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is a significant concern for physicians. Central
, f( Q. j+ `4 |- A: lprecocious puberty (CPP), which is mediated+ U! `) w( P/ o& K
through the hypothalamic pituitary gonadal axis, has
+ @: \+ n2 z( M5 Va higher incidence of organic central nervous system o! K0 J9 D6 W" N* S
lesions in boys.1,2 Virilization in boys, as manifested
; b$ |' W* S1 l0 hby enlargement of the penis, development of pubic
2 p4 q! v( D5 w+ _. qhair, and facial acne without enlargement of testi-
" ^2 F+ q; Y5 l/ Scles, suggests peripheral or pseudopuberty.1-3 We
3 J- c x3 j$ |( lreport a 16-month-old boy who presented with the
/ W' h( n/ D, E; ?( j8 O" w/ {enlargement of the phallus and pubic hair develop-3 v& W; |: A$ l1 l0 B' c6 i
ment without testicular enlargement, which was due
7 y! N% m. M" g- kto the unintentional exposure to androgen gel used by
3 B' Y4 O) X$ }. d! U! ]the father. The family initially concealed this infor-
/ @* f( c9 S, u! a5 t# bmation, resulting in an extensive work-up for this8 n2 K$ p; s9 ^8 Y/ b9 r; W
child. Given the widespread and easy availability of
/ }* J/ X- P0 m" w3 F. l8 e& {% Y) ktestosterone gel and cream, we believe this is proba-6 u$ l+ X- u' D. B8 R
bly more common than the rare case report in the
* C3 p. @: H0 w2 P% `literature.49 F' G. z3 {- A3 o W7 c! d% h6 H' D
Patient Report* ~ K& @! T w4 h; H
A 16-month-old white child was referred to the
& X5 l1 h. K$ b9 ?endocrine clinic by his pediatrician with the concern
3 A% n2 F0 g( u7 _0 m2 z7 i; ]of early sexual development. His mother noticed
8 R) E# u2 E8 X2 D/ X. h) Olight colored pubic hair development when he was) }5 e. S% j( }- ^
From the 1Division of Pediatric Endocrinology, 2University of
+ d( H q( X: B" j- rSouth Alabama Medical Center, Mobile, Alabama.. l3 s9 H- }+ u( @
Address correspondence to: Samar K. Bhowmick, MD, FACE,
% A- K& e8 u N* L1 QProfessor of Pediatrics, University of South Alabama, College of/ z$ b7 o8 _. d4 o
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
, F! _1 n6 z& b* me-mail: [email protected].' {9 f/ b5 |' s: i! E4 P
about 6 to 7 months old, which progressively became
6 B) Y$ v0 X6 x6 @! v K6 Vdarker. She was also concerned about the enlarge-
4 ^+ z% ~& d+ [4 A" L8 @7 ]ment of his penis and frequent erections. The child
; \' }6 I2 ]$ u# @was the product of a full-term normal delivery, with
l% q1 s3 J: z/ V9 p8 ua birth weight of 7 lb 14 oz, and birth length of
" Q& T2 ~- C6 W, n# O5 H5 M+ A20 inches. He was breast-fed throughout the first year
/ n$ q( Z' k7 X$ R0 Zof life and was still receiving breast milk along with0 f5 s% {; }* y2 h: o
solid food. He had no hospitalizations or surgery,. d4 S" h# J/ B4 S
and his psychosocial and psychomotor development
0 y* R1 e3 ?& w5 o# j! w- i3 n5 Ywas age appropriate.
# W0 q; M* D( r6 L2 b. bThe family history was remarkable for the father,% m9 C, T) o7 g+ k/ @1 H/ [1 i
who was diagnosed with hypothyroidism at age 16,: I( t; q( |- `- Z2 i0 P$ Z
which was treated with thyroxine. The father’s
; M9 d: C3 F" p) b9 q8 Q, Gheight was 6 feet, and he went through a somewhat% b7 n* v+ W2 v) L- x
early puberty and had stopped growing by age 14.
