- 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
- m& s* A5 J4 W- d9 _( F! @& hprecocious puberty (CPP), which is mediated# {! Q, a. X" ]
through the hypothalamic pituitary gonadal axis, has! ^0 p+ E! p; z+ C6 K' J& @' i
a higher incidence of organic central nervous system" U4 n3 W, b, w4 A3 _; j, q% @% G
lesions in boys.1,2 Virilization in boys, as manifested# U/ k" `" i. }3 T
by enlargement of the penis, development of pubic
( j9 E" ]" ~6 g8 L* Thair, and facial acne without enlargement of testi-
6 y* |4 c; `* |( r2 q9 gcles, suggests peripheral or pseudopuberty.1-3 We, B; c q3 ^ b0 V1 O5 n% S
report a 16-month-old boy who presented with the
, `: T" r) S% kenlargement of the phallus and pubic hair develop-7 p& f5 _& c# K2 Y. x
ment without testicular enlargement, which was due
& V" B+ l; o9 P: A1 _4 Ito the unintentional exposure to androgen gel used by& R9 U6 ?$ f, F2 f8 J
the father. The family initially concealed this infor-
% z% i7 }$ f! ~0 ymation, resulting in an extensive work-up for this
1 G1 `1 l- |7 Dchild. Given the widespread and easy availability of
9 l" w) s! ?! w7 F+ [- U/ B" u6 ptestosterone gel and cream, we believe this is proba-* H* |3 K9 l3 k, i$ d
bly more common than the rare case report in the
7 @5 ?8 l% e, Oliterature.4
7 a7 z9 B" v% ?, VPatient Report" F& }- G5 T. ]- J8 u% ^$ y
A 16-month-old white child was referred to the
8 p2 z7 D, E/ ] F( V% Iendocrine clinic by his pediatrician with the concern
& N5 Z' n( X% |& u- `- d! oof early sexual development. His mother noticed" p; o0 U4 s9 k9 E) ^. o+ G. [
light colored pubic hair development when he was
+ M _* O- h$ l( NFrom the 1Division of Pediatric Endocrinology, 2University of; \) n" ?0 i$ _6 |' f) ~
South Alabama Medical Center, Mobile, Alabama.2 p6 [* l! s* r) g! m
Address correspondence to: Samar K. Bhowmick, MD, FACE,
B8 Q4 F' K8 J: r0 G: a- xProfessor of Pediatrics, University of South Alabama, College of
& f" X- d: G. z- y* N" n6 T5 {Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;4 I$ p4 O* U/ [3 Z/ D. Q3 b
e-mail: [email protected].3 {) x X" Q# `3 |; i
about 6 to 7 months old, which progressively became1 P/ n5 U, S2 F* R
darker. She was also concerned about the enlarge-( a1 K% v6 J4 D* R8 ^8 G
ment of his penis and frequent erections. The child
" W, _6 P9 C# ~was the product of a full-term normal delivery, with$ o j5 f' l5 r* I' |" i
a birth weight of 7 lb 14 oz, and birth length of
: I4 J6 P1 v1 h( @0 X) _5 b20 inches. He was breast-fed throughout the first year
/ h0 `& o' a' R" tof life and was still receiving breast milk along with/ N# l. V$ i! y" M S
solid food. He had no hospitalizations or surgery,
) @$ P' |3 p+ Tand his psychosocial and psychomotor development
9 B/ ~4 M( a, ]" S8 G# m, `; rwas age appropriate./ V6 o! ?2 U7 y& E$ b2 V
The family history was remarkable for the father,
2 j2 F3 q3 L2 F8 ^' f4 Iwho was diagnosed with hypothyroidism at age 16,
U+ |1 ^( w$ ?5 z& bwhich was treated with thyroxine. The father’s5 O* u: g3 X0 ~8 ^4 H0 [8 r
height was 6 feet, and he went through a somewhat+ q ]& e6 W+ v: S% h$ ~
early puberty and had stopped growing by age 14.
