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is a significant concern for physicians. Central
5 ~) b( R- H) Vprecocious puberty (CPP), which is mediated
- U, K6 r0 S# Z$ @& @# ?through the hypothalamic pituitary gonadal axis, has0 g x+ ~# G: D" Z1 I' T
a higher incidence of organic central nervous system
6 u G9 \5 h1 O* g! |lesions in boys.1,2 Virilization in boys, as manifested9 Q9 H% t# K$ ^. ?; L) }& u+ s3 i
by enlargement of the penis, development of pubic
" `1 X8 |0 ^% f' _, i, Thair, and facial acne without enlargement of testi-0 g4 l& l1 |; T* x7 l7 c5 {$ o
cles, suggests peripheral or pseudopuberty.1-3 We6 G# a! v4 {) J# I7 L
report a 16-month-old boy who presented with the
4 r" H! R: L; e7 G, Aenlargement of the phallus and pubic hair develop-; I% i: Y- d, l8 J% C1 m. x. Q
ment without testicular enlargement, which was due
g5 J: p* A: b8 G$ B4 y, P, eto the unintentional exposure to androgen gel used by9 W, B% y' l0 _3 C7 ?. z
the father. The family initially concealed this infor-
Q5 S8 ]$ P1 Emation, resulting in an extensive work-up for this3 j6 B, Y: O, W& d C% S
child. Given the widespread and easy availability of
9 ?! i$ N% W; q3 T a7 Htestosterone gel and cream, we believe this is proba-! y( @# c) @ [' @+ F
bly more common than the rare case report in the
: @. t0 Z; B% {# z9 n( a* I) ]- \literature.4
6 |' c* I7 K/ Z w+ ~, p- Q- @Patient Report1 U" n3 v, `3 x/ n' C# s+ t3 E
A 16-month-old white child was referred to the H$ N! s- k- T4 h! u4 t
endocrine clinic by his pediatrician with the concern @1 C+ y) k- I
of early sexual development. His mother noticed) k: L) J. j6 x( B
light colored pubic hair development when he was
: `$ C. d2 O3 K5 n5 h bFrom the 1Division of Pediatric Endocrinology, 2University of# E# Z0 n. H$ E0 k
South Alabama Medical Center, Mobile, Alabama.
7 }* S! ^. D- g% T0 |Address correspondence to: Samar K. Bhowmick, MD, FACE,
: h$ N* \3 ?8 C4 R) I; UProfessor of Pediatrics, University of South Alabama, College of
+ |$ f6 L" k% T% U: @# H% G) V5 fMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;* u0 ~' J+ b$ {. h6 \9 y) H
e-mail: [email protected].
: A" {$ j" K2 ~about 6 to 7 months old, which progressively became
! N0 E. r% [4 r0 U0 {darker. She was also concerned about the enlarge-" H( p1 ^. D& x- z/ G% a: l6 E
ment of his penis and frequent erections. The child4 u& Y: G. L7 {4 _0 A! J4 a
was the product of a full-term normal delivery, with
' H# h( e# ^/ Z; K) p7 W9 {; Fa birth weight of 7 lb 14 oz, and birth length of
3 Z- d& C( U2 I5 G20 inches. He was breast-fed throughout the first year( }# Q3 v9 x9 m8 I. Y! i
of life and was still receiving breast milk along with
8 D8 H5 u7 w- R, U8 i4 }solid food. He had no hospitalizations or surgery,4 O$ ?/ _# O# M% G" Z
and his psychosocial and psychomotor development
9 [1 ~ ]7 @4 T4 G8 g. vwas age appropriate.; b, K8 e" I& f4 m# C1 l, W
The family history was remarkable for the father,
1 D& }; Z% k% Uwho was diagnosed with hypothyroidism at age 16,
& Y. y1 Y. M% Swhich was treated with thyroxine. The father’s5 T4 ^, n5 @/ N. ], q3 d
height was 6 feet, and he went through a somewhat
! f! Y" H& L5 e4 W2 L0 r' u6 cearly puberty and had stopped growing by age 14.