" f% I! V) L& L, FThe father denied taking any other medication. The
+ z/ j" h2 c' `# qchild’s mother was in good health. Her menarche+ T Q! |2 j Q X! C9 l, V8 l
was at 11 years of age, and her height was at 5 feet
+ z# d0 ]$ ?; g Q) @) a2 A5 inches. There was no other family history of pre-; d( w+ _, x' S/ @; |
cocious sexual development in the first-degree rela-0 [7 V! ]& y# f
tives. There were no siblings.
. g6 P o" [* `- UPhysical Examination
7 @2 ^5 V& L: v- d4 OThe physical examination revealed a very active,
* j0 I1 J a# T0 y0 qplayful, and healthy boy. The vital signs documented1 l( S' S& } d8 M z
a blood pressure of 85/50 mm Hg, his length was, r, p2 b/ t Z( Y3 i+ J
90 cm (>97th percentile), and his weight was 14.4 kg f. O1 q. ^3 `6 p
(also >97th percentile). The observed yearly growth, k4 w1 J- u" X( G8 z8 g3 y! D
velocity was 30 cm (12 inches). The examination of! d- p$ R- x) a$ \: m8 n
the neck revealed no thyroid enlargement.
, Y' O# [( |4 f S- \8 hThe genitourinary examination was remarkable for. ^* s) e. `( \9 e$ z$ d& ]# E& G. k" Z
enlargement of the penis, with a stretched length of4 y3 T+ T% |' N& g" h9 _ Y: B1 W
8 cm and a width of 2 cm. The glans penis was very well# C) i! U0 s$ B' ?: y2 `* a
developed. The pubic hair was Tanner II, mostly around9 \" G- D6 l1 H3 I2 H1 W3 n, f
540
" `9 S1 L S" [at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from( @ a6 J2 X# X9 q
the base of the phallus and was dark and curled. The
0 o+ h) g; q \8 e0 Y4 Stesticular volume was prepubertal at 2 mL each.
& T5 ?: M \. n+ }1 ` L9 dThe skin was moist and smooth and somewhat
" g% ? C# S/ w, ~oily. No axillary hair was noted. There were no
( ?6 A0 g6 {6 c: o5 Kabnormal skin pigmentations or café-au-lait spots.
2 D) f2 u7 d1 F& y" Y& j+ P8 fNeurologic evaluation showed deep tendon reflex 2+
3 y$ }) d7 E- R. I$ X4 W4 rbilateral and symmetrical. There was no suggestion
5 U& u7 L- l$ z; Y7 @) Aof papilledema.
4 i- R9 W! g9 P- c% oLaboratory Evaluation
/ C: L8 C; n; mThe bone age was consistent with 28 months by
* p6 V K6 r, W/ b( N$ Husing the standard of Greulich and Pyle at a chrono- T$ [) q( N4 M7 I: H1 V
logic age of 16 months (advanced).5 Chromosomal9 }4 T, n5 E1 l0 p, J3 _. {$ h
karyotype was 46XY. The thyroid function test; U$ ~7 E" f, |1 k( k% B( m! y
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
0 Z0 q: ]5 R4 f `2 Rlating hormone level was 1.3 µIU/mL (both normal).- C4 R5 D9 k/ Q4 O% ~. p
The concentrations of serum electrolytes, blood
1 e3 W$ h4 a; Surea nitrogen, creatinine, and calcium all were9 B7 C6 M! u6 T- _0 t
within normal range for his age. The concentration* n8 ^% ^/ b& R5 `' `7 @, v% P3 F4 T( z
of serum 17-hydroxyprogesterone was 16 ng/dL6 {; |6 H; M; d- Y$ B7 v3 R/ N! |
