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is a significant concern for physicians. Central
. l% M4 q8 C3 K* |+ X9 Sprecocious puberty (CPP), which is mediated9 s* s% X: r; \$ G Q% C; }, i# V
through the hypothalamic pituitary gonadal axis, has
+ c# m) B( }0 za higher incidence of organic central nervous system8 j* r( `5 M" S
lesions in boys.1,2 Virilization in boys, as manifested
3 q1 m n5 j' D6 zby enlargement of the penis, development of pubic8 h* g# {5 }. Q/ j" v* ]* H" d
hair, and facial acne without enlargement of testi-
5 V# Q1 Z: I0 V: o! u* |cles, suggests peripheral or pseudopuberty.1-3 We# G4 E" r: r! J( w7 X% _1 f7 t
report a 16-month-old boy who presented with the( W" _5 S1 `! ~8 V# K, F
enlargement of the phallus and pubic hair develop-. I* j4 S3 O+ a% p' g: l5 Y
ment without testicular enlargement, which was due$ l9 b) T- j% t. I/ a# e! X
to the unintentional exposure to androgen gel used by
0 B# N! e6 T" Mthe father. The family initially concealed this infor-4 X6 U- _( |* X
mation, resulting in an extensive work-up for this
9 k. G& M c5 m& h/ @$ x/ o0 [child. Given the widespread and easy availability of) Q B& } i5 W# Q0 |
testosterone gel and cream, we believe this is proba- x. h3 l; _: @' X5 n$ R9 F
bly more common than the rare case report in the
+ ?: n7 Z! m0 ~4 i% q! x) qliterature.48 k5 n9 {. V! w9 [2 ]6 R1 r/ q7 l
Patient Report" ~) Q( ^/ T) Q1 q: i
A 16-month-old white child was referred to the
& F( i6 K$ M" ]6 r$ c3 F; Nendocrine clinic by his pediatrician with the concern. S% o, r1 c$ T& Q$ k& o" t
of early sexual development. His mother noticed
7 ?; s; Z! K& ^& E% alight colored pubic hair development when he was
" W# @9 Y2 ~+ |' g& ZFrom the 1Division of Pediatric Endocrinology, 2University of* O- {1 r* o0 t7 O$ a4 g
South Alabama Medical Center, Mobile, Alabama.
( J) E$ R) n* M! M; VAddress correspondence to: Samar K. Bhowmick, MD, FACE,
* l2 f0 ^5 Q% {/ jProfessor of Pediatrics, University of South Alabama, College of
4 a8 K" r4 I2 B3 ^, L/ k! ?Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
1 Y+ Y$ b/ ?# r' S1 W( {e-mail: [email protected].6 m+ z$ |. R* y1 ?
about 6 to 7 months old, which progressively became
' [) _% Q$ p3 ldarker. She was also concerned about the enlarge-, u: }7 K: o$ V& M) U) ~. z6 ^
ment of his penis and frequent erections. The child5 | @/ f7 T$ Q; Q* s! e
was the product of a full-term normal delivery, with2 H- K4 E3 w8 C% X9 ^* j* R. P
a birth weight of 7 lb 14 oz, and birth length of# ~1 z# E9 k# N9 Z6 w
20 inches. He was breast-fed throughout the first year+ ~& v( a0 n8 e% |8 s" r- E
of life and was still receiving breast milk along with3 l7 ^; W/ \3 E, B1 ~; j6 _4 g' K9 K
solid food. He had no hospitalizations or surgery,
) `/ S& W$ _* T# @2 `and his psychosocial and psychomotor development
/ R; W) V" W% Y4 f9 U5 \was age appropriate.$ X' v% U7 F8 M! b
The family history was remarkable for the father,/ p) j; R2 o' v
who was diagnosed with hypothyroidism at age 16,1 b1 }8 u; h8 Q
which was treated with thyroxine. The father’s
* ~/ u* v% L0 n1 dheight was 6 feet, and he went through a somewhat
5 ]# c0 G; z0 K2 `5 m" \3 P0 wearly puberty and had stopped growing by age 14." d0 s% B1 W/ g4 O) \+ A4 T
The father denied taking any other medication. The+ ^) s e0 j5 O9 i: L; Z
child’s mother was in good health. Her menarche$ K: x7 y& L9 I2 v
was at 11 years of age, and her height was at 5 feet
