- 註冊時間
- 2023-5-6
- 精華
- 在線時間
- 小時
- 米币
-
- 最後登錄
- 1970-1-1
|
發表於 2025-1-4 03:38:58
|
顯示全部樓層
is a significant concern for physicians. Central; m0 W- T! L3 T) G8 q
precocious puberty (CPP), which is mediated
! H+ @0 r( `+ Bthrough the hypothalamic pituitary gonadal axis, has
E$ A2 b' V7 f: U- wa higher incidence of organic central nervous system5 j: Y9 W# w D. { ]4 \8 L7 A
lesions in boys.1,2 Virilization in boys, as manifested3 m9 B! d4 H5 Q( S7 V. X
by enlargement of the penis, development of pubic
3 Q1 T& ~# H* i3 _! p" dhair, and facial acne without enlargement of testi-" i$ @/ N, f' t7 T
cles, suggests peripheral or pseudopuberty.1-3 We
1 W1 N1 E. p# Z8 F) f$ Oreport a 16-month-old boy who presented with the
" U" I. j. H; x& u* d% K( Senlargement of the phallus and pubic hair develop-7 j) _" M4 R* ~8 ~$ O
ment without testicular enlargement, which was due2 I {9 _3 y, A1 Q- C( c# r, Z, H
to the unintentional exposure to androgen gel used by
2 I! W7 T: ]/ Ithe father. The family initially concealed this infor-
, J `- I$ J0 }& |mation, resulting in an extensive work-up for this
! F0 F! w5 E; ichild. Given the widespread and easy availability of
4 A6 R) c G! |* h- v, \testosterone gel and cream, we believe this is proba-8 J5 q% M8 L* n3 ~
bly more common than the rare case report in the% r- `& d8 C: y. M: Q; S" K+ Z( X
literature.4' L+ T4 j9 p5 _8 h" k4 @* T2 `' b
Patient Report# L0 Z; L- V9 F# Z6 ~
A 16-month-old white child was referred to the# e( u, E3 ~* I/ v7 {
endocrine clinic by his pediatrician with the concern
0 X, B- a4 L( J7 P& H! _* E0 Kof early sexual development. His mother noticed( ]8 g6 k' S' L( p
light colored pubic hair development when he was- M0 D3 ^& \0 T3 | o1 l9 ~6 K
From the 1Division of Pediatric Endocrinology, 2University of
$ ^0 c' h# u3 V" c$ Q$ d+ dSouth Alabama Medical Center, Mobile, Alabama.% J/ S* ]$ s! V4 A9 ?
Address correspondence to: Samar K. Bhowmick, MD, FACE,
! G1 a- y( s3 t) J( A2 W/ q2 p, ~3 _Professor of Pediatrics, University of South Alabama, College of/ [: q* b) i1 u' |5 H$ |# h) [
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
7 s& e- ]4 g/ L8 m& e( W/ ]e-mail: [email protected].+ e, O+ k$ Y* H. x. a
about 6 to 7 months old, which progressively became
5 \: j% o" L' |4 H, `' y* Bdarker. She was also concerned about the enlarge-* t4 u1 J8 \5 X, r
ment of his penis and frequent erections. The child
+ Q. y* t6 v O' E& j9 P2 f; J, |2 z; Owas the product of a full-term normal delivery, with1 G2 Q9 i' P4 R! @! d# i' Q4 h
a birth weight of 7 lb 14 oz, and birth length of
0 t: ]" a. s4 U% x20 inches. He was breast-fed throughout the first year' J4 f8 T9 W$ \' o5 g
of life and was still receiving breast milk along with
& ^0 f5 _1 L! e. b. l7 Fsolid food. He had no hospitalizations or surgery,+ f8 {- L/ E. R1 |