9 l: X* ^" X" l! ]- xThe father denied taking any other medication. The$ H0 Y( o" l# M' A/ {: J- N# I
child’s mother was in good health. Her menarche
, B8 C8 a( `" h! y$ g: @/ B* Kwas at 11 years of age, and her height was at 5 feet9 M4 O: R# m; \ @9 W$ o( ^
5 inches. There was no other family history of pre-
; B/ G; K7 B( K0 a3 rcocious sexual development in the first-degree rela-6 {* V& w! B$ L8 k; L
tives. There were no siblings." d: @( |% J0 D7 j) _1 I7 A9 x
Physical Examination
# ]5 Z; Q2 Q( S3 j7 iThe physical examination revealed a very active,
8 Y9 x+ X; J8 F2 G/ }# Oplayful, and healthy boy. The vital signs documented
& K8 m2 U! v* l! ^& la blood pressure of 85/50 mm Hg, his length was i9 g+ C3 G2 V# _
90 cm (>97th percentile), and his weight was 14.4 kg! p$ |: e% ^9 U+ R! n; |. Z
(also >97th percentile). The observed yearly growth
, U) E5 |: ]) o0 N# U Cvelocity was 30 cm (12 inches). The examination of2 ?- {8 }) ~% Y& j$ H* @% w
the neck revealed no thyroid enlargement.
, u$ C( P" K( A7 m; O1 b; O) Y! D' iThe genitourinary examination was remarkable for
* q; y& g9 |$ X7 e' y! Nenlargement of the penis, with a stretched length of
% N! @; S. A9 ?6 h3 t/ [+ { m8 cm and a width of 2 cm. The glans penis was very well
) l6 |$ j: |, P, I$ e; C1 @. Mdeveloped. The pubic hair was Tanner II, mostly around
8 M: d3 B+ @& u( y) H5 Q540* ]) E; ^6 \& }9 a) Y
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
% ?- q$ K+ B2 fthe base of the phallus and was dark and curled. The
$ ?& S- f" I% ?; G, l1 h- m7 ]testicular volume was prepubertal at 2 mL each.
% e) }* f4 L% E% {The skin was moist and smooth and somewhat; F) S# n1 v! \: u1 p! |
oily. No axillary hair was noted. There were no D+ e6 ^3 Z5 G5 f& T6 l; X5 O
abnormal skin pigmentations or café-au-lait spots.
! o/ u9 Y/ e1 i! k O+ A5 _ MNeurologic evaluation showed deep tendon reflex 2+
9 W4 A5 m) X( ?5 u) Vbilateral and symmetrical. There was no suggestion
3 [9 \8 n* R# \. u6 d9 n/ _4 Iof papilledema.% b+ t o6 v( M* V2 d' X* t0 z
Laboratory Evaluation
- a7 ]; A" o6 G f% {7 X& [The bone age was consistent with 28 months by4 g: T$ O9 ?7 }
using the standard of Greulich and Pyle at a chrono-
6 W' I/ J* e, B5 A, dlogic age of 16 months (advanced).5 Chromosomal
' u" r! F. n2 A5 _/ Hkaryotype was 46XY. The thyroid function test
1 F1 a5 Z `. y3 C, s6 jshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
; ~5 U" |5 h3 g) ]1 x/ b! b9 zlating hormone level was 1.3 µIU/mL (both normal).- F) f' H" Y" {8 e( A
The concentrations of serum electrolytes, blood
- I% T! d E' q" ]: z0 kurea nitrogen, creatinine, and calcium all were( \: D4 C9 g" y; d; J0 \! N
within normal range for his age. The concentration# d. C$ i8 D( l1 x! ~5 |% V
of serum 17-hydroxyprogesterone was 16 ng/dL
6 Y* s& M: T( d% e(normal, 3 to 90 ng/dL), androstenedione was 20
8 k J2 a7 D6 tng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-. H! B% u3 T* \; G& Z
terone was 38 ng/dL (normal, 50 to 760 ng/dL),* h t5 H" G/ z5 l* T
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
6 t7 o, V8 t& M: F. S E4 |49ng/dL), 11-desoxycortisol (specific compound S)
% E9 e/ ^% z% F/ Y" f. X1 Vwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
# m* O2 ~$ C" _, d& ]7 Ytisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total7 O: h0 ^; _0 [- C
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),3 ]0 ^: q+ b( `5 M+ h: [$ G" J9 d
and β-human chorionic gonadotropin was less than
# D3 D1 a) A: ]- D w7 Y5 mIU/mL (normal <5 mIU/mL). Serum follicular
; {4 v T9 r$ Zstimulating hormone and leuteinizing hormone0 c4 ^8 D( h# o; B
concentrations were less than 0.05 mIU/mL
' _4 ~! W/ U0 R2 j y8 L) M1 V(prepubertal).
