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Sexual Precocity in a 16-Month-Old: y( T. R R! g3 Q
Boy Induced by Indirect Topical
. C5 z9 U- Z {( fExposure to Testosterone
( D# o' r% j# ?( NSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
0 A" i/ n5 Q+ ?& e" Aand Kenneth R. Rettig, MD1( q' z! r4 U0 }' A3 K8 q
Clinical Pediatrics; K% @5 r7 X+ _4 F* s
Volume 46 Number 6
4 p7 Q& i. a: }4 x" t! QJuly 2007 540-543
% `0 k9 q* Q, S© 2007 Sage Publications
% [$ j, W5 [; P! }: E10.1177/0009922806296651
( E9 x% x6 e- J7 [9 @" x8 G, nhttp://clp.sagepub.com
2 Z1 g4 t, o5 _2 S4 Yhosted at
1 |7 g) \7 S5 M* z7 T; Jhttp://online.sagepub.com6 W( Y, C# K ^! t b0 l. M. u/ I' [
Precocious puberty in boys, central or peripheral,
( m j- W0 ^9 q5 ^, m5 z( q0 o/ `* `is a significant concern for physicians. Central
+ ~, _; E( m, f, h& b, Iprecocious puberty (CPP), which is mediated
" @/ J' e) C% R5 u) k6 \' b3 tthrough the hypothalamic pituitary gonadal axis, has) S* w' }! _3 w# F
a higher incidence of organic central nervous system
, E* D# f/ c5 h6 G; Jlesions in boys.1,2 Virilization in boys, as manifested
4 Z% x1 O" `7 [; _by enlargement of the penis, development of pubic, T8 t9 ?* t/ U% n0 K; l: r4 d
hair, and facial acne without enlargement of testi-/ P. W0 \; m; v6 L; g) G+ J( o
cles, suggests peripheral or pseudopuberty.1-3 We
8 ]: S. u" }6 h% Breport a 16-month-old boy who presented with the! Y$ z6 B8 d/ v" M6 L6 {. I/ Y& \
enlargement of the phallus and pubic hair develop-
: i0 F. T7 @+ n8 Gment without testicular enlargement, which was due
9 J4 P" F, e7 q8 z# Qto the unintentional exposure to androgen gel used by& ^% B/ E1 f z' T& a! X
the father. The family initially concealed this infor-" M" G# X2 Y0 R3 Y+ T+ v2 O
mation, resulting in an extensive work-up for this2 N# h6 A% ]$ t3 c
child. Given the widespread and easy availability of
# D9 w" }3 u0 G. L& ^! y# |testosterone gel and cream, we believe this is proba-
( @; T5 g! q5 v3 Ibly more common than the rare case report in the
* l. q2 H4 E- C5 c9 k$ \ |" pliterature.4
: \9 l$ V$ D! wPatient Report
& j2 i0 s7 F$ [" R( P. S5 K" CA 16-month-old white child was referred to the
; C9 x( M+ Z" N% x* sendocrine clinic by his pediatrician with the concern
! D0 ]0 l( H* }1 n5 k% p" zof early sexual development. His mother noticed
U9 h+ A& @7 [ y( p; Z) ^+ ?light colored pubic hair development when he was! [- w7 [. [/ `& s' X9 K
From the 1Division of Pediatric Endocrinology, 2University of
/ x2 @4 ~/ i4 }! Y6 ]" Q' B8 U xSouth Alabama Medical Center, Mobile, Alabama.
