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is a significant concern for physicians. Central
% W6 s4 a9 F0 S3 L! K+ x4 uprecocious puberty (CPP), which is mediated
2 W/ l. \) j) l1 G; g7 Zthrough the hypothalamic pituitary gonadal axis, has: M. i! f2 Q8 S) R" x
a higher incidence of organic central nervous system$ t3 q, c2 v3 a2 T, a
lesions in boys.1,2 Virilization in boys, as manifested
$ d+ X4 E* Z( V2 M9 ^0 n7 ?( c) yby enlargement of the penis, development of pubic
) j2 ]2 A. O* y0 g$ c, qhair, and facial acne without enlargement of testi-
* l* J, s" H! k9 g5 l. |; H0 Y1 f8 acles, suggests peripheral or pseudopuberty.1-3 We
) b2 F- |) Q5 |# q* e; Xreport a 16-month-old boy who presented with the
: m/ l$ C) @7 h4 q: |( @enlargement of the phallus and pubic hair develop-
m0 {- n7 E2 L4 Xment without testicular enlargement, which was due
, H0 w, {' a: Jto the unintentional exposure to androgen gel used by9 \7 w( |( O, k' U3 R3 \0 w" A' s
the father. The family initially concealed this infor-
) c8 k% W9 T2 y- S9 e) Q# W5 Omation, resulting in an extensive work-up for this: c$ B0 O% p7 z8 c# B
child. Given the widespread and easy availability of1 _& f: W9 D% e
testosterone gel and cream, we believe this is proba-. s' g/ D9 s' d# ~ P
bly more common than the rare case report in the4 D$ J2 G% T. Q; N( m4 g
literature.4. B$ u. g# ?! H& T% t
Patient Report
3 w7 _0 A% v1 }- U% c1 F$ M3 YA 16-month-old white child was referred to the) _+ y5 L) `5 a" M( P
endocrine clinic by his pediatrician with the concern
, ?: _7 S) [" V: k3 ^' k% @of early sexual development. His mother noticed8 Q5 F8 n/ y; i Q* q
light colored pubic hair development when he was5 j v8 d% k$ S9 {" [* k) p- z
From the 1Division of Pediatric Endocrinology, 2University of& V! D% c1 j {& Y- ]; N# I( Y5 h4 K- `
South Alabama Medical Center, Mobile, Alabama.' X) f- X1 {9 d7 ? X5 l5 ~: F
Address correspondence to: Samar K. Bhowmick, MD, FACE,
0 T& f4 ^5 c0 _( ?Professor of Pediatrics, University of South Alabama, College of
r) s0 B- Z4 G( L" @- UMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
8 _7 Y N2 c; U, F! P5 w9 {7 }e-mail: sbhowmick@usouthal.edu.7 s" l) P" u$ r3 l: b$ t3 B
about 6 to 7 months old, which progressively became
3 f( T) G3 Q2 Rdarker. She was also concerned about the enlarge-* S8 x( g' B: i0 f" G- m! _
ment of his penis and frequent erections. The child
: w* q. L3 Z# @ ^8 a1 nwas the product of a full-term normal delivery, with
) i# q) x+ ^6 \' ja birth weight of 7 lb 14 oz, and birth length of
8 f$ O& l- H# t/ j20 inches. He was breast-fed throughout the first year) Q I7 g$ h% v) R
of life and was still receiving breast milk along with
4 r5 {8 r9 [% b7 T% n6 k1 Esolid food. He had no hospitalizations or surgery,3 k' N7 u* @& }8 |! R/ {
and his psychosocial and psychomotor development; V, W$ ]! q2 X3 ?# P
was age appropriate.0 u; _2 l9 Y0 R V5 H4 @: z6 G
The family history was remarkable for the father,
5 d8 k2 c' Z) L/ h# l0 w6 Uwho was diagnosed with hypothyroidism at age 16,
) s; `- T9 ~0 u7 ^8 gwhich was treated with thyroxine. The father’s* C0 z$ k4 u3 c
height was 6 feet, and he went through a somewhat
; w" f+ P0 y( i* b3 hearly puberty and had stopped growing by age 14./ Q! @8 X) a% `( A3 b5 m
The father denied taking any other medication. The
" I9 w _. v( k, p6 k1 O! k. v- l9 uchild’s mother was in good health. Her menarche. o( u% ^6 o! ^
was at 11 years of age, and her height was at 5 feet
$ v# x" u. a$ V3 w5 inches. There was no other family history of pre-
- O7 I, A3 ~! E0 h7 Vcocious sexual development in the first-degree rela-
: S9 \6 F3 F/ h! qtives. There were no siblings.* G# l. h/ M7 Y7 p/ R
Physical Examination
: h& ^8 l% W! t! p9 N: JThe physical examination revealed a very active,
- |+ n# `7 J, f& Q3 c- cplayful, and healthy boy. The vital signs documented+ k8 P9 [2 D o3 q
a blood pressure of 85/50 mm Hg, his length was
( Q% ^9 ?2 S6 G90 cm (>97th percentile), and his weight was 14.4 kg
$ Z; L7 c. f& x) d6 n0 O3 ?" I(also >97th percentile). The observed yearly growth9 p6 |8 v' f: i. f
velocity was 30 cm (12 inches). The examination of
/ U4 x& B* `" M, p" Mthe neck revealed no thyroid enlargement.
