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is a significant concern for physicians. Central
0 \" h% c2 a5 \$ a+ [- Y) o% s4 ]# a Qprecocious puberty (CPP), which is mediated
2 {+ J: \1 [7 g+ [5 P4 d9 Tthrough the hypothalamic pituitary gonadal axis, has9 K% P1 O; m% E" ]. R# P* z! N
a higher incidence of organic central nervous system
$ V2 G& L J0 T+ ?lesions in boys.1,2 Virilization in boys, as manifested- z$ ?3 ^! r/ U! B u
by enlargement of the penis, development of pubic
" A! p# Y; A6 F, Z8 D2 _- H$ y1 X# ghair, and facial acne without enlargement of testi-$ Q3 C. U% E% @
cles, suggests peripheral or pseudopuberty.1-3 We" c& M2 Q9 r) ]" `6 L5 _
report a 16-month-old boy who presented with the: t7 f# w f- ?( u: k9 _
enlargement of the phallus and pubic hair develop-# f' b/ d$ m+ M! E4 e8 k. O
ment without testicular enlargement, which was due
2 w- }6 k% M2 S, T; Y! ito the unintentional exposure to androgen gel used by
9 d+ C c* I$ w( K9 {% u/ A, E5 ?3 rthe father. The family initially concealed this infor-
$ V n) X7 ^0 U3 w7 Smation, resulting in an extensive work-up for this) V% S* U$ a; }0 g
child. Given the widespread and easy availability of( d5 u3 c2 z3 w5 d" K( o
testosterone gel and cream, we believe this is proba-
: W5 r1 N0 g3 u- O( j) Lbly more common than the rare case report in the- A7 x6 B( G0 A4 w4 y* C
literature.4
l* A/ l" y0 _Patient Report
8 p0 ?2 }/ s% zA 16-month-old white child was referred to the
4 [# ]: v2 V* w0 b" Q; o9 c; ]endocrine clinic by his pediatrician with the concern
! f8 z" [3 p/ r. K: kof early sexual development. His mother noticed. j2 K- Q* {7 V" {& H2 j/ {% O
light colored pubic hair development when he was
5 X/ s. P" w6 g* {! M8 k" V6 tFrom the 1Division of Pediatric Endocrinology, 2University of
4 Z3 V A5 Y/ A. d9 \2 d, D5 ?South Alabama Medical Center, Mobile, Alabama., ^; ^' Y& E3 z
Address correspondence to: Samar K. Bhowmick, MD, FACE,# n; C; b/ i; G/ J: s
Professor of Pediatrics, University of South Alabama, College of
+ z: J& ?& a9 ]Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;" c' z E& a/ C5 }% D( f
e-mail: [email protected].
& c$ |6 p9 J( _7 E( f) oabout 6 to 7 months old, which progressively became/ O. w! M8 K: F7 h
darker. She was also concerned about the enlarge-
+ d `- C' L% G; bment of his penis and frequent erections. The child
2 h% T( J& P5 dwas the product of a full-term normal delivery, with) V! G9 Q0 u9 l5 |, t. `: I
a birth weight of 7 lb 14 oz, and birth length of
5 A) M/ }! K5 H5 W: F20 inches. He was breast-fed throughout the first year `; q* t+ T$ T- I# r0 E D* }
of life and was still receiving breast milk along with
: h9 Y# Z8 g: f$ S+ _" h* msolid food. He had no hospitalizations or surgery,2 O" v7 W. _9 s: j r) Q
and his psychosocial and psychomotor development" O$ t: ~' G& P4 K% X( T
was age appropriate.7 p6 f+ @" F, e% W8 _0 u
The family history was remarkable for the father,) X3 n7 W2 y5 I2 N- B' _& T; N! A
who was diagnosed with hypothyroidism at age 16,
5 _, T0 [7 T swhich was treated with thyroxine. The father’s/ E: X; l! ~, u9 q/ n9 Q: s X; k s
height was 6 feet, and he went through a somewhat) o4 j0 B( Q+ }2 Z9 y# l
early puberty and had stopped growing by age 14." S" ]; _# L: l0 [) j* g/ A/ \
The father denied taking any other medication. The h& y& [% C& Z) U5 \
child’s mother was in good health. Her menarche8 r( n# y& B( u) H& Y0 c
was at 11 years of age, and her height was at 5 feet
1 i8 P) V) T9 ~3 ?5 inches. There was no other family history of pre-2 F) \/ {2 _$ g0 n9 ]
cocious sexual development in the first-degree rela-* L. |+ a$ a1 T
tives. There were no siblings.3 y( z8 }, c0 G8 ?$ f) Z& }