) C1 l& G& W* m2 S7 OThe parents were notified about the laboratory& V/ y h0 j1 l8 S5 A# }& l4 Y$ H
results and were informed that all of the tests were
- p* {, G9 I2 k- G2 |. pnormal except the testosterone level was high. The
3 Z) r7 P2 f0 @! I8 }* c0 l. @- Q7 Zfollow-up visit was arranged within a few weeks to
3 B# @/ L: @* J( ]: x9 U* \obtain testicular and abdominal sonograms; how-. r- @( [6 C4 W8 p7 {( g
ever, the family did not return for 4 months., [, L1 k0 h h. @% \4 O
Physical examination at this time revealed that the
4 y4 x8 d$ _! ^child had grown 2.5 cm in 4 months and had gained
9 @) z0 ]8 _3 ]* Q9 Z) T$ R- v7 }3 u. Z2 kg of weight. Physical examination remained
( i2 Y' @/ v' x" y! nunchanged. Surprisingly, the pubic hair almost com-8 O; e q% c( N$ x) n0 i: q- {" W! Y
pletely disappeared except for a few vellous hairs at
4 U. z5 P# T I: ]% F. ^* zthe base of the phallus. Testicular volume was still 2) Z/ e7 ` b. \# H6 c1 p
mL, and the size of the penis remained unchanged.
6 X# s) f% J' j7 f/ aThe mother also said that the boy was no longer hav-! X9 a1 n b8 l& ?6 W
ing frequent erections.4 J" k' s! q5 a# F9 r
Both parents were again questioned about use of
0 F5 q' Y& x/ a$ \) V4 {# yany ointment/creams that they may have applied to
/ V: U6 Q+ v3 X" r3 e: ethe child’s skin. This time the father admitted the
) a! e. X* @: \% ~Topical Testosterone Exposure / Bhowmick et al 541% q6 v: y: [/ a/ T {
use of testosterone gel twice daily that he was apply-
: D) d- J9 v8 M% B$ _* f/ Aing over his own shoulders, chest, and back area for
" g3 B) j3 N/ l. D; wa year. The father also revealed he was embarrassed
7 K j k6 G3 u( P T T8 `* V3 Pto disclose that he was using a testosterone gel pre-
. G h( U/ R4 s/ }7 p/ lscribed by his family physician for decreased libido
6 i0 d6 L8 B4 k$ t! P4 ?& T5 U4 vsecondary to depression.) b0 T( l! t H) C R1 ?1 k5 i
The child slept in the same bed with parents.
( ~/ g3 C/ R: x+ b& S7 m( ^3 fThe father would hug the baby and hold him on his3 l* n# M9 g# Z' [& D& H: ^
chest for a considerable period of time, causing sig-
4 @7 g6 ^ K( znificant bare skin contact between baby and father.