0 b6 v0 u" }; ^9 I# G3 cThe genitourinary examination was remarkable for
( u" w6 V% t8 e, i8 denlargement of the penis, with a stretched length of* p2 @' A' y7 s, N7 v& z2 F$ M
8 cm and a width of 2 cm. The glans penis was very well
0 m* N9 Q# }* V. I% o% ydeveloped. The pubic hair was Tanner II, mostly around" |, D- U$ Z+ I- K& Y. u
540+ r, _3 m% n8 Y3 c3 _, l1 x" f# o
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from0 x& a2 T4 V# v; A$ i, k
the base of the phallus and was dark and curled. The
- I( j6 |/ z* |9 k* R0 m, W: p0 [& gtesticular volume was prepubertal at 2 mL each.
# p6 H/ ]" S# Q6 UThe skin was moist and smooth and somewhat
; y( j0 X- ?7 {! P* d U4 S3 Koily. No axillary hair was noted. There were no' {5 T6 o; B; K# m2 m C+ q4 c
abnormal skin pigmentations or café-au-lait spots.
1 J3 h" x0 ]6 e9 g; o; ~; k: Q; L) b& dNeurologic evaluation showed deep tendon reflex 2+2 K; Q' T+ d2 w2 v, I. l
bilateral and symmetrical. There was no suggestion% X& O$ v; d# Y, K3 m# n
of papilledema.
Z# g1 U) D3 w! B; ^4 y ]' kLaboratory Evaluation
: k! c0 C2 W; q- kThe bone age was consistent with 28 months by- {" c$ e; J/ B7 c/ [
using the standard of Greulich and Pyle at a chrono-
, Z6 k& L. m/ Llogic age of 16 months (advanced).5 Chromosomal
2 C8 f' S$ F- z; b! g- Ukaryotype was 46XY. The thyroid function test# p- @1 v+ k a
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
5 W6 S/ o3 d. T. w9 D7 t# flating hormone level was 1.3 µIU/mL (both normal).
, i1 U. a$ ~( f: @5 Y; EThe concentrations of serum electrolytes, blood! \" Y, W- b4 A* K' J. A* \. ?
urea nitrogen, creatinine, and calcium all were
3 ?8 j- G0 ~6 U$ cwithin normal range for his age. The concentration
( t# p4 o/ G# b: L3 Zof serum 17-hydroxyprogesterone was 16 ng/dL
% W/ u. i8 [" p! V2 \(normal, 3 to 90 ng/dL), androstenedione was 201 [4 M6 D7 h2 M3 E" g
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-# K; S$ _2 Z' P& m6 I: f
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
9 p& s! e: y- h$ udesoxycorticosterone was 4.3 ng/dL (normal, 7 to
1 ]# w- F5 a0 l6 K) f49ng/dL), 11-desoxycortisol (specific compound S)( O4 t. ^8 W/ m3 O# d& B* h
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
. k. x1 Z6 r: Itisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total3 W, Z- U$ m6 X: i# Y$ B& X0 Y
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),$ X. I" {6 i0 \
and β-human chorionic gonadotropin was less than; ]! a8 j* [- J; u2 `0 H
5 mIU/mL (normal <5 mIU/mL). Serum follicular
; t( y8 I. i% A, N! qstimulating hormone and leuteinizing hormone4 |, `5 U) x! k2 d" b2 f% ]
concentrations were less than 0.05 mIU/mL* @. i8 x5 V }
(prepubertal).
