- 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! g1 q' S( U6 w2 ?( S4 W
precocious puberty (CPP), which is mediated0 x$ `5 f$ X( L, J0 }( M- U* c* ?
through the hypothalamic pituitary gonadal axis, has$ q ]* r9 J J
a higher incidence of organic central nervous system
5 [; b% I! Q$ L2 D9 H1 X$ Qlesions in boys.1,2 Virilization in boys, as manifested# D; T' [$ j* g. F1 w r
by enlargement of the penis, development of pubic# t) H' i6 b" _8 u" O( J
hair, and facial acne without enlargement of testi-
# j! x6 q W" D b, W. b7 Vcles, suggests peripheral or pseudopuberty.1-3 We
& H3 p# f; d& a3 xreport a 16-month-old boy who presented with the
5 \0 [; _( \( o& y9 H" yenlargement of the phallus and pubic hair develop-& [, r) O2 W; P# \1 S, ]- d
ment without testicular enlargement, which was due* h% f2 S" ]5 d5 ^) ?" K4 K
to the unintentional exposure to androgen gel used by0 }4 Z6 i6 i- a* s
the father. The family initially concealed this infor-) P( L6 x6 i. M5 K7 Z8 h
mation, resulting in an extensive work-up for this0 k+ |* X7 K9 L/ @4 X+ ]: c
child. Given the widespread and easy availability of
8 c& y* P, d; {1 Itestosterone gel and cream, we believe this is proba-3 n' s* d- o/ T2 M5 f. |' W
bly more common than the rare case report in the
) x }" D% m3 z; ?3 {$ g! [5 {literature.4* o6 {9 [/ I9 S& |: ]2 J& K- D$ i1 Z
Patient Report
9 T1 ]) A8 h4 i- m6 |- n) D& PA 16-month-old white child was referred to the
- l' F7 C. v; rendocrine clinic by his pediatrician with the concern
: E% H) R0 A7 D+ ]+ s0 l- tof early sexual development. His mother noticed! g6 J" c) u8 g4 v$ r# ^
light colored pubic hair development when he was0 g+ i0 O- ^$ g* K, r
From the 1Division of Pediatric Endocrinology, 2University of
& Y# C7 }6 W* {South Alabama Medical Center, Mobile, Alabama.
1 d7 R& _! N+ W+ w* U' MAddress correspondence to: Samar K. Bhowmick, MD, FACE,
! k/ s& ~0 F, IProfessor of Pediatrics, University of South Alabama, College of3 K- L8 W: F; h
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
1 ]0 M: ~7 g9 {( ye-mail: [email protected].8 V7 H/ r. T: u/ _) ~* D" x+ Y& i
about 6 to 7 months old, which progressively became
" L! {; Y: v+ @ {: s$ H8 Sdarker. She was also concerned about the enlarge-
" `$ W+ A6 P+ R! Fment of his penis and frequent erections. The child
' M0 J& a7 ^0 U/ o* Q* Cwas the product of a full-term normal delivery, with4 w. {( v, m9 ]. c
a birth weight of 7 lb 14 oz, and birth length of2 B& y2 H1 ^ i d5 D2 ?! o& _, Z$ H
20 inches. He was breast-fed throughout the first year: m6 ?% v! [/ f1 B7 i! U" ^3 x
of life and was still receiving breast milk along with# t9 N# i! V/ i& F }
solid food. He had no hospitalizations or surgery,- Q& m" h4 J% _& h
and his psychosocial and psychomotor development- b5 b9 y4 ^% C5 _9 r' ?. V' r
was age appropriate.* r! a. h( R- ^" g% H
The family history was remarkable for the father,5 Y9 f; H, Z' M1 ^
who was diagnosed with hypothyroidism at age 16,- t: K! s! ] G
which was treated with thyroxine. The father’s9 ~" U; N% [; Y% P r* f$ m$ p
height was 6 feet, and he went through a somewhat
! X; \- {0 k, v/ g y2 Kearly puberty and had stopped growing by age 14.2 f3 t& g, @& o; v, {, f. K0 _3 r
The father denied taking any other medication. The
3 s! [% }! M3 S% M+ p4 y( Xchild’s mother was in good health. Her menarche
" {1 b: K5 G& |2 M) E4 G+ }. G# `9 ~was at 11 years of age, and her height was at 5 feet# m8 u. M# R3 m. q) X. e
5 inches. There was no other family history of pre-; [, F$ F& s# E2 @5 [8 l
cocious sexual development in the first-degree rela-
; D, e; p& u! G" { wtives. There were no siblings.
