- 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
/ k( f4 I: w* {) Eprecocious puberty (CPP), which is mediated1 j0 p9 y/ X e3 w/ A: n/ E8 h' A/ _
through the hypothalamic pituitary gonadal axis, has
& S" L% u* Q% n: V0 ia higher incidence of organic central nervous system& A% C+ `) t0 R( L- z
lesions in boys.1,2 Virilization in boys, as manifested
, ~. R9 `8 g: J" H+ Yby enlargement of the penis, development of pubic, `: V2 ?! z8 e" o+ {% z* o& ^* W$ s
hair, and facial acne without enlargement of testi-1 A+ C- Q* ^. P! k4 Z$ s! e
cles, suggests peripheral or pseudopuberty.1-3 We
, \- ~0 |9 ]3 E$ l2 Y( {' ~report a 16-month-old boy who presented with the5 t0 ^3 J! Z6 s5 R4 x3 B
enlargement of the phallus and pubic hair develop-
6 T4 x1 e$ T0 ?/ Pment without testicular enlargement, which was due A1 E. K5 t! }
to the unintentional exposure to androgen gel used by# K) Y3 R0 b% r. P8 R+ e5 Q
the father. The family initially concealed this infor-9 D( i6 M& z8 R) C
mation, resulting in an extensive work-up for this# x- e+ Q8 w" x n' Q! b
child. Given the widespread and easy availability of2 Y+ D! m& K" x# {
testosterone gel and cream, we believe this is proba- `" Z5 P2 H( ]
bly more common than the rare case report in the
" R7 J+ Y5 l; {literature.4
U8 ]$ o, }; M' e+ ~: w D" ~Patient Report: |5 J% X$ D. x* [6 b) B- J
A 16-month-old white child was referred to the8 E5 D; U4 i ^! u3 {/ g) h- q
endocrine clinic by his pediatrician with the concern
8 p! U9 B8 X* G. x0 Sof early sexual development. His mother noticed
! q- @# k) N& x! vlight colored pubic hair development when he was
1 C7 o1 z. C6 `& |2 E2 s: @* MFrom the 1Division of Pediatric Endocrinology, 2University of
1 B3 H8 z) q1 X4 S# lSouth Alabama Medical Center, Mobile, Alabama.
" K" x& c( h! S, r' k# CAddress correspondence to: Samar K. Bhowmick, MD, FACE,
x/ M6 q; m) B G2 ZProfessor of Pediatrics, University of South Alabama, College of
2 z0 E8 m' g/ T, M2 eMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
2 h- J2 t2 P3 h; W6 g" Se-mail: [email protected].
' [1 [' `3 f Y, sabout 6 to 7 months old, which progressively became8 a# F: C& K# K: `! s) L
darker. She was also concerned about the enlarge-' \% {3 _5 x+ d3 i
ment of his penis and frequent erections. The child
' I W# h! N1 T* V& Fwas the product of a full-term normal delivery, with, ?1 f. p* A% k9 [5 q
a birth weight of 7 lb 14 oz, and birth length of, ~7 ^9 \, E: o
20 inches. He was breast-fed throughout the first year
5 d o @, b3 z' P% Bof life and was still receiving breast milk along with
( b, x. p/ n: c- O1 ksolid food. He had no hospitalizations or surgery,
$ J9 s9 F% M: j$ aand his psychosocial and psychomotor development( ^8 Z" W1 `7 Y6 R5 @- x; W; V
was age appropriate.7 g# {4 K5 m1 G$ y
The family history was remarkable for the father,
A5 B6 G a* \& ~0 ]who was diagnosed with hypothyroidism at age 16,
0 u9 [. O; t% U" rwhich was treated with thyroxine. The father’s
. o2 ^/ K) L9 dheight was 6 feet, and he went through a somewhat; y! ]- |: b! S$ J4 g+ P( t# |3 J0 Y
early puberty and had stopped growing by age 14.