and his psychosocial and psychomotor development
# o- d$ \# s* [0 J1 D3 y M( \% ewas age appropriate.
; |& M6 z9 O# |/ y: h, ^$ Y+ bThe family history was remarkable for the father,. a- Q) _1 M S9 _
who was diagnosed with hypothyroidism at age 16,
: H2 m! ~( Z+ C4 uwhich was treated with thyroxine. The father’s
8 Q" v, I! w8 y8 {8 c$ G4 p) uheight was 6 feet, and he went through a somewhat- Q s$ Q4 t6 x/ ]% N7 |* D; _) E
early puberty and had stopped growing by age 14.' c; d; Z* |6 e% _
The father denied taking any other medication. The
7 V* ?& P* z/ Y! j5 P5 d* F Qchild’s mother was in good health. Her menarche
" x! q v1 r5 i4 B& ~- Twas at 11 years of age, and her height was at 5 feet
p/ k3 f0 \' Z4 N" ~# |5 inches. There was no other family history of pre-
P( L3 @! Q3 V5 Q( G! scocious sexual development in the first-degree rela-
4 s) J+ U$ T2 B9 x+ b# g: vtives. There were no siblings.
+ k+ d$ N) v$ c% ?6 y' a$ j3 b; RPhysical Examination
& r$ L3 [, o: T5 iThe physical examination revealed a very active,/ e' l0 t9 Z5 ^4 ]$ G3 i/ G1 M2 N, d/ E
playful, and healthy boy. The vital signs documented/ P1 q9 b ^1 ?& O* o
a blood pressure of 85/50 mm Hg, his length was% v, S. J. N( z. v f3 w# |
90 cm (>97th percentile), and his weight was 14.4 kg
; p( W5 S5 m. l4 g0 @ B) }(also >97th percentile). The observed yearly growth
- J; R( J& ~8 M! n% H; Gvelocity was 30 cm (12 inches). The examination of
& A' r; M$ k1 b. G% Qthe neck revealed no thyroid enlargement.
* E! f) i. t( ?0 A* K3 UThe genitourinary examination was remarkable for
C/ O2 ?4 E/ h- H5 C; @0 {enlargement of the penis, with a stretched length of7 L1 R% F6 o- Z
8 cm and a width of 2 cm. The glans penis was very well
' t8 v. k v4 o! S" J2 @- i4 i0 xdeveloped. The pubic hair was Tanner II, mostly around
3 d0 T Y5 U" l540
" E2 s2 D7 K& @; m. O; bat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
) i& Z! @8 A& Qthe base of the phallus and was dark and curled. The
3 N+ [9 L: g' L7 [- |7 I7 @testicular volume was prepubertal at 2 mL each." p/ O& ]$ M- E4 s3 o
The skin was moist and smooth and somewhat! f$ h! p4 t& x9 }+ [0 [
oily. No axillary hair was noted. There were no- ^. K+ q9 i1 d2 `. O
abnormal skin pigmentations or café-au-lait spots.# }6 E6 E* ]. e( H
Neurologic evaluation showed deep tendon reflex 2+
( g( D5 F2 Q- E- E1 p/ zbilateral and symmetrical. There was no suggestion- G; o" k* l5 _& Q s
of papilledema." E2 I) ^: Z7 n" I
Laboratory Evaluation
! G# M! e4 j' Q2 f3 }The bone age was consistent with 28 months by( Z) g r7 ~; U! ?! C3 c
using the standard of Greulich and Pyle at a chrono-5 i* O* j g: P
logic age of 16 months (advanced).5 Chromosomal
4 z1 o* g) G; q( d; D2 [/ skaryotype was 46XY. The thyroid function test
4 q( c1 H4 c! o7 _0 N5 a1 f! Bshowed a free T4 of 1.69 ng/dL, and thyroid stimu-& _# Y1 j) J0 h: y/ Z" A
lating hormone level was 1.3 µIU/mL (both normal).
. k% Z2 f1 b! a3 S; @The concentrations of serum electrolytes, blood
( ]" ^9 d+ C, D7 p* A6 {! Surea nitrogen, creatinine, and calcium all were* {* {# `& d1 R5 b9 O
within normal range for his age. The concentration
3 O& a5 _6 |2 F' m8 g h$ Cof serum 17-hydroxyprogesterone was 16 ng/dL
& t2 d* i1 q' m/ V6 T(normal, 3 to 90 ng/dL), androstenedione was 20
* U! @, L" w3 g9 x h4 W' wng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-5 d6 _+ c J. Q# T8 x h ~
terone was 38 ng/dL (normal, 50 to 760 ng/dL),9 S. y! ^7 n/ M! F( S! S
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
+ J9 Q0 E' Y- |1 \% o" ?: I49ng/dL), 11-desoxycortisol (specific compound S)3 Q* r5 @4 {: X( c7 k2 c- d8 z2 W8 ?
