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is a significant concern for physicians. Central
# K/ _0 G4 {7 h( M) Pprecocious puberty (CPP), which is mediated% @ q6 X) x8 J3 e# f3 n" z
through the hypothalamic pituitary gonadal axis, has$ Q- B/ ~, x' H0 e: d
a higher incidence of organic central nervous system
8 f! |- ~3 S7 O% Olesions in boys.1,2 Virilization in boys, as manifested
" `9 r2 k% q& U% `8 y& [( G; Y$ [by enlargement of the penis, development of pubic5 x0 S8 p. P% e& Z. g. q
hair, and facial acne without enlargement of testi-
/ r6 K( \0 w: u' \3 D" ]cles, suggests peripheral or pseudopuberty.1-3 We: }6 |% b: A, j. U/ H# Q
report a 16-month-old boy who presented with the# n7 ^* g+ X; D" z% S
enlargement of the phallus and pubic hair develop-
/ ?6 X: l! ]/ Q* dment without testicular enlargement, which was due" e/ c M9 T4 z" w) b3 \9 f2 m4 w |
to the unintentional exposure to androgen gel used by# a9 r! {& y$ n2 l. U: y! D
the father. The family initially concealed this infor-6 Y) i0 Y7 b: u5 a% r6 O
mation, resulting in an extensive work-up for this
' z8 M6 z+ J8 f0 O& tchild. Given the widespread and easy availability of, ~0 |( l% d5 N5 H* G* g
testosterone gel and cream, we believe this is proba-# v2 G9 O+ y4 {4 n
bly more common than the rare case report in the$ R/ g& E; v, ]6 \' \% e4 q+ n
literature.4
7 ^% j8 q1 m2 J6 @) IPatient Report
6 X( i! k z* b9 h$ sA 16-month-old white child was referred to the7 W2 v! C6 a" t3 q! Y& S' ]
endocrine clinic by his pediatrician with the concern
3 v: k; l7 ~' Iof early sexual development. His mother noticed" O: ^% @5 P& Z0 ]
light colored pubic hair development when he was$ u4 U, @9 k" p) l+ n1 A
From the 1Division of Pediatric Endocrinology, 2University of1 U$ h7 m) [/ K- m
South Alabama Medical Center, Mobile, Alabama.$ t3 u$ X; r4 I) e- Y* x+ D
Address correspondence to: Samar K. Bhowmick, MD, FACE,. Y- a' E c4 W. I" h/ ?
Professor of Pediatrics, University of South Alabama, College of
. P6 F* i1 h! @3 vMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;1 J1 I1 |$ y7 @
e-mail: [email protected].
" T1 i! [$ r y( Iabout 6 to 7 months old, which progressively became4 T9 r/ F6 ^; n- r# p; f9 }* E4 l
darker. She was also concerned about the enlarge-* @: U" ~" Y% t2 |1 S* x% y. l
ment of his penis and frequent erections. The child
7 O( l! B! C. N; `( k1 _was the product of a full-term normal delivery, with
6 P" w- P/ P7 {5 E3 \4 Ra birth weight of 7 lb 14 oz, and birth length of! ]% x8 j3 [* B! k% X! x
20 inches. He was breast-fed throughout the first year# L2 {2 S/ @9 p L6 R
of life and was still receiving breast milk along with
- P3 X2 I' v- r& S2 S0 Isolid food. He had no hospitalizations or surgery,
9 r7 F9 g* B$ ]7 v) Nand his psychosocial and psychomotor development
- e* Y4 U9 E6 ^ rwas age appropriate.
