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is a significant concern for physicians. Central
$ s8 ]7 a$ H4 C$ _0 d7 Tprecocious puberty (CPP), which is mediated
6 U; }+ R. y. |9 D, {- _8 Vthrough the hypothalamic pituitary gonadal axis, has1 I7 R! D d6 n' n# z
a higher incidence of organic central nervous system! A7 e$ @8 K. {" m% A) J
lesions in boys.1,2 Virilization in boys, as manifested
6 _6 {% m2 D# g) h& p+ Tby enlargement of the penis, development of pubic. T+ o# S* ?0 Z: u; n7 ]
hair, and facial acne without enlargement of testi-" ^; K/ I {6 D& v0 I4 A( M
cles, suggests peripheral or pseudopuberty.1-3 We
8 \0 H' p: M* i7 s# creport a 16-month-old boy who presented with the/ @* G3 J/ u8 O
enlargement of the phallus and pubic hair develop-: |8 }. M& W% h
ment without testicular enlargement, which was due
& W0 r1 f7 W! S" g7 kto the unintentional exposure to androgen gel used by
& I/ M% Y/ J& a! V- ^9 U/ _the father. The family initially concealed this infor-3 `! r% q: L, J
mation, resulting in an extensive work-up for this4 Y9 E2 D/ `4 U8 q
child. Given the widespread and easy availability of5 ], r% Q+ B, l* N* u( k! {
testosterone gel and cream, we believe this is proba-, \, G5 a6 L5 n" L9 K4 X
bly more common than the rare case report in the- S9 J' a. ^8 y7 l F# x& D- b
literature.4& L4 B( K- k7 ?- L
Patient Report
1 ?# X+ c* O6 p% V5 \' }% ^A 16-month-old white child was referred to the0 h$ c/ A" R2 U1 R) S3 B( H4 f, E ]
endocrine clinic by his pediatrician with the concern
; r. H) a7 @9 ~, c0 R/ [* fof early sexual development. His mother noticed: E* d- z5 D) Z; T# i
light colored pubic hair development when he was
# n- M4 Q* m `8 eFrom the 1Division of Pediatric Endocrinology, 2University of
( m7 h8 G; l6 SSouth Alabama Medical Center, Mobile, Alabama.* N4 j+ r' F+ |& p% k
Address correspondence to: Samar K. Bhowmick, MD, FACE,
5 f1 ], L' P- \% L0 BProfessor of Pediatrics, University of South Alabama, College of6 v! t3 D& W/ O, Z$ V
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;3 }, y3 h6 Z* L
e-mail: [email protected].. s- a1 k7 o! _ K. z
about 6 to 7 months old, which progressively became% L5 e' C p8 h V6 C/ W
darker. She was also concerned about the enlarge-
) H3 s4 d- s1 B5 Iment of his penis and frequent erections. The child6 k2 R& V- h; |4 _
was the product of a full-term normal delivery, with
* L- j% x& E! w$ f. C4 j& z0 ~a birth weight of 7 lb 14 oz, and birth length of9 o5 f/ b4 s1 e6 K
20 inches. He was breast-fed throughout the first year. F, n" X9 V! _4 p
of life and was still receiving breast milk along with& t- ` _: b; v: y; F
solid food. He had no hospitalizations or surgery,
0 m& b& G" R+ m$ Y4 |and his psychosocial and psychomotor development
1 V( b, K& E+ Z3 q$ Rwas age appropriate.
& V/ A" B6 r9 }0 pThe family history was remarkable for the father,
6 x6 T9 i1 P3 @+ o" a3 q; R) Iwho was diagnosed with hypothyroidism at age 16,6 @. m1 L$ j; m
which was treated with thyroxine. The father’s
1 ~% M6 F: V7 jheight was 6 feet, and he went through a somewhat
; z1 [* S4 [9 m, Cearly puberty and had stopped growing by age 14.6 J# U4 U$ w: I. W1 _+ | M
The father denied taking any other medication. The
( a, C) x9 K1 E1 Ychild’s mother was in good health. Her menarche
7 z* W' A2 \0 s5 dwas at 11 years of age, and her height was at 5 feet
6 H2 {3 X! H- M- F/ K5 inches. There was no other family history of pre-
( s1 n! h) e: b, |. D" }2 V4 _cocious sexual development in the first-degree rela-
