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is a significant concern for physicians. Central
6 \, F5 z4 T) _ p' F& B [precocious puberty (CPP), which is mediated4 W) K4 J! h2 C" g4 M% `
through the hypothalamic pituitary gonadal axis, has. a B. N' W( m. _$ ^1 }
a higher incidence of organic central nervous system
* }( B/ q( ]) d4 q" g: P. U% Hlesions in boys.1,2 Virilization in boys, as manifested( I w/ Y4 {& S: }9 Q x% Z/ q
by enlargement of the penis, development of pubic
( u+ T5 Y. j* Shair, and facial acne without enlargement of testi-1 X! J8 z1 x* r
cles, suggests peripheral or pseudopuberty.1-3 We1 a0 u' y+ P4 o" P% K6 m% u
report a 16-month-old boy who presented with the* }1 n1 d- c W0 V, N
enlargement of the phallus and pubic hair develop-4 U1 w5 [% t, g; \9 n9 i( c! E
ment without testicular enlargement, which was due
8 S0 A4 ^2 z" g: `to the unintentional exposure to androgen gel used by6 a: l8 h' U/ D6 H: W
the father. The family initially concealed this infor-
6 l3 G$ H- M- q- O4 q# |mation, resulting in an extensive work-up for this
5 N8 ?& K- p- C% V t) N& cchild. Given the widespread and easy availability of/ ~1 Z/ }6 `) \" x# X
testosterone gel and cream, we believe this is proba-; k' \3 R/ A/ j" F8 u0 o
bly more common than the rare case report in the
# m, x/ q( e# [$ a, D' K; sliterature.4# n3 M& o$ k9 [7 i' W) l) Q% W
Patient Report
8 P5 z; c! r" ^( NA 16-month-old white child was referred to the
2 [1 j% g! C+ {+ { k. S: O6 q& Bendocrine clinic by his pediatrician with the concern
% O0 i* Q; c/ Yof early sexual development. His mother noticed* R+ `' U( A- W6 Q% r9 N' C0 P3 X+ V
light colored pubic hair development when he was
2 z6 @4 h( Z& N# z- ^: \, M! XFrom the 1Division of Pediatric Endocrinology, 2University of% _+ \0 k- G* V9 n" F3 Q
South Alabama Medical Center, Mobile, Alabama.
5 c: z" ?+ k! aAddress correspondence to: Samar K. Bhowmick, MD, FACE,
5 I; Y& ~. G% U! e7 RProfessor of Pediatrics, University of South Alabama, College of! D1 Z0 b2 g$ ~: l
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;5 b5 {/ k \! N. C
e-mail: [email protected].
+ N9 ~* j0 _2 labout 6 to 7 months old, which progressively became
. z3 K% v% L$ F ]6 Fdarker. She was also concerned about the enlarge-
' I+ O. Y9 `9 C! T/ j tment of his penis and frequent erections. The child
( c9 h( e9 h4 f$ M2 _- S, w* Dwas the product of a full-term normal delivery, with
/ ~3 u5 H7 K: {1 o0 `" Na birth weight of 7 lb 14 oz, and birth length of. Y" C7 z$ L! R% [: m( S: t- G% t
20 inches. He was breast-fed throughout the first year, ]- b! d. S' M% x
of life and was still receiving breast milk along with) i5 A' V! C* P6 w9 h: V8 V
solid food. He had no hospitalizations or surgery,
. |" Z4 L9 D0 P @& X1 J- ^and his psychosocial and psychomotor development
' h: f; O& p; R- ` c& {( p6 ?was age appropriate.. e) q: S* T- u' S0 R
The family history was remarkable for the father,) W9 o* r: ]9 K4 y7 u' W" t
who was diagnosed with hypothyroidism at age 16,8 S+ B! c! Q4 Z- t% [# ^6 S
which was treated with thyroxine. The father’s
6 F. k* X. _3 Q8 D% Z& xheight was 6 feet, and he went through a somewhat3 ?% e' R1 [ _1 N2 ?2 [. T
early puberty and had stopped growing by age 14.* c+ U( ~# @0 X' M" u( g1 X- f
The father denied taking any other medication. The/ }4 T6 j, U7 ~4 q ]
child’s mother was in good health. Her menarche" h z2 M; I; l; ]
was at 11 years of age, and her height was at 5 feet V0 h) w: V0 n* ]
5 inches. There was no other family history of pre-) |8 O, R: ^+ B* {2 u4 [
cocious sexual development in the first-degree rela-
6 d9 x4 m7 k' R q1 btives. There were no siblings.