' _ T1 F/ b7 s( A/ |. z- h& QThe parents were notified about the laboratory; y2 }8 E4 I- x4 {- i; [
results and were informed that all of the tests were
* Y6 ]# j4 G6 \8 S! Dnormal except the testosterone level was high. The
. ^- G2 S$ n$ ^7 j" ~/ Ofollow-up visit was arranged within a few weeks to: G1 _2 {) R- S, K) [' M4 y4 U
obtain testicular and abdominal sonograms; how-
9 Z# L, R# A: ~ever, the family did not return for 4 months./ N/ s3 p' ~9 |; i4 Q r ?
Physical examination at this time revealed that the
% i" E0 ?. {- A' vchild had grown 2.5 cm in 4 months and had gained
9 R) \- | e. {' u# W4 j2 kg of weight. Physical examination remained. \/ v( l$ m) U! M5 h
unchanged. Surprisingly, the pubic hair almost com-
8 ^$ ^- o2 c* |: vpletely disappeared except for a few vellous hairs at4 r* Z9 F! c( T+ g
the base of the phallus. Testicular volume was still 2
* x6 e5 F; T2 t% [5 SmL, and the size of the penis remained unchanged.+ U' k7 {7 Z! Y; S
The mother also said that the boy was no longer hav-
1 h& [, l F0 d% k/ f- king frequent erections.
; {8 S4 r. G$ L* K( G" QBoth parents were again questioned about use of
' I" N, m. m# lany ointment/creams that they may have applied to
/ G8 O' h. P9 }3 w0 f7 _# ~2 rthe child’s skin. This time the father admitted the
$ N" N m" L2 {7 ^& {# g4 U" }Topical Testosterone Exposure / Bhowmick et al 541
) ]- o. ~# A) Z( w1 B! j) euse of testosterone gel twice daily that he was apply-
+ i' t4 z2 i5 f( Y6 H7 Ling over his own shoulders, chest, and back area for* V8 p& h0 a$ B! U4 C
a year. The father also revealed he was embarrassed
. M' R% C) h- z$ {( gto disclose that he was using a testosterone gel pre-
0 F3 F+ S9 M8 n! o. k/ p* {scribed by his family physician for decreased libido% [! ?3 Y6 T3 r1 c5 E1 U
secondary to depression.* O3 l2 V! y4 F- v4 j q7 b
The child slept in the same bed with parents.+ K8 R- s- o) ^# e0 e5 l8 p
The father would hug the baby and hold him on his, M* x8 p O! y$ }7 b* G5 f( j
chest for a considerable period of time, causing sig-" Y ^4 K K" c7 R) {
nificant bare skin contact between baby and father.
* u1 L! C d/ `2 z3 f9 L/ EThe father also admitted that after the phone call,% ~" ?- p5 z) h" l. @: A, L# X
when he learned the testosterone level in the baby
! w3 z7 C# g: jwas high, he then read the product information
/ n) i9 b' f' `packet and concluded that it was most likely the rea-5 X: ]6 F9 {! q/ Y0 d7 D
son for the child’s virilization. At that time, they
. M* |5 z) _6 n9 {# Ndecided to put the baby in a separate bed, and the
2 ^8 \$ D4 ^ v! ^' hfather was not hugging him with bare skin and had
: \1 w( {( s! Z5 a4 `; Mbeen using protective clothing. A repeat testosterone. V+ i' Q- o6 Q3 _0 D" Z" d8 e# c
test was ordered, but the family did not go to the
5 s$ j. B7 B' g" b* jlaboratory to obtain the test.2 Q2 V8 ~9 C3 Z4 q$ Q+ b
Discussion6 I) ]' }3 h' b2 P/ }) B4 v, Y" c
Precocious puberty in boys is defined as secondary- v% d( _6 Q+ l( p# b
sexual development before 9 years of age.1,4; K; ~ H+ a: ^& j3 T; @
Precocious puberty is termed as central (true) when
- j3 i- b, B. j$ k/ D" |1 w, uit is caused by the premature activation of hypo-
" q8 ]+ A6 S' ], mthalamic pituitary gonadal axis. CPP is more com-4 o5 h0 r9 M- }+ Q% g
mon in girls than in boys.1,3 Most boys with CPP, r8 w9 A% _; a* U, o
may have a central nervous system lesion that is
. p4 L! H( O2 ?, Fresponsible for the early activation of the hypothal-3 w& D3 o: _2 W" t* I2 Q
amic pituitary gonadal axis.1-3 Thus, greater empha-
& Q0 h2 s: z' p- `$ ssis has been given to neuroradiologic imaging in
: g9 H- k$ C; a( ^( O! }, S7 r2 }boys with precocious puberty. In addition to viril-+ `" e# ^/ U z" D1 x% X5 C
ization, the clinical hallmark of CPP is the symmet-$ ]3 v2 L# H. X' m/ ]