3 q' y. l& }6 ]- }, R3 c1 ^5 inches. There was no other family history of pre-2 w7 M8 H9 v0 A. U
cocious sexual development in the first-degree rela-: s9 @, p' @- b$ @0 n# z
tives. There were no siblings.3 V2 T% t/ ], o4 ~; E
Physical Examination
% p! L/ ]5 [5 b1 CThe physical examination revealed a very active,: k1 V. g5 h* H2 B5 R
playful, and healthy boy. The vital signs documented, u& J7 x9 s0 l) U+ V9 v: I
a blood pressure of 85/50 mm Hg, his length was
n3 j j5 g$ Y% ]% T90 cm (>97th percentile), and his weight was 14.4 kg1 y8 P& M+ t- q' H
(also >97th percentile). The observed yearly growth: `, Y* a3 A; t0 Z
velocity was 30 cm (12 inches). The examination of
3 g5 ^ H3 o6 _8 _) `* sthe neck revealed no thyroid enlargement.( f5 D. D6 y4 g+ N
The genitourinary examination was remarkable for6 b: L& G+ {; }, [3 x1 u- Q U
enlargement of the penis, with a stretched length of! T3 o% E; I. D4 G9 s# T( T
8 cm and a width of 2 cm. The glans penis was very well
9 E, b, j6 O. Bdeveloped. The pubic hair was Tanner II, mostly around8 c+ Z, v: O' m7 g
540
* Y6 ]6 \( R ^at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from( \) i& Q2 k4 x$ Z. h1 {
the base of the phallus and was dark and curled. The
% E9 S8 E0 `/ L: r# @, Y7 etesticular volume was prepubertal at 2 mL each.6 @/ L# Y3 U( i* ^3 m. u% O9 M
The skin was moist and smooth and somewhat
+ A1 U& \- ^. V$ i% Eoily. No axillary hair was noted. There were no3 F* o! \- ]- ?) X) z. s/ D6 z# i
abnormal skin pigmentations or café-au-lait spots.( e" p5 M( d. o Q
Neurologic evaluation showed deep tendon reflex 2+
, Q; n# x1 o$ V8 U0 k4 _/ Nbilateral and symmetrical. There was no suggestion7 ? [* h$ U0 v. K
of papilledema.
! e" P* R: e1 j* p0 s( C+ u9 O& K5 rLaboratory Evaluation" M$ X) {3 @0 S# ?1 k) H% K
The bone age was consistent with 28 months by
6 W! f7 U1 b0 A$ g0 nusing the standard of Greulich and Pyle at a chrono-- M7 q! p9 X% k+ b6 \
logic age of 16 months (advanced).5 Chromosomal
- |" e$ V# s4 Q- j4 Nkaryotype was 46XY. The thyroid function test$ k: W3 a0 ]( N; w! y
showed a free T4 of 1.69 ng/dL, and thyroid stimu-8 f5 R; N0 x3 G1 W
lating hormone level was 1.3 µIU/mL (both normal).. W) h0 B, {/ p" p, m& T* R( v
The concentrations of serum electrolytes, blood+ I1 o: @; D( ?5 k' v2 r4 k# G" x
urea nitrogen, creatinine, and calcium all were
% J* v% r5 t) o8 A2 V8 swithin normal range for his age. The concentration
: J2 `& z" v- ]# B: S. iof serum 17-hydroxyprogesterone was 16 ng/dL
* n0 A1 J2 i2 y* j8 h7 n, D(normal, 3 to 90 ng/dL), androstenedione was 20
H: L" B Z. d1 J" Dng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-1 M& D3 p5 {; w. O' d# g* f! U9 [
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
/ k7 E5 a0 B0 A% h0 ?desoxycorticosterone was 4.3 ng/dL (normal, 7 to- o4 V) Y1 X# k* e- |# J* X
49ng/dL), 11-desoxycortisol (specific compound S)( w" {+ v! n; p; ^1 l+ {2 W
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
6 _( O. N9 }7 C- U8 f5 S7 p/ a4 vtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total7 R' y6 e' L( v9 _8 y# A
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
+ x- ~' g( n" M7 n( }4 T4 l2 D6 aand β-human chorionic gonadotropin was less than
0 Q) \ C. v- y# I% E8 b5 mIU/mL (normal <5 mIU/mL). Serum follicular
5 c7 r& v- ^" e$ J) |stimulating hormone and leuteinizing hormone
8 w. S6 G& B& Y2 s4 I0 ~concentrations were less than 0.05 mIU/mL
$ J6 u x9 t U! d(prepubertal).
