- 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
2 y0 R- P; i/ E% I rprecocious puberty (CPP), which is mediated7 E% V0 ]# c( y o( V
through the hypothalamic pituitary gonadal axis, has
: ?# I: J1 ?, T: h* N) D9 \a higher incidence of organic central nervous system2 c% H& H3 U1 ~$ O
lesions in boys.1,2 Virilization in boys, as manifested# B- ]9 q2 ~4 x l
by enlargement of the penis, development of pubic
7 M: V' B; l- U% H% Jhair, and facial acne without enlargement of testi-
9 c% F: u5 {7 q3 ^' Ocles, suggests peripheral or pseudopuberty.1-3 We! H. v" _! N8 J) R& L
report a 16-month-old boy who presented with the
$ Q6 d0 N' m' b. `4 E/ Fenlargement of the phallus and pubic hair develop-
& G( q4 o& i' \; o# Xment without testicular enlargement, which was due
. K! {% d$ Y& `; r) B- U& N1 Fto the unintentional exposure to androgen gel used by* L% f t+ ^# E' T7 m g2 j
the father. The family initially concealed this infor-
( [" {3 t- C F3 g" e/ M' Dmation, resulting in an extensive work-up for this
% j' R l1 d$ A; W. N8 t+ ochild. Given the widespread and easy availability of
& v) ~' E( g- D7 k0 Etestosterone gel and cream, we believe this is proba-2 u+ [* i# y3 P# g: r
bly more common than the rare case report in the# f# w2 ?1 N7 c
literature.43 B0 m4 g$ I$ }9 K( b
Patient Report
. R3 @! J; r' }, Z2 PA 16-month-old white child was referred to the
) b4 I9 G4 _8 S n4 yendocrine clinic by his pediatrician with the concern4 p3 L" ]) N2 R9 a1 C
of early sexual development. His mother noticed
" y; M! }. p- ylight colored pubic hair development when he was; C2 w: a3 u3 P. b2 G1 z1 A9 S
From the 1Division of Pediatric Endocrinology, 2University of/ z# i y8 X$ w9 [
South Alabama Medical Center, Mobile, Alabama.5 H7 V1 w9 s/ F1 G0 F7 K, I
Address correspondence to: Samar K. Bhowmick, MD, FACE,
* y1 |* I7 p6 ?5 |Professor of Pediatrics, University of South Alabama, College of
% {; y: ?% i% U2 @( aMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
, J5 `4 ^: s% g C4 ?e-mail: [email protected].
1 d) `! M% C2 l6 t( b T6 |; babout 6 to 7 months old, which progressively became
: F! O I! A) n2 H9 [% tdarker. She was also concerned about the enlarge-
& _* X1 {8 q( E2 o0 X! C& ]ment of his penis and frequent erections. The child5 T( h8 M' |- j5 }% e2 R# t" C L* S
was the product of a full-term normal delivery, with
' J' S. ]1 H- ra birth weight of 7 lb 14 oz, and birth length of. w( z; E9 O0 ~3 ?( S% M" g* ?" o
20 inches. He was breast-fed throughout the first year/ J5 `0 [8 R- ?! X; e0 n) V6 Z
of life and was still receiving breast milk along with
6 p* X: w- `( f) s3 q- esolid food. He had no hospitalizations or surgery,
4 {* _+ V- R1 Y/ Hand his psychosocial and psychomotor development
6 S7 u) s- D3 ?1 z8 ~3 |2 b# kwas age appropriate.% k `2 k2 P5 Z
The family history was remarkable for the father,
f# c3 I6 G/ ~5 w; h7 H* ~who was diagnosed with hypothyroidism at age 16,; _. ]# B2 s" S+ T' m1 v5 D6 b0 K
which was treated with thyroxine. The father’s
2 o9 x! `) J, `6 Q6 k4 cheight was 6 feet, and he went through a somewhat
7 M9 |7 @2 }. m7 P7 K4 f+ H3 P$ ]early puberty and had stopped growing by age 14.3 `; b5 m5 _" o4 E5 C% o
The father denied taking any other medication. The
+ R9 ?1 O9 u6 C0 e( U7 k# j. J- Rchild’s mother was in good health. Her menarche
3 B( @: A' g# x/ Lwas at 11 years of age, and her height was at 5 feet
7 Z& _ H4 ~+ s( Z" U; I' k3 n5 inches. There was no other family history of pre-
4 {2 E9 ]' Z9 M ncocious sexual development in the first-degree rela-
, k3 f5 g" a; ?5 l7 b2 c, Gtives. There were no siblings.