5 W) {! ]. i% X* h& Q* Z& OThe father denied taking any other medication. The& C0 {! r3 } o$ X6 X2 G
child’s mother was in good health. Her menarche" U3 ^* u! `8 s% E4 D+ {9 v$ u% {: R
was at 11 years of age, and her height was at 5 feet* ]: r8 n- S- r
5 inches. There was no other family history of pre-5 F- F6 P5 i2 [2 ]6 S# ]
cocious sexual development in the first-degree rela-
! T0 L8 x7 e& i: w5 ?tives. There were no siblings.
' J/ p0 G" |" C* l4 u/ mPhysical Examination
5 K& L$ q2 h! {- x, w' q f( wThe physical examination revealed a very active,# x( Q: {; a8 I9 H Z+ l3 A
playful, and healthy boy. The vital signs documented
% e U% ?% ^- I) J) M; Va blood pressure of 85/50 mm Hg, his length was
( k, Z) ~ r# A3 }/ n5 {; S90 cm (>97th percentile), and his weight was 14.4 kg
7 W+ v0 j2 {' f4 i( O' ^(also >97th percentile). The observed yearly growth. A: L+ B' F1 \$ d
velocity was 30 cm (12 inches). The examination of
$ @4 u! D6 T4 ~+ z$ Ythe neck revealed no thyroid enlargement.( Y9 l3 v0 M/ t# B% L8 u7 q# }
The genitourinary examination was remarkable for
& p4 L' p* n8 G! k' f6 E, {4 Genlargement of the penis, with a stretched length of2 ]+ w5 ?# |& g2 e7 t
8 cm and a width of 2 cm. The glans penis was very well
' F5 x+ C/ C1 v; M+ S+ S9 ?( gdeveloped. The pubic hair was Tanner II, mostly around
1 l) Y `: @4 N/ G7 ~/ G540
; _: v: [ H8 d" K' Q; D( ^/ K2 U* Gat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
/ u7 T7 Q! o& k7 J4 xthe base of the phallus and was dark and curled. The
, q6 B5 t' l k$ Z* N* s8 Htesticular volume was prepubertal at 2 mL each. k) R5 W$ ^" [
The skin was moist and smooth and somewhat
& b& o: q/ t6 \$ \$ Xoily. No axillary hair was noted. There were no4 x$ T& E5 i4 G |
abnormal skin pigmentations or café-au-lait spots.# N% U+ D; n. ~0 n* K. n
Neurologic evaluation showed deep tendon reflex 2+; J: S, `3 w- H
bilateral and symmetrical. There was no suggestion. [& k8 h. a5 x! s& E7 I2 k
of papilledema.& M9 r9 t( ~1 W' F5 o* K" l
Laboratory Evaluation
( q7 g7 w$ M' n$ Z- s* gThe bone age was consistent with 28 months by
( x2 _- A2 e/ d- h( a# [ Dusing the standard of Greulich and Pyle at a chrono-
3 d8 f4 f5 h# R0 |8 |0 Rlogic age of 16 months (advanced).5 Chromosomal
# a4 N5 |; `2 E4 Ukaryotype was 46XY. The thyroid function test- k; F7 u+ T- H, B. {" s6 H. c4 `9 r
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
& Q+ r7 C; |+ S/ ^! ^lating hormone level was 1.3 µIU/mL (both normal)./ ~+ A" H v7 M8 ]6 F% a+ H1 \
The concentrations of serum electrolytes, blood7 E, M9 j6 D% v
urea nitrogen, creatinine, and calcium all were2 F9 N9 F$ s6 V, {- ^! G
within normal range for his age. The concentration9 U1 e0 ~# r0 W1 G7 |5 m/ Z
of serum 17-hydroxyprogesterone was 16 ng/dL
; p, z# t# A1 X* @9 g' s; X(normal, 3 to 90 ng/dL), androstenedione was 20, G* @! E8 |/ U* |& o2 t
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-4 q" ?, T0 k4 e( v
terone was 38 ng/dL (normal, 50 to 760 ng/dL)," D9 l4 ?* }6 `5 b! @4 _% a
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
2 z T' [8 M! ?( W: K! z49ng/dL), 11-desoxycortisol (specific compound S)( S. R1 N7 q9 g
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
& ~' x' f8 X% @: L; V2 S& Ttisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total8 Y1 F( b' U& j