0 [6 j& X/ ?6 E# G2 M* LThe parents were notified about the laboratory- f4 L, m. d2 g) w
results and were informed that all of the tests were
( S( H- J/ m' a! ~8 Hnormal except the testosterone level was high. The: a+ A7 T) c X' O" }- Z0 c
follow-up visit was arranged within a few weeks to% \( z" f. c5 q L7 M# \! o ?: X$ u
obtain testicular and abdominal sonograms; how-
- _6 p' T) J+ uever, the family did not return for 4 months.
' [& Y, K3 Y3 `# H$ d: }Physical examination at this time revealed that the% r7 s K. G) g- K# D' [
child had grown 2.5 cm in 4 months and had gained
- d' X: |- Y4 P; l2 kg of weight. Physical examination remained
3 v) j" z/ Z: F- [, ~, u3 z: Punchanged. Surprisingly, the pubic hair almost com-
6 U- |% ?+ Q) F+ e( [. J4 ~pletely disappeared except for a few vellous hairs at7 }) Y: N# I* g
the base of the phallus. Testicular volume was still 2
! n6 P& R' {) N1 k" ]2 _3 @. smL, and the size of the penis remained unchanged.# s1 L, e. w& O( ^4 p6 ~
The mother also said that the boy was no longer hav-
' g3 B! v) p# a. Uing frequent erections.
# z3 J4 H6 u# i$ A/ U! gBoth parents were again questioned about use of
4 I- W' G2 \* j' Sany ointment/creams that they may have applied to9 [" ?, ?# x8 l4 r+ z1 i% E
the child’s skin. This time the father admitted the" t' u* P; z/ C ?1 D
Topical Testosterone Exposure / Bhowmick et al 5415 X6 F5 |' |2 ~; W1 @/ K, Q
use of testosterone gel twice daily that he was apply-, I* v |" u8 a# t: ] d
ing over his own shoulders, chest, and back area for$ b3 W! A4 N3 V* e' t8 c2 ^) D
a year. The father also revealed he was embarrassed
+ k& {' f b- P9 _to disclose that he was using a testosterone gel pre-: O5 [/ Y+ c( |
scribed by his family physician for decreased libido# J# X& g5 S- t
secondary to depression.2 U# ^. x( M M t, ]' f
The child slept in the same bed with parents.
9 n( \, l) `) z# z, K1 F- EThe father would hug the baby and hold him on his; }* @1 |- N$ N% I4 h. k$ {
chest for a considerable period of time, causing sig-3 w/ a. E3 ~8 x& ^
nificant bare skin contact between baby and father.
$ ~8 G& y) Q6 _# J! M8 [) rThe father also admitted that after the phone call,
2 G1 k. L' L% g1 o; ^- o3 a( B+ u+ Hwhen he learned the testosterone level in the baby2 L" K5 j& @1 r! M3 B, i3 g
was high, he then read the product information
' U1 f. ^9 Z3 C0 `packet and concluded that it was most likely the rea-: t: h& r) }8 c! I$ R% C% G
son for the child’s virilization. At that time, they/ k" Z9 @3 X2 N; f# O! v
decided to put the baby in a separate bed, and the/ u0 a7 J: a: ^+ ^
father was not hugging him with bare skin and had4 w* L9 f1 G/ t K( w V
been using protective clothing. A repeat testosterone; o9 P4 ^6 J) R
test was ordered, but the family did not go to the$ a2 g1 _9 e; T) K
laboratory to obtain the test.$ k5 q1 K' r: J B$ R* ~" D- ?