(normal, 3 to 90 ng/dL), androstenedione was 200 Y3 |2 A" n+ p; [
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-7 j* d$ g& Q1 e) Z% W
terone was 38 ng/dL (normal, 50 to 760 ng/dL),# f# X+ ? n1 O0 D
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
) |9 o8 f3 l$ O1 [; ~49ng/dL), 11-desoxycortisol (specific compound S)) i. _& l3 ~4 C" T9 l
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
& K5 W& z S/ V; c e4 x: dtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
5 R$ l8 v7 f7 G3 ]" l; o+ g( rtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
. q% c$ q$ B# g; B6 uand β-human chorionic gonadotropin was less than* H% Y J# @6 ~0 O
5 mIU/mL (normal <5 mIU/mL). Serum follicular
7 d9 Y6 S: u8 J l5 tstimulating hormone and leuteinizing hormone
4 D l: }* W0 _ t* L$ {. N6 d. [concentrations were less than 0.05 mIU/mL
) L$ r" e, M2 W! ^4 x(prepubertal).+ I% C* w, L+ v
The parents were notified about the laboratory
( h2 @2 U, V# }results and were informed that all of the tests were; z3 u; K4 ]: g% b s, I7 r
normal except the testosterone level was high. The; c7 T1 I) ]- ^9 ]+ s: f
follow-up visit was arranged within a few weeks to. a2 s3 [! m" A: y5 E
obtain testicular and abdominal sonograms; how-
+ Z. y, j& a4 v; F0 R+ ]& b! Tever, the family did not return for 4 months.- ]) `) u$ q' K4 U- o
Physical examination at this time revealed that the
; V# G4 v5 A8 s r: Schild had grown 2.5 cm in 4 months and had gained
1 ~% X/ O( _5 F+ ?% ?' N; ?2 kg of weight. Physical examination remained
8 M. ~6 G& x3 i; S/ bunchanged. Surprisingly, the pubic hair almost com-3 d- c! @% o$ X# {9 y# j" ?
pletely disappeared except for a few vellous hairs at6 _1 F) v! A- |) l, ~1 b
the base of the phallus. Testicular volume was still 2
0 y, `9 N9 ^# v/ L5 i; T. ~ QmL, and the size of the penis remained unchanged.
* J( w4 X, C4 O% }The mother also said that the boy was no longer hav- @$ m& b X; z% l3 H( \! L
ing frequent erections.$ z5 p6 U& J$ S1 v
Both parents were again questioned about use of
# a- [5 \" b/ |+ n- s! h# Dany ointment/creams that they may have applied to! k: R- r2 k' ?% Y
the child’s skin. This time the father admitted the' F1 C) E9 ?, ^& j
Topical Testosterone Exposure / Bhowmick et al 541# r& \9 U' r4 |6 S
use of testosterone gel twice daily that he was apply-
/ u$ W# z' W2 {) U* Sing over his own shoulders, chest, and back area for& @3 j$ |' S6 S# c% y/ p' X, E/ e Y S
a year. The father also revealed he was embarrassed( `- z) _& I0 a7 m! k
to disclose that he was using a testosterone gel pre-8 h" B ^0 o4 Z$ q8 u E
scribed by his family physician for decreased libido" m) i5 z4 N- k: z
secondary to depression.! a* R: w5 a/ e
The child slept in the same bed with parents.
