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Sexual Precocity in a 16-Month-Old
+ Y# U3 a9 t- i& g hBoy Induced by Indirect Topical. b8 V+ g$ z$ L# Z. x2 a# o9 t. Y
Exposure to Testosterone, M$ P) H; ]1 O
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2% Y& q! i' {% q! d4 Z) G# Q
and Kenneth R. Rettig, MD1' _0 C9 O% e$ v, Z, h* Q
Clinical Pediatrics6 n; L7 w+ Y6 }" Z( g
Volume 46 Number 6, x$ d: Y& ]0 k8 w3 h. C/ V
July 2007 540-543
2 c0 \% @3 H$ [; J+ H1 B/ {) |, Y/ z© 2007 Sage Publications
& a' ~7 @; B7 r2 e10.1177/0009922806296651
1 g4 O% U; @8 |- S0 B% \/ zhttp://clp.sagepub.com1 V" h. g; C- N5 S5 x
hosted at0 ^6 f! P& t7 {: o3 [2 X6 P( v6 J
http://online.sagepub.com
8 k! ^+ H' L; e" l" I' PPrecocious puberty in boys, central or peripheral,, A: p2 X# y4 Y1 `; t2 t$ q5 C
is a significant concern for physicians. Central( X& l) Q( B8 G' p1 Z: Q
precocious puberty (CPP), which is mediated8 u: c1 M( e2 G
through the hypothalamic pituitary gonadal axis, has# C8 H" J" @' Y. _, N" F% w
a higher incidence of organic central nervous system' m. |' t8 t5 o) s9 @
lesions in boys.1,2 Virilization in boys, as manifested
' ?5 b- ~/ z1 G1 L; Xby enlargement of the penis, development of pubic+ Q% R* l- ~+ y q; v3 i
hair, and facial acne without enlargement of testi-
( [4 c, Z: ^. o5 E5 ]: mcles, suggests peripheral or pseudopuberty.1-3 We, e0 K) F- l. ^+ p3 j3 o( v, N& N. ~
report a 16-month-old boy who presented with the, X, l: k( M4 Z& d# z
enlargement of the phallus and pubic hair develop-
7 M! B9 X5 B$ i, R! g: Gment without testicular enlargement, which was due
J g( f* k% }to the unintentional exposure to androgen gel used by- s& F7 k3 g( h
the father. The family initially concealed this infor-
1 Y4 H/ O* B# n- ?0 Lmation, resulting in an extensive work-up for this- R! y3 z' H7 z' } i
child. Given the widespread and easy availability of
' X+ g, T) L5 u+ o) t. dtestosterone gel and cream, we believe this is proba-7 O* m4 C. {" w
bly more common than the rare case report in the3 A' A6 y" a0 \ p
literature.4/ ~# H- {, a) b0 q) B
Patient Report. u2 n$ E2 ?; n
A 16-month-old white child was referred to the. U3 a1 ?- B' b; W. Y3 c0 f3 j/ p
endocrine clinic by his pediatrician with the concern
0 j. J1 r0 Q2 K3 o* fof early sexual development. His mother noticed3 ~6 H! ^2 C; `, e
light colored pubic hair development when he was% m) A6 B. R8 y( l
From the 1Division of Pediatric Endocrinology, 2University of
5 ?' h9 O- t& V# q3 T+ s8 G, lSouth Alabama Medical Center, Mobile, Alabama. E$ \# d! Q$ P* |; X
Address correspondence to: Samar K. Bhowmick, MD, FACE,2 {; } B4 z* [+ G' n
Professor of Pediatrics, University of South Alabama, College of
7 O+ x2 O8 v7 O; V- ~Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;6 }' v3 X* ~5 Q: G% w: ^( }
e-mail: [email protected].0 x; ~! W( V* x
about 6 to 7 months old, which progressively became+ Q3 {' @, j' w% o. |+ l
darker. She was also concerned about the enlarge-
" c3 n+ z7 P3 _8 {3 Pment of his penis and frequent erections. The child
8 u$ {( n7 y0 e$ z1 O, Uwas the product of a full-term normal delivery, with
% P0 W0 ^" t: [: fa birth weight of 7 lb 14 oz, and birth length of
" s9 g: H0 I& W2 N% O+ S* W20 inches. He was breast-fed throughout the first year
/ }# K: G+ C% s# X, p9 T# p1 }of life and was still receiving breast milk along with
6 d8 U1 \4 ]: m; S0 u# csolid food. He had no hospitalizations or surgery,5 a5 d( f2 v9 }
and his psychosocial and psychomotor development
|: D1 ^4 n* k, W* M3 D: Nwas age appropriate.: g. c' v, }$ r$ o% h
The family history was remarkable for the father,
* z7 X/ J4 j+ S5 ^% Z/ T# dwho was diagnosed with hypothyroidism at age 16,. m& P! `9 v* |, B, J' p
which was treated with thyroxine. The father’s
# }5 h! _' a/ m. W- R hheight was 6 feet, and he went through a somewhat" ~8 Y! p7 O0 [+ t; N
early puberty and had stopped growing by age 14.