rical testicular growth secondary to stimulation by5 C+ w' n+ o0 ]! N8 B: ]) v
gonadotropins.1,3( g5 }- z' F1 W) J" [
Gonadotropin-independent peripheral preco-
' J# g+ |4 f! k! a( {. M6 {$ lcious puberty in boys also results from inappropriate
3 \- [* n* y1 z1 Iandrogenic stimulation from either endogenous or
& W3 k" I F, fexogenous sources, nonpituitary gonadotropin stim-7 \5 Y4 z# B: w3 z6 o O+ N* o
ulation, and rare activating mutations.3 Virilizing
! N2 }0 e5 ~9 t5 o$ ~4 i0 pcongenital adrenal hyperplasia producing excessive
5 r1 {! A; I4 r+ C% L$ eadrenal androgens is a common cause of precocious1 Y( O3 n9 @: x5 d$ L- W
puberty in boys.3,45 M; E2 }9 o8 D: Q6 s
The most common form of congenital adrenal* g/ i; C% U. o, T& h
hyperplasia is the 21-hydroxylase enzyme deficiency.
6 H( T8 h" Z2 P& q+ PThe 11-β hydroxylase deficiency may also result in
/ z% W t1 N6 [excessive adrenal androgen production, and rarely,
) r( s8 \1 Z+ |4 r: ]" wan adrenal tumor may also cause adrenal androgen4 p7 s$ L7 n; {1 R
excess.1,3
! G O/ r# X, Lat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
3 ^8 Q7 A9 h# e8 \5 @4 m9 O! z. g542 Clinical Pediatrics / Vol. 46, No. 6, July 2007( Z) B0 \5 h# X, a7 p" m( D# b* N
A unique entity of male-limited gonadotropin-5 s. W3 ?! X, d% G- w! ^9 Z
independent precocious puberty, which is also known" j( z: o5 q" |! s/ v3 w7 e. a
as testotoxicosis, may cause precocious puberty at a
$ m( `, c- S/ D* X0 nvery young age. The physical findings in these boys
2 i+ z5 c4 g2 d& o/ vwith this disorder are full pubertal development,) k4 R w- T1 Y
including bilateral testicular growth, similar to boys
( A- a0 v* P/ y Rwith CPP. The gonadotropin levels in this disorder
& T/ j; q2 ~2 dare suppressed to prepubertal levels and do not show/ x; O, [8 o) l4 ~3 {3 E0 {; L6 ]
pubertal response of gonadotropin after gonadotropin-
# q* o6 s0 k& q8 c- d9 R( Zreleasing hormone stimulation. This is a sex-linked
- J' ]6 W# y, M* Nautosomal dominant disorder that affects only
: w0 x+ k$ Q, J5 [) i( }$ a+ `% kmales; therefore, other male members of the family$ d h" l: ]7 q( x! B0 i" a. M! W
may have similar precocious puberty.3
8 |! C5 a2 \8 [. w0 IIn our patient, physical examination was incon-
( Q% M9 x; e" C; I$ ?sistent with true precocious puberty since his testi-1 k$ k. c9 c& [3 b; S
cles were prepubertal in size. However, testotoxicosis
) g& l3 ]9 H: ~, p! ?( p zwas in the differential diagnosis because his father) w' F4 x! X1 g* q$ \/ a1 K
started puberty somewhat early, and occasionally," N6 \( k' p) b: @
testicular enlargement is not that evident in the: c1 v' Y% X6 f3 L6 C
beginning of this process.1 In the absence of a neg-
4 n: s4 p/ Q$ Q _4 e' @ dative initial history of androgen exposure, our+ E7 K* P' }( m
biggest concern was virilizing adrenal hyperplasia,6 N; w0 C9 n M. D! w% s) _
either 21-hydroxylase deficiency or 11-β hydroxylase
; _ O( p( g7 u. ^' e5 B2 _7 Z4 Ydeficiency. Those diagnoses were excluded by find-. E- ]. P/ s1 N0 L m8 V9 \6 N
ing the normal level of adrenal steroids. E9 ]( c- q# S3 H0 T$ S
The diagnosis of exogenous androgens was strongly/ I8 E: G' B8 s8 o
suspected in a follow-up visit after 4 months because
9 X N8 P' s+ {% n/ S2 z: f/ @the physical examination revealed the complete disap- V5 v" d+ d) x Q# j
pearance of pubic hair, normal growth velocity, and
% X) j* Q& ]: Qdecreased erections. The father admitted using a testos-) ~# p7 O9 s" S) U9 n$ z
terone gel, which he concealed at first visit. He was* f+ j$ A' V1 T/ S- H) }; a6 ~
using it rather frequently, twice a day. The Physicians’, L! [7 W8 @, J* O# S
Desk Reference, or package insert of this product, gel or3 e3 O6 j+ V/ n( O, P
cream, cautions about dermal testosterone transfer to
- r; M) Y; F- M! K( cunprotected females through direct skin exposure.
