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Sexual Precocity in a 16-Month-Old; D1 N0 J4 I3 r/ Y ]6 n& Y7 y7 h( S
Boy Induced by Indirect Topical% S* }2 F5 F5 M
Exposure to Testosterone
# q& G/ ]) J6 ]Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
2 @) u% m, u/ z3 Y& ` E( Land Kenneth R. Rettig, MD1
' `2 F4 l: [: Y1 {( c$ j$ eClinical Pediatrics$ V! s/ M) ^. ^6 k
Volume 46 Number 6
2 y8 I) g. s; e( l: ]! ^" \July 2007 540-543" B/ S! _( n" Q
© 2007 Sage Publications' `7 |3 c/ h! A3 l3 ]8 \
10.1177/00099228062966513 _ s3 I- Z. Z' L
http://clp.sagepub.com
4 ^- Z6 l! {3 e: B( f7 j5 Q- m& Rhosted at4 N- V& T4 o7 O4 J$ W* ^
http://online.sagepub.com
/ |% ?. [1 A! b+ b! ^. s! iPrecocious puberty in boys, central or peripheral,# T" _$ x6 A/ d& Y7 o4 o- J. W
is a significant concern for physicians. Central
! V& [/ Z ~* K9 s+ z( N6 nprecocious puberty (CPP), which is mediated
4 `8 s/ P; @$ v6 S5 q4 ]& Othrough the hypothalamic pituitary gonadal axis, has
! H+ p; R2 F" ^; ia higher incidence of organic central nervous system" v& d; |+ ^ J. E$ y
lesions in boys.1,2 Virilization in boys, as manifested- B) o1 L3 k r; v( t
by enlargement of the penis, development of pubic
! d8 f2 P; { qhair, and facial acne without enlargement of testi- T+ E5 [- p2 J
cles, suggests peripheral or pseudopuberty.1-3 We8 V7 z! f& Q5 t" ~: J, t
report a 16-month-old boy who presented with the
7 r c! N9 h+ } {5 q( N6 `5 `enlargement of the phallus and pubic hair develop-
7 I5 k# |' t# wment without testicular enlargement, which was due
- V0 ^, O6 r$ `* E K; Sto the unintentional exposure to androgen gel used by7 ]* c9 z6 B9 S2 B! p$ h/ e" X
the father. The family initially concealed this infor-. U. G! l- r% }( ^# V! D0 A
mation, resulting in an extensive work-up for this0 V7 Z2 R/ \8 w4 h
child. Given the widespread and easy availability of
) U. U: n4 @8 G# M, Ltestosterone gel and cream, we believe this is proba-
4 ~2 L: I# W- x1 J8 dbly more common than the rare case report in the% _6 l# r4 K. d# D1 ^3 h
literature.4
* R$ E4 N' E0 l' hPatient Report( B7 p+ R) ?- w& N1 u$ c% p* ~# m
A 16-month-old white child was referred to the
! p) G9 x' V4 n+ j3 A. f; L1 C# [endocrine clinic by his pediatrician with the concern4 L% Y( a( a* P
of early sexual development. His mother noticed
, c1 B k. r1 k/ e& U' ]8 Y; vlight colored pubic hair development when he was
: K% w3 `/ g- ^! j: Z2 L. t3 jFrom the 1Division of Pediatric Endocrinology, 2University of7 z1 |1 y3 d! i9 k! P0 V2 L4 F' N
South Alabama Medical Center, Mobile, Alabama.
8 ]6 L. c. l1 W/ M9 p" w+ {8 xAddress correspondence to: Samar K. Bhowmick, MD, FACE, w' Q' [1 [0 G0 b3 c& |: `
Professor of Pediatrics, University of South Alabama, College of$ M, a8 T' z0 F( {- Z
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;+ s% o" W. {; D8 j4 |+ C. v- K# n
e-mail: [email protected].
8 ]" t ~6 C1 B: x, [! Labout 6 to 7 months old, which progressively became
- f% F" R( b7 p% _0 ^7 C: v+ Ndarker. She was also concerned about the enlarge-. [5 \9 F" E# |5 n+ o
ment of his penis and frequent erections. The child+ [( m. T% e; s- ]) E
was the product of a full-term normal delivery, with
S2 i9 ]. g7 Pa birth weight of 7 lb 14 oz, and birth length of
8 I3 v- H. n! V+ h20 inches. He was breast-fed throughout the first year
. P$ ^3 V! C6 c9 F8 a! F! Yof life and was still receiving breast milk along with' F7 [) }9 K6 S% _6 U
solid food. He had no hospitalizations or surgery,
( b: @: k1 h! D1 M; Q4 T0 u& vand his psychosocial and psychomotor development0 ^9 F, |/ n! ?, q3 `' ~& h
was age appropriate.1 Z+ u* y1 [. }! i
The family history was remarkable for the father,8 G% {0 G4 f- a7 A
who was diagnosed with hypothyroidism at age 16,% F" P! P9 ]6 T9 u
which was treated with thyroxine. The father’s
) ?3 h1 W2 n6 T$ q% A5 o4 k# C2 `height was 6 feet, and he went through a somewhat
* O3 l0 ^- k K/ ]' {early puberty and had stopped growing by age 14.
: r" h5 T' Z w( U, U4 Q) @: ZThe father denied taking any other medication. The) h3 Y% u3 E2 w+ C* v4 _
child’s mother was in good health. Her menarche
1 ?6 {: k) O$ y( J9 m" A8 Iwas at 11 years of age, and her height was at 5 feet g/ o8 ^, P/ ]
5 inches. There was no other family history of pre-
# h. D* I$ f3 w; Icocious sexual development in the first-degree rela-
b, Y: l% |- `( ~( K% U% ?tives. There were no siblings.' d% N6 I5 s4 W- i! g- [1 i
Physical Examination
4 t/ M9 `- v" e1 h* m& V5 ~The physical examination revealed a very active,
8 ?! M, v" C! Y+ `" Fplayful, and healthy boy. The vital signs documented+ ^6 m+ h. z. `, I9 ?
a blood pressure of 85/50 mm Hg, his length was; l' I3 ?. U, K5 e
90 cm (>97th percentile), and his weight was 14.4 kg
. [( ]) E% W6 |% r# k7 |3 q; w(also >97th percentile). The observed yearly growth m% @8 s$ k* J
velocity was 30 cm (12 inches). The examination of
8 G/ b4 m- y5 S, P* o. Athe neck revealed no thyroid enlargement.+ E; |: f* A; f9 W& G6 N( y
The genitourinary examination was remarkable for
: D& N$ j) r- p* I( ienlargement of the penis, with a stretched length of4 {% k) z9 H' j* z- f
8 cm and a width of 2 cm. The glans penis was very well+ s4 j: X2 ]1 V7 n
developed. The pubic hair was Tanner II, mostly around5 Y: y3 d( \; C6 I9 t+ ~
540
) O7 J, Q! H/ A: l4 F- mat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from. A) {4 K" J9 c1 A( p' H; B
the base of the phallus and was dark and curled. The( h+ [- U; I: Z& Y
testicular volume was prepubertal at 2 mL each.
. _% V" z8 v& E/ `; oThe skin was moist and smooth and somewhat! j; Q, T0 ~# i6 y; x" f$ R" X* G
oily. No axillary hair was noted. There were no8 ~7 H' Z* H( n4 @
abnormal skin pigmentations or café-au-lait spots./ Q) Z% e I9 |5 E5 k1 H. H5 E
Neurologic evaluation showed deep tendon reflex 2+
" c8 A+ B" P- M, e7 S$ x7 X& J4 V4 Jbilateral and symmetrical. There was no suggestion
, ^. A+ q8 J5 I0 X) @of papilledema.- A) h m2 G9 Q. Y7 L0 O
Laboratory Evaluation
7 m8 V; [9 E) ?& x0 F; ^5 k+ t6 WThe bone age was consistent with 28 months by
" h; {" X9 L1 R- b' s* Kusing the standard of Greulich and Pyle at a chrono-1 C. O! j ]& C$ x7 t. o
logic age of 16 months (advanced).5 Chromosomal2 A) z) X: X3 [- ~
karyotype was 46XY. The thyroid function test) v) f) j; A* e( j5 ~1 E8 D8 R; ]5 }: S
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
5 y2 g& i3 X$ e0 slating hormone level was 1.3 µIU/mL (both normal)./ A3 k1 R4 g. B4 m6 x2 o
The concentrations of serum electrolytes, blood
% C; O9 V# t% I: b+ eurea nitrogen, creatinine, and calcium all were9 B7 X8 r, R8 S& z0 T* {* a
within normal range for his age. The concentration' W+ ~- E4 c7 x
of serum 17-hydroxyprogesterone was 16 ng/dL# K, R8 C R: R {# O: l
(normal, 3 to 90 ng/dL), androstenedione was 20+ `; [( \9 w0 | X1 v+ R
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-. D; I2 g. c0 ], ^9 e
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
9 ]% s; A$ Q; {+ z) Z3 V4 O( s: Qdesoxycorticosterone was 4.3 ng/dL (normal, 7 to
0 z* M: M& T2 J; O4 s9 e3 `* w% ~# k49ng/dL), 11-desoxycortisol (specific compound S) i! [7 Y/ T" z5 P+ {- D2 m5 O9 J
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-% A! X; O# N3 q, l
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total* D9 {/ v0 e# S% L: g C, \
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),6 x9 ~- U5 S) G
and β-human chorionic gonadotropin was less than& d2 j9 R) P* U5 y$ G
5 mIU/mL (normal <5 mIU/mL). Serum follicular: x8 P" e/ t! F H
stimulating hormone and leuteinizing hormone6 e6 S2 ?' m" Q
concentrations were less than 0.05 mIU/mL
" }6 N5 [8 L# w" X(prepubertal).8 q% l2 t6 \2 g& T/ O9 T
The parents were notified about the laboratory
# ]! X+ ~1 ?6 Qresults and were informed that all of the tests were
- R2 I1 t& W3 A! ~5 r3 d7 cnormal except the testosterone level was high. The
% a1 h) p7 N1 M( b" w: `2 C! i5 Zfollow-up visit was arranged within a few weeks to2 n( K5 N' B o' V* F7 t
obtain testicular and abdominal sonograms; how-
6 J4 \! p, X4 C, H, G! g) ?! }ever, the family did not return for 4 months.
* k* m* Z* j; [- ?/ d% X0 LPhysical examination at this time revealed that the6 N7 {2 x) N# L! J" Y
child had grown 2.5 cm in 4 months and had gained4 ]) z9 ]2 h: e& V' |
2 kg of weight. Physical examination remained: `2 Z' S! U; I& _7 J
unchanged. Surprisingly, the pubic hair almost com-5 H2 v1 o2 B3 |2 T" W
pletely disappeared except for a few vellous hairs at, D Q6 m, ^! ?* R' l: E2 T
the base of the phallus. Testicular volume was still 2" Z2 [$ o* x" W. P8 I
mL, and the size of the penis remained unchanged. [5 J5 R3 r3 w0 ~- u4 x& o
The mother also said that the boy was no longer hav-
0 H5 P! V1 n0 b! H# t' _ing frequent erections.5 y+ v3 U0 J( [; K1 D
Both parents were again questioned about use of/ y2 C6 V+ Y3 }2 U9 f0 B3 H
any ointment/creams that they may have applied to
# E' b9 Q! V, Y [0 Z7 H2 Xthe child’s skin. This time the father admitted the
1 [7 }' Q8 V4 n v" MTopical Testosterone Exposure / Bhowmick et al 541% x$ Q0 J3 U$ b, S, D. B8 e' q% p
use of testosterone gel twice daily that he was apply-% Y; x2 s% v# H' ]# L
ing over his own shoulders, chest, and back area for
) X" W0 }4 C& R1 z; W. |a year. The father also revealed he was embarrassed+ M% Y1 ]: s# V3 B
to disclose that he was using a testosterone gel pre-
3 p3 G3 s" u- x/ {scribed by his family physician for decreased libido1 U7 f0 Q+ V$ _: `
secondary to depression.
! E4 e' h, `. N; z" |The child slept in the same bed with parents.9 O( T A, k) Y
The father would hug the baby and hold him on his& m$ l) K$ G! l& @! V
chest for a considerable period of time, causing sig-' {! I! Y9 p9 d! Y
nificant bare skin contact between baby and father.
0 y4 ~! b& p2 k \1 }# T0 F" p- yThe father also admitted that after the phone call,
: x8 H/ M& u: U6 @when he learned the testosterone level in the baby& a0 E+ o* |8 }% [0 ~# ~
was high, he then read the product information
; R0 z& d) } L+ _ mpacket and concluded that it was most likely the rea-! M# c0 K0 y. M4 N6 }3 s! e
son for the child’s virilization. At that time, they. W4 V- T8 W/ k( Q
decided to put the baby in a separate bed, and the
$ J% ?+ H, F# I+ s: A9 A! \father was not hugging him with bare skin and had
5 w8 Q1 N6 ^9 C+ Xbeen using protective clothing. A repeat testosterone7 H+ E- \' _! M h% r
test was ordered, but the family did not go to the
( F1 t5 m0 W) J2 {! S2 ^5 y slaboratory to obtain the test.
2 V+ E3 l9 Z2 i! k7 \- NDiscussion& U1 j0 U/ j4 }% M
Precocious puberty in boys is defined as secondary: S# t; O3 E+ K
sexual development before 9 years of age.1,4: i' r7 P$ ?; v0 E
Precocious puberty is termed as central (true) when
* N2 |; y, k. D3 Hit is caused by the premature activation of hypo-& j; n0 r' |# n4 n
thalamic pituitary gonadal axis. CPP is more com-
- H. e' J, S4 Q) tmon in girls than in boys.1,3 Most boys with CPP5 J- b$ M% z) p1 p1 y3 i) H
may have a central nervous system lesion that is
" M- P: _, G3 r0 ?% yresponsible for the early activation of the hypothal-- B2 J6 Q8 [$ c' K% R
amic pituitary gonadal axis.1-3 Thus, greater empha-
* \ l8 M$ y$ c; q: V2 z0 C3 Vsis has been given to neuroradiologic imaging in
+ ^( C9 j& ?+ b' X1 kboys with precocious puberty. In addition to viril-+ a, p/ g2 V/ ~3 [
ization, the clinical hallmark of CPP is the symmet-, [, O8 e5 e* R* y+ t" ~
rical testicular growth secondary to stimulation by1 T( t7 t, ?7 }' w" X7 ^/ z
gonadotropins.1,3. G, J+ l& J- @( X: W
Gonadotropin-independent peripheral preco-
1 X! ~) ], n& { |cious puberty in boys also results from inappropriate
* D$ P" y' ?8 P! T8 |7 Uandrogenic stimulation from either endogenous or1 s) }( M( e) A0 c N8 E- w) T
exogenous sources, nonpituitary gonadotropin stim-+ {2 _* @8 v2 S3 i) w
ulation, and rare activating mutations.3 Virilizing( t4 S! l* d1 P* l
congenital adrenal hyperplasia producing excessive( b1 f3 y3 I1 n& B1 Q( K& Y' h
adrenal androgens is a common cause of precocious d, e* ^; o9 g% ]2 k W
puberty in boys.3,4
( t6 V8 @0 Z/ h. h; i) Z1 _" Z7 bThe most common form of congenital adrenal
4 F$ u" J5 ?( G; Q/ X2 |5 x( [+ A9 C! ^hyperplasia is the 21-hydroxylase enzyme deficiency.
' l2 \& {+ W. kThe 11-β hydroxylase deficiency may also result in
, s1 h% ^; c" V! mexcessive adrenal androgen production, and rarely,
6 R- o6 k; S! ]" u7 U1 @an adrenal tumor may also cause adrenal androgen
+ F% u( N: I8 c% M: Wexcess.1,3& o7 z3 {9 g# r) D
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from, }8 t F& _; ]. A# q, {5 Y
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007. A. F/ H! A6 e# W1 U% H5 M8 O
A unique entity of male-limited gonadotropin-! `% \! I4 \2 e9 C1 d5 d6 x
independent precocious puberty, which is also known
2 V+ k5 ?. @) F) v+ Eas testotoxicosis, may cause precocious puberty at a ]: ^( f/ |2 {$ l/ U
very young age. The physical findings in these boys
: f1 R* Q" h! P1 i0 i5 y$ I/ |3 kwith this disorder are full pubertal development,
7 I( K. W# {/ Q# M8 ^including bilateral testicular growth, similar to boys
5 P* o4 u: w+ n! I5 X' Awith CPP. The gonadotropin levels in this disorder
/ m3 G0 D4 N; |6 ?' g7 f, {are suppressed to prepubertal levels and do not show
& c6 X& F4 t2 P$ V) y' l8 e* cpubertal response of gonadotropin after gonadotropin-. B( e7 o- \9 u1 R0 U o, V
releasing hormone stimulation. This is a sex-linked
4 U! V$ k7 j9 s3 k1 _autosomal dominant disorder that affects only
: o K4 {; j. _) B5 }0 m# mmales; therefore, other male members of the family& H( }! X! F+ F8 J* I" Q6 S/ E6 ]! a
may have similar precocious puberty.3
; j/ V/ Z0 \ w; e6 x" gIn our patient, physical examination was incon-4 K3 L/ R. @' \: M7 ]
sistent with true precocious puberty since his testi-
% l4 O9 f2 ?8 O" D# f6 f3 a+ r1 ncles were prepubertal in size. However, testotoxicosis9 F9 m+ t7 D, J. P. b; {
was in the differential diagnosis because his father
. X& ~/ x- U" v; ]9 q8 L) Istarted puberty somewhat early, and occasionally,2 c! J* b9 q% }; t9 P6 n9 `
testicular enlargement is not that evident in the
# X b2 J! r2 tbeginning of this process.1 In the absence of a neg-$ M/ K& N1 y: T, _5 f
ative initial history of androgen exposure, our! E; d$ k) x) f4 F" B
biggest concern was virilizing adrenal hyperplasia,
5 l% a, I+ L1 F" {' deither 21-hydroxylase deficiency or 11-β hydroxylase
- r! Q* U+ O! _; {deficiency. Those diagnoses were excluded by find-
3 a6 L1 l8 `( V5 w N |, jing the normal level of adrenal steroids.7 ?$ `) @4 N, i$ y8 |5 `
The diagnosis of exogenous androgens was strongly) w) Y5 o7 R( l8 Q8 \: r* z" D/ C
suspected in a follow-up visit after 4 months because6 e8 k0 ~& q3 t' D0 e/ O0 U# d
the physical examination revealed the complete disap-& j6 u9 l$ y2 ]1 s
pearance of pubic hair, normal growth velocity, and. C, U+ H" V8 y7 r3 k, N) g
decreased erections. The father admitted using a testos-
5 b- ?2 L- i+ b) Gterone gel, which he concealed at first visit. He was9 k% l+ Z. {: _, }
using it rather frequently, twice a day. The Physicians’
2 p1 v, `6 W( uDesk Reference, or package insert of this product, gel or# P/ V, W& v; [
cream, cautions about dermal testosterone transfer to
& s" t. Y' z" W3 @: {' a& Punprotected females through direct skin exposure.
& i) e0 C5 B% o7 q3 Q3 tSerum testosterone level was found to be 2 times the
+ W5 b; X6 X5 F& rbaseline value in those females who were exposed to
$ T, M6 j; }' L. |$ e* y: peven 15 minutes of direct skin contact with their male
/ Z8 T- L/ C5 zpartners.6 However, when a shirt covered the applica-
2 D% c. r7 ^2 ^) @. m, `tion site, this testosterone transfer was prevented.% [4 `, \, l/ F5 l$ \: q+ O3 ~# ^
Our patient’s testosterone level was 60 ng/mL,
q+ d4 l' |, b. j4 v0 }' vwhich was clearly high. Some studies suggest that
& K4 S' N4 P6 P/ ?5 v! \" Y6 j2 J; fdermal conversion of testosterone to dihydrotestos-
3 L& p0 K7 m" ^( \( U' j4 z) z dterone, which is a more potent metabolite, is more, g/ I0 t2 B$ r" {4 v- v a
active in young children exposed to testosterone
3 |- i4 L; v. L: |$ mexogenously7; however, we did not measure a dihy-
7 `$ O* a; j6 r1 J( a" ^5 Xdrotestosterone level in our patient. In addition to; O; k; y1 l4 y9 ]0 l1 z6 I, q
virilization, exposure to exogenous testosterone in
8 ~# f, q* D1 A: _9 {children results in an increase in growth velocity and3 O& P7 z' M- f- \8 A
advanced bone age, as seen in our patient.
1 o- q( z% {' J; a. ^The long-term effect of androgen exposure during
. T: _+ ~* r* A( z" F5 Z- Mearly childhood on pubertal development and final& o# h& ?+ |7 n( J6 `
adult height are not fully known and always remain9 a. J7 ~4 x2 {8 ~% h
a concern. Children treated with short-term testos-
' l+ d2 p5 I, Eterone injection or topical androgen may exhibit some+ M E" Q, y, o( ]# I
acceleration of the skeletal maturation; however, after: M8 N) G2 f! I, q1 N! v
cessation of treatment, the rate of bone maturation
8 b: X- q) z. |. ]& hdecelerates and gradually returns to normal.8,9
) N) O# n+ N6 i9 gThere are conflicting reports and controversy& G) Z, w% Q* V* U
over the effect of early androgen exposure on adult' @# ?3 q; y; x0 x5 O+ G
penile length.10,11 Some reports suggest subnormal6 J, v, h$ {# t
adult penile length, apparently because of downreg-+ y+ k ]. g% U$ `2 c4 N: b z7 \
ulation of androgen receptor number.10,12 However,
: K. A: ?1 i3 L" u: i5 @# [Sutherland et al13 did not find a correlation between# P- x- z! |. j* f' [! a% {
childhood testosterone exposure and reduced adult
6 D$ f9 d) v* G% h8 Qpenile length in clinical studies.
i& y' R Z: a( \5 K$ R v% t1 c8 bNonetheless, we do not believe our patient is
9 B4 {5 n2 Q" X9 p5 u7 H$ jgoing to experience any of the untoward effects from1 U7 k5 v5 T9 P k( k0 C
testosterone exposure as mentioned earlier because
8 v# P+ z6 k8 u' r `! othe exposure was not for a prolonged period of time.
5 `6 t! m( [: w, KAlthough the bone age was advanced at the time of
/ Z! Q7 y( s' Gdiagnosis, the child had a normal growth velocity at: U" S2 o3 u, e
the follow-up visit. It is hoped that his final adult
( n% N; T0 g9 mheight will not be affected.% @2 W; d8 z- C3 @
Although rarely reported, the widespread avail-
8 D, B$ |' z6 lability of androgen products in our society may* }# I, @" Z- j2 p
indeed cause more virilization in male or female: J1 }. |* ^ b& a+ b# f6 |; R* I% r
children than one would realize. Exposure to andro-: k, L* a! n. l* X) G" b. ^' @
gen products must be considered and specific ques-% I9 k$ J5 h. d7 ]# @
tioning about the use of a testosterone product or+ b% r/ K% Y+ h X. @% v
gel should be asked of the family members during
9 _6 e9 m5 C u+ I. w E# {* wthe evaluation of any children who present with vir-
2 ]- F. h) [1 p. p7 iilization or peripheral precocious puberty. The diag-
9 x3 V% M% s7 n4 X+ P% A4 h0 gnosis can be established by just a few tests and by
& T2 l I8 X- ?. N8 x# cappropriate history. The inability to obtain such a
9 \4 Q2 K3 u, m: A& y1 whistory, or failure to ask the specific questions, may
6 Z3 t, a; l) \: _* presult in extensive, unnecessary, and expensive
0 h& V8 a. m, Pinvestigation. The primary care physician should be
* k0 f0 L: [# } N7 Iaware of this fact, because most of these children% q$ K* R, s; z/ _' h
may initially present in their practice. The Physicians’6 f3 A. G" H1 Z* e c9 L
Desk Reference and package insert should also put a0 T8 k$ H. Y) Y! ^
warning about the virilizing effect on a male or' g6 I6 |& m5 ^4 n% C) _
female child who might come in contact with some-( _: {$ s5 _( f% x: Y3 X
one using any of these products.
" H2 \$ [/ W; ^, c" A* LReferences
, W& l( t( W6 b& y+ B5 d+ ~. l* l1. Styne DM. The testes: disorder of sexual differentiation
1 [# A4 Q: z- K! f# W6 x# Xand puberty in the male. In: Sperling MA, ed. Pediatric
( m$ \. w) j8 P$ \! e- B BEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;2 |- I3 O5 D/ e- O
2002: 565-628.9 \/ q1 `" ]# Q0 w2 v1 r$ Y d
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
% C* K8 K- x7 ~puberty in children with tumours of the suprasellar pineal |
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