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
3 x7 R2 s M5 w1 r1 ?7 j5 Yand β-human chorionic gonadotropin was less than
5 B7 k8 @+ ]2 }8 O: y5 mIU/mL (normal <5 mIU/mL). Serum follicular5 c" i. N1 c3 ^/ b- }
stimulating hormone and leuteinizing hormone
8 n! P* f0 u( e) ~% [- Aconcentrations were less than 0.05 mIU/mL
5 P! d/ ~* Q% ~(prepubertal).
3 W- ~$ m# f& e9 s9 J& U6 zThe parents were notified about the laboratory
/ i( D3 f Q' n8 Y+ Rresults and were informed that all of the tests were! G; |4 \/ j. e$ ]8 [: C
normal except the testosterone level was high. The
?+ E2 L# c' B$ s$ S) P' Afollow-up visit was arranged within a few weeks to- _2 C7 |5 s5 B3 h
obtain testicular and abdominal sonograms; how-
- i: ]) M5 h9 u3 M# y h+ G M! k0 ~ever, the family did not return for 4 months.
5 b( ]* v: x+ y* ]Physical examination at this time revealed that the3 d2 h6 w' |0 F0 T4 [
child had grown 2.5 cm in 4 months and had gained; E4 P& V( z+ r! \1 Q1 p( y" W
2 kg of weight. Physical examination remained) \& D! P) I& M) C6 P+ l
unchanged. Surprisingly, the pubic hair almost com-
5 b) L4 x8 i1 W: l K' xpletely disappeared except for a few vellous hairs at5 P2 @* u( b. t7 x7 y0 f6 [
the base of the phallus. Testicular volume was still 2
5 L& _. m5 }" M- {mL, and the size of the penis remained unchanged.% z7 B) e$ Y9 f$ d: ]
The mother also said that the boy was no longer hav-
8 z- `1 d ^! G% z8 M/ Ting frequent erections.
# q) j$ N3 h6 t# M* w4 _- ABoth parents were again questioned about use of- C) ]5 Q' X; U9 W0 x$ a: r4 u& V: t) n
any ointment/creams that they may have applied to
$ b+ b7 |6 Q7 ]5 Y5 M) dthe child’s skin. This time the father admitted the. E5 B" Z. ^2 f- v( }
Topical Testosterone Exposure / Bhowmick et al 541
0 V0 g: }; b+ r& |use of testosterone gel twice daily that he was apply-' j4 q* w4 N! c* K e+ s
ing over his own shoulders, chest, and back area for# Z/ Q1 b: X+ q# Z
a year. The father also revealed he was embarrassed/ h4 F9 k6 m* e
to disclose that he was using a testosterone gel pre-3 z4 m3 J' O$ W5 T
scribed by his family physician for decreased libido( r( g4 @/ x5 Q5 t2 F
secondary to depression.* p) p4 k9 n2 T6 {, {
The child slept in the same bed with parents.
