i# ^(also >97th percentile). The observed yearly growth
: @5 G) \6 Z! G% ?velocity was 30 cm (12 inches). The examination of
6 s" ^3 Z) x) q9 F3 N3 hthe neck revealed no thyroid enlargement.
4 j' h# s" L7 ~8 f. CThe genitourinary examination was remarkable for9 W" P0 N+ l, L/ c6 O
enlargement of the penis, with a stretched length of n! S* N3 e D# p" A, l
8 cm and a width of 2 cm. The glans penis was very well
, ~$ k8 S8 p. s( f8 ]! rdeveloped. The pubic hair was Tanner II, mostly around
) r3 e. _- U$ X' ^9 x: k9 Q! Q5403 {+ B) f5 F @% f2 o/ w* v
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
# L2 c R8 z) ]- b1 s7 d$ U8 zthe base of the phallus and was dark and curled. The9 N' [. M0 c/ K7 ]* `/ ^; E
testicular volume was prepubertal at 2 mL each.
& u1 U, Z0 o9 R9 _" g/ F& JThe skin was moist and smooth and somewhat
, B0 s! q, ^) y6 [: P0 d: ~- _oily. No axillary hair was noted. There were no4 H8 t; K: `) o0 M( I% B2 ]2 {
abnormal skin pigmentations or café-au-lait spots.
/ q8 u2 e9 y2 @/ cNeurologic evaluation showed deep tendon reflex 2+
. J! G3 n j; _" |4 b2 y2 z) r/ Bbilateral and symmetrical. There was no suggestion; ?4 j& l7 k/ F' N( v" n' ^
of papilledema.' D. g* L. W0 N/ r
Laboratory Evaluation' S& n6 x3 a# O, v, f
The bone age was consistent with 28 months by4 ~8 w' H) K' Y# l- S
using the standard of Greulich and Pyle at a chrono-, |5 S3 x2 S$ F8 E' |$ K7 |
logic age of 16 months (advanced).5 Chromosomal- H5 [1 f* j7 u3 @" k* B D
karyotype was 46XY. The thyroid function test
0 e. j! \8 p& k2 dshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
; a i- Q& ]; y0 c# ylating hormone level was 1.3 µIU/mL (both normal).
" a7 _8 U& i$ g5 WThe concentrations of serum electrolytes, blood! s P! i* D3 G* a8 n( C: i; R6 N
urea nitrogen, creatinine, and calcium all were
( C7 X. e7 i( J! m6 L Ywithin normal range for his age. The concentration
. f7 ?% O9 T8 \2 Tof serum 17-hydroxyprogesterone was 16 ng/dL- E- E3 } o+ ]' ], ]( ]
(normal, 3 to 90 ng/dL), androstenedione was 20
% K$ O2 r) `* G2 G# `- Yng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-4 O- ^& N( s- H8 @ K, f) x4 R* @
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
7 p- o0 N* D4 T" l. X, qdesoxycorticosterone was 4.3 ng/dL (normal, 7 to
S% v# W6 e t+ L" H49ng/dL), 11-desoxycortisol (specific compound S)
- q6 y! Q. _8 [, Z! W9 gwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-# H. |! Z/ b1 w% Z- n3 e
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total1 ?. t6 ]) ?$ W$ {
testosterone was 60 ng/dL (normal <3 to 10 ng/dL)," f& }; [! ^) `: l- f L
and β-human chorionic gonadotropin was less than
9 ^' l3 ]& `" M6 Q5 mIU/mL (normal <5 mIU/mL). Serum follicular9 j* k( N6 i7 x5 O& r
stimulating hormone and leuteinizing hormone
p& K1 C2 c- i6 t( z! Sconcentrations were less than 0.05 mIU/mL" c/ A- ^. S1 Z2 I0 q( L3 I
(prepubertal).