% C: i0 z5 s$ E( l# Y0 e I# ESerum testosterone level was found to be 2 times the' y0 Y- F7 p9 P
baseline value in those females who were exposed to
2 \0 n+ u: N+ |* `even 15 minutes of direct skin contact with their male
8 @1 V/ i% a8 x/ e; v; u6 _partners.6 However, when a shirt covered the applica-
" `- b5 m" q% k: [ ztion site, this testosterone transfer was prevented.; ]- v: K6 ?: x O" l% F$ y% y
Our patient’s testosterone level was 60 ng/mL,5 ` v9 n9 k" m8 b* U7 u l
which was clearly high. Some studies suggest that
6 }( t" ~* W, c$ Z8 E5 Sdermal conversion of testosterone to dihydrotestos-
! \% |+ G7 ]7 w" F$ H8 Lterone, which is a more potent metabolite, is more5 n* A% u* k3 ~- A. F: w0 E
active in young children exposed to testosterone
+ Y- j( v" v0 P* l: Hexogenously7; however, we did not measure a dihy-
" J4 T l$ @, K2 mdrotestosterone level in our patient. In addition to0 v, B( d' }/ Y* b! v; c; N
virilization, exposure to exogenous testosterone in
0 ?* p" g* L3 f# B0 ychildren results in an increase in growth velocity and
# E! L. p& s( I+ e# L8 kadvanced bone age, as seen in our patient.# `% \% w, T6 Q: H# A
The long-term effect of androgen exposure during8 W( _! _! ^/ O. |4 Y/ V8 k( [( Q
early childhood on pubertal development and final
0 m0 U- m& d( v% ladult height are not fully known and always remain
$ a0 L" }3 u! U. r3 Q9 |a concern. Children treated with short-term testos-7 D; N0 a) J- y$ N( V
terone injection or topical androgen may exhibit some
5 G2 R/ x C' O& Y+ X gacceleration of the skeletal maturation; however, after; _* x. k4 w) }. z1 w. B( C
cessation of treatment, the rate of bone maturation, r. @% N4 U: q% @9 b3 C) B" t- w
decelerates and gradually returns to normal.8,9& H% V( R4 A/ ^& z6 W5 H1 f
There are conflicting reports and controversy3 @% E2 t# S: T
over the effect of early androgen exposure on adult; t: G$ Z$ s' `: w& w) S: h, E3 r
penile length.10,11 Some reports suggest subnormal' `* d( v. u! f1 t6 j* M3 X
adult penile length, apparently because of downreg-
0 E: E5 n. z) V" y0 \, yulation of androgen receptor number.10,12 However,/ q' ]- v4 S$ T+ F/ x
Sutherland et al13 did not find a correlation between
# F/ G0 p# A) y9 Pchildhood testosterone exposure and reduced adult
0 X# d/ e- S/ ^penile length in clinical studies.% T; | e- F4 A# s z
Nonetheless, we do not believe our patient is: Y3 Q! e. ?& i! z- _4 H7 S: k9 v: i