) w1 Q' g+ X3 i* V' aThe family history was remarkable for the father,; Y' ^4 D9 I- n
who was diagnosed with hypothyroidism at age 16,
4 v2 M1 F B3 W+ J' u; ywhich was treated with thyroxine. The father’s" U, J- J' S1 ]) t5 R4 K) r
height was 6 feet, and he went through a somewhat2 j! m% I& B" L W; k+ o. n
early puberty and had stopped growing by age 14.( k1 K8 c6 G* e/ |0 A
The father denied taking any other medication. The
, ]8 s" i- X+ o$ x; E% ochild’s mother was in good health. Her menarche, U! N- D% i* _7 @$ v
was at 11 years of age, and her height was at 5 feet4 j1 ] o2 w# T# {, C
5 inches. There was no other family history of pre-
% e. s$ `' J8 J6 ^% a Acocious sexual development in the first-degree rela-2 l! ^6 ^* ]. c% g
tives. There were no siblings.0 d, [8 m4 o/ G
Physical Examination# x8 y) }% a" I2 H5 [
The physical examination revealed a very active,! }% ]* {6 z& x
playful, and healthy boy. The vital signs documented' C, p; ]. V; T- |- A" F8 K
a blood pressure of 85/50 mm Hg, his length was' Y, B/ v/ C; {' e
90 cm (>97th percentile), and his weight was 14.4 kg' E$ d% {2 e- X- Y: d) }# }
(also >97th percentile). The observed yearly growth
* H# A \- W) h0 ~& Avelocity was 30 cm (12 inches). The examination of
( R0 z. Z6 q/ xthe neck revealed no thyroid enlargement.
# q4 j0 b( {! \' P1 NThe genitourinary examination was remarkable for
& q4 ^8 b' R0 Z! y# R# ?. u$ renlargement of the penis, with a stretched length of
1 c6 s- ?7 D; A# E% @2 U H8 i* t8 cm and a width of 2 cm. The glans penis was very well
6 H* T% I0 J, k2 H! e* Ddeveloped. The pubic hair was Tanner II, mostly around' i+ N8 U1 c7 u6 G$ s$ o7 R
540+ Q0 u, l3 Q0 W: h1 P
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
9 j0 D, N) i* O) v( W' qthe base of the phallus and was dark and curled. The! K6 ^! r( h, c' V3 J4 @ r' C
testicular volume was prepubertal at 2 mL each.
# c( E, d5 [' U% X4 P; xThe skin was moist and smooth and somewhat8 Z2 k/ f. h/ u+ M2 @ Y
oily. No axillary hair was noted. There were no; |' M% Y2 ]- l
abnormal skin pigmentations or café-au-lait spots.
, l# _6 v& k% f5 z$ B* NNeurologic evaluation showed deep tendon reflex 2+% j$ f2 z' L$ S, D" ?" ]9 A; B
bilateral and symmetrical. There was no suggestion$ L/ {# n' F+ L7 ]5 a, v
of papilledema.
4 y3 r$ U& L/ {- u9 }Laboratory Evaluation
K7 @/ N* f2 W$ |! i3 M/ VThe bone age was consistent with 28 months by2 v& ?* k# d- U; V% c& R
using the standard of Greulich and Pyle at a chrono-
$ N9 v" ]" J6 Ylogic age of 16 months (advanced).5 Chromosomal
2 ~ U5 H* F: Y8 u! k" Mkaryotype was 46XY. The thyroid function test2 v% f ^: q9 {" B9 r$ v
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
$ P! ]( j% C- A9 y# M" y* _4 Nlating hormone level was 1.3 µIU/mL (both normal).' O$ _& w2 v! }8 }7 W
The concentrations of serum electrolytes, blood
5 o* m5 U- |+ r) h% Durea nitrogen, creatinine, and calcium all were
+ u+ P8 u/ Q8 K4 t8 S% V* u# ~0 ]8 ?within normal range for his age. The concentration6 _2 w3 g; a: I. b) z. U1 U( X
of serum 17-hydroxyprogesterone was 16 ng/dL* p, D& F3 I) {% c- e0 u: y( p1 ^
(normal, 3 to 90 ng/dL), androstenedione was 201 a+ M9 \7 b7 h7 `* q3 W9 x2 g6 |
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-$ m# X1 G! f# F4 v0 U7 _; p+ y0 g
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
% z" n8 p& D& n' s1 L! y/ B+ l) Ldesoxycorticosterone was 4.3 ng/dL (normal, 7 to
9 T4 `' q( X1 Q) `49ng/dL), 11-desoxycortisol (specific compound S)9 ?0 N0 Z; T0 T% A0 I3 r& E! H V
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
- k9 n+ l- J( [2 Ctisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total4 A0 o& }% m! o; j: v5 Z
testosterone was 60 ng/dL (normal <3 to 10 ng/dL), C3 T$ k0 j4 M' {# ?
and β-human chorionic gonadotropin was less than( c/ Z- a% I: i) s
5 mIU/mL (normal <5 mIU/mL). Serum follicular
% x+ e/ k& K- i. X* istimulating hormone and leuteinizing hormone( S' z( w! g; K6 ~
concentrations were less than 0.05 mIU/mL
& K3 M9 w5 {" Q$ l7 j3 T) q(prepubertal).