5 g. w1 R, p8 h; k' J3 y1 hThe parents were notified about the laboratory1 D, N6 R0 K" k" k
results and were informed that all of the tests were! {+ M+ S3 q5 Q6 c
normal except the testosterone level was high. The. }3 b/ L5 E9 `3 I
follow-up visit was arranged within a few weeks to
- e# W) l: L' T- g, gobtain testicular and abdominal sonograms; how-
5 X* D5 k D0 w5 y- {ever, the family did not return for 4 months.
, L7 E _; X3 r' A* A9 F- ?+ |% WPhysical examination at this time revealed that the0 N1 W* Z1 M0 ^% \ V- Z" c0 f
child had grown 2.5 cm in 4 months and had gained9 n* r/ `; j' B
2 kg of weight. Physical examination remained
) r$ A _% a. e- c4 ]# w6 l5 E1 Iunchanged. Surprisingly, the pubic hair almost com-9 I+ H0 G' F4 z/ q6 K
pletely disappeared except for a few vellous hairs at
/ S: c7 F) _/ L' t$ k+ Athe base of the phallus. Testicular volume was still 2
9 Y) J7 K- }9 `6 ]# A& l6 G MmL, and the size of the penis remained unchanged.
( k* {/ L. Y* f/ IThe mother also said that the boy was no longer hav-
9 v7 j! p/ S4 H( n3 v& Qing frequent erections.0 W* H) V- b9 a1 ?- w8 i) F# f' a
Both parents were again questioned about use of, n+ W6 }$ o) Y
any ointment/creams that they may have applied to
& z' O( a) _3 D, W/ Z* s! q; e* Nthe child’s skin. This time the father admitted the& `. h% h1 p9 _2 \! M/ c! G
Topical Testosterone Exposure / Bhowmick et al 541
3 m& C2 a _ P. z& o$ kuse of testosterone gel twice daily that he was apply-
: t6 h6 M. @9 m/ z+ B: r4 Aing over his own shoulders, chest, and back area for, _$ a7 [% N0 m/ L8 n$ ?! K) z8 I
a year. The father also revealed he was embarrassed$ B) x5 ^$ Z% j5 r" e& |
to disclose that he was using a testosterone gel pre-# _$ E" J7 J# \, I2 u) S) w4 n
scribed by his family physician for decreased libido0 A9 _ b8 T) a) s% y- G0 b
secondary to depression., G, N% I. n5 s" m3 q
The child slept in the same bed with parents.
$ L0 `" j, v& k* Q9 n. _- ^* G- BThe father would hug the baby and hold him on his( f% P1 R6 @! h7 r* c( {5 q
chest for a considerable period of time, causing sig-
7 @; r3 G7 C8 o1 B- G" F% b0 vnificant bare skin contact between baby and father.0 D% C6 b( F# F0 v+ _) x
The father also admitted that after the phone call,9 R, G3 I, N G2 u3 ]- ~: c
when he learned the testosterone level in the baby
, |9 c# t3 y C9 [! mwas high, he then read the product information
; |7 e1 G; L3 S1 Cpacket and concluded that it was most likely the rea-
6 f2 {! c3 B ?3 [- E) yson for the child’s virilization. At that time, they
% f3 E. Q5 o E! W; r! cdecided to put the baby in a separate bed, and the
- j1 F. f4 K- T+ `& v0 ffather was not hugging him with bare skin and had1 a5 c; {$ @; l. v W
been using protective clothing. A repeat testosterone
. ?, x# @+ e! n; ?/ E7 B* \( Xtest was ordered, but the family did not go to the& u" H7 Z' a( s2 w4 l' e2 @9 |
laboratory to obtain the test.
