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Sexual Precocity in a 16-Month-Old) ^- e, C6 }/ X. a! z2 ]
Boy Induced by Indirect Topical
) k9 e. q6 u, ^Exposure to Testosterone: E, x4 h4 V) r' n9 @
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2+ w5 D9 D: w* E3 T' N# _- w) b( {
and Kenneth R. Rettig, MD1
3 ]& O. v- i) U7 _; m& v }Clinical Pediatrics0 m/ w; g. Z6 U5 {; x1 c
Volume 46 Number 6
: A- {: E; k) c8 dJuly 2007 540-543! @9 R+ _$ j! ]2 p; m) W- R9 a
© 2007 Sage Publications7 \8 A, Y, k0 H U
10.1177/00099228062966517 Z; P2 B9 h( P* a; |
http://clp.sagepub.com( b2 ^1 K/ q/ b/ w+ Q
hosted at
0 ^! h: u# h1 p: O+ |3 r+ shttp://online.sagepub.com m" e; W+ f$ u0 _3 o
Precocious puberty in boys, central or peripheral," f; F5 w- l4 ]9 ?
is a significant concern for physicians. Central
$ `& a- ]" k6 M# _( }" \" gprecocious puberty (CPP), which is mediated
6 Q% K6 T" W$ i1 s* Y; Cthrough the hypothalamic pituitary gonadal axis, has
9 s3 h r8 @* [9 Y' Xa higher incidence of organic central nervous system d, \% p, Y0 c0 V8 ?
lesions in boys.1,2 Virilization in boys, as manifested+ c7 ~2 D0 i0 V7 f# G$ \2 D
by enlargement of the penis, development of pubic6 J+ p( d' k U7 O
hair, and facial acne without enlargement of testi-
H- X/ r- O" p' z, z* Wcles, suggests peripheral or pseudopuberty.1-3 We: U4 \2 M( b" _ _, ^1 V: J; H
report a 16-month-old boy who presented with the
0 [2 h+ U* W6 m. Z1 n H7 y' b# Eenlargement of the phallus and pubic hair develop-
3 R& s3 K7 o8 a! O& h7 s+ w& `; }ment without testicular enlargement, which was due) b# W+ s' }- A
to the unintentional exposure to androgen gel used by1 z5 m1 ^( {9 b. Z: G+ E
the father. The family initially concealed this infor-% l6 C4 \- t. O7 F+ N2 |
mation, resulting in an extensive work-up for this
' `8 x& ~9 W( x0 u- I nchild. Given the widespread and easy availability of
. e" M7 A. ]. i( M/ n* ~( a$ ptestosterone gel and cream, we believe this is proba-7 U8 S. h& C) [' }- p' O2 ]
bly more common than the rare case report in the
2 O( f% i7 w9 b. `literature.4( ^& s, E& z% y. u q3 ?) q
Patient Report1 }: ?0 M9 `8 Z& j- }! A
A 16-month-old white child was referred to the
* r1 M8 [2 U1 f& Mendocrine clinic by his pediatrician with the concern
/ e) W0 f- E+ Oof early sexual development. His mother noticed1 k; b( }) d2 Q
light colored pubic hair development when he was
6 Q/ s0 |# h6 U% @& j& lFrom the 1Division of Pediatric Endocrinology, 2University of
7 T u1 P0 `3 R; C" l8 uSouth Alabama Medical Center, Mobile, Alabama.
! u& K8 C% i4 R v) o9 }Address correspondence to: Samar K. Bhowmick, MD, FACE,
) @ Q6 _6 ^7 Q. e0 QProfessor of Pediatrics, University of South Alabama, College of! n% R k# ]" D7 H
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;4 K4 F% ?" q; \2 K( s
e-mail: [email protected].