7 _) c" J3 [' T) rThe father denied taking any other medication. The: W7 J0 T$ b2 b% M L8 N
child’s mother was in good health. Her menarche
8 x' O; B" \1 ] {+ X- h9 nwas at 11 years of age, and her height was at 5 feet4 f3 S8 ?* p6 ]: ?! }* o
5 inches. There was no other family history of pre-$ o5 u3 A: V* O- h$ I8 N
cocious sexual development in the first-degree rela-4 _* O4 t, A: n# x: V
tives. There were no siblings.. B, U- e; V+ V9 A4 [
Physical Examination
" {; [8 V) P: H$ k3 z" a: XThe physical examination revealed a very active,, R, @( d* }8 ^% ?4 I- w
playful, and healthy boy. The vital signs documented! e( ]/ D# Q4 _
a blood pressure of 85/50 mm Hg, his length was
$ L# E% v, k, q, K/ L90 cm (>97th percentile), and his weight was 14.4 kg! Y5 D$ m1 b- J* B3 Z
(also >97th percentile). The observed yearly growth" d5 g/ ?5 F: l% {6 q
velocity was 30 cm (12 inches). The examination of
L% t9 y" O3 ?# c1 ~4 `the neck revealed no thyroid enlargement./ Y6 \8 O( a2 F! C/ q8 J
The genitourinary examination was remarkable for
# g5 ?' A$ h! |: h- W9 g/ W& Yenlargement of the penis, with a stretched length of j( B$ j" e7 Q t7 {5 R! K8 L
8 cm and a width of 2 cm. The glans penis was very well& e1 P' c+ R; @! G) @) H# h0 [
developed. The pubic hair was Tanner II, mostly around
6 V) h3 o" i* ~540# M% g& m/ d* m- Q
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from% |& ~% X- H0 h: a% F% m6 L7 W# ?
the base of the phallus and was dark and curled. The
3 t# k7 `* q/ s+ ~! J. f3 Ytesticular volume was prepubertal at 2 mL each.
; h/ o0 a# R( Q7 c. n7 o3 x: C' JThe skin was moist and smooth and somewhat
' a% p, w; r# ]6 eoily. No axillary hair was noted. There were no% P. b( g( M! T2 q- W) C8 X, H
abnormal skin pigmentations or café-au-lait spots., C$ @: ?* [1 I5 L0 i; D7 @
Neurologic evaluation showed deep tendon reflex 2+
0 h( B1 l9 {% _3 n+ _" C( [, ]bilateral and symmetrical. There was no suggestion; H/ f( V, [1 U6 Y' |( B
of papilledema.
5 l+ u7 |; j* R4 C5 C+ N8 [4 DLaboratory Evaluation
+ S1 a- B$ L; C: zThe bone age was consistent with 28 months by) ]* U( p+ d* Q1 R
using the standard of Greulich and Pyle at a chrono-# I+ e, M3 N! Z' A3 I) a1 {' Z
logic age of 16 months (advanced).5 Chromosomal: C. V$ Y$ z! a! o9 T' G
karyotype was 46XY. The thyroid function test
$ Z( t! C2 T( Z4 Hshowed a free T4 of 1.69 ng/dL, and thyroid stimu-% w6 M" ~# R% f6 z9 c P+ V i
lating hormone level was 1.3 µIU/mL (both normal).