) ]; O9 z$ d( Q; m9 A, pAddress correspondence to: Samar K. Bhowmick, MD, FACE,
+ p) @" b1 I, d" R7 FProfessor of Pediatrics, University of South Alabama, College of! ?/ z) Y# D# [, x, k: ~; F. @
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
% ]+ a8 e$ o$ J& be-mail: [email protected].: m2 u0 I, x+ \' M3 D- ]6 `1 {
about 6 to 7 months old, which progressively became
5 B o6 q' p# h8 b+ h1 h. p1 sdarker. She was also concerned about the enlarge-7 p: j1 {- q3 L V, Y5 w/ P
ment of his penis and frequent erections. The child
, T$ o) G6 x. S* ]! n4 b3 O4 o8 ywas the product of a full-term normal delivery, with
: }) ?" R5 E; s# L( Z8 r# ]& xa birth weight of 7 lb 14 oz, and birth length of
' L3 e. C) S. U6 N# M: A20 inches. He was breast-fed throughout the first year
( W7 ^& M# U3 Z; @- C; Fof life and was still receiving breast milk along with. {$ S. t Q7 a3 P: O' }
solid food. He had no hospitalizations or surgery,8 u. Y. c9 d# E* f$ \
and his psychosocial and psychomotor development
* a9 R& u# X: T! \- Kwas age appropriate./ ~5 e2 w+ ~' j: G3 h' a. z: E
The family history was remarkable for the father,
; D& b; n/ \3 [8 `who was diagnosed with hypothyroidism at age 16,+ r/ O! o. Z7 `. s
which was treated with thyroxine. The father’s
F4 B! e9 P5 [5 {$ v4 q# Y6 Dheight was 6 feet, and he went through a somewhat
2 ~9 E- W0 J. Q/ ^9 \( `& Q9 p5 Gearly puberty and had stopped growing by age 14.
5 ` N4 \& p$ A" X+ `2 A3 T- T# zThe father denied taking any other medication. The7 }4 P- V8 `0 t; M" E" V3 M
child’s mother was in good health. Her menarche2 X" k" E2 ^* T! A
was at 11 years of age, and her height was at 5 feet6 n2 Z; n$ O+ C" C5 H. T
5 inches. There was no other family history of pre-7 Q6 a1 W9 n5 Y: V
cocious sexual development in the first-degree rela-
7 T, ~+ S) I0 o7 H% J( }. Ntives. There were no siblings.# x B1 I0 l0 ^/ T4 w
Physical Examination
3 S) Y6 ~. g1 G, ^# p4 ~2 WThe physical examination revealed a very active,
% q( s1 q0 h2 O3 v5 }; \3 Bplayful, and healthy boy. The vital signs documented
l+ V+ z3 m, ] |/ Ma blood pressure of 85/50 mm Hg, his length was
1 C' ]' W. m9 z4 ], N* w6 G' [4 R90 cm (>97th percentile), and his weight was 14.4 kg
$ j' |* v5 R7 x# y$ a& Z(also >97th percentile). The observed yearly growth
; L% p! B0 e9 o }0 gvelocity was 30 cm (12 inches). The examination of
' Z( o1 a; G1 lthe neck revealed no thyroid enlargement.; j5 u0 |4 d8 f: Q, P/ r& [2 R0 p
The genitourinary examination was remarkable for
+ B: O% |) `7 q# U8 denlargement of the penis, with a stretched length of
6 K7 j) @: g( s/ L9 v; d# _- B8 cm and a width of 2 cm. The glans penis was very well1 x! W3 ?# a( E* W* e* a. ?
developed. The pubic hair was Tanner II, mostly around/ A2 F' h0 }; E- S) o
540; S- A- ^4 A0 j+ |! G# ?9 J. p5 p
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
, Q, z- i. S b6 o4 a1 Cthe base of the phallus and was dark and curled. The+ m/ T: s. @" |+ U
testicular volume was prepubertal at 2 mL each.
/ S6 Z: _& F2 H+ W# J7 h2 v5 NThe skin was moist and smooth and somewhat4 v. Y3 }2 ~8 c1 \2 x$ C3 ^# B# Y
oily. No axillary hair was noted. There were no/ i. n6 o( W4 A) ?' ^
abnormal skin pigmentations or café-au-lait spots.3 \) O4 P, j- X- y3 ?
Neurologic evaluation showed deep tendon reflex 2+* a, o N; w* _: Z8 c
bilateral and symmetrical. There was no suggestion
0 U& ?1 o4 s- K4 j0 \" ]; f, ^of papilledema.) a; S' Y# R: C2 X
Laboratory Evaluation
6 b6 e+ ^. {0 Z9 W$ FThe bone age was consistent with 28 months by
2 e$ S. B3 j, y" e7 D$ n$ n( ~" Ousing the standard of Greulich and Pyle at a chrono-
: D% i, J+ G% j# O6 plogic age of 16 months (advanced).5 Chromosomal
; A% p- S) A" ?4 gkaryotype was 46XY. The thyroid function test k7 @; M+ F% P) {; d# H
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
; b5 }" S' ` |; G' ulating hormone level was 1.3 µIU/mL (both normal).