( O$ I8 B4 ~' w8 Iabout 6 to 7 months old, which progressively became; M/ O, j( F: o4 Z
darker. She was also concerned about the enlarge-# D- ~+ ^ H5 Z$ E. T0 ?
ment of his penis and frequent erections. The child k# `8 C% n/ F$ k# a) C: n
was the product of a full-term normal delivery, with+ W6 Y' g. }* L" B- |
a birth weight of 7 lb 14 oz, and birth length of
( N7 [0 l1 p8 ]& Y1 e' p20 inches. He was breast-fed throughout the first year
5 ]/ R! s) M. C' a3 [# Zof life and was still receiving breast milk along with' j o, k+ W% y1 I1 b
solid food. He had no hospitalizations or surgery,! V6 j6 h: E! E
and his psychosocial and psychomotor development
# b, v3 `- x' z, O+ X' C3 s7 K/ Swas age appropriate.) }- C& n6 r, [1 ^+ D! i
The family history was remarkable for the father,0 A7 q0 x/ m1 o6 M. D) n5 h
who was diagnosed with hypothyroidism at age 16,
; i. r9 f. j4 C- t1 H/ j6 f: S. Ewhich was treated with thyroxine. The father’s
; d8 a* n% a$ L% {height was 6 feet, and he went through a somewhat
- ~& F4 z: v2 ~2 z1 A" bearly puberty and had stopped growing by age 14.9 Z* p6 P' |- V) s3 X; c8 g
The father denied taking any other medication. The) ^2 e6 T4 P: t& ^5 W5 z
child’s mother was in good health. Her menarche
4 ?1 ]+ C, f b: [8 \2 twas at 11 years of age, and her height was at 5 feet0 o( H5 o& j2 R4 ?, G
5 inches. There was no other family history of pre-" r) g/ a7 d# {
cocious sexual development in the first-degree rela-( ]. h1 L* y# \4 I9 D
tives. There were no siblings.
9 q3 p, j0 U& R e" E. H2 BPhysical Examination( _) F& F/ O3 e7 V, ?% L7 c2 {0 f
The physical examination revealed a very active,6 s D/ k7 x g6 G, M' e# n
playful, and healthy boy. The vital signs documented
7 t7 e9 @$ ?" H( G; ?" |, `5 ?4 Za blood pressure of 85/50 mm Hg, his length was
$ P% c t- H( x& y: x90 cm (>97th percentile), and his weight was 14.4 kg) N3 e5 ]& t9 J( n! [. ~# U% n+ j( s
(also >97th percentile). The observed yearly growth3 q" X7 A( x# h! r0 j! T% Y+ w
velocity was 30 cm (12 inches). The examination of
8 C* Z2 X9 ^5 Y% s7 t2 o6 D: zthe neck revealed no thyroid enlargement.
- S% b+ z3 s& q6 n: @; w: fThe genitourinary examination was remarkable for U* n4 e4 b. W& K% Q
enlargement of the penis, with a stretched length of
! C6 F+ d8 l) K0 K8 cm and a width of 2 cm. The glans penis was very well1 }" ?2 G# Z2 n1 J
developed. The pubic hair was Tanner II, mostly around
2 n! b) Y8 F" p- D) Q5408 `3 k2 L; I0 i* x- t1 B
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
8 f4 t; }. V" c6 H) O1 xthe base of the phallus and was dark and curled. The- F5 Q' j7 A# Y4 A& O: U: D8 {! g
testicular volume was prepubertal at 2 mL each., B; Z8 m& C5 c
The skin was moist and smooth and somewhat4 C% y5 `& y4 ]& K0 X4 n
oily. No axillary hair was noted. There were no4 K3 \8 V- [3 c# n5 k7 @& u4 I
abnormal skin pigmentations or café-au-lait spots.
* ?1 o$ i; ?; f) f! O: e) ?Neurologic evaluation showed deep tendon reflex 2+5 c, P J* L6 x+ I/ W2 X
bilateral and symmetrical. There was no suggestion
4 j" T6 `/ o. o$ Gof papilledema.0 { n1 b: {; L# b- z% h
Laboratory Evaluation
. _2 n3 C( x3 d6 dThe bone age was consistent with 28 months by8 `' u. s$ L9 T" S' Z) d
using the standard of Greulich and Pyle at a chrono-
7 c3 J4 u6 Y' ?logic age of 16 months (advanced).5 Chromosomal
* n9 q& a4 y3 c6 o% }+ E2 \karyotype was 46XY. The thyroid function test }/ h/ D( ?' h/ N. A/ s. @