: ?1 j7 T) L) O9 U8 ?+ GThe father denied taking any other medication. The
- e/ P/ J3 e. \. n s4 ]child’s mother was in good health. Her menarche
X9 f0 g5 |; X8 w% f, e) S/ Iwas at 11 years of age, and her height was at 5 feet
3 m7 G- i3 ~$ L7 s) }2 g7 ?5 inches. There was no other family history of pre-" I* n+ @' n& e, \ f/ m
cocious sexual development in the first-degree rela-, y9 t$ L" ^5 m) p3 _8 V) y
tives. There were no siblings.( Z6 }9 A+ e# V/ T- a7 I
Physical Examination
* ~% l$ Z! m' k: S- vThe physical examination revealed a very active,
; n: }# ]9 O: fplayful, and healthy boy. The vital signs documented
0 Z+ L0 M7 j" c7 v& o- ?a blood pressure of 85/50 mm Hg, his length was
' \% q6 a. P6 z1 ^" x90 cm (>97th percentile), and his weight was 14.4 kg) o3 r+ N, d2 E! S( X% N
(also >97th percentile). The observed yearly growth! X) g6 z f+ J
velocity was 30 cm (12 inches). The examination of
3 W+ s6 t) ]: W6 E; r6 N4 C0 Vthe neck revealed no thyroid enlargement., k8 K* M) }% K, s
The genitourinary examination was remarkable for) t w/ r3 I" g8 {: G4 F9 T
enlargement of the penis, with a stretched length of
+ l; ?% C6 P0 x8 cm and a width of 2 cm. The glans penis was very well
, o7 b- Q/ N% ^0 Ddeveloped. The pubic hair was Tanner II, mostly around+ \2 P9 x0 u9 j) f. w9 r" ]
540
8 F8 {; w, D- `- k5 cat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from9 W: _' `" w9 S/ N
the base of the phallus and was dark and curled. The/ f+ q: [6 l+ w9 [$ }6 Q+ b% }
testicular volume was prepubertal at 2 mL each.
; x) }& e$ A% ^" n A2 NThe skin was moist and smooth and somewhat
8 j7 ~& h" A% foily. No axillary hair was noted. There were no
8 f; B7 O3 M* |( `! j8 O$ e5 qabnormal skin pigmentations or café-au-lait spots.; ]& D ^3 ?, z: w
Neurologic evaluation showed deep tendon reflex 2+
! \$ s& `, N3 j0 E- v v U$ Mbilateral and symmetrical. There was no suggestion. [) U6 C5 K( f# a4 K; }; m
of papilledema.
1 X$ e7 Q" E9 F- O; c. W7 kLaboratory Evaluation' m% f" Z8 u& Q, g0 q
The bone age was consistent with 28 months by* V ?8 G4 g# Z( [% y) `
using the standard of Greulich and Pyle at a chrono-
2 X& @0 m" @$ [+ f1 `4 ^1 x7 ~* plogic age of 16 months (advanced).5 Chromosomal
& S: u$ C* Q! |9 i5 ?5 J1 p. tkaryotype was 46XY. The thyroid function test% I. \ c V2 }% D+ }+ z) h8 B
showed a free T4 of 1.69 ng/dL, and thyroid stimu-* y y2 @7 D5 ?
lating hormone level was 1.3 µIU/mL (both normal).1 x" S9 s( `8 q- ~' G$ C
The concentrations of serum electrolytes, blood! i5 {! z; w0 S2 O/ M
urea nitrogen, creatinine, and calcium all were( c# H, Y; l+ `: D p" e
within normal range for his age. The concentration
* `# I; @/ I) ^ tof serum 17-hydroxyprogesterone was 16 ng/dL
$ {9 d1 H9 `8 h/ ]) j# \: N(normal, 3 to 90 ng/dL), androstenedione was 20
$ ]8 S* C% `% e; ?. _$ B* e/ Wng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-! b! `8 w! D: w, |6 j+ o
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
" i( C4 l- [& ] Rdesoxycorticosterone was 4.3 ng/dL (normal, 7 to! Q3 D/ l" W9 j+ M6 J; G; @7 {
49ng/dL), 11-desoxycortisol (specific compound S)
' P/ O. @/ Z4 ~& F: i% Dwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-, @3 W, N* }# X: D9 z# `6 B9 e
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
" u* n/ G4 P! R( N4 @! r& H/ vtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
# @7 l/ ]; ]! w! w: z1 Q3 iand β-human chorionic gonadotropin was less than
7 {, p0 d, }1 g6 e9 }# d2 F* u5 mIU/mL (normal <5 mIU/mL). Serum follicular
+ T. p8 }) e8 B/ Q6 ?stimulating hormone and leuteinizing hormone7 a) `/ G, w: c" S9 C7 ?: S7 d1 S
concentrations were less than 0.05 mIU/mL
( _6 W$ Q Y% G+ X7 ~(prepubertal).