3 Q7 F" |. j. n& Atives. There were no siblings.
O. ~' b) ?2 a; {% Y0 Q( qPhysical Examination
K/ s( G. a' V8 VThe physical examination revealed a very active, u/ |4 X4 e0 z) M- I' T! |, x
playful, and healthy boy. The vital signs documented$ n1 A5 ]( v6 H, R+ l
a blood pressure of 85/50 mm Hg, his length was* e% [5 l1 h+ Q, C2 F. s& t
90 cm (>97th percentile), and his weight was 14.4 kg: G3 O* P& a$ g/ S
(also >97th percentile). The observed yearly growth$ `. G! A( @ g* u8 t h2 L
velocity was 30 cm (12 inches). The examination of
$ N! V# X' d. v7 q! fthe neck revealed no thyroid enlargement./ P1 M8 m, C; n7 e! i' ~
The genitourinary examination was remarkable for
1 A$ S$ n; M* O+ t! Eenlargement of the penis, with a stretched length of
: x/ @( D) t) j+ o9 v7 e8 cm and a width of 2 cm. The glans penis was very well
! c: Y5 N" G" V( `developed. The pubic hair was Tanner II, mostly around+ x, d$ l& v& P, d' v; B+ D: v
540. Z" s! Z9 ?. i2 ?$ Q5 z0 `1 M
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from' e, `5 d% |9 m( X
the base of the phallus and was dark and curled. The* g Q5 V% j# j: p6 [* l
testicular volume was prepubertal at 2 mL each.: @9 @+ \5 O( e" _
The skin was moist and smooth and somewhat1 S5 x3 u5 V7 v
oily. No axillary hair was noted. There were no
8 b) J1 O, Y! Cabnormal skin pigmentations or café-au-lait spots.& }! X4 x) u" P4 s' R
Neurologic evaluation showed deep tendon reflex 2+
% A! W( V/ Z1 W+ m4 qbilateral and symmetrical. There was no suggestion* Y. g, t! X$ Q7 t0 O# y5 ^
of papilledema.5 }* @/ G: w, a1 t9 b6 {1 d1 \
Laboratory Evaluation- z3 Z7 d+ ` q# ]
The bone age was consistent with 28 months by
+ t4 @, I* D4 D# k! ? Qusing the standard of Greulich and Pyle at a chrono-& ]/ R$ G' A2 A% U3 C; V) ]
logic age of 16 months (advanced).5 Chromosomal. @/ r5 z, V2 _0 Z
karyotype was 46XY. The thyroid function test
# v4 i( g; Y9 j0 U8 _9 [5 e2 ~showed a free T4 of 1.69 ng/dL, and thyroid stimu-
# a* `7 K; m6 vlating hormone level was 1.3 µIU/mL (both normal).( R8 Z! t C5 R/ h. |' K, q. C
The concentrations of serum electrolytes, blood5 q8 c/ r! }. Z* N" W6 N
urea nitrogen, creatinine, and calcium all were
- b5 C6 m0 c/ ?8 W; U7 C* ~within normal range for his age. The concentration( l2 L0 k' Y( C8 M1 b: w; _
of serum 17-hydroxyprogesterone was 16 ng/dL( R5 k; `8 g6 h8 z
(normal, 3 to 90 ng/dL), androstenedione was 20
* Q: @7 i. e( s! T8 Lng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-% k3 Y0 i( p1 l' Y2 g& N; I2 {
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
$ L0 q4 P$ o d* V; Cdesoxycorticosterone was 4.3 ng/dL (normal, 7 to2 |2 l3 @4 d# W7 D" x% j2 e8 g
49ng/dL), 11-desoxycortisol (specific compound S)
& P3 i+ b R/ j: ^" r* Q$ o4 W8 m5 F% Pwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
/ o ]9 m$ {0 O3 r, \; Dtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
) s5 T0 m& h6 j- etestosterone was 60 ng/dL (normal <3 to 10 ng/dL),' \' @( h. D% d
and β-human chorionic gonadotropin was less than# O) x" b/ a9 n: w/ b
5 mIU/mL (normal <5 mIU/mL). Serum follicular/ C+ \' W/ D; d
