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Sexual Precocity in a 16-Month-Old: m) Q6 e" D2 r& s
Boy Induced by Indirect Topical
& i: Y5 _; ]/ K# d% e IExposure to Testosterone/ O7 i8 M6 n1 J4 R" T/ K3 R
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2, L8 G4 t2 W9 D1 Z2 f) c) t; r0 m: Q
and Kenneth R. Rettig, MD15 [9 _+ D5 b3 r" V* _6 x
Clinical Pediatrics5 D3 [3 _8 m2 c( y0 g
Volume 46 Number 6
! t- M. r& N. ?6 b" gJuly 2007 540-5432 J( y: y# h2 c9 p8 R
© 2007 Sage Publications
: n$ I3 [% d$ w, o10.1177/0009922806296651
0 F' z( y9 ^1 T% X. y1 w# uhttp://clp.sagepub.com# R) c( H7 m' _" Q9 g+ K
hosted at
; h- h* ^0 N, R$ C2 G6 O7 ghttp://online.sagepub.com' _1 N9 c7 |# i; }" c& @
Precocious puberty in boys, central or peripheral,
g" z' O- W# l. d8 uis a significant concern for physicians. Central
9 X3 o. [; l9 Rprecocious puberty (CPP), which is mediated
: d$ Z4 R) m# zthrough the hypothalamic pituitary gonadal axis, has& o$ M$ T- ?3 w, m7 W# {7 D- |
a higher incidence of organic central nervous system
- G2 `$ V$ v" D- m7 g6 i4 j3 slesions in boys.1,2 Virilization in boys, as manifested- t4 A( E: ?% |
by enlargement of the penis, development of pubic3 \& z: r8 M2 J4 d& ]8 G
hair, and facial acne without enlargement of testi-
% Y7 o- D. l- V: fcles, suggests peripheral or pseudopuberty.1-3 We
) V# q( h. a1 f: `- i& z! Xreport a 16-month-old boy who presented with the
T R& x! H4 henlargement of the phallus and pubic hair develop-$ B' O& h+ ^" M" P8 G, N9 Y8 D
ment without testicular enlargement, which was due
0 j# r2 C3 x( z8 @to the unintentional exposure to androgen gel used by, t( U, J9 M) E) X* r
the father. The family initially concealed this infor-$ L0 r5 ]' X9 x3 ]: e
mation, resulting in an extensive work-up for this, l n' g1 d( m0 W7 A6 a
child. Given the widespread and easy availability of* m5 h% i& m0 ?; p
testosterone gel and cream, we believe this is proba-
1 L U' R5 e* n" ]bly more common than the rare case report in the% J/ [1 v4 a O3 S* `
literature.48 Y/ A' v! g x( t) M& K
Patient Report, E8 ] y& W X1 J" G+ O
A 16-month-old white child was referred to the; H% F9 h2 q3 X6 I/ Q
endocrine clinic by his pediatrician with the concern3 i) ^7 y, a( f
of early sexual development. His mother noticed
" O. W# V. R9 R- E7 Clight colored pubic hair development when he was& G3 x0 [ w5 @1 c
From the 1Division of Pediatric Endocrinology, 2University of
; L" h& D/ t/ Z/ f4 N( k+ RSouth Alabama Medical Center, Mobile, Alabama.; ]" b6 J O" Z! |, x" h7 V$ _
Address correspondence to: Samar K. Bhowmick, MD, FACE,: U) f9 c( F; Q8 P( C' s
Professor of Pediatrics, University of South Alabama, College of4 u( @9 e2 }* F$ p( y: B
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;, X: T* l: X9 E `; H8 b0 t
e-mail: [email protected]., K- |4 @' `& e
about 6 to 7 months old, which progressively became
: Q: t N* L2 N: edarker. She was also concerned about the enlarge-5 m( ?2 |/ I9 j4 E I) Z2 F
ment of his penis and frequent erections. The child9 g: {# z; c; Z7 [( i
was the product of a full-term normal delivery, with+ X" t: U2 d0 J. H; [
a birth weight of 7 lb 14 oz, and birth length of5 w. I7 ^: ~' J1 p( o1 t& @" V
20 inches. He was breast-fed throughout the first year0 ^% J A' T- W9 @! |& S
of life and was still receiving breast milk along with
9 j4 `6 Z' t- L6 Lsolid food. He had no hospitalizations or surgery,
( X6 r" {( U) iand his psychosocial and psychomotor development
: W8 j- r Z0 u2 j- M% Bwas age appropriate.