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-+ W' ]. q2 E# m$ n: X- q/ t- N
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total* s- R1 R& o% F! a4 J
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
! W5 t7 r1 q- t9 Y, x h5 cand β-human chorionic gonadotropin was less than- z4 @; [" e. B q! B. O. y9 J; u
5 mIU/mL (normal <5 mIU/mL). Serum follicular
! [! o7 {) {* x( m3 p- T- _- }stimulating hormone and leuteinizing hormone# D9 ?4 J+ p" f
concentrations were less than 0.05 mIU/mL, ^8 @& ?! Z0 t1 J
(prepubertal).3 D' N& m3 t4 i6 h1 A
The parents were notified about the laboratory q1 A+ p3 D& e1 X0 y
results and were informed that all of the tests were) ~ e* D% I" g/ | _1 b* E
normal except the testosterone level was high. The
, w7 [* Q( [6 n" X$ Zfollow-up visit was arranged within a few weeks to
3 H# d/ w6 a% R4 Iobtain testicular and abdominal sonograms; how-( ~ [% q6 ~9 ~. z4 F( X% r$ O
ever, the family did not return for 4 months.
" g3 g( o4 U" Q2 M$ cPhysical examination at this time revealed that the! i% }! T3 f: h3 I: V
child had grown 2.5 cm in 4 months and had gained: H/ _/ F/ J7 y3 Y( z
2 kg of weight. Physical examination remained5 a" T1 {0 n: I& B
unchanged. Surprisingly, the pubic hair almost com-
; m+ X) f2 ]/ |2 Q& _. ^pletely disappeared except for a few vellous hairs at" u" U2 h1 y9 i x H
the base of the phallus. Testicular volume was still 2) |) x8 s; H- M. i" r
mL, and the size of the penis remained unchanged.4 e# E* X/ E g+ e H9 M( U
The mother also said that the boy was no longer hav-+ l9 f* ?: O. [. [- I. c
ing frequent erections.0 i: E/ G. }' G/ h$ L! H2 m
Both parents were again questioned about use of' P8 X9 |" B, f& g
any ointment/creams that they may have applied to$ i9 o6 x) s! L
the child’s skin. This time the father admitted the
8 f4 ?& g W" P( H+ g6 kTopical Testosterone Exposure / Bhowmick et al 541/ e* |& f/ Q! U3 ]" L7 _
use of testosterone gel twice daily that he was apply-' d- R0 L$ G1 S5 |, _: u$ y% H
ing over his own shoulders, chest, and back area for
! y& I3 ~* V7 |4 c# ma year. The father also revealed he was embarrassed
; x) W! {- J1 I gto disclose that he was using a testosterone gel pre-! O7 l, c$ y- e! k
scribed by his family physician for decreased libido9 |2 W5 c, U3 ^! c/ ~ Q1 T2 H
secondary to depression.
7 L# b4 J) ^0 ]The child slept in the same bed with parents.9 p$ D, p, D, J# g
The father would hug the baby and hold him on his# S8 l6 s$ q) s/ a! r- b2 E. S/ T5 T
chest for a considerable period of time, causing sig-2 v3 w* ]5 z. m8 }+ ^
nificant bare skin contact between baby and father.
