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Sexual Precocity in a 16-Month-Old( o3 L3 j: M6 r, F) h& |2 i2 M
Boy Induced by Indirect Topical& V% I# K9 }, w8 V
Exposure to Testosterone0 [! q) W2 O9 ~/ ~; i! h9 s; U3 s
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2+ Q' }$ y5 O. J! R1 J
and Kenneth R. Rettig, MD1+ P: k7 [' ^7 w5 {6 v( z
Clinical Pediatrics
" T7 n( h7 f+ j) {, RVolume 46 Number 6
7 w& j, K! C6 }5 u$ wJuly 2007 540-543& [, y. X$ }7 j3 Y4 f9 b
© 2007 Sage Publications* p, ?/ a1 p- W7 \2 ^; F' _$ l
10.1177/0009922806296651
$ u' Z+ v5 j! K* ~http://clp.sagepub.com
1 x7 i4 B# S0 ]hosted at: h q1 n/ k, Z/ G5 q
http://online.sagepub.com8 J% {8 I9 M* V( w
Precocious puberty in boys, central or peripheral,) p5 y& _# l& U
is a significant concern for physicians. Central2 M& f1 S) H. W5 a
precocious puberty (CPP), which is mediated
, P# @" |0 Q5 T& T. ^- k$ ?; Y+ P7 Athrough the hypothalamic pituitary gonadal axis, has$ ^3 g, X8 x$ g2 {4 K8 C1 x
a higher incidence of organic central nervous system
! K& F0 V+ h0 Z: llesions in boys.1,2 Virilization in boys, as manifested3 r! X% n/ z) `% p/ i2 E$ ` `# e
by enlargement of the penis, development of pubic1 r" U" H! G# b$ u
hair, and facial acne without enlargement of testi-! F5 l5 P6 K% `! T6 A7 ?
cles, suggests peripheral or pseudopuberty.1-3 We
( i2 Y$ o4 H# `# @report a 16-month-old boy who presented with the
# P, I- h: t: a4 `; Yenlargement of the phallus and pubic hair develop-
B8 t& s# V" K& g4 Jment without testicular enlargement, which was due
/ F8 w X! l3 rto the unintentional exposure to androgen gel used by6 y( Z2 F! v" C) I
the father. The family initially concealed this infor-; j. b4 O; u7 I8 Y
mation, resulting in an extensive work-up for this* x; y: ~5 W& H
child. Given the widespread and easy availability of; \% p' ^ d# n/ [1 [ u
testosterone gel and cream, we believe this is proba-0 n# r) ^- i" {1 H
bly more common than the rare case report in the
; r' H; c5 R/ B2 M! sliterature.4
' C$ T0 \! c6 F) aPatient Report
2 f* B& H7 \1 K0 J8 X* d: rA 16-month-old white child was referred to the
8 i% F$ ]5 [: _ X* M! Y+ X; c* Gendocrine clinic by his pediatrician with the concern
" w1 R( @ C& _2 d- C0 g# o! r, wof early sexual development. His mother noticed
; @3 C; }$ P7 X7 c J' ilight colored pubic hair development when he was( I# m. w8 P( M) x( @0 |$ _6 i
From the 1Division of Pediatric Endocrinology, 2University of3 I6 M V4 \% v7 V3 i! K* K
South Alabama Medical Center, Mobile, Alabama." p; Q, |3 t9 Z3 b7 u
Address correspondence to: Samar K. Bhowmick, MD, FACE," {1 m5 s) ^' X$ i. n. a: ] z
Professor of Pediatrics, University of South Alabama, College of
3 z r) A" m5 f9 h2 _9 c" U9 Z& ?Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;& _6 U$ E7 M- b5 M
e-mail: [email protected].0 Y- u' ^& J( b( p# }
about 6 to 7 months old, which progressively became# e6 U2 m! _0 g9 W6 B9 a" p' N
darker. She was also concerned about the enlarge-" n7 s- W; H6 E9 ^( e
ment of his penis and frequent erections. The child
& T2 M7 ]; J" ^1 W: h' b; [( x0 _was the product of a full-term normal delivery, with& Y; H2 Z% M- I. x1 \: B6 J9 T
a birth weight of 7 lb 14 oz, and birth length of
I1 ~/ O) O; t& k20 inches. He was breast-fed throughout the first year2 U5 @$ Z3 s" A# R9 O
of life and was still receiving breast milk along with9 l `! U7 v0 j1 f5 S
solid food. He had no hospitalizations or surgery,. X2 I* r- W3 ^/ U
and his psychosocial and psychomotor development
2 b- t/ M/ n7 h- a5 I! jwas age appropriate.