( D6 [, R/ \! |! }9 I- mThe parents were notified about the laboratory6 C2 }1 u- w! ~6 Y
results and were informed that all of the tests were
% Q& O( _* ^3 U9 Y9 jnormal except the testosterone level was high. The: y) s$ X0 O) h% {% Z% W. R
follow-up visit was arranged within a few weeks to) y D- b* V/ [: v% ?+ |2 A9 q
obtain testicular and abdominal sonograms; how-: B2 I4 V& o' o
ever, the family did not return for 4 months.2 b* ~9 Z' W+ H+ f% ~ Q
Physical examination at this time revealed that the
- L) n+ z* h2 z3 y1 O3 P; Q9 {. a w- Wchild had grown 2.5 cm in 4 months and had gained0 }& |- j) S! n; X
2 kg of weight. Physical examination remained. i; f2 e K7 A- s: H) U9 D
unchanged. Surprisingly, the pubic hair almost com-3 f/ H3 K' w/ ^ K: n9 n- O( G# C
pletely disappeared except for a few vellous hairs at
3 e( _' N) Y# P# {& wthe base of the phallus. Testicular volume was still 2
* \0 W* O- d, I7 b2 B* i6 K4 J1 d* vmL, and the size of the penis remained unchanged.
0 E3 h+ p0 b$ ~4 b; \8 JThe mother also said that the boy was no longer hav-
4 K& `" c* P( _: o7 f2 p; Ving frequent erections.
9 }% h5 S8 N2 V8 y( D- _' H5 B0 FBoth parents were again questioned about use of
) Z! {0 A n/ D% rany ointment/creams that they may have applied to
N% ?5 t* W" P2 H0 J& }the child’s skin. This time the father admitted the, Z5 {( U; b/ R5 I
Topical Testosterone Exposure / Bhowmick et al 541
4 ^* ], ~' K. h9 G: H5 d4 c1 Ouse of testosterone gel twice daily that he was apply-
6 G- _2 ?8 F0 B) ning over his own shoulders, chest, and back area for
& O; s3 x, ~- Y F' na year. The father also revealed he was embarrassed
; i8 G) Y4 {( L( r' G5 b! ~to disclose that he was using a testosterone gel pre-- n! Q' N# N3 K" D, D
scribed by his family physician for decreased libido
4 j0 g' w, X0 Y% ]9 dsecondary to depression., i8 H% c9 n6 r1 N% v* Y* e
The child slept in the same bed with parents.
4 V9 A3 w" J: k) |/ b0 LThe father would hug the baby and hold him on his
9 p' u/ U" k, K6 \. D3 }chest for a considerable period of time, causing sig-
, I, d9 |7 I+ `nificant bare skin contact between baby and father. b) c f s5 H- G8 Y
The father also admitted that after the phone call,% M9 R7 H4 `8 h
when he learned the testosterone level in the baby! i3 ?4 F- k, _5 Y3 i
was high, he then read the product information+ k6 K. n9 }$ D9 M. t9 W
packet and concluded that it was most likely the rea-
/ C, g4 \. F' T1 Ison for the child’s virilization. At that time, they
7 B% N; q4 C; {1 f9 qdecided to put the baby in a separate bed, and the
, `1 l# a# N4 f( yfather was not hugging him with bare skin and had
6 ^5 Z- E' V. H- O+ @. L1 F* r8 ]been using protective clothing. A repeat testosterone