going to experience any of the untoward effects from: q7 z( ]+ f* p0 n3 o
testosterone exposure as mentioned earlier because
# M) r* x# }1 ?+ E0 dthe exposure was not for a prolonged period of time.
7 }0 a6 ~" d8 _! N3 @3 J/ g1 G$ A+ j, CAlthough the bone age was advanced at the time of x4 Y' W7 d( f K9 r& _
diagnosis, the child had a normal growth velocity at; E4 [9 [+ V: e. e
the follow-up visit. It is hoped that his final adult
* {+ a7 k7 E; G7 Iheight will not be affected.) n' `/ `; p0 B/ k1 }
Although rarely reported, the widespread avail-6 X. }- x. j U1 i% j& A' q
ability of androgen products in our society may+ J% a2 {: q. B- n& x. v: t, K
indeed cause more virilization in male or female' a j1 _. ^: S R( K0 w1 j
children than one would realize. Exposure to andro-
2 ]6 H6 B) q4 K& i, ~5 m& l. Qgen products must be considered and specific ques-1 J3 N9 m5 {% Q
tioning about the use of a testosterone product or
6 {* @7 n& f1 I% J. ]! X) dgel should be asked of the family members during( u2 x% Z8 K: X5 l' ?/ P' M% Y4 m
the evaluation of any children who present with vir-/ n3 F+ S% \5 J) Q- e/ B' j
ilization or peripheral precocious puberty. The diag-" Q7 v l" \6 N; {5 m! [4 }; m4 `4 }
nosis can be established by just a few tests and by; C" _, T" p8 T! U4 s6 W+ d8 r
appropriate history. The inability to obtain such a
) {4 x( C2 d' q; ?history, or failure to ask the specific questions, may
" F1 x V, F t& u/ g+ Zresult in extensive, unnecessary, and expensive
$ E/ [8 D o, ~+ tinvestigation. The primary care physician should be' _* x2 S5 s5 ^4 J
aware of this fact, because most of these children
% S" O d8 _2 ?- k& z1 E$ W: Umay initially present in their practice. The Physicians’2 W9 n, ?5 [6 K: {! Y% Q
Desk Reference and package insert should also put a7 j' s( m, K$ r& {, h& W9 |! b
warning about the virilizing effect on a male or
; t# |5 X( f9 yfemale child who might come in contact with some-
4 c5 F7 P+ _. }- Uone using any of these products.
" l5 K) h- D% D' r& ~References: ^6 b0 ^7 ?* A" B* K5 n% J
1. Styne DM. The testes: disorder of sexual differentiation
+ D m& O }1 c6 Mand puberty in the male. In: Sperling MA, ed. Pediatric
* e; W+ c/ M; CEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
5 o! ^" o9 e: y' u3 y# p' l2002: 565-628.
" I# X1 }$ H& A( Z# d3 H [$ v! G2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
. n9 N( Q$ o( o# I7 gpuberty in children with tumours of the suprasellar pineal; n: N6 M" L/ ?# u# u) h. `
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from8 |' k: ~9 V. P+ Q
Topical Testosterone Exposure / Bhowmick et al 5438 Y, \$ x: \2 M: B: x p+ v4 S
areas: organic central precocious puberty. Acta Paediatr.1 w6 V2 N& F5 V3 f3 |( x, \& ?
2001;90:751-756. f- }: E; n6 x0 O: s/ E
3. Lee PA. Puberty and its disorders. In: Lifshitz F, ed.- [! \2 I% [# ~. X6 ]" a) a' m, y3 _
Pediatric Endocrinology. 4th ed. New York, NY: Marcel
; `# Y( `7 K* C' D) B% cDekker Inc; 2003:211-238.2 H$ `5 S- _% Y# J; t
4. Yu YM, Punyasavatsu N, Elder D, D’Ercole AJ. Sexual6 V3 b) m$ ]& z0 u
development in a two-year-old boy induced by topical
0 C* r& v2 b1 b5 Pexposure to testosterone. Pediatrics. 1999;104:e23.
, o# `; ]% J0 q1 J( ]$ i5. Greulich WW, Pyle SI, eds. Radiographic Atlas of
! w) r1 J! m) Y, z0 a7 H9 w# N( aSkeletal Development of the Hand and Wrist. 2nd ed.' [0 P' y ], F% w6 ~% |: |+ a
Stanford, CA: Stanford University Press; 1959.
6 k$ E5 q2 U/ M F3 ^* ?6. Physicians’ Desk Reference. Androgel 1% testosterone,
$ D# S: a( y) s+ _/ SUnimed Pharmaceutical Inc. Montvale, NJ: Medical1 ]5 x4 P4 b& R' f
Economics Company, Inc; 2004:3239-3241.
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