stimulating hormone and leuteinizing hormone
' O" z9 n; u/ S" nconcentrations were less than 0.05 mIU/mL
- e3 V& `. Z- B0 D; K(prepubertal).6 Q) d+ f& j* r' Q- _7 G
The parents were notified about the laboratory$ P1 O6 y. ~9 ^* z2 K. ^7 {7 a* n" o
results and were informed that all of the tests were
3 r, S# e5 {6 H' Pnormal except the testosterone level was high. The4 b: E0 ~0 V3 D ^$ K
follow-up visit was arranged within a few weeks to
# V. [& h! b+ i( P Jobtain testicular and abdominal sonograms; how-
4 d" K+ ^9 ^& _( X: sever, the family did not return for 4 months.* T/ V, C4 m: N# l8 r* P5 d
Physical examination at this time revealed that the. @/ v$ s4 b2 o4 q9 l# ~7 n: \! _
child had grown 2.5 cm in 4 months and had gained# e$ w0 L. l- Z
2 kg of weight. Physical examination remained2 k V( a1 b/ A, d8 s, Z$ I# i7 @
unchanged. Surprisingly, the pubic hair almost com-$ T8 e0 }( L, D* V8 o. u9 X8 q. }
pletely disappeared except for a few vellous hairs at. X( s/ ^6 R! J
the base of the phallus. Testicular volume was still 2
1 n8 T$ o$ c* T$ O, Q9 OmL, and the size of the penis remained unchanged.: j7 s. c0 N0 o4 z! {3 T% x4 l1 h
The mother also said that the boy was no longer hav-2 x3 T7 K7 _/ L* K, f9 j
ing frequent erections.
0 x7 c- P) |: eBoth parents were again questioned about use of0 j6 B& {; N" K7 N
any ointment/creams that they may have applied to
: b3 C/ H$ ~, ^2 ^/ \* }" vthe child’s skin. This time the father admitted the
% |, `7 U. B; @: OTopical Testosterone Exposure / Bhowmick et al 541
0 N2 K s; ]2 L9 a) ?0 Zuse of testosterone gel twice daily that he was apply-
* B9 V/ _8 \' ]1 H$ S9 Q; i0 I2 o' ting over his own shoulders, chest, and back area for
, O x$ z! A+ z8 xa year. The father also revealed he was embarrassed
, U: L! Z$ I' x& E; [6 ^to disclose that he was using a testosterone gel pre-
% A+ Z/ \5 B& D! [& k, I( u, Jscribed by his family physician for decreased libido
2 |) _9 g) J: F+ Msecondary to depression.( i, u; D; F2 Q* R2 T7 {
The child slept in the same bed with parents.; N4 H0 l8 N* M9 t/ c4 N
The father would hug the baby and hold him on his# p( K1 X& y9 A- x3 c$ y
chest for a considerable period of time, causing sig-
l) u! u; u+ h3 D. ?nificant bare skin contact between baby and father.5 i( W, B; n, ^2 T; N
The father also admitted that after the phone call,4 ?; S% [* o( D( m8 x- j* D9 k+ W
when he learned the testosterone level in the baby
: `0 k1 b( V+ x0 `8 ]9 Swas high, he then read the product information3 V0 ^* Q9 H {& H/ B8 ~1 R) N
packet and concluded that it was most likely the rea-
t+ k: U F$ c' u: v4 F) Vson for the child’s virilization. At that time, they$ H9 v8 {( n3 `6 s& r( ~, `+ T
decided to put the baby in a separate bed, and the* D( y1 e5 s7 E: v- r! R) \5 V; a
father was not hugging him with bare skin and had
* T3 n) |+ _$ r/ y5 B+ E, Mbeen using protective clothing. A repeat testosterone
& V& [( Z& u. f c* P: V% I9 w) mtest was ordered, but the family did not go to the
* Z1 r% y5 A1 o6 K! Vlaboratory to obtain the test.