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
7 G( ^2 F' S0 w3 A4 |! I+ e1 ulating hormone level was 1.3 µIU/mL (both normal).
2 V1 ~. _+ L0 i6 D# gThe concentrations of serum electrolytes, blood
3 I* @0 A' X( C# z, L$ I3 m7 turea nitrogen, creatinine, and calcium all were6 g P( U3 c. |+ \
within normal range for his age. The concentration- o! P2 x2 v. O7 ~8 V, G
of serum 17-hydroxyprogesterone was 16 ng/dL) B" @6 h( H/ C" \- T+ q; L$ B
(normal, 3 to 90 ng/dL), androstenedione was 20
, J, [9 `2 j* W4 L3 ~ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
+ J: d8 B( s2 W0 L8 Pterone was 38 ng/dL (normal, 50 to 760 ng/dL),
$ f! i+ |! v2 ]' G9 V$ vdesoxycorticosterone was 4.3 ng/dL (normal, 7 to
0 L8 w% j, D c$ s) t2 [' s49ng/dL), 11-desoxycortisol (specific compound S)1 O9 b8 {+ a( ^; Y1 H) X
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-2 B# u9 ~; D" W9 \; _: m- B/ \
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
; e8 D. ~& {% ]+ N6 F0 Ktestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
3 V+ N, J; `' G! \ ~# n9 rand β-human chorionic gonadotropin was less than8 w; M* |/ [1 R# I- q( J; B. u
5 mIU/mL (normal <5 mIU/mL). Serum follicular9 D x# q f) y% H: C. y) M" q
stimulating hormone and leuteinizing hormone
6 m* |" T$ r9 P" X' c: j, X9 ^( Kconcentrations were less than 0.05 mIU/mL
7 P! f( O, I6 ^8 b(prepubertal).
" Q7 E% z2 ^" e. T9 oThe parents were notified about the laboratory
$ Q9 e- v1 _: X8 A1 u4 qresults and were informed that all of the tests were
% f5 V9 ^0 M: E1 I" h2 ynormal except the testosterone level was high. The: V. i% ~$ @- O4 o8 y
follow-up visit was arranged within a few weeks to
1 l1 g8 } [5 G' h5 f8 w+ w1 O8 bobtain testicular and abdominal sonograms; how-" m- c! K* T3 E# @
ever, the family did not return for 4 months.
% }* v! l$ `) U/ N5 ?2 WPhysical examination at this time revealed that the
' {- V4 ?( ?" c( S- I* tchild had grown 2.5 cm in 4 months and had gained
& R' N: c* S7 k! t2 kg of weight. Physical examination remained
* H# m: z* c' j: F( N& ^unchanged. Surprisingly, the pubic hair almost com-
: {; d: B5 f- c. X9 ~pletely disappeared except for a few vellous hairs at$ _+ v. F2 ]6 Q; J) Q
the base of the phallus. Testicular volume was still 2
3 }! A% k, N+ ?! {5 zmL, and the size of the penis remained unchanged., q; ?% [- Z9 c$ T7 ?/ U% l
The mother also said that the boy was no longer hav-. q4 J# e& Y3 F! t- {: H
ing frequent erections.
- r& `7 G& t; y3 [% J( O- Y2 NBoth parents were again questioned about use of1 ?" x4 K" Y' E6 F# [# p2 \+ O
any ointment/creams that they may have applied to
+ B0 {8 g+ C2 b2 j Gthe child’s skin. This time the father admitted the
( w& _/ u5 x0 _' Y4 {9 u. BTopical Testosterone Exposure / Bhowmick et al 541: M& W/ b1 t3 E* U G2 `0 h
use of testosterone gel twice daily that he was apply-" N: r, V8 ?: h" p+ T# P
ing over his own shoulders, chest, and back area for9 S2 Z$ S7 j, J/ }
a year. The father also revealed he was embarrassed! P) _( o6 u( A) j; O
to disclose that he was using a testosterone gel pre-
3 }- B1 r7 a$ r" \+ J0 w, ?scribed by his family physician for decreased libido% g. I; R3 Q. i) ?+ \; p8 D7 q& b
secondary to depression. n( c% r+ l0 I
The child slept in the same bed with parents.