4 v8 n! Y; o5 W' B, k* }8 ctest was ordered, but the family did not go to the
7 U$ ^8 N- W* M H! Qlaboratory to obtain the test.
8 Z! g+ r5 i$ L2 @ T+ JDiscussion
o# S& Y* F2 M8 H- vPrecocious puberty in boys is defined as secondary: O7 d. {1 U Y9 t0 z6 B. n Q
sexual development before 9 years of age.1,4
1 o4 e& ~2 \( T2 {6 sPrecocious puberty is termed as central (true) when2 q. k/ i- W& Q' s
it is caused by the premature activation of hypo-
^/ W6 z% M6 J) D! p6 ^thalamic pituitary gonadal axis. CPP is more com-. M! c% ?% v+ y$ u0 a
mon in girls than in boys.1,3 Most boys with CPP
. i; O$ S& {( e4 Y- C. f4 Tmay have a central nervous system lesion that is
8 C. n J# I6 h" h; G7 Cresponsible for the early activation of the hypothal-. H! q3 P8 t0 O7 F* n
amic pituitary gonadal axis.1-3 Thus, greater empha-
4 R U( M6 ]# T& m! Lsis has been given to neuroradiologic imaging in# a; n0 a, M# h8 q) |; O
boys with precocious puberty. In addition to viril-$ W' V9 K8 n' ?( L9 {1 _
ization, the clinical hallmark of CPP is the symmet-
, `$ t3 ~) U' S5 n: mrical testicular growth secondary to stimulation by
7 }0 [! y/ @- w* w/ n/ s1 R8 v5 Lgonadotropins.1,3
9 W4 E4 W5 w0 V6 H, s& }Gonadotropin-independent peripheral preco-
9 ]9 d% B' X$ ^! W& g0 a! D& kcious puberty in boys also results from inappropriate8 \0 c9 y2 R* I: j
androgenic stimulation from either endogenous or2 N( y6 S$ M5 U2 j$ c
exogenous sources, nonpituitary gonadotropin stim-" j7 [2 \) M0 ^9 c- Q
ulation, and rare activating mutations.3 Virilizing
$ x" F3 ]* p! ^$ K1 n" l9 Mcongenital adrenal hyperplasia producing excessive
" b2 Y, B% t; [4 radrenal androgens is a common cause of precocious: T+ B( N1 V2 m. t0 r0 H
puberty in boys.3,49 s! l, j/ @* @8 X: _
The most common form of congenital adrenal
6 y5 E7 c$ R: H9 X7 y% Chyperplasia is the 21-hydroxylase enzyme deficiency.0 m, |4 J* n5 ^) N2 {
The 11-β hydroxylase deficiency may also result in
( B- i8 Q: C1 M9 r3 \excessive adrenal androgen production, and rarely,3 h5 ~6 N& o, `: Y/ ]4 F3 A
an adrenal tumor may also cause adrenal androgen2 J' j$ ~( E) T& {, n) R
excess.1,3
! q. y' u1 B$ n- l9 i% n0 B$ G. D* w3 ^7 J: Oat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
$ l5 s4 q$ F; U4 P( k542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
( G- {8 N, I W# L5 r. [$ wA unique entity of male-limited gonadotropin-
b/ q4 q" B& F8 t( h& w: nindependent precocious puberty, which is also known9 E. S7 ]& ]6 K4 ^$ [
as testotoxicosis, may cause precocious puberty at a" b1 `. o, p( ~+ q, ^
very young age. The physical findings in these boys
1 R. r/ |/ s$ ~0 R* D( rwith this disorder are full pubertal development,4 {3 `9 A/ ~$ E+ @% j* Z
including bilateral testicular growth, similar to boys
" j. v" u# y1 L$ p0 fwith CPP. The gonadotropin levels in this disorder& w" p. i# ]* J; d& v1 _
are suppressed to prepubertal levels and do not show
. M o- M/ d/ ^. a: Fpubertal response of gonadotropin after gonadotropin-, k; l5 N/ x& i. O! \
releasing hormone stimulation. This is a sex-linked' b- c8 H3 {) s) q" X
autosomal dominant disorder that affects only
$ M: X( v. d$ {& M2 h& Dmales; therefore, other male members of the family
9 R/ H2 a8 ^" P6 Ymay have similar precocious puberty.37 w2 a0 t/ a0 x9 s; }
In our patient, physical examination was incon-
9 S; R4 n" |9 Ksistent with true precocious puberty since his testi-: r6 m: }9 N( h3 ^
cles were prepubertal in size. However, testotoxicosis/ y! N4 _7 H' w, a% B- v
was in the differential diagnosis because his father
+ H+ k" ^& | @7 X2 B& i! _started puberty somewhat early, and occasionally,' ?; w7 h J" F; C, w
testicular enlargement is not that evident in the
5 H/ [: R! L7 Z' B& ^0 Tbeginning of this process.1 In the absence of a neg-2 I5 v$ w3 q& H6 @! y$ E* C( S
ative initial history of androgen exposure, our) w! b: w$ q# d- |5 I: T% H
biggest concern was virilizing adrenal hyperplasia,
* O8 F1 k0 u9 V' N5 }either 21-hydroxylase deficiency or 11-β hydroxylase
/ t* F3 k& P' I: t2 Fdeficiency. Those diagnoses were excluded by find-
, ^7 a( r2 H+ |2 {5 v$ J3 v! Ling the normal level of adrenal steroids.
- q9 A. d. R! D4 v; B; S, G: XThe diagnosis of exogenous androgens was strongly' i; A" Z {( L$ c# \
suspected in a follow-up visit after 4 months because0 N, I# l" }) U; b: M; M5 q
the physical examination revealed the complete disap-# @0 H1 O. _3 F* a
pearance of pubic hair, normal growth velocity, and8 e4 O4 w9 a, w$ A3 e" p
decreased erections. The father admitted using a testos-
' B* i: O" h6 ~terone gel, which he concealed at first visit. He was7 m2 g; E" V2 V3 s) R7 G: T
using it rather frequently, twice a day. The Physicians’! Y, P0 ?2 @$ }8 q( F# J* H* ]
Desk Reference, or package insert of this product, gel or1 ?0 j) D* s! {! P% N7 f
cream, cautions about dermal testosterone transfer to
D1 y3 \, i Ounprotected females through direct skin exposure.
+ g# W+ R" V: P) ^" NSerum testosterone level was found to be 2 times the3 s2 e) Q2 V: Z: y, ~ |$ @
baseline value in those females who were exposed to7 w# {! R6 y4 y0 f: r4 N" `
even 15 minutes of direct skin contact with their male1 ^! v' D$ l7 J) m2 ~
partners.6 However, when a shirt covered the applica-5 c- \# t5 G0 T& X
tion site, this testosterone transfer was prevented. y/ O; s! Q" Y- J, Y4 }; @! Z
Our patient’s testosterone level was 60 ng/mL,
8 ^& ^/ X& v! F s+ ~8 F$ k. @which was clearly high. Some studies suggest that
2 d" W, ^& E+ `8 E2 P0 r5 L! wdermal conversion of testosterone to dihydrotestos-6 M: W0 D, R9 H: F! k
terone, which is a more potent metabolite, is more
( u* o; A# i' I/ Dactive in young children exposed to testosterone7 d& q: c& `4 w8 i% z8 R" T
exogenously7; however, we did not measure a dihy-
) O+ b5 Q$ ?. i0 _5 O, l0 L: Ddrotestosterone level in our patient. In addition to& {: ]; z. `. A- o$ u; ?- J
virilization, exposure to exogenous testosterone in
% \* g, d! i* {( I& bchildren results in an increase in growth velocity and
4 o' }5 t1 @/ E' B. r& v! Nadvanced bone age, as seen in our patient.
c/ t m4 p6 r3 MThe long-term effect of androgen exposure during
! }3 w8 e4 q, h% Zearly childhood on pubertal development and final+ E( r$ A8 ~* v3 [2 e& l1 ~
adult height are not fully known and always remain
* b3 `6 A/ a+ I! m* y1 Za concern. Children treated with short-term testos-
' G$ W, U8 K& K6 Jterone injection or topical androgen may exhibit some( Y+ W' {6 p6 f z, w; H- k
acceleration of the skeletal maturation; however, after
+ e: D! v: t& K- ^& ?cessation of treatment, the rate of bone maturation" \6 h) x0 {2 w8 ~1 a( i9 N
decelerates and gradually returns to normal.8,9
( d% e5 `' g6 \4 [There are conflicting reports and controversy
5 I' W5 g# l: ]1 C* E6 yover the effect of early androgen exposure on adult
$ E' d3 ?9 l+ A: ]) spenile length.10,11 Some reports suggest subnormal" [/ F; i0 x+ j
adult penile length, apparently because of downreg-; i" z1 U \$ L r, p# Y9 `
ulation of androgen receptor number.10,12 However,* ]' ^6 C( W3 k5 |+ Z# g
Sutherland et al13 did not find a correlation between5 O5 P- g& m3 F1 _
childhood testosterone exposure and reduced adult
8 z5 {& o% x9 I) f! ?/ P: [. |penile length in clinical studies.8 K, G1 _2 d: @4 n+ V/ K! N) M I6 f
Nonetheless, we do not believe our patient is( u) f' e, F9 S; D
going to experience any of the untoward effects from
2 l- }6 n4 ~2 y- \ vtestosterone exposure as mentioned earlier because y" l9 w9 O1 ^ `# h) t9 H" a/ N9 C, i
the exposure was not for a prolonged period of time. y, C4 {3 y( p
Although the bone age was advanced at the time of. h) `" b' c% F- r: }
diagnosis, the child had a normal growth velocity at- `" G0 p% k1 }- ?; ?* X/ T* R% b
the follow-up visit. It is hoped that his final adult3 V2 l+ g( d4 p9 b' H+ ^9 \
height will not be affected.