Discussion* c( ?8 c/ r% b5 P
Precocious puberty in boys is defined as secondary
& \( I6 h; w" G5 Asexual development before 9 years of age.1,4
1 z _2 M7 v& K+ B: WPrecocious puberty is termed as central (true) when
/ h0 x3 s0 R7 f# W Iit is caused by the premature activation of hypo-
( n! P& A6 o4 k( g; e! Nthalamic pituitary gonadal axis. CPP is more com-5 \; f+ i- d! F2 A* N7 j( L( q! T1 b& M
mon in girls than in boys.1,3 Most boys with CPP6 J& `4 g6 n" @0 \7 S# Q# ~% O
may have a central nervous system lesion that is
" `6 J/ v. d; G( k" Q; bresponsible for the early activation of the hypothal-
% C8 o6 J" u1 g% O. l" F: c eamic pituitary gonadal axis.1-3 Thus, greater empha-
* b8 r' B5 M5 ]; \8 @/ b* usis has been given to neuroradiologic imaging in# h$ m: C" F0 B- c8 t$ N! t
boys with precocious puberty. In addition to viril-
5 E' D8 E0 S/ X [- }1 _ization, the clinical hallmark of CPP is the symmet-/ R3 L$ v/ f& j# g3 |) E/ M7 q' s# k
rical testicular growth secondary to stimulation by6 g h- i9 V( `( G
gonadotropins.1,3
% }$ \1 r+ U) S+ sGonadotropin-independent peripheral preco-
1 k- J# }2 p, [, mcious puberty in boys also results from inappropriate* @; a. o2 f, U! h" w& r) Y" J
androgenic stimulation from either endogenous or
! Y, k4 ^& d& dexogenous sources, nonpituitary gonadotropin stim-
* d. {- L& ?6 R9 d& oulation, and rare activating mutations.3 Virilizing
* L f$ X9 B# E- {6 S6 Hcongenital adrenal hyperplasia producing excessive
% H: ~4 v3 {1 w g& ladrenal androgens is a common cause of precocious
4 T- B% o; ?! s3 V5 T% cpuberty in boys.3,4
6 i9 p2 T c# G, f# T1 WThe most common form of congenital adrenal
+ ]7 P2 ]6 x8 Z6 ohyperplasia is the 21-hydroxylase enzyme deficiency.8 t2 f1 O8 j1 |' q
The 11-β hydroxylase deficiency may also result in- K" V; F; J; q; x8 K8 a
excessive adrenal androgen production, and rarely,
6 `8 w+ X- o9 R$ \; fan adrenal tumor may also cause adrenal androgen) T% E6 @ H4 n; x# N! z
excess.1,3- m1 f. f: o8 w2 M4 i- k8 `
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
+ B* h$ W9 l U6 p542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
6 r% n A) X8 ^5 k1 c" z0 xA unique entity of male-limited gonadotropin-
2 h' t; }4 ]" v+ w( j% Sindependent precocious puberty, which is also known
2 C8 x+ Q; f' X! c1 was testotoxicosis, may cause precocious puberty at a7 I8 b. @- G4 v( Z
very young age. The physical findings in these boys* q6 O' v, v) e" l* O( X! _
with this disorder are full pubertal development,
0 `% ~! ]3 s7 Q5 B2 D$ m, L/ @! vincluding bilateral testicular growth, similar to boys
* W3 `3 f& H- P' f. ]8 T" xwith CPP. The gonadotropin levels in this disorder
/ Z5 a! K3 ?% m% Y; F, Ware suppressed to prepubertal levels and do not show! l' B5 y4 b4 z# C% [* ^$ ?
pubertal response of gonadotropin after gonadotropin-
* A' o; q& `4 jreleasing hormone stimulation. This is a sex-linked
J3 u9 ?+ T! Y! sautosomal dominant disorder that affects only
9 i+ ^0 R; }9 L1 J6 Wmales; therefore, other male members of the family
1 m# j+ @0 @% M9 a. Zmay have similar precocious puberty.3
4 @! z; _9 b- Q( ~6 bIn our patient, physical examination was incon-( C' ]! n1 S2 J: d
sistent with true precocious puberty since his testi-
6 L$ H0 P5 J" E4 w7 ccles were prepubertal in size. However, testotoxicosis( M: v# v) x; H. \
was in the differential diagnosis because his father
; c7 H, d8 `% [1 ~" N4 a3 Xstarted puberty somewhat early, and occasionally,
+ E3 |5 W8 B! d/ w0 R# n. dtesticular enlargement is not that evident in the3 z6 K/ y7 U5 @$ `& V+ m0 o; r; K
beginning of this process.1 In the absence of a neg-
- m: y) D, p1 Xative initial history of androgen exposure, our
4 l G; L( F+ J9 V: u" xbiggest concern was virilizing adrenal hyperplasia,
/ y. K% X: U9 r# N6 q3 eeither 21-hydroxylase deficiency or 11-β hydroxylase+ g" _6 p" E& T; X8 [
deficiency. Those diagnoses were excluded by find-2 f8 E& J& R7 [4 P) u" e
ing the normal level of adrenal steroids.