( z% t& b2 B+ P" F. lThe father would hug the baby and hold him on his
, f) m7 S. S# J; D8 Schest for a considerable period of time, causing sig-
# ^' ^% x% h# R4 cnificant bare skin contact between baby and father.
& i T2 G" p @- l0 DThe father also admitted that after the phone call,
. a. S8 U% ~2 x/ h4 P5 R" g# Wwhen he learned the testosterone level in the baby: p8 ~' S6 {1 c% {. P; {* w H
was high, he then read the product information: ] w* e ~8 L. J M& f- f+ C
packet and concluded that it was most likely the rea-
6 ]" Z" [! l: w4 j! Bson for the child’s virilization. At that time, they
3 A" }. g M5 E' D# m, v6 mdecided to put the baby in a separate bed, and the
0 h# b5 I# E. P x4 ^* Ofather was not hugging him with bare skin and had" Y7 a4 q* e, D
been using protective clothing. A repeat testosterone: `, n0 g8 x3 }# E; ~ l( Y6 E
test was ordered, but the family did not go to the
3 L0 W. l- t- @0 xlaboratory to obtain the test.! U9 h2 w' {1 P, @. `. [0 n0 ?) W0 T
Discussion
# \0 K1 P+ [. T/ [% Z& I5 WPrecocious puberty in boys is defined as secondary
5 }" h, I X: H$ h. O4 v; ssexual development before 9 years of age.1,4
# y' Y( r7 E0 Q$ |9 H) HPrecocious puberty is termed as central (true) when$ V- f2 n4 ~( D. ~! E" H8 Q5 q; q9 C
it is caused by the premature activation of hypo- V- x% I& X% _/ Y( e
thalamic pituitary gonadal axis. CPP is more com-
8 Z& f2 K# o' w4 ^. |mon in girls than in boys.1,3 Most boys with CPP
3 m' p) W; A+ B) F8 e* t1 u; fmay have a central nervous system lesion that is' |' v# I& E: W; w) E5 v
responsible for the early activation of the hypothal-
$ n% T' y }8 s6 ]6 v8 zamic pituitary gonadal axis.1-3 Thus, greater empha-
: T9 R# _. `9 D$ lsis has been given to neuroradiologic imaging in
# ~3 E3 C g. h ?' tboys with precocious puberty. In addition to viril-
* {+ @7 d) f2 H8 ~ization, the clinical hallmark of CPP is the symmet-
* p4 N: s- R. [2 C. l2 B+ c8 frical testicular growth secondary to stimulation by
; B) u. M& H& R) q: p' c/ Egonadotropins.1,3
9 \7 G2 e% M) W/ S6 x% t, \Gonadotropin-independent peripheral preco-) C8 G2 w0 V" P7 p2 N9 `
cious puberty in boys also results from inappropriate' T6 x# F, j8 F& b0 X
androgenic stimulation from either endogenous or
P8 i4 o; j- D" l% T/ p( Xexogenous sources, nonpituitary gonadotropin stim-
; D D* \) s6 T" i uulation, and rare activating mutations.3 Virilizing& K2 S6 l" `1 M& F3 Z# g
congenital adrenal hyperplasia producing excessive
/ E0 S, l2 m) i; O4 ^7 oadrenal androgens is a common cause of precocious
# ^; s. ? K0 t7 e/ \puberty in boys.3,43 L9 Z/ U0 ~( F1 B
The most common form of congenital adrenal
( U$ u7 k& w9 Zhyperplasia is the 21-hydroxylase enzyme deficiency.
