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is a significant concern for physicians. Central' z( ?- i; Z7 [' C( m
precocious puberty (CPP), which is mediated) S; C4 k( {& n" \
through the hypothalamic pituitary gonadal axis, has
! R6 a( u3 D- n# |) P$ \a higher incidence of organic central nervous system0 Q$ w1 m$ f- l' V
lesions in boys.1,2 Virilization in boys, as manifested/ P; l1 a: O. {5 ?
by enlargement of the penis, development of pubic
: k. V& {# E4 |- I" G! c* |hair, and facial acne without enlargement of testi-7 j# V, n1 f* A$ l0 `8 |6 f9 N
cles, suggests peripheral or pseudopuberty.1-3 We' X. s4 F. P6 X6 ]; p" m( g
report a 16-month-old boy who presented with the
$ H$ Z; o+ r& O; ~ }enlargement of the phallus and pubic hair develop-/ D& A$ p" n( I4 L a6 U
ment without testicular enlargement, which was due
: v1 x1 d# z/ e3 gto the unintentional exposure to androgen gel used by
, X4 r1 K, A9 G6 s5 vthe father. The family initially concealed this infor-
7 y! k6 z- w2 pmation, resulting in an extensive work-up for this
) H: V/ C) o9 m1 i8 g. H `child. Given the widespread and easy availability of
) h8 J# {* x$ t3 C- T' H1 j. xtestosterone gel and cream, we believe this is proba-
& E$ j: K. |6 i2 U- |* Gbly more common than the rare case report in the
`1 O4 X- x* P* O8 Qliterature.4. h4 n- }3 p: f* U- p
Patient Report
+ E a: Q! x9 I2 L% R% sA 16-month-old white child was referred to the% y; E6 X5 S# L5 c/ S% E8 D1 a6 O8 p
endocrine clinic by his pediatrician with the concern
( j$ e$ d `& y- \2 V8 F8 e1 D5 xof early sexual development. His mother noticed
S, g, O0 O5 H' ~+ R+ Hlight colored pubic hair development when he was% o% c* j! ~" |; q5 Y
From the 1Division of Pediatric Endocrinology, 2University of' _# j8 T( @! ], J7 @7 a
South Alabama Medical Center, Mobile, Alabama. i8 f2 |. m" J* @& E% I: H4 j
Address correspondence to: Samar K. Bhowmick, MD, FACE,
1 ?# ^- {6 M6 [' B& X6 JProfessor of Pediatrics, University of South Alabama, College of( ~0 x, o/ x+ @" O" o5 x$ H- v
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;% n" t$ g5 S: d: {
e-mail: [email protected].
! @! [+ ?/ P' P. ]* Dabout 6 to 7 months old, which progressively became2 X1 C, q9 E1 z* b
darker. She was also concerned about the enlarge-; E0 \2 X" l! }8 r5 A$ @
ment of his penis and frequent erections. The child* k- r6 o. T# {, K3 q0 \' y
was the product of a full-term normal delivery, with
) P$ u+ l* B! M4 ~; V" ba birth weight of 7 lb 14 oz, and birth length of( q7 z" c% ?5 F4 H/ B4 A" L
20 inches. He was breast-fed throughout the first year; K2 [' @& F5 g1 u
of life and was still receiving breast milk along with
2 G& L g, }7 Q* M; C) I4 }solid food. He had no hospitalizations or surgery,
! r, j3 b( p0 {- hand his psychosocial and psychomotor development; d% ~2 H/ ?7 I8 I4 `/ ~1 u
was age appropriate.