6 d6 A( c( w6 i& m# W3 XDiscussion
" H+ ~! y* ?4 qPrecocious puberty in boys is defined as secondary, L1 T! X* n4 s5 Z
sexual development before 9 years of age.1,46 ?" A4 ]" X7 U% o, ]( D
Precocious puberty is termed as central (true) when
% _( }3 D! x2 u! lit is caused by the premature activation of hypo-9 X9 I" z* k, o# A* h
thalamic pituitary gonadal axis. CPP is more com-" I0 j8 U; k5 c5 I
mon in girls than in boys.1,3 Most boys with CPP# H' z' G7 a+ Z% S$ c
may have a central nervous system lesion that is
& }# O3 ]; E; m8 v: Yresponsible for the early activation of the hypothal-
" i+ `& d& I! f) h: v( A8 Famic pituitary gonadal axis.1-3 Thus, greater empha-5 J0 c1 J5 k5 O$ m2 m
sis has been given to neuroradiologic imaging in
/ `4 s0 r0 o7 q! z! ?0 Wboys with precocious puberty. In addition to viril-
" U! I7 \' w6 b* \% M5 R8 kization, the clinical hallmark of CPP is the symmet-/ W! x h" r3 O: u; ?# U
rical testicular growth secondary to stimulation by! @/ q$ w; t' k( a* G) u S% f/ x
gonadotropins.1,3
/ C0 v: c4 i0 \ Y5 y/ l( n) @2 gGonadotropin-independent peripheral preco-
9 F) l7 [8 E: c# N4 [4 |, Gcious puberty in boys also results from inappropriate
@+ I* y1 c, U! Vandrogenic stimulation from either endogenous or# ?7 h. F8 m' b9 {6 m
exogenous sources, nonpituitary gonadotropin stim-
7 B6 {. v [ X4 S4 d. o, _ulation, and rare activating mutations.3 Virilizing
7 l7 v9 x) B }/ ?; Fcongenital adrenal hyperplasia producing excessive
; |2 K. t/ a0 d$ {" iadrenal androgens is a common cause of precocious
) p$ ~* p1 w. L R) ]puberty in boys.3,4
$ @$ b3 v. K$ T8 z) @The most common form of congenital adrenal3 _3 O% {4 E1 {/ `
hyperplasia is the 21-hydroxylase enzyme deficiency.
* B2 W" y( K) g$ @6 m" eThe 11-β hydroxylase deficiency may also result in( q0 O! J/ O' E
excessive adrenal androgen production, and rarely,
$ q, z. N5 D2 J, U9 n) P6 qan adrenal tumor may also cause adrenal androgen
5 n" j! @8 I+ H* b. Y( c9 jexcess.1,33 \+ F% s( v/ A; C! o# h; Q
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
( z, O+ Q* w& O, _: B5 @542 Clinical Pediatrics / Vol. 46, No. 6, July 2007& D. |( a# L; F
A unique entity of male-limited gonadotropin-- e. i$ a4 o0 z& B/ z5 Q, E
independent precocious puberty, which is also known
# `; w0 y ]4 O( {& L; C2 U6 {/ h! Nas testotoxicosis, may cause precocious puberty at a
2 \. Z) Z/ @- F. p% J/ F" yvery young age. The physical findings in these boys" X# ^# L, ]5 m1 ~
with this disorder are full pubertal development,6 q9 ]) G1 M+ I5 k" a) B( i
including bilateral testicular growth, similar to boys
' k0 W! R( F. Q4 _with CPP. The gonadotropin levels in this disorder
i' F, x# Y9 z( B3 [1 k" s, C& Zare suppressed to prepubertal levels and do not show- T) z5 d7 M% d( O, Q" i( j
pubertal response of gonadotropin after gonadotropin-7 L3 o: ~ k5 y- J