% Q E8 z) n: J* ?! J$ G" SThe concentrations of serum electrolytes, blood
. J* v5 i2 y: o( V9 O* L) C t% hurea nitrogen, creatinine, and calcium all were$ W3 R5 }' C. R0 k, T4 z
within normal range for his age. The concentration# \# \# l5 j0 a+ u0 k$ f
of serum 17-hydroxyprogesterone was 16 ng/dL
; ]/ Q F* R+ e R; Y(normal, 3 to 90 ng/dL), androstenedione was 20# T6 R X7 l" U4 A$ E
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-- s: Z, k% W. L9 I1 e4 \
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
$ ]# y# v% q( c* m. d4 n2 M2 O. fdesoxycorticosterone was 4.3 ng/dL (normal, 7 to2 [7 {+ `2 J6 j* ^
49ng/dL), 11-desoxycortisol (specific compound S)
% J/ A8 P0 e( `3 I3 X4 qwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
$ P. _8 I4 v* E; s' Ptisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total4 ? B/ F; a Z$ m% h- [- u
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),! I9 c3 S& g" J1 d) Z3 t5 N: ?
and β-human chorionic gonadotropin was less than
+ b% t" b8 A! D! F4 z; H5 mIU/mL (normal <5 mIU/mL). Serum follicular3 U# T) E c F$ w% G+ ~6 [
stimulating hormone and leuteinizing hormone
( l& }0 ^% ?" V3 A# T% \" r+ Q$ Fconcentrations were less than 0.05 mIU/mL7 p' e. M5 g7 \9 A
(prepubertal).
" d k. z% N1 v) G+ O' ^The parents were notified about the laboratory9 `: N0 l1 v# G: i& Y
results and were informed that all of the tests were9 r% y+ ?+ I& ~6 l3 T( ^
normal except the testosterone level was high. The( f6 Y2 ?, I& |! R0 v |0 Z
follow-up visit was arranged within a few weeks to \- l( m. }# N6 h- @$ t6 S$ D
obtain testicular and abdominal sonograms; how-
& j+ L! a! r9 V2 I% }7 Z6 Sever, the family did not return for 4 months.& K- a9 V# j+ \) {
Physical examination at this time revealed that the% |5 t" I t9 X+ i
child had grown 2.5 cm in 4 months and had gained4 y0 c* k0 N' E4 T! K
2 kg of weight. Physical examination remained
# }" Z U) e8 B) ^% y, Gunchanged. Surprisingly, the pubic hair almost com- {- o$ D6 E: T: {7 v" t, a5 \) y0 ]
pletely disappeared except for a few vellous hairs at
0 O4 Y& w/ C" L- E0 Othe base of the phallus. Testicular volume was still 25 S2 K$ R/ X4 |( b2 @
mL, and the size of the penis remained unchanged.
2 y( j! f& y+ c! u; Q1 qThe mother also said that the boy was no longer hav-( ^5 T* {$ d5 u k& W8 [ f/ r
ing frequent erections.
+ t! ~' T! i# m2 u" CBoth parents were again questioned about use of @8 `, r# P2 M: z1 s
any ointment/creams that they may have applied to
( i8 c$ w; }4 T; U$ I. S) |" ~# D2 _the child’s skin. This time the father admitted the, V6 Z) k3 x" ]1 w! U" k
Topical Testosterone Exposure / Bhowmick et al 541$ J5 I& r3 p8 ]+ q+ p/ g7 M4 U
use of testosterone gel twice daily that he was apply-
/ v- j$ I. k7 T( V3 Z# m4 Hing over his own shoulders, chest, and back area for! o; ~' J; H$ K/ B, C
a year. The father also revealed he was embarrassed; m1 R" L6 l, B( h: l- @$ x
to disclose that he was using a testosterone gel pre-" [+ F- j# L8 W/ D
scribed by his family physician for decreased libido
" `+ A8 O4 i& ]' i4 Z# l+ lsecondary to depression.
8 m$ o8 @2 H! i" P9 X8 {$ MThe child slept in the same bed with parents., H( I- F9 S( D& H7 } R
The father would hug the baby and hold him on his3 \/ B' q$ ` i
chest for a considerable period of time, causing sig-: |3 u4 M9 B# U* t7 t5 v3 k: u( O
nificant bare skin contact between baby and father.