. h: C' b5 C) EThe father would hug the baby and hold him on his O! V! t+ n0 D! J; u
chest for a considerable period of time, causing sig-9 I5 E4 x2 t8 K. {
nificant bare skin contact between baby and father.- V. [; ]! J- D0 P0 b
The father also admitted that after the phone call,4 i6 K6 v* P: _( s
when he learned the testosterone level in the baby/ ~6 Y' m- ^# T: D) n4 n* Q9 S
was high, he then read the product information: }+ D1 t. A7 t2 g: b
packet and concluded that it was most likely the rea-
2 p' c5 f# s% Ison for the child’s virilization. At that time, they. F8 O4 ~# z8 r6 J0 @# @
decided to put the baby in a separate bed, and the
0 t( u$ T# y, Rfather was not hugging him with bare skin and had& b6 Y) G' w5 W, u
been using protective clothing. A repeat testosterone% H) v9 N' |$ T( b; M5 K& h
test was ordered, but the family did not go to the
1 ^ E+ ?7 h# F' ?: Q4 ?laboratory to obtain the test.4 n8 |9 `1 P0 U8 Z- V
Discussion
- v* g/ x- L: W/ p/ W0 }9 [/ L/ nPrecocious puberty in boys is defined as secondary
, A% Z% R" S% L1 ]% z9 ]. lsexual development before 9 years of age.1,4
' m, A2 i. ]4 E/ u+ t8 H8 B! pPrecocious puberty is termed as central (true) when/ o: c' E/ [) z1 l
it is caused by the premature activation of hypo-- m c& L. A L( ^" s" o6 I, F9 s! U
thalamic pituitary gonadal axis. CPP is more com-
* V( D: k: f# j8 l( Dmon in girls than in boys.1,3 Most boys with CPP1 _3 Q" c/ T* w; D! d) K+ J
may have a central nervous system lesion that is
5 a2 p' r& `! p$ o" ]& b; E+ `) _responsible for the early activation of the hypothal-8 a0 d, J: `. {) u: S- p
amic pituitary gonadal axis.1-3 Thus, greater empha-: _9 o. D7 t3 U0 H
sis has been given to neuroradiologic imaging in2 y J k+ S0 A2 X1 o8 q
boys with precocious puberty. In addition to viril-2 R# p/ I/ z. D6 d8 Q7 P7 L9 Q# W7 \
ization, the clinical hallmark of CPP is the symmet-7 `+ ]$ P- m9 C
rical testicular growth secondary to stimulation by3 q% \8 [" _- ^4 L
gonadotropins.1,3
4 ^2 l' p7 P* r; O$ i! i2 IGonadotropin-independent peripheral preco-
1 u2 K, \8 H( J8 K5 pcious puberty in boys also results from inappropriate4 Y* y" C! K- x& @! o
androgenic stimulation from either endogenous or' Q) ^) G$ e% v! ^, G. h
exogenous sources, nonpituitary gonadotropin stim-
/ S+ E9 X$ Q" A/ n1 vulation, and rare activating mutations.3 Virilizing( U- u5 v* s, Y7 t
congenital adrenal hyperplasia producing excessive7 K% ~* g' {+ B" t
adrenal androgens is a common cause of precocious
. X" n$ L# `8 Z$ K* v$ ypuberty in boys.3,4
9 Z/ F0 }' B" \& \# T4 ~The most common form of congenital adrenal) p' F7 j U/ J1 p/ ]* u
hyperplasia is the 21-hydroxylase enzyme deficiency.
; s$ ~# D/ f2 H; TThe 11-β hydroxylase deficiency may also result in2 R4 {! `. m$ G8 D/ a) ~
excessive adrenal androgen production, and rarely,3 `4 Q- H) T" r" c/ ^2 ~! k! v
an adrenal tumor may also cause adrenal androgen/ W; u6 }* ~9 u3 }
excess.1,31 ^. p/ L8 \8 v) O3 ~2 t
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
: |( b# c# O+ ^/ G6 c3 k$ Y542 Clinical Pediatrics / Vol. 46, No. 6, July 2007+ b# ]7 r M; P. x$ F
A unique entity of male-limited gonadotropin-
& [" H* h( ]) E8 y! qindependent precocious puberty, which is also known
4 O5 }0 z9 \; C+ xas testotoxicosis, may cause precocious puberty at a9 W5 a8 z$ a& n$ Z
very young age. The physical findings in these boys! y- @ c: A- s% _% j V3 A- l7 I
with this disorder are full pubertal development,
: D2 g2 {0 N5 z+ l( C* c- Dincluding bilateral testicular growth, similar to boys
) p% H# N$ q- U: V5 }" v7 x/ ?; [; ywith CPP. The gonadotropin levels in this disorder
& t6 F. v9 z- u+ E Dare suppressed to prepubertal levels and do not show& i& A( k# o$ @/ ]
pubertal response of gonadotropin after gonadotropin-
/ Z% ~2 A4 p( h7 Q0 O( a- V1 W7 r9 Vreleasing hormone stimulation. This is a sex-linked
6 Z/ s% O) P8 s; Kautosomal dominant disorder that affects only1 W5 z4 p9 b3 G* ^# e( [
males; therefore, other male members of the family5 H" A6 V2 X' m* a" E
may have similar precocious puberty.3
! v" o. z' g! C# ~+ Q9 z9 S" ~In our patient, physical examination was incon-/ f @. V$ r- ?