releasing hormone stimulation. This is a sex-linked
1 o8 D+ x5 H8 E' tautosomal dominant disorder that affects only. _9 n3 L; a" l; _- B
males; therefore, other male members of the family3 e7 N7 n9 V1 P: b. e
may have similar precocious puberty.3
3 e6 m6 R0 b, M/ Q" ^In our patient, physical examination was incon-
3 G) X( Z3 g }3 Wsistent with true precocious puberty since his testi-# j. E3 o4 L- b: Z; }& e/ s5 @8 l. p
cles were prepubertal in size. However, testotoxicosis8 v$ P5 S- b1 |, X; ~% { O
was in the differential diagnosis because his father
. d6 o0 z' z) |) [0 S& estarted puberty somewhat early, and occasionally,
\" F$ L* z2 E/ y4 e! vtesticular enlargement is not that evident in the
/ p3 [: P- M5 q7 D. V# d' tbeginning of this process.1 In the absence of a neg-
6 E# G' k* W5 B" f# Dative initial history of androgen exposure, our7 i7 D# `) w9 j1 c& N) P& h9 j
biggest concern was virilizing adrenal hyperplasia,6 G! r4 o6 D. b
either 21-hydroxylase deficiency or 11-β hydroxylase
9 `: `9 u: {& @. a2 tdeficiency. Those diagnoses were excluded by find-
- b5 x7 a m- c5 c$ Ving the normal level of adrenal steroids.& A% D/ w7 _1 J$ ]9 N% {$ [
The diagnosis of exogenous androgens was strongly
* W( \4 _; f% B1 ^7 E p, Y$ ^suspected in a follow-up visit after 4 months because
" N/ \% Q! |; x6 m, G# _the physical examination revealed the complete disap-
8 w! ] p9 E" r+ N) G' Kpearance of pubic hair, normal growth velocity, and
# N8 T" E& T. Ldecreased erections. The father admitted using a testos-$ M! F. @; W1 }" a. b$ T$ E' Z1 S' ^
terone gel, which he concealed at first visit. He was; H, X, m' r2 P4 }3 g* F
using it rather frequently, twice a day. The Physicians’
% F1 G0 Y1 t k/ `, B3 LDesk Reference, or package insert of this product, gel or) ^ y6 r) F$ ~
cream, cautions about dermal testosterone transfer to
) Z& t- O2 G' g8 E) gunprotected females through direct skin exposure.
0 A1 `0 a6 U- ^, h9 H BSerum testosterone level was found to be 2 times the
; M9 i1 O0 S* K: l2 _0 @, t' pbaseline value in those females who were exposed to' x: [% i* S2 G* q
even 15 minutes of direct skin contact with their male T1 z5 X# m$ u' U( m& B( A% w
partners.6 However, when a shirt covered the applica-0 n; v/ ]; q0 u+ Y9 S
tion site, this testosterone transfer was prevented.
* n1 ~* D# S G& l4 j2 p m1 SOur patient’s testosterone level was 60 ng/mL,
! ~( T' C% H( _0 K4 p' [! Iwhich was clearly high. Some studies suggest that" i5 s. a9 d' E5 i
dermal conversion of testosterone to dihydrotestos-5 A5 o8 P0 i5 d n; [% w8 s
terone, which is a more potent metabolite, is more
" @* N, [9 U6 D3 v, j/ ?/ C; Mactive in young children exposed to testosterone
8 b0 K8 W' }( Y* p e8 Cexogenously7; however, we did not measure a dihy-! n% p! y9 R; e$ L* t+ v& j