; ^: h$ k# n3 PThe parents were notified about the laboratory7 @ d: Q4 h( c$ M; |: S) m+ ]9 t9 A
results and were informed that all of the tests were, _7 |% G: u2 A3 h+ s* I
normal except the testosterone level was high. The
2 ~% C) r. I( w% [( wfollow-up visit was arranged within a few weeks to
2 U. h. F$ L. h6 p5 {/ robtain testicular and abdominal sonograms; how-
% O# F Q" x4 Sever, the family did not return for 4 months.( ^( }$ p9 |, D! f; O5 B' r
Physical examination at this time revealed that the
: ^' l: }5 @ Z0 l: I. r, Tchild had grown 2.5 cm in 4 months and had gained4 e: X" }6 N6 F/ V6 u
2 kg of weight. Physical examination remained
6 b% O. l5 r# N9 [* yunchanged. Surprisingly, the pubic hair almost com-. f$ F' c1 A: a- ~; C4 `
pletely disappeared except for a few vellous hairs at
- ?5 W+ |/ @1 d+ J. Othe base of the phallus. Testicular volume was still 2% ?/ O" k$ R4 R( r* K
mL, and the size of the penis remained unchanged.0 H8 v3 u2 A6 w1 |5 A
The mother also said that the boy was no longer hav-
' d% N/ D) b7 y" u( z% _3 Ging frequent erections.
, I$ }, K( z/ ~- HBoth parents were again questioned about use of" J( m1 r, c% ?( ]" F
any ointment/creams that they may have applied to2 G6 b H7 T0 a' E+ U
the child’s skin. This time the father admitted the
0 k+ Q* ]7 ~1 j5 d! j* eTopical Testosterone Exposure / Bhowmick et al 541, Z& l+ Q! u! ~7 b4 X- n
use of testosterone gel twice daily that he was apply-& |' D8 n o8 q( C0 {8 i
ing over his own shoulders, chest, and back area for5 |+ @4 Y+ {4 }
a year. The father also revealed he was embarrassed1 L7 p& u, G {" i: [" T0 o# A) f
to disclose that he was using a testosterone gel pre-
( m+ J3 Q# P- A8 z' z0 Y- F/ jscribed by his family physician for decreased libido
) l: R9 f6 _( _5 l) [secondary to depression.
* v7 ~9 C8 Q& l4 W2 p2 ~% CThe child slept in the same bed with parents.
8 [5 h% m# f. Z1 _The father would hug the baby and hold him on his
( H! n* r& ~1 \; ^chest for a considerable period of time, causing sig-
' `' ^2 r4 [9 k0 d; `7 l1 k9 N1 mnificant bare skin contact between baby and father.. G! ~6 F/ l, Z+ `
The father also admitted that after the phone call,
# Q* C% w# t; X9 W7 Cwhen he learned the testosterone level in the baby
+ A! B2 F) q X. x( v8 ]was high, he then read the product information2 K8 I. O9 a; H% ]/ J( z* B
packet and concluded that it was most likely the rea-$ O9 r/ g8 e8 X6 ]3 m2 w ?3 w+ U
son for the child’s virilization. At that time, they/ ^. ^8 K B+ A; W/ g
decided to put the baby in a separate bed, and the
- M. _, F" l! ?' Z, h" \' H; ?father was not hugging him with bare skin and had5 D& L, Z+ b# w. k: `5 J8 ?
been using protective clothing. A repeat testosterone
/ T1 v' z# }; h$ T1 btest was ordered, but the family did not go to the* G+ c, Q; _: B# E, D% w h
laboratory to obtain the test.6 r# U7 ]! i5 r4 j3 K. K
Discussion
# b) S' D+ Y R, FPrecocious puberty in boys is defined as secondary+ m( A' Q4 i% ^- s4 E
sexual development before 9 years of age.1,4/ T5 s, B* W3 w$ |3 d
Precocious puberty is termed as central (true) when- D4 S7 H( u& F/ ]
it is caused by the premature activation of hypo-
8 Z3 }7 i, S4 o; {, Uthalamic pituitary gonadal axis. CPP is more com-: i( |5 B# _6 i' f: Z& k5 N
mon in girls than in boys.1,3 Most boys with CPP2 @* v/ C+ h% {
may have a central nervous system lesion that is8 t$ G* Z( Z$ C! j& A. f
responsible for the early activation of the hypothal-8 g) }; B1 F: H7 q
amic pituitary gonadal axis.1-3 Thus, greater empha-2 Z* |( N8 i e9 z1 ]& a$ o
sis has been given to neuroradiologic imaging in
* B( _/ H# D2 Mboys with precocious puberty. In addition to viril-
) n" A- O6 a/ h$ I2 `3 mization, the clinical hallmark of CPP is the symmet-* P, f+ l( Z+ G9 c7 Z7 L8 K
rical testicular growth secondary to stimulation by7 ^* F* N7 C# }: U0 p1 M
gonadotropins.1,3
: O2 y$ o$ [4 [' {Gonadotropin-independent peripheral preco-
+ @/ ~% g* a* T6 O& C( I0 Tcious puberty in boys also results from inappropriate
7 e8 K8 H) K& x! _* B2 S. {' W& `androgenic stimulation from either endogenous or
& H7 {" j3 A+ J3 V' dexogenous sources, nonpituitary gonadotropin stim-2 r0 t% h! s c7 e
ulation, and rare activating mutations.3 Virilizing) g3 X1 K. I- V5 u7 L
congenital adrenal hyperplasia producing excessive/ B) ~6 n6 \) C0 Z
adrenal androgens is a common cause of precocious P( ?) u6 C' d& y/ i/ h4 l
puberty in boys.3,4
. g" V- j5 J7 g" f- AThe most common form of congenital adrenal" `1 A; f9 ]. w0 B5 n7 v" d; X- }
hyperplasia is the 21-hydroxylase enzyme deficiency.
C- Z' B6 A$ XThe 11-β hydroxylase deficiency may also result in+ S$ B4 w: Z0 d1 H+ _7 B5 a$ D
excessive adrenal androgen production, and rarely,
* N7 P& ]/ d( r! n3 san adrenal tumor may also cause adrenal androgen6 \' c! C( K/ w2 t* X" O; B
excess.1,3
" e( y3 p) @2 r5 v; H9 @$ _. Dat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
- H# t3 t# z' m) X1 V- `542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
K. X9 B) }. I1 B" J& cA unique entity of male-limited gonadotropin-( P0 l+ S* K/ ~9 M, ~0 A2 p
independent precocious puberty, which is also known! X, W$ a* u/ m8 U. V, h- D+ p
as testotoxicosis, may cause precocious puberty at a
; j! |$ {( w1 G; p3 y! e: E4 _& Ivery young age. The physical findings in these boys
/ r6 p7 D9 `& |- d3 C& d$ Wwith this disorder are full pubertal development,
9 v/ u' r% Q0 H$ m. _1 ^& yincluding bilateral testicular growth, similar to boys
! m& q+ `6 H: N+ w+ _; o5 Kwith CPP. The gonadotropin levels in this disorder
7 X/ {# r( n4 s. ~4 i7 O/ u, S2 Vare suppressed to prepubertal levels and do not show
3 o& v X8 q/ F& epubertal response of gonadotropin after gonadotropin-" d: C3 W6 W8 a# y2 c2 D3 S& }