7 U$ X/ F: i$ RThe family history was remarkable for the father,
& v, \' u7 u4 p2 \who was diagnosed with hypothyroidism at age 16,) u3 t) g, [; z% | C9 {- q7 \
which was treated with thyroxine. The father’s
4 Q2 X5 {7 d; _height was 6 feet, and he went through a somewhat
. `. O T( @' F3 p7 f# N5 oearly puberty and had stopped growing by age 14.9 c) P. p4 L! {# O0 N! I& Z6 O6 E9 \( ~
The father denied taking any other medication. The
% a. o3 q: |1 Z3 n/ k- |child’s mother was in good health. Her menarche
; h* G v0 M, L- o9 x4 P, Q, xwas at 11 years of age, and her height was at 5 feet) `. `2 s" n% w2 J- Q& }0 {& d
5 inches. There was no other family history of pre-; P+ q+ _2 z9 g4 L3 \, c
cocious sexual development in the first-degree rela-. H, h% u8 R! t- }! I# S5 T
tives. There were no siblings., o) K/ q# m0 W" H
Physical Examination
3 d. w, A9 K3 K) F5 F* ]The physical examination revealed a very active,
" N ?" d3 m" } `" ^/ Q% Aplayful, and healthy boy. The vital signs documented
) i$ `, r$ w) t5 M' L& ]; N* `- Ea blood pressure of 85/50 mm Hg, his length was
1 f3 O$ k; e( m# [. }" p0 p90 cm (>97th percentile), and his weight was 14.4 kg
* g( ~1 q1 h4 M$ a(also >97th percentile). The observed yearly growth6 x; t% n2 h0 w7 |" `8 z
velocity was 30 cm (12 inches). The examination of
" m6 a) S8 A! C6 D4 u) Wthe neck revealed no thyroid enlargement.- a' ^( [* F7 x% }6 t9 D
The genitourinary examination was remarkable for
) T! D& w. }* j8 O! Kenlargement of the penis, with a stretched length of
3 e5 P9 ~2 }" E" Z* R' n9 f8 cm and a width of 2 cm. The glans penis was very well
, X+ C+ w5 N& vdeveloped. The pubic hair was Tanner II, mostly around
0 f3 x+ P0 U3 N- n: G# n% [4 A540
O- h9 w1 {& y' W7 H, f6 R* o) }at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from' B- n* F8 R8 `7 v) d. R
the base of the phallus and was dark and curled. The# X N% n" M; K
testicular volume was prepubertal at 2 mL each.
X. Q( ~) F7 HThe skin was moist and smooth and somewhat* u" U2 p) k6 ]. ^) [; N* e
oily. No axillary hair was noted. There were no0 d. q# ~0 @3 z- I1 A
abnormal skin pigmentations or café-au-lait spots.
) \6 c& u$ a1 q4 K! [0 rNeurologic evaluation showed deep tendon reflex 2+6 }! w, ~5 q* O) z
bilateral and symmetrical. There was no suggestion4 U0 G9 C+ [9 J# K- t5 S/ X9 |
of papilledema.
9 v9 ^# z( E A8 \+ vLaboratory Evaluation1 i+ h2 r3 M0 o1 c! h
The bone age was consistent with 28 months by5 G: {; t! H+ \1 Y
using the standard of Greulich and Pyle at a chrono-
. J: ]: u, ^4 o& |" N4 Z2 {logic age of 16 months (advanced).5 Chromosomal5 y/ E$ P7 U. |; }+ E! s8 ?
karyotype was 46XY. The thyroid function test
. F% a: m' b4 T) h4 F( Jshowed a free T4 of 1.69 ng/dL, and thyroid stimu-, Y5 k' ^, c& k
lating hormone level was 1.3 µIU/mL (both normal).
6 S( _. d1 }5 c4 nThe concentrations of serum electrolytes, blood
/ b1 r: z9 V4 W" Iurea nitrogen, creatinine, and calcium all were5 z$ e% D6 ?! j
within normal range for his age. The concentration9 A# S4 O5 i& M; Q' E2 g
of serum 17-hydroxyprogesterone was 16 ng/dL2 ~, i) H( i; F' S9 w$ u1 W4 H
(normal, 3 to 90 ng/dL), androstenedione was 20! V) j0 e2 d0 E2 q7 S( M; N4 o1 v
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-$ l0 I. E2 `& R( ~- m
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
1 A2 f8 [$ G( ^( @1 N8 p: I Ddesoxycorticosterone was 4.3 ng/dL (normal, 7 to. s1 L& l B& D5 L9 F- S- M2 r6 `
49ng/dL), 11-desoxycortisol (specific compound S)) _( O% b5 b+ L0 V
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor- g/ E9 Y2 f+ f: e6 j/ j
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
0 ~6 T0 Q7 ^8 j5 ]3 [testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
5 S5 Q' j7 Q9 k4 C4 wand β-human chorionic gonadotropin was less than
: s, \9 D% c" z6 | |5 mIU/mL (normal <5 mIU/mL). Serum follicular% [. }& s$ H) a! y, L: i g% ]4 K: \
stimulating hormone and leuteinizing hormone
- C% j* y" h- b3 p" \concentrations were less than 0.05 mIU/mL7 w! I8 {4 f2 c& T: J: |1 k( p
(prepubertal).
