- 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- d/ Z1 C4 I5 ]" `% @7 p; Z
precocious puberty (CPP), which is mediated
~0 N" i. Y0 T9 b5 \' m. S) Athrough the hypothalamic pituitary gonadal axis, has7 j9 |# H/ d" _% l8 H7 A' {
a higher incidence of organic central nervous system* g' c) l) R+ e! c$ B3 f* ^, K# U
lesions in boys.1,2 Virilization in boys, as manifested
5 l, l, H; s# ]4 s# N' H. ?by enlargement of the penis, development of pubic. p5 w9 @8 a2 S
hair, and facial acne without enlargement of testi-0 S, [5 P# y6 P9 j; y( A" Z" O
cles, suggests peripheral or pseudopuberty.1-3 We
, T% D; k& n d p$ K M' U* Yreport a 16-month-old boy who presented with the
; V! T& Z- N7 q% l! ?1 n& `enlargement of the phallus and pubic hair develop-
( q. j: u! n$ R" i" cment without testicular enlargement, which was due& p5 ^5 A, D# S1 J) w0 w$ E, l6 x
to the unintentional exposure to androgen gel used by
+ o; t6 o& ?: `& I# [the father. The family initially concealed this infor-& ~" k. K5 y4 ]8 H0 g
mation, resulting in an extensive work-up for this
B3 N7 J) ` [$ k+ vchild. Given the widespread and easy availability of8 Q1 [2 u$ Y/ i# V8 M3 d$ q
testosterone gel and cream, we believe this is proba-
* I( | Y0 ]3 d/ `3 N& sbly more common than the rare case report in the) O) e/ t5 c( a' [+ o
literature.4 I7 I2 O5 t9 n0 S. m! a
Patient Report
4 U4 X' N5 V9 P" [) yA 16-month-old white child was referred to the
. z- E6 X# p5 C9 g# [endocrine clinic by his pediatrician with the concern
1 f M6 ]: B+ d; @of early sexual development. His mother noticed
: n0 p8 X {9 G) Y1 M. Tlight colored pubic hair development when he was
# S+ n$ p% r- h6 X2 C# i/ }From the 1Division of Pediatric Endocrinology, 2University of5 x# N: ?9 v( E* @% {# p$ b8 q
South Alabama Medical Center, Mobile, Alabama.# t/ j2 N, C6 w U+ P
Address correspondence to: Samar K. Bhowmick, MD, FACE,
7 ~+ u9 ^ X. g% j& |1 _: ~Professor of Pediatrics, University of South Alabama, College of
' ^( t; F1 ` p5 R C! ~8 pMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
2 R' U& x5 M% l$ B9 i9 S! Ue-mail: [email protected].% I. h9 ]2 u# o e; |
about 6 to 7 months old, which progressively became8 ?- S, V6 t0 v9 R; }7 q
darker. She was also concerned about the enlarge-6 f7 g$ Q4 l' i5 y
ment of his penis and frequent erections. The child! y# j- r7 R" B9 @3 {& e6 c
was the product of a full-term normal delivery, with+ }6 X4 u% n6 X( F$ o' t1 L
a birth weight of 7 lb 14 oz, and birth length of
/ C' w0 a2 B3 a$ T& L: K6 N: b20 inches. He was breast-fed throughout the first year
1 N, @; s( ?) g+ s% R1 z% qof life and was still receiving breast milk along with
, p: {( V/ W7 {+ w! T' P9 b# Psolid food. He had no hospitalizations or surgery,2 j1 |# T$ z- H8 p
and his psychosocial and psychomotor development5 Q; U: w8 S1 l( a# ~
was age appropriate.3 H% O( ~) z; ~, r2 |, k+ v6 r' g% V
The family history was remarkable for the father,7 l7 r' k7 G4 N+ U0 x5 e
who was diagnosed with hypothyroidism at age 16,
8 R! j; U. I5 d! \' h! ~. u# ?which was treated with thyroxine. The father’s1 S. y1 d8 U9 X* \
height was 6 feet, and he went through a somewhat
, Z7 N" w( J4 d& L) M, eearly puberty and had stopped growing by age 14.; L* `+ F; y" f/ t
The father denied taking any other medication. The
K# X% r8 P% I9 ]1 Q2 e. ?child’s mother was in good health. Her menarche3 W' e3 Y x( O3 H1 `
was at 11 years of age, and her height was at 5 feet
9 p" _# Z0 `9 v0 H5 inches. There was no other family history of pre-' e7 P% a# r4 r+ k, N
cocious sexual development in the first-degree rela-" g2 [4 B* `# q/ ?( H
tives. There were no siblings.