6 \% P9 g% J3 V: }Physical Examination5 G! ^1 Y* p- u: W4 k) k
The physical examination revealed a very active,, [6 C7 k) D$ \6 D+ t! m9 p
playful, and healthy boy. The vital signs documented; B* M' _$ M) @
a blood pressure of 85/50 mm Hg, his length was
; O+ u( ~! h% h8 n7 p90 cm (>97th percentile), and his weight was 14.4 kg
8 \& e+ {5 }! K k(also >97th percentile). The observed yearly growth
/ m3 }/ \; a/ ^, evelocity was 30 cm (12 inches). The examination of
# h$ w( E; d0 w0 C, Kthe neck revealed no thyroid enlargement.
7 S# q6 x) C9 K9 P8 ^) g7 i8 X7 DThe genitourinary examination was remarkable for
" Y- o1 {) O* I# denlargement of the penis, with a stretched length of# C! H# l/ R* j G; w! a
8 cm and a width of 2 cm. The glans penis was very well
6 u' u4 p2 L2 [8 @% e1 ]developed. The pubic hair was Tanner II, mostly around
" c) }5 [6 P2 r: `" u; J" L: p540
# E: r; `( y4 U' R5 O" Zat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from' }. r+ n# Y1 P- P% Z
the base of the phallus and was dark and curled. The0 k( b6 A- p z' e2 K; N
testicular volume was prepubertal at 2 mL each.
% G2 s. g5 m" q0 @! KThe skin was moist and smooth and somewhat7 h4 `" P% I4 o
oily. No axillary hair was noted. There were no
; |' o: _9 l2 L& O- w' b8 N0 Wabnormal skin pigmentations or café-au-lait spots.; o9 i8 U0 r6 I9 l- {- q, {- R2 b7 V
Neurologic evaluation showed deep tendon reflex 2+; f/ ]* @1 R* s/ }$ c
bilateral and symmetrical. There was no suggestion
* ^$ Z9 s$ O5 p$ Z" h5 tof papilledema.
' E1 |! H2 Y0 p4 D+ \. ^. aLaboratory Evaluation) |, z h3 ~, G! ^5 n r5 Y X
The bone age was consistent with 28 months by- y B2 @ E6 A! `. a" S
using the standard of Greulich and Pyle at a chrono-
! t8 u0 D6 p1 w) h# L1 i/ N4 \logic age of 16 months (advanced).5 Chromosomal
0 M2 h. }" n7 z- ^karyotype was 46XY. The thyroid function test
$ }+ q; g f) i% a! s5 wshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
- m/ X' J7 [$ X2 {- L9 [& D% Flating hormone level was 1.3 µIU/mL (both normal).9 c- J6 R0 F A& ^( C# ?
The concentrations of serum electrolytes, blood
+ `8 ?( N2 p2 C+ }6 T( F0 @urea nitrogen, creatinine, and calcium all were
8 e d9 G5 e" m D( d; hwithin normal range for his age. The concentration h' o7 z% _2 ~$ X& F
of serum 17-hydroxyprogesterone was 16 ng/dL7 W/ j, Z1 c3 {1 b8 Y
(normal, 3 to 90 ng/dL), androstenedione was 20, x2 j( n5 t, i
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-6 ?( {4 g- c$ e. m
terone was 38 ng/dL (normal, 50 to 760 ng/dL),. h: }3 g4 e1 C+ ]
desoxycorticosterone was 4.3 ng/dL (normal, 7 to" N' a: J" G/ o4 k
49ng/dL), 11-desoxycortisol (specific compound S)& d- \$ A2 }# m: U1 o6 c
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
1 K B' u: m8 c& q3 Atisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total, N. i! ]# H) Q* r; H8 S8 }/ s1 o
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),1 |+ Y4 K" Q+ q' B. w; L
and β-human chorionic gonadotropin was less than$ c6 q0 x0 z8 g# w$ ?& R: b
5 mIU/mL (normal <5 mIU/mL). Serum follicular- A0 E! K- j1 M+ }+ S/ \2 @* J
stimulating hormone and leuteinizing hormone
: M: g) Z2 l" M6 h( b/ `concentrations were less than 0.05 mIU/mL
0 c* B2 g$ E$ ` w4 R9 e8 C(prepubertal).