; k# S. o4 Q' X7 \, [# G% q, vPhysical Examination
. L8 a1 j$ Z; y3 J& X% D# q3 {The physical examination revealed a very active,
% t, s5 l/ z5 Q. g* a, Uplayful, and healthy boy. The vital signs documented
5 h) u& [, J0 S( z4 `a blood pressure of 85/50 mm Hg, his length was2 [' o1 W1 }9 e; C
90 cm (>97th percentile), and his weight was 14.4 kg6 n3 {/ B1 {8 J3 k
(also >97th percentile). The observed yearly growth& ?! r; b' o5 l0 z% S; m
velocity was 30 cm (12 inches). The examination of5 j6 B8 k* \/ U c S# i: G
the neck revealed no thyroid enlargement.
5 }) k4 q' M/ y% F( GThe genitourinary examination was remarkable for C1 z; I& g2 o$ [) T* H# k" O
enlargement of the penis, with a stretched length of
; P7 H5 v7 ~* }% D& r5 }2 r+ n8 cm and a width of 2 cm. The glans penis was very well
+ U5 u. i7 W4 T5 j; Ddeveloped. The pubic hair was Tanner II, mostly around
+ T) w0 f6 V+ ~9 y540
6 ~- \9 A. u" i: Jat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from g: k/ x* d% h0 m- c. ]: h; x a
the base of the phallus and was dark and curled. The' Q( Y, Q9 h* |9 K# _! j
testicular volume was prepubertal at 2 mL each.+ l8 l1 s4 ]6 I3 R
The skin was moist and smooth and somewhat
$ K% i; O G* l4 q4 S2 Roily. No axillary hair was noted. There were no
! z8 ?! N4 E) H; |5 wabnormal skin pigmentations or café-au-lait spots.) W6 J# ^ {$ O; j2 Z2 M5 P7 k
Neurologic evaluation showed deep tendon reflex 2+
3 d: h4 J" `8 b6 Z3 r/ X" c4 x6 dbilateral and symmetrical. There was no suggestion4 ^& p! Q4 i+ x; C
of papilledema.
: N4 ?1 c1 `% W& h# ]Laboratory Evaluation
2 F& p v+ M: F( _ X5 Z9 p, mThe bone age was consistent with 28 months by0 p9 {* _) e) C W
using the standard of Greulich and Pyle at a chrono-
- v% A2 m+ `% N. g3 ~4 flogic age of 16 months (advanced).5 Chromosomal' |# @% |& C% ` c4 r% D
karyotype was 46XY. The thyroid function test- Q0 n/ a5 z. g; o) l9 Y" u
showed a free T4 of 1.69 ng/dL, and thyroid stimu-& }; f2 t; ]0 a. M3 t1 Y' B9 Z
lating hormone level was 1.3 µIU/mL (both normal).+ V) C. q. |* W9 }5 u
The concentrations of serum electrolytes, blood S2 }7 w N% X4 M
urea nitrogen, creatinine, and calcium all were: x: m! ?0 e/ \3 N+ v/ n
within normal range for his age. The concentration
* [) A: Z c1 G4 x; ^of serum 17-hydroxyprogesterone was 16 ng/dL, Y3 y# Q$ H) u M
(normal, 3 to 90 ng/dL), androstenedione was 20; w, @5 }: w# U& q7 q, i+ }6 d
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-9 ?9 ^: |; W' [4 [
terone was 38 ng/dL (normal, 50 to 760 ng/dL),7 o8 Z5 F. p2 G4 Z, }+ u, u
desoxycorticosterone was 4.3 ng/dL (normal, 7 to* a }, z; F5 z/ P
49ng/dL), 11-desoxycortisol (specific compound S)
' ?! k5 `& H" \1 H5 E6 dwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-. x* z5 S: g. j5 O6 n
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
$ Y8 ?0 D* W- R- G0 | G* M/ ftestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
/ v p8 y- y1 D0 b# C: y9 Vand β-human chorionic gonadotropin was less than: f* F7 ]7 L/ N4 @0 z
5 mIU/mL (normal <5 mIU/mL). Serum follicular