$ j* t$ h. y6 R8 X# _: @The father would hug the baby and hold him on his1 P6 ^. @ s( \ g' E9 ?$ k3 E3 W
chest for a considerable period of time, causing sig-0 b* L; i" u! h
nificant bare skin contact between baby and father.7 S9 Q% E e2 W/ r( G( o% P
The father also admitted that after the phone call,
$ x& [3 L1 b- t! d8 Bwhen he learned the testosterone level in the baby
1 k1 R/ V* E3 X0 y- }7 i9 Rwas high, he then read the product information
% [8 V' n( ^8 _+ \' ` Apacket and concluded that it was most likely the rea-" o2 Z5 V3 W$ G9 l9 Z
son for the child’s virilization. At that time, they
2 Q1 m% U) W8 Mdecided to put the baby in a separate bed, and the+ @/ P# t( U. s& c. n% z$ G
father was not hugging him with bare skin and had
# _" C( L2 E& |. X5 dbeen using protective clothing. A repeat testosterone; g" _* ^4 \$ Y/ k4 Y' F! Q+ d
test was ordered, but the family did not go to the
9 [0 ?* p6 g4 z" _laboratory to obtain the test.+ o6 n$ W2 J; w0 {- D4 ^
Discussion' E$ B7 \8 [6 ]* A
Precocious puberty in boys is defined as secondary' p L* Y# _4 @$ y. S2 j$ {4 j: g
sexual development before 9 years of age.1,43 D( j) a% M# [' p5 n8 F. Q% `
Precocious puberty is termed as central (true) when
8 Y6 L2 X0 C* U$ ait is caused by the premature activation of hypo-
) h9 N) |* f5 w: p' rthalamic pituitary gonadal axis. CPP is more com-' J, }; \+ S" m) G
mon in girls than in boys.1,3 Most boys with CPP
# C0 g/ E3 J4 g- ?may have a central nervous system lesion that is
% p* R# A: e* j6 J/ U+ k, aresponsible for the early activation of the hypothal-
6 ^$ O% i8 \9 z- e& L qamic pituitary gonadal axis.1-3 Thus, greater empha-# w$ }/ n+ p x8 z9 v( B
sis has been given to neuroradiologic imaging in
: v5 l6 O( Z1 C: C7 _- r4 Sboys with precocious puberty. In addition to viril-* j" e( H, s% H. R, j5 M
ization, the clinical hallmark of CPP is the symmet-
# Z4 d/ v0 i' [9 J" Q3 c6 O& arical testicular growth secondary to stimulation by( t* t b4 A% ]5 z9 d1 Z: M, `* p
gonadotropins.1,3
0 V) x- h1 T0 M* a' Z: j; Z i" q5 S, NGonadotropin-independent peripheral preco-
R9 ?3 Z! D0 E8 s& r0 J5 ]+ x$ W; ycious puberty in boys also results from inappropriate
k/ k ]* E" [; oandrogenic stimulation from either endogenous or# t5 B+ o4 y: \. d ?
exogenous sources, nonpituitary gonadotropin stim-% y$ Q% r, E" y8 D8 S/ }
ulation, and rare activating mutations.3 Virilizing
% p) S- |# `5 X) H# Jcongenital adrenal hyperplasia producing excessive
8 {; Q/ }; ^3 b" M5 D, ladrenal androgens is a common cause of precocious
% {/ k1 Q1 L! Bpuberty in boys.3,4& c4 X1 M9 \/ u/ }# _+ \
The most common form of congenital adrenal
& ?/ u1 n! J* ]5 x; m( `# \2 ahyperplasia is the 21-hydroxylase enzyme deficiency.9 h$ [3 I9 b% ~* ~ t* {, [/ P, [5 D) l
The 11-β hydroxylase deficiency may also result in- o: V7 L. A6 S/ h
excessive adrenal androgen production, and rarely,
4 M2 z2 W' m* w% |an adrenal tumor may also cause adrenal androgen
* F4 {, B" r8 p$ }# mexcess.1,3
1 m; R, J' J2 H1 ~% f- qat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
; R6 L. U3 g* B$ C542 Clinical Pediatrics / Vol. 46, No. 6, July 2007# @9 ]' | `% Z# K
A unique entity of male-limited gonadotropin-7 e9 |3 x% n5 G3 v6 L
independent precocious puberty, which is also known
9 ]% W/ |! J+ l/ W+ X7 aas testotoxicosis, may cause precocious puberty at a( P7 }; j1 r3 E7 C: F$ d, _
very young age. The physical findings in these boys" ~$ b& K6 w9 F- M$ k' _3 q" [
with this disorder are full pubertal development,
" x* L8 S: Y1 H' U4 Bincluding bilateral testicular growth, similar to boys! \2 s" k$ k) k% b- ?