sistent with true precocious puberty since his testi-6 W1 e) v( ^* M1 A6 e$ J3 l5 z
cles were prepubertal in size. However, testotoxicosis
$ _- F2 y' M G* F6 Fwas in the differential diagnosis because his father) Z8 F' l" p# f* N
started puberty somewhat early, and occasionally,% I4 I5 |2 V9 f1 L( a
testicular enlargement is not that evident in the
0 g( s6 z, V' W7 f- ubeginning of this process.1 In the absence of a neg-
+ B1 Y* }* U4 @+ G2 o! r. lative initial history of androgen exposure, our
7 S6 @/ @, l/ G( W6 Mbiggest concern was virilizing adrenal hyperplasia,
8 F$ V: O8 Q# g; U0 L( deither 21-hydroxylase deficiency or 11-β hydroxylase
0 H1 q4 x$ m% m# g7 u8 odeficiency. Those diagnoses were excluded by find-8 ~, P- Z8 E$ E, N# d4 W
ing the normal level of adrenal steroids.$ w3 V6 a! X5 M" J0 r4 ~
The diagnosis of exogenous androgens was strongly
7 `) ^5 o6 F1 c% [5 ?/ z' p: fsuspected in a follow-up visit after 4 months because
8 u3 O3 ]0 ^* Wthe physical examination revealed the complete disap-
3 b8 v$ j" e) P8 Y5 d" k$ Zpearance of pubic hair, normal growth velocity, and
% S; o8 S) w$ f+ M) S. x: Zdecreased erections. The father admitted using a testos-
( d0 Z+ L9 E' [terone gel, which he concealed at first visit. He was5 W2 }( f- @0 @/ N3 S- O7 e
using it rather frequently, twice a day. The Physicians’
$ c! B& H+ A0 s% N+ n! \+ u, nDesk Reference, or package insert of this product, gel or
; z$ W- W( S, @3 {3 [# i J5 @cream, cautions about dermal testosterone transfer to8 q7 N% d' A9 M u" K- |
unprotected females through direct skin exposure.- \4 g* E- `6 G( T5 J, \2 ~# y
Serum testosterone level was found to be 2 times the; C m4 m2 j5 L
baseline value in those females who were exposed to
% M! T/ @/ h7 l" i1 G+ k# F, neven 15 minutes of direct skin contact with their male
- I. O; g$ ^4 m5 ?" Vpartners.6 However, when a shirt covered the applica-! \ x B7 F1 d0 z( c9 S
tion site, this testosterone transfer was prevented.
& A/ r# K" Z% G, I8 N% ]$ ~; sOur patient’s testosterone level was 60 ng/mL,5 h4 o% f8 ?/ g% m R4 y
which was clearly high. Some studies suggest that
9 m! B. K& H( ~7 Ydermal conversion of testosterone to dihydrotestos-' G- i0 G1 \, }5 {( f
terone, which is a more potent metabolite, is more3 t# X5 @+ x+ O8 A
active in young children exposed to testosterone9 M4 v9 B) Y. J% b" G8 T1 P
exogenously7; however, we did not measure a dihy-
( B- a) Z. N1 Jdrotestosterone level in our patient. In addition to) D1 B* m Q0 P+ |: G4 x5 L# o! u
virilization, exposure to exogenous testosterone in; w8 N; \+ I$ \+ \2 k0 D
children results in an increase in growth velocity and, G3 Z; }! f: c" J, B
advanced bone age, as seen in our patient." T' ]& |) b1 M* q# i/ h. C. ^
The long-term effect of androgen exposure during3 O- k" E+ u* M7 S1 n/ r5 f; S
early childhood on pubertal development and final
$ w2 ^8 r+ z f3 E! qadult height are not fully known and always remain
: S+ E# B8 g4 {* va concern. Children treated with short-term testos-. N, P! |0 F+ J
terone injection or topical androgen may exhibit some! q q! t$ m8 e
acceleration of the skeletal maturation; however, after! b. y/ b9 C, s
cessation of treatment, the rate of bone maturation* X0 l6 t7 F% q5 d2 u' J' g0 U( ~' Y
decelerates and gradually returns to normal.8,9# C6 G9 J1 E" r6 @8 J4 h5 l
There are conflicting reports and controversy0 o) Q* |6 [2 ?/ K1 k+ ?