Physical Examination
/ \ }$ n" b3 hThe physical examination revealed a very active,' r5 P# w' K3 ?8 H9 c: Y
playful, and healthy boy. The vital signs documented8 q- b1 F" g# |6 {$ s( Z/ D$ C& @
a blood pressure of 85/50 mm Hg, his length was" ^( y {1 w+ m8 m1 A5 B
90 cm (>97th percentile), and his weight was 14.4 kg0 a$ [4 o( ?' ?: N {: K' I( d) [! F
(also >97th percentile). The observed yearly growth% \# L& t% m0 Z# o+ @" h$ _3 h
velocity was 30 cm (12 inches). The examination of
6 ?* s& q8 \0 ^& \9 f, {! \% W3 E8 dthe neck revealed no thyroid enlargement.- S! [6 L: A% K1 A% C0 b
The genitourinary examination was remarkable for
/ `+ H0 c/ h7 r3 cenlargement of the penis, with a stretched length of
8 d8 a: M. N8 S' Q8 H+ Q8 cm and a width of 2 cm. The glans penis was very well% D: V1 w& G. ?8 `- [( U& E
developed. The pubic hair was Tanner II, mostly around
( ?( K6 w: G: {540
3 r4 `; d9 v: a% Z1 ?at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from3 } n5 S/ R+ \5 C$ e
the base of the phallus and was dark and curled. The
9 _8 G! `2 B) z' }testicular volume was prepubertal at 2 mL each.+ m0 k8 p" c5 S5 @5 U
The skin was moist and smooth and somewhat; j& v O! G. J( i+ U: c; e
oily. No axillary hair was noted. There were no7 r& R0 B" g* R" q' u
abnormal skin pigmentations or café-au-lait spots.
& P# G" \/ |3 ]6 PNeurologic evaluation showed deep tendon reflex 2+& Z8 @- F; B' J* C, F7 P
bilateral and symmetrical. There was no suggestion
, o$ K5 h. Q4 y9 _" L' Dof papilledema.
. v! u z/ {# f: c' \9 ULaboratory Evaluation
; }( Q0 o* z- \" N5 |The bone age was consistent with 28 months by: ^% ]8 t& t" ]* j* Z& e& T8 y
using the standard of Greulich and Pyle at a chrono-$ [! l( R; w# l! e) L* Y$ f
logic age of 16 months (advanced).5 Chromosomal
* f2 b) M7 P% P5 c) ekaryotype was 46XY. The thyroid function test
7 p2 T: K& @( }showed a free T4 of 1.69 ng/dL, and thyroid stimu-$ I+ H5 {. M) ^# ]2 F$ n4 l+ l
lating hormone level was 1.3 µIU/mL (both normal).
7 u9 H* I/ l; WThe concentrations of serum electrolytes, blood; d* L- _9 z: d% R8 y0 n
urea nitrogen, creatinine, and calcium all were
7 X5 O' W/ h4 A) F* n! x n+ Pwithin normal range for his age. The concentration* w1 x% }, d( f
of serum 17-hydroxyprogesterone was 16 ng/dL; K: v* {+ j4 s; c! b; u. J
(normal, 3 to 90 ng/dL), androstenedione was 207 I/ r% r1 h, I
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
$ @, e- H6 y5 Qterone was 38 ng/dL (normal, 50 to 760 ng/dL),2 N( p0 [3 h4 J8 e5 W# [
desoxycorticosterone was 4.3 ng/dL (normal, 7 to# G2 r/ `/ b0 b$ T3 d0 t
49ng/dL), 11-desoxycortisol (specific compound S)/ k n v# ~/ S1 d
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-, c1 m3 }- k" j% w
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
0 d6 o* B; e; d, Y) V$ W) Btestosterone was 60 ng/dL (normal <3 to 10 ng/dL),, q2 N+ P. n& Q0 ]: T; |/ ]$ @
and β-human chorionic gonadotropin was less than
3 E' Y( T5 ]5 f/ P4 D) ]: @( G5 mIU/mL (normal <5 mIU/mL). Serum follicular3 q8 @$ f: {4 y% T# K" L( e) ~
stimulating hormone and leuteinizing hormone; b/ e$ K3 ? }5 U7 U- [8 _. G
concentrations were less than 0.05 mIU/mL" ?" p# i/ V$ G7 E- ~8 M" ~
(prepubertal).4 s, n$ [. ~$ X
The parents were notified about the laboratory% P @9 v' H/ D$ x3 r
results and were informed that all of the tests were
" X$ [' L6 ^' L3 v h: {( n7 Snormal except the testosterone level was high. The; o- o, W# Q2 R9 w, J8 o# U! \
follow-up visit was arranged within a few weeks to3 o6 s f( P/ D2 O, E
obtain testicular and abdominal sonograms; how-. h7 d. @5 ?# i7 Z( f0 g, d
ever, the family did not return for 4 months.