& c5 X" j2 p% wThe concentrations of serum electrolytes, blood
: {8 W) G- y0 v7 P. T) }+ N! Qurea nitrogen, creatinine, and calcium all were( B& v2 N3 y( _; y
within normal range for his age. The concentration
0 K9 C& s" S6 m: vof serum 17-hydroxyprogesterone was 16 ng/dL
( W; o2 j2 V8 w$ a. H- U(normal, 3 to 90 ng/dL), androstenedione was 20
* U6 {! a! g9 D: f3 w! G1 rng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
$ N; n m+ v) |* A5 G6 Yterone was 38 ng/dL (normal, 50 to 760 ng/dL),
9 ^- R$ F! \( w8 l& `3 tdesoxycorticosterone was 4.3 ng/dL (normal, 7 to
# _! m0 G1 M- v& {49ng/dL), 11-desoxycortisol (specific compound S)
. r0 P i" I6 M9 \% p! x5 L9 Ywas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-7 _2 P1 J4 S6 @
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
* e' P/ [9 f: ^/ S5 b( l s0 k) ftestosterone was 60 ng/dL (normal <3 to 10 ng/dL),! p7 L, D' V) K, J1 c
and β-human chorionic gonadotropin was less than/ l1 M. a P" J2 Y V: p1 v Q
5 mIU/mL (normal <5 mIU/mL). Serum follicular7 w9 o( g) I7 ^' L3 K
stimulating hormone and leuteinizing hormone
0 |+ J6 O( ?" [5 [0 o- [/ gconcentrations were less than 0.05 mIU/mL
I7 E0 j9 h/ X2 {; L(prepubertal).0 z+ e/ m$ ~, r3 l+ v' U% s
The parents were notified about the laboratory( B1 \: z5 c0 x: ?
results and were informed that all of the tests were; K$ @' J" V2 `" G3 A
normal except the testosterone level was high. The' s% _& x) q, l/ w
follow-up visit was arranged within a few weeks to6 x0 T1 m2 J; B$ c
obtain testicular and abdominal sonograms; how-; `/ [) m3 O7 l! N) ]
ever, the family did not return for 4 months.
3 B8 d# N+ ^: V* |Physical examination at this time revealed that the
, ]" F2 O: ~0 Y2 W7 }/ l; Q1 \child had grown 2.5 cm in 4 months and had gained' |: c% M1 Z, j) `& E; P3 Y
2 kg of weight. Physical examination remained$ W% s0 R/ V2 w: r' ~8 t
unchanged. Surprisingly, the pubic hair almost com-6 k; V; G3 T) Z1 m6 D
pletely disappeared except for a few vellous hairs at, Q' y# h; s) j; ?
the base of the phallus. Testicular volume was still 2
) |& D) D/ d) g: ymL, and the size of the penis remained unchanged.
9 J( p6 Z, F3 k! rThe mother also said that the boy was no longer hav-
M! V1 a# m9 G Jing frequent erections.
) i6 Q: \3 H: jBoth parents were again questioned about use of! I9 o' s+ a. L5 v
any ointment/creams that they may have applied to. `" ?4 H3 V- M
the child’s skin. This time the father admitted the
$ v$ v, j& u H1 k# P* UTopical Testosterone Exposure / Bhowmick et al 5414 j7 R6 x# @) [! G' [3 |! x$ j
use of testosterone gel twice daily that he was apply-1 D* T" f9 |6 @: g* P) ?- A: u
ing over his own shoulders, chest, and back area for
% ]) i. g' F& L5 ?0 n6 Aa year. The father also revealed he was embarrassed+ A' a- V- W7 u* A9 m( Y
to disclose that he was using a testosterone gel pre-% g3 w p. j' c* Q) A1 u
scribed by his family physician for decreased libido
0 ]* y2 @- @. ^; ?secondary to depression.
6 `$ Y5 U: T2 c, eThe child slept in the same bed with parents.