+ a' T4 M' s' ?2 i1 g( w9 LThe family history was remarkable for the father,
% n2 B5 z o6 Iwho was diagnosed with hypothyroidism at age 16,) L' j: ~% G7 W' r( p* N x) R
which was treated with thyroxine. The father’s
4 \4 D3 p: o, ~2 ^1 @* F# ]: k; Hheight was 6 feet, and he went through a somewhat
& K# k0 I* M9 Q, q. ^" n- searly puberty and had stopped growing by age 14.
' p1 ]) {5 K- o, FThe father denied taking any other medication. The
' M3 V; Q9 |- m. k+ Z# |7 R- wchild’s mother was in good health. Her menarche7 b" @- @* r& G' J2 z! s1 j
was at 11 years of age, and her height was at 5 feet* K' ]. a t, Q
5 inches. There was no other family history of pre-
) G! Q% M+ ~$ y% `2 P/ Ccocious sexual development in the first-degree rela-% F+ B7 c( k; E( g9 N. B
tives. There were no siblings.
& W! o l O1 o' n% SPhysical Examination3 x& s1 M$ ^0 Y. \
The physical examination revealed a very active,3 G" G2 t% `! ?1 s, U
playful, and healthy boy. The vital signs documented! y5 Q5 e+ z- @2 [" p: b
a blood pressure of 85/50 mm Hg, his length was
- P% B/ X7 ^; x' n$ f90 cm (>97th percentile), and his weight was 14.4 kg; p1 m @8 F( M
(also >97th percentile). The observed yearly growth3 @! G( b1 D# J+ t- E* f% H2 ]
velocity was 30 cm (12 inches). The examination of( r% ]+ F- c4 B7 H. c- {1 \
the neck revealed no thyroid enlargement.
; B; G' J, o* Q- L& j3 j, MThe genitourinary examination was remarkable for
' q4 g: ]- k; O. Y* j. l! Nenlargement of the penis, with a stretched length of' g: [/ o8 c$ U* L0 c9 D& b: h
8 cm and a width of 2 cm. The glans penis was very well2 u1 k+ g: M7 H( d; i
developed. The pubic hair was Tanner II, mostly around: d4 t( z+ H+ d2 e9 b1 @( M( Y9 t
540
7 K& w; A T) `; R, W2 oat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from9 ~* v/ a" f4 G$ \1 n( Z
the base of the phallus and was dark and curled. The
. j0 f) ^2 d! t6 t, Htesticular volume was prepubertal at 2 mL each.0 V- n8 t$ D6 J" q8 y; f
The skin was moist and smooth and somewhat
' Q# E& e( p4 M# I2 m, Aoily. No axillary hair was noted. There were no1 ?. v; t; V: `' z3 }$ Q% u
abnormal skin pigmentations or café-au-lait spots., u4 }0 ~ `, _5 ?5 U
Neurologic evaluation showed deep tendon reflex 2+# A- ?& K- X2 v
bilateral and symmetrical. There was no suggestion
: m) j, C; M8 O8 _+ L+ r" C6 gof papilledema." m. O) @2 c% u, ?
Laboratory Evaluation+ {; A! d% p3 r) Z
The bone age was consistent with 28 months by" ~, h+ n7 P& V9 y6 n% D" ]
using the standard of Greulich and Pyle at a chrono-
( _% M/ a* ?/ jlogic age of 16 months (advanced).5 Chromosomal
7 S5 j! Q% j& z6 c3 y3 zkaryotype was 46XY. The thyroid function test
9 F6 c9 [- W3 R# c7 x2 f: tshowed a free T4 of 1.69 ng/dL, and thyroid stimu-) p' P9 j {! i$ ?6 V
lating hormone level was 1.3 µIU/mL (both normal).