) B( t% V. M: {6 Rstimulating hormone and leuteinizing hormone
$ w" y( d/ C$ @9 `8 xconcentrations were less than 0.05 mIU/mL2 x) a$ U7 l1 l# K3 Y! B P
(prepubertal).! U3 m# {/ b- t6 B: Z6 B
The parents were notified about the laboratory* A/ w* l: t: G
results and were informed that all of the tests were
9 O8 V+ ]! h) B, f8 X9 O: l# f" Xnormal except the testosterone level was high. The: V1 |" f# [) |
follow-up visit was arranged within a few weeks to
$ m$ ~7 U) L: C. i0 }- p3 Oobtain testicular and abdominal sonograms; how-
6 E$ J6 _8 @8 z z0 l- L4 z3 [ever, the family did not return for 4 months.( Y8 w: O6 l3 ~- ]2 t0 A
Physical examination at this time revealed that the. n2 G" B5 q) @9 X5 A/ |3 Z9 _
child had grown 2.5 cm in 4 months and had gained
- x0 e4 P7 A7 n ]. I2 kg of weight. Physical examination remained: ^' i2 i& f5 [4 a; E# e
unchanged. Surprisingly, the pubic hair almost com-+ g" b1 g3 U# X7 ~/ c1 {
pletely disappeared except for a few vellous hairs at: E3 R/ B# T. ]4 w+ c2 k+ z$ g
the base of the phallus. Testicular volume was still 2
6 @' x* x( D7 umL, and the size of the penis remained unchanged.
9 a( h3 d$ A; O6 v' c B) H! _( r: YThe mother also said that the boy was no longer hav-& w; J9 j$ E8 U
ing frequent erections.
+ B+ k1 g; o, C$ s3 q! yBoth parents were again questioned about use of
7 t; Q3 [; L! m6 j- n( t# X5 U' C: hany ointment/creams that they may have applied to
! r# o5 K( k9 N: l0 ~6 ythe child’s skin. This time the father admitted the+ D' y0 u& p% A! z- Q7 B6 B
Topical Testosterone Exposure / Bhowmick et al 541
! [7 g. \5 t V# C! e4 d& O* E% }use of testosterone gel twice daily that he was apply-. C# A5 l8 r4 e, V8 S
ing over his own shoulders, chest, and back area for
/ C9 u4 k& `* |, ]' A" T! R" Ta year. The father also revealed he was embarrassed
# V0 q" ^/ f* z; Yto disclose that he was using a testosterone gel pre-
1 f% N. |5 i F; C4 M' Uscribed by his family physician for decreased libido3 _2 b# L6 e A2 Z$ P# E% M- _, m
secondary to depression.. {: K2 x# I3 z5 _' S
The child slept in the same bed with parents.
% b% c1 L" Y$ [* A3 r3 HThe father would hug the baby and hold him on his
b9 |) B" r1 Q( k& }+ S. Qchest for a considerable period of time, causing sig-1 Y/ W- f. o# V, H( D/ _
nificant bare skin contact between baby and father.* c" T, J6 J* B6 u$ m
The father also admitted that after the phone call,
# A/ d" ~* j; k: e1 zwhen he learned the testosterone level in the baby
% B& o/ Q8 D# w0 k0 iwas high, he then read the product information; ]2 k5 K# |# m$ X; K r7 D- k
packet and concluded that it was most likely the rea-% u+ k$ J6 g- L9 D3 `* c( o
son for the child’s virilization. At that time, they: G9 ~! I# a; v/ {% w, v1 y
decided to put the baby in a separate bed, and the
. j* I4 V# \7 a# Sfather was not hugging him with bare skin and had
3 s# g7 P, p& X6 F c8 N& L/ u6 Pbeen using protective clothing. A repeat testosterone
8 o, I9 x% v, J: k, y$ w0 U. Wtest was ordered, but the family did not go to the
: _# R7 c4 k: R8 b8 W1 y8 `( blaboratory to obtain the test.