# O5 o5 l0 H: D2 U: A0 t* iThe father also admitted that after the phone call,
R+ d; c" [ ^! Q- [0 Kwhen he learned the testosterone level in the baby
2 P" i7 q( u" P( s- G+ Wwas high, he then read the product information& d" e& _2 V9 z- c/ S9 k/ l% ?
packet and concluded that it was most likely the rea-6 k2 o- d8 O; ^6 y: y
son for the child’s virilization. At that time, they
" U2 j4 ]" b( @+ Q# @# pdecided to put the baby in a separate bed, and the
9 x1 N# O9 o4 Sfather was not hugging him with bare skin and had
) {4 k6 z+ `9 `- h& I$ lbeen using protective clothing. A repeat testosterone
: \. F7 N9 l1 i0 ^test was ordered, but the family did not go to the
/ A' x) g$ w, P( o0 |laboratory to obtain the test.: r$ ~# r5 B$ A4 B: I
Discussion( r7 n: w% F/ O2 ^4 t
Precocious puberty in boys is defined as secondary
+ Z5 ~6 |) c. K' r' M, r2 d4 _: h7 u7 ssexual development before 9 years of age.1,4 C' }6 ^' T0 f0 P5 J
Precocious puberty is termed as central (true) when2 d7 F9 x' M& y1 m& R4 W+ n* r$ ^
it is caused by the premature activation of hypo-
8 S' T5 ]' p' u* |7 s8 S# Ethalamic pituitary gonadal axis. CPP is more com-7 B7 L w4 f& w! n1 O5 L7 X6 ?
mon in girls than in boys.1,3 Most boys with CPP" r0 p$ N( ~" w; X
may have a central nervous system lesion that is8 J1 ^7 t @( M7 i6 F: W
responsible for the early activation of the hypothal-; \# h5 v% u& g8 m0 ?% u7 K
amic pituitary gonadal axis.1-3 Thus, greater empha-! C* d+ p3 Y# t* I$ u! Z
sis has been given to neuroradiologic imaging in
& U/ V% m" R2 k6 Bboys with precocious puberty. In addition to viril-
* ~, M/ i0 P5 ], p9 {2 I( Vization, the clinical hallmark of CPP is the symmet-
% T# x6 }: C5 Y& K9 d$ @rical testicular growth secondary to stimulation by0 V. B3 ]3 b2 Q9 B& P1 q7 h
gonadotropins.1,3; K6 X# a+ ~* x
Gonadotropin-independent peripheral preco-0 M' a4 D! @/ ?1 a6 ^$ U
cious puberty in boys also results from inappropriate/ y4 _8 M8 z, s- N k" p
androgenic stimulation from either endogenous or
/ \( c# T3 a& v3 V( W cexogenous sources, nonpituitary gonadotropin stim-
5 V7 E' u) H! n+ Eulation, and rare activating mutations.3 Virilizing
* x$ q @& P' _% [ _' M2 d' J0 ncongenital adrenal hyperplasia producing excessive
) A+ c- W( g: A' A' Wadrenal androgens is a common cause of precocious
, Q* Z: J* G% C) Fpuberty in boys.3,4
. o8 o: D" c5 n& w @" mThe most common form of congenital adrenal
5 B' z4 s8 _5 K0 P" A# g, r' b) [hyperplasia is the 21-hydroxylase enzyme deficiency.# }: \- N, E2 z' U) N' X
The 11-β hydroxylase deficiency may also result in. U( O0 |7 ?+ O0 q$ `( [. ~
excessive adrenal androgen production, and rarely,2 I7 {7 C9 ` v6 ]0 N$ w/ G% ^
an adrenal tumor may also cause adrenal androgen% T1 k8 ]) G2 y& H! e8 u
excess.1,3: B& s- X( h0 L1 H. X: W
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
6 S ]/ Z( K- Y8 P% @" J# P$ l542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
0 Q! P/ E4 J8 c+ BA unique entity of male-limited gonadotropin-
0 Z Z d) c \0 {; k% Pindependent precocious puberty, which is also known
, P, j( t: w) h8 sas testotoxicosis, may cause precocious puberty at a' E' B- G9 f2 O; f
very young age. The physical findings in these boys2 K6 a3 J0 Y1 k" R/ p
with this disorder are full pubertal development,$ X- F! s/ |6 s
including bilateral testicular growth, similar to boys