3 b, P- k$ L& u E' VThe father also admitted that after the phone call,. v+ u8 k+ F$ U& s5 B0 i
when he learned the testosterone level in the baby
( y! Y/ X( `2 M' X' Zwas high, he then read the product information5 r: X! _9 D! y8 s$ r$ {
packet and concluded that it was most likely the rea-/ m/ f" g# W$ c! |6 y
son for the child’s virilization. At that time, they
: y8 j0 p5 \4 J; B6 D0 ], z! Ddecided to put the baby in a separate bed, and the
+ ~) K2 R" V9 e% L2 xfather was not hugging him with bare skin and had' m& k; A0 D3 v" l% K0 d
been using protective clothing. A repeat testosterone7 C8 F6 M7 E/ } B" Z: o# ^0 Y5 z
test was ordered, but the family did not go to the
5 U) U! k4 L4 ~. l7 Dlaboratory to obtain the test.' m3 Z. `( w1 o" I1 N! P9 y0 u' H1 }
Discussion) X$ |1 f) u; w& M+ {9 K; a
Precocious puberty in boys is defined as secondary) l* N L& b; j
sexual development before 9 years of age.1,4
2 j0 o7 N! ^3 t; \5 TPrecocious puberty is termed as central (true) when
9 z8 y, ~+ U# l3 p+ A1 d7 Z4 j1 v. ~it is caused by the premature activation of hypo-& {) {+ E, |. \5 D8 ?9 _' x6 J
thalamic pituitary gonadal axis. CPP is more com-
" {& k! V4 a/ s( ]mon in girls than in boys.1,3 Most boys with CPP; A( w4 ?0 D E) f( X6 ?7 m/ Z
may have a central nervous system lesion that is
( \4 w2 T* Y) iresponsible for the early activation of the hypothal-
6 W2 {( ?( v+ s3 j- K+ ?, @amic pituitary gonadal axis.1-3 Thus, greater empha-
5 T5 h" m$ w% Q7 Ksis has been given to neuroradiologic imaging in
) q0 \( F( G0 @boys with precocious puberty. In addition to viril-
! r: t8 v) J' d; Q' qization, the clinical hallmark of CPP is the symmet- X" B: T/ L$ J( O8 A
rical testicular growth secondary to stimulation by3 i f( ]% a( i- H( k
gonadotropins.1,35 ]" P {2 t: z
Gonadotropin-independent peripheral preco-
h( p9 ^" {5 q& }5 w" I2 Gcious puberty in boys also results from inappropriate6 z( Y4 Q$ V8 ?/ m7 _. V/ B+ H/ ~: s8 ~
androgenic stimulation from either endogenous or
% @9 q' U4 h( Q. I) G' Oexogenous sources, nonpituitary gonadotropin stim-7 k# ~) _. G8 t: @) D
ulation, and rare activating mutations.3 Virilizing
+ K' X% E$ q! {' G8 scongenital adrenal hyperplasia producing excessive) s! h1 v4 l) ^; I
adrenal androgens is a common cause of precocious
# c9 V4 r$ Q ]4 R$ vpuberty in boys.3,4
0 C$ m4 f) X3 G) Z, i! C# ?+ r: ]The most common form of congenital adrenal
; d/ o& S* q0 ^: T6 ?, Q1 Whyperplasia is the 21-hydroxylase enzyme deficiency.
" y$ h$ ?3 { F) h2 w5 P g! MThe 11-β hydroxylase deficiency may also result in V5 h6 p5 J+ E9 b$ g
excessive adrenal androgen production, and rarely,- S2 |: Q% ]( C8 m! j6 @
an adrenal tumor may also cause adrenal androgen) c O% m& i- V# N V# M
excess.1,3$ j8 u/ @ L; o0 N
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
* h ^6 W) K/ W# T3 f542 Clinical Pediatrics / Vol. 46, No. 6, July 20075 J6 D/ W7 y% i; w* q9 [1 D; `3 O
A unique entity of male-limited gonadotropin-5 o" [3 N! F( ?: p
independent precocious puberty, which is also known
5 _# C. p$ C# O7 }/ C' n& H1 fas testotoxicosis, may cause precocious puberty at a
' t, e( R; ~; `$ [3 Q) v% E+ Yvery young age. The physical findings in these boys2 E: K- }- Z( k% ?5 [1 C
with this disorder are full pubertal development,