4 ?! C% i+ D/ x8 X5 x' p/ ADiscussion
+ K$ V5 p+ Y9 m9 K3 A/ p& WPrecocious puberty in boys is defined as secondary
* O. t: g& z. ~# p8 vsexual development before 9 years of age.1,48 \! m; n6 W5 M& v1 n- ]! E
Precocious puberty is termed as central (true) when
X" b( e0 M& C# ~it is caused by the premature activation of hypo-" K) |. T8 b, b) ^8 M+ B
thalamic pituitary gonadal axis. CPP is more com-3 K" S0 U( c% P( Q7 s8 ?. J! n7 n
mon in girls than in boys.1,3 Most boys with CPP+ G* w. ]& y& o2 h. O7 ~1 s# }/ b
may have a central nervous system lesion that is F1 `* f* @8 B5 H3 T5 x6 ?7 `
responsible for the early activation of the hypothal-, W) _; F2 W' y
amic pituitary gonadal axis.1-3 Thus, greater empha-
' O: b8 d$ P5 Z1 p2 m" Ksis has been given to neuroradiologic imaging in
, q! f- R) x- v: N- }3 t" mboys with precocious puberty. In addition to viril-9 w, E3 H( J2 o; s2 N. Y7 O' P$ K O
ization, the clinical hallmark of CPP is the symmet-+ P" p; D5 s0 j
rical testicular growth secondary to stimulation by' x! y- {$ ?$ R. L( w1 O L% J
gonadotropins.1,3% ~( U2 C, ]3 H+ c
Gonadotropin-independent peripheral preco-
0 r- t$ b1 J# R, E% ocious puberty in boys also results from inappropriate4 @! e' D$ T0 f9 }6 e
androgenic stimulation from either endogenous or
2 Z7 T4 h9 O' J" [exogenous sources, nonpituitary gonadotropin stim-
0 f4 a7 w2 C" h6 x3 Culation, and rare activating mutations.3 Virilizing; g0 J( j. Y2 s" \
congenital adrenal hyperplasia producing excessive, U( c' V8 O8 {/ M, Q6 Y. @
adrenal androgens is a common cause of precocious
6 w" U6 ?. E; tpuberty in boys.3,49 k/ J8 V! n8 x/ |8 G/ j1 l' `
The most common form of congenital adrenal
1 _% U# v. M N3 Mhyperplasia is the 21-hydroxylase enzyme deficiency.' l+ S6 P$ u. w
The 11-β hydroxylase deficiency may also result in+ S5 L1 C6 x2 F) {
excessive adrenal androgen production, and rarely,8 X/ n( n# ?, h$ d" p9 p8 l2 V
an adrenal tumor may also cause adrenal androgen2 D3 w- M( v7 u8 G( i) M9 Y% ?