: a+ J( _$ E+ F4 i2 z% FPhysical examination at this time revealed that the7 a+ v$ g: P' F+ _/ w
child had grown 2.5 cm in 4 months and had gained E- [) W* c8 Z' Q
2 kg of weight. Physical examination remained8 k* Q4 P0 l8 |9 K7 P, B; P
unchanged. Surprisingly, the pubic hair almost com-: T: \: c. E3 H. t; j' x: Z1 d
pletely disappeared except for a few vellous hairs at, k u7 R& J2 a/ q. m3 P; I
the base of the phallus. Testicular volume was still 2
1 d, w* I8 F3 tmL, and the size of the penis remained unchanged.
8 ?) r" e V5 Q4 S$ rThe mother also said that the boy was no longer hav-3 v8 }" m3 z6 _7 a
ing frequent erections.
' p t1 u# X4 P2 n. `, FBoth parents were again questioned about use of
, j$ e; k, Y. U! K0 {' gany ointment/creams that they may have applied to
& H: Z; z# R" ^& ?) T6 |the child’s skin. This time the father admitted the& v9 K5 m5 K# i& o9 @
Topical Testosterone Exposure / Bhowmick et al 541
2 ?) k: G: ~: Ruse of testosterone gel twice daily that he was apply-
0 {! T- R7 _% N n& V6 U) v2 G# king over his own shoulders, chest, and back area for
) u+ l9 s& [0 q; I, Fa year. The father also revealed he was embarrassed7 j4 q5 Z; D& ]( y+ y
to disclose that he was using a testosterone gel pre-) u6 D0 F ?% k7 B! o: T, n
scribed by his family physician for decreased libido
+ w% i* Z' W0 h$ v3 Ssecondary to depression.
+ H$ C9 y. U0 i" P5 t0 G' B. QThe child slept in the same bed with parents.
) O4 { D8 W$ n; [8 y' U. s1 FThe father would hug the baby and hold him on his
' v! c- u( Q8 V; q2 \& zchest for a considerable period of time, causing sig-+ o* x2 h5 x5 u7 i
nificant bare skin contact between baby and father., G" x7 E! U9 m( `
The father also admitted that after the phone call,
1 P f0 i' S6 s7 R. W8 R( |5 {when he learned the testosterone level in the baby' K3 O }" U6 @2 g
was high, he then read the product information0 C8 Y2 Y$ d3 @
packet and concluded that it was most likely the rea-) J1 K* n5 [: ]: `' y4 t$ s$ S! |
son for the child’s virilization. At that time, they* D( O E! b9 `$ _8 f+ V. i
decided to put the baby in a separate bed, and the$ `: A7 {+ M; u! H
father was not hugging him with bare skin and had+ I( k5 d+ C, ]; m8 R! Y
been using protective clothing. A repeat testosterone+ Z" T! e- s/ G Q j9 e
test was ordered, but the family did not go to the* W& V1 o8 g+ B
laboratory to obtain the test.4 v9 R! ^2 n! L( h2 S. E
Discussion0 O5 d$ G2 N. U b
Precocious puberty in boys is defined as secondary& R$ X; r# @3 x3 Y, Z1 l4 ~" w, b4 `
sexual development before 9 years of age.1,49 v9 a- j0 _: n8 j5 ?( K/ [7 O
Precocious puberty is termed as central (true) when2 f: z2 m3 d$ r4 u W* _1 J' F, Q
it is caused by the premature activation of hypo-
2 X( K8 k x/ h2 F' Fthalamic pituitary gonadal axis. CPP is more com-
; k9 Q6 l* a3 _% j4 z2 x" i) hmon in girls than in boys.1,3 Most boys with CPP6 _- O$ S, M9 N3 t
may have a central nervous system lesion that is
' v( B. M8 g8 ]8 G2 W7 d" hresponsible for the early activation of the hypothal-8 P+ ?5 N% l" n( p( d, H
amic pituitary gonadal axis.1-3 Thus, greater empha-4 a5 P2 r% {' r& N S7 m
sis has been given to neuroradiologic imaging in
" v. U) H) A. B* g+ s$ L! oboys with precocious puberty. In addition to viril-