. c& g- Q; L% s" F* gThe 11-β hydroxylase deficiency may also result in$ [( `% `3 m; q
excessive adrenal androgen production, and rarely,, Y3 i4 ?1 H! _- k5 ? d
an adrenal tumor may also cause adrenal androgen" o* n" W( S7 }' ?, K
excess.1,3/ |( ~3 A: I4 w8 p3 \+ s2 K
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
& P" C ]2 x. e6 d8 I) T c542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
# e3 j; q% c, H$ o( V* [A unique entity of male-limited gonadotropin-$ u' Y4 q* c' A# Y( i& B8 V
independent precocious puberty, which is also known+ d, o; {4 |5 x# C/ @
as testotoxicosis, may cause precocious puberty at a, X M& C' @; v
very young age. The physical findings in these boys R" `9 n( z0 h, a
with this disorder are full pubertal development,# G# n' k% d" Y5 f, a! D1 s: B' z
including bilateral testicular growth, similar to boys
5 z1 ?. V& M D, W" t! r' \with CPP. The gonadotropin levels in this disorder) k5 ]4 ?, F9 X1 Z- \' B
are suppressed to prepubertal levels and do not show, L8 l1 I9 [8 {6 M- F9 Z
pubertal response of gonadotropin after gonadotropin-0 q3 n4 G0 t' P
releasing hormone stimulation. This is a sex-linked
+ F" K) e6 i8 H4 s- c8 E' y. rautosomal dominant disorder that affects only
6 B3 E; P( E; H& Vmales; therefore, other male members of the family/ z( d; \$ {; d0 W8 F4 ` K
may have similar precocious puberty.3
. I* _& X7 ~# s- K6 J! O9 _9 dIn our patient, physical examination was incon-0 o( g- _( m/ y- d
sistent with true precocious puberty since his testi-
5 ^3 H. i: x$ Wcles were prepubertal in size. However, testotoxicosis) ?0 c6 g/ q. O- [
was in the differential diagnosis because his father
' ^: i) `4 K, v$ ~( h3 Tstarted puberty somewhat early, and occasionally,) A8 ^% {/ N) e, G. T- E
testicular enlargement is not that evident in the
- S* c% o, r+ a) wbeginning of this process.1 In the absence of a neg-
! Y1 h* {! |! ?- M7 u4 b; B9 J5 Aative initial history of androgen exposure, our
9 R+ f( B; o& b* g4 Sbiggest concern was virilizing adrenal hyperplasia,
$ G) ]- {# [) S# n. D l: n7 Teither 21-hydroxylase deficiency or 11-β hydroxylase
8 ]2 ?8 B* |* P' X" m0 ddeficiency. Those diagnoses were excluded by find-
|; q5 D4 M7 b3 I3 `6 `- qing the normal level of adrenal steroids.
8 n3 M" O% G# |The diagnosis of exogenous androgens was strongly/ E: X5 z6 W( ]: ]7 _6 R; ~
suspected in a follow-up visit after 4 months because
! \" [) Y2 G0 p4 Ethe physical examination revealed the complete disap-
2 Y5 A- \: q4 b) @% @7 Opearance of pubic hair, normal growth velocity, and; o+ {* ~- a8 x% V C
decreased erections. The father admitted using a testos-& Q. l, ~) X# I. h3 U
terone gel, which he concealed at first visit. He was/ l/ y9 b6 K7 u" K/ v
using it rather frequently, twice a day. The Physicians’) ~! q d6 R2 E4 F( k6 r7 r4 U
Desk Reference, or package insert of this product, gel or% U! I1 Z z* t
cream, cautions about dermal testosterone transfer to* r2 j- Q, |% _) V3 @: b. h
unprotected females through direct skin exposure.6 i- E& m2 H3 f: ]* [6 g
Serum testosterone level was found to be 2 times the
! E C4 {' ~. O' y& {3 n" Ybaseline value in those females who were exposed to
+ g$ }) B* y2 y6 c `9 yeven 15 minutes of direct skin contact with their male0 c9 x5 l# M; {+ X$ S5 f
partners.6 However, when a shirt covered the applica-4 |9 |4 b! ]9 U% w
tion site, this testosterone transfer was prevented.