& Y q% L w; Z5 s7 |. ]5 QThe parents were notified about the laboratory
% [7 a7 b; o' B! \* ^3 N, I Vresults and were informed that all of the tests were
* E( L& K" _. O! f9 a. ^. tnormal except the testosterone level was high. The
3 k: x% Q+ w! ^( d5 x! ?follow-up visit was arranged within a few weeks to
; q* @( J7 c* j7 bobtain testicular and abdominal sonograms; how-/ D9 C! g* `4 U
ever, the family did not return for 4 months., H- I* ?( c- I3 O) l" M$ z
Physical examination at this time revealed that the( Q- n* f3 V- L0 \0 l
child had grown 2.5 cm in 4 months and had gained& j, x, ~! v* T( F
2 kg of weight. Physical examination remained* o1 r7 G' Q: z" @$ o; G6 N( C
unchanged. Surprisingly, the pubic hair almost com-
& r5 {& a. V9 t5 J0 U4 }1 d! Ypletely disappeared except for a few vellous hairs at
4 V- F: {" y, U; `0 ^/ |% G$ g6 H1 X* bthe base of the phallus. Testicular volume was still 21 D: q! l7 C8 g, \# \4 W+ L/ o: c
mL, and the size of the penis remained unchanged.
" a6 b) r V3 I0 k% J8 {The mother also said that the boy was no longer hav-4 r- x8 N; J1 k7 S$ l. b. ]
ing frequent erections.
" l8 _. d, X2 [0 HBoth parents were again questioned about use of- L8 z: N7 y, x+ E! z6 a5 U
any ointment/creams that they may have applied to/ @1 j; }/ F. P, v
the child’s skin. This time the father admitted the
u4 J8 R! H. vTopical Testosterone Exposure / Bhowmick et al 541
5 R1 g9 B, U* D3 {+ ]use of testosterone gel twice daily that he was apply-
4 ]' |: f/ j5 H9 r. @ing over his own shoulders, chest, and back area for, F8 @ f/ v2 b8 F- f/ s
a year. The father also revealed he was embarrassed$ z" ]2 _1 S& {: L. ^4 j6 Y3 n
to disclose that he was using a testosterone gel pre-
4 V& \0 `( K t, X* b0 w0 Qscribed by his family physician for decreased libido0 z& U+ G& l7 Q/ N& @: d8 l
secondary to depression.
8 G/ T. [- d& }' K% D) CThe child slept in the same bed with parents.: i" e3 F9 e; M e" Y1 H# }
The father would hug the baby and hold him on his
6 n8 y1 R4 v3 O5 \$ U' u4 Vchest for a considerable period of time, causing sig-
- z7 M0 ~9 c7 g4 ?( @$ c* Dnificant bare skin contact between baby and father.+ u/ ?4 E! m8 V( t+ L& _9 h: E
The father also admitted that after the phone call,7 I; F4 R( F+ o
when he learned the testosterone level in the baby
9 f7 {* l ?+ Rwas high, he then read the product information/ z: @$ n7 G9 E' j G
packet and concluded that it was most likely the rea-
' Y+ y' i2 T8 J8 p( V* y2 X$ v+ r0 ison for the child’s virilization. At that time, they
- l( P3 M% I: Tdecided to put the baby in a separate bed, and the
3 Y/ g: j5 r' g+ h& a! n9 X' E; \3 Afather was not hugging him with bare skin and had c: g, h S# x5 \0 m5 a W( k
been using protective clothing. A repeat testosterone- ]% \3 o" N6 i: l* k
test was ordered, but the family did not go to the
& P. V# i6 `4 P" B4 Alaboratory to obtain the test.5 i; L; |2 U9 u! I
Discussion ]2 q. ~5 A3 p$ w A3 v; u
Precocious puberty in boys is defined as secondary k5 x. S" B, W1 |( K/ K
sexual development before 9 years of age.1,4
2 U! o7 M" s# j1 `7 z! PPrecocious puberty is termed as central (true) when
( s6 r1 p1 {, t3 [it is caused by the premature activation of hypo-
; J5 M1 O: q9 I% Ethalamic pituitary gonadal axis. CPP is more com-5 A5 Y( x( S8 o# n2 L7 H( M9 o
mon in girls than in boys.1,3 Most boys with CPP8 f' m6 U9 l1 b% y) r
may have a central nervous system lesion that is
# [8 k7 e( V5 O% k: ^& J( ]responsible for the early activation of the hypothal-
0 a c8 |) D# E8 A E% aamic pituitary gonadal axis.1-3 Thus, greater empha-/ E! M( T' G* ]+ Z8 b: ^. R, Y
sis has been given to neuroradiologic imaging in6 ~) n$ p( f, b# }4 X$ r; {
boys with precocious puberty. In addition to viril-5 p3 @1 }- T0 E8 _2 H5 Z
ization, the clinical hallmark of CPP is the symmet-
- j- A) [& f$ w1 f1 T* I5 t/ ]rical testicular growth secondary to stimulation by
5 J7 M0 ^: \4 {0 W* J4 t# K- Pgonadotropins.1,3
4 c5 [5 i' X: ^5 f/ F, z8 ` }Gonadotropin-independent peripheral preco-
' o( p! I" Q2 h t1 Tcious puberty in boys also results from inappropriate
$ N; E `1 i# |/ V1 Wandrogenic stimulation from either endogenous or
! E9 P7 c. c2 S1 ~+ p. Yexogenous sources, nonpituitary gonadotropin stim-
9 q$ J; |1 i5 N9 Q. I) W0 aulation, and rare activating mutations.3 Virilizing
# X4 R- |! w: o9 ^ r0 vcongenital adrenal hyperplasia producing excessive
% [7 E1 I9 D1 V: S3 O) C' Qadrenal androgens is a common cause of precocious
% g* x# s. E2 F5 C- t; V% }( [1 ^& Xpuberty in boys.3,4, V/ F; h! M. v0 K/ {& l8 ^
The most common form of congenital adrenal; e$ f8 R% R- y/ B6 r
hyperplasia is the 21-hydroxylase enzyme deficiency./ u$ A+ g, k5 ?4 ?. `
The 11-β hydroxylase deficiency may also result in* S" ^& J1 e5 F. v- F9 j. X
excessive adrenal androgen production, and rarely,; }( r; O0 K/ ]
an adrenal tumor may also cause adrenal androgen
3 E6 O! u* ^. Fexcess.1,30 Y% m) n" F/ Y3 T) q
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
: S# A: i# y( V) |$ c& z542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
; Y& u* W& F X8 E" O. cA unique entity of male-limited gonadotropin-
4 M5 F$ k* Q9 qindependent precocious puberty, which is also known
5 h2 ?5 [4 o3 }8 _/ l6 V2 A% jas testotoxicosis, may cause precocious puberty at a
5 S4 r2 ?$ n" P1 ^0 t+ s8 Wvery young age. The physical findings in these boys
% d) r' O$ J; H: j6 K" f& Nwith this disorder are full pubertal development,
! V" ]1 x& N* J# h+ c7 {. Oincluding bilateral testicular growth, similar to boys
6 p4 B5 h% B3 c( F2 ]* nwith CPP. The gonadotropin levels in this disorder- H0 [- S, f) J" r" Q( i1 @& ], \9 l; D
are suppressed to prepubertal levels and do not show
$ [% m l# P2 @5 W& Ppubertal response of gonadotropin after gonadotropin-+ F* Q! k' B) g- M" \" i( W$ |: H
releasing hormone stimulation. This is a sex-linked% B- g5 {* m# m
autosomal dominant disorder that affects only
& y9 d( l+ f/ q$ vmales; therefore, other male members of the family( A$ C( P8 N/ d2 n3 V8 j
may have similar precocious puberty.38 |% ^" P/ e% t, E
In our patient, physical examination was incon-
2 Y9 v. m7 c! E/ ]. O( _1 K5 Lsistent with true precocious puberty since his testi-0 ]$ W* `8 g7 H7 z4 i' F$ z
cles were prepubertal in size. However, testotoxicosis) \$ n- P) r u8 T3 X6 J
was in the differential diagnosis because his father7 U! C0 [. \7 _4 l! v
started puberty somewhat early, and occasionally,
, ~; r8 R5 q& ~6 Utesticular enlargement is not that evident in the
" h0 F0 Y, o4 V& Q, Mbeginning of this process.1 In the absence of a neg-6 o# D8 |) P8 {* r/ d( E. P
ative initial history of androgen exposure, our. g& V" V6 E: v6 U3 @
biggest concern was virilizing adrenal hyperplasia, D, O' G( ]6 j" F/ Y. b. s5 ]
either 21-hydroxylase deficiency or 11-β hydroxylase
+ Q5 p( o7 C$ X% n4 }/ ]9 Ydeficiency. Those diagnoses were excluded by find-
" H# `- o W) c( G: [ing the normal level of adrenal steroids.
0 ^+ b v! K: C7 g5 q1 Z' ~* E8 ?The diagnosis of exogenous androgens was strongly
% {7 q7 L3 L, d, _7 d; bsuspected in a follow-up visit after 4 months because7 Y$ ^5 J6 N7 G! t6 h; r7 p! O
the physical examination revealed the complete disap-
: l, k3 w u$ i+ Mpearance of pubic hair, normal growth velocity, and$ p" C+ [2 G: P
decreased erections. The father admitted using a testos-
4 x( j5 Y$ z$ yterone gel, which he concealed at first visit. He was
0 P; [ O4 ]7 C' {. R: Wusing it rather frequently, twice a day. The Physicians’6 }0 e) G6 y2 Q$ G( S
Desk Reference, or package insert of this product, gel or! D3 o( m2 _9 i: ~% U4 E. A
cream, cautions about dermal testosterone transfer to
" `) Y }1 o, B/ ?! X5 J1 E8 k% Hunprotected females through direct skin exposure.
. q( m2 J/ `! L6 W; HSerum testosterone level was found to be 2 times the/ x1 Q- N4 r/ a
baseline value in those females who were exposed to
1 B0 b6 u% u+ f$ Heven 15 minutes of direct skin contact with their male, X/ ^7 N1 s9 G8 s- T: s
partners.6 However, when a shirt covered the applica-3 a7 b2 T+ C( t$ ~
tion site, this testosterone transfer was prevented." z7 m( t6 \! |- t% q8 `& N
Our patient’s testosterone level was 60 ng/mL,9 I( a8 x- w8 e' g" M X
which was clearly high. Some studies suggest that; T$ x1 \/ v/ Y' h- U
dermal conversion of testosterone to dihydrotestos-; c0 J, A* }( e
terone, which is a more potent metabolite, is more. S' v; b, R: E; z. W. o
active in young children exposed to testosterone
, [3 d2 }4 h4 o4 j! Cexogenously7; however, we did not measure a dihy-' {: h; h4 O7 R6 }& L
drotestosterone level in our patient. In addition to0 Q" K7 H; W- L" Q& `
virilization, exposure to exogenous testosterone in* v% ?- r- x6 }2 [" E! p
children results in an increase in growth velocity and0 {1 n. [! x" T( M$ J
advanced bone age, as seen in our patient.2 ?1 d9 Q9 k6 f+ T& f5 R6 m
The long-term effect of androgen exposure during% Y8 I" [5 z% Z8 w+ v9 d% q& k# x
early childhood on pubertal development and final
- v7 S' `/ V7 v8 `3 b1 Oadult height are not fully known and always remain( U' f8 r6 Z+ [4 j* {& {! I
a concern. Children treated with short-term testos-
2 O: p( m' ^/ i+ R2 f& a$ z& m- rterone injection or topical androgen may exhibit some
. j# s7 P# ]/ q, U' y* pacceleration of the skeletal maturation; however, after- [) m* b3 @" r/ n3 o, w% p+ ?
cessation of treatment, the rate of bone maturation3 [: L3 ^" Z' e# {1 H( N" [1 ^( g
decelerates and gradually returns to normal.8,9
: T; [% i( g; ?/ sThere are conflicting reports and controversy. o% Y4 q- ?2 G( h. @5 c4 c. j
over the effect of early androgen exposure on adult
7 `1 I0 _5 v/ k, f+ J" i& kpenile length.10,11 Some reports suggest subnormal
! r# ~9 r% }1 U7 W: l+ Kadult penile length, apparently because of downreg-" p2 A/ s$ M7 B5 t
ulation of androgen receptor number.10,12 However,
; a" T- m. v! jSutherland et al13 did not find a correlation between
# i7 R+ Z' o0 V0 `# g. bchildhood testosterone exposure and reduced adult& ^4 z. N! Y2 `8 q0 k
penile length in clinical studies.0 W; v R l- M5 {# h
Nonetheless, we do not believe our patient is7 r! h2 o0 w& Q' L$ O K
going to experience any of the untoward effects from* y1 t; u: m4 J6 X! d: N5 t& ^
testosterone exposure as mentioned earlier because
: ~7 x: n8 ~" A- ?the exposure was not for a prolonged period of time.. b3 F9 \: a" U7 @
Although the bone age was advanced at the time of
1 R j; [3 g; z8 O3 G1 Tdiagnosis, the child had a normal growth velocity at
( X1 h& }# \$ Y6 lthe follow-up visit. It is hoped that his final adult
# e e4 w. a. J G2 n- l$ k1 d; vheight will not be affected.2 t3 C; o( q B* v+ J2 d6 J' I
Although rarely reported, the widespread avail-
- r1 ?7 n9 i+ T: Mability of androgen products in our society may
& P5 |1 F1 Z: z+ `% `6 f; Vindeed cause more virilization in male or female; K, r R4 a3 B1 Y9 j: J
children than one would realize. Exposure to andro-0 m, a# g1 c, f0 h U3 d T, M Y) C
gen products must be considered and specific ques-1 U/ h/ ~3 A( F4 V8 E0 Q) L
tioning about the use of a testosterone product or" H) l5 z% L( b. N
gel should be asked of the family members during
5 k( ?& g! @5 f: uthe evaluation of any children who present with vir-
" t' w" x2 {0 v# k" Z6 Xilization or peripheral precocious puberty. The diag-
" e* g5 R) ^2 R$ h+ D9 E# Dnosis can be established by just a few tests and by, P3 X7 [3 z X9 B
appropriate history. The inability to obtain such a
# B+ w" v7 J0 y7 d! B" Hhistory, or failure to ask the specific questions, may/ ?7 ^% \8 w' ^' {' Q: p
result in extensive, unnecessary, and expensive
' {1 v J" P2 J$ A8 e7 X7 ~8 uinvestigation. The primary care physician should be
8 |0 ~4 d' `# h# L2 a1 G& \aware of this fact, because most of these children
& J( j. C) q* b2 E! ^may initially present in their practice. The Physicians’+ r1 Z+ `3 T w# E- C, D* T/ X8 @
Desk Reference and package insert should also put a) x, b$ ]: Q: p9 J2 T% ^
warning about the virilizing effect on a male or
8 q- b. k9 A$ ?% \7 G% Hfemale child who might come in contact with some-
1 }# a( h& l2 o# h L2 J M. _one using any of these products.
1 k9 i/ U1 [1 N) k$ Z* dReferences/ E$ V4 ]% \/ t" x6 @' m
1. Styne DM. The testes: disorder of sexual differentiation# |( {2 p0 A4 }2 j4 d
and puberty in the male. In: Sperling MA, ed. Pediatric
# c0 ?6 Q- T" [Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;1 r9 T |7 f- [
2002: 565-628.8 J% M1 W7 Z' U" o/ W* k: L) D3 O
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious& B8 {+ D& z6 `/ M3 B0 f
puberty in children with tumours of the suprasellar pineal
7 X/ I: z! x3 p0 e1 D1 ?7 Rat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
( T* P$ j% g( P+ WTopical Testosterone Exposure / Bhowmick et al 543% n, Z5 [3 |8 g
areas: organic central precocious puberty. Acta Paediatr.
9 V, [) ^) y* W, j s1 X, G) z7 f. @2001;90:751-756.: T- s. B0 U$ m/ p& A" t
3. Lee PA. Puberty and its disorders. In: Lifshitz F, ed.( z' Q# [" v- t4 M& V
Pediatric Endocrinology. 4th ed. New York, NY: Marcel. U" H X: J7 z; F8 a
Dekker Inc; 2003:211-238.
5 h3 e V( |8 ~3 a7 S7 }4. Yu YM, Punyasavatsu N, Elder D, D’Ercole AJ. Sexual( Q9 r, g8 y* g. W# `# |
development in a two-year-old boy induced by topical
?. @& a- h: t9 Qexposure to testosterone. Pediatrics. 1999;104:e23.
: F! l1 {( L' ]" w# p9 U5. Greulich WW, Pyle SI, eds. Radiographic Atlas of" e7 x3 J6 Y: y7 ^8 q& t5 b
Skeletal Development of the Hand and Wrist. 2nd ed.3 r4 C; l6 ?8 U3 a! k# S
Stanford, CA: Stanford University Press; 1959.
% C0 g6 o0 G% D6. Physicians’ Desk Reference. Androgel 1% testosterone, F$ V1 y7 w- h5 ~
Unimed Pharmaceutical Inc. Montvale, NJ: Medical) _% j6 B/ \* s( c7 @/ X* `
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