7 q, ^/ }8 \. L& cPhysical Examination2 D% H. Y8 d$ V, O4 ?% Q P
The physical examination revealed a very active,, q, Z ]( _% d: K
playful, and healthy boy. The vital signs documented- @. Y! P4 S+ D
a blood pressure of 85/50 mm Hg, his length was5 x# S- U" m" @4 a2 I
90 cm (>97th percentile), and his weight was 14.4 kg
4 j* C: ?. M2 M5 W; J7 t$ l(also >97th percentile). The observed yearly growth& s0 u' L* w& v: m! Y6 k- C; c- j
velocity was 30 cm (12 inches). The examination of
4 _* N' W! r* A, zthe neck revealed no thyroid enlargement.
. \: E. X5 X+ U) ^4 G( RThe genitourinary examination was remarkable for
& R2 t8 o# F/ @" senlargement of the penis, with a stretched length of
H: W# N2 _4 L! e3 [- r8 cm and a width of 2 cm. The glans penis was very well
7 F/ {) i4 m$ r. y4 m, S8 y! ]developed. The pubic hair was Tanner II, mostly around
# ^4 x; U7 R: t) N$ |540# A: \* J2 c4 m9 \3 e
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
2 L1 s7 W; r7 ~! Y' U6 E. {the base of the phallus and was dark and curled. The- C" y" M5 ]0 V k+ P
testicular volume was prepubertal at 2 mL each.
: M$ c t2 g: p3 s" e7 ^. x' ?The skin was moist and smooth and somewhat9 f. c* k/ \) h6 f+ _, `, G. Y- z6 H
oily. No axillary hair was noted. There were no' u: j; D ~& a" I
abnormal skin pigmentations or café-au-lait spots." g( a1 K( x- O0 @
Neurologic evaluation showed deep tendon reflex 2+' D' v" [" c8 N
bilateral and symmetrical. There was no suggestion
9 s4 i; e, K# p3 vof papilledema.
% D; H6 _$ k& z! KLaboratory Evaluation. H( z" L Z# R) E# `/ L$ ]. H' I- e
The bone age was consistent with 28 months by( A( ~) ~- n- E3 f: p3 ]" c- n7 y
using the standard of Greulich and Pyle at a chrono-
Q& R t& `0 s x# X w, I+ Zlogic age of 16 months (advanced).5 Chromosomal+ C6 L1 i! \' Y9 `. X
karyotype was 46XY. The thyroid function test
/ G3 Z. Q( T pshowed a free T4 of 1.69 ng/dL, and thyroid stimu-6 D: ]/ ?' F/ d @" E6 p+ G
lating hormone level was 1.3 µIU/mL (both normal).