3 I) U! s% ~/ T0 t/ z. Q' W1 xThe family history was remarkable for the father, ?: x6 G1 k- w8 P" X( N0 }5 a$ L6 {9 I
who was diagnosed with hypothyroidism at age 16,5 E0 ^2 [* ^$ _- ~; H' p4 {
which was treated with thyroxine. The father’s# c* a: |: ^2 J+ `$ ~+ r
height was 6 feet, and he went through a somewhat- Y: f6 P) q' u) _9 E" {2 W/ ~/ ?. b
early puberty and had stopped growing by age 14.
5 w T' k; G: C$ M% Q7 \& _) K2 @+ RThe father denied taking any other medication. The. d% B+ y: Q. z$ I6 `. P# k
child’s mother was in good health. Her menarche
0 H+ \7 I! r- s& A% U5 D Vwas at 11 years of age, and her height was at 5 feet7 D# {6 `. q! k( o" ~
5 inches. There was no other family history of pre-
- `2 b3 U: b$ f/ ccocious sexual development in the first-degree rela-6 Y6 x8 a8 d: u& M# q
tives. There were no siblings.
* T' D( ^% {3 K; C- i dPhysical Examination
4 [4 K9 J/ v9 n! {) tThe physical examination revealed a very active,( `' S d$ j, v2 G+ [
playful, and healthy boy. The vital signs documented+ `: T+ _. H4 q5 S2 J# P
a blood pressure of 85/50 mm Hg, his length was' U" N, y: x, y- c: |5 m4 x; [
90 cm (>97th percentile), and his weight was 14.4 kg# \, x# e' o' R/ b" q
(also >97th percentile). The observed yearly growth
. M" B2 V1 h/ E9 I2 g" d/ pvelocity was 30 cm (12 inches). The examination of/ ~6 o6 i! T+ J! Q- T
the neck revealed no thyroid enlargement.
" t% C v' P$ ~4 j5 H1 b5 uThe genitourinary examination was remarkable for
+ G5 b. q6 k8 Y" a5 D, }3 _enlargement of the penis, with a stretched length of
( q$ C+ M8 u, i9 M6 T+ N# Y8 cm and a width of 2 cm. The glans penis was very well
$ N4 ^" Z; P- Y8 Y! i4 bdeveloped. The pubic hair was Tanner II, mostly around
) b7 M; w3 H/ {2 x5404 J! c( @, j( H9 R4 q8 v0 W
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from7 [9 t$ Z6 _7 `4 x
the base of the phallus and was dark and curled. The
/ X$ m6 c3 Y+ P6 f5 C$ M* o9 ctesticular volume was prepubertal at 2 mL each.
1 }% G' O2 d1 X$ d1 VThe skin was moist and smooth and somewhat
; b9 g$ g- C- i K' _& E- } [8 Noily. No axillary hair was noted. There were no
7 ^! M# `1 B' |1 Z5 Y5 ^abnormal skin pigmentations or café-au-lait spots.