7 j. q+ K# i6 SThe parents were notified about the laboratory) S& s. ~+ C/ W
results and were informed that all of the tests were
7 ^; c+ L$ N3 P5 ^- R0 @5 f+ cnormal except the testosterone level was high. The
w. G1 K6 @& ]9 T! p5 X, J0 _follow-up visit was arranged within a few weeks to
/ U" t( v- H/ w5 qobtain testicular and abdominal sonograms; how-0 M! v! c) {/ h, }
ever, the family did not return for 4 months.7 A, o8 \* |5 s4 I V+ c" Z7 I# x5 ~
Physical examination at this time revealed that the, t- K3 E0 j& \8 r: E2 J) `3 q
child had grown 2.5 cm in 4 months and had gained, @8 ^: i% W" S- U
2 kg of weight. Physical examination remained
* c' I: M9 _8 r4 a' Runchanged. Surprisingly, the pubic hair almost com-) x5 P. \" J o7 x8 \ L7 H0 H
pletely disappeared except for a few vellous hairs at! G0 N/ D9 c- q1 k' F9 H: @! s z2 k
the base of the phallus. Testicular volume was still 25 ?! z+ |4 v& P# t9 A
mL, and the size of the penis remained unchanged. \4 M+ d! _; O3 i
The mother also said that the boy was no longer hav-" Y/ [0 D4 \8 o+ e
ing frequent erections.) L4 E$ Y* S& `% ^# Y
Both parents were again questioned about use of
' i9 I7 i0 t% Eany ointment/creams that they may have applied to9 H) h1 l: ~& [ w
the child’s skin. This time the father admitted the+ B$ W* n+ k# c( L
Topical Testosterone Exposure / Bhowmick et al 5416 a- p/ T) k6 |5 I
use of testosterone gel twice daily that he was apply-
( o. n4 k& Q6 o+ g' G, ]$ ming over his own shoulders, chest, and back area for3 X: U' b) d8 d4 Z% b# r9 v
a year. The father also revealed he was embarrassed
, o; E+ A3 A0 M* b0 ]to disclose that he was using a testosterone gel pre-
& c" I8 D: B9 H2 e/ x, ascribed by his family physician for decreased libido- L" U9 h0 Y; m7 t* _- X$ {& r
secondary to depression.. d3 V/ @5 o! j) I" r. L
The child slept in the same bed with parents." F' @7 l% t) t& I2 f
The father would hug the baby and hold him on his+ ]: n: R+ u: S% I. v
chest for a considerable period of time, causing sig-! r; h) d5 k8 c6 u! x
nificant bare skin contact between baby and father.' {9 l! P. k U. f" u3 c
The father also admitted that after the phone call,
# K' y) d, H/ v7 p' u. ^when he learned the testosterone level in the baby
3 B! p7 q! M- n% U4 a. _7 Z1 ]was high, he then read the product information# W& n6 o: Q/ \1 P1 n: H+ K
packet and concluded that it was most likely the rea-+ f% |2 M& z, s/ [4 g0 S
son for the child’s virilization. At that time, they
- x# v2 \9 j2 J2 |. u; m& x; tdecided to put the baby in a separate bed, and the8 P+ x% N: R+ Z2 S" g
father was not hugging him with bare skin and had
3 } i$ e4 n/ O; U- v8 bbeen using protective clothing. A repeat testosterone7 i) N% b% X& ?
test was ordered, but the family did not go to the
' e4 l" w+ u$ \' j8 dlaboratory to obtain the test.