) V0 P( b0 V4 ]) F# _, p d2 C% ^The father would hug the baby and hold him on his" ~! S+ `6 k: u& H& C; W
chest for a considerable period of time, causing sig-% c9 c1 R# v7 B, Y& J. R
nificant bare skin contact between baby and father.8 [. d3 V$ g& I# i9 k- `2 R
The father also admitted that after the phone call,% h8 M& l+ e' ~ D5 q
when he learned the testosterone level in the baby0 g- h( b) s1 r9 K' g7 p5 u2 g
was high, he then read the product information0 R, y: M. o( A0 F: F% e& p, i" i" S
packet and concluded that it was most likely the rea-
7 b" r8 m; W1 pson for the child’s virilization. At that time, they
- a. _ T" v$ k% Z* l1 f' idecided to put the baby in a separate bed, and the
5 q, \0 H' r# C' z* D6 P/ cfather was not hugging him with bare skin and had, j- f8 V& p) ^$ }) D6 E
been using protective clothing. A repeat testosterone
# Z/ y8 Y* @/ f0 o k: J2 htest was ordered, but the family did not go to the# |! P6 a8 i9 Z, E# \
laboratory to obtain the test.' A) t4 d& ~! v8 i4 b+ k5 {* I
Discussion
& h& {' r* L4 j5 n) M$ ?Precocious puberty in boys is defined as secondary e' G+ q* B6 C
sexual development before 9 years of age.1,4# w* ^$ b: Z& i; v
Precocious puberty is termed as central (true) when( c U0 c- S( l, G0 R
it is caused by the premature activation of hypo-
$ f2 p* S+ ]6 Q2 ]6 U% t$ rthalamic pituitary gonadal axis. CPP is more com-, R) ~# y' M4 W7 `
mon in girls than in boys.1,3 Most boys with CPP4 a W# w3 } `
may have a central nervous system lesion that is+ y* v( G7 u$ t$ s }% c2 E
responsible for the early activation of the hypothal-0 Z4 `+ V4 O% V5 ^0 W" X" {
amic pituitary gonadal axis.1-3 Thus, greater empha-6 D( `7 x/ y5 j) d6 Z1 Y! j& T
sis has been given to neuroradiologic imaging in
: R7 ~( y! Z% b* y; R2 o# d; iboys with precocious puberty. In addition to viril-1 B1 w# k* i# E9 e5 B; G( K4 m
ization, the clinical hallmark of CPP is the symmet-
3 I+ k3 m) h1 Q6 m/ Frical testicular growth secondary to stimulation by2 w+ D- y& S. l1 K% E$ w
gonadotropins.1,3
' J) ^$ I9 g+ h2 d9 ~1 J D- I. fGonadotropin-independent peripheral preco-
7 U0 g9 f2 y/ u0 qcious puberty in boys also results from inappropriate
( k f9 ?. \! M* B! h. handrogenic stimulation from either endogenous or
; x, q9 m- W6 a, S2 gexogenous sources, nonpituitary gonadotropin stim-: e( m- X# w& ~( {+ }- L1 e
ulation, and rare activating mutations.3 Virilizing
3 ?# f% j! n! Q8 T6 z9 Z4 r" H; \ V( Jcongenital adrenal hyperplasia producing excessive) \+ A# f+ [+ C7 }" r$ s
adrenal androgens is a common cause of precocious9 n) _/ H! C- h! x7 K' n- ]
puberty in boys.3,46 j% X3 N0 B% _/ E
The most common form of congenital adrenal. E; s$ _5 k: Z- ^- n
hyperplasia is the 21-hydroxylase enzyme deficiency." o( N" g% Z* A5 E" {; J$ q9 z
The 11-β hydroxylase deficiency may also result in g8 r, K0 {: w; ?