4 m! g% h P2 f2 {Neurologic evaluation showed deep tendon reflex 2+, k* P2 l( d8 H' U2 n8 g4 H, ^
bilateral and symmetrical. There was no suggestion
! F V2 a* v- }6 X- ]# s. O$ Jof papilledema.0 z( @! |& w; W7 a- D) }* k
Laboratory Evaluation
. a* c5 d8 S' e7 T' DThe bone age was consistent with 28 months by: k% A" @3 l! b4 G! J e4 U
using the standard of Greulich and Pyle at a chrono-9 g3 c0 k% F( O+ W( R! Y
logic age of 16 months (advanced).5 Chromosomal
' n# b& U7 g3 y: j5 m) p1 z4 gkaryotype was 46XY. The thyroid function test8 D3 F" a# w1 R# K9 D, B
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
, X8 n5 F& }) L' |' g; w" Nlating hormone level was 1.3 µIU/mL (both normal).& ^# ?5 v) D1 Y8 g7 E& b7 e
The concentrations of serum electrolytes, blood( m% S. s3 p! A" L$ K' d
urea nitrogen, creatinine, and calcium all were0 V" h2 I1 v1 w6 B$ N
within normal range for his age. The concentration% y+ C5 d# ?+ N# e0 E1 |. H
of serum 17-hydroxyprogesterone was 16 ng/dL
8 _; M5 X% c' Q! K$ B- m(normal, 3 to 90 ng/dL), androstenedione was 205 j1 j7 v: z& ~
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-7 B2 O6 T* r" D( m. P( L0 V+ j
terone was 38 ng/dL (normal, 50 to 760 ng/dL),7 P1 M$ t9 s: ?( R% @. d
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
" U7 e9 q' z4 o& g- M% a* b49ng/dL), 11-desoxycortisol (specific compound S)
1 b0 D; F$ p+ {was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-" O1 j- _) p! \' z; k
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total0 ?+ J4 U& i9 Z# l6 d7 c
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),7 r# m, v8 S0 A A
and β-human chorionic gonadotropin was less than' N# e- M# |6 V9 C: J
5 mIU/mL (normal <5 mIU/mL). Serum follicular2 }+ i1 y$ e8 J. C* @' r5 f
stimulating hormone and leuteinizing hormone
1 u) @, @8 _- h# m" }$ b# Y3 B. [concentrations were less than 0.05 mIU/mL
) O) U; l8 b2 B( \ G t/ T(prepubertal).- m8 K F% l6 T$ u# ]
The parents were notified about the laboratory
1 w$ S; E' A6 b0 F2 @ p* \results and were informed that all of the tests were7 j) ^8 X: ]5 O$ @6 X' t
normal except the testosterone level was high. The& A& \! H4 \5 D5 ~
follow-up visit was arranged within a few weeks to1 ^4 j) `7 r3 |" S' {
obtain testicular and abdominal sonograms; how-
: ^* K* c9 ?: R( ], k/ U/ Yever, the family did not return for 4 months.
. L1 |1 R) Z6 R( R) y4 X5 PPhysical examination at this time revealed that the
* b2 U$ J. N' w) F8 f tchild had grown 2.5 cm in 4 months and had gained
+ S1 L) j. c0 e% l- u2 kg of weight. Physical examination remained
* A/ S0 K, t i( C' _unchanged. Surprisingly, the pubic hair almost com-) j+ k% T. G" f' U8 H0 [! v
pletely disappeared except for a few vellous hairs at+ P# T. [4 T( j2 n" x) \: k. v3 _
the base of the phallus. Testicular volume was still 2
4 K1 o, c0 S4 \: `; m( AmL, and the size of the penis remained unchanged." H- y7 Z0 g# \4 |
The mother also said that the boy was no longer hav-
% d) u5 }+ f7 j6 n% p( C5 D+ {' b! Jing frequent erections.$ b8 [) \" Q9 {2 K3 B! d! Z
Both parents were again questioned about use of+ { U3 r0 G- @" ~3 ?; c
any ointment/creams that they may have applied to& P# n' {* H/ D2 v0 ~5 m, k. V
the child’s skin. This time the father admitted the* V8 G: ]& m+ d' [1 c- p% i
Topical Testosterone Exposure / Bhowmick et al 541& \# J6 R' K! x1 `1 j5 f0 K0 j- u4 w" b
use of testosterone gel twice daily that he was apply-
/ o T! A& Z8 o. l* Iing over his own shoulders, chest, and back area for- O+ L9 G5 y& m0 J+ v% n) t
a year. The father also revealed he was embarrassed
4 i9 c3 q h& X' A1 s( m( @to disclose that he was using a testosterone gel pre-
8 u; L8 q2 r* e3 X4 Hscribed by his family physician for decreased libido* g" E0 T# R C2 q/ T0 H# j
secondary to depression.
. Z# T8 N4 n; X+ d9 I- CThe child slept in the same bed with parents.0 e0 |6 O6 D$ E+ C
The father would hug the baby and hold him on his& u. l# H' m6 l. d6 j8 _
chest for a considerable period of time, causing sig-; n U) l6 }# ?7 M9 e" S
nificant bare skin contact between baby and father.