- E/ N2 j: F( O7 Uincluding bilateral testicular growth, similar to boys
6 A }! w/ f* C: w7 k1 Gwith CPP. The gonadotropin levels in this disorder
4 P! L I( i2 v+ v( a( Yare suppressed to prepubertal levels and do not show8 M' t1 o( {% L8 i
pubertal response of gonadotropin after gonadotropin-
. J% n m' U$ ^! H( W" Kreleasing hormone stimulation. This is a sex-linked8 r, i i3 @3 m& p! m
autosomal dominant disorder that affects only
4 G; b0 M" Y A U; gmales; therefore, other male members of the family& v2 U ] T' ^9 V. d. D) `
may have similar precocious puberty.3, y W h! ?; J- W& I( |* O* V: |
In our patient, physical examination was incon-* ]& e, Y" M4 C# q' A7 g) O1 Y
sistent with true precocious puberty since his testi-/ c1 P: C. O8 M8 P+ m( S3 R
cles were prepubertal in size. However, testotoxicosis
$ c# Z; J' J9 _; vwas in the differential diagnosis because his father& i. W# d% Z% c: y0 ~, \
started puberty somewhat early, and occasionally,
1 u s0 W8 z, v- S% Rtesticular enlargement is not that evident in the' G# b2 x7 X; L0 [) ]' v
beginning of this process.1 In the absence of a neg-1 I6 d' f# Y6 L* L3 h8 [& X
ative initial history of androgen exposure, our+ D! t' a3 W& A1 d6 Y
biggest concern was virilizing adrenal hyperplasia,
/ ?* B7 Q$ ~( Aeither 21-hydroxylase deficiency or 11-β hydroxylase# \) V/ a& o2 _! ^ d
deficiency. Those diagnoses were excluded by find-* v. b- J" K n7 [- K
ing the normal level of adrenal steroids.
5 [! s& J7 v; j2 G2 o' Q. QThe diagnosis of exogenous androgens was strongly1 ]% [) ?3 I4 ~! H/ T
suspected in a follow-up visit after 4 months because
4 d" L+ ~! x1 c6 |* g& othe physical examination revealed the complete disap-
9 S7 P* x0 ?/ C7 Opearance of pubic hair, normal growth velocity, and
/ m8 z% T: R8 Q. f8 X1 C3 Xdecreased erections. The father admitted using a testos-/ d3 r0 ?- [8 V4 M+ m3 X
terone gel, which he concealed at first visit. He was9 q2 Z; d# x5 s) A# X" ]; w
using it rather frequently, twice a day. The Physicians’& w' l2 F9 b# U$ A
Desk Reference, or package insert of this product, gel or
- k o# t, m1 d0 Dcream, cautions about dermal testosterone transfer to3 [* R$ b6 ?2 c+ g$ x0 Z
unprotected females through direct skin exposure.6 J7 p& O I Q% ]5 D7 l
Serum testosterone level was found to be 2 times the
8 k; H. h, b- `0 N* p5 Xbaseline value in those females who were exposed to- R6 L' q; q) ]" N! h
even 15 minutes of direct skin contact with their male# u) W& \. E# l- [
partners.6 However, when a shirt covered the applica-; ~; \# O. X) Q
tion site, this testosterone transfer was prevented.
9 L8 Q+ }3 o2 a6 k/ h6 |Our patient’s testosterone level was 60 ng/mL,6 V$ w- O. a) @, Q
which was clearly high. Some studies suggest that* @6 m- m! V, L" o* {
dermal conversion of testosterone to dihydrotestos-
6 E: d; ~5 M0 \* T+ Z) w8 \& jterone, which is a more potent metabolite, is more" d# g: C, E- j7 i: R& X) y
active in young children exposed to testosterone
' l/ A4 q6 H: T, ~exogenously7; however, we did not measure a dihy-
. d; C* Q$ y' \drotestosterone level in our patient. In addition to" e$ y1 v# ?. E
virilization, exposure to exogenous testosterone in: o1 }1 j% `/ N8 D
children results in an increase in growth velocity and3 `+ Z; E R9 [( w1 C
advanced bone age, as seen in our patient.