excessive adrenal androgen production, and rarely," Y5 b0 t7 C0 g: \9 n- [
an adrenal tumor may also cause adrenal androgen
& l( f3 [& F. u0 Bexcess.1,3
]0 v7 C/ Y+ }9 V+ ?: Nat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from% A0 g' X% O4 I3 y
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
6 T# d0 v9 l3 m9 V( u+ ]9 W; ]4 R6 GA unique entity of male-limited gonadotropin-
/ g H t& |4 ?& h! x, F4 Dindependent precocious puberty, which is also known7 e# L9 m2 N$ P: U2 h% A
as testotoxicosis, may cause precocious puberty at a
# |' e4 ]; D/ avery young age. The physical findings in these boys
{# \& u3 `5 d. p2 ]with this disorder are full pubertal development,' Q6 n& h$ M, m1 g$ M* X& _7 o4 N
including bilateral testicular growth, similar to boys
+ }- m& V1 W7 _6 i+ {3 @) X5 P& Cwith CPP. The gonadotropin levels in this disorder( y( z2 G' \' g0 R& y( }8 R
are suppressed to prepubertal levels and do not show
) C7 m) p* l; l# Z2 spubertal response of gonadotropin after gonadotropin-
. B4 \- r' H0 x4 ?8 k0 Dreleasing hormone stimulation. This is a sex-linked% u- J- \& L5 ^1 y8 P' v v
autosomal dominant disorder that affects only) C% d6 R, C2 g Y5 X( a
males; therefore, other male members of the family
# l0 T( a; G2 J% Pmay have similar precocious puberty.3; j. X l& f( ?& l
In our patient, physical examination was incon-
' J% i6 f- m/ K9 asistent with true precocious puberty since his testi-
5 O+ Q# C7 \6 V. Y" O1 ]. p8 Fcles were prepubertal in size. However, testotoxicosis- C+ I/ X/ E% V y' C0 o* ]7 |
was in the differential diagnosis because his father2 Z# l, T6 O( i. {5 W+ _1 V
started puberty somewhat early, and occasionally,; ?' h+ {) ]4 K% j% ?! Y) b: e
testicular enlargement is not that evident in the
* l/ [- @# a, M8 Bbeginning of this process.1 In the absence of a neg-
: Y$ n4 V+ @2 B8 l' ?( oative initial history of androgen exposure, our, J5 K, d9 W- J: d% X
biggest concern was virilizing adrenal hyperplasia,( G4 k3 S% E. [8 w: \' ^3 M
either 21-hydroxylase deficiency or 11-β hydroxylase
5 r' M+ s4 G% `1 J% I1 kdeficiency. Those diagnoses were excluded by find-6 `0 l" z. ?& F) ?2 Y. r5 E' q
ing the normal level of adrenal steroids.
6 X/ c8 L" j- R- O' pThe diagnosis of exogenous androgens was strongly
K8 w0 z- m2 {9 Wsuspected in a follow-up visit after 4 months because
. s& e. g% s0 r% r4 @the physical examination revealed the complete disap-) m% j+ v1 \2 R6 e
pearance of pubic hair, normal growth velocity, and
+ l/ ^; V+ _& t# Bdecreased erections. The father admitted using a testos-3 k+ j( U' s% r& C! R( S
terone gel, which he concealed at first visit. He was
4 L1 Z1 a. k3 z2 Q }using it rather frequently, twice a day. The Physicians’2 E# k9 L! O+ w4 _
Desk Reference, or package insert of this product, gel or* R+ c2 S5 Z% D
cream, cautions about dermal testosterone transfer to
2 K3 ]' N: |$ Y' [2 A+ H3 r! x Vunprotected females through direct skin exposure.* g @" r! y, j, l# Y6 x* u
Serum testosterone level was found to be 2 times the
( p) s1 x- P6 h" }* S; H' }; I& l3 _baseline value in those females who were exposed to
$ V8 F0 {% [1 S) [+ H' Xeven 15 minutes of direct skin contact with their male
4 |5 d& f1 ]6 ^: Vpartners.6 However, when a shirt covered the applica-
. L0 d. ~# ~. ~* I- Mtion site, this testosterone transfer was prevented.
( L: J7 |: W# gOur patient’s testosterone level was 60 ng/mL,0 l( i* P" T# L: c+ T$ {
which was clearly high. Some studies suggest that
8 L2 {/ N4 ?$ }. _dermal conversion of testosterone to dihydrotestos-
" a. e. @+ f9 K' B, lterone, which is a more potent metabolite, is more1 _2 r& x2 r* d. P
active in young children exposed to testosterone
& l0 Z5 z2 [, T9 H, ]& |exogenously7; however, we did not measure a dihy-! A; L# p' i) s- ?5 v3 i9 _+ Q
drotestosterone level in our patient. In addition to
5 f4 W- s! B6 y3 Avirilization, exposure to exogenous testosterone in, u) R3 m3 I/ Y, q
children results in an increase in growth velocity and
. E. u3 t$ L( g$ h5 q; m7 sadvanced bone age, as seen in our patient.
8 z: O% Q- z& A: wThe long-term effect of androgen exposure during/ P4 S$ I, x% n' O9 u
early childhood on pubertal development and final/ _" _* k! Q/ `; z
adult height are not fully known and always remain6 P- E, ]" O2 H/ }1 g: c1 h
a concern. Children treated with short-term testos-
. c$ u4 W6 t, A9 n0 ~terone injection or topical androgen may exhibit some
; ?5 ] q- D; \8 ]5 D! b t' jacceleration of the skeletal maturation; however, after
7 s5 m% c- K- t8 `cessation of treatment, the rate of bone maturation D1 y2 N) K# W# Y( W
decelerates and gradually returns to normal.8,9$ G; ?$ G0 c7 T; A
There are conflicting reports and controversy7 w0 G5 G) p+ S3 L' t4 K
over the effect of early androgen exposure on adult
& k2 v5 I& o% V% z7 Y$ I1 ?penile length.10,11 Some reports suggest subnormal, v$ z& C: C- i" A3 _+ [+ a
adult penile length, apparently because of downreg-2 p0 W8 W$ [( m* R/ K
ulation of androgen receptor number.10,12 However,, t# k$ p- B# \5 S* f& ]5 |5 v g
Sutherland et al13 did not find a correlation between) Z/ h% j5 b- I: ?. m' g. @# G
childhood testosterone exposure and reduced adult; q: v* J8 l! j3 t- i
penile length in clinical studies.5 o! i y) h4 B% U* @( U
Nonetheless, we do not believe our patient is
( V8 M" i: C- n% o; W# B' |going to experience any of the untoward effects from- h* w8 }( @: s: n- \9 L& ]
testosterone exposure as mentioned earlier because/ B0 w, m5 p5 Z2 g7 S7 N
the exposure was not for a prolonged period of time.- j+ v$ Q; `; b" P: r
Although the bone age was advanced at the time of
. {& `/ ?! ]. Ddiagnosis, the child had a normal growth velocity at N* E. L2 J7 X( I( _4 `% q
the follow-up visit. It is hoped that his final adult: Q9 s5 ]; v4 b) q. F0 M2 w
height will not be affected.
! W$ ?7 O4 z: w# E) P* UAlthough rarely reported, the widespread avail-% M M$ b( O: q
ability of androgen products in our society may
4 i( c& g8 G- xindeed cause more virilization in male or female
! g' ]. J( E0 r; k7 Rchildren than one would realize. Exposure to andro-
3 W9 b k3 n) e: V9 v: V& p7 S% pgen products must be considered and specific ques-
4 x/ _- \8 W% Ktioning about the use of a testosterone product or
# n0 ]1 k) `6 D H. agel should be asked of the family members during& _* i+ `! v) w* o3 t
the evaluation of any children who present with vir-
. Q4 y0 J: P+ @) m, ?5 C2 Ailization or peripheral precocious puberty. The diag-( x7 t+ i8 Z; E( o) F
nosis can be established by just a few tests and by
7 D+ D8 ] E/ uappropriate history. The inability to obtain such a7 W; C( Q3 {" E% x# \
history, or failure to ask the specific questions, may; E0 T, l' o& a+ v- a9 k& B
result in extensive, unnecessary, and expensive
/ L3 M5 S. C# A kinvestigation. The primary care physician should be* Z: A5 g- W2 V3 L; q1 C+ y( _6 w
aware of this fact, because most of these children. d+ I- \" e9 g
may initially present in their practice. The Physicians’ ^, W2 B/ @1 E& A+ B
Desk Reference and package insert should also put a
+ f2 U2 t- e1 _' _) Vwarning about the virilizing effect on a male or
B7 |8 ?8 M' e$ mfemale child who might come in contact with some-
_4 t& b7 V/ A6 \/ uone using any of these products.% X. i, I! ^; e1 Q. l8 ~
References
4 F/ V; A$ K9 u1. Styne DM. The testes: disorder of sexual differentiation4 O* C+ O7 \$ f: E
and puberty in the male. In: Sperling MA, ed. Pediatric
) a! ^* C" T9 b8 [/ ?/ bEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;) E% [, M5 R# K8 Q4 {; C
2002: 565-628.4 p; @2 v! h. ]$ U& Z
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious }7 e+ _. `; E4 A: I
puberty in children with tumours of the suprasellar pineal |
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