' H) J: ^9 o7 lThe father also admitted that after the phone call,
, P. @ A5 g2 I6 ?) Ewhen he learned the testosterone level in the baby
* {& V, ^; \+ h( x2 [$ e Z: I9 jwas high, he then read the product information) f) r' u$ I1 E2 U3 ~" I ^, M% w
packet and concluded that it was most likely the rea-
$ S& ?) W) R% K" Yson for the child’s virilization. At that time, they1 \) ]5 P( F1 T! C
decided to put the baby in a separate bed, and the6 ?1 c$ Y; W$ T3 z- x. n
father was not hugging him with bare skin and had2 e2 t& W; U9 f; l
been using protective clothing. A repeat testosterone1 g1 m: c7 c7 }, l
test was ordered, but the family did not go to the) e3 L! d: r/ G6 ~9 E. _ X
laboratory to obtain the test.. g! f5 w- f) C- m4 @+ j
Discussion" c$ V- f& h$ S" L3 }" E3 ~
Precocious puberty in boys is defined as secondary
% b+ j( l8 M/ H! W3 E4 {) msexual development before 9 years of age.1,43 M) q/ h5 Y, l( f8 p) U" P
Precocious puberty is termed as central (true) when6 y" R; D2 m8 S2 | E
it is caused by the premature activation of hypo-& a! D: I6 m' a
thalamic pituitary gonadal axis. CPP is more com-- k! l8 G+ o+ Z4 n- o
mon in girls than in boys.1,3 Most boys with CPP
. p6 V) r D3 F# j6 ^! F, j2 Xmay have a central nervous system lesion that is
/ I5 e2 ?* k% d: @7 Fresponsible for the early activation of the hypothal-
" F, r/ k: R3 b% `2 j, X1 `amic pituitary gonadal axis.1-3 Thus, greater empha-
( l* {, K Y; e1 I* n; ]* {sis has been given to neuroradiologic imaging in7 x$ X% z5 T: k5 `4 G
boys with precocious puberty. In addition to viril-
0 S3 g* S3 Q! _5 c! i7 Gization, the clinical hallmark of CPP is the symmet-
5 R" t q( Y. Krical testicular growth secondary to stimulation by# F. T) Q& E* J4 Y: }( b) a
gonadotropins.1,3
6 }% W" f% }; t4 |7 CGonadotropin-independent peripheral preco-
) e+ Y1 d& i- h, P# t5 Vcious puberty in boys also results from inappropriate4 A5 o& b+ O- j- L
androgenic stimulation from either endogenous or o5 F4 ^# u3 D( k
exogenous sources, nonpituitary gonadotropin stim-; C5 U! b% U4 w1 g- B2 S# |& ]2 o( y
ulation, and rare activating mutations.3 Virilizing
) i4 R: j0 }; e; x& b# W4 ~congenital adrenal hyperplasia producing excessive, ?/ _! j& ~# }# |9 D0 N
adrenal androgens is a common cause of precocious; H/ J% @3 ~. Y o
puberty in boys.3,4/ c' ?9 c% ^; |; W, p: s3 D P
The most common form of congenital adrenal) `2 j3 b6 Q, T
hyperplasia is the 21-hydroxylase enzyme deficiency.
^& N" y! ~& Y% GThe 11-β hydroxylase deficiency may also result in5 Z5 B( a4 N: o6 r$ G# u
excessive adrenal androgen production, and rarely,- G+ a9 j) p. f1 L6 X% `1 [, ?5 f. f
an adrenal tumor may also cause adrenal androgen
9 k/ W4 [. R% Y, I( G8 @excess.1,3
* D' ? N, R+ I! e, x/ K1 oat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
; t" U# k. X% v, e3 Z542 Clinical Pediatrics / Vol. 46, No. 6, July 2007 P. }; d* `) X- _4 p
A unique entity of male-limited gonadotropin-
. Z0 `( N' N/ T9 {independent precocious puberty, which is also known
N" F" d: f X# x$ }, x6 [* ?as testotoxicosis, may cause precocious puberty at a+ E t* C! _+ G9 U0 [2 }
very young age. The physical findings in these boys
1 p, d$ U7 B" n" twith this disorder are full pubertal development,
) }- u+ Y, b' p( H2 Z" N8 z0 q# |including bilateral testicular growth, similar to boys
* _, d+ D0 Q5 ]# M4 lwith CPP. The gonadotropin levels in this disorder
" U5 C- g' P! p5 f2 U9 z3 mare suppressed to prepubertal levels and do not show
) ]! q% `, c5 ]& c% |" p, W9 A# wpubertal response of gonadotropin after gonadotropin-
7 ^! P" n3 G% ?5 x) Freleasing hormone stimulation. This is a sex-linked$ M5 O* U& P8 I0 x8 I
autosomal dominant disorder that affects only5 B. E" g& }; i4 P3 m; F
males; therefore, other male members of the family
1 G+ `" Q+ Y7 \; Q3 L2 _may have similar precocious puberty.3 _8 q( d1 |( d4 T y) s, |$ ~; a3 U
In our patient, physical examination was incon-) ~4 C6 H9 S, R5 S B
sistent with true precocious puberty since his testi-
. b; W6 y, s+ g6 N) r7 q4 b _cles were prepubertal in size. However, testotoxicosis
* ]3 m& G$ E, t5 Nwas in the differential diagnosis because his father2 U% l6 N: k) |
started puberty somewhat early, and occasionally,; K ~$ J. n. d' t* a! t
testicular enlargement is not that evident in the
! q1 ~) @7 @0 gbeginning of this process.1 In the absence of a neg-! M/ W& N4 T9 s: H1 _+ m& X
ative initial history of androgen exposure, our( M8 n5 V' r" T! A, ?' Q$ C3 ?/ ]
biggest concern was virilizing adrenal hyperplasia,
6 C6 P% f; @ r7 V+ u& heither 21-hydroxylase deficiency or 11-β hydroxylase
) I) S( t2 f" V! U wdeficiency. Those diagnoses were excluded by find-
- r) \+ Z1 X4 b; Q9 {. ping the normal level of adrenal steroids.' N5 m" I' }" n1 o% X8 g
The diagnosis of exogenous androgens was strongly
+ h5 q9 b4 w5 K5 }+ E- m$ F' Jsuspected in a follow-up visit after 4 months because5 |$ L2 O0 O; ]8 X& z& ?
the physical examination revealed the complete disap-
. U/ B2 }* [ z" s; G* Npearance of pubic hair, normal growth velocity, and
9 q4 g7 x3 @" Z/ T4 t8 g4 qdecreased erections. The father admitted using a testos-! w, g4 j% x, }) q) p
terone gel, which he concealed at first visit. He was
: w! g5 f4 l) s m2 }+ jusing it rather frequently, twice a day. The Physicians’
# T* T$ F! n! z* e, x- P) `Desk Reference, or package insert of this product, gel or
( j3 Z* |, m2 y% ^- v1 M( K) |cream, cautions about dermal testosterone transfer to
* Z1 I G% R4 bunprotected females through direct skin exposure.8 k; }1 s- F4 x! @1 v
Serum testosterone level was found to be 2 times the C1 ^- @1 ^3 W" p
baseline value in those females who were exposed to8 C8 `* @8 s7 L% H9 G
even 15 minutes of direct skin contact with their male
/ P( }% _. c% k* opartners.6 However, when a shirt covered the applica-
8 N3 o) y G8 u8 mtion site, this testosterone transfer was prevented.
5 a$ C7 c; o) ^; `, \3 L2 `3 m- iOur patient’s testosterone level was 60 ng/mL,1 {% S5 Z& c" M$ C9 A
which was clearly high. Some studies suggest that" i+ u) d+ O( N u9 r
dermal conversion of testosterone to dihydrotestos-5 A8 [* l J3 g L; m8 f
terone, which is a more potent metabolite, is more0 ~4 F; l6 z8 V* N2 `2 f/ L
active in young children exposed to testosterone% U: d2 p# W V, k* G$ p1 S9 G
exogenously7; however, we did not measure a dihy-1 I) S! F; [9 g( K
drotestosterone level in our patient. In addition to) D0 g' P# M. l- I
virilization, exposure to exogenous testosterone in
6 x" |! J# W6 j7 l$ ^, k' @( vchildren results in an increase in growth velocity and
* X, e* i1 w, b1 Nadvanced bone age, as seen in our patient.