" {: H! T4 ^! u `' s% @& P) ~Discussion
9 ]5 S: F4 Z5 L0 D" K2 P& W$ u& |Precocious puberty in boys is defined as secondary
% @$ ~; P8 t- l! b- ?sexual development before 9 years of age.1,4- {! J7 B5 `5 }
Precocious puberty is termed as central (true) when
# S9 [% G. w% \8 z, G) E: Q. uit is caused by the premature activation of hypo-( [) W. I5 P, b$ K* f
thalamic pituitary gonadal axis. CPP is more com-
, F% `% k* J0 m. _* rmon in girls than in boys.1,3 Most boys with CPP
; K1 S* H/ A7 A3 p- _$ emay have a central nervous system lesion that is$ H4 I2 S: N1 ? ]: M
responsible for the early activation of the hypothal-
/ @2 j, N' o' D" f' z. b% e& Yamic pituitary gonadal axis.1-3 Thus, greater empha-6 k) Q7 ~7 k/ H6 K' |! [
sis has been given to neuroradiologic imaging in
O& e2 x q Cboys with precocious puberty. In addition to viril-; [( M3 ]3 g) A' k) c, L% |
ization, the clinical hallmark of CPP is the symmet- x7 p# M3 d" \ Q
rical testicular growth secondary to stimulation by
: K* O7 N9 ?' |0 M! lgonadotropins.1,3
) u8 z# t% S5 X; p8 j) x7 v+ hGonadotropin-independent peripheral preco-- v' `+ V, K# x+ o w
cious puberty in boys also results from inappropriate
8 X# i+ F% d, kandrogenic stimulation from either endogenous or
- C% J* E6 f: k1 \exogenous sources, nonpituitary gonadotropin stim-6 I5 }4 x6 {1 D6 T4 s3 B9 V# r2 Y: V
ulation, and rare activating mutations.3 Virilizing, x- z9 v6 h& j7 z! ]
congenital adrenal hyperplasia producing excessive5 P7 g7 ~# A3 w
adrenal androgens is a common cause of precocious
9 l. S: \5 B; a( H) F9 j) mpuberty in boys.3,4
! ?! @4 G$ ~2 H. m, g7 C0 FThe most common form of congenital adrenal- @8 D8 m+ T* { m [
hyperplasia is the 21-hydroxylase enzyme deficiency.
" u. J# Y) V wThe 11-β hydroxylase deficiency may also result in
/ `7 G6 y/ |( d. |2 ?2 K; lexcessive adrenal androgen production, and rarely,
- j1 G* z9 b% nan adrenal tumor may also cause adrenal androgen9 g' U7 h* b: }/ X2 \9 Q4 `
excess.1,3$ p) o/ N% ~7 H' s. X9 f
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from0 J* K4 S& u. L1 H3 L1 p9 h
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007' X3 Y+ n6 M* O
A unique entity of male-limited gonadotropin-
7 ^0 [: J; {& r/ H8 M- J3 |independent precocious puberty, which is also known; K0 T* N; ?- G
as testotoxicosis, may cause precocious puberty at a
- D }9 W6 Q; ]' V, J$ Zvery young age. The physical findings in these boys
& d' W! A! U- }7 ~with this disorder are full pubertal development,
* U5 U8 z3 |8 u6 Q$ Sincluding bilateral testicular growth, similar to boys
( T+ J# _' i7 d- r$ e7 z [9 g) gwith CPP. The gonadotropin levels in this disorder
+ Y4 j" A, `0 a5 v( u% N- {% Ware suppressed to prepubertal levels and do not show
1 R) e- C, A" j* Kpubertal response of gonadotropin after gonadotropin-: ?+ @1 c. z7 h# Q+ z: d2 l
releasing hormone stimulation. This is a sex-linked$ R+ u2 f0 J) H5 q
autosomal dominant disorder that affects only
1 b6 ?+ F) F) ]3 G8 F1 r/ Smales; therefore, other male members of the family
2 `) m3 n" H! h0 N' g. k, tmay have similar precocious puberty.3
1 g1 A! Y# [- I. X [1 JIn our patient, physical examination was incon-
) G4 A" |( g: b/ v( H; H- n7 L) Q0 Csistent with true precocious puberty since his testi- D3 @! x2 h# i: D' `! X0 [: Z
cles were prepubertal in size. However, testotoxicosis; Y3 h# x) o4 {4 W4 [
was in the differential diagnosis because his father9 G Z8 I3 B0 ?' i8 e* L' U
started puberty somewhat early, and occasionally,$ A4 t! Y1 |( ~& L5 F