with CPP. The gonadotropin levels in this disorder7 t$ @ }, U, H% S) y9 M
are suppressed to prepubertal levels and do not show
* z }, Z. J/ D7 q4 V( jpubertal response of gonadotropin after gonadotropin-
# u4 ^: ]8 X3 c. v t+ ^, ^releasing hormone stimulation. This is a sex-linked5 t; G7 W4 F5 Y
autosomal dominant disorder that affects only0 m: x+ z& t$ u3 J1 U2 v
males; therefore, other male members of the family7 D9 L6 C8 a5 Y+ N
may have similar precocious puberty.3
! e! B- \: d) d, qIn our patient, physical examination was incon-
' P% e2 s9 x4 J9 j6 ^. g7 Xsistent with true precocious puberty since his testi-) [2 J) ?+ I/ T% r; L
cles were prepubertal in size. However, testotoxicosis; U: @# A; z; L& J3 {
was in the differential diagnosis because his father: x! C" {" k1 l
started puberty somewhat early, and occasionally,
% V7 e! o; }8 utesticular enlargement is not that evident in the& C p1 @( V' |4 ^: p6 n) l' Z; A
beginning of this process.1 In the absence of a neg-
1 ~1 T2 @0 n |6 F) q7 Mative initial history of androgen exposure, our
5 ]/ i; w6 ]$ Ebiggest concern was virilizing adrenal hyperplasia,# G/ ^4 h0 k ?9 o; h
either 21-hydroxylase deficiency or 11-β hydroxylase
D$ Y9 y. x8 T/ Qdeficiency. Those diagnoses were excluded by find-" c8 X/ l6 c, P) R b) [
ing the normal level of adrenal steroids." U* Y% l1 W& o$ \
The diagnosis of exogenous androgens was strongly
0 u/ x6 v' b ususpected in a follow-up visit after 4 months because
" ~9 a [- p: U+ T, ithe physical examination revealed the complete disap-
: }9 K. `0 n, f. ^* y* hpearance of pubic hair, normal growth velocity, and: v a4 A: Z9 v
decreased erections. The father admitted using a testos-
4 B, S7 e- f. ?, [% zterone gel, which he concealed at first visit. He was' ?# l+ d4 Y+ @/ G
using it rather frequently, twice a day. The Physicians’
) G9 x& U3 [8 X! `/ s8 `Desk Reference, or package insert of this product, gel or( K, S( }. u5 S
cream, cautions about dermal testosterone transfer to* M% W' [6 k. G& ^: s6 E0 X+ H
unprotected females through direct skin exposure.( R8 d u$ a x4 s( ]
Serum testosterone level was found to be 2 times the
! V6 \7 J; {+ I) T) mbaseline value in those females who were exposed to5 a" w& {# A8 |# ?5 K2 @- h" `
even 15 minutes of direct skin contact with their male
) W4 }" t" w" t+ r% v$ `2 s& o$ `- k8 spartners.6 However, when a shirt covered the applica-' h O2 G8 v' @8 h. G
tion site, this testosterone transfer was prevented.
" t. j6 }. P9 v" u* z7 F. }6 Q+ EOur patient’s testosterone level was 60 ng/mL,
& `% N5 W! D( ?) zwhich was clearly high. Some studies suggest that. W( u& }0 M6 b
dermal conversion of testosterone to dihydrotestos-
Y7 w X6 F6 b8 X. v, G; ?terone, which is a more potent metabolite, is more6 F6 v, f9 E( n. Q# r
active in young children exposed to testosterone! g: T! M- E( }; W$ \
exogenously7; however, we did not measure a dihy- \- R1 k4 e) A0 R. Z
drotestosterone level in our patient. In addition to
+ @' w7 D$ j0 u9 d3 y/ I( fvirilization, exposure to exogenous testosterone in
% o9 {$ E3 X& p0 J6 m+ J& C# r0 hchildren results in an increase in growth velocity and
, d$ x6 p2 N- P# V) nadvanced bone age, as seen in our patient.