/ U) l* ^9 g5 g# _- |% y, ^Physical Examination- e+ T+ M2 A! n: N; v
The physical examination revealed a very active,
# E$ j7 z! U7 v* Aplayful, and healthy boy. The vital signs documented' k. ]+ p% |5 \9 X3 x
a blood pressure of 85/50 mm Hg, his length was
! ]: F Z! R) q2 x, }6 e90 cm (>97th percentile), and his weight was 14.4 kg
3 }# L) [/ y) B" ~- W, B! D! x: X: T0 I(also >97th percentile). The observed yearly growth# M2 b/ N8 R; y- F1 ~) {0 n
velocity was 30 cm (12 inches). The examination of: O* _2 ?: K1 k! K
the neck revealed no thyroid enlargement.! r4 k% U+ s" F5 G6 [' z
The genitourinary examination was remarkable for
$ ]+ X2 m ]2 j& aenlargement of the penis, with a stretched length of
6 G; a+ P. G$ W1 v& Q8 cm and a width of 2 cm. The glans penis was very well
9 ~8 ]6 ~1 J" C! Q* P! c6 P% adeveloped. The pubic hair was Tanner II, mostly around0 K, A) p# t5 r: u& ?
540+ j( F8 V$ o0 k
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from8 f/ o2 Z$ Q/ E
the base of the phallus and was dark and curled. The
1 _0 `( J) ~9 Htesticular volume was prepubertal at 2 mL each.5 [ M" [5 [* K0 x$ S
The skin was moist and smooth and somewhat6 w9 z+ V. u3 E( w1 A7 l
oily. No axillary hair was noted. There were no
; g0 L$ j/ ?+ Rabnormal skin pigmentations or café-au-lait spots.
5 j4 r) U6 t5 Q2 xNeurologic evaluation showed deep tendon reflex 2+
. k6 X9 x j/ T8 l. gbilateral and symmetrical. There was no suggestion
4 K$ G5 H% n( h9 s6 [of papilledema.
* q' g% b! `/ H) `1 pLaboratory Evaluation0 [1 |. s% }% n; Y. S
The bone age was consistent with 28 months by
/ X+ s; o- O4 }2 Susing the standard of Greulich and Pyle at a chrono-
/ z; ?+ x0 j9 l% J; r' r5 qlogic age of 16 months (advanced).5 Chromosomal2 W: m% G. Z: h& |* b/ ?! n$ e# V
karyotype was 46XY. The thyroid function test
! Y( P) Z2 ~1 i3 U" `3 m' lshowed a free T4 of 1.69 ng/dL, and thyroid stimu-' @$ `; g5 y6 O* z/ C
lating hormone level was 1.3 µIU/mL (both normal).8 w& S/ M5 ^! V- Y1 V0 h
The concentrations of serum electrolytes, blood- V* A. \0 Z! N% S* ~
urea nitrogen, creatinine, and calcium all were
7 `8 u9 F O4 Q: Owithin normal range for his age. The concentration$ z) U" R) Q* E6 @6 j5 _$ L5 g
of serum 17-hydroxyprogesterone was 16 ng/dL0 C' n+ _8 k5 e% w8 C* @" ~
(normal, 3 to 90 ng/dL), androstenedione was 201 H- Y& _( P& a0 E& A4 g: @
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
! ~" F3 G8 n1 S2 j+ {: ^1 gterone was 38 ng/dL (normal, 50 to 760 ng/dL),7 H! m( \9 f; H0 _6 a
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
7 f( x4 Y( A+ Z6 q# Z49ng/dL), 11-desoxycortisol (specific compound S): g: X+ y0 _7 y6 I3 k# K
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-2 y. w# |, E5 q
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
- ~4 S3 f {. |0 ~testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
, J7 @, D% s, F" X w& c9 aand β-human chorionic gonadotropin was less than
4 b( M. E0 p& L: [% Y9 `$ O5 mIU/mL (normal <5 mIU/mL). Serum follicular5 i' h. _2 Q8 t! `
stimulating hormone and leuteinizing hormone# E* [4 [5 g/ `9 ~1 L% y) |8 t6 g
concentrations were less than 0.05 mIU/mL$ J+ U2 {7 o4 a$ v/ M# f
(prepubertal).
7 }' s! |+ l% I% bThe parents were notified about the laboratory% c, Y U1 M( p6 L
results and were informed that all of the tests were& A, l# U6 |6 Z" d8 T# C5 v
normal except the testosterone level was high. The
5 S& W. V5 ~2 P L4 i0 J K3 Bfollow-up visit was arranged within a few weeks to/ @& S5 @& C( m8 `% Y# c6 O
obtain testicular and abdominal sonograms; how-& D {" q5 X7 s9 f$ J# B
ever, the family did not return for 4 months.
! l' y. X7 j$ ~; U g3 f6 w; q% uPhysical examination at this time revealed that the
! ^5 c; l* ]/ m9 i9 x+ Z1 uchild had grown 2.5 cm in 4 months and had gained& c' W+ N8 c4 A) }3 y5 u4 d
2 kg of weight. Physical examination remained
\6 P8 S4 X: Wunchanged. Surprisingly, the pubic hair almost com-: N4 f: L5 m# H. u/ ^% D: c* [
pletely disappeared except for a few vellous hairs at3 l. T- i7 x' I: L p* z4 O
the base of the phallus. Testicular volume was still 2
2 d2 J. q7 N, Q2 ?& hmL, and the size of the penis remained unchanged.- m- m5 f R4 D: \4 {% p! i% ?
The mother also said that the boy was no longer hav-
. p' Y' t2 x/ wing frequent erections.0 Y" {# H0 |! K8 c
Both parents were again questioned about use of
]* d* Z+ N. W/ J4 kany ointment/creams that they may have applied to
% S9 T" k1 a) gthe child’s skin. This time the father admitted the
, P3 c/ o0 n/ I7 MTopical Testosterone Exposure / Bhowmick et al 541$ @$ A# R+ B: p. w: \
use of testosterone gel twice daily that he was apply-
% s' j0 r+ l% z) L8 A' ping over his own shoulders, chest, and back area for/ A2 s* l' d, ?& |
a year. The father also revealed he was embarrassed; G% [# |3 {- q* Y
to disclose that he was using a testosterone gel pre-
3 n6 Q+ b6 j" w3 x6 Wscribed by his family physician for decreased libido4 T1 C- F5 n3 {8 _7 U/ V0 C* b
secondary to depression.
. m9 {" n, h- O+ P7 P% _& {0 uThe child slept in the same bed with parents.
) y) w4 e, S0 B \. C" V6 N8 x- F" ?The father would hug the baby and hold him on his
9 m8 X) h4 B& \! \& |chest for a considerable period of time, causing sig-
6 E( Y' i; ]1 {( snificant bare skin contact between baby and father." P/ W7 V1 |' O8 M f$ J
The father also admitted that after the phone call,
4 q, b5 D U4 i9 n5 ^9 o" Y* Nwhen he learned the testosterone level in the baby- P: b9 A$ M" W2 c; [; W/ u
was high, he then read the product information
; F" |# R# n3 [* n Ppacket and concluded that it was most likely the rea-6 [- }% [- C# z# q
son for the child’s virilization. At that time, they, Z$ B8 }0 C. e+ D; c; M" t9 f
decided to put the baby in a separate bed, and the
- v. C0 P+ ?7 pfather was not hugging him with bare skin and had9 v# L; f5 |1 q! ^! h. Q% g
been using protective clothing. A repeat testosterone
8 m& S4 E/ c0 P6 r% l) h% Dtest was ordered, but the family did not go to the& j; O& w$ m# l# S4 f4 b
laboratory to obtain the test.
) \7 E* p" q6 A" ~- s% LDiscussion( V$ |5 y6 S2 u W d, Q+ F
Precocious puberty in boys is defined as secondary* b# `* n' d; H. F0 e/ P
sexual development before 9 years of age.1,4
/ ]% U* q0 w+ \0 c# e7 gPrecocious puberty is termed as central (true) when
6 f0 q7 C+ W1 J7 [0 @1 Kit is caused by the premature activation of hypo-
4 m" g6 N4 K8 F$ othalamic pituitary gonadal axis. CPP is more com-
/ U: G- {- V3 M! ~: L0 C0 U' umon in girls than in boys.1,3 Most boys with CPP: e8 L c8 G1 i
may have a central nervous system lesion that is0 r. C- H8 c2 a3 p4 m7 D4 \
responsible for the early activation of the hypothal-# O% ^, l, p8 g% }- a+ p
amic pituitary gonadal axis.1-3 Thus, greater empha-
/ j! r- M, S8 e# q# A9 vsis has been given to neuroradiologic imaging in/ r3 P' J7 X7 l3 I0 B0 F, a, P
boys with precocious puberty. In addition to viril-; \/ G: m- I, p3 [6 |
ization, the clinical hallmark of CPP is the symmet-
$ s/ m9 x! |$ J* krical testicular growth secondary to stimulation by5 r( P+ M8 }/ \) w' l6 _# v E# J
gonadotropins.1,3) Y) W1 s4 r1 Q
Gonadotropin-independent peripheral preco-
' G0 K& H* ~1 [6 {+ y# Icious puberty in boys also results from inappropriate
) U( W6 [: f& B4 V! y8 v1 sandrogenic stimulation from either endogenous or/ S( L2 a) y' b5 y
exogenous sources, nonpituitary gonadotropin stim-
& O3 q+ Y$ [/ b2 ~* w- Hulation, and rare activating mutations.3 Virilizing
4 _3 T6 ~7 E& U) r/ K5 o( {congenital adrenal hyperplasia producing excessive
: B+ K2 q3 ^1 Badrenal androgens is a common cause of precocious6 ^4 Y5 }' F8 G5 Q/ ?7 Z# M9 }. D
puberty in boys.3,4, b- } |5 @6 u
The most common form of congenital adrenal
, G' N5 J: B0 \hyperplasia is the 21-hydroxylase enzyme deficiency.
& {# g+ h/ b9 N) V7 ~' xThe 11-β hydroxylase deficiency may also result in7 R' l( t' L! k6 m+ L
excessive adrenal androgen production, and rarely,
/ Z5 O1 F/ P" h# uan adrenal tumor may also cause adrenal androgen
6 w7 I; D- ^& V$ G& d4 f+ jexcess.1,3
2 \% m& d: T7 d) _2 Z9 wat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from" e7 P' n& t1 D9 H
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007$ F- ?9 L0 h) K; I0 @ R
A unique entity of male-limited gonadotropin-- o p# K+ h0 s- P9 v5 {; C6 h
independent precocious puberty, which is also known) Y; @6 Y% u/ g
as testotoxicosis, may cause precocious puberty at a
$ X8 t# ^" G6 J) Wvery young age. The physical findings in these boys/ u4 L% |! l) N/ f
with this disorder are full pubertal development,
8 I# k: k5 s7 A% b4 t9 _including bilateral testicular growth, similar to boys
6 \9 U6 j$ U/ S: Xwith CPP. The gonadotropin levels in this disorder
* ]" T7 }" ?1 x" Oare suppressed to prepubertal levels and do not show* r3 l. ]: D" I, V3 t
pubertal response of gonadotropin after gonadotropin-5 B( L$ {7 K( Z6 w; g
releasing hormone stimulation. This is a sex-linked
& O W$ @* J5 e1 c* R- o9 U# [autosomal dominant disorder that affects only- T! P) Y& }. }0 M2 d; X. o. m
males; therefore, other male members of the family* H. A3 J3 K' s! g
may have similar precocious puberty.39 c2 l7 I7 P4 r& n% F2 p M5 l8 l5 y
In our patient, physical examination was incon-
+ i9 k1 q- c% j. A/ W) I- K5 N# }sistent with true precocious puberty since his testi-/ L' q6 T3 g3 I
cles were prepubertal in size. However, testotoxicosis7 P9 L7 t& O4 `5 m+ Y1 E
was in the differential diagnosis because his father
% K b8 P+ G3 N8 I% _0 pstarted puberty somewhat early, and occasionally,' Q. Z( C5 E- V6 }
testicular enlargement is not that evident in the, I7 @! u( X% e) [- ]. o [
beginning of this process.1 In the absence of a neg-1 Z. I+ ? s( x* K6 r9 \1 |
ative initial history of androgen exposure, our- Z: b) v6 `$ e9 ?
biggest concern was virilizing adrenal hyperplasia,
Y- z: k* [5 h& Xeither 21-hydroxylase deficiency or 11-β hydroxylase
' [. d$ d _' p m( w! }1 _0 gdeficiency. Those diagnoses were excluded by find-- Q5 C0 L3 V4 {' G- B* X! }
ing the normal level of adrenal steroids.% I' m4 p3 I% J6 N5 b6 j$ {
The diagnosis of exogenous androgens was strongly& _( i$ B: U3 {
suspected in a follow-up visit after 4 months because$ s) Y: }# b! @* }6 [2 C" Z
the physical examination revealed the complete disap-
9 i# Q2 i) {6 A. r8 e8 L+ kpearance of pubic hair, normal growth velocity, and) R/ C5 p' V' O s* B
decreased erections. The father admitted using a testos-
! W8 n4 }1 S, ~$ M3 {& `1 G8 y4 Rterone gel, which he concealed at first visit. He was
9 h2 X0 S( |- w' m7 {using it rather frequently, twice a day. The Physicians’+ f9 c( P1 k3 v2 B6 v6 r
Desk Reference, or package insert of this product, gel or
A6 u$ k' A1 H" P9 D' g6 ~cream, cautions about dermal testosterone transfer to
1 \. y( ]9 Q. I6 u! g& B7 @unprotected females through direct skin exposure.
0 R1 R* g3 k1 d4 ZSerum testosterone level was found to be 2 times the9 u& |+ }+ q" k+ |+ U9 `$ v4 D. l
baseline value in those females who were exposed to
( D: r7 V' t* Seven 15 minutes of direct skin contact with their male
' E4 y$ R8 c2 h/ M$ t0 _partners.6 However, when a shirt covered the applica-4 u! t/ i' O* c8 D; \ @( Z
tion site, this testosterone transfer was prevented.* G2 ^5 u: T A7 ]( p" Q
Our patient’s testosterone level was 60 ng/mL,
; z( {2 g$ g( c. n. Pwhich was clearly high. Some studies suggest that
$ v6 S7 h7 b8 ]2 ?8 }" x" Tdermal conversion of testosterone to dihydrotestos-# H; J! H& i. e- j! }% `& t% u
terone, which is a more potent metabolite, is more) q2 S" U" b, ]
active in young children exposed to testosterone% \( [6 B* h5 `
exogenously7; however, we did not measure a dihy-
6 ?3 g' d+ V: A! s, b2 R# }( jdrotestosterone level in our patient. In addition to
4 \: a. s9 X, avirilization, exposure to exogenous testosterone in9 n5 w8 D( w+ L6 E! ?, _
children results in an increase in growth velocity and% K4 g6 y2 i! P2 M [; |
advanced bone age, as seen in our patient.
% h; b! v6 J% _" m4 [$ wThe long-term effect of androgen exposure during
8 [" |2 H9 Q; z, Q, V1 Y6 G. oearly childhood on pubertal development and final
8 k& ]; K" {; {7 Hadult height are not fully known and always remain; \; @. G/ P( @+ ] k( u
a concern. Children treated with short-term testos-
J$ R# H. K6 A/ i5 W! Fterone injection or topical androgen may exhibit some
- A( {* Z! ~% o. Pacceleration of the skeletal maturation; however, after5 y0 \# r, G- J& D) W: Z
cessation of treatment, the rate of bone maturation
% h0 u5 b$ Y$ L6 v5 j E6 ^9 @1 pdecelerates and gradually returns to normal.8,9
: R* b% u1 |: Y5 v" e2 _There are conflicting reports and controversy) B+ A% c: _. t5 K U1 k( X# X# t4 {
over the effect of early androgen exposure on adult& g* _% ^ C' r5 C, f: {1 K
penile length.10,11 Some reports suggest subnormal
/ J' E+ M- |2 @, k9 c$ @# N6 Yadult penile length, apparently because of downreg-) O. {, ~+ f. [' q
ulation of androgen receptor number.10,12 However,& y- |# I# w4 l T; {/ v' [* Y
Sutherland et al13 did not find a correlation between: B$ G# c+ i( `( u* M
childhood testosterone exposure and reduced adult
% z$ q l% T5 c. n; W5 Wpenile length in clinical studies.
4 h1 { l( O& \Nonetheless, we do not believe our patient is
/ L' K1 a2 m' A, o2 V4 Lgoing to experience any of the untoward effects from& |6 G. x" D, A; v& j
testosterone exposure as mentioned earlier because
* W0 e2 e5 Y. @8 R# x' rthe exposure was not for a prolonged period of time.
, i1 ^/ c; r5 E4 DAlthough the bone age was advanced at the time of- L& Z9 h/ c1 \; S' o0 J$ a
diagnosis, the child had a normal growth velocity at
7 n) a: W; o0 [6 Gthe follow-up visit. It is hoped that his final adult
. _$ b0 R8 r4 O- K% `height will not be affected.
/ l9 s' Q1 @- B8 I* pAlthough rarely reported, the widespread avail-
. f2 R) w$ S% dability of androgen products in our society may
2 |" i+ Y8 C% B: j+ S8 v0 s; Zindeed cause more virilization in male or female+ S" m: M+ Q% g2 U! E* D4 _( J
children than one would realize. Exposure to andro-! `& u/ B# g/ W6 G
gen products must be considered and specific ques-
! s, n" i0 d7 M X! H& rtioning about the use of a testosterone product or
5 a8 P, c* K5 C1 `5 ugel should be asked of the family members during& ~* ]1 S. j" q% Q; G( N i! K6 P" r
the evaluation of any children who present with vir-
) w. I- ?$ @( C1 Filization or peripheral precocious puberty. The diag-$ b3 E: E- A) ~# P
nosis can be established by just a few tests and by
* [! \% I' T8 x) B% _: n: l( @) K' i1 @5 Qappropriate history. The inability to obtain such a
: Q4 f2 M3 e7 a9 }/ Hhistory, or failure to ask the specific questions, may, a1 Z' P2 Q4 u; @ d- f8 p
result in extensive, unnecessary, and expensive* N' r" d2 _' O2 ], d8 i
investigation. The primary care physician should be
' {! ~( i/ }' T' daware of this fact, because most of these children8 w" g5 C+ L. O
may initially present in their practice. The Physicians’
$ d9 m2 a' ^" r) ]# \$ w3 xDesk Reference and package insert should also put a% e$ w J, M; E& m4 K* w) ^6 K8 d& v7 l
warning about the virilizing effect on a male or; U) N7 ?3 d6 P* t+ Q5 F2 N1 A
female child who might come in contact with some-
4 O k k2 n4 m& I3 none using any of these products.; w, B& `/ B7 ]
References0 e9 m0 X! J* M$ g- ^
1. Styne DM. The testes: disorder of sexual differentiation
6 ~/ H6 b0 h1 Z2 Fand puberty in the male. In: Sperling MA, ed. Pediatric
9 t. |; |# g2 v$ U( l) hEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
8 G' A0 _2 w( I! M8 z, n* d2002: 565-628.. b9 b2 f; C7 j8 I2 `" |; U
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious X* u$ i. {3 W/ F$ q; P
puberty in children with tumours of the suprasellar pineal. j; }1 Q, J" M
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from' V- w: U- s: l
Topical Testosterone Exposure / Bhowmick et al 543
7 ]0 i: T; B2 _6 pareas: organic central precocious puberty. Acta Paediatr.
# K5 u1 {5 Q' E9 Z7 Q7 O% n2001;90:751-756.
4 y8 O" \; g& {3. Lee PA. Puberty and its disorders. In: Lifshitz F, ed.1 j0 s P5 a3 l( p
Pediatric Endocrinology. 4th ed. New York, NY: Marcel
( g5 l L' \3 E9 _1 L# }6 o0 i9 nDekker Inc; 2003:211-238.
; q( d6 k4 P" m4. Yu YM, Punyasavatsu N, Elder D, D’Ercole AJ. Sexual9 h& ^5 S6 o5 p4 x
development in a two-year-old boy induced by topical
: m# c5 A& L: n3 B+ ^exposure to testosterone. Pediatrics. 1999;104:e23.
. t8 g' y% K- n0 F* K5. Greulich WW, Pyle SI, eds. Radiographic Atlas of/ B: l0 H& P9 }+ S3 c
Skeletal Development of the Hand and Wrist. 2nd ed.6 E" c2 }7 [! p
Stanford, CA: Stanford University Press; 1959.
0 f2 H3 m) {) h$ ?7 X* N. S$ e6. Physicians’ Desk Reference. Androgel 1% testosterone," a6 s" J: ?" V# o3 P: w$ u
Unimed Pharmaceutical Inc. Montvale, NJ: Medical
% J% V4 g2 o( J5 o7 |7 HEconomics Company, Inc; 2004:3239-3241.
5 g- ]8 ^; V+ J$ S7. Klugo RC, Cerny JC. Response of micropenis to topical# f1 p1 N" K" C& d' G$ Q
testosterone and gonadotropin. J Urol. 1978;119: j( Y$ t' l: e- z9 U9 [
667-668./ @5 k# z; Z/ G6 Q. |, J) L6 V! N
8. Guthrie RD, Smith DW, Graham CB. Testosterone$ ?9 }$ w: c* [
treatment for micropenis during early childhood. J Pediatr.
0 |8 y5 B T8 }8 h9 v" w1973;83:247-252.4 x) b/ a1 z0 o
9. Jacobs SC, Kaplan GW, Gittes RF. Topical testosterone
3 h8 z4 t6 u8 m4 x3 ctherapy for penile growth. Urol. 1975;6:708-710./ Z/ A3 W$ d9 [7 @8 b- a' i
10. Husmann DA, Cain MP. Microphallus: eventual phallic' M8 M! a8 ~) Q
size is dependent on the timing of androgen administra-' P9 d% A5 `4 n
tion. J Urol. 1994;152:734-739. ~6 {& T8 ^+ z( v1 n- X) m) K% K
11. McMahon DR, Kramer SA, Husmann DA. Micropenis:; N6 ~& U4 a2 y# V4 A) l
does early treatment with testosterone do more harm% k# _& _% `2 f5 _0 f
than good? J Urol. 1995;154:825-829.
9 g; b8 A$ {( q( f9 v12. Takane KK, George FW, Wilson JD. Androgen receptor
4 b) t5 a! r( L, ~1 q0 mof rat penis is down-regulated by androgen. Am J Physiol.7 y9 t$ A4 @1 J+ k/ C0 K( f5 q3 l. y
1990;258:E46-E50.* D( H3 T/ Z! D; i+ e! ]
13. Sutherland RS, Kogan BA, Baskin LS, et al. The effect" J0 G7 G6 A ?' n2 W; K2 D+ X
of prepubertal androgen exposure on adult penile' e! j! v6 \4 b$ h% k9 V( U' k, d
length. J Urol. 1996;156:783-787. |
|