testicular enlargement is not that evident in the$ V1 w# I" m O) S) s5 G) v
beginning of this process.1 In the absence of a neg-
3 @ ?6 Z1 ?: J' a* x6 @ative initial history of androgen exposure, our
: n6 x3 S( Z% @: w6 c+ q$ Obiggest concern was virilizing adrenal hyperplasia,; M& g8 c- t! b, Z9 _! u# @: H
either 21-hydroxylase deficiency or 11-β hydroxylase' M9 M$ Z( o0 I% q6 F, U
deficiency. Those diagnoses were excluded by find-
$ m+ @8 Y$ G# h4 s* Iing the normal level of adrenal steroids.) I2 f( f, A+ \" M6 t& b
The diagnosis of exogenous androgens was strongly0 b# w8 q, w t1 z: l; o
suspected in a follow-up visit after 4 months because
3 g' t$ \1 ]5 P% \; othe physical examination revealed the complete disap-
1 W9 J) E* f! }$ z& ~+ K3 H( cpearance of pubic hair, normal growth velocity, and3 ~# W q# F0 s; V% |4 J+ P
decreased erections. The father admitted using a testos-
6 Q9 N, B* u: M1 g7 r/ Fterone gel, which he concealed at first visit. He was, C0 G u6 ^& b5 e1 H* c( ~8 @
using it rather frequently, twice a day. The Physicians’! Q# C1 p8 \) \8 `; A3 o) `3 n
Desk Reference, or package insert of this product, gel or4 a1 B/ r, F+ N: K5 E v( U/ j4 p
cream, cautions about dermal testosterone transfer to
9 g t. g8 {, v, w- K$ f' K! Vunprotected females through direct skin exposure.0 Q" o1 E+ b5 |& H3 ?5 c& G. x! w
Serum testosterone level was found to be 2 times the; V0 Q# C7 n g- J0 x: i0 ~
baseline value in those females who were exposed to
, J& m6 a4 J2 v! eeven 15 minutes of direct skin contact with their male
# V7 p2 g- ]$ Z+ F5 }7 N$ v1 @; ?partners.6 However, when a shirt covered the applica-6 ~6 k- H6 ^/ ]: f, T
tion site, this testosterone transfer was prevented.
" Y2 s0 f1 A( aOur patient’s testosterone level was 60 ng/mL,
4 w, b/ m# T3 e+ Jwhich was clearly high. Some studies suggest that8 U2 |6 b7 f; P1 a* G$ O
dermal conversion of testosterone to dihydrotestos-+ Z' `% B9 U/ ~/ M3 s; ~
terone, which is a more potent metabolite, is more4 H. b2 E4 ?" l) q
active in young children exposed to testosterone& s' _/ R5 N5 B
exogenously7; however, we did not measure a dihy-
0 C+ r) h; x6 d8 Jdrotestosterone level in our patient. In addition to i) z" F* e$ P5 c0 p5 }
virilization, exposure to exogenous testosterone in+ `- o a* g! y( |, j
children results in an increase in growth velocity and S! |6 `/ ]$ Y3 u6 Z
advanced bone age, as seen in our patient.
5 [* g% B1 h" H9 V$ j4 IThe long-term effect of androgen exposure during5 |# ?8 }! \& [/ i
early childhood on pubertal development and final3 J* B ^# Z0 b0 H1 o8 n- l
adult height are not fully known and always remain8 @" I* a: y# c4 X- E+ R. {' S" G
a concern. Children treated with short-term testos-
& \0 T8 c: W3 ] V: W1 Kterone injection or topical androgen may exhibit some3 e2 X; s3 ^6 t5 O. c, f4 Z; D
acceleration of the skeletal maturation; however, after$ W" m' N+ h, n) _# V
cessation of treatment, the rate of bone maturation
1 ?( c5 }1 f o: wdecelerates and gradually returns to normal.8,9
- O& k* {0 J% q' {: Z1 xThere are conflicting reports and controversy
3 T# r0 H$ u* j E" j# Tover the effect of early androgen exposure on adult* T' q$ ~* c* W
penile length.10,11 Some reports suggest subnormal
5 Y, _7 }5 Y& ]adult penile length, apparently because of downreg- K _- y4 s) A2 g
ulation of androgen receptor number.10,12 However,
$ v9 t- m* O$ [2 K) ]Sutherland et al13 did not find a correlation between
; n+ P8 S) {: g6 ~& Y& J! }childhood testosterone exposure and reduced adult
; N! S7 |$ ~6 ]) o* |penile length in clinical studies.