5 W" n7 Q8 r; EThe long-term effect of androgen exposure during0 B/ J' T6 v' q4 X
early childhood on pubertal development and final' G6 B: f1 ~% `) l/ E0 Y
adult height are not fully known and always remain' w, Y. R( @; r: S$ b6 Z2 @& w
a concern. Children treated with short-term testos-6 |& h1 G+ P4 Q* L8 G
terone injection or topical androgen may exhibit some
+ a. C% u" X5 ?acceleration of the skeletal maturation; however, after
0 p. ^' r4 h$ N$ |# \4 pcessation of treatment, the rate of bone maturation
7 t& P) E7 H! O6 c/ Xdecelerates and gradually returns to normal.8,9. A- s7 t' v6 ?# }: [+ f0 A& d
There are conflicting reports and controversy. m6 q2 J: C( I
over the effect of early androgen exposure on adult) {* J- \& D' \- n* U1 F3 Y
penile length.10,11 Some reports suggest subnormal
, w7 q% C0 M% d( q7 G8 v7 U* radult penile length, apparently because of downreg-
- _/ u: y3 z7 C1 \3 L# m$ Hulation of androgen receptor number.10,12 However,
' o9 Y; f. F) i* JSutherland et al13 did not find a correlation between. C) V4 O& {( [' R0 m
childhood testosterone exposure and reduced adult
4 ~3 ~1 o$ n1 B5 ~) I( I4 A- j" j. ~( p- tpenile length in clinical studies.) {2 E- ?8 B9 D! q5 F
Nonetheless, we do not believe our patient is/ j) ]2 ?: [2 _1 j
going to experience any of the untoward effects from* c3 n( K. r+ @8 R3 U
testosterone exposure as mentioned earlier because
; I( T& N- S0 K" B( Y8 N! r' G" Jthe exposure was not for a prolonged period of time.$ e4 h! y, @* f" y ~
Although the bone age was advanced at the time of
/ Z5 O6 O2 B$ Y. w8 E2 T/ H( \diagnosis, the child had a normal growth velocity at% q/ f% A1 h+ c4 f( `
the follow-up visit. It is hoped that his final adult# ~" l3 W$ F7 [5 e5 h4 t
height will not be affected.3 B7 k4 R# c4 a0 G
Although rarely reported, the widespread avail-, e3 n5 B( \# X; L
ability of androgen products in our society may! Y$ S# P: P/ K
indeed cause more virilization in male or female2 f X2 k& `2 D; }, W/ X! a/ L
children than one would realize. Exposure to andro-7 `8 X$ {% I2 i F2 g
gen products must be considered and specific ques-. x2 Z& ?1 P7 }* W% ]
tioning about the use of a testosterone product or( ^* C3 i9 H' p+ f
gel should be asked of the family members during- t) }( K5 ?# J
the evaluation of any children who present with vir-
- ?% \& Z; ~+ e& k' [9 v uilization or peripheral precocious puberty. The diag-$ ?% J/ b3 P" y- t( e
nosis can be established by just a few tests and by
; V1 v- u% X$ H$ H+ j$ i, Oappropriate history. The inability to obtain such a K& u0 h e. c Z) S
history, or failure to ask the specific questions, may3 y& Q; |( G i6 k* `
result in extensive, unnecessary, and expensive
' E n: n- E1 p3 H5 N1 [investigation. The primary care physician should be
( ?! F0 a, S8 _% l: maware of this fact, because most of these children
- h3 h9 {& D7 f" z1 W/ H( z$ f! `& lmay initially present in their practice. The Physicians’+ d. z5 R% F+ a
Desk Reference and package insert should also put a
Y% C& M9 X. ]6 [warning about the virilizing effect on a male or& |, r0 }$ m. N6 S! i' B
female child who might come in contact with some-
, J7 _8 K% W. m% q! k, j9 M4 [one using any of these products.; ~/ ^0 R+ c' N, N1 [7 W
References
8 z! ]' w. Q" X# n' V q2 K( G1. Styne DM. The testes: disorder of sexual differentiation
' c" B6 j" y- P5 R: Q# a. x4 Qand puberty in the male. In: Sperling MA, ed. Pediatric) r; q$ [4 R: [
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
4 T8 x5 I& j. Y$ N7 l8 s2002: 565-628.5 ^. a: Y/ M( u2 J0 U1 g
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious( m* F1 D! `! Z( s
puberty in children with tumours of the suprasellar pineal
2 J3 ?$ r) G. Z+ Lat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
' ~$ T- O: J5 M) ~3 }9 hTopical Testosterone Exposure / Bhowmick et al 543
# ]2 S$ I C/ l: Bareas: organic central precocious puberty. Acta Paediatr.9 J1 v" O, H! N$ N* l
2001;90:751-756.
! F9 l. i( o h4 ]) g5 g3. Lee PA. Puberty and its disorders. In: Lifshitz F, ed.
5 ?6 A& f N6 L' fPediatric Endocrinology. 4th ed. New York, NY: Marcel2 q, Q/ |1 P& z7 j2 D; m
Dekker Inc; 2003:211-238.8 K$ k0 h e+ @" u
4. Yu YM, Punyasavatsu N, Elder D, D’Ercole AJ. Sexual
( u8 p5 Z; J! z8 n& C8 |9 zdevelopment in a two-year-old boy induced by topical8 @( q" t% h" R8 b. X
exposure to testosterone. Pediatrics. 1999;104:e23.; o+ V& d: x2 G |; O. ~
5. Greulich WW, Pyle SI, eds. Radiographic Atlas of; H0 I1 G) z. Y- Q% P" O z
Skeletal Development of the Hand and Wrist. 2nd ed.
3 b" E: ^2 b9 T% C gStanford, CA: Stanford University Press; 1959.
% d4 F' _+ v1 K) x4 ~6. Physicians’ Desk Reference. Androgel 1% testosterone,
; H$ ]- l7 F) ?+ ~0 c! MUnimed Pharmaceutical Inc. Montvale, NJ: Medical0 t# T( d+ o; N0 w! P3 ]/ n
Economics Company, Inc; 2004:3239-3241.: y$ `, i {( j8 P( r9 s
7. Klugo RC, Cerny JC. Response of micropenis to topical
9 m' K4 c! G. u6 A, wtestosterone and gonadotropin. J Urol. 1978;119:
5 x$ Q2 b" q" ^) z5 G667-668." p6 Q3 \! r+ C" r& \( o& f) T
8. Guthrie RD, Smith DW, Graham CB. Testosterone
2 ^1 ]! V* H9 j$ O. \treatment for micropenis during early childhood. J Pediatr.
4 X. L, [5 V* Z; a6 x1 V [0 h/ G1973;83:247-252.' u' l# O5 t$ l& v
9. Jacobs SC, Kaplan GW, Gittes RF. Topical testosterone/ L6 x5 s0 s3 q D9 `* {6 {) O
therapy for penile growth. Urol. 1975;6:708-710.& W, N+ M3 a2 ^8 h
10. Husmann DA, Cain MP. Microphallus: eventual phallic" H. g- B, M) A- P8 E; _4 ~' _& i
size is dependent on the timing of androgen administra-
# X8 p3 T- X! W) j0 n2 Xtion. J Urol. 1994;152:734-739.5 s8 [! e! r9 H0 e* ]" c; U6 e( l
11. McMahon DR, Kramer SA, Husmann DA. Micropenis: Z1 q2 s% O1 ]* `& h
does early treatment with testosterone do more harm/ d. @ Z2 I! F7 R- o+ Z; E
than good? J Urol. 1995;154:825-829.' k; H* w" y5 d% b. ^
12. Takane KK, George FW, Wilson JD. Androgen receptor$ ^8 d' j4 E5 U) d! t1 ?
of rat penis is down-regulated by androgen. Am J Physiol. }- _* o9 H/ ]- o) e6 b
1990;258:E46-E50.
9 ?8 X, I+ {' o/ b. R$ M& A13. Sutherland RS, Kogan BA, Baskin LS, et al. The effect3 L8 o8 u' R& d* |" a
of prepubertal androgen exposure on adult penile/ {8 [$ P D2 Y
length. J Urol. 1996;156:783-787. |
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