1 q! g2 b9 t4 PThe long-term effect of androgen exposure during
2 G4 c+ O2 |* r8 [; n, V5 v' S9 {& xearly childhood on pubertal development and final( G7 D! ~6 @. v
adult height are not fully known and always remain, s/ P5 n; L2 [/ a" x
a concern. Children treated with short-term testos-
% w' V+ [0 e4 z0 \; {- hterone injection or topical androgen may exhibit some4 Z0 A# R+ G% k: ?- @8 b- I8 ~
acceleration of the skeletal maturation; however, after
; F4 ^( A/ o2 S& Tcessation of treatment, the rate of bone maturation& w0 o5 I! g# D
decelerates and gradually returns to normal.8,95 r/ V3 _) P2 H0 z3 P& m
There are conflicting reports and controversy6 g( Q* G# Q% [. F
over the effect of early androgen exposure on adult" O1 Z+ f. L/ R+ a
penile length.10,11 Some reports suggest subnormal
& F& X& J s! j& g8 ]6 l6 |0 ladult penile length, apparently because of downreg-# e H5 \* W0 B$ _7 I' ?
ulation of androgen receptor number.10,12 However,
! Q4 X4 o+ g) O9 ?Sutherland et al13 did not find a correlation between% H) {- U) G, V, a0 U% E
childhood testosterone exposure and reduced adult
0 u% P( K; @. I; o# K5 [penile length in clinical studies.! z5 s; _4 t% Y* c c
Nonetheless, we do not believe our patient is
2 D) N6 A' ~+ h/ c4 [going to experience any of the untoward effects from
% _' t* Y0 F4 v, g0 e* Q0 U2 rtestosterone exposure as mentioned earlier because" G( C# c# [% a% [* V4 W
the exposure was not for a prolonged period of time.
6 }; B6 _0 f- A8 S5 O" EAlthough the bone age was advanced at the time of
+ x' a5 a& O; Ydiagnosis, the child had a normal growth velocity at! R" N! q& p! y ~/ D9 G u+ \6 ]
the follow-up visit. It is hoped that his final adult1 E7 J* w2 a: r9 ?$ W3 K
height will not be affected.
$ S! T* L6 e. u3 y# cAlthough rarely reported, the widespread avail-
& W9 H- V4 ]! }; P3 \' K8 M. X& lability of androgen products in our society may
, n" N- D# |1 Z9 k7 Aindeed cause more virilization in male or female
- f4 w; D$ R8 d( ] ^) d5 ~* Fchildren than one would realize. Exposure to andro-
( y0 ]+ T% j u. s$ ^gen products must be considered and specific ques-1 R: g T9 f% d4 s& a1 L) v/ g
tioning about the use of a testosterone product or9 x5 Z4 q0 r) q. O* I+ h
gel should be asked of the family members during
6 c5 ?; N5 D4 ~% _% Hthe evaluation of any children who present with vir- J5 |% ]$ x9 i7 B
ilization or peripheral precocious puberty. The diag-
7 q7 B+ P H1 d2 D fnosis can be established by just a few tests and by) c1 i/ t V: [- D% J
appropriate history. The inability to obtain such a
! y$ Q1 \# ]) v8 E% w, M2 T: Nhistory, or failure to ask the specific questions, may
1 l# m" ^9 S* s5 C" l# s" zresult in extensive, unnecessary, and expensive, q' S7 M( b c- e: @* p
investigation. The primary care physician should be+ K) G+ [ i8 H$ b
aware of this fact, because most of these children
M5 r9 r# X/ Umay initially present in their practice. The Physicians’! y( I3 g: A/ x% q
Desk Reference and package insert should also put a
7 Z3 a/ E$ A! G* Dwarning about the virilizing effect on a male or/ b/ T; d2 J( c7 Z- o
female child who might come in contact with some-4 a7 _5 k# o$ N& c# r, B) J) F
one using any of these products., R+ l' w- U1 C) u( F
References
) s1 O# e9 @5 r9 W7 f4 O X0 q0 d1. Styne DM. The testes: disorder of sexual differentiation
0 l/ C# x( f7 Eand puberty in the male. In: Sperling MA, ed. Pediatric* ?6 i; E3 g# ^* q6 }+ Q( H. r6 l
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;$ x, l7 e D# f4 e: m
2002: 565-628.; K6 ~8 O% S0 ~+ x* l1 K6 B
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
9 C" E9 G" j6 h0 ?/ l1 t0 F1 vpuberty in children with tumours of the suprasellar pineal
& H9 p7 H1 w8 R! q7 \4 Y( u2 E- {at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from+ ^ L/ }+ h+ c1 Z6 q1 ^& x
Topical Testosterone Exposure / Bhowmick et al 5439 A u2 z0 S3 @( p' f
areas: organic central precocious puberty. Acta Paediatr.1 i3 P& Q8 g' E5 f, ?% s7 c/ v1 Q