: R* j: y9 X5 ?3 l k0 hwith CPP. The gonadotropin levels in this disorder
! S) @7 Y8 W; O/ j$ |! qare suppressed to prepubertal levels and do not show
4 k) S7 ?: U7 G6 [5 ~pubertal response of gonadotropin after gonadotropin-
]: |+ v; m: `* \; A; Zreleasing hormone stimulation. This is a sex-linked( d- b. H+ v* ~
autosomal dominant disorder that affects only
6 @3 K( j0 I/ u0 ]* H) i" ]0 @males; therefore, other male members of the family* H4 \, q0 x) k- a6 V
may have similar precocious puberty.3& @: E, y6 Y8 K" n9 m/ P- ]" p
In our patient, physical examination was incon-
0 M+ i- t" r+ nsistent with true precocious puberty since his testi-
- L& t8 n7 B/ @7 t7 bcles were prepubertal in size. However, testotoxicosis$ y, x9 Z7 e% G
was in the differential diagnosis because his father0 O; U& [& _+ \) Q. H
started puberty somewhat early, and occasionally, W2 g. u; _& W9 L. z# e% `: F
testicular enlargement is not that evident in the. H& W6 X. g) S' w7 \8 z Y
beginning of this process.1 In the absence of a neg-
. S+ o" }- d2 A4 Native initial history of androgen exposure, our
3 T! f; m4 q5 h8 n3 q2 ebiggest concern was virilizing adrenal hyperplasia,' x: ^# g4 W" Z( c
either 21-hydroxylase deficiency or 11-β hydroxylase, `7 X2 V. Q& z" R7 Y
deficiency. Those diagnoses were excluded by find-3 y6 h# T2 Z& i/ L
ing the normal level of adrenal steroids.+ s* Q; B3 d: v
The diagnosis of exogenous androgens was strongly2 Z1 i2 t; k# s6 G9 f0 m. H
suspected in a follow-up visit after 4 months because/ y2 `$ j. A! O: O) y
the physical examination revealed the complete disap-
- p# q! l4 N) G+ M+ p! _ Apearance of pubic hair, normal growth velocity, and
# g7 Y! s' n# E% u7 pdecreased erections. The father admitted using a testos-! J% r# y' M) j6 t! x. s8 ?
terone gel, which he concealed at first visit. He was
1 m" V8 e$ M8 _* p, iusing it rather frequently, twice a day. The Physicians’
2 \. A0 A; _- ^2 M) R5 gDesk Reference, or package insert of this product, gel or
! h$ X3 W2 L5 @! F4 Vcream, cautions about dermal testosterone transfer to
' s$ n4 f6 ?& W4 N7 P3 a: g Q! Uunprotected females through direct skin exposure.
% o3 _2 [6 j0 U4 o. {Serum testosterone level was found to be 2 times the s7 L" d0 r, V% M& ^
baseline value in those females who were exposed to
& n: K$ G6 j, b' oeven 15 minutes of direct skin contact with their male' l: ?# J6 H p3 h
partners.6 However, when a shirt covered the applica-
( e5 T5 A) D3 w5 J, Btion site, this testosterone transfer was prevented./ S* P& S! s. I9 E% S
Our patient’s testosterone level was 60 ng/mL,/ r% H8 i8 D" X3 G! v2 U! |4 Y
which was clearly high. Some studies suggest that
1 L- _5 ^7 ^8 O+ p6 Q9 `dermal conversion of testosterone to dihydrotestos-& o) A1 [: S u0 x3 ]8 x0 q
terone, which is a more potent metabolite, is more
. n6 k' Z0 n! H# cactive in young children exposed to testosterone
, ?9 | P& x; o% M2 I6 R" |- F) sexogenously7; however, we did not measure a dihy-; s' c. k; ~0 k0 z4 E
drotestosterone level in our patient. In addition to
1 V5 l- g2 r. q1 x! `' ~) m4 ivirilization, exposure to exogenous testosterone in
- Q. u5 `: t+ ^/ a" e7 C" lchildren results in an increase in growth velocity and
8 B& T9 r% s8 u/ t$ s9 t5 u+ t$ oadvanced bone age, as seen in our patient.1 A! h6 P3 M. d% d
The long-term effect of androgen exposure during
3 {8 x! {, g4 m s) s; Nearly childhood on pubertal development and final
) R# n& k5 a) ~( B* aadult height are not fully known and always remain6 R& u3 i" @$ B9 N t2 t/ O2 ~
a concern. Children treated with short-term testos-' D1 N: u% V: [% d
terone injection or topical androgen may exhibit some
& ^* {2 m' r& b. N$ a' Iacceleration of the skeletal maturation; however, after0 g; n) P* D, L7 L
cessation of treatment, the rate of bone maturation/ b' y% @1 A- |5 w; X
decelerates and gradually returns to normal.8,9) k. ^2 x: }) F' s+ C% A
There are conflicting reports and controversy. I& x8 y N. B" `
over the effect of early androgen exposure on adult z% d( a6 S5 E7 n( j" H: s
penile length.10,11 Some reports suggest subnormal7 @" i& m% R0 |- `0 _) ]: M
adult penile length, apparently because of downreg-5 p# A# ]4 S- P" g
ulation of androgen receptor number.10,12 However,
& o8 {8 \- n3 j8 jSutherland et al13 did not find a correlation between
; V5 X" v/ x8 {& O) achildhood testosterone exposure and reduced adult% K( M' W* g9 [- {" T) U
penile length in clinical studies.
" X5 }/ |+ z" }1 ^Nonetheless, we do not believe our patient is
3 @( [( h1 K. c' X- e' pgoing to experience any of the untoward effects from
4 x" i9 ^0 t% l8 w% y3 n* A$ { Dtestosterone exposure as mentioned earlier because
' F: W; _+ I2 d) _the exposure was not for a prolonged period of time.
/ [2 T* b3 K$ M( Z* X+ Q, RAlthough the bone age was advanced at the time of: Q8 C& V/ z% y. \& b
diagnosis, the child had a normal growth velocity at
5 B/ q" r3 n2 ]$ W6 F( fthe follow-up visit. It is hoped that his final adult. t2 n/ r$ H5 a u
height will not be affected.
$ o5 `9 y+ Q, {. ? Z: W% pAlthough rarely reported, the widespread avail-! `$ t0 u7 W3 x8 y6 i9 b ^( T
ability of androgen products in our society may
7 ?, ?) o/ f" [, Lindeed cause more virilization in male or female
# f% E" c2 q3 pchildren than one would realize. Exposure to andro-, ?, N7 _" ]" N: D- p% {
gen products must be considered and specific ques-
- Y% M" P% {! ]" l8 Q% Dtioning about the use of a testosterone product or
# h( p: f6 B3 H% u' Fgel should be asked of the family members during
: R. q+ _/ @, S: ]the evaluation of any children who present with vir-( p4 \9 f& N8 ^
ilization or peripheral precocious puberty. The diag-
, k( t7 J/ c, Y1 [nosis can be established by just a few tests and by0 M) U; ^3 ` q0 f l
appropriate history. The inability to obtain such a
: f% T/ R/ u4 _history, or failure to ask the specific questions, may8 S M7 M: L0 m* D" L' R8 O3 W
result in extensive, unnecessary, and expensive" W# r. y6 C' a6 n9 E
investigation. The primary care physician should be0 u$ S4 q3 y' P" |, L
aware of this fact, because most of these children7 p$ t l5 T' s2 G b: m# X
may initially present in their practice. The Physicians’; W3 n. P6 L" d" }. t
Desk Reference and package insert should also put a7 x5 X Q* I' [; @* U
warning about the virilizing effect on a male or( K' ^$ ^% V( W, }
female child who might come in contact with some-/ P [5 L# O9 U0 R* x$ u1 u8 x
one using any of these products.
. m5 N6 L) P7 {References9 `" G' O9 V6 ?6 P R* B
1. Styne DM. The testes: disorder of sexual differentiation
% X% [4 g, d2 |and puberty in the male. In: Sperling MA, ed. Pediatric
% }# v I3 R& P; HEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;% h4 R5 O8 Q. y% e/ x
2002: 565-628.
$ {+ P# g; V/ v( ~9 l9 Q2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
1 I6 [: I x8 J2 \7 r# qpuberty in children with tumours of the suprasellar pineal
% q' M' w" y I' iat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from1 Y$ k' n9 @7 r6 ^3 @
Topical Testosterone Exposure / Bhowmick et al 543
7 K1 b. i, f! {3 @1 H! f6 Kareas: organic central precocious puberty. Acta Paediatr.) R% k2 y7 E* l k! {6 G* I
2001;90:751-756.
/ i6 Z! {5 D4 e) h* k$ J7 L3. Lee PA. Puberty and its disorders. In: Lifshitz F, ed.+ G) o3 r- ~! _7 g1 t9 D# C, `; b( A
Pediatric Endocrinology. 4th ed. New York, NY: Marcel
( u3 d" ~) `& o/ I+ \Dekker Inc; 2003:211-238.& R' R4 I) o8 t0 R2 t2 \7 y
4. Yu YM, Punyasavatsu N, Elder D, D’Ercole AJ. Sexual
3 A) ?+ o! t" ~: ~: p% C- `development in a two-year-old boy induced by topical
7 g4 N3 z7 b% v6 F! V) x8 zexposure to testosterone. Pediatrics. 1999;104:e23.5 s8 }0 K8 J/ g/ o5 D% K6 l
5. Greulich WW, Pyle SI, eds. Radiographic Atlas of- J% B. j' Z; G M7 R" `( ]9 T
Skeletal Development of the Hand and Wrist. 2nd ed.( ?$ |* {$ d" m2 I$ ]
Stanford, CA: Stanford University Press; 1959.
$ g) V( S) [4 E+ ^& B8 Y6. Physicians’ Desk Reference. Androgel 1% testosterone,
9 p& K2 z/ w# z' K* |' `Unimed Pharmaceutical Inc. Montvale, NJ: Medical
- `/ @+ t. q- n. ?1 |* eEconomics Company, Inc; 2004:3239-3241.3 T; N8 c- S, t6 h5 w" M1 f/ |, E. p
7. Klugo RC, Cerny JC. Response of micropenis to topical
V. w( e# b' o' f1 K+ K$ M0 C. ztestosterone and gonadotropin. J Urol. 1978;119:$ j% q, G+ w$ O0 s0 J
667-668.7 ?" ] y Y# a9 d
8. Guthrie RD, Smith DW, Graham CB. Testosterone) \, S: Q3 \, {
treatment for micropenis during early childhood. J Pediatr.
; }7 P) y: u; r1973;83:247-252.- e/ }! Q$ C. W# X
9. Jacobs SC, Kaplan GW, Gittes RF. Topical testosterone
, D- ^( t; N2 k1 X! _/ ytherapy for penile growth. Urol. 1975;6:708-710.
, Z* \& F" e |" m7 l/ d10. Husmann DA, Cain MP. Microphallus: eventual phallic
l, h4 D8 S( d# {$ _" X/ asize is dependent on the timing of androgen administra-% u+ [9 Q9 y6 T# l: U/ a9 @
tion. J Urol. 1994;152:734-739.
, F$ i% n6 S! y& `/ h3 O11. McMahon DR, Kramer SA, Husmann DA. Micropenis:: y: q# B3 |& \& a2 P2 D1 `1 b
does early treatment with testosterone do more harm3 B7 N$ {& w m/ c" N- w/ E
than good? J Urol. 1995;154:825-829.
. l5 Q% K2 m* |! p$ ~- P y0 Q12. Takane KK, George FW, Wilson JD. Androgen receptor8 m0 ~0 Z! v! ^: c, X
of rat penis is down-regulated by androgen. Am J Physiol./ f2 J6 W' \% ?! d4 O
1990;258:E46-E50., Z. j) B; q5 F3 L3 N0 k
13. Sutherland RS, Kogan BA, Baskin LS, et al. The effect
; `9 l" z2 @6 X5 ~3 q. uof prepubertal androgen exposure on adult penile I* K: U- @% y9 N
length. J Urol. 1996;156:783-787. |
|