- @6 d4 l; [$ `- pThe concentrations of serum electrolytes, blood
- H. o! w# O% H- M; c* r. nurea nitrogen, creatinine, and calcium all were; ]5 Y U2 \5 A4 k. O& ]
within normal range for his age. The concentration8 |: F& [& P/ O7 C) b& t
of serum 17-hydroxyprogesterone was 16 ng/dL
9 ?7 v4 F {% q' m3 F$ F- n( O8 z(normal, 3 to 90 ng/dL), androstenedione was 20 O" W y" Z0 c) C5 h
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-7 s2 i* _0 A3 o6 s. O; V
terone was 38 ng/dL (normal, 50 to 760 ng/dL),9 ~1 a, b |. _' t
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
/ z$ I. c+ W" P6 I% `0 K49ng/dL), 11-desoxycortisol (specific compound S). Q7 N, ~4 u+ y- |; y* Z+ K
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
4 f/ a9 v2 E$ ^tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total/ Q3 |: T6 P) d& ^1 M/ e
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),7 |5 Y7 U/ [( n* k0 L8 @# C- |) U
and β-human chorionic gonadotropin was less than
$ l- N2 I/ d( Z: a3 n7 f5 mIU/mL (normal <5 mIU/mL). Serum follicular3 f- Z R& M0 z6 O W0 \
stimulating hormone and leuteinizing hormone2 D$ W) Z$ G; e
concentrations were less than 0.05 mIU/mL8 } R, p% |3 v/ e# v7 J( [
(prepubertal). I' s! N6 L1 B$ G
The parents were notified about the laboratory
- x" X( m$ w" Presults and were informed that all of the tests were- V$ }2 N# @ ?& t0 p# y# Y/ @- `
normal except the testosterone level was high. The1 U- e1 i3 U+ a
follow-up visit was arranged within a few weeks to
! q* ]5 i( `+ [* W( wobtain testicular and abdominal sonograms; how-6 y' g" }% B4 q! A) _
ever, the family did not return for 4 months.
' V9 z; ]3 t* P, j/ k+ sPhysical examination at this time revealed that the9 T0 w# v9 j- P# W& I, C# M0 f' e
child had grown 2.5 cm in 4 months and had gained
4 K. A) w7 L9 Z8 F$ M' a8 u8 Y2 kg of weight. Physical examination remained, M* p0 Y! y# R+ W! @" l% j: M
unchanged. Surprisingly, the pubic hair almost com-
" ^) L" g* N { V* {pletely disappeared except for a few vellous hairs at, Q0 ~3 o+ R) u1 d
the base of the phallus. Testicular volume was still 2
+ N `" B; F) w4 G# u$ h! HmL, and the size of the penis remained unchanged.
; ?# V6 S4 u+ |/ _The mother also said that the boy was no longer hav-' [- T5 u6 O+ } b& P
ing frequent erections.
! i: ^& F# G6 O9 `) P( uBoth parents were again questioned about use of9 [. W/ V' L' c% L6 s% w: S
any ointment/creams that they may have applied to' U% M' u ?2 x
the child’s skin. This time the father admitted the
8 F- `4 D- R7 d& DTopical Testosterone Exposure / Bhowmick et al 541
, d9 q" c3 R( @( ~! r5 ouse of testosterone gel twice daily that he was apply-4 q* {& e ^# t( t6 x3 A( ]. ]: w
ing over his own shoulders, chest, and back area for8 T! D2 v/ ]- G# j
a year. The father also revealed he was embarrassed
& e/ D2 f. c+ T( |1 R: xto disclose that he was using a testosterone gel pre-
; `2 _. ~! g; w* bscribed by his family physician for decreased libido. m" ?* O; ^0 D9 M2 W: {1 e# I
secondary to depression.
$ N1 @* v, ^5 {) OThe child slept in the same bed with parents.( O4 R% {5 D f
The father would hug the baby and hold him on his
* a8 W0 f# Y# {. l6 E1 _* M7 z' f0 H, schest for a considerable period of time, causing sig- Z: k1 d/ f& b$ {9 P
nificant bare skin contact between baby and father.
$ M9 W- J: i3 S& ^7 kThe father also admitted that after the phone call,- H) I7 F. r# s) H& g
when he learned the testosterone level in the baby
5 y6 @# x2 O. y. k- [2 t: z4 @was high, he then read the product information
2 l' a2 m: N8 b. H2 E! O p; Wpacket and concluded that it was most likely the rea-
+ P' s4 u3 x3 [+ Qson for the child’s virilization. At that time, they
. R D9 [( I- k9 }decided to put the baby in a separate bed, and the: \3 Z7 {$ J8 O- M w
father was not hugging him with bare skin and had: q4 J6 O4 e% I* P
been using protective clothing. A repeat testosterone# s! T3 p; I! e/ J; E1 j: t
test was ordered, but the family did not go to the4 U$ y! s% w/ q% w$ x$ ] _+ f) o6 h
laboratory to obtain the test.% t) t6 b) V8 W# r" O a+ w$ X! p
Discussion
' \# f' W. l0 D, vPrecocious puberty in boys is defined as secondary% N" d0 E) }9 R6 J& V. i
sexual development before 9 years of age.1,4
7 W8 V; P( Q& I7 X2 T, YPrecocious puberty is termed as central (true) when
0 [8 X3 F: ^' b, B' M) j$ [it is caused by the premature activation of hypo-
9 W, a5 p& u5 Y( A3 vthalamic pituitary gonadal axis. CPP is more com-3 v5 ?% r7 G) B1 Z- X
mon in girls than in boys.1,3 Most boys with CPP
[& E0 s$ I7 U0 N2 M$ Y' s; o4 Dmay have a central nervous system lesion that is' l# I, G% O( u# c/ x& {2 Z4 E
responsible for the early activation of the hypothal-
' e5 u, m0 H8 M5 Y$ T+ Wamic pituitary gonadal axis.1-3 Thus, greater empha-
/ q. Y" F; P# D& v+ M. Rsis has been given to neuroradiologic imaging in* y z3 \4 b) W1 F/ Z: X! i
boys with precocious puberty. In addition to viril-0 \2 {7 }9 P+ z+ X, p5 H8 U: P" n
ization, the clinical hallmark of CPP is the symmet-
1 C$ n7 J' o3 q# Brical testicular growth secondary to stimulation by4 |8 C3 L4 s y1 ]1 X
gonadotropins.1,3
+ l. M% u% x& c% hGonadotropin-independent peripheral preco-& v7 |* m* N) ]5 e) t1 x
cious puberty in boys also results from inappropriate& F& ?* X% \* `5 M' q0 b
androgenic stimulation from either endogenous or
1 K2 R% a) o; ~! k% Bexogenous sources, nonpituitary gonadotropin stim- X, b; Y E. Q `0 V D1 I
ulation, and rare activating mutations.3 Virilizing- N$ P; C. M# x$ n7 N4 ^
congenital adrenal hyperplasia producing excessive
6 B8 l* }3 I8 L, g; @3 v4 qadrenal androgens is a common cause of precocious
* C( a) X9 O' m W5 a' {puberty in boys.3,4
3 U( @# g9 t, _7 HThe most common form of congenital adrenal
" O$ }2 q% N! x# ihyperplasia is the 21-hydroxylase enzyme deficiency.
1 [. c5 s/ t GThe 11-β hydroxylase deficiency may also result in+ l( ^& B; R$ X& {* \
excessive adrenal androgen production, and rarely,9 w7 `) z' t4 L" _
an adrenal tumor may also cause adrenal androgen
6 v7 L" {( s" J8 C. a% g) {9 ^% texcess.1,3 V9 Z/ K. c. L, w- R0 V* L
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
8 R! J6 [6 `* u2 m542 Clinical Pediatrics / Vol. 46, No. 6, July 2007& q- m: G- o8 X
A unique entity of male-limited gonadotropin-. `0 Y: ~& r a3 {: F1 N4 ^
independent precocious puberty, which is also known! V: `5 K- L9 h( @: H: T
as testotoxicosis, may cause precocious puberty at a
1 Q; Q4 [% E3 N; ?! R& }very young age. The physical findings in these boys
% I0 {4 _0 d2 j P% ?7 f3 nwith this disorder are full pubertal development,
, d" N4 [5 H! {+ Rincluding bilateral testicular growth, similar to boys; ?2 N. e y8 _& t
