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is a significant concern for physicians. Central. @ B; R4 B0 F O6 c
precocious puberty (CPP), which is mediated# j, b" Y8 @" j% e) V
through the hypothalamic pituitary gonadal axis, has0 F& a+ n( a* F' c
a higher incidence of organic central nervous system
8 w1 G# q1 T/ t; e, X$ u* ?lesions in boys.1,2 Virilization in boys, as manifested
! C% U. y# o; }$ w: ~) D( R Iby enlargement of the penis, development of pubic) W/ @# L$ B# a0 p# z8 O% e% }3 H
hair, and facial acne without enlargement of testi-
2 S2 J( C1 Q; ^: E Icles, suggests peripheral or pseudopuberty.1-3 We
' l& f. f( f' Z6 t4 [5 D3 Greport a 16-month-old boy who presented with the
8 E l7 A0 R& T9 `4 venlargement of the phallus and pubic hair develop-
3 ]& E# K6 ]7 g9 Rment without testicular enlargement, which was due
% Q) O K9 x* r: m% a1 rto the unintentional exposure to androgen gel used by$ ^2 r2 M8 S0 S# g, L
the father. The family initially concealed this infor-9 J2 Q5 G! l6 O1 v/ j
mation, resulting in an extensive work-up for this
- t, i. @+ p: Z+ M: }child. Given the widespread and easy availability of
% P+ F4 t8 {9 ^6 ~* j6 W9 ~testosterone gel and cream, we believe this is proba-3 e8 M7 A9 Y$ }. m7 u
bly more common than the rare case report in the
( W# X. G, t# C! F! b {8 iliterature.4+ r: i# }+ {/ E. L8 A1 t
Patient Report( I- {1 C7 s7 t! J
A 16-month-old white child was referred to the
+ a0 D8 m! R* B4 ^endocrine clinic by his pediatrician with the concern
" [. s" j* o# ^7 ^+ b% ~of early sexual development. His mother noticed
" h+ z3 P( k! e! f) L# Q6 ~light colored pubic hair development when he was# S6 C# A5 B' h% w9 \/ e
From the 1Division of Pediatric Endocrinology, 2University of' z0 u9 T* B1 z9 a3 f ~
South Alabama Medical Center, Mobile, Alabama.. x+ W0 v5 m9 f& X/ \4 ~( E
Address correspondence to: Samar K. Bhowmick, MD, FACE,
3 I; l- F: z% S, s# Y# b4 eProfessor of Pediatrics, University of South Alabama, College of+ S- u$ S4 l/ _4 L6 C
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
0 E8 Z4 q0 m* x7 Q. a0 ce-mail: [email protected].0 }+ U2 [, h, ?5 K% X* p9 Z
about 6 to 7 months old, which progressively became
* h0 I& L8 a s4 L1 S& [darker. She was also concerned about the enlarge-
" K) {0 I' j; J6 U/ @ment of his penis and frequent erections. The child& V$ \ m, x5 b ]8 F
was the product of a full-term normal delivery, with
. g. X2 ?4 B. S) [a birth weight of 7 lb 14 oz, and birth length of% v6 q; R/ Q& A) c: j) i& C
20 inches. He was breast-fed throughout the first year* _1 {2 o2 N* i' j
of life and was still receiving breast milk along with
/ O, {, G3 a3 U& a7 C& rsolid food. He had no hospitalizations or surgery,8 @# ~$ B% B! o
and his psychosocial and psychomotor development
0 s* y: n% [$ ?" P* W# Hwas age appropriate.
4 W0 W8 N- R! ^% ~The family history was remarkable for the father,
. W" B# z) Y1 M/ {5 Lwho was diagnosed with hypothyroidism at age 16,
$ S' o% K0 ~1 K$ [which was treated with thyroxine. The father’s
" s" B' Y3 m0 D) q+ \: Lheight was 6 feet, and he went through a somewhat( L# y- \8 U6 ^: s0 f3 E
early puberty and had stopped growing by age 14.' R+ K/ f: m. T, e2 u
The father denied taking any other medication. The [' C8 Z" j( p" J! [3 l- l1 M
child’s mother was in good health. Her menarche
: r' Y5 w7 D2 B/ Mwas at 11 years of age, and her height was at 5 feet! [1 n1 e+ I1 _# W: M' o% B) {
5 inches. There was no other family history of pre-
6 f6 ?. I$ N; `; h6 Ecocious sexual development in the first-degree rela-! k) c" L- b: _! y4 P; {- x
tives. There were no siblings.
7 `& x$ i0 G, @) e2 g) D3 {Physical Examination
& w' X6 X7 Q* e' ]" v3 cThe physical examination revealed a very active,
& M7 v8 n9 b( y# W: K0 Bplayful, and healthy boy. The vital signs documented
& [1 y5 v/ s2 A. |7 W. wa blood pressure of 85/50 mm Hg, his length was# J" W8 u. r. Z8 E, ~
90 cm (>97th percentile), and his weight was 14.4 kg3 c, E* ^6 P$ A
(also >97th percentile). The observed yearly growth
' @% t9 [- V% Cvelocity was 30 cm (12 inches). The examination of$ c! v4 ^6 l' i# }
the neck revealed no thyroid enlargement.: m5 x/ G# Y7 ~, m) F h
The genitourinary examination was remarkable for
5 @% D# E7 k" \7 _5 benlargement of the penis, with a stretched length of5 D- O* x2 ^+ e% b
8 cm and a width of 2 cm. The glans penis was very well
% C0 R) ~2 N" F. Udeveloped. The pubic hair was Tanner II, mostly around9 ~7 ?, W% s% y& e4 o6 `- E6 H
5400 i K7 P9 V4 U# l- \ g/ ]; l
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from$ |% G( O3 d" j' t6 e5 y
the base of the phallus and was dark and curled. The0 z* g7 q3 u M5 r+ F
testicular volume was prepubertal at 2 mL each.2 \0 A' Q1 V; t8 M3 M
The skin was moist and smooth and somewhat
# k' T/ b% X: E8 }oily. No axillary hair was noted. There were no2 k7 E7 ~, s+ B( u4 J9 h
abnormal skin pigmentations or café-au-lait spots.
9 v( [' N# c. _6 ?* I+ u# `. ENeurologic evaluation showed deep tendon reflex 2+
, [$ h8 o: `) U% g' fbilateral and symmetrical. There was no suggestion( f: {2 S2 v: s' B' a; Y
of papilledema.8 U3 O$ Q! J. p3 k; P" n
Laboratory Evaluation- E# a4 s8 a/ B: l6 j6 t! U
The bone age was consistent with 28 months by7 q! W: y; M" {
using the standard of Greulich and Pyle at a chrono-
6 Q, v' {: @1 Klogic age of 16 months (advanced).5 Chromosomal# ]2 t9 j! U5 n; M. q) c( J
karyotype was 46XY. The thyroid function test
; g" W- X5 K: F1 ]; {$ s+ Q3 Vshowed a free T4 of 1.69 ng/dL, and thyroid stimu-0 q9 {6 Q& o8 z5 ?! n* p- y5 g
lating hormone level was 1.3 µIU/mL (both normal).
6 s: t7 k) o" |! Z1 p2 x1 E1 z+ OThe concentrations of serum electrolytes, blood! V8 a0 U" l7 }9 K
urea nitrogen, creatinine, and calcium all were2 X: J" j$ u3 c# ]1 m [
within normal range for his age. The concentration
- t" Z6 b) d' U% g! G f* eof serum 17-hydroxyprogesterone was 16 ng/dL
. I" X: K7 L2 \% s/ V8 U) j' @(normal, 3 to 90 ng/dL), androstenedione was 20
& e- G. q+ w' ~# U- E/ }; X0 Fng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-2 D( {) G1 Q7 ^5 N; i
terone was 38 ng/dL (normal, 50 to 760 ng/dL),8 }% _2 r0 `: s. ]$ h0 T
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
' _8 j1 C+ m) \49ng/dL), 11-desoxycortisol (specific compound S)( d1 f; T9 C4 [- S: ^
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-! ?5 o0 R6 k M5 C0 D: f( B& P
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total1 |) }* j4 |, W& S/ Q( M5 V
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
r5 C1 ?- R4 U6 `# uand β-human chorionic gonadotropin was less than
2 I8 ~/ X3 c: [" ~4 l: L( e" e5 mIU/mL (normal <5 mIU/mL). Serum follicular
) G5 \ d9 G; A9 @2 wstimulating hormone and leuteinizing hormone
) N. t2 L8 @6 ?5 ~8 b5 dconcentrations were less than 0.05 mIU/mL0 L4 ?: n' z r' c' R. R' {
(prepubertal).
; ?' r1 M& a: O; {; {The parents were notified about the laboratory
4 }+ `0 l2 `+ L3 Q1 uresults and were informed that all of the tests were' h- W: G' a0 W" W: I
normal except the testosterone level was high. The/ r& ^3 v" A/ o3 X1 l% g( r
follow-up visit was arranged within a few weeks to0 \( _2 m: [+ P3 j7 s8 e
obtain testicular and abdominal sonograms; how-
6 b" |$ w t! \. @1 z+ \: Lever, the family did not return for 4 months.
) O# R( q1 V! E8 b9 \; V; j* j; }Physical examination at this time revealed that the
' y: D: C8 @; H9 Uchild had grown 2.5 cm in 4 months and had gained# }/ y5 N- F6 T5 J" y
2 kg of weight. Physical examination remained7 }% H3 M0 Q3 `
unchanged. Surprisingly, the pubic hair almost com-
8 `5 l# l, p7 x; g4 {$ Upletely disappeared except for a few vellous hairs at& ]5 S b$ y k! z: B/ H
the base of the phallus. Testicular volume was still 2
# e/ V* V1 [' o8 m4 I" Z) XmL, and the size of the penis remained unchanged.
& c( P8 C6 }' nThe mother also said that the boy was no longer hav-$ H% b( b( x0 \
ing frequent erections.$ ~. ]" e, ~* }
Both parents were again questioned about use of
a3 z7 r0 b& J9 ^any ointment/creams that they may have applied to8 R2 v G; }" }3 p3 b
the child’s skin. This time the father admitted the
* Q0 P1 \2 E$ E$ rTopical Testosterone Exposure / Bhowmick et al 541
& m7 L* B$ x4 x4 Q J: M, Quse of testosterone gel twice daily that he was apply-
; r, U2 L- n. Q; fing over his own shoulders, chest, and back area for
: l6 D4 l& y9 Y: r5 r4 u. D. fa year. The father also revealed he was embarrassed
5 X9 c/ Y& p4 D4 c; }! }7 vto disclose that he was using a testosterone gel pre-& n( p6 Y7 y- |; V: k! z+ m, H B
scribed by his family physician for decreased libido: m. J+ O( C1 z& M( |9 a
secondary to depression.# _- U7 X+ M- Y5 D. @' B
The child slept in the same bed with parents.
+ i0 _% i3 E6 l7 |The father would hug the baby and hold him on his, t5 r" Q1 A/ [+ A4 h
chest for a considerable period of time, causing sig-
. G& U' ]2 P% v) M% C [nificant bare skin contact between baby and father.
/ J& h" S! F1 j' Q$ zThe father also admitted that after the phone call,) e6 q2 m# m* K& b4 ?2 v& T, v; T
when he learned the testosterone level in the baby; S# U+ ~* E7 a" y
was high, he then read the product information
7 p( I6 v4 G, ?1 t" Mpacket and concluded that it was most likely the rea-
' ^- ~9 Y) f: k& L. q% H9 F8 eson for the child’s virilization. At that time, they
: q+ D. m! ^- _& ?, q9 Xdecided to put the baby in a separate bed, and the0 }/ D' i7 b; r1 v: N1 H
father was not hugging him with bare skin and had$ e* t! Z/ b0 b8 l2 |3 w: p7 g2 f
been using protective clothing. A repeat testosterone0 Q% ]7 }, w/ K6 E& j" a
test was ordered, but the family did not go to the
( `" h' O' m0 w/ Elaboratory to obtain the test.
/ [; U4 s: n$ f9 z$ r N( R3 DDiscussion
) [- j% i4 e$ a3 o( x) x! p7 w# LPrecocious puberty in boys is defined as secondary7 |3 ]: L2 ~& U3 h+ n. Z" X
sexual development before 9 years of age.1,4
, X( R0 s: `7 [3 cPrecocious puberty is termed as central (true) when; S# I, c$ E& Z( a
it is caused by the premature activation of hypo-. B- j! |$ `' B, @; G8 m: d
thalamic pituitary gonadal axis. CPP is more com-
; q; y% y( c( F8 jmon in girls than in boys.1,3 Most boys with CPP# w% y1 a" a- X Z( Z) c# A* _
may have a central nervous system lesion that is
1 B; ]1 m9 o. qresponsible for the early activation of the hypothal-
1 X+ _8 w2 e5 f4 @0 s. ramic pituitary gonadal axis.1-3 Thus, greater empha-
- d. p6 s) u# j5 Xsis has been given to neuroradiologic imaging in
7 e$ c1 n8 R T4 q( gboys with precocious puberty. In addition to viril-/ r1 c9 d; w/ V3 k$ ]
ization, the clinical hallmark of CPP is the symmet-# b: }1 V& E2 R
rical testicular growth secondary to stimulation by$ Z1 q& }% L# V, b( v4 G& Q
gonadotropins.1,3
) |! e' E M* ?1 s& N8 U* X& XGonadotropin-independent peripheral preco-. ^. Z7 f9 N# W8 b, X
cious puberty in boys also results from inappropriate. S& n4 X, `' M: i" J6 B
androgenic stimulation from either endogenous or1 e) t/ Q9 y7 _2 x$ N
exogenous sources, nonpituitary gonadotropin stim-
( `7 h' X& J; O- a2 R9 sulation, and rare activating mutations.3 Virilizing
0 w, J5 o% a7 Q1 d3 ~congenital adrenal hyperplasia producing excessive: K) ` s1 C+ {7 H9 W
adrenal androgens is a common cause of precocious
7 ?0 z9 `5 j2 ~* ?0 x1 npuberty in boys.3,4& \* n' m* H+ {8 e
The most common form of congenital adrenal5 `. e& @4 k3 I: b6 ?) C
hyperplasia is the 21-hydroxylase enzyme deficiency.' W7 `/ _: Z& q# ]9 g
The 11-β hydroxylase deficiency may also result in# A9 P& z* n& P: i4 o) k" h2 t
excessive adrenal androgen production, and rarely,* O# ^; Y4 v; d0 b
an adrenal tumor may also cause adrenal androgen
5 F) z3 A# k7 E) w* B% Cexcess.1,3
0 y* {" F$ K3 r1 {, B) v( Fat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from7 l* l3 `4 R& F" l u
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
# c1 D% p9 J/ e, d0 L9 d% aA unique entity of male-limited gonadotropin-
5 B; J& g! ?7 q" Q* {independent precocious puberty, which is also known. H' h( k) s8 {
as testotoxicosis, may cause precocious puberty at a* x; i, {6 T$ g- M
very young age. The physical findings in these boys4 e6 _; C) F, W3 Z, n1 I5 h
with this disorder are full pubertal development,! t2 p: z. L5 L; u5 u
including bilateral testicular growth, similar to boys; h% P8 R3 U- P$ D; l
with CPP. The gonadotropin levels in this disorder+ j b6 |8 F. D. R+ d3 ~9 e
are suppressed to prepubertal levels and do not show
. p, P3 o' d; K3 [0 C. d: v0 ~pubertal response of gonadotropin after gonadotropin-
' p4 Z$ s$ E2 Y+ F, P0 z% ]: k; rreleasing hormone stimulation. This is a sex-linked! o. f7 D: K. y& X4 V
autosomal dominant disorder that affects only8 }3 d/ b: F1 k- I6 _
males; therefore, other male members of the family4 H. @' D/ x, R3 a( a ?4 Q7 }
may have similar precocious puberty.3: {/ y/ b/ r7 q9 n( ]. Z+ y4 I
In our patient, physical examination was incon- }; c9 x* J" e
sistent with true precocious puberty since his testi-
8 i9 D# w5 b3 M. p* ]2 |# ycles were prepubertal in size. However, testotoxicosis
' P( ^4 G) h: k. P8 w. T$ u5 e1 _was in the differential diagnosis because his father
7 I& G, j, P% Q ]started puberty somewhat early, and occasionally,
# Z! W2 U# c. M& t7 {( htesticular enlargement is not that evident in the5 i, j& M+ V' q
beginning of this process.1 In the absence of a neg-- v9 Y4 ~; Z% E6 K
ative initial history of androgen exposure, our& W8 B6 W) E9 y
biggest concern was virilizing adrenal hyperplasia,
& x: k+ q! w! P D& g# yeither 21-hydroxylase deficiency or 11-β hydroxylase
6 g1 H' \5 z/ a4 n5 v2 Rdeficiency. Those diagnoses were excluded by find-
. }2 _0 f( C, _: P# Y, B9 k& Xing the normal level of adrenal steroids.
. e9 c& `3 J7 U- A$ HThe diagnosis of exogenous androgens was strongly6 g% E8 J3 ]. S. A/ m: y: A
suspected in a follow-up visit after 4 months because9 ?; \; a$ a4 B9 k4 v/ ]' ~, n5 ^
the physical examination revealed the complete disap-% J2 m9 E# q0 \$ j/ r ]
pearance of pubic hair, normal growth velocity, and
" c% c9 \$ w7 w; O7 Q; c6 x) q9 ndecreased erections. The father admitted using a testos-. \" e3 H' z" _
terone gel, which he concealed at first visit. He was/ Z9 ~4 V/ L7 D$ G
using it rather frequently, twice a day. The Physicians’1 [ U# ?/ c) }
Desk Reference, or package insert of this product, gel or
$ h [6 K6 l1 O# c2 y6 G5 s7 {cream, cautions about dermal testosterone transfer to7 ^( }& A3 L0 o, Z, ^* G
unprotected females through direct skin exposure.' {6 W- y. b4 }! _
Serum testosterone level was found to be 2 times the
8 W: g% T; y/ @7 ]# \# g- C( @3 S8 C. obaseline value in those females who were exposed to
8 E$ u. i" W7 d2 l$ j5 S+ jeven 15 minutes of direct skin contact with their male
( C1 \6 p W' Jpartners.6 However, when a shirt covered the applica-! m$ f7 ~( c+ W6 e8 C& H( G$ ^
tion site, this testosterone transfer was prevented.& R2 ~/ i4 _9 M" w
Our patient’s testosterone level was 60 ng/mL,
, M, P* [0 U9 J* y6 F7 Vwhich was clearly high. Some studies suggest that; Q4 S+ ?; f1 ^" W6 x0 Q( a1 o- c
dermal conversion of testosterone to dihydrotestos-' I: ~, q2 a. w) N Q
terone, which is a more potent metabolite, is more. |. Y! ~6 u' ~! X$ V" {" \- ^; Z$ k
active in young children exposed to testosterone5 B9 Z$ k' x2 [# f9 }; ?$ n, `
exogenously7; however, we did not measure a dihy-) B4 R! y2 ^# a4 F$ Q
drotestosterone level in our patient. In addition to
) O1 O$ a, ` z* J3 I& E4 w7 _$ tvirilization, exposure to exogenous testosterone in
" P5 l" @7 ]6 uchildren results in an increase in growth velocity and
" ^- C, t2 t: b: x& X: L* l7 @advanced bone age, as seen in our patient.