" p/ m, S! \) ^* m( G0 UThe diagnosis of exogenous androgens was strongly
' b) o. u6 X c9 p% f9 }3 b$ }: dsuspected in a follow-up visit after 4 months because) E& N& e( s/ @/ ] g
the physical examination revealed the complete disap-: } n7 s/ e6 U, l8 U% T0 q2 g
pearance of pubic hair, normal growth velocity, and5 M$ h A4 y/ ]# Q
decreased erections. The father admitted using a testos-
- F7 Q" Z+ c' `8 f9 wterone gel, which he concealed at first visit. He was
5 F# u6 W0 u/ ]& ]using it rather frequently, twice a day. The Physicians’
; a1 }9 S' b, ?! g8 J6 n% _3 TDesk Reference, or package insert of this product, gel or
( [( k' Y; O; ~% Y y+ ucream, cautions about dermal testosterone transfer to0 T. t" t. p3 j( M
unprotected females through direct skin exposure., g! ]5 F0 \* I: a& y6 l% b
Serum testosterone level was found to be 2 times the
& J/ g8 h9 x7 Sbaseline value in those females who were exposed to
8 J% ?6 L6 r: S6 j' ~0 H d: ]even 15 minutes of direct skin contact with their male
T1 U) H; G! n6 W7 V% n# Ppartners.6 However, when a shirt covered the applica-
# A6 ?# k) e& Y5 k7 ?( Q3 ]0 o1 F$ [tion site, this testosterone transfer was prevented. r$ ?) n* q5 O7 S' c/ a
Our patient’s testosterone level was 60 ng/mL,
) c& |$ C, T2 I# m4 J( t( f( b1 Lwhich was clearly high. Some studies suggest that
$ F" j2 T5 B/ V! y- Y. i( Zdermal conversion of testosterone to dihydrotestos-
3 E, K3 J9 z; s/ k( ?# uterone, which is a more potent metabolite, is more) P, _7 Y; [+ A
active in young children exposed to testosterone
+ B8 f- z# a; ^+ `$ ?! Qexogenously7; however, we did not measure a dihy-( q1 I8 @8 X7 q/ w! t
drotestosterone level in our patient. In addition to
2 U* t) ?' M" gvirilization, exposure to exogenous testosterone in
7 k. b) ?) n6 k' ^" Ichildren results in an increase in growth velocity and' t6 A7 j* r) s* e+ ^4 V
advanced bone age, as seen in our patient.& r. i9 Y2 u, K& S. v! h
The long-term effect of androgen exposure during* S8 ?; h; i' ^4 @
early childhood on pubertal development and final7 S* t& e" N, k/ V
adult height are not fully known and always remain
) b* s% J. s" G za concern. Children treated with short-term testos-/ M- |3 J# v; P
terone injection or topical androgen may exhibit some
8 V4 B3 [# P3 A; Q0 D" zacceleration of the skeletal maturation; however, after
I3 f* I9 O3 t# ~& Q* d! Y8 mcessation of treatment, the rate of bone maturation# _1 l4 ]* _/ Q+ U- T" w8 D
decelerates and gradually returns to normal.8,9* z2 U9 Q- _. C# S3 [6 }
There are conflicting reports and controversy
3 x9 Z4 `9 G! u- d4 p5 \over the effect of early androgen exposure on adult
' t3 k3 ~* p9 _; f0 {. gpenile length.10,11 Some reports suggest subnormal
+ F7 O) P# J2 E8 [3 @9 Z1 e. f* jadult penile length, apparently because of downreg-
6 T# y! i: m7 aulation of androgen receptor number.10,12 However,% i R' `" l6 E" A' h- _8 U7 [% O
Sutherland et al13 did not find a correlation between1 }, ^& A' d B7 X/ P$ y$ n$ L
childhood testosterone exposure and reduced adult8 ?4 [) S& ?# B/ s' H9 g
penile length in clinical studies.