excess.1,32 R9 J) s- X; b( p8 b# T% e/ ]
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from- n- U( V# I, L) Y
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
" p7 Y ~( a9 eA unique entity of male-limited gonadotropin-
/ @# [6 X; A/ s' J- C, T4 Gindependent precocious puberty, which is also known1 d& d" y4 }; b* Q `: |
as testotoxicosis, may cause precocious puberty at a+ q3 U2 [! u7 J2 `. l9 U; ]- J
very young age. The physical findings in these boys
: Z7 q; x/ p" N( B5 ^( i7 ywith this disorder are full pubertal development,
# B' K5 u) s' `3 B9 t' kincluding bilateral testicular growth, similar to boys
- ~4 n# F1 `/ o7 N6 r' H9 n0 {/ Swith CPP. The gonadotropin levels in this disorder. W0 v3 G% X; P% z
are suppressed to prepubertal levels and do not show+ C) ^0 W7 r3 B: c$ Z
pubertal response of gonadotropin after gonadotropin-- L% e( V+ d$ Z( H; I# D8 Q9 y
releasing hormone stimulation. This is a sex-linked0 L+ V& Y7 ?" r6 M) |
autosomal dominant disorder that affects only2 P7 p( A7 ], l! o# G
males; therefore, other male members of the family0 _) g" g: N+ ^. X% p
may have similar precocious puberty.3+ S2 K3 }- \7 s; T# t
In our patient, physical examination was incon-* Z. B2 B2 Q5 Q5 `6 G) k) ]
sistent with true precocious puberty since his testi-5 q6 X4 o* H5 n a; l6 p
cles were prepubertal in size. However, testotoxicosis
% P2 Q& l$ n' M( R! @was in the differential diagnosis because his father
8 e3 d# g5 D1 A _! G. S4 istarted puberty somewhat early, and occasionally,' t8 a& K0 b, W: B e. s7 U
testicular enlargement is not that evident in the# C+ V- x5 \# o
beginning of this process.1 In the absence of a neg-
: ~3 H# g+ x) h% J: kative initial history of androgen exposure, our# _9 I8 c+ ^/ j2 Y# r0 c
biggest concern was virilizing adrenal hyperplasia,
6 i; s+ T: J( @+ Peither 21-hydroxylase deficiency or 11-β hydroxylase$ i" u5 k o9 j: @. f3 o
deficiency. Those diagnoses were excluded by find-
9 z3 y- y8 O) x) ping the normal level of adrenal steroids.0 a( D/ @ J, l$ e( N2 _
The diagnosis of exogenous androgens was strongly
$ u$ J6 [* m. ^, x5 Y+ t% I. Zsuspected in a follow-up visit after 4 months because
+ c [+ J1 v% j9 Athe physical examination revealed the complete disap-+ M4 V8 P2 @) O! n2 {- b
pearance of pubic hair, normal growth velocity, and
/ j1 g+ C b( F6 G. L/ Udecreased erections. The father admitted using a testos-0 K8 \9 Z6 p6 l7 l9 D8 G4 L; n& @
terone gel, which he concealed at first visit. He was
$ C6 h* I! T# u# ?& Xusing it rather frequently, twice a day. The Physicians’
. H6 r9 Q2 ]9 n# J4 ODesk Reference, or package insert of this product, gel or0 `. j. n: W2 J4 _
cream, cautions about dermal testosterone transfer to
! H9 [5 C8 ]2 D( f7 Gunprotected females through direct skin exposure.0 n$ p" E6 x7 f! H* X- f
Serum testosterone level was found to be 2 times the
! ^! S0 B/ n( T+ c: Obaseline value in those females who were exposed to
; K# r; h! j1 geven 15 minutes of direct skin contact with their male! G& p/ t" ]0 |& U9 E8 p
partners.6 However, when a shirt covered the applica-
0 [6 U/ O. [/ r8 |. |. ation site, this testosterone transfer was prevented.
! J: ?( g* u6 O3 J: O. J8 ^8 FOur patient’s testosterone level was 60 ng/mL,
2 ?" l$ N2 a! r, Q7 E0 S! l9 i1 awhich was clearly high. Some studies suggest that
( w" h( A$ k+ x) N. J, zdermal conversion of testosterone to dihydrotestos-8 T- v6 I4 I: P& Q3 u
terone, which is a more potent metabolite, is more
0 I. m6 j# }; x! U ?active in young children exposed to testosterone
* M6 @$ O9 P8 J3 k& Jexogenously7; however, we did not measure a dihy-
) J. z: d# M4 W [- f, ~( Kdrotestosterone level in our patient. In addition to1 v& d0 p6 h1 d0 g
virilization, exposure to exogenous testosterone in
/ ?! h6 O) o% {* k% P, {children results in an increase in growth velocity and
4 [ Y: v0 h, x7 H: [$ ^advanced bone age, as seen in our patient.