releasing hormone stimulation. This is a sex-linked
* v' l3 b$ }( `+ o6 F1 hautosomal dominant disorder that affects only
* |; ]* N; j9 Zmales; therefore, other male members of the family
* C' F/ P- G B! {4 nmay have similar precocious puberty.3
) s+ J K. d1 b1 ?! CIn our patient, physical examination was incon-
) S& \* p5 [* s! N" L: o/ l1 _sistent with true precocious puberty since his testi-7 E0 {7 }, s1 R1 ~% s
cles were prepubertal in size. However, testotoxicosis
% h; ^% l. r, ]3 l0 R0 m& J& jwas in the differential diagnosis because his father: h, Q2 A; g+ L$ s6 ~
started puberty somewhat early, and occasionally,: \2 b7 w" s& l8 t! ]" R
testicular enlargement is not that evident in the
' b7 R! S9 E, A( f' ^5 {+ Lbeginning of this process.1 In the absence of a neg-8 P N. p: D1 C, S; G. v$ E
ative initial history of androgen exposure, our' @1 \/ i* u) v; o
biggest concern was virilizing adrenal hyperplasia,3 @+ L) C2 F; v$ G
either 21-hydroxylase deficiency or 11-β hydroxylase# B* d# [' _ V) S
deficiency. Those diagnoses were excluded by find-4 {6 T" Q4 f' L8 d: U( j
ing the normal level of adrenal steroids." c; ?1 w3 I' ?4 m
The diagnosis of exogenous androgens was strongly; g: f3 ^5 I8 L( j6 n$ P
suspected in a follow-up visit after 4 months because
4 ]1 p$ t2 y$ p; {! ythe physical examination revealed the complete disap-
& B# ~0 r# S4 O: W4 B4 _3 K6 Bpearance of pubic hair, normal growth velocity, and
# \+ S# v2 H* y7 I+ j3 k$ j5 vdecreased erections. The father admitted using a testos-5 X* u7 x5 u* L n9 F, f/ [
terone gel, which he concealed at first visit. He was3 n, X: m/ j) `1 z) j) ^" V' {
using it rather frequently, twice a day. The Physicians’
- c5 b8 O% \0 F1 W% M& vDesk Reference, or package insert of this product, gel or
6 m% P4 m1 i E4 @) dcream, cautions about dermal testosterone transfer to* D" ^3 B( K' L7 N9 G, }
unprotected females through direct skin exposure.- ?1 s/ P9 _3 j" S* O+ K
Serum testosterone level was found to be 2 times the
2 N2 \ E0 M' _' |+ Vbaseline value in those females who were exposed to
* _7 `4 M5 O/ S$ ^# N' T7 Ceven 15 minutes of direct skin contact with their male
9 m y3 K" G9 R# Epartners.6 However, when a shirt covered the applica-
/ z) ^! E0 S* c) n' z/ Z* Ytion site, this testosterone transfer was prevented.
# J/ c2 }+ O( fOur patient’s testosterone level was 60 ng/mL,
' f* H; e2 _1 {* Fwhich was clearly high. Some studies suggest that
2 o D) Q& k: v: y: N% X+ bdermal conversion of testosterone to dihydrotestos-
: E" E0 {, V3 ~5 N: c' ]terone, which is a more potent metabolite, is more* j g) w3 ~* h# f5 p8 q
active in young children exposed to testosterone
( G3 }9 Q& z7 A8 y& @' X" K, Hexogenously7; however, we did not measure a dihy-( v% z! g& ?0 n, y6 G- S
drotestosterone level in our patient. In addition to
! V8 Y8 }7 Q! Q a2 ^virilization, exposure to exogenous testosterone in
& o4 W& }, Z5 q- nchildren results in an increase in growth velocity and
: l7 K8 \( |1 o" padvanced bone age, as seen in our patient.