* Q2 g) [: T/ W6 ~Nonetheless, we do not believe our patient is7 F( r, A3 c* g3 p% j- D4 v
going to experience any of the untoward effects from6 {; M& E7 h" k- y; X* n
testosterone exposure as mentioned earlier because7 U+ W4 }+ B& U0 s6 d [/ Z$ y# P
the exposure was not for a prolonged period of time.$ g- r5 M( w) L( u5 n5 K( t) _
Although the bone age was advanced at the time of
# k/ s- U6 |# Y5 ndiagnosis, the child had a normal growth velocity at# M$ w. S" x0 p. E5 [. Q
the follow-up visit. It is hoped that his final adult! R' s2 p; A5 m2 ^
height will not be affected.8 ^- P& W# e* j& m
Although rarely reported, the widespread avail-
& a, r# Y1 K! S- c7 r$ u2 E0 Kability of androgen products in our society may
% X: I% ~' B+ A( bindeed cause more virilization in male or female
, J. C. `+ p# j* Q. rchildren than one would realize. Exposure to andro-
# d0 u5 `0 N% _, v4 Lgen products must be considered and specific ques-
% D4 h4 x, m, y4 jtioning about the use of a testosterone product or3 Y n2 f& h: H( D
gel should be asked of the family members during
9 a9 x" Y* h) ~* Cthe evaluation of any children who present with vir-
' A7 W6 b. r+ X1 Jilization or peripheral precocious puberty. The diag-
% v5 x6 W1 x$ z, pnosis can be established by just a few tests and by
! \: Z2 U# ~' G# Q) w# ~% |appropriate history. The inability to obtain such a" E' Q; E# U% z; l
history, or failure to ask the specific questions, may0 v+ c% g$ n" O9 @" r
result in extensive, unnecessary, and expensive
; a m- m7 ]1 vinvestigation. The primary care physician should be
9 Q) d- _( N% J8 z2 A) w laware of this fact, because most of these children
8 s+ G" d5 a) \7 c% |: jmay initially present in their practice. The Physicians’. H3 p- H$ @3 Q; b1 q6 j3 m
Desk Reference and package insert should also put a
6 }# }# @2 K/ l: S& ?3 R( x% ywarning about the virilizing effect on a male or
1 s! D- y& i- k" n+ tfemale child who might come in contact with some-
" b: ~; e; U6 _7 O9 r; Y) E& Tone using any of these products.
& e9 o h2 R# Z5 ?2 L/ [References) H+ v& s0 r; O
1. Styne DM. The testes: disorder of sexual differentiation
; d% i) V) y- y4 h6 Yand puberty in the male. In: Sperling MA, ed. Pediatric
o: F+ H; K% ]( W O, N3 @Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;2 b2 ^1 t7 r3 e! T
2002: 565-628.6 j. x1 o, ^0 P) u0 N3 f
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
- l' Z2 e+ M" c9 A, [puberty in children with tumours of the suprasellar pineal; H) N; o7 C# v5 y4 a$ ^
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from3 N* o" B* i/ d' `+ R
Topical Testosterone Exposure / Bhowmick et al 543
; e0 @: M; v. o' I6 oareas: organic central precocious puberty. Acta Paediatr. L3 S: ]; Y4 G; n2 v5 \
2001;90:751-756.8 d8 y( x' D9 K7 k% t
3. Lee PA. Puberty and its disorders. In: Lifshitz F, ed.
( m! }- i& z, J3 _Pediatric Endocrinology. 4th ed. New York, NY: Marcel9 i% ?5 x3 V. n" j/ n
Dekker Inc; 2003:211-238.
' I% N7 J6 r! ] j4. Yu YM, Punyasavatsu N, Elder D, D’Ercole AJ. Sexual7 Q& ]; z* v; v z6 u7 ~! j
development in a two-year-old boy induced by topical# w3 d0 k4 n. P/ `% p
exposure to testosterone. Pediatrics. 1999;104:e23.
, F' z4 [$ t" B! y+ O: h9 H; ?% s [5. Greulich WW, Pyle SI, eds. Radiographic Atlas of
8 y, I. M6 K- V, bSkeletal Development of the Hand and Wrist. 2nd ed.
# ^; X {& Q! N5 C/ Y! L, VStanford, CA: Stanford University Press; 1959.3 c& z/ l! U% s8 K; @
6. Physicians’ Desk Reference. Androgel 1% testosterone,0 M5 U2 Y- _7 ?. g0 \" v0 c% F
Unimed Pharmaceutical Inc. Montvale, NJ: Medical
; r0 u1 |, o) `8 Q6 a. _# cEconomics Company, Inc; 2004:3239-3241. O% ^$ m# }2 _+ ~) U& M+ w
7. Klugo RC, Cerny JC. Response of micropenis to topical
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