with CPP. The gonadotropin levels in this disorder
8 K0 M8 Z" U$ E/ S! vare suppressed to prepubertal levels and do not show6 ~* v- `) K0 t: F& m% s
pubertal response of gonadotropin after gonadotropin-9 y4 C- B6 [" U) h* v3 L8 ]
releasing hormone stimulation. This is a sex-linked: J2 i. }& ?- D: \: ^9 ~" c
autosomal dominant disorder that affects only, O. [5 P, a9 c8 _: b% [
males; therefore, other male members of the family
7 O4 }7 C) `% {may have similar precocious puberty.36 Q d+ p' U- j6 p* V0 S) D, L! q
In our patient, physical examination was incon-
* @) R. ?) X5 m) N" x) \sistent with true precocious puberty since his testi-- n1 _3 T+ W! z, r1 k1 M' F
cles were prepubertal in size. However, testotoxicosis
) s. t/ b( N3 \/ M7 ~! `" hwas in the differential diagnosis because his father7 k* J9 K w" C4 @8 J( r- s
started puberty somewhat early, and occasionally,
6 g# y$ l9 e8 V2 x) f! etesticular enlargement is not that evident in the
. ]; `4 r8 U/ ?% jbeginning of this process.1 In the absence of a neg-4 y) i& t+ }) L7 | S. `# @2 r
ative initial history of androgen exposure, our
' r% B1 T! V; r3 Z+ U/ I+ d* hbiggest concern was virilizing adrenal hyperplasia,
P5 D7 I7 l# b% r$ ~# peither 21-hydroxylase deficiency or 11-β hydroxylase
* F, d' y2 f/ T: u$ Z6 ]deficiency. Those diagnoses were excluded by find-, H6 f, G, O( m5 a
ing the normal level of adrenal steroids.
4 N0 Q8 A, t/ v N1 l' YThe diagnosis of exogenous androgens was strongly
& S) P( V: q5 J, W- ususpected in a follow-up visit after 4 months because
, j' k2 I* l) T7 s& Y0 S% z0 W9 Rthe physical examination revealed the complete disap-
; R1 [1 a4 l d* D; r! I8 ~pearance of pubic hair, normal growth velocity, and
" l5 \6 U( b5 f6 H/ Kdecreased erections. The father admitted using a testos-
! D, ^( r& y* j. kterone gel, which he concealed at first visit. He was
$ V6 _) Y& ~9 {+ Cusing it rather frequently, twice a day. The Physicians’
& ~( e9 r+ g% Z/ ^# pDesk Reference, or package insert of this product, gel or# ]" _# \* K5 o' u( [: F5 f
cream, cautions about dermal testosterone transfer to
: c0 Q! w9 ?3 ?) }; O) nunprotected females through direct skin exposure.# v# @3 X$ F6 z% n
Serum testosterone level was found to be 2 times the
{2 s- X1 I6 l i' abaseline value in those females who were exposed to
9 f* N1 s8 X7 \: z6 }+ M1 J* seven 15 minutes of direct skin contact with their male, C% ^& l# c, T ]9 H- {
partners.6 However, when a shirt covered the applica-
# K7 M( h- a0 \. a- h2 p& `; Ption site, this testosterone transfer was prevented.
! Y, Q5 g9 j; fOur patient’s testosterone level was 60 ng/mL,
: f% b& w3 ] G* I% owhich was clearly high. Some studies suggest that3 G+ \: X# d7 `, ^) Z2 o+ m
dermal conversion of testosterone to dihydrotestos-
4 W% a9 R y$ Y& f( k; d8 ]terone, which is a more potent metabolite, is more' H9 m! G, k& X. ^( u
active in young children exposed to testosterone
+ o6 i, P/ X0 @* `! ]exogenously7; however, we did not measure a dihy-
7 Y$ u' L9 x \ y l: }' b8 Wdrotestosterone level in our patient. In addition to
- I2 r9 X P3 v: [9 P$ `# B9 }virilization, exposure to exogenous testosterone in
: i1 {# v- t. Z5 wchildren results in an increase in growth velocity and$ A6 f, P3 T* K Q8 Q) P
advanced bone age, as seen in our patient.
3 m7 S0 I8 s8 B* E- a$ W: tThe long-term effect of androgen exposure during
: W9 i, G0 m& S" Rearly childhood on pubertal development and final7 L- c2 L& ?7 [/ w$ c0 O, @
adult height are not fully known and always remain0 k+ _+ N( S) Z( d" @2 k
a concern. Children treated with short-term testos-0 ]* u' O2 W, a& @0 u7 e
terone injection or topical androgen may exhibit some, z A5 b+ N1 w+ N7 o
acceleration of the skeletal maturation; however, after
j; h& p- x2 ^1 |5 @cessation of treatment, the rate of bone maturation
0 U, _0 S0 l W9 Z: r" A( t# |decelerates and gradually returns to normal.8,9
3 K. y _9 \! P9 p/ l& _There are conflicting reports and controversy' T4 ^2 q3 b! p. y( D4 _0 _
over the effect of early androgen exposure on adult% g! N2 P8 [9 Q5 w% e' K/ L
penile length.10,11 Some reports suggest subnormal3 P+ B! j$ Y# x, a
adult penile length, apparently because of downreg-
" R* Q# q2 f) F0 p; ?* Q+ [ulation of androgen receptor number.10,12 However,& g F' F( E! {5 ]( ?/ B: x
Sutherland et al13 did not find a correlation between
0 h& @2 r2 J! c. q3 Z/ Z* Echildhood testosterone exposure and reduced adult
( t8 A" F; `6 w. i/ u1 zpenile length in clinical studies.; p- Q; l! K& n' I1 o) x8 i
Nonetheless, we do not believe our patient is# f# c# c; j. ]# ?: n
going to experience any of the untoward effects from* J0 e9 d$ M' Z; A2 E
testosterone exposure as mentioned earlier because0 `8 l& i. z/ ~ R
the exposure was not for a prolonged period of time.
: g) R5 g C: F& h9 G* }* @Although the bone age was advanced at the time of
" P; w3 g; P/ \% }8 ediagnosis, the child had a normal growth velocity at% T& H/ ]. D t7 d( w1 @
the follow-up visit. It is hoped that his final adult
2 e4 Z5 C% ?+ h5 @8 Bheight will not be affected.
+ s3 Q* F- c6 [. X, O8 h7 B; p) D. sAlthough rarely reported, the widespread avail-
% o2 K! U2 @, N+ D1 vability of androgen products in our society may
0 c! `4 C4 M2 p9 W, l0 S+ findeed cause more virilization in male or female
1 M* I' `) F7 s; w5 r2 h3 cchildren than one would realize. Exposure to andro-3 ^. p7 Y, P5 q$ s
gen products must be considered and specific ques-
+ k+ P$ `. c( Rtioning about the use of a testosterone product or0 ^9 h, X1 `. l4 `9 e9 _/ J
gel should be asked of the family members during
6 G; W4 r# Z0 ^: bthe evaluation of any children who present with vir-+ V' d1 _( B% [/ _9 u7 J
ilization or peripheral precocious puberty. The diag-
7 `! [+ C* }9 H) }: j6 x8 ~ c$ \$ znosis can be established by just a few tests and by
0 ?7 v: `. }, nappropriate history. The inability to obtain such a
, o$ k3 a4 O3 q2 q% E+ E5 p: Yhistory, or failure to ask the specific questions, may
( f9 X8 ?$ O3 h) w/ W3 J$ S! ~result in extensive, unnecessary, and expensive0 [( {7 s' e: w3 r* y! {
investigation. The primary care physician should be
; _, Q* o2 T4 j0 Oaware of this fact, because most of these children
" M( f( ]2 Q" q* Zmay initially present in their practice. The Physicians’6 s9 M' c( @8 F
Desk Reference and package insert should also put a& N$ u# e1 _" N) y% n3 Y' J
warning about the virilizing effect on a male or4 t) s" c" S* r- @. I/ a* P- s
female child who might come in contact with some-9 Y! Q/ O) |6 H# Z, T/ ^6 B
one using any of these products.; Q% q/ m$ }, f4 U" J
References0 O( J; C1 f" \; O% s+ h
1. Styne DM. The testes: disorder of sexual differentiation
6 b3 u" D6 x& b' Aand puberty in the male. In: Sperling MA, ed. Pediatric/ R4 R2 [% v- \. E. c4 n' _
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
5 ?% V. B' K4 f# ]1 ?9 }- m' y2002: 565-628.- C% w& R9 m5 J+ S6 x
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
! u5 X1 y. Y& T. j2 G* Npuberty in children with tumours of the suprasellar pineal# U1 C) ?; N/ E% R+ x/ S3 j6 q# k
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from5 k/ m, i: R Y w- L
Topical Testosterone Exposure / Bhowmick et al 543
* D* O4 J8 Z; L* v& @0 tareas: organic central precocious puberty. Acta Paediatr.0 Y4 K7 E( z+ v6 Z; q5 O
2001;90:751-756.' d2 Z' y# E+ g; e- C- W, [9 `
3. Lee PA. Puberty and its disorders. In: Lifshitz F, ed.' z' x X8 x1 P! \* b
Pediatric Endocrinology. 4th ed. New York, NY: Marcel
* B0 |+ @# ~3 S4 G, Z2 n" L/ WDekker Inc; 2003:211-238.