; m- q2 S+ ?1 h! P9 Z, z' _The long-term effect of androgen exposure during
. D A2 @% p7 K) y! oearly childhood on pubertal development and final5 @0 O3 G/ x0 E3 f
adult height are not fully known and always remain
2 x# V' O3 p. r( K' Z# Q. }% H( Za concern. Children treated with short-term testos-
# M1 @5 l; K7 w; |' Vterone injection or topical androgen may exhibit some, `0 _2 y2 m# g! H. m; d1 k4 D
acceleration of the skeletal maturation; however, after% }5 m: l. e, S. o
cessation of treatment, the rate of bone maturation
% S& |, @- g1 G. }( |7 ndecelerates and gradually returns to normal.8,90 p% |0 g; K. U( z$ m
There are conflicting reports and controversy- v; G( P& P4 t6 Q9 z7 e: ^: `+ e: m
over the effect of early androgen exposure on adult
1 x; ]% r3 Q `* S+ g5 H. _9 kpenile length.10,11 Some reports suggest subnormal: O5 y# E9 {+ W6 }( s5 {5 e/ Y4 a
adult penile length, apparently because of downreg-: Q' B5 L6 A; c E) O9 h
ulation of androgen receptor number.10,12 However,& M7 k% f" G- l! I: M
Sutherland et al13 did not find a correlation between
+ G+ c' b& u; }, B: achildhood testosterone exposure and reduced adult: a% P8 E3 u$ x: a
penile length in clinical studies." s5 V1 Y3 w0 X
Nonetheless, we do not believe our patient is
P+ I' b2 X4 |going to experience any of the untoward effects from$ g+ [0 \/ x% k: R* _& _
testosterone exposure as mentioned earlier because/ V/ w3 G1 u# P( d. O3 I! l
the exposure was not for a prolonged period of time.
0 U3 \' a! a' F" e1 tAlthough the bone age was advanced at the time of4 s3 G/ ~: H/ i8 @7 z
diagnosis, the child had a normal growth velocity at ?4 Y* R: ?0 y& Z8 V4 Z3 |5 z
the follow-up visit. It is hoped that his final adult: ^0 R' d! ^# l! A4 N
height will not be affected.+ O8 a4 w, V. B- r" }
Although rarely reported, the widespread avail-) b0 u$ \- r+ y; r
ability of androgen products in our society may D) a0 y: }7 [; W2 @
indeed cause more virilization in male or female4 P. m' u; j' k6 ?: R6 N
children than one would realize. Exposure to andro-
( H# H! Q ?/ e5 Q$ P9 bgen products must be considered and specific ques-
+ t7 R! a, e& F: M" Q, g6 w7 n4 n M8 o( etioning about the use of a testosterone product or
6 H" ]2 g% n8 V: n4 W/ D' egel should be asked of the family members during- I2 V Y& Q) p
the evaluation of any children who present with vir-
( Q. D" I' J ^* \/ ^) ~ilization or peripheral precocious puberty. The diag-
9 H6 l6 C9 q, Z, ^; G0 D! M0 enosis can be established by just a few tests and by( T" z% z, l, i: E9 G8 F
appropriate history. The inability to obtain such a
+ M8 ]0 g( r9 [1 B6 K6 c2 u4 @$ Y6 vhistory, or failure to ask the specific questions, may; Y% d% O# {2 Y" E) G" y5 s
result in extensive, unnecessary, and expensive
* H& w& |8 J& W8 H @4 z+ Zinvestigation. The primary care physician should be
4 l2 r! Z8 T4 B7 }$ h' P" @aware of this fact, because most of these children( l3 U8 w* V5 r. U1 K& U
may initially present in their practice. The Physicians’
& \# x# S5 L6 {2 _Desk Reference and package insert should also put a% `" W" ]1 O1 i
warning about the virilizing effect on a male or
( S1 {* Q6 F4 Qfemale child who might come in contact with some-' k; K2 c. L: s9 t# w$ w4 w* Z
one using any of these products.