! |* f# D* W* F0 v, eDiscussion8 {, p% v& ]0 Z2 W b+ o
Precocious puberty in boys is defined as secondary5 x% _( h3 z, |3 B+ J; L
sexual development before 9 years of age.1,49 ?# }* g1 v+ c
Precocious puberty is termed as central (true) when
9 H& b, x; l. L( Q/ @1 Uit is caused by the premature activation of hypo-5 R; n$ h( E' f8 F( G. c
thalamic pituitary gonadal axis. CPP is more com-2 p% q$ g: `, ~. |; C
mon in girls than in boys.1,3 Most boys with CPP7 H5 {# e7 l9 M0 ~
may have a central nervous system lesion that is4 \! q3 p* w7 q L5 c3 @' |
responsible for the early activation of the hypothal-
. \" {4 j* J0 aamic pituitary gonadal axis.1-3 Thus, greater empha-
% l: u4 E8 a1 Y0 @- |( R* esis has been given to neuroradiologic imaging in+ H$ f6 W2 F% f
boys with precocious puberty. In addition to viril-, \& _1 l6 P# Y: r4 c
ization, the clinical hallmark of CPP is the symmet-
& e8 u9 @8 q1 R5 qrical testicular growth secondary to stimulation by+ k8 R0 K5 H+ D( n9 S9 A
gonadotropins.1,3
, i( }5 Z, L* q% \2 }Gonadotropin-independent peripheral preco-
! o) A/ q( S. \4 k" ~. [$ pcious puberty in boys also results from inappropriate
8 S* C. B' ~+ A; W2 g" N+ d! C# s1 o$ yandrogenic stimulation from either endogenous or5 b7 y7 K0 Y# k0 ^" C
exogenous sources, nonpituitary gonadotropin stim-
1 ~+ K" m. x" Kulation, and rare activating mutations.3 Virilizing' x" a& ~- h p6 v! n- c4 H H. R
congenital adrenal hyperplasia producing excessive& m- [$ A# P+ j( M' ?
adrenal androgens is a common cause of precocious$ L, W& P- {" r8 @
puberty in boys.3,4- n4 t# y- z, c: K6 ]
The most common form of congenital adrenal
9 S' S: S: e) r, @) M, D2 N9 hhyperplasia is the 21-hydroxylase enzyme deficiency.
5 j5 S6 V" ?9 o" ~The 11-β hydroxylase deficiency may also result in
0 T" W- V$ D/ y& z3 v' Wexcessive adrenal androgen production, and rarely,
$ o2 P, h* j3 h+ e7 C0 J/ p7 I4 z. Van adrenal tumor may also cause adrenal androgen
7 N3 m# q& r3 S$ S; j# g3 eexcess.1,3
% U5 s" G; {8 U* Z6 j$ B: v1 ~2 v. qat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from) T+ } M3 F/ u& |
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007& w- i$ T3 ~$ a
A unique entity of male-limited gonadotropin-
( w& c- @4 D6 L9 S o6 mindependent precocious puberty, which is also known
7 T* @* \9 I$ I/ H, f- Xas testotoxicosis, may cause precocious puberty at a
8 S9 j8 H1 ^4 g2 X$ Bvery young age. The physical findings in these boys
6 p" w' D: f2 P: J0 ?with this disorder are full pubertal development,
3 h" G4 Y% j5 Q! X+ |6 Qincluding bilateral testicular growth, similar to boys
$ @$ h0 d ^5 z$ M- D owith CPP. The gonadotropin levels in this disorder- P) I+ Q0 \- ^
are suppressed to prepubertal levels and do not show' d4 W3 S( _) t3 K
pubertal response of gonadotropin after gonadotropin-/ |5 O: M) Q- I7 G# C$ K5 F
releasing hormone stimulation. This is a sex-linked
, x" A4 g8 {7 Uautosomal dominant disorder that affects only+ ^7 f; P$ i/ P) m- F8 y; e
males; therefore, other male members of the family
4 h7 P/ C: v& o6 d. ~0 m, h/ qmay have similar precocious puberty.3- w5 N& F8 e- i; Z. j! d
In our patient, physical examination was incon-
) r2 j) s4 c, P6 Q, |sistent with true precocious puberty since his testi-
/ K9 h( w! Y+ f4 Q& Pcles were prepubertal in size. However, testotoxicosis0 y7 \( K2 \8 a( Q
was in the differential diagnosis because his father
6 B1 ?* K4 C2 k7 W. Ustarted puberty somewhat early, and occasionally,
1 `+ K2 r7 V' N2 ?5 {testicular enlargement is not that evident in the
& l6 o* j8 x2 g# n& q2 wbeginning of this process.1 In the absence of a neg-
8 K1 R( p# M& S0 W7 T; Vative initial history of androgen exposure, our+ q/ l7 j" u" Z- d/ h+ _( v) G
biggest concern was virilizing adrenal hyperplasia,* s0 n' k6 T" y+ E2 S
either 21-hydroxylase deficiency or 11-β hydroxylase) t7 g; O( P; x
deficiency. Those diagnoses were excluded by find-
2 e( g' h2 |0 n S- n$ `ing the normal level of adrenal steroids., o S2 O: F% C* M
The diagnosis of exogenous androgens was strongly! J4 C$ P- I8 {: w/ H, }
suspected in a follow-up visit after 4 months because
, o) _' i1 \# T0 N3 w3 f; e8 h! jthe physical examination revealed the complete disap-
% u' g* Y: |! H0 mpearance of pubic hair, normal growth velocity, and
3 E9 t% X9 F3 j5 ^- n' kdecreased erections. The father admitted using a testos-
8 R* q2 v4 `1 F1 c+ s% ~terone gel, which he concealed at first visit. He was% x( C/ M3 e1 J' B Z
using it rather frequently, twice a day. The Physicians’# k# ]9 C* c( K' T5 L
Desk Reference, or package insert of this product, gel or
0 V. l7 p" \3 h7 B6 \' xcream, cautions about dermal testosterone transfer to" R: p- j1 {+ F
unprotected females through direct skin exposure.