" w+ l* N( A7 R! }4 F5 iNonetheless, we do not believe our patient is
* F/ y) E7 T5 }- ygoing to experience any of the untoward effects from
; G1 w0 W3 \; Y1 Htestosterone exposure as mentioned earlier because( C4 y7 w2 I) G, \
the exposure was not for a prolonged period of time.6 _. _! I& v- S8 S0 v
Although the bone age was advanced at the time of
1 T& A. F5 ]$ Z; _9 V' E. xdiagnosis, the child had a normal growth velocity at
* P2 q1 Z8 U/ N; qthe follow-up visit. It is hoped that his final adult( ]' D' u; D) w4 ?( \( {" g6 i
height will not be affected.+ w- w) n3 `! V/ i) W+ r% Q- O
Although rarely reported, the widespread avail-3 W/ n q! C7 j& g
ability of androgen products in our society may+ B) H$ G$ R0 u
indeed cause more virilization in male or female( p$ j( D1 c7 M, M; m% j2 m
children than one would realize. Exposure to andro-
1 {& L& J; W+ b" G) S) A7 igen products must be considered and specific ques- s& R! q3 R ~( Q! G6 X% I+ Y
tioning about the use of a testosterone product or
7 M3 |: B( y" ^( E! S( W0 Vgel should be asked of the family members during
4 U: g! G5 W7 R! Athe evaluation of any children who present with vir-
% a3 a# n6 w( d" ~9 |% C8 _% Zilization or peripheral precocious puberty. The diag-& u! R6 q4 N! ?) Q# Z0 m! O! p
nosis can be established by just a few tests and by
7 V/ s1 v5 A+ A! [! w* _2 h1 ?% j6 ?appropriate history. The inability to obtain such a
7 ]" M( r# G3 n$ A4 Qhistory, or failure to ask the specific questions, may
1 _9 w& U% W' h9 M( Q; Lresult in extensive, unnecessary, and expensive& I$ Q8 p5 g7 ?, n3 w8 G5 s
investigation. The primary care physician should be7 }7 ]% e' S1 g( o. ~6 W: D. J
aware of this fact, because most of these children
5 b ]5 z2 U1 e; C, `may initially present in their practice. The Physicians’
7 K7 W# h% V8 r& k2 ]: b# b! UDesk Reference and package insert should also put a
9 ?4 z, s6 e* _. k% c7 d; r3 t( g9 Zwarning about the virilizing effect on a male or
5 S& g( b1 b1 m0 B- U4 ]2 P$ A! v/ g7 i+ Sfemale child who might come in contact with some-
" j+ C# A0 Q+ {' Yone using any of these products.6 s& c4 t/ A" q( m' n$ y
References/ n3 ~5 W% Y' }. ~" c K& n
1. Styne DM. The testes: disorder of sexual differentiation/ l4 Y: R$ O3 H- F) F
and puberty in the male. In: Sperling MA, ed. Pediatric" @8 N$ D' Q0 x, [8 H! O/ O5 w. {
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
9 |# e0 i' U( d8 k6 e2 ^9 k6 p6 r2002: 565-628.
6 F& W: E, a' M4 n/ s5 {" Z2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious# C) k% T& J! X" s; a& ~
puberty in children with tumours of the suprasellar pineal; O. s1 h- s! K* U
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
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areas: organic central precocious puberty. Acta Paediatr.2 ]7 O" m) v" V" j' j
2001;90:751-756.
. ]1 F7 O( L& Z( E F5 l/ Q3. Lee PA. Puberty and its disorders. In: Lifshitz F, ed.
- M2 e+ t8 f! L: [, u) ePediatric Endocrinology. 4th ed. New York, NY: Marcel+ q% Y' Z" |3 g7 Q' W
Dekker Inc; 2003:211-238.4 J, ?8 J8 J0 H0 p$ ^5 v
4. Yu YM, Punyasavatsu N, Elder D, D’Ercole AJ. Sexual+ c# \$ \! @; u9 O0 v, L% \" D( Z
development in a two-year-old boy induced by topical) |( [1 d9 Y/ D6 E8 B
exposure to testosterone. Pediatrics. 1999;104:e23.
7 X3 f5 `; J3 [$ Q: W! K* b5. Greulich WW, Pyle SI, eds. Radiographic Atlas of
, k& `3 U& z1 I! A Z. k' KSkeletal Development of the Hand and Wrist. 2nd ed.5 Y, Y; u" {: D% G: D* n7 D
Stanford, CA: Stanford University Press; 1959.
; L' r4 }7 U5 Q% D6. Physicians’ Desk Reference. Androgel 1% testosterone,
* B7 u) b/ u8 n; A! n7 s3 FUnimed Pharmaceutical Inc. Montvale, NJ: Medical1 `( U- Z" @' }2 P( v
Economics Company, Inc; 2004:3239-3241. b% o5 c( L6 ] J0 j
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