drotestosterone level in our patient. In addition to; `6 x2 Q$ S3 ?3 f2 g+ ^
virilization, exposure to exogenous testosterone in
' w2 ~3 m+ |, bchildren results in an increase in growth velocity and
6 P/ b6 b) G! p( `advanced bone age, as seen in our patient.
5 B& @3 L- W# x; b4 HThe long-term effect of androgen exposure during
# N( K6 N! c) N* N5 }early childhood on pubertal development and final$ a8 i+ t) o7 m4 ~: e
adult height are not fully known and always remain
* `1 h. Z" G! j! `8 Ea concern. Children treated with short-term testos-
l. s4 ^% U5 n: J9 P6 fterone injection or topical androgen may exhibit some9 _, _( U( Q2 d0 \( e! T& |
acceleration of the skeletal maturation; however, after+ ?. f! B. ]' p/ p
cessation of treatment, the rate of bone maturation7 {0 V( z- H: O3 _( K
decelerates and gradually returns to normal.8,9
( Y$ a% A2 l% z8 w9 b G* z2 VThere are conflicting reports and controversy3 l1 g& I& y7 _! n% b
over the effect of early androgen exposure on adult+ W4 _: l/ f& b/ E! g
penile length.10,11 Some reports suggest subnormal
6 T/ B. u6 A9 G9 W& r! k# r( Vadult penile length, apparently because of downreg-
" ?0 Q# h5 ~% l! Xulation of androgen receptor number.10,12 However,. d6 M) _* m7 ^( O; R Z" Y, E2 n
Sutherland et al13 did not find a correlation between
+ [! P6 \* C" gchildhood testosterone exposure and reduced adult. A+ _! f& V1 Y# R5 f
penile length in clinical studies.' b& @' [; w4 u8 P# A3 U5 c
Nonetheless, we do not believe our patient is9 g: _% w$ R# d7 q
going to experience any of the untoward effects from
4 M, p2 y( G4 }8 t4 c' L" Xtestosterone exposure as mentioned earlier because1 F& Q( q: a' `+ u) w
the exposure was not for a prolonged period of time.+ o8 K- ^& n% X' Z/ h2 p9 R; Y
Although the bone age was advanced at the time of
& [. d$ m0 b9 i4 [* ^4 T, }* y# ndiagnosis, the child had a normal growth velocity at
; e1 q, O+ K4 i# H; e& {the follow-up visit. It is hoped that his final adult4 T6 N% z% P7 B5 Y/ M+ Y" Y
height will not be affected.
9 D9 ^) S4 }- H9 BAlthough rarely reported, the widespread avail-
) A( k4 ^, I, G' _0 s) Eability of androgen products in our society may: U" [+ s" M( y
indeed cause more virilization in male or female
4 i, D6 w, Y' q% Ichildren than one would realize. Exposure to andro-
: A* ~) G9 [7 G4 M( t( E' E0 S" Ggen products must be considered and specific ques-" w4 L0 a, D8 Z& o' {
tioning about the use of a testosterone product or
" A& b+ n. ~2 B' x9 J1 ~gel should be asked of the family members during
, B" \# c% |( O6 F0 l) T" M6 S, G) gthe evaluation of any children who present with vir-
8 A i7 M$ j, milization or peripheral precocious puberty. The diag-# }& {2 P8 E' M: y9 e
nosis can be established by just a few tests and by3 Q( F. {) h2 t
appropriate history. The inability to obtain such a
: F6 M6 x" K. @: M8 V$ i7 R# zhistory, or failure to ask the specific questions, may
" w4 r* i, L. ^! Y. l! Oresult in extensive, unnecessary, and expensive6 f" F% \, a+ N0 X( L/ o* D( J
investigation. The primary care physician should be$ G. d( I/ S q% Z. U! l# K! ~
aware of this fact, because most of these children
6 Z9 n* \" r3 K' K3 U7 C; ?may initially present in their practice. The Physicians’
+ f' ~2 g7 x6 v1 Y9 j7 VDesk Reference and package insert should also put a5 T" A- f- O/ x: k
warning about the virilizing effect on a male or
0 `; _) l, o; O. Z- p# x2 l0 M% z; Lfemale child who might come in contact with some-
/ y/ B' B! P! ?one using any of these products.5 z/ S6 h+ F3 d/ w- _
References
# O# M! A( m7 s R3 z$ w; s! Y1. Styne DM. The testes: disorder of sexual differentiation
6 U/ W" I8 u$ a# G, S9 qand puberty in the male. In: Sperling MA, ed. Pediatric8 {3 m, G+ w7 {3 R! c$ v A' q! g
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;6 |3 b7 c! V, t" |4 g
2002: 565-628. O5 b* N7 d6 \$ N- H3 P
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
$ A6 \0 r! r9 G- V- Y7 n Ipuberty in children with tumours of the suprasellar pineal |
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