& G/ d) e" C( f0 N4 KThe long-term effect of androgen exposure during
( s: l- O9 @: y4 F, U/ Aearly childhood on pubertal development and final. Y# Q$ _% n- H: B9 D# ` a
adult height are not fully known and always remain# j- k9 D' t7 a* {. w' I% {
a concern. Children treated with short-term testos-4 B7 v- p! k* M0 l$ G
terone injection or topical androgen may exhibit some# j& O' ^4 A5 g' r
acceleration of the skeletal maturation; however, after7 ?$ S0 z( M' z5 ]
cessation of treatment, the rate of bone maturation
. c7 L8 q0 d2 M' edecelerates and gradually returns to normal.8,92 ^. S& {/ t. _$ n' W
There are conflicting reports and controversy! E+ e3 `( ?. j8 m3 O8 ~6 P4 H
over the effect of early androgen exposure on adult
% w! `, W a: e3 a; S3 o% l9 Kpenile length.10,11 Some reports suggest subnormal" J P+ d% c& u; h* y
adult penile length, apparently because of downreg-7 r6 t4 I: Z/ y/ t1 h" w6 t
ulation of androgen receptor number.10,12 However,4 i- {# d+ [5 Q
Sutherland et al13 did not find a correlation between
, q! X: u- H$ q, vchildhood testosterone exposure and reduced adult
; t2 g: |: l; K% Zpenile length in clinical studies.
, |$ z& w+ k! Q3 F J7 XNonetheless, we do not believe our patient is
: J+ I( R& ?# r( q$ H: Z' i+ d; Qgoing to experience any of the untoward effects from' Q l$ u; X7 i( f0 g" d, i# F
testosterone exposure as mentioned earlier because |/ _4 X" X/ I- n6 U- Z
the exposure was not for a prolonged period of time.
- C! F- D0 n% X1 M( v* tAlthough the bone age was advanced at the time of1 w9 Z$ H% V2 j. {
diagnosis, the child had a normal growth velocity at" t% ~6 ?% J3 k9 V
the follow-up visit. It is hoped that his final adult
1 b4 _$ S* r$ j0 K( Qheight will not be affected.; D; t& t1 }, O/ }9 o
Although rarely reported, the widespread avail-
8 i$ \3 V0 b4 N# g; Z% y3 sability of androgen products in our society may
U7 }8 U8 G" t* a0 n) ?8 S2 \indeed cause more virilization in male or female* ]2 t; ^1 e' H6 P9 W4 G
children than one would realize. Exposure to andro-; m$ ?0 L. ~3 k# {/ R9 F
gen products must be considered and specific ques-/ k0 y5 [) `' ]# T2 ~4 r- K
tioning about the use of a testosterone product or
+ Y$ H/ j6 K+ j! D K4 T4 s5 |, s# q- {gel should be asked of the family members during
6 t; `5 K0 k' j6 Dthe evaluation of any children who present with vir-
' F. h8 d& |2 Q9 N$ y* o- y+ Wilization or peripheral precocious puberty. The diag-
3 s. | U+ z3 x/ d& h' t s$ _% Onosis can be established by just a few tests and by
) O3 m' ?8 x" T5 g: ~1 ^6 bappropriate history. The inability to obtain such a
% K% o0 q* y: T, j2 Ohistory, or failure to ask the specific questions, may
5 F4 Q7 c& a8 v% Bresult in extensive, unnecessary, and expensive
0 x W; |/ Q( b5 finvestigation. The primary care physician should be
$ a$ z0 b# r! haware of this fact, because most of these children2 m6 `7 E4 h% D7 k2 Y
may initially present in their practice. The Physicians’8 F9 t- h2 F; e% S& c, I
Desk Reference and package insert should also put a
3 R V. J5 C5 q1 \& `. dwarning about the virilizing effect on a male or
8 ^0 u7 k% U7 T0 X! H7 ?female child who might come in contact with some-( I3 Z: |2 p9 _9 \; R; N4 W
one using any of these products.6 Q {, i' L4 P9 \; o' p4 T0 e
References
# A! z0 Q& e- N2 h# E2 Q1. Styne DM. The testes: disorder of sexual differentiation
# d" T8 Z- U7 {" E6 @and puberty in the male. In: Sperling MA, ed. Pediatric) e0 | e/ F* I- H9 r9 E
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
: j; ~ W' T' X6 ?5 Y5 U2002: 565-628.6 {" A: g7 n, b8 [: G
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious0 l# E. n; E) w$ H% h$ v. f7 f+ U
puberty in children with tumours of the suprasellar pineal. y# V; [6 m% m4 G6 T" n
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from) s3 ^- E& A, V1 G2 I. u
Topical Testosterone Exposure / Bhowmick et al 543' s' W( a. \$ `, c& i" L/ U" ]9 _
areas: organic central precocious puberty. Acta Paediatr. S' G9 ^5 [2 k: q8 t% K
2001;90:751-756.
