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is a significant concern for physicians. Central
3 l! Y6 e' {: r& X, xprecocious puberty (CPP), which is mediated* d! x5 [/ [% J: K
through the hypothalamic pituitary gonadal axis, has& r) j- q# Q+ T, U
a higher incidence of organic central nervous system
2 N& }: Q- u. v( N6 ~lesions in boys.1,2 Virilization in boys, as manifested' q" B8 C; }9 H* r2 a
by enlargement of the penis, development of pubic
9 i8 \# K) E& Ahair, and facial acne without enlargement of testi-
/ D/ {6 A+ S- i; `8 \% Icles, suggests peripheral or pseudopuberty.1-3 We; z' w4 R5 `" p
report a 16-month-old boy who presented with the
. d" m7 h+ Z0 W' D, benlargement of the phallus and pubic hair develop-; V: c/ l4 w4 U% l4 m+ F8 m
ment without testicular enlargement, which was due" }% u9 {! x! s5 D8 _2 E4 n
to the unintentional exposure to androgen gel used by
. ^. G! v- W! [4 W- g- K& O, T9 r7 d5 Q8 }the father. The family initially concealed this infor-
# ~, Z5 z \" J8 q1 m# Bmation, resulting in an extensive work-up for this. K' a# U; z2 U% v6 c
child. Given the widespread and easy availability of
& \& a9 e7 C, L ^5 ftestosterone gel and cream, we believe this is proba-/ A( t- n2 i1 H
bly more common than the rare case report in the
2 G1 o# t5 P* V& n' gliterature.43 t7 ?5 ~2 G. A, U
Patient Report
7 z" k/ k6 B1 p% Z2 @6 ~' ^6 g2 wA 16-month-old white child was referred to the! N8 D0 K% [. E1 R) G* E
endocrine clinic by his pediatrician with the concern0 V3 Z/ B4 A/ c6 t. G. h0 I: ?6 _
of early sexual development. His mother noticed
( I: A: i6 g9 X1 G" t" s9 I3 ?* nlight colored pubic hair development when he was
1 w$ ^7 J! X' _# I( }From the 1Division of Pediatric Endocrinology, 2University of
8 w1 t/ M" ?- B4 h- |+ \+ w/ w- S$ XSouth Alabama Medical Center, Mobile, Alabama.) P B% D& H. x6 y3 i# E
Address correspondence to: Samar K. Bhowmick, MD, FACE,
' H# u: {2 T7 ~6 b9 c/ X' TProfessor of Pediatrics, University of South Alabama, College of
( _6 g* i, T3 D" ^+ I( zMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;* S' K* j8 W7 W
e-mail: [email protected].' \1 q) \0 U) F* Z7 Z$ U0 f- o
about 6 to 7 months old, which progressively became
: F) X3 ~: I6 ^& @, Y, ydarker. She was also concerned about the enlarge-
3 n% Z6 A5 _7 d: O. z5 S1 B- yment of his penis and frequent erections. The child
1 ]% C0 g3 K! xwas the product of a full-term normal delivery, with
; E, V: v% n, p* Ba birth weight of 7 lb 14 oz, and birth length of
: z# ]3 m2 B; e1 [$ K20 inches. He was breast-fed throughout the first year6 m/ _1 `3 k2 e# P" G
of life and was still receiving breast milk along with
2 |, M3 h" [/ h" Jsolid food. He had no hospitalizations or surgery,
% t3 [, l& ^# ~6 \& Aand his psychosocial and psychomotor development- w9 R0 u0 w0 V" H7 [2 |/ q
was age appropriate.' h; |' D3 N- V5 z, ~9 Y
The family history was remarkable for the father,( g3 b$ o! u' @
who was diagnosed with hypothyroidism at age 16,6 V# w. S8 p1 K
which was treated with thyroxine. The father’s
/ [3 B5 `) q' Aheight was 6 feet, and he went through a somewhat
+ J% F& y3 R `: u+ Vearly puberty and had stopped growing by age 14.