, f' W+ X% Y- g: pAlthough rarely reported, the widespread avail-
5 l' K0 E# l9 w9 Yability of androgen products in our society may7 n5 l0 m! k4 a2 f* A; O1 e" N: m- Q1 F
indeed cause more virilization in male or female! V& Q3 N0 H9 ?/ {# ?
children than one would realize. Exposure to andro-
`6 L# `, ]5 C- n6 a- z4 ogen products must be considered and specific ques-& j7 K3 y' ]* L7 q. R2 d
tioning about the use of a testosterone product or a6 b5 c. M7 X/ V0 r
gel should be asked of the family members during/ G; Q& y/ o( { ]8 D. P# ^% B
the evaluation of any children who present with vir-
$ T V1 G; S* f* a6 W; }& g! X" Cilization or peripheral precocious puberty. The diag-
* s/ i" o, \# [* W1 g' N6 Wnosis can be established by just a few tests and by
% ~9 g4 _5 o# E. b7 E2 r2 @0 Sappropriate history. The inability to obtain such a* y X% w: j3 f) s |
history, or failure to ask the specific questions, may) T$ o) @7 C% W" ~( z; S7 D
result in extensive, unnecessary, and expensive
1 N. \/ |( M- Z1 Z; ?4 Zinvestigation. The primary care physician should be. J2 ?) M( o9 ]5 V* _. k
aware of this fact, because most of these children
- _$ b5 m; X5 Z, ]; E( A4 jmay initially present in their practice. The Physicians’1 l% |6 f6 J8 S7 {
Desk Reference and package insert should also put a# A8 I* u' N1 l1 g% m0 R
warning about the virilizing effect on a male or( \0 v+ m |! p! A+ b; H! f8 n
female child who might come in contact with some-% ~! D8 f2 U# c3 L4 ^9 p
one using any of these products.# _" M. w$ O, `; q3 \: \
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# i1 o1 y3 F3 ], x1. Styne DM. The testes: disorder of sexual differentiation! a" O' R0 ~& R) \
and puberty in the male. In: Sperling MA, ed. Pediatric" i% ~. A* E- ]4 y3 u
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;$ }$ K- l8 M6 g( ^
2002: 565-628.5 w' P) Y! o Q6 s. R
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
0 o* e$ H* {1 B+ i& Qpuberty in children with tumours of the suprasellar pineal
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development in a two-year-old boy induced by topical. L/ G3 n# ?8 H7 s' i
exposure to testosterone. Pediatrics. 1999;104:e23.
3 l; v' W: q7 w* r; V5. Greulich WW, Pyle SI, eds. Radiographic Atlas of8 _- @/ g0 C; G5 ?/ Z v" }
Skeletal Development of the Hand and Wrist. 2nd ed.
* K4 g' W2 `# {! HStanford, CA: Stanford University Press; 1959.
8 A6 l( J' m% B9 e: s9 H' \6. Physicians’ Desk Reference. Androgel 1% testosterone,8 x; z6 W5 ^2 v+ o* c: m2 b0 I
Unimed Pharmaceutical Inc. Montvale, NJ: Medical; c, n" N5 z. X& m
Economics Company, Inc; 2004:3239-3241.5 b- _. E% I% f( Q
7. Klugo RC, Cerny JC. Response of micropenis to topical' z0 P8 p! Q( w6 \
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