; Z7 d `6 O! z1 N" aSerum testosterone level was found to be 2 times the
/ h. |3 i# I' v8 D) C9 Fbaseline value in those females who were exposed to
+ @; j0 S$ _: U4 {even 15 minutes of direct skin contact with their male/ d" \8 O1 U4 g+ H% Y
partners.6 However, when a shirt covered the applica-
/ P/ \3 y0 b9 l" T" `) ktion site, this testosterone transfer was prevented.! Y5 a) o6 P' A8 s' @) w, [7 p
Our patient’s testosterone level was 60 ng/mL,9 r8 Z% x$ \' t4 s8 X
which was clearly high. Some studies suggest that0 o; G# v. G L7 i* u( @ X
dermal conversion of testosterone to dihydrotestos-
/ q2 W. u$ B5 u' e2 C" D1 H1 |: Wterone, which is a more potent metabolite, is more" t' }9 D+ x3 Z5 [# M& O
active in young children exposed to testosterone
2 L+ d( V% _7 V, b5 ?* U; ~exogenously7; however, we did not measure a dihy-
' Y7 z+ J& m% e1 C4 Ddrotestosterone level in our patient. In addition to! Z9 _% z E+ N A
virilization, exposure to exogenous testosterone in
% y* @; e! R' d$ Uchildren results in an increase in growth velocity and
# s( j1 H" ]/ F) N9 o0 eadvanced bone age, as seen in our patient.$ [! {3 D3 N( c* V9 L
The long-term effect of androgen exposure during
- `# k7 ?! Z% F1 Cearly childhood on pubertal development and final
" D" G3 Y( E& k }# X* A0 Dadult height are not fully known and always remain
* D7 n! V: l$ U, ?# H2 c+ C7 `a concern. Children treated with short-term testos- H; E* x2 ? Q2 R' R% l$ f' i
terone injection or topical androgen may exhibit some
* o3 P3 z& B3 P# p9 macceleration of the skeletal maturation; however, after% A Q L. z) t( r) K
cessation of treatment, the rate of bone maturation
8 o- I* u6 X# H; Z( Ydecelerates and gradually returns to normal.8,9
$ Q3 g; f7 H% c2 J' v/ e. OThere are conflicting reports and controversy
: U" [0 B P! Q' r+ a5 ^: ~over the effect of early androgen exposure on adult& M) ?* H: T/ h% p# T0 a! d) k5 @
penile length.10,11 Some reports suggest subnormal: v4 s% V# I; P4 Q
adult penile length, apparently because of downreg-
# }- s! r/ U, [9 U. I& @# Oulation of androgen receptor number.10,12 However,
. N2 F" [. D) B+ L8 \+ Q: S* _% tSutherland et al13 did not find a correlation between8 S q% F& b. t6 F) J/ }0 U
childhood testosterone exposure and reduced adult2 R( x9 N* h: n* ?1 X& P
penile length in clinical studies.