# r1 n+ u. K2 m; ]/ ]( hThe father denied taking any other medication. The* K4 l" A. P& W# j5 Q6 d
child’s mother was in good health. Her menarche
- x* L( r* R2 }, s. ?/ C# vwas at 11 years of age, and her height was at 5 feet- G' D' A! T7 a' f: T3 M
5 inches. There was no other family history of pre-' {& c- | w+ d3 G
cocious sexual development in the first-degree rela-
u. Z" h% N/ w! d& Rtives. There were no siblings.
7 k! [/ h9 K! c$ z" X! Q. HPhysical Examination
+ P( ~, J$ D8 w3 NThe physical examination revealed a very active,) I+ m9 Y" y8 ]: y+ w1 x! h. U
playful, and healthy boy. The vital signs documented
; P' M5 ~# O6 xa blood pressure of 85/50 mm Hg, his length was) N) w/ k7 g7 \2 }
90 cm (>97th percentile), and his weight was 14.4 kg
7 i/ S+ y" M( B: S! E(also >97th percentile). The observed yearly growth
6 b0 _% t2 ?4 nvelocity was 30 cm (12 inches). The examination of# \! X- j; P) ^* o* {
the neck revealed no thyroid enlargement.
" u* n! a* A% a1 aThe genitourinary examination was remarkable for
1 Y+ E0 ?9 @% s6 Y* Zenlargement of the penis, with a stretched length of
* m8 I( u1 z' S( y0 e( A1 N8 cm and a width of 2 cm. The glans penis was very well" ~0 I! ~( J" V4 k
developed. The pubic hair was Tanner II, mostly around
, Z' ?7 x; O% W M540# Z* X! x# c6 P% S
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from* V# S9 A6 M! B1 ?3 ]! Q5 s
the base of the phallus and was dark and curled. The
/ M1 W/ f! s0 n# {: }1 Q# F, ?testicular volume was prepubertal at 2 mL each.
- p, @ d0 g0 t8 [$ |2 ?- j, \" vThe skin was moist and smooth and somewhat
( Q3 Q5 O4 r/ [: _; {oily. No axillary hair was noted. There were no2 M8 q2 \9 y5 m5 k7 i/ y1 y0 |
abnormal skin pigmentations or café-au-lait spots.
" z' {* n, i; Q, r) t; W; h, YNeurologic evaluation showed deep tendon reflex 2+) K& N- h6 x; ^0 v
bilateral and symmetrical. There was no suggestion7 ~! o) F$ y q
of papilledema.! T$ J; o& a4 {3 l, C9 x
Laboratory Evaluation. V9 H9 ?. @3 G3 V9 F* }
The bone age was consistent with 28 months by
; ~/ U' n" S9 r& x# `: l) Husing the standard of Greulich and Pyle at a chrono- } v/ G# ~7 O2 y9 u7 \# g6 h
logic age of 16 months (advanced).5 Chromosomal, a. o6 S5 f$ b# I0 x
karyotype was 46XY. The thyroid function test
8 M/ `; i. @+ C/ J) C9 Eshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
2 h. E- b; A Y/ ~# p8 Y1 Ylating hormone level was 1.3 µIU/mL (both normal).
6 o9 C4 ], n3 u% j; T* ?The concentrations of serum electrolytes, blood$ \% `* l( B: ]3 c' f1 }4 k# }4 j
urea nitrogen, creatinine, and calcium all were" q4 w$ }$ D" o/ V& b& I4 l! o* z
within normal range for his age. The concentration! d: k) y' d0 s5 k* d
of serum 17-hydroxyprogesterone was 16 ng/dL% l8 W j V$ q) q7 L
(normal, 3 to 90 ng/dL), androstenedione was 20
6 R! i! P& S( q# `8 b6 D8 ^ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
5 Z5 u) X9 Q! [terone was 38 ng/dL (normal, 50 to 760 ng/dL),- `4 m8 W: Z' z D' t" C+ M) I
desoxycorticosterone was 4.3 ng/dL (normal, 7 to/ ~4 ~. K! \$ t9 j( K
49ng/dL), 11-desoxycortisol (specific compound S)7 N( _+ D" H! o/ A& {8 y
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
7 R. u. j* r/ r7 ftisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total' P* u" O" U! p* a8 V) F9 U. [
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
: J1 X. `2 ^4 v# H0 D$ y! t( C( [and β-human chorionic gonadotropin was less than
, a; P d! e4 o% g0 ^5 mIU/mL (normal <5 mIU/mL). Serum follicular/ R* i$ e4 D; S" t+ k$ ^
stimulating hormone and leuteinizing hormone
& N: U i" D: p' Yconcentrations were less than 0.05 mIU/mL' w" S- M; n5 k! ]4 d! ^/ [0 g3 L
(prepubertal).