! l5 u6 z0 Y- l* _8 {9 W; O) s; x2 `( hThe father also admitted that after the phone call,
" t5 w @, E2 p+ ~; P3 lwhen he learned the testosterone level in the baby
/ S" i: h- D5 ?2 U8 u# Zwas high, he then read the product information0 e& p$ R; t% F8 P) w9 T
packet and concluded that it was most likely the rea-
$ o% R& \1 n2 e9 |- x, I- P. wson for the child’s virilization. At that time, they
0 z: v% J8 x. V! ^" [. A; N4 bdecided to put the baby in a separate bed, and the
# ]7 b- y3 F: X. w( d% S8 k1 [father was not hugging him with bare skin and had
1 h& L6 _" E4 t- Pbeen using protective clothing. A repeat testosterone
2 z; ^/ i1 {6 vtest was ordered, but the family did not go to the7 Z5 n3 N0 _$ l( H. F
laboratory to obtain the test.+ Y) }. h3 Y- d* E, M
Discussion: k+ g& V! {6 B3 a" B& s
Precocious puberty in boys is defined as secondary- U+ z H3 b: G& W% M
sexual development before 9 years of age.1,4
- g' q5 d# h s( TPrecocious puberty is termed as central (true) when
* d0 |) ?1 {9 n* xit is caused by the premature activation of hypo-* _ s; ]4 C) n- y' {
thalamic pituitary gonadal axis. CPP is more com-6 g" r5 l Q$ i4 D
mon in girls than in boys.1,3 Most boys with CPP; Z z' r9 c: r1 m7 D% s
may have a central nervous system lesion that is+ J9 C9 q# d9 x9 L
responsible for the early activation of the hypothal-5 J) l* x/ E/ ?& F8 Y6 q( ]
amic pituitary gonadal axis.1-3 Thus, greater empha-5 X1 S r9 U. w2 p
sis has been given to neuroradiologic imaging in3 u5 L- k$ g# U
boys with precocious puberty. In addition to viril-
) [; z5 X' [% C/ ?ization, the clinical hallmark of CPP is the symmet-3 J0 E1 W1 `2 o" V: J
rical testicular growth secondary to stimulation by
+ O% |, x" j2 e) pgonadotropins.1,3/ S( S$ G5 ^2 a; I/ o5 D# `) T
Gonadotropin-independent peripheral preco-
. E6 Z/ J% G" p; Lcious puberty in boys also results from inappropriate# i, ]) r& d! w1 \$ L9 i
androgenic stimulation from either endogenous or
( W& S2 F7 H8 g2 F( nexogenous sources, nonpituitary gonadotropin stim-4 M; P- Y6 R6 m- e; m R$ E
ulation, and rare activating mutations.3 Virilizing, b1 k% K/ ]4 T" W# Z2 {. g
congenital adrenal hyperplasia producing excessive" Y; u3 M9 R; V4 m/ D4 O
adrenal androgens is a common cause of precocious& N/ O8 R. ]1 R! W7 Q: i' P/ a
puberty in boys.3,43 n2 V! R6 W5 V7 u. i4 l( B
The most common form of congenital adrenal
/ C/ u( ~& g- k0 g+ _hyperplasia is the 21-hydroxylase enzyme deficiency.; \9 ^1 M0 r6 n
The 11-β hydroxylase deficiency may also result in+ k0 V) J- x$ D( n/ I3 U" {
excessive adrenal androgen production, and rarely,7 G$ G3 B" O) s5 G
an adrenal tumor may also cause adrenal androgen5 y5 y( }# {& S, p8 u7 F+ J. h) `
excess.1,39 F. n9 W) c' H) K
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
/ B& x- n0 R8 }542 Clinical Pediatrics / Vol. 46, No. 6, July 20070 I$ \7 J* u+ J' d7 d! K! w; z% h
A unique entity of male-limited gonadotropin-( {6 S+ @8 N7 q8 }
independent precocious puberty, which is also known, Y+ g( s2 Y/ K. A3 t
as testotoxicosis, may cause precocious puberty at a: g3 Z6 ]7 F/ Z5 g
very young age. The physical findings in these boys0 f* U( V4 x4 T, a9 _6 a# c: [ Z
with this disorder are full pubertal development, ^0 H, g# M! }" {+ m
including bilateral testicular growth, similar to boys
6 o6 a- `: X$ G1 Qwith CPP. The gonadotropin levels in this disorder! g J# Y3 `, s3 W$ E, B ?/ [
are suppressed to prepubertal levels and do not show% u1 p2 T! Q+ o' x