, Y2 t j8 m& q- l; w8 ] q( `7 A. u9 [The long-term effect of androgen exposure during2 E. j- d) i$ m; I
early childhood on pubertal development and final0 w, L" f! F7 @0 Q; l2 {
adult height are not fully known and always remain
. f( L- R. z6 Ha concern. Children treated with short-term testos-
7 T* T+ w4 i' m( f7 C! M# pterone injection or topical androgen may exhibit some8 y- m V" Q+ n% g+ n- N) H+ B
acceleration of the skeletal maturation; however, after0 f" F* T5 r# ^) X% U' ?; {: ]
cessation of treatment, the rate of bone maturation% S% [" s3 B# T1 u3 F9 Y
decelerates and gradually returns to normal.8,90 H* l5 t% Z A F& D
There are conflicting reports and controversy! q* z. y' y: R" a* g: p
over the effect of early androgen exposure on adult7 X6 Z+ ?* t% z4 Y L6 h# t1 Q: m
penile length.10,11 Some reports suggest subnormal
' _3 T I1 M* i1 n$ Dadult penile length, apparently because of downreg-% f: ~' j! w5 |1 P& q
ulation of androgen receptor number.10,12 However,1 a5 U* S/ j: B
Sutherland et al13 did not find a correlation between; R- m( u( z$ [
childhood testosterone exposure and reduced adult
+ R. |! o1 ^- o) ]5 Spenile length in clinical studies.- S, g& l1 H" |5 y
Nonetheless, we do not believe our patient is! Y* o% m' i f f, ]( Q, G
going to experience any of the untoward effects from
, K8 z j1 f1 T$ \" N6 Ztestosterone exposure as mentioned earlier because
- G( T) A9 W" |/ H+ p9 i% Jthe exposure was not for a prolonged period of time.5 G" q- z& c( x6 D' \
Although the bone age was advanced at the time of L) S0 l, V$ k) \, t5 v
diagnosis, the child had a normal growth velocity at
( P& C' I2 j: F0 `the follow-up visit. It is hoped that his final adult6 e% K" H3 G4 }9 R
height will not be affected., W! e7 f4 z `5 U& n: `: w" V1 v4 a
Although rarely reported, the widespread avail-
Z f, O7 H5 x mability of androgen products in our society may" t) \! m/ s% o& Y3 h+ x! k: s
indeed cause more virilization in male or female, Z/ r, a0 N, Z! L2 m0 a# Y) s
children than one would realize. Exposure to andro-
0 z5 L9 U- ?+ }3 \; ?; `7 w Qgen products must be considered and specific ques-3 A$ z- a$ U- ]1 s
tioning about the use of a testosterone product or1 D6 Z' C, e% G( G* P
gel should be asked of the family members during& Y" v( ]+ L" x$ B7 @
the evaluation of any children who present with vir-
4 W2 e8 s5 ^# gilization or peripheral precocious puberty. The diag-
6 `; K7 ]+ b) Y; v$ U5 Tnosis can be established by just a few tests and by) u7 ~6 }5 F# y9 E$ `" f
appropriate history. The inability to obtain such a
0 i% }2 [' s) P' T% k' mhistory, or failure to ask the specific questions, may
' N" V M) T6 z& w3 M' d uresult in extensive, unnecessary, and expensive- C5 f/ G" m4 I
investigation. The primary care physician should be
6 {3 B! k6 E* B" C" caware of this fact, because most of these children
) x4 R1 U, {0 C! Wmay initially present in their practice. The Physicians’
. ~" |" k' G J$ _3 ~$ A/ bDesk Reference and package insert should also put a
) m4 ]) L- ~) v; l; l/ s7 A% `warning about the virilizing effect on a male or
T# L+ ]9 m, Z8 V) T3 bfemale child who might come in contact with some-: c) [" c, o/ D% U9 M5 Y( p# X- [
one using any of these products.
( ]" f5 r1 X% Z* BReferences
" z% I# o9 o( _# R2 M8 @! i& P; t$ L7 X1. Styne DM. The testes: disorder of sexual differentiation
7 n( Y) k+ {- ~4 E/ ^3 Band puberty in the male. In: Sperling MA, ed. Pediatric
8 U6 E X4 W4 |& s; bEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
' U7 Z# D/ H( I0 Z9 d2 l2002: 565-628.# e- [3 X" i6 D8 o6 J% U
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious C6 n! p* W- e( w8 m
puberty in children with tumours of the suprasellar pineal |
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