+ R; Q# i) e8 W& ~The parents were notified about the laboratory6 m7 Z! T. r* \- D: `2 x! U" d
results and were informed that all of the tests were
+ l7 m- {* V- d" W( e. i2 `) Tnormal except the testosterone level was high. The
8 u) y; I4 P$ u2 d9 j! }: Jfollow-up visit was arranged within a few weeks to
4 r) ]1 c c# I5 E/ h" z/ Cobtain testicular and abdominal sonograms; how-
. L. D- y' i/ m6 qever, the family did not return for 4 months.
8 y6 `! B/ |' ?; W- u. j6 `- lPhysical examination at this time revealed that the' h; {0 d' V3 U6 ~$ C
child had grown 2.5 cm in 4 months and had gained
9 P& S0 t9 V5 i# u+ o5 V6 g2 kg of weight. Physical examination remained/ n, U7 z' L# q9 |# \
unchanged. Surprisingly, the pubic hair almost com-
9 q. i; r9 ]3 y- Apletely disappeared except for a few vellous hairs at
/ B4 C' v( I) f5 xthe base of the phallus. Testicular volume was still 2! f4 K) T* n$ E1 Y8 u9 I
mL, and the size of the penis remained unchanged.
8 N3 [' r& p! A- i7 B1 r1 [6 |1 `The mother also said that the boy was no longer hav-
& J- |4 X3 T* Ding frequent erections.7 c% c, J& h) K( O
Both parents were again questioned about use of0 c% M& ? v8 U
any ointment/creams that they may have applied to: P3 M1 c5 `% S0 v" |
the child’s skin. This time the father admitted the) p4 a M* W, X# J. V
Topical Testosterone Exposure / Bhowmick et al 541
3 I# u6 {5 V- @6 J9 n, Juse of testosterone gel twice daily that he was apply-* T8 v& m A! b7 n7 R! h
ing over his own shoulders, chest, and back area for
. b1 C4 A6 l! V' S. pa year. The father also revealed he was embarrassed
8 |/ Y5 Z' ?& Nto disclose that he was using a testosterone gel pre-% A/ n9 ^' S0 x6 G: o
scribed by his family physician for decreased libido: d4 Y0 r( P0 d+ z) e
secondary to depression.
; S% l! x9 n% O! Y* j# j( G. {The child slept in the same bed with parents.
1 z# u+ A$ U/ s pThe father would hug the baby and hold him on his
% e# X6 k q6 @* nchest for a considerable period of time, causing sig-
- J) S7 n2 X4 V% qnificant bare skin contact between baby and father.
" P/ i* Z* F4 @, @- o% o. ZThe father also admitted that after the phone call,2 g! s( G! C! V: p- F! A' I- N
when he learned the testosterone level in the baby
' O! ]! B9 b% [was high, he then read the product information
' r/ N3 o3 `, N9 wpacket and concluded that it was most likely the rea-
2 Q# D, J0 W$ b( J7 fson for the child’s virilization. At that time, they( \6 J6 n6 w: ] m; D7 d3 Q
decided to put the baby in a separate bed, and the8 D. [6 C6 g8 U5 A# w
father was not hugging him with bare skin and had
3 H1 i$ ~9 `1 x) c: J0 xbeen using protective clothing. A repeat testosterone
, L. S d( X7 c# p" ?( X, ~ Ztest was ordered, but the family did not go to the
% |' f- D6 I6 a0 ?/ T$ [laboratory to obtain the test.
; q) |! {7 i. t( u& s& X- N/ y$ sDiscussion
. W' r" d4 a: Q5 @; ?9 a% \Precocious puberty in boys is defined as secondary; X5 s6 P8 D- G; U
sexual development before 9 years of age.1,4
/ `1 \+ a% f' L k! T2 @/ RPrecocious puberty is termed as central (true) when* T5 }- q7 l) g+ X' f2 _5 u
it is caused by the premature activation of hypo-
2 u% X {1 j9 }. z& p ], X5 D7 ~thalamic pituitary gonadal axis. CPP is more com-
; @( p3 h1 ^" S) umon in girls than in boys.1,3 Most boys with CPP% J) C, y/ H3 E1 R$ r" z
may have a central nervous system lesion that is
, T$ H9 j9 t3 Z5 @8 o9 |- Cresponsible for the early activation of the hypothal-
/ x. i! y0 |3 L) namic pituitary gonadal axis.1-3 Thus, greater empha-* M) {! Y5 P* E$ @8 h. {
sis has been given to neuroradiologic imaging in: u6 z) h0 l- O2 E2 \; m9 t2 v2 E m! K
boys with precocious puberty. In addition to viril-" F) B9 |8 x4 R6 J
ization, the clinical hallmark of CPP is the symmet-7 K. e0 r' a/ A& s
rical testicular growth secondary to stimulation by
; O) n) c9 r& Y9 q+ A/ {gonadotropins.1,3+ n; n* Z1 b0 H1 T. H
Gonadotropin-independent peripheral preco-! b9 A3 U" O- B5 o
cious puberty in boys also results from inappropriate
* G( d# Z% c- Yandrogenic stimulation from either endogenous or
% g' f+ |0 ?. d7 Iexogenous sources, nonpituitary gonadotropin stim-) {1 n* A4 z* i& ?4 @: e0 N
ulation, and rare activating mutations.3 Virilizing! m9 Z; m* M5 ?) {8 |5 V
congenital adrenal hyperplasia producing excessive0 g q3 p( @. `: ?: r( r) Q
adrenal androgens is a common cause of precocious
! J& x% U& y: S( Mpuberty in boys.3,49 Y% Q3 l9 G3 V \' h8 V2 B ^, |
The most common form of congenital adrenal
4 Z7 p5 t: ]0 I& jhyperplasia is the 21-hydroxylase enzyme deficiency.
: |& u' v/ o, H8 M* x+ U _ u* ^% m# |The 11-β hydroxylase deficiency may also result in0 R, a( ~) Z4 }9 _! q
excessive adrenal androgen production, and rarely,# {. h1 k* G* g$ K4 R+ c5 o9 N4 J
an adrenal tumor may also cause adrenal androgen
7 m- t! ]8 H$ }+ Xexcess.1,3) }! l1 v; | W- x- o/ [4 p0 v& B
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from& K( d# r7 Y( u
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
% v, F; N4 \: _- a/ v4 z4 U' k! gA unique entity of male-limited gonadotropin-
9 K7 k" c' h$ F8 n% l/ |/ |independent precocious puberty, which is also known9 l7 {& m& }, k7 r$ `
as testotoxicosis, may cause precocious puberty at a6 W5 t' V0 ]" D' l
very young age. The physical findings in these boys6 p+ \! U" l0 {7 e/ s3 I5 W7 Z
with this disorder are full pubertal development,
, ^8 a: f. H. s6 G7 p/ g4 B* eincluding bilateral testicular growth, similar to boys5 @5 O, ]3 |6 v- X( g
with CPP. The gonadotropin levels in this disorder2 Q% ^+ i9 d0 \; v. m4 F9 ^8 ^
are suppressed to prepubertal levels and do not show" R! n$ o! ]5 L# R: F. s4 b* N
pubertal response of gonadotropin after gonadotropin-
$ e: g6 Q# w4 F4 D7 jreleasing hormone stimulation. This is a sex-linked
v$ G& J6 d D) B/ u. Dautosomal dominant disorder that affects only1 ~, j9 V6 K8 y5 ^# A
males; therefore, other male members of the family+ j* k# a& k) [! C7 j
may have similar precocious puberty.3& c$ `" `$ b4 a/ K; [
In our patient, physical examination was incon-3 C( \$ s+ Y; {3 ?$ P+ a* \ s% o& j) h
sistent with true precocious puberty since his testi-0 ]0 {& @& j! w6 E, q+ A7 x) @
cles were prepubertal in size. However, testotoxicosis
6 C+ B. q! k* G) Gwas in the differential diagnosis because his father3 i5 R9 M5 p& F) @
started puberty somewhat early, and occasionally,0 R& `. U6 W2 `/ D- v4 v; g
testicular enlargement is not that evident in the
3 s+ g( p$ ~8 r% vbeginning of this process.1 In the absence of a neg-9 V/ x1 z& ^' k `6 `7 ^
ative initial history of androgen exposure, our# G/ ?& T) F5 m' C
biggest concern was virilizing adrenal hyperplasia,' I" k/ J; I& ?+ Z) z- { K; W" w, q
either 21-hydroxylase deficiency or 11-β hydroxylase; o% [% N, @% r3 T9 P
deficiency. Those diagnoses were excluded by find-; J" b- `4 N4 C s
ing the normal level of adrenal steroids.8 @! b1 p0 q7 K# f
The diagnosis of exogenous androgens was strongly7 `& z4 L9 l( U( ?, a/ z
suspected in a follow-up visit after 4 months because
8 g9 e8 r( u/ a; ?- N$ a9 jthe physical examination revealed the complete disap-) _3 x+ X5 u& H4 t. P6 C
pearance of pubic hair, normal growth velocity, and1 S1 p1 f" ~$ R7 m- M8 T
decreased erections. The father admitted using a testos-
% |9 E4 a# [3 Hterone gel, which he concealed at first visit. He was7 x! h" ^2 o9 w% z1 v4 g& ^
using it rather frequently, twice a day. The Physicians’
" `5 R% u7 r; K- n A; c+ LDesk Reference, or package insert of this product, gel or9 S O( `% q5 \6 e1 {' i g
cream, cautions about dermal testosterone transfer to+ d4 a1 ` g4 p2 {
unprotected females through direct skin exposure.
0 s# E& t) V9 o" @9 ^Serum testosterone level was found to be 2 times the
: G! W7 T% h# b/ Zbaseline value in those females who were exposed to
" N' k; Y/ V( P* E! beven 15 minutes of direct skin contact with their male3 y7 O+ B( D1 r# p) I. v2 z" K
partners.6 However, when a shirt covered the applica-$ B! Y( c. ?6 a
tion site, this testosterone transfer was prevented.7 Q7 I8 M5 R( L+ ^4 `
Our patient’s testosterone level was 60 ng/mL,
, g7 k @2 P4 m9 Rwhich was clearly high. Some studies suggest that
1 u9 v$ ^+ m. P# I/ Zdermal conversion of testosterone to dihydrotestos-
7 |7 {! U# ?$ B2 O! U' E: G" ]terone, which is a more potent metabolite, is more
+ @( }: y3 y1 r# e4 B$ factive in young children exposed to testosterone
$ S5 ?6 b. W. W4 [8 }# }exogenously7; however, we did not measure a dihy-! n' B7 \% q8 N& G F! Q
drotestosterone level in our patient. In addition to9 g* u3 W- N/ ^" h t
virilization, exposure to exogenous testosterone in9 w$ W+ T& I V
children results in an increase in growth velocity and
! B8 a' E) X( h0 zadvanced bone age, as seen in our patient.
9 t% _+ }+ J; V; F6 SThe long-term effect of androgen exposure during
, O& F% U3 [8 d/ M! X+ Gearly childhood on pubertal development and final2 E/ y9 r& I# ]* T& n. B) l( l f
adult height are not fully known and always remain
n8 B+ x6 b4 z; |* v1 Ca concern. Children treated with short-term testos-
! q9 }7 c% H( M, S7 M# rterone injection or topical androgen may exhibit some( k9 G1 p5 i5 |' [- G; I
acceleration of the skeletal maturation; however, after
2 i8 C# t* X$ h+ P1 Z- ~: ]cessation of treatment, the rate of bone maturation
" G2 @7 h9 V' g. H% a6 qdecelerates and gradually returns to normal.8,91 \3 }5 i1 ]4 ]1 ?
There are conflicting reports and controversy& _3 X9 }8 U3 ?5 u, C$ O1 q
over the effect of early androgen exposure on adult
0 R9 {6 E: v) R, g" p5 y3 jpenile length.10,11 Some reports suggest subnormal
2 n4 W* Z( c' _2 gadult penile length, apparently because of downreg-
# d( c/ S& b( B: m! q/ ~ulation of androgen receptor number.10,12 However,
8 q( }! l7 Z# w2 W. `) YSutherland et al13 did not find a correlation between
( i* V% K! I) v" N8 y& \$ Wchildhood testosterone exposure and reduced adult7 I6 Z( A. k3 j, B' `
penile length in clinical studies.+ L. E% U9 j# m5 q: w" y
Nonetheless, we do not believe our patient is
( z @% {1 Q2 Z) }$ N9 r" Qgoing to experience any of the untoward effects from
( O0 h$ R1 m9 u1 p" U! Q( Atestosterone exposure as mentioned earlier because
" } H. c. N/ X5 }- }% Hthe exposure was not for a prolonged period of time.* C2 ]! e4 D+ h* ?) o
Although the bone age was advanced at the time of1 b6 k/ h2 q5 v; s/ z$ t; w
diagnosis, the child had a normal growth velocity at& Y2 X g" {8 H# X5 @# ?& O
the follow-up visit. It is hoped that his final adult
1 r, W6 w9 k$ e7 v8 q5 V( kheight will not be affected.) v; j2 {& I/ R4 O( q7 Q) P
Although rarely reported, the widespread avail-
) T. s) p- O& U4 E+ gability of androgen products in our society may' `7 {9 j# D6 q$ |5 p3 e! q
indeed cause more virilization in male or female4 k* W# G" }! I; B* @9 ^
children than one would realize. Exposure to andro-. O. w% q7 } R: x! e* r) A
gen products must be considered and specific ques-, P; ~+ P* t7 B \* _5 M0 \8 d% X% L, L
tioning about the use of a testosterone product or
6 d* Y. j% ]1 H- c# t4 u: |. Agel should be asked of the family members during
1 c, H( x- D$ ~$ P* jthe evaluation of any children who present with vir-( u+ K" Z8 p5 n. s# x" o; ^( W# ]) A
ilization or peripheral precocious puberty. The diag-" \0 X' Z! G; O; @3 t& `% o
nosis can be established by just a few tests and by3 o0 A+ V+ b% ]# R1 t U
appropriate history. The inability to obtain such a
0 Z3 L3 m+ k; e2 B7 vhistory, or failure to ask the specific questions, may$ ~9 S$ z. T q
result in extensive, unnecessary, and expensive
: y" e7 X3 |' U# N) vinvestigation. The primary care physician should be
0 ?+ k4 w M4 s. p/ F- F- saware of this fact, because most of these children/ \! d- L$ K0 ^* S, F
may initially present in their practice. The Physicians’
- V6 J$ X* ]7 \$ |& x% r; d- d8 oDesk Reference and package insert should also put a
8 Q, m. z5 {: m4 ~2 Nwarning about the virilizing effect on a male or C/ d$ }, S P+ m& z0 z- F' F
female child who might come in contact with some-' J' D0 V: z, t3 k: ^4 }
one using any of these products.4 f# l. b) q; M2 _7 n7 T
References" k3 I* z2 v7 F
1. Styne DM. The testes: disorder of sexual differentiation
; m! Q: k4 ^4 a4 i* ^, C% I( r% Wand puberty in the male. In: Sperling MA, ed. Pediatric
4 ? E+ L; U% U8 Y8 c- JEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders; P) h( ]. \8 e
2002: 565-628.
, o# Y E' Q+ c2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious. h0 X% w/ ` w+ I0 G% \& B
puberty in children with tumours of the suprasellar pineal/ Q7 ]: U' [$ H% H3 ^5 Z
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from. W/ P% ^+ @ O. n. V& s/ m
Topical Testosterone Exposure / Bhowmick et al 543
/ A. l3 L% H! `4 h9 t5 lareas: organic central precocious puberty. Acta Paediatr.7 c5 a( }+ `! `( K4 i( }
2001;90:751-756.
$ R+ l9 k% H. L& r3. Lee PA. Puberty and its disorders. In: Lifshitz F, ed.
, K( ^) e) h2 pPediatric Endocrinology. 4th ed. New York, NY: Marcel8 x. H3 B! g' E; V5 l' z
Dekker Inc; 2003:211-238.
- F; c( ~8 P% j7 ?) t3 v. U4. Yu YM, Punyasavatsu N, Elder D, D’Ercole AJ. Sexual
3 N/ Q4 J* R8 j8 i) b7 Edevelopment in a two-year-old boy induced by topical+ C7 [: j" G" o8 j/ q
exposure to testosterone. Pediatrics. 1999;104:e23.
2 e+ _8 X ?7 x- w' ?! c% N5. Greulich WW, Pyle SI, eds. Radiographic Atlas of$ O" g* P j* V. F; g, w
Skeletal Development of the Hand and Wrist. 2nd ed.. z% k. `* D/ ?' j E1 X
Stanford, CA: Stanford University Press; 1959.6 Z& t: m0 F6 K* N6 k' s
6. Physicians’ Desk Reference. Androgel 1% testosterone,/ m: w( C7 B9 j; d8 q/ ~7 j) Q1 W Z& Z
Unimed Pharmaceutical Inc. Montvale, NJ: Medical
* n3 t5 S+ R$ |9 v6 J% _Economics Company, Inc; 2004:3239-3241., k) D7 H7 J0 g" p7 ^' [1 k' b
7. Klugo RC, Cerny JC. Response of micropenis to topical
( i9 t9 }1 g$ M6 ~. j8 xtestosterone and gonadotropin. J Urol. 1978;119:
' h/ ~- S8 y: j0 `; y& a667-668.
5 M: I5 o( Q3 A) u4 u5 J8. Guthrie RD, Smith DW, Graham CB. Testosterone
# Y+ _! m( J M6 b8 J4 }treatment for micropenis during early childhood. J Pediatr.
: B* ~& i2 c5 W' g2 [1973;83:247-252.
$ ?! x& q5 s6 J+ o! y9. Jacobs SC, Kaplan GW, Gittes RF. Topical testosterone
5 j# p N; p2 x: U9 j8 etherapy for penile growth. Urol. 1975;6:708-710.9 d0 u- o5 z- M; X6 i' k1 Y
10. Husmann DA, Cain MP. Microphallus: eventual phallic8 K$ H7 E _5 Q2 y9 D: q& C# Z
size is dependent on the timing of androgen administra-
) D) O8 ^/ H3 E( wtion. J Urol. 1994;152:734-739.- U7 T9 R: d7 Z* ^2 K
11. McMahon DR, Kramer SA, Husmann DA. Micropenis:
% g) U; R0 j& E) d7 W Kdoes early treatment with testosterone do more harm
. _. v& w, i6 l! n9 U' s6 }than good? J Urol. 1995;154:825-829.6 _& R0 w1 A/ K2 l# J: ?* Q: ~
12. Takane KK, George FW, Wilson JD. Androgen receptor
. ]# Y; p4 u2 x4 B5 Z9 `of rat penis is down-regulated by androgen. Am J Physiol.
/ e, o# K) p+ s# C: E1990;258:E46-E50." |* F% a3 E0 K
13. Sutherland RS, Kogan BA, Baskin LS, et al. The effect- ~* t' `! ?# S, d0 D& _
of prepubertal androgen exposure on adult penile
9 L( Q% ?, L! tlength. J Urol. 1996;156:783-787. |
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