over the effect of early androgen exposure on adult# f( b, j& ]- N/ h$ x
penile length.10,11 Some reports suggest subnormal
9 e$ _* F4 \( Z/ J( tadult penile length, apparently because of downreg-7 g) t7 H; V1 z
ulation of androgen receptor number.10,12 However,$ }) j! J3 u0 U P& ^% Y
Sutherland et al13 did not find a correlation between
2 ?- r+ C! A. r* K) D' X* Kchildhood testosterone exposure and reduced adult
! Q+ ]9 b8 Z2 x7 }penile length in clinical studies.
; D( y9 ?. M/ d, m8 BNonetheless, we do not believe our patient is
7 O( O7 ^/ J0 m: G A+ h1 B# q, Rgoing to experience any of the untoward effects from
9 l9 [) m# g6 A+ }# ytestosterone exposure as mentioned earlier because' g$ A% h1 R6 h4 b' L
the exposure was not for a prolonged period of time.0 r' N0 g; G! {* S" {
Although the bone age was advanced at the time of
6 {8 S$ E8 y' odiagnosis, the child had a normal growth velocity at* t* v& [- l3 |/ B/ S6 f' F i- t' x
the follow-up visit. It is hoped that his final adult
! V2 w. |3 d! `) [. t# x2 Uheight will not be affected.# A; ?! p$ `. h: n% r- @! E2 Z
Although rarely reported, the widespread avail-8 B `/ k0 ]0 s* I; [5 F3 g
ability of androgen products in our society may; \+ T# Q7 M# U1 S
indeed cause more virilization in male or female8 J6 P, o9 a3 ~0 r* y
children than one would realize. Exposure to andro-( l( m& o# b- R" p. J2 Y3 X
gen products must be considered and specific ques-
% A4 J' y' B$ [% a% ntioning about the use of a testosterone product or
2 [( S& W' n( G/ m* a9 }gel should be asked of the family members during
. _* Z! h& M: Z: n$ Bthe evaluation of any children who present with vir-
" E- y3 h+ A/ I' o+ P, ^ilization or peripheral precocious puberty. The diag-
& c4 G* f" j1 {nosis can be established by just a few tests and by0 |* I( T ^0 w; T1 X. g9 N$ i
appropriate history. The inability to obtain such a
+ e+ H/ [- v2 yhistory, or failure to ask the specific questions, may
4 h; D0 V. | R2 d, Nresult in extensive, unnecessary, and expensive0 t" P; P! e8 c0 Z
investigation. The primary care physician should be L; P9 }, g7 \* X
aware of this fact, because most of these children) c8 L- P* i3 [* Y
may initially present in their practice. The Physicians’
a0 M' O, x+ s, |Desk Reference and package insert should also put a# t( P# Z! u3 u& I6 D* F
warning about the virilizing effect on a male or
' c5 m% J& f2 K- \; J( Ofemale child who might come in contact with some-1 Q1 w+ u4 s5 H8 m1 W6 R4 e
one using any of these products.
+ h( a# Q7 h5 l" N- H) TReferences
9 d' K& |" }# J7 f- {# Z1. Styne DM. The testes: disorder of sexual differentiation
5 Q$ [/ c7 M- Y1 [ aand puberty in the male. In: Sperling MA, ed. Pediatric
5 W+ ?* C" a; u yEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;9 `/ @. I' V9 Q" p3 Y% e: E
2002: 565-628.
! v, S/ T; e! J) U2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
/ e, ~- g( I* I5 g# I9 @' qpuberty in children with tumours of the suprasellar pineal
# p+ r% }( C Q) k4 _at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from9 J. q/ a: l# O. B% Q, |6 ?9 z; h
Topical Testosterone Exposure / Bhowmick et al 543
# a! h4 c6 y7 S9 ^4 m2 {& b( |' pareas: organic central precocious puberty. Acta Paediatr.3 Q1 j& |8 Q# n7 H3 T
2001;90:751-756.
$ d+ H2 n2 m* J' K$ e3. Lee PA. Puberty and its disorders. In: Lifshitz F, ed.7 _$ [/ @5 \9 O! M
Pediatric Endocrinology. 4th ed. New York, NY: Marcel
2 @1 z# L0 S( G& w- O Z" DDekker Inc; 2003:211-238.
6 H9 a$ N8 @6 i8 o+ V8 x4. Yu YM, Punyasavatsu N, Elder D, D’Ercole AJ. Sexual/ N6 J; n$ M3 O8 X3 d
development in a two-year-old boy induced by topical
* ?8 }, u$ N$ L) x0 oexposure to testosterone. Pediatrics. 1999;104:e23. t0 v- c: K# ~* \
5. Greulich WW, Pyle SI, eds. Radiographic Atlas of8 ?6 i( }" x/ S- m
Skeletal Development of the Hand and Wrist. 2nd ed.
F3 @* n; T. d- V! V% r: xStanford, CA: Stanford University Press; 1959.) R0 P% m, L0 ^! w( j* k/ U
6. Physicians’ Desk Reference. Androgel 1% testosterone,
4 ~% M5 _, w' g7 h( h; |Unimed Pharmaceutical Inc. Montvale, NJ: Medical
' x8 H1 V4 o4 E0 K( t# B* @Economics Company, Inc; 2004:3239-3241.
5 E6 k, K. o; `% y- D# Q8 ]( A3 O7. Klugo RC, Cerny JC. Response of micropenis to topical
) `5 g5 y: }/ Z+ M z1 vtestosterone and gonadotropin. J Urol. 1978;119:
9 L) K$ |; _) N6 X! t% Y2 @" q667-668.3 }0 w7 F t* U
8. Guthrie RD, Smith DW, Graham CB. Testosterone
$ T& |* t. t0 Ltreatment for micropenis during early childhood. J Pediatr.
( b) T: r+ d. b) j! r) Y1973;83:247-252.
5 x- K! n" _- D9. Jacobs SC, Kaplan GW, Gittes RF. Topical testosterone
) k* a5 h. Z [2 }therapy for penile growth. Urol. 1975;6:708-710.2 Y& o4 k8 c- O3 @ }* y1 S z# q
10. Husmann DA, Cain MP. Microphallus: eventual phallic+ q0 b: h( b; e7 v
size is dependent on the timing of androgen administra-- K. g( ]3 z( t: ]' n8 u0 K
tion. J Urol. 1994;152:734-739.
m( e8 [) d( n1 a* B) H1 t11. McMahon DR, Kramer SA, Husmann DA. Micropenis:
8 B6 Q0 r4 L6 B9 X, a+ f0 Odoes early treatment with testosterone do more harm0 E# V6 |4 N) d' I4 J
than good? J Urol. 1995;154:825-829.
0 r% O4 e, P+ Y8 o12. Takane KK, George FW, Wilson JD. Androgen receptor
Q! u* r* y; S5 k7 Cof rat penis is down-regulated by androgen. Am J Physiol.% ^! @1 Q0 h4 C7 V
1990;258:E46-E50.0 t! m% @/ L; e7 g
13. Sutherland RS, Kogan BA, Baskin LS, et al. The effect
# F; e# s# |5 X4 |. n) dof prepubertal androgen exposure on adult penile* B4 w! ~; e+ `% Q! Q0 q2 l
length. J Urol. 1996;156:783-787. |
|