0 U' c/ x+ [6 ]4. Yu YM, Punyasavatsu N, Elder D, D’Ercole AJ. Sexual8 \/ R% z- }9 e% L3 |
development in a two-year-old boy induced by topical
+ e0 d n- Z8 N5 P2 @exposure to testosterone. Pediatrics. 1999;104:e23.
9 Z, i9 e& s1 l: j v5. Greulich WW, Pyle SI, eds. Radiographic Atlas of
! }( Y( z# v* L- K! |# |Skeletal Development of the Hand and Wrist. 2nd ed.
( E' A$ X4 R4 s% a1 jStanford, CA: Stanford University Press; 1959.
, |, o( N& r# F8 U+ @; a. d; r6. Physicians’ Desk Reference. Androgel 1% testosterone,
- M+ u; p0 y- {- E* G7 o8 @Unimed Pharmaceutical Inc. Montvale, NJ: Medical, `4 V C0 d4 _: g. k/ H
Economics Company, Inc; 2004:3239-3241.* @+ O' L3 Z/ w3 }3 H
7. Klugo RC, Cerny JC. Response of micropenis to topical
4 e; X1 s8 [" Wtestosterone and gonadotropin. J Urol. 1978;119:% M) I; z w7 Y2 [3 n
667-668.+ S2 z0 i( k* S7 Q8 x' H! P. G
8. Guthrie RD, Smith DW, Graham CB. Testosterone6 d) o, w9 R% e/ o4 M
treatment for micropenis during early childhood. J Pediatr.6 V6 T$ l7 l/ w0 F; g
1973;83:247-252.9 P9 ~& l0 V& V! H; W* N e. l
9. Jacobs SC, Kaplan GW, Gittes RF. Topical testosterone
7 D R" \. m* V3 C- ]+ U0 ftherapy for penile growth. Urol. 1975;6:708-710.
, N% B! B J; }10. Husmann DA, Cain MP. Microphallus: eventual phallic
6 \! l. i& B4 w6 o R& V/ K, h7 Qsize is dependent on the timing of androgen administra-
! Q' @( s$ L5 W6 @2 V+ d7 Ption. J Urol. 1994;152:734-739.
5 j8 P3 t* O" J( l9 ]! a11. McMahon DR, Kramer SA, Husmann DA. Micropenis:
- l/ w0 r, D( n8 f" Sdoes early treatment with testosterone do more harm
7 C+ E6 F% j1 W; rthan good? J Urol. 1995;154:825-829.
7 ]0 e" U) c" Q12. Takane KK, George FW, Wilson JD. Androgen receptor. M) l( x5 Z! ~6 s) Z7 c
of rat penis is down-regulated by androgen. Am J Physiol.
+ Z5 [6 D" B$ W$ g& T1990;258:E46-E50.
! s9 V' a' C! J: G4 M; U13. Sutherland RS, Kogan BA, Baskin LS, et al. The effect, x$ A, v: D% K5 _# M
of prepubertal androgen exposure on adult penile) q+ K' u. U3 A2 G7 u D. `1 o8 G+ m
length. J Urol. 1996;156:783-787. |
|