5 X! i5 }7 d o+ j: V. ]& z4 `% cOur patient’s testosterone level was 60 ng/mL,
( d9 O+ Z$ m. P2 x; S$ Dwhich was clearly high. Some studies suggest that
1 F. d, n. C/ P* U: ^+ _dermal conversion of testosterone to dihydrotestos-" ]( E# ^& ?/ y2 R( q
terone, which is a more potent metabolite, is more0 H3 m- N% h9 B: ?# e+ F; w
active in young children exposed to testosterone
$ c- m0 ^* i u9 I! jexogenously7; however, we did not measure a dihy-
! P! u/ j( S: t) s9 wdrotestosterone level in our patient. In addition to
2 N' e% ?. M2 B& X5 f& S) M- |virilization, exposure to exogenous testosterone in9 V0 d) q k" ~4 W1 i* L' l' l
children results in an increase in growth velocity and- ]5 E; t- z9 {# t2 g S
advanced bone age, as seen in our patient.6 d* v3 y1 L$ {! F) E* K# _
The long-term effect of androgen exposure during" L8 h' K. p4 K
early childhood on pubertal development and final" O/ c$ c$ g) T
adult height are not fully known and always remain1 K& v; K4 c4 O n4 o. ^
a concern. Children treated with short-term testos-
4 |* i) k2 [% Z: a: |9 t7 qterone injection or topical androgen may exhibit some, V- [8 A; L6 P1 i5 G
acceleration of the skeletal maturation; however, after
4 x% c8 e q% h- c; r, z; Mcessation of treatment, the rate of bone maturation/ e. Z/ H o3 r* o9 a
decelerates and gradually returns to normal.8,9, R3 M% g8 _, q
There are conflicting reports and controversy
7 B) ?+ u% M' q* ^: tover the effect of early androgen exposure on adult
! ?# E; r8 Y6 I; ?/ f- [, }( Ppenile length.10,11 Some reports suggest subnormal& N6 [8 M, g8 H/ w
adult penile length, apparently because of downreg-
$ R! t2 ?+ u7 C! Aulation of androgen receptor number.10,12 However," M- i0 f! ^6 M4 C
Sutherland et al13 did not find a correlation between/ t# \7 V$ Y8 n
childhood testosterone exposure and reduced adult: ^5 @: i+ B6 J. n P
penile length in clinical studies.
5 m0 w# I% w2 c9 F# {Nonetheless, we do not believe our patient is
9 F9 v( u$ t$ |8 e! Jgoing to experience any of the untoward effects from
+ q* B3 C1 o4 Q. j. A+ `! Y( Z% ptestosterone exposure as mentioned earlier because
( z3 v% b; o5 r/ r3 l0 L* Gthe exposure was not for a prolonged period of time. E1 u2 J9 @* m- }( I
Although the bone age was advanced at the time of
s6 e7 u: u# \6 V3 ?diagnosis, the child had a normal growth velocity at$ a% Y3 J0 p9 [2 V4 l/ C
the follow-up visit. It is hoped that his final adult. e$ E7 t8 l# \8 v2 C6 b
height will not be affected.
5 X/ A0 J" w8 Z s( w8 I8 v9 P# bAlthough rarely reported, the widespread avail-
6 ]+ E! B( X$ n, D0 aability of androgen products in our society may
/ _% c) ]# @5 A4 `4 iindeed cause more virilization in male or female
' h, W- X6 [$ \- t; l) p$ [; {children than one would realize. Exposure to andro-$ V7 |2 p5 |7 o) L! d; H9 f% \8 ^ F
gen products must be considered and specific ques-0 b1 f" {5 U/ W2 Q8 D6 w/ R
tioning about the use of a testosterone product or+ e+ @4 u0 P: y
gel should be asked of the family members during2 T% i( {0 `- _2 ^$ C# x# ^3 Q% o
the evaluation of any children who present with vir-
+ F y2 U* }6 E: Y ailization or peripheral precocious puberty. The diag-
, a% z( n3 _+ ]# Onosis can be established by just a few tests and by: r, t! r H% {3 X' W
appropriate history. The inability to obtain such a
; y' _) w% F3 t7 p7 X/ ihistory, or failure to ask the specific questions, may% ~+ o' n2 j* |0 v6 q
result in extensive, unnecessary, and expensive
* b, O* H- d: n( d7 Ninvestigation. The primary care physician should be
: v& G( a" Z; F! n, Raware of this fact, because most of these children3 t# V; q2 t# R8 O, j4 k9 y
may initially present in their practice. The Physicians’
( i9 C% T m: `/ B J0 lDesk Reference and package insert should also put a
% B; y+ _4 W" I2 x8 {, Jwarning about the virilizing effect on a male or
# [2 }! A; d+ u: [6 M' Qfemale child who might come in contact with some-
8 [: E1 `) d4 d4 Y3 b2 tone using any of these products.
y% l& M: t/ Z! }7 q7 F. n; IReferences* U5 r8 S M( e- c- j
1. Styne DM. The testes: disorder of sexual differentiation
, R: P* l! i3 oand puberty in the male. In: Sperling MA, ed. Pediatric3 t+ w: {! n; j. n/ }
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;7 R3 U) O! p6 H0 W8 e! c
2002: 565-628.
4 h, `6 N& {! f( t2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
& X' m# @1 y+ N# ^! }0 g: Fpuberty in children with tumours of the suprasellar pineal |
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