+ M L9 i' w- @0 V' V& P1 C8 i. F0 zization, the clinical hallmark of CPP is the symmet-
# S3 d F* ]3 ]rical testicular growth secondary to stimulation by
5 n. E1 X( h) v# P0 x2 J: o' mgonadotropins.1,3
% X$ i" [) O- n' `* [3 Q& eGonadotropin-independent peripheral preco-% S& D* o4 \8 Y
cious puberty in boys also results from inappropriate
! q' p, C; [7 J+ sandrogenic stimulation from either endogenous or
2 H4 I% N9 N D! f) B6 J0 cexogenous sources, nonpituitary gonadotropin stim-& M5 N9 d) }8 q6 _6 l
ulation, and rare activating mutations.3 Virilizing. l1 i$ x$ K5 @' \& @# _! }
congenital adrenal hyperplasia producing excessive
- {* Z4 T& @' b& Y8 v8 oadrenal androgens is a common cause of precocious
+ Y& @, J- e8 o1 `; R2 ~; O% E( y/ Qpuberty in boys.3,4
, P! f1 P1 z8 B% q' ], A- U$ ^- [The most common form of congenital adrenal9 {3 ~$ q6 ?' l0 s
hyperplasia is the 21-hydroxylase enzyme deficiency.
! [ x B! o9 P' Y3 M }% b5 _) r# @; l6 [The 11-β hydroxylase deficiency may also result in
4 s8 n7 `. n b }, Pexcessive adrenal androgen production, and rarely,2 Y4 L. _4 f" p+ Y! N6 W; T
an adrenal tumor may also cause adrenal androgen$ ~* `: U8 m6 T; |8 Z
excess.1,3
% y* p$ e% c5 H) a7 W# i( ^at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from6 j- Q& l h+ v& H8 H: {
542 Clinical Pediatrics / Vol. 46, No. 6, July 20073 t' A0 O" r% y8 j, x
A unique entity of male-limited gonadotropin-
3 n& L) R' {* G: n1 _independent precocious puberty, which is also known
9 ?7 ~1 |5 Z5 Z ]0 Z* n d! i2 Uas testotoxicosis, may cause precocious puberty at a* ?% Q5 g5 Z x) v( a
very young age. The physical findings in these boys( M' `+ V. i5 R$ }6 J
with this disorder are full pubertal development,
0 p5 r0 a9 A' r+ O1 ]# x" i5 c7 O, Xincluding bilateral testicular growth, similar to boys2 ]+ ?- e$ M3 D- \- _, Y4 A/ w8 r
with CPP. The gonadotropin levels in this disorder
* C0 ] X0 Y/ `are suppressed to prepubertal levels and do not show
- F6 E) m9 ^7 x) z7 y: qpubertal response of gonadotropin after gonadotropin-/ H; ~$ D4 I) B6 U
releasing hormone stimulation. This is a sex-linked
6 ~! {% \2 |1 v; y& I/ ?6 V* Qautosomal dominant disorder that affects only
; _6 D' C$ b8 g. C/ ~males; therefore, other male members of the family7 l) ~" `3 e$ m3 d3 F& |& R
may have similar precocious puberty.39 n2 a2 f: A" G Y1 r
In our patient, physical examination was incon-- s7 f' V9 q) f9 ` {5 V
sistent with true precocious puberty since his testi-1 T; Z1 d' e) Q
cles were prepubertal in size. However, testotoxicosis+ S9 ~/ e* \ l# f, _0 _. A# @
was in the differential diagnosis because his father
4 d) G, c/ ~9 L! C: l8 x+ jstarted puberty somewhat early, and occasionally,3 h: |# [; U |
testicular enlargement is not that evident in the, N6 M4 E5 X3 `1 V/ ~
beginning of this process.1 In the absence of a neg-) b4 B3 n1 y p0 a; [5 y
ative initial history of androgen exposure, our
- X# j, l2 d$ p, Z7 _: gbiggest concern was virilizing adrenal hyperplasia,) K) h, w; k) B
either 21-hydroxylase deficiency or 11-β hydroxylase$ F, o) t7 f, _* O+ t
deficiency. Those diagnoses were excluded by find-
$ C- m2 c% d8 C& n) f, ]' aing the normal level of adrenal steroids.