$ { N3 Q" V9 D7 ?; U8 X4 s% Z8 pReferences
6 @9 y6 H% k' \8 ]1. Styne DM. The testes: disorder of sexual differentiation
I4 K& i0 [) @: band puberty in the male. In: Sperling MA, ed. Pediatric
! e& W3 I( _1 G5 }7 N2 J7 @Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
0 P2 p* q. _1 b5 k8 u7 ^2002: 565-628.' Z# V2 ~% G( k1 |2 L4 w" L* O& {
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious. ]% ~8 a: G+ }
puberty in children with tumours of the suprasellar pineal& |( \ L* c9 J" P4 m. [, b p' H' a
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
, ^, @ X* D" x2 j5 |' R- [8 mTopical Testosterone Exposure / Bhowmick et al 543; y9 T$ f0 ^ P) N
areas: organic central precocious puberty. Acta Paediatr.
6 P1 g" v, N! C0 h2001;90:751-756.
5 Q# q4 T' p# @0 v3. Lee PA. Puberty and its disorders. In: Lifshitz F, ed.
* p0 n, D6 I; v% NPediatric Endocrinology. 4th ed. New York, NY: Marcel
# h7 L q. m2 F1 \( eDekker Inc; 2003:211-238.6 a1 r; C6 R4 U6 r0 S
4. Yu YM, Punyasavatsu N, Elder D, D’Ercole AJ. Sexual
6 \5 A; p% I6 z9 {) T3 Vdevelopment in a two-year-old boy induced by topical
% \3 S/ w9 r' |- m, Yexposure to testosterone. Pediatrics. 1999;104:e23.4 p8 j3 u6 {+ c; o1 M
5. Greulich WW, Pyle SI, eds. Radiographic Atlas of$ ^$ P+ k4 P7 w: |8 P0 [
Skeletal Development of the Hand and Wrist. 2nd ed.8 P H; [- C2 @
Stanford, CA: Stanford University Press; 1959.
& }$ D5 }$ F; Q2 p, V6 L% \ R0 H6. Physicians’ Desk Reference. Androgel 1% testosterone,; J$ D/ q$ [$ \! V) _' R* M4 J
Unimed Pharmaceutical Inc. Montvale, NJ: Medical
! B5 w K0 u3 v/ y7 cEconomics Company, Inc; 2004:3239-3241.' G [" D, M7 a% [
7. Klugo RC, Cerny JC. Response of micropenis to topical- x1 E% F2 c2 I
testosterone and gonadotropin. J Urol. 1978;119:
! P8 D% ~' |1 z) Z667-668.4 T2 W3 X9 q1 Y1 L- S5 s
8. Guthrie RD, Smith DW, Graham CB. Testosterone5 Q; Z5 L: _" x# A+ ?
treatment for micropenis during early childhood. J Pediatr.
* t) _3 t! @6 b' V1973;83:247-252.
; ]5 K( s) x* q& H9 C9. Jacobs SC, Kaplan GW, Gittes RF. Topical testosterone
( j, I8 d& k4 Etherapy for penile growth. Urol. 1975;6:708-710.
; L0 t: l" J% Y& ~' }. s/ I10. Husmann DA, Cain MP. Microphallus: eventual phallic6 Z4 |+ _1 N' t1 c2 G1 T
size is dependent on the timing of androgen administra-
4 ?* @4 |3 M( |8 B, T" jtion. J Urol. 1994;152:734-739.
F4 Z* @, Q) S; c1 o; O2 w11. McMahon DR, Kramer SA, Husmann DA. Micropenis:
" c( h+ ]1 l. \does early treatment with testosterone do more harm
+ A! m8 h" c# G# R8 F( E$ o! ?than good? J Urol. 1995;154:825-829." w7 U" \- L2 c# j) I$ G, ]
12. Takane KK, George FW, Wilson JD. Androgen receptor" |4 `2 Z) g" j+ \
of rat penis is down-regulated by androgen. Am J Physiol.
4 Q, u# f" H2 E7 ^. f1990;258:E46-E50.
, _8 k7 `- A" g' T13. Sutherland RS, Kogan BA, Baskin LS, et al. The effect, h( w6 f, f, u; S, Y
of prepubertal androgen exposure on adult penile
0 z! o$ H2 u3 Y) V% p# a5 ylength. J Urol. 1996;156:783-787. |
|