$ H% m& A+ X& D& a; f: A1 oThe concentrations of serum electrolytes, blood/ H& Q3 |; x2 b9 b0 D @
urea nitrogen, creatinine, and calcium all were
( k6 B* h- U% M' a. l6 k, Gwithin normal range for his age. The concentration" E& h$ z5 U, ?$ H: _9 I
of serum 17-hydroxyprogesterone was 16 ng/dL' Q; X% {+ h8 V1 s/ f2 |
(normal, 3 to 90 ng/dL), androstenedione was 206 y6 D8 {8 Z! a( M) F# H
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-" A9 |* g1 D' V2 A6 n
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
/ y2 [5 A$ [6 ?8 _" v* {desoxycorticosterone was 4.3 ng/dL (normal, 7 to
, j! s) H3 l, F7 G! D+ [# [2 v. j( g1 }49ng/dL), 11-desoxycortisol (specific compound S)# p& ]6 v ?8 i% M& c
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
Z1 S; E) V. }8 A2 ~" O3 |tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total4 L) A# `( P$ |+ P4 O6 i4 \) X
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
) [9 x4 G& I3 Q. _# k* f3 M3 ^) q1 }and β-human chorionic gonadotropin was less than
) A& ^. \& r4 U: u* k9 |5 mIU/mL (normal <5 mIU/mL). Serum follicular
' o/ x5 |9 m0 n: d/ h' Fstimulating hormone and leuteinizing hormone
7 Z& R( u# ^% E2 Q. O" U/ \$ S4 qconcentrations were less than 0.05 mIU/mL
, M: A) g5 O3 n! E! s) X(prepubertal).
4 A, C) E4 g. {- W6 vThe parents were notified about the laboratory+ @1 o5 V8 C6 f) P& M- x# b
results and were informed that all of the tests were
6 o; H& a5 i( fnormal except the testosterone level was high. The
& C* j* P: x, A2 {9 z5 \; u1 gfollow-up visit was arranged within a few weeks to9 a" k. j: H- f1 ^0 D! _8 a7 [
obtain testicular and abdominal sonograms; how-; T1 z" \! U+ O& p
ever, the family did not return for 4 months.2 O. T0 ^) h" [/ B. a6 a
Physical examination at this time revealed that the
9 C7 G. v2 g( ^, Zchild had grown 2.5 cm in 4 months and had gained
0 A7 D9 H5 g* q+ n ?4 U5 K2 kg of weight. Physical examination remained
9 x" G1 q( O) j) j8 [# ~/ Runchanged. Surprisingly, the pubic hair almost com-3 P& L9 K+ ]8 M+ R& ]4 }
pletely disappeared except for a few vellous hairs at
: Q9 t U9 Z% j, n- K0 G$ J3 F# @the base of the phallus. Testicular volume was still 2$ ~1 N4 C/ p9 U! j
mL, and the size of the penis remained unchanged.
$ d3 ]3 j: X) t. n+ w" CThe mother also said that the boy was no longer hav-
$ `% D- ?) Z8 K# s' K) W; F% a9 zing frequent erections.* [5 {3 Z9 q$ @/ P# E0 {, ]3 f
Both parents were again questioned about use of
' v/ o6 U$ \2 J' m$ }' ?any ointment/creams that they may have applied to
: X7 g) c, ]( b( e) Bthe child’s skin. This time the father admitted the
; j0 B7 x, m) Z9 ~, q; N i8 kTopical Testosterone Exposure / Bhowmick et al 541
- v/ s- G W' F6 o$ ^use of testosterone gel twice daily that he was apply-
3 z" Z$ O' y/ `% }8 Wing over his own shoulders, chest, and back area for
/ f9 \' {& E- M) Q# g& {7 `a year. The father also revealed he was embarrassed
3 ] |3 |- i) I) ~' ? kto disclose that he was using a testosterone gel pre-' Y3 \+ Y$ U7 Y" _
scribed by his family physician for decreased libido
1 c" Y2 y1 Y: e" N% N* m% D8 l, fsecondary to depression.
& G* _8 a7 v1 E$ i) iThe child slept in the same bed with parents.% y, Q) u; X. @
The father would hug the baby and hold him on his6 k9 ^* z5 `& t# {
chest for a considerable period of time, causing sig-
$ Q3 k- c( G8 F2 Nnificant bare skin contact between baby and father.9 W. L; s6 a/ t" z6 {# p& o- V' o
The father also admitted that after the phone call,
! j- A( p7 _' B4 J6 F8 n0 s! wwhen he learned the testosterone level in the baby8 L; y) n8 \$ _: B
was high, he then read the product information3 O4 \( n3 y" r$ O5 u2 q' \$ l, x
packet and concluded that it was most likely the rea-
& V6 V! H, T8 H o2 P! yson for the child’s virilization. At that time, they
F$ x' G6 F5 Bdecided to put the baby in a separate bed, and the" b! P; }( W! \0 c0 {. u) e
father was not hugging him with bare skin and had
0 W; e& I' Q5 }" rbeen using protective clothing. A repeat testosterone
$ h% r/ @0 V7 x3 wtest was ordered, but the family did not go to the- v8 c" e8 P$ J2 t$ F* b& A8 c/ \
laboratory to obtain the test.
0 ]6 i7 ~) c1 g: p: JDiscussion1 S3 h: [; }2 S' K8 [5 z u& [$ i
Precocious puberty in boys is defined as secondary
. U z! C3 o4 y% C7 k* J) L9 C2 Ssexual development before 9 years of age.1,44 j( R1 u. l) T, j
Precocious puberty is termed as central (true) when% v* T, j3 n2 N6 w( W" r
it is caused by the premature activation of hypo-
# a G1 H6 {9 H( Q9 Uthalamic pituitary gonadal axis. CPP is more com-
, P& S3 ^5 N, {mon in girls than in boys.1,3 Most boys with CPP/ i+ T, ~% ~6 d( x' Q
may have a central nervous system lesion that is5 Q3 Y. B/ p: { M
responsible for the early activation of the hypothal-0 o7 s" z+ T7 w1 d2 h* M, U6 l
amic pituitary gonadal axis.1-3 Thus, greater empha-, C! c* g7 c& G3 |9 @! ~) r
sis has been given to neuroradiologic imaging in
% ]7 y* V t# j, W wboys with precocious puberty. In addition to viril-! C- H! N" T. t+ n" w* H" I. q
ization, the clinical hallmark of CPP is the symmet-, i6 }% G$ r7 U$ [/ S5 S
rical testicular growth secondary to stimulation by
+ `5 N: M+ f5 Z2 w6 E* n* ?gonadotropins.1,3
# g6 c/ A2 u( ?" H, W' j6 `/ y8 iGonadotropin-independent peripheral preco-
% T/ F% Z4 V% X: _$ R0 r+ Qcious puberty in boys also results from inappropriate8 F" k, ]5 x, v0 E2 N
androgenic stimulation from either endogenous or
3 \6 \/ t, v3 g C1 V+ sexogenous sources, nonpituitary gonadotropin stim-
' c, P9 \( g# \+ Hulation, and rare activating mutations.3 Virilizing
" r' r' w$ F# z' }) B$ Mcongenital adrenal hyperplasia producing excessive
2 P1 K( M0 c) W. m6 Dadrenal androgens is a common cause of precocious
4 W2 p9 X* e# p* z& g( |* Qpuberty in boys.3,4
9 \4 b1 H7 H6 u* p) h0 MThe most common form of congenital adrenal* g! L: P/ p4 \6 U$ c7 V, { A
hyperplasia is the 21-hydroxylase enzyme deficiency.
. o" w; X5 V8 p' b. p; c$ J- XThe 11-β hydroxylase deficiency may also result in
4 Q' e6 }' _8 ^% Y" p4 y4 ^6 e/ Eexcessive adrenal androgen production, and rarely,
$ u' F2 B. O$ c& ]an adrenal tumor may also cause adrenal androgen) J8 l. Y' s/ V' S
excess.1,3( x3 r6 P3 g# f- l; `$ c8 ?
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from2 U# R7 p2 k, z; |0 J+ Z+ l
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007* _5 M( ^, C1 Q8 l0 Y
A unique entity of male-limited gonadotropin-
' m4 w2 }( {' C/ ?) Pindependent precocious puberty, which is also known
0 t+ G+ I! z# O8 Aas testotoxicosis, may cause precocious puberty at a% I2 U3 l% o, ^) ?. h
very young age. The physical findings in these boys
S& s: t( A3 hwith this disorder are full pubertal development,& J7 B/ K, [9 @' }' |
including bilateral testicular growth, similar to boys' G' u/ H# N# o8 j/ ]
with CPP. The gonadotropin levels in this disorder
% e# b. ~) J/ jare suppressed to prepubertal levels and do not show) d$ l0 c0 Z$ J* N) T, P, l) z
pubertal response of gonadotropin after gonadotropin-8 W( U' t1 C% A! b
releasing hormone stimulation. This is a sex-linked' |1 j" s; r% P! J5 Q0 ^$ q3 Q. s
autosomal dominant disorder that affects only+ ~# ~1 `) M( O" N7 r* @+ b
males; therefore, other male members of the family
5 b9 g1 \" m9 ^, }5 }' A- V- n0 Umay have similar precocious puberty.3' @7 M7 k- f$ R/ p% e/ D
In our patient, physical examination was incon-
& A9 u3 l2 l" t, b( i1 C; {% Asistent with true precocious puberty since his testi-, H, c) P* M* m. P. K# V
cles were prepubertal in size. However, testotoxicosis# h% z! {/ K6 n! F; `+ N: p0 z
was in the differential diagnosis because his father
: z/ `2 R5 x7 M% F9 v+ ?. h/ [started puberty somewhat early, and occasionally,& f/ y3 d% ?4 G$ b: l) P
testicular enlargement is not that evident in the
$ }, Z4 L6 {: k- p" p7 Mbeginning of this process.1 In the absence of a neg-; A) q h4 e4 E s
ative initial history of androgen exposure, our7 z1 e( S. I. e/ u
biggest concern was virilizing adrenal hyperplasia,
: O0 A2 Y) ~: ^/ G9 _either 21-hydroxylase deficiency or 11-β hydroxylase8 y) n" X0 @5 V9 Y) E
deficiency. Those diagnoses were excluded by find-
" j" q7 z. l3 w: U9 \" Ping the normal level of adrenal steroids.
" n& z' |& \% S: U6 q/ j2 W! NThe diagnosis of exogenous androgens was strongly0 K$ z* o( s3 h! x3 Z' x* y
suspected in a follow-up visit after 4 months because1 c6 L9 H' |* w- L- w
the physical examination revealed the complete disap-0 L3 r7 ^+ A. Y" C
pearance of pubic hair, normal growth velocity, and3 e% r0 ]# r* ?. [
decreased erections. The father admitted using a testos-
Z6 E7 Z; |, p) l& I, Q; ~terone gel, which he concealed at first visit. He was
2 `& Y6 q; x8 t! dusing it rather frequently, twice a day. The Physicians’
$ [' \7 x7 }: j+ qDesk Reference, or package insert of this product, gel or, a' V' O' }% M4 L
cream, cautions about dermal testosterone transfer to9 j6 d" p$ G) T0 I3 |9 q& Q( C. Q
unprotected females through direct skin exposure.6 b. u& d) j! R6 A8 E6 A
Serum testosterone level was found to be 2 times the+ n+ r9 E3 g r$ N6 p2 X
baseline value in those females who were exposed to5 }5 b/ ^: ~2 N" w/ ]
even 15 minutes of direct skin contact with their male
8 C- B( j, n/ L4 r) N; Mpartners.6 However, when a shirt covered the applica-
3 c6 I: R6 ^% k$ T/ G7 Ytion site, this testosterone transfer was prevented.$ Z; e; E/ @! O6 ?+ P8 K" r4 R+ ~
Our patient’s testosterone level was 60 ng/mL,
; d% L# M4 [4 F& q6 G) F9 u; qwhich was clearly high. Some studies suggest that: N, k) N& R% X0 E% v& k$ o1 [, w
dermal conversion of testosterone to dihydrotestos-
- @' d# d# s! I5 @2 A8 |& Nterone, which is a more potent metabolite, is more
% e: n5 i% w9 ?active in young children exposed to testosterone
" M: q5 K. T5 y' Z: P+ qexogenously7; however, we did not measure a dihy-. Z- l( O! g" [
drotestosterone level in our patient. In addition to2 P- c& o- L( {3 |9 z, X
virilization, exposure to exogenous testosterone in6 U9 f3 Y8 Z( v- X2 T
children results in an increase in growth velocity and
9 N; ?" ~- O1 g6 Z$ {advanced bone age, as seen in our patient.- s7 h( w+ l: Y
The long-term effect of androgen exposure during5 o1 d: ^! f% ?: g& A" {- ?
early childhood on pubertal development and final2 t/ o6 [. \$ b& M, O. ]" p
adult height are not fully known and always remain3 a. M) C# b. Y
a concern. Children treated with short-term testos-
6 f2 D8 r1 w, J: jterone injection or topical androgen may exhibit some
$ X( k' m& v3 [* A9 ?. a, a9 G0 D& v; h Hacceleration of the skeletal maturation; however, after
- G4 W% N6 L* t4 ycessation of treatment, the rate of bone maturation
% E) j3 M$ s1 Y, Z% `; \decelerates and gradually returns to normal.8,94 C& ? M) s8 y g/ y9 k: L
There are conflicting reports and controversy
$ F' g3 [: k( u' d9 X; d& u. ]) P- Cover the effect of early androgen exposure on adult" }6 O) X: ?8 v$ X% C
penile length.10,11 Some reports suggest subnormal; c5 N+ |9 w: ]
adult penile length, apparently because of downreg-( T1 _' f8 F, h) ]: w- ]6 H7 d
ulation of androgen receptor number.10,12 However,
( }$ L% A* U+ z/ WSutherland et al13 did not find a correlation between% X2 S; p+ B5 l [) Y
childhood testosterone exposure and reduced adult
6 a& z! N- @0 L" ^+ ]penile length in clinical studies.- F9 S5 ] }! M& v' K
Nonetheless, we do not believe our patient is4 g$ ]( D- w" e5 _. w& s
going to experience any of the untoward effects from
% e# [0 k* n3 O7 I! Q7 ?/ atestosterone exposure as mentioned earlier because
% e, j; y( w) |) d" Zthe exposure was not for a prolonged period of time.
" H3 T" c& r E9 E4 u4 U7 cAlthough the bone age was advanced at the time of
0 r6 o. m- I5 }5 S/ Idiagnosis, the child had a normal growth velocity at* d4 Z2 ~3 u! j+ z ~1 I0 f+ I9 ?
the follow-up visit. It is hoped that his final adult" u! N: l0 w) Y5 p4 O
height will not be affected.. r$ Q# i" }: L( y
Although rarely reported, the widespread avail-
$ p5 a# z0 ]- G7 Iability of androgen products in our society may# n, L" Z2 c5 H# V% }
indeed cause more virilization in male or female
( T6 P9 T5 p0 O- c. O3 lchildren than one would realize. Exposure to andro-
' `+ D# j: m0 U. c3 j) fgen products must be considered and specific ques-
+ d+ m3 p V& `/ x! n, }2 X0 }tioning about the use of a testosterone product or
1 T: Y G* _+ Zgel should be asked of the family members during
* f9 j' t8 N) S+ b3 athe evaluation of any children who present with vir-
6 Z2 A( l+ x. e" [( x3 dilization or peripheral precocious puberty. The diag-7 I' ~# D! [) ^+ K) [* k- w/ \
nosis can be established by just a few tests and by5 K0 ^6 U3 @+ U9 d0 C
appropriate history. The inability to obtain such a# G* A: Y9 _; f
history, or failure to ask the specific questions, may
( v3 C# C! z6 P- E: x$ p, Mresult in extensive, unnecessary, and expensive
6 x- Y" ?4 _5 U# f" Z- uinvestigation. The primary care physician should be" H, ]5 v8 H5 \! ~1 B
aware of this fact, because most of these children; ]+ t8 s7 z) x4 K+ c
may initially present in their practice. The Physicians’
l& e% D* N1 H9 XDesk Reference and package insert should also put a
( I1 O% }% b* Q) T4 Q$ H8 }warning about the virilizing effect on a male or9 I7 l3 w' @+ C
female child who might come in contact with some-3 B! b, H, ? s$ z0 o
one using any of these products.
5 c* ^0 D. t& R2 n, bReferences
. M" U" K# b5 x: W$ f" @1. Styne DM. The testes: disorder of sexual differentiation. Z. F: G6 w9 h
and puberty in the male. In: Sperling MA, ed. Pediatric! c. m5 N/ G% `: E
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
" M/ ]+ y( X6 U+ B8 E4 P2002: 565-628.5 k' H5 [) `% X5 H7 `) ^& _
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
& `% U, r# r% C5 s0 f: Ppuberty in children with tumours of the suprasellar pineal |
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