3 y* ~5 T( R0 y) rThe diagnosis of exogenous androgens was strongly- w4 F$ W. [8 V% h
suspected in a follow-up visit after 4 months because3 M1 T/ ~ E# S4 W
the physical examination revealed the complete disap-
' m& _6 |. i% H$ i8 | g8 C! S8 c/ Mpearance of pubic hair, normal growth velocity, and6 ]. E# f4 y" _' k: c
decreased erections. The father admitted using a testos-
4 A$ Y Q/ o) e3 ~, T; M& Z# Yterone gel, which he concealed at first visit. He was
. W, }4 g4 c6 M$ y9 `using it rather frequently, twice a day. The Physicians’
2 q8 `' h. q4 y9 p. G L, T- wDesk Reference, or package insert of this product, gel or% b( U6 ]9 n- Y1 q9 R
cream, cautions about dermal testosterone transfer to/ s N/ R( v" x6 o _+ f
unprotected females through direct skin exposure.8 Z n& F" r5 F1 C5 r0 |
Serum testosterone level was found to be 2 times the
9 @ h4 C( e- {, i f; nbaseline value in those females who were exposed to
* e4 k3 X2 i; j" D' L5 t5 B. peven 15 minutes of direct skin contact with their male; N0 m% v8 Z/ P8 x: |
partners.6 However, when a shirt covered the applica-
0 r8 M, d4 x+ [3 Dtion site, this testosterone transfer was prevented./ A! y+ S% w( Q2 v1 [. b# i
Our patient’s testosterone level was 60 ng/mL,& t, Z- E5 _ E7 T8 Z
which was clearly high. Some studies suggest that
. ~6 H2 C% Z4 b+ i+ cdermal conversion of testosterone to dihydrotestos-
: J0 g: r: z* [' J* v2 ^terone, which is a more potent metabolite, is more
1 Q) n! C8 ~! }. v- u9 Y2 }active in young children exposed to testosterone: d# r8 ]( V8 k1 J0 x, V
exogenously7; however, we did not measure a dihy-7 [* I( Z9 r. f. A- A1 O
drotestosterone level in our patient. In addition to
' J- k# l+ c" j& a0 U$ u) Yvirilization, exposure to exogenous testosterone in
; ~, b$ [! @3 m$ rchildren results in an increase in growth velocity and
1 w2 U5 u }& J badvanced bone age, as seen in our patient.1 K# q3 `2 }9 T9 M+ C# S0 L4 c0 w
The long-term effect of androgen exposure during
7 E, B& J1 k/ {: p* R/ F1 `: D$ l8 Searly childhood on pubertal development and final# k8 L( t5 M( B3 H( E' x& I+ F* u
adult height are not fully known and always remain# ^0 E/ a7 j$ E! o' C0 ]' Y
a concern. Children treated with short-term testos-
: C1 R; p0 L! I- s1 `2 ]+ rterone injection or topical androgen may exhibit some2 c6 j$ V' ^5 R% S$ a0 Q* h
acceleration of the skeletal maturation; however, after
- E2 R# a% o7 V; j+ c" Rcessation of treatment, the rate of bone maturation
# G% T3 Y( f( F2 D* w5 fdecelerates and gradually returns to normal.8,9
: J0 s2 ]( P/ D; A* r8 v; vThere are conflicting reports and controversy
, d8 S$ U# b$ Q% p( L6 M. gover the effect of early androgen exposure on adult
7 ?3 v4 J; c2 P2 _0 `penile length.10,11 Some reports suggest subnormal
! z' ]* @& W' q7 ?6 O* [adult penile length, apparently because of downreg-- _/ r0 x: }6 e& T$ |& W' `
ulation of androgen receptor number.10,12 However,
. J8 u5 f# Y3 U6 @& R, fSutherland et al13 did not find a correlation between+ e* o% P3 K- S- W+ `; o
childhood testosterone exposure and reduced adult$ J6 J7 o* ?8 V
penile length in clinical studies.
; O2 s; M$ l7 K, K7 o. ~8 cNonetheless, we do not believe our patient is5 ?7 t v5 ]9 ]" g G. }; v; e
going to experience any of the untoward effects from
, x( a. G) k- i. [8 d" K* Ktestosterone exposure as mentioned earlier because
0 n, T+ U% m9 P" I3 @/ C9 i6 J! V* Ethe exposure was not for a prolonