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Sexual Precocity in a 16-Month-Old6 w% w& u% }! x" y$ F- U; S
Boy Induced by Indirect Topical
; M# E9 F9 w& y; d: O& cExposure to Testosterone
$ I" S+ Z9 z8 c7 h S1 D$ ~Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
/ c) w* d$ k! G' m tand Kenneth R. Rettig, MD1* B' e4 a( a3 }' {9 Q4 y% g
Clinical Pediatrics$ y0 P; y1 N+ k" N+ [& I' q8 K+ w
Volume 46 Number 6
* S3 ]( l# x* `. ^' j; eJuly 2007 540-543
; ?+ e8 c) |2 a' H1 h8 A' k+ Q- U( w! J© 2007 Sage Publications
0 j$ `3 R6 l6 m/ S* K10.1177/0009922806296651/ b) {6 |/ H! J
http://clp.sagepub.com
( i7 W4 P8 I8 D% F* V* [hosted at6 B& O, T: G/ ^8 I& F. l! C
http://online.sagepub.com+ E9 s% V+ F; r# p
Precocious puberty in boys, central or peripheral,
0 n4 U$ o! y7 L( B+ cis a significant concern for physicians. Central2 I0 Z* z8 k1 F: }
precocious puberty (CPP), which is mediated
* |$ v$ ]3 h" L: O2 Gthrough the hypothalamic pituitary gonadal axis, has( J2 M5 p, | r7 q4 ~
a higher incidence of organic central nervous system
/ m: }5 B: X" I+ r4 `% mlesions in boys.1,2 Virilization in boys, as manifested
1 a v: m+ X8 `by enlargement of the penis, development of pubic
2 b$ ~2 R3 _ d8 Z$ N$ ~( dhair, and facial acne without enlargement of testi-
9 D; }5 O( L. L. Gcles, suggests peripheral or pseudopuberty.1-3 We0 b; K, E |! {' I
report a 16-month-old boy who presented with the
7 p7 o4 D" p$ g( [7 v9 jenlargement of the phallus and pubic hair develop-
6 |6 F1 b/ t8 ^4 X+ Rment without testicular enlargement, which was due
. B/ M$ E% c. x, o" h8 u% h4 yto the unintentional exposure to androgen gel used by4 w$ v# t, v) a! M5 m# w4 _# A! r
the father. The family initially concealed this infor-
! b. O* g/ S2 x6 ]mation, resulting in an extensive work-up for this
- \+ t9 K: I9 y; t9 Y* r1 y5 Schild. Given the widespread and easy availability of
2 b3 Z+ q$ e- `# Ktestosterone gel and cream, we believe this is proba-
! D1 p) A9 X% l" ] d1 gbly more common than the rare case report in the
+ p( l9 w! b: a4 S2 h! B+ {literature.4
/ u" q1 I0 K+ L$ }9 I5 _, `Patient Report# G7 X* @) {& u3 @; i; e5 k1 I
A 16-month-old white child was referred to the
; p6 i( |& E1 D6 Aendocrine clinic by his pediatrician with the concern4 @9 V8 `; }1 u$ x( v9 o8 p
of early sexual development. His mother noticed
6 J7 B9 A, G, m" l' \( H7 s6 zlight colored pubic hair development when he was4 p- u$ I7 U/ N; o
From the 1Division of Pediatric Endocrinology, 2University of) D9 ?/ a8 y: y0 g
South Alabama Medical Center, Mobile, Alabama.5 H5 I4 i5 r: l' c& B0 |! J
Address correspondence to: Samar K. Bhowmick, MD, FACE,0 V% c2 c' v+ Y6 a8 b- t9 W( Q
Professor of Pediatrics, University of South Alabama, College of
( z* O5 Y6 Q# a6 A1 P+ VMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
2 y2 A) @) [" E. ue-mail: [email protected].
! B* x& N: L" m6 D3 Babout 6 to 7 months old, which progressively became
4 R- [4 t" F! y: Fdarker. She was also concerned about the enlarge-
. G& E& u! U: s. B8 g% ament of his penis and frequent erections. The child
7 d$ d, [4 ] T9 }1 Hwas the product of a full-term normal delivery, with0 v+ s4 t5 ?5 r3 O+ c7 L, Q" V
a birth weight of 7 lb 14 oz, and birth length of
% {2 R1 Y$ H* z* o20 inches. He was breast-fed throughout the first year$ X' u N' ^" M' P3 K2 k, _
of life and was still receiving breast milk along with
) y' I( L! i: Q/ b o/ Bsolid food. He had no hospitalizations or surgery,; l5 ]: D$ l* l0 w( `
and his psychosocial and psychomotor development
- g$ d; t/ o5 t9 dwas age appropriate. `( U, U! f: s. P
The family history was remarkable for the father,5 Y2 d% T/ G# P& \9 B$ Z+ z
who was diagnosed with hypothyroidism at age 16,
- [$ }4 _) F) T- Lwhich was treated with thyroxine. The father’s1 Z% E/ L9 x1 [" V/ ], c$ i+ a/ y
height was 6 feet, and he went through a somewhat
( F2 S) b0 T2 o( n* R# O8 n uearly puberty and had stopped growing by age 14.5 ~$ b) _% X0 k
The father denied taking any other medication. The
- P7 N' i w3 u4 [# L, |- j3 Vchild’s mother was in good health. Her menarche7 ?& V4 R- q- \
was at 11 years of age, and her height was at 5 feet" X3 k. {3 o/ x3 ?4 j
5 inches. There was no other family history of pre-
$ j' @% H. N, a* f; ncocious sexual development in the first-degree rela-
, i0 O/ B, d7 g; N0 d6 ttives. There were no siblings.
1 n- c2 {" ]6 q6 ]5 ?! KPhysical Examination( D% ~& n8 Z+ |( q. V7 h1 z
The physical examination revealed a very active,4 L0 l* ?$ r# j
playful, and healthy boy. The vital signs documented
1 E+ r" d2 b/ |( {a blood pressure of 85/50 mm Hg, his length was
# V; T( |. U& E9 X# P3 @90 cm (>97th percentile), and his weight was 14.4 kg, W7 B0 ?: A" C- d3 K
(also >97th percentile). The observed yearly growth
/ i, ?' `. z" J; P" ?: Vvelocity was 30 cm (12 inches). The examination of
. Q3 f3 l9 Z1 w }2 h( @9 p# sthe neck revealed no thyroid enlargement.
" D$ |+ ~( P0 mThe genitourinary examination was remarkable for6 P \! l9 P% u$ \
enlargement of the penis, with a stretched length of
* ~9 E& w. X1 R3 S, |# V: B8 cm and a width of 2 cm. The glans penis was very well
t- m0 G+ b5 N+ n! [, Vdeveloped. The pubic hair was Tanner II, mostly around
% N% B- W5 ?0 r& j% g/ T& W/ J540# x. C7 H! S. c r* {! w9 K( Y$ b2 d
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
7 M; V9 Y# S% E1 x% K6 ithe base of the phallus and was dark and curled. The" Y9 A% O3 [& p
testicular volume was prepubertal at 2 mL each.* U% o4 Q! [" o1 A; I8 y% }; p
The skin was moist and smooth and somewhat
$ Q& C p# d6 b" noily. No axillary hair was noted. There were no5 l* }) {7 I. B6 m$ J+ \
abnormal skin pigmentations or café-au-lait spots.
# W' N' R2 A8 k; s uNeurologic evaluation showed deep tendon reflex 2+
3 s( w6 R- S6 @' ~2 ^, K3 `bilateral and symmetrical. There was no suggestion
, P" \4 l5 v5 X6 N, }$ Vof papilledema.
: u7 e( R: E' D7 }9 [Laboratory Evaluation
1 n# d9 Z) U J" l) t' NThe bone age was consistent with 28 months by
- ?1 v2 p! b! j9 Yusing the standard of Greulich and Pyle at a chrono-3 i) R& i4 u2 N
logic age of 16 months (advanced).5 Chromosomal0 j1 [* t4 U& W- G
karyotype was 46XY. The thyroid function test
2 L7 B2 ^/ R7 h4 ishowed a free T4 of 1.69 ng/dL, and thyroid stimu-
5 e3 @- b! {) \, @& g8 alating hormone level was 1.3 µIU/mL (both normal).6 J4 E9 s! x9 R8 Y: s! [
The concentrations of serum electrolytes, blood
1 o m+ c( m) d6 f3 o1 A% e( j: `urea nitrogen, creatinine, and calcium all were' R8 K `! X0 D) _( ?
within normal range for his age. The concentration# c" H7 h5 c& b! H8 f+ C
of serum 17-hydroxyprogesterone was 16 ng/dL
1 h5 p! z( ?0 B, S% ^(normal, 3 to 90 ng/dL), androstenedione was 200 c% J. ?5 h( _/ B) i; _9 Q
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-8 ~' \# ~0 }) r* @4 c! A/ S6 {
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
2 ?- B9 Q J9 x7 t$ O5 N5 `$ Bdesoxycorticosterone was 4.3 ng/dL (normal, 7 to
* P! b4 K6 |2 _2 o49ng/dL), 11-desoxycortisol (specific compound S) f ?' o& f4 H5 K( Y Y2 J8 V
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
: r d2 Y( m. M9 @$ Q' n8 D9 T- J& ytisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total* S( j: `0 P5 h( v
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),% W& [5 Q- ?- E& C' U' A
and β-human chorionic gonadotropin was less than
: p/ X% g5 a: a3 E+ s( m5 mIU/mL (normal <5 mIU/mL). Serum follicular
, ]8 F! p* ? } y* Z$ Zstimulating hormone and leuteinizing hormone
! u+ n6 v9 h8 t2 Fconcentrations were less than 0.05 mIU/mL
& }0 K: q# r4 l Z(prepubertal).
, ^! w. B. w/ |/ dThe parents were notified about the laboratory& P8 d5 Q& S8 {3 N* b) }/ p# X
results and were informed that all of the tests were$ Z: \* q3 o5 ]6 F7 k& L: F
normal except the testosterone level was high. The6 ` W( A- Y( J6 d3 I
follow-up visit was arranged within a few weeks to
3 w) d* n* E0 u/ @3 |' |obtain testicular and abdominal sonograms; how-. @5 ^" g% Y% @. J/ R1 p
ever, the family did not return for 4 months.
- N& T/ r# H) X% J& k5 }Physical examination at this time revealed that the5 E- M: C/ b5 E7 a7 M
child had grown 2.5 cm in 4 months and had gained1 O% l2 o2 K8 b+ ^9 p) D; V
2 kg of weight. Physical examination remained
% N/ j% ~: m! ?! I0 e4 I& @unchanged. Surprisingly, the pubic hair almost com-0 R+ e) m0 R, e9 M s
pletely disappeared except for a few vellous hairs at
# y% d4 V A0 G/ o9 ~the base of the phallus. Testicular volume was still 2
1 D. S, x; K7 _4 j- Q/ _mL, and the size of the penis remained unchanged.9 D1 J! o) d5 ]' r. {
The mother also said that the boy was no longer hav-# P9 |% b, N% Y1 J5 i
ing frequent erections.' ~( c# v: @- }+ D, S
Both parents were again questioned about use of. H( e8 h" s$ |. @" {% t
any ointment/creams that they may have applied to0 ?% q/ U* }5 T' a; \: H% q
the child’s skin. This time the father admitted the
/ }! y8 ?) x) l8 _; e7 D& l' k9 [Topical Testosterone Exposure / Bhowmick et al 541
; U9 T Q, f3 O2 ?) guse of testosterone gel twice daily that he was apply-
$ d! g, w( H5 X0 k& g/ Qing over his own shoulders, chest, and back area for* ^( P7 w" a* P9 ^( j+ V
a year. The father also revealed he was embarrassed5 d: z& }( x& g+ g: p
to disclose that he was using a testosterone gel pre-+ b/ s1 a! G* \2 O
scribed by his family physician for decreased libido
4 l% \- }" S6 Q9 J/ Fsecondary to depression.! m1 x0 Y* H! U+ P; Z
The child slept in the same bed with parents.
& v8 B. @' V7 C2 @$ r! @The father would hug the baby and hold him on his
0 C. I/ @. T2 h4 Tchest for a considerable period of time, causing sig-
! r" Y" e, w" _, `7 F! m* x7 ?* @nificant bare skin contact between baby and father.
- H/ Y3 G9 q/ BThe father also admitted that after the phone call,6 p: L# ]5 Y( H% I6 @7 B
when he learned the testosterone level in the baby
$ e9 e, M- j6 owas high, he then read the product information
1 ^5 K6 s* o& v; |packet and concluded that it was most likely the rea-8 }) G3 P2 T! O% I
son for the child’s virilization. At that time, they9 D. D3 j' Q: B0 \: [" D5 S
decided to put the baby in a separate bed, and the3 t/ }5 O9 S C: L' V& k
father was not hugging him with bare skin and had' J) C, R Y3 H% V( s
been using protective clothing. A repeat testosterone
5 `* Y% H F( E" t7 [9 Jtest was ordered, but the family did not go to the
1 z, n$ y$ F( {4 ^laboratory to obtain the test.( ^0 G+ F: W- Y+ i6 s0 K
Discussion
$ q( h$ q* D* Z9 I0 O! uPrecocious puberty in boys is defined as secondary+ j/ [- E% s" Q1 ?+ ?) w
sexual development before 9 years of age.1,4
- [ F$ }( k$ [& J& hPrecocious puberty is termed as central (true) when
; W8 y! W# W3 E+ y; K+ Vit is caused by the premature activation of hypo-
* Q0 C9 Q0 \3 B8 r. zthalamic pituitary gonadal axis. CPP is more com-
' f' h; [& F" L% s o3 Cmon in girls than in boys.1,3 Most boys with CPP; |- |5 Z4 i) d8 n( ]. }8 v
may have a central nervous system lesion that is3 U; Y2 \. l5 M
responsible for the early activation of the hypothal-
: d; q) U6 z7 Z' J( _: ]amic pituitary gonadal axis.1-3 Thus, greater empha-9 y5 Z, C, |% M( F& G3 N; g* C1 ^7 J+ H
sis has been given to neuroradiologic imaging in
8 J; b5 \$ ~* P" \boys with precocious puberty. In addition to viril-; M: G. g4 e4 T; {* ]
ization, the clinical hallmark of CPP is the symmet-( r' `7 w, k9 Y3 Q
rical testicular growth secondary to stimulation by* f7 ~/ `6 K1 s) x8 W
gonadotropins.1,3; a" Z# T, s b5 Z0 [3 m
Gonadotropin-independent peripheral preco-
& I, c& ?0 m+ J6 I" G6 d3 Rcious puberty in boys also results from inappropriate
" q0 q( i. `$ v% M. n5 x) T+ bandrogenic stimulation from either endogenous or- }) K+ V- b0 p8 E/ z
exogenous sources, nonpituitary gonadotropin stim-( g- V4 u& ?$ Q( p; w# }
ulation, and rare activating mutations.3 Virilizing* p" k i% Z& C" [3 k; o5 C$ ?8 f+ g
congenital adrenal hyperplasia producing excessive, o t, x8 J& `7 A M
adrenal androgens is a common cause of precocious
, s2 L6 o- A9 I; V# Bpuberty in boys.3,4" G6 R4 ^+ y& v* P) i, R+ |+ N* E
The most common form of congenital adrenal ~+ a1 a) ]+ [/ g
hyperplasia is the 21-hydroxylase enzyme deficiency.) g+ L: R g; `; o4 M
The 11-β hydroxylase deficiency may also result in' w, e5 \- N. j: j: V
excessive adrenal androgen production, and rarely,
F1 _* j3 _# u& M! Q# h) Yan adrenal tumor may also cause adrenal androgen
6 Z% e$ k" p$ \; q7 i) @# nexcess.1,3
8 O1 G1 m& o# U5 d- gat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from( b. p5 X# C* p6 i2 F3 H% q0 _! j! g
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
% [6 ?0 U4 H' c. |5 y) uA unique entity of male-limited gonadotropin-* h, s4 \/ R' Z$ `1 Z
independent precocious puberty, which is also known+ p: S" q$ D% U3 r% Y% R
as testotoxicosis, may cause precocious puberty at a$ g- Q0 X& |+ V' d
very young age. The physical findings in these boys+ z; o" O6 F/ t( r$ s* n6 b/ A
with this disorder are full pubertal development,
8 _& w/ d; l! C7 B/ d" Hincluding bilateral testicular growth, similar to boys
/ R& Z- C& i$ f9 _6 t" wwith CPP. The gonadotropin levels in this disorder" c. M: ~: l2 N$ t
are suppressed to prepubertal levels and do not show( k3 `7 w) T% D0 R E
pubertal response of gonadotropin after gonadotropin-* H3 X8 c" E+ T8 }/ h4 i7 y
releasing hormone stimulation. This is a sex-linked! u7 u( S' t& | q
autosomal dominant disorder that affects only1 s. T# r' s( \* ^
males; therefore, other male members of the family& _3 ~* \3 F' b
may have similar precocious puberty.3
1 e# a& f8 f2 {5 ?0 A6 w! nIn our patient, physical examination was incon-3 ]8 F) m# o* ^7 }, g) f4 v! U
sistent with true precocious puberty since his testi-
, b2 Q' ]5 R8 v+ vcles were prepubertal in size. However, testotoxicosis
* n# c, ]; i8 X1 Iwas in the differential diagnosis because his father
$ d- X p/ N+ t1 Gstarted puberty somewhat early, and occasionally,2 o3 K- u, I* I" ~$ m
testicular enlargement is not that evident in the
" ^( d" v B9 r1 ibeginning of this process.1 In the absence of a neg-
, d* U+ H! E1 M2 Q$ z5 cative initial history of androgen exposure, our
% S" E0 u; P J5 k4 Ibiggest concern was virilizing adrenal hyperplasia,6 y+ X8 u/ b: X
either 21-hydroxylase deficiency or 11-β hydroxylase* W4 K% Z0 U! t. h" b& D4 [
deficiency. Those diagnoses were excluded by find-) o n3 A' x9 u; u. d
ing the normal level of adrenal steroids.& n, B, x, f# c7 @; `, T4 J, p% C
The diagnosis of exogenous androgens was strongly
, T9 o6 T2 s9 i# m1 u8 W& M {1 V5 }8 ]suspected in a follow-up visit after 4 months because
1 P$ k6 T) m, q: ~; Vthe physical examination revealed the complete disap-
$ F; s" D. i6 Epearance of pubic hair, normal growth velocity, and0 Z( o3 d& J2 s* a$ H S4 [
decreased erections. The father admitted using a testos-
0 ?+ }6 j* S$ F4 N8 Qterone gel, which he concealed at first visit. He was
) b4 ?: _7 Y- E/ \$ fusing it rather frequently, twice a day. The Physicians’
2 _4 m _1 Q" G% O# e oDesk Reference, or package insert of this product, gel or n0 k' z' I. v$ \" r
cream, cautions about dermal testosterone transfer to( U% D J; j# J1 O3 e: q
unprotected females through direct skin exposure.1 P& n7 D6 `/ o* V; K9 j; |
Serum testosterone level was found to be 2 times the
2 U0 K% s; N0 F) P- Xbaseline value in those females who were exposed to
0 X3 z l( |+ A" `0 b( D% ieven 15 minutes of direct skin contact with their male
`; t2 ~" r/ `& |7 U" h7 a5 Xpartners.6 However, when a shirt covered the applica-
8 ~, I2 _6 v8 s8 w# Y* z6 Jtion site, this testosterone transfer was prevented.1 q% X( N( j' b8 f+ H1 j$ Y
Our patient’s testosterone level was 60 ng/mL,( v% ^+ ~ f. \9 \5 z* X, O- C. N
which was clearly high. Some studies suggest that: }4 t, i( ?2 z
dermal conversion of testosterone to dihydrotestos-
2 W4 ?. u( v, f3 f* Rterone, which is a more potent metabolite, is more
/ w! L4 w! i# n c1 A, Q4 m! zactive in young children exposed to testosterone
& ?- O; Z9 s6 o& ]9 u$ zexogenously7; however, we did not measure a dihy-! |; i3 F, g( H' b: S# V
drotestosterone level in our patient. In addition to
! I+ O2 H, g* D) Fvirilization, exposure to exogenous testosterone in
9 ?! ?7 a, r$ u; `$ z5 C( ^7 ^7 kchildren results in an increase in growth velocity and/ B' E5 N) k2 L8 w& A
advanced bone age, as seen in our patient./ V+ m S) l5 j, d: l& @- E# `
The long-term effect of androgen exposure during. ?9 d6 \6 y/ o7 R. I
early childhood on pubertal development and final
1 C% n! n% {0 g( aadult height are not fully known and always remain
# i- q. _! C' I5 L! k. Ca concern. Children treated with short-term testos-+ E `" r, {# }% b. }/ Y, o* V0 Q
terone injection or topical androgen may exhibit some
3 W1 h& `9 T+ q" Xacceleration of the skeletal maturation; however, after2 X. v$ L3 h3 ~0 x, N+ f0 a
cessation of treatment, the rate of bone maturation
2 G2 r9 V+ u1 |% ], z4 L }% jdecelerates and gradually returns to normal.8,9
( U. M+ L9 l+ f0 gThere are conflicting reports and controversy" R: R. V! a- k
over the effect of early androgen exposure on adult
. Q9 Z' W' n: {penile length.10,11 Some reports suggest subnormal
1 K) ^9 \ P# n' C6 dadult penile length, apparently because of downreg-
3 O' C. b' } Culation of androgen receptor number.10,12 However,
i" c) q5 i+ q; w- v* z9 JSutherland et al13 did not find a correlation between# M8 Z/ ]; v: G+ V' u8 S
childhood testosterone exposure and reduced adult9 R( S n4 d* N* \
penile length in clinical studies.
7 Y. f9 A5 l4 Q$ _( `Nonetheless, we do not believe our patient is
" X/ q R0 R& e4 U4 p; Qgoing to experience any of the untoward effects from1 u) o$ R7 j3 ?/ V& o
testosterone exposure as mentioned earlier because1 l$ h* Q0 s. J Z8 t( y2 D. S
the exposure was not for a prolonged period of time.: x; O6 ]2 {3 |; V% }
Although the bone age was advanced at the time of
5 h" F1 U3 v+ q C% B4 Ddiagnosis, the child had a normal growth velocity at+ o0 a0 f/ D; S1 v; ^/ Y
the follow-up visit. It is hoped that his final adult: p# K3 A/ S2 b/ e; [7 N1 X* V0 i
height will not be affected.
% f+ Y8 i) e: l. KAlthough rarely reported, the widespread avail-
4 N0 B) Q4 F) i7 Q# { H: i% ?ability of androgen products in our society may
. I" H' F, c6 T& t- R3 Zindeed cause more virilization in male or female/ _) _" j0 _$ x* ]" v
children than one would realize. Exposure to andro-
3 ^/ W6 F! L& \9 ^4 G0 P& `gen products must be considered and specific ques-
# E: N+ i% D f: N6 p) ktioning about the use of a testosterone product or# C: h2 `5 X4 K$ G1 @& c; o) w
gel should be asked of the family members during0 V6 H2 p; d5 K d! v* r
the evaluation of any children who present with vir-
9 `$ M7 W( h( Z8 l% lilization or peripheral precocious puberty. The diag-
, X7 n# S$ |8 v+ |8 @nosis can be established by just a few tests and by
5 n( j6 N" i, O0 Nappropriate history. The inability to obtain such a
; g0 ? k8 } n( h0 ^; [$ q* P- Khistory, or failure to ask the specific questions, may
/ Y2 [5 F8 y6 i) t9 m6 }% Qresult in extensive, unnecessary, and expensive
- f/ f4 l8 G3 n& L' Yinvestigation. The primary care physician should be
" P! S# d6 l: a: ]aware of this fact, because most of these children
: E: q% h+ s) ?! F/ E$ F5 tmay initially present in their practice. The Physicians’
; ^5 y0 S0 N) i$ [4 |7 n0 y1 i, eDesk Reference and package insert should also put a
6 m$ B# k- f! O kwarning about the virilizing effect on a male or
5 c, A# h8 L1 W, v8 bfemale child who might come in contact with some-; W+ R7 A( u0 F, [
one using any of these products.
/ V. N1 v; ^- L l+ I+ UReferences1 \0 w6 O, p+ T/ ?0 E4 a8 @2 t j
1. Styne DM. The testes: disorder of sexual differentiation! ? A Z! P8 j) [0 t
and puberty in the male. In: Sperling MA, ed. Pediatric& @2 O$ @2 E! u9 n: V7 R
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
; f5 ^( }7 F7 y2 u4 c! j" a- D2002: 565-628.6 e3 c4 X J8 K4 t
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious* m; Z' ~! R, S
puberty in children with tumours of the suprasellar pineal |
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