1 s2 K) T. V$ q2 [: _) G9 tNonetheless, we do not believe our patient is
: G. c; `: a* V0 d! ggoing to experience any of the untoward effects from
' ]8 c$ t& w8 \" K( c# S; \testosterone exposure as mentioned earlier because
) s/ H: e( P1 kthe exposure was not for a prolonged period of time.& S# t1 i8 F: o, s% C
Although the bone age was advanced at the time of
$ J5 q) ^5 l, Z. \& m* Kdiagnosis, the child had a normal growth velocity at
# g4 v: {/ x0 c- c& p4 gthe follow-up visit. It is hoped that his final adult
+ q" F# L& M9 G, h6 wheight will not be affected.0 U6 r$ g4 v9 N8 D; ^* R
Although rarely reported, the widespread avail-) x- [/ l5 w9 x& }
ability of androgen products in our society may, I* R, {" p: w1 K$ G3 O
indeed cause more virilization in male or female* ^! ]" O* x P5 ?6 |/ v9 c. i
children than one would realize. Exposure to andro-* a5 m+ K2 f# J! Y
gen products must be considered and specific ques-
3 A0 a) g, r# v M1 h; Jtioning about the use of a testosterone product or, M+ T, y) Y# u% ]! h% `& X8 n& G" ?
gel should be asked of the family members during
6 ]' G- E% s; @$ _4 R8 p3 {the evaluation of any children who present with vir-
, K4 g3 M/ S# @; P; ^' o$ silization or peripheral precocious puberty. The diag-( j% }, _2 Z& ~; c+ I- M. \
nosis can be established by just a few tests and by
* E& j0 w# l3 f5 k- {7 ^/ uappropriate history. The inability to obtain such a
3 e w& }& N' a9 v3 K5 uhistory, or failure to ask the specific questions, may$ N: s7 N4 e" U$ P! E
result in extensive, unnecessary, and expensive
. U/ ]# W+ ~4 ninvestigation. The primary care physician should be6 i, o# O/ \# t8 u/ F# d1 g" z
aware of this fact, because most of these children0 K" T3 m. J3 s7 A
may initially present in their practice. The Physicians’" F' B0 K3 O$ v: P6 n! ~
Desk Reference and package insert should also put a
- k g3 v& r j; _warning about the virilizing effect on a male or5 O. h: X/ I: }3 ^- e
female child who might come in contact with some-' b0 w/ s: Z. _% v, T [4 D
one using any of these products.% o/ E4 ]0 Q9 n1 W+ v
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: H5 S$ s0 c8 mEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;, D( g8 I( j0 L& x' t; p- J
2002: 565-628.
! f' p- D* O# p/ Q6 }2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
2 S' a% B) X2 \5 [, y7 r1 S/ Ipuberty in children with tumours of the suprasellar pineal
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, m8 a; \. G. E+ oareas: organic central precocious puberty. Acta Paediatr.0 R1 m9 K# f0 a, N0 j
2001;90:751-756. H4 N$ E% P' j1 a* U8 u4 [4 e
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Pediatric Endocrinology. 4th ed. New York, NY: Marcel
Y% J$ U5 }5 L* ^! s& l( S2 }$ VDekker Inc; 2003:211-238.
& `4 N+ X- j1 G) Q1 r) y4. Yu YM, Punyasavatsu N, Elder D, D’Ercole AJ. Sexual; O5 v! M; u2 Q
development in a two-year-old boy induced by topical
+ a# Z0 O& p2 S& B- [0 `. O8 E+ H4 Eexposure to testosterone. Pediatrics. 1999;104:e23.) z- F5 C/ S. o& n
5. Greulich WW, Pyle SI, eds. Radiographic Atlas of
( B8 J Y7 `+ ?! n9 GSkeletal Development of the Hand and Wrist. 2nd ed.) R+ P0 n4 H! f* K
Stanford, CA: Stanford University Press; 1959.9 l& G3 F0 P% a" o! X5 J% Y' _. v
6. Physicians’ Desk Reference. Androgel 1% testosterone,& \9 q9 b5 k' Q
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Economics Company, Inc; 2004:3239-3241.
% [1 x: r. E! _' M2 X! f& Q7. Klugo RC, Cerny JC. Response of micropenis to topical3 @* w5 y. h& N4 ~2 M
testosterone and gonadotropin. J Urol. 1978;119:, [3 l, v0 X; `" E
667-668.. |2 }: @0 i" B" H
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