pubertal response of gonadotropin after gonadotropin-% C6 [) ^4 U* p7 x
releasing hormone stimulation. This is a sex-linked1 m% y. G5 w# [' r! ]. O5 Y5 F
autosomal dominant disorder that affects only0 L* T$ |) K6 g, `4 Q
males; therefore, other male members of the family
- [! x& U( P+ y8 ~/ }/ g: L4 [may have similar precocious puberty.3( E, l Q, i: z' j9 I
In our patient, physical examination was incon-# t4 W- v3 ]" Q
sistent with true precocious puberty since his testi-
$ L2 G0 N; x) F4 ncles were prepubertal in size. However, testotoxicosis
) } k' Z/ h3 x" d& q+ r, Ywas in the differential diagnosis because his father
1 `( D( K# [3 q$ p7 r; Sstarted puberty somewhat early, and occasionally,3 U$ N5 e f: V& J
testicular enlargement is not that evident in the
1 R3 v. b7 W6 N( xbeginning of this process.1 In the absence of a neg-
' u7 f6 G" T h1 s% H3 J7 g( S- x$ Y6 Aative initial history of androgen exposure, our W2 {! ^/ K: s X% r/ j8 x8 z
biggest concern was virilizing adrenal hyperplasia,4 { C; v: E K4 H. G! [' H
either 21-hydroxylase deficiency or 11-β hydroxylase* u k- U" c( ]9 k g
deficiency. Those diagnoses were excluded by find-
+ K/ _ k# B& I# N4 o7 J, aing the normal level of adrenal steroids.( z) y* _9 \$ D% r( h0 f/ `& e$ R
The diagnosis of exogenous androgens was strongly- h0 B/ A! F/ R5 a W8 ^
suspected in a follow-up visit after 4 months because
+ u3 @+ a& ^% H m2 u% _/ ^4 Xthe physical examination revealed the complete disap-
( y* V% T2 g5 C* k& _; dpearance of pubic hair, normal growth velocity, and
) m# ]: ?5 b4 G! _decreased erections. The father admitted using a testos-6 u4 ]# b% V8 X$ I3 |
terone gel, which he concealed at first visit. He was5 \1 k, h1 Q1 }
using it rather frequently, twice a day. The Physicians’
2 A$ x& D( w+ R3 P LDesk Reference, or package insert of this product, gel or
1 f) R7 |) V* r+ L2 H9 ?" z* h- }8 rcream, cautions about dermal testosterone transfer to
; Y- s; `2 Y1 Y5 b* e8 hunprotected females through direct skin exposure.
6 q5 j# L0 i( `Serum testosterone level was found to be 2 times the
0 N9 T7 U6 p: c6 [ } Kbaseline value in those females who were exposed to
2 u' k; H) b$ T$ h& heven 15 minutes of direct skin contact with their male1 o/ c/ g& J5 u+ n7 v. m# k/ C
partners.6 However, when a shirt covered the applica-$ M& T3 r A4 ~
tion site, this testosterone transfer was prevented.3 h1 N+ G: m" ~& F7 t
Our patient’s testosterone level was 60 ng/mL,: D$ M( Q/ M# c+ M3 [$ s: n
which was clearly high. Some studies suggest that
7 u7 b g4 z. U5 udermal conversion of testosterone to dihydrotestos-
1 f5 r" T3 |2 u. l3 ~$ \+ Pterone, which is a more potent metabolite, is more6 W* |" k2 _/ J, L; P4 s4 B
active in young children exposed to testosterone
$ Q# r; N" Q6 n4 |1 V0 Xexogenously7; however, we did not measure a dihy-: E+ \0 A& \! i. l
drotestosterone level in our patient. In addition to
. a6 n3 T* i/ i0 Z8 M/ Tvirilization, exposure to exogenous testosterone in. V; I1 V) z; o: c/ q. A% y) ^- \; H/ i
children results in an increase in growth velocity and
9 h3 p2 o& P! h. Dadvanced bone age, as seen in our patient. C6 m v+ p7 M+ A) F& D* x V
The long-term effect of androgen exposure during7 a$ `7 g z0 E% Q0 K9 b7 ]* }
early childhood on pubertal development and final: ?! L% T3 h* B0 A6 V" S
adult height are not fully known and always remain
1 ?- ~- W* J3 `+ Za concern. Children treated with short-term testos-" O$ h- N+ @4 X& g