) b, ^. W' e( {( c2 t3. Lee PA. Puberty and its disorders. In: Lifshitz F, ed.
) e( g4 h: V9 } i$ P5 CPediatric Endocrinology. 4th ed. New York, NY: Marcel4 W% V. r8 n I: w! I4 g+ h
Dekker Inc; 2003:211-238.% A* G6 r* T* D
4. Yu YM, Punyasavatsu N, Elder D, D’Ercole AJ. Sexual8 C5 I1 G# d9 H
development in a two-year-old boy induced by topical
/ n# f# N: g$ v- C$ W+ Hexposure to testosterone. Pediatrics. 1999;104:e23.( f. z: C1 x8 x& g4 t5 @
5. Greulich WW, Pyle SI, eds. Radiographic Atlas of: R9 d2 v2 J& S0 _% W* v! d8 |# @
Skeletal Development of the Hand and Wrist. 2nd ed.: U7 O9 U% @7 z1 u) Y6 K/ k+ C
Stanford, CA: Stanford University Press; 1959.- L9 i( Q2 [% I g, F* [' A
6. Physicians’ Desk Reference. Androgel 1% testosterone,. Y9 _' K1 c7 U( z l& r
Unimed Pharmaceutical Inc. Montvale, NJ: Medical
/ r) |/ i& A, d. c" XEconomics Company, Inc; 2004:3239-3241.
- c/ u1 I; N6 \4 A0 O; _7. Klugo RC, Cerny JC. Response of micropenis to topical1 Z& t0 T( x4 y0 L4 I9 p
testosterone and gonadotropin. J Urol. 1978;119:
* X: b) J0 T1 V( V2 H667-668.) d/ |2 U4 v/ Y5 Y( i2 u, D
8. Guthrie RD, Smith DW, Graham CB. Testosterone
% D7 @+ \" a7 m: c4 vtreatment for micropenis during early childhood. J Pediatr.
1 Q; ?0 \, q7 y1973;83:247-252.
1 |# `5 q& b9 S- V9. Jacobs SC, Kaplan GW, Gittes RF. Topical testosterone
0 S1 i/ F0 ~) p E6 Ytherapy for penile growth. Urol. 1975;6:708-710.
r2 U* @8 R0 z' x2 I5 G10. Husmann DA, Cain MP. Microphallus: eventual phallic
7 |1 R S) e, p% A4 N. Rsize is dependent on the timing of androgen administra-% o% |8 u, y6 V6 u& z
tion. J Urol. 1994;152:734-739.6 n* y; t8 @0 ?. F: T6 k0 K
11. McMahon DR, Kramer SA, Husmann DA. Micropenis:
/ I" v/ b) C" R/ M( V; ydoes early treatment with testosterone do more harm
( d* y; p- F+ W) x% {$ O; kthan good? J Urol. 1995;154:825-829.# x5 a# V. y( p+ z1 d
12. Takane KK, George FW, Wilson JD. Androgen receptor4 N9 B" e2 c- _3 E! h) i$ C- N
of rat penis is down-regulated by androgen. Am J Physiol." |, V( I/ x1 c. _
1990;258:E46-E50.$ i5 h# ?, u$ K( y
13. Sutherland RS, Kogan BA, Baskin LS, et al. The effect
3 S2 I8 H1 ]& B; F+ ^' K, p$ w; Oof prepubertal androgen exposure on adult penile9 N) j7 Y) s) o* i0 R- J- M
length. J Urol. 1996;156:783-787. |
|