2001;90:751-756.1 O* P8 i7 Q) a) l
3. Lee PA. Puberty and its disorders. In: Lifshitz F, ed.
0 G. y# E! s: i6 T4 A! EPediatric Endocrinology. 4th ed. New York, NY: Marcel# e( O5 W V1 \ V* [
Dekker Inc; 2003:211-238." ]4 `# }7 ?6 p/ i7 d7 E+ z' q2 k. {) K
4. Yu YM, Punyasavatsu N, Elder D, D’Ercole AJ. Sexual
# v7 U4 y7 e# ]1 w! ^/ Sdevelopment in a two-year-old boy induced by topical2 E3 m0 q: r& i' \7 n3 t7 m
exposure to testosterone. Pediatrics. 1999;104:e23.9 s& E5 R9 Z$ l4 ]* j
5. Greulich WW, Pyle SI, eds. Radiographic Atlas of
- h5 v2 v& G3 X# w; j! s# m2 fSkeletal Development of the Hand and Wrist. 2nd ed.
% t }: s) R7 H, WStanford, CA: Stanford University Press; 1959.9 S6 G& q7 t1 @6 k# d- b
6. Physicians’ Desk Reference. Androgel 1% testosterone,/ n5 y, P# E0 ]/ `' A
Unimed Pharmaceutical Inc. Montvale, NJ: Medical( X W. f" T& ?3 h
Economics Company, Inc; 2004:3239-3241.
: K6 v* |4 U5 h# p5 p- C# d& W6 ?7. Klugo RC, Cerny JC. Response of micropenis to topical
) [: U, h. I+ y+ {$ ^ q: y& Otestosterone and gonadotropin. J Urol. 1978;119:0 j! V( ?% e: T
667-668.5 @) y3 s$ [3 ^( p* b1 ^7 a
8. Guthrie RD, Smith DW, Graham CB. Testosterone$ ~" F$ q; h5 ?. S& F. I" K
treatment for micropenis during early childhood. J Pediatr.+ t9 U3 O2 N, a" g( x( N* h' F: m
1973;83:247-252.
1 |' {3 b( A, C% g: z; P& _, o9. Jacobs SC, Kaplan GW, Gittes RF. Topical testosterone
% p6 d! o. O3 |# j- vtherapy for penile growth. Urol. 1975;6:708-710.
" F! M( C, A# K, t3 K5 P10. Husmann DA, Cain MP. Microphallus: eventual phallic; r) ]/ F! x3 h) v F4 \
size is dependent on the timing of androgen administra-' P! {0 F2 Q/ _& K% m+ T
tion. J Urol. 1994;152:734-739.
9 D" ^0 u/ x& N4 L0 _. [) S11. McMahon DR, Kramer SA, Husmann DA. Micropenis:# n V# V' Y4 h
does early treatment with testosterone do more harm
1 i6 E( q) q I: w# qthan good? J Urol. 1995;154:825-829.
; ?$ c: a- G0 `) G12. Takane KK, George FW, Wilson JD. Androgen receptor4 ^* j: `/ |8 h/ S& L: {* h
of rat penis is down-regulated by androgen. Am J Physiol." s$ U3 ^$ ?0 ?) i' n9 q- {7 p
1990;258:E46-E50.- z' [8 W- F+ I, z& H U+ X9 P
13. Sutherland RS, Kogan BA, Baskin LS, et al. The effect( Q8 m7 @* }9 ]- M
of prepubertal androgen exposure on adult penile
3 _; Y7 C* c% Q0 Ilength. J Urol. 1996;156:783-787. |
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