terone injection or topical androgen may exhibit some
" ~: @7 Y9 A5 ~# N3 @2 N: T8 oacceleration of the skeletal maturation; however, after
: {; j3 |5 u" o$ ocessation of treatment, the rate of bone maturation
2 m" H4 L4 p4 e5 Zdecelerates and gradually returns to normal.8,9, B4 K& D `" S o
There are conflicting reports and controversy
2 D% m. d& h) m3 Vover the effect of early androgen exposure on adult F1 s( T5 s% n1 u. T+ z. b
penile length.10,11 Some reports suggest subnormal
& p/ B8 w5 [) eadult penile length, apparently because of downreg-
# D6 E& U# S+ w" z0 l5 eulation of androgen receptor number.10,12 However,
3 ?: k7 `0 V( j* [Sutherland et al13 did not find a correlation between
& |/ x9 H4 `0 I% _0 p, c9 Tchildhood testosterone exposure and reduced adult7 k+ O, u, H9 F6 v8 G' I* {
penile length in clinical studies./ A; r5 D3 C, ~! y3 K
Nonetheless, we do not believe our patient is2 A- V. P$ N" M7 o! G* }
going to experience any of the untoward effects from
8 d( |, e# f) T( ]! U5 W+ [( [testosterone exposure as mentioned earlier because
; g6 M+ g7 J. fthe exposure was not for a prolonged period of time.
2 a) \% k3 e) i# DAlthough the bone age was advanced at the time of
" Y) O/ e* y" [, N/ ediagnosis, the child had a normal growth velocity at
$ A! E- @$ F) D# t1 e3 e; r) K( D% Dthe follow-up visit. It is hoped that his final adult
/ _6 P P. S ]% bheight will not be affected.3 [" l" H0 L, J
Although rarely reported, the widespread avail-
) M, i0 x8 U, I! qability of androgen products in our society may
! C, D- [) K; W- l5 h* {indeed cause more virilization in male or female
5 T/ E, C& \+ b- Hchildren than one would realize. Exposure to andro-
- U) @+ Q& U0 V3 ~; \3 fgen products must be considered and specific ques-
) o5 r" M0 q1 g0 C5 E) H( etioning about the use of a testosterone product or
& A+ Y. }! [' G& ~) P, Cgel should be asked of the family members during4 V! k% t$ u$ s# ~
the evaluation of any children who present with vir-
: Y% h& A" h9 k6 _2 |& Wilization or peripheral precocious puberty. The diag-) ~9 `& I" g4 a) n0 |) l& H
nosis can be established by just a few tests and by
" _- H6 ?* o r) Nappropriate history. The inability to obtain such a
% x% \2 Z) {4 f# f3 I- Ihistory, or failure to ask the specific questions, may
* V9 ]/ p z% |7 n# eresult in extensive, unnecessary, and expensive
& }# J a: n0 R0 P" h* ainvestigation. The primary care physician should be
* ~$ U) k; [& I9 J# faware of this fact, because most of these children
/ \$ l4 Z( _) l/ D/ A+ t8 c, F9 {may initially present in their practice. The Physicians’
% u( K& { @2 o( b; h3 S$ \3 SDesk Reference and package insert should also put a
9 T4 e! ^* \: n6 Lwarning about the virilizing effect on a male or5 A( k: Q6 A+ h: C3 g" N* c6 p( p3 a. h
female child who might come in contact with some-6 \* T/ Q6 x4 t
one using any of these products.
8 x5 E7 z3 r- w1 e! C: ]$ KReferences3 s- ~+ ^. W% X! R! [0 t0 M
1. Styne DM. The testes: disorder of sexual differentiation
% A& ~* \; E$ z( r2 f( j5 |- ^and puberty in the male. In: Sperling MA, ed. Pediatric
" E/ j# o0 {: B9 c \0 u9 u! @5 @5 WEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;5 Z5 K) w4 l* f7 \/ ]4 B7 g6 Z1 ]
2002: 565-628.2 h, A8 u0 A. E
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
& M9 v$ Q& d H: ~# Kpuberty in children with tumours of the suprasellar pineal |
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