4 D* R3 n6 X- r" }+ K9 a+ w9 ]The long-term effect of androgen exposure during
1 g- g4 w `! ~/ x% D: x& X8 eearly childhood on pubertal development and final
, e) z- i' h& j0 Nadult height are not fully known and always remain2 O' z) R7 c4 T4 P% C
a concern. Children treated with short-term testos-
d- B1 i$ @8 I! W. W: O9 c% Fterone injection or topical androgen may exhibit some% ?% ]$ B" R9 R3 p4 e0 w' z
acceleration of the skeletal maturation; however, after& G0 A! |, B6 l% E! i. k
cessation of treatment, the rate of bone maturation7 a5 N4 Q5 _. u% s% Y, D j1 @
decelerates and gradually returns to normal.8,96 u" h. q' B' G. L( P
There are conflicting reports and controversy& A* C: k% E) u- v+ s) X' \9 ^
over the effect of early androgen exposure on adult8 |# f4 h: V: v
penile length.10,11 Some reports suggest subnormal
" P' x: v9 e# W2 `9 radult penile length, apparently because of downreg-
3 i) ? A2 x- Z; ?ulation of androgen receptor number.10,12 However,
, z& M2 y& X& k# X" I- Y0 R9 v: Y4 LSutherland et al13 did not find a correlation between
9 h: u2 ^2 p2 o( O% Z3 o4 Xchildhood testosterone exposure and reduced adult
0 i/ ]+ S0 V. d$ x6 L7 T# D8 mpenile length in clinical studies./ @- W0 E' w% {5 E8 k1 W3 @
Nonetheless, we do not believe our patient is
& w4 \# L; t+ |/ N- n+ c$ r: t5 `going to experience any of the untoward effects from! c, ^# r& f/ {+ @# F/ h. c
testosterone exposure as mentioned earlier because
) F/ F0 V* q$ x6 D* B: d4 H, mthe exposure was not for a prolonged period of time.: O6 w# g9 I& V. X5 j
Although the bone age was advanced at the time of( m6 R+ ? J5 ~
diagnosis, the child had a normal growth velocity at
( h9 A: x; F- `0 f: Sthe follow-up visit. It is hoped that his final adult4 V" v3 L8 l5 H8 @, R2 @! P
height will not be affected." e4 r- Z# [ V/ E
Although rarely reported, the widespread avail-& N- V. `: y3 o" b6 D8 d, B( Z+ E+ i& {
ability of androgen products in our society may
" Q4 I1 m3 L { eindeed cause more virilization in male or female. o/ z: ]: j4 a; R! @
children than one would realize. Exposure to andro-
9 `' d9 S: O; D' fgen products must be considered and specific ques-. S2 o# q4 d; t% r, O
tioning about the use of a testosterone product or
. n' K- o$ D1 K4 Zgel should be asked of the family members during2 e/ \$ r1 s9 Y }1 }
the evaluation of any children who present with vir-4 k; X# r1 t) `% \8 n* q l
ilization or peripheral precocious puberty. The diag-
) p3 u& l/ x* ]2 I$ R9 rnosis can be established by just a few tests and by4 b6 `! V3 h! O
appropriate history. The inability to obtain such a" v1 u1 S& ~& L5 t2 l9 k! H" V
history, or failure to ask the specific questions, may
, n( E) z5 H. wresult in extensive, unnecessary, and expensive
7 x* o7 N2 ~5 o+ Y2 Y' kinvestigation. The primary care physician should be1 b5 _# Z* Z( _
aware of this fact, because most of these children
9 h, G6 [+ b# d, G( Dmay initially present in their practice. The Physicians’ X. K4 r1 B) z; Y# J" T
Desk Reference and package insert should also put a
7 r8 w: }, J$ H2 H$ O) D, _+ {warning about the virilizing effect on a male or, E( Q0 H# ?, b; @# D O
female child who might come in contact with some-
! F' m2 ?/ ]& c% ]- S% v1 d( x% c5 z pone using any of these products.7 T) c3 ^, k$ H! `* d- K( U
References
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Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
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puberty in children with tumours of the suprasellar pineal( Z- ^" A5 |9 @1 E. H/ R
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Topical Testosterone Exposure / Bhowmick et al 543
' }+ s0 P' B! S& t% W; K* d3 s2 Jareas: organic central precocious puberty. Acta Paediatr.8 A9 I9 g+ ^: q6 r+ S
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Dekker Inc; 2003:211-238./ ~; J0 l0 t* f
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+ w- X8 C6 ^! [& ^/ pexposure to testosterone. Pediatrics. 1999;104:e23.
& V# b. V8 A1 J0 D2 B5. Greulich WW, Pyle SI, eds. Radiographic Atlas of
% K8 u# f' C7 Q |Skeletal Development of the Hand and Wrist. 2nd ed.
! `6 l- K/ P2 p) sStanford, CA: Stanford University Press; 1959.
1 A) e9 M. q+ }& t% B7 f" \6. Physicians’ Desk Reference. Androgel 1% testosterone,8 S: i+ v3 t8 \4 ]! D+ O+ l
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Economics Company, Inc; 2004:3239-3241.0 L; q; Z% K6 R9 v& ^; b
7. Klugo RC, Cerny JC. Response of micropenis to topical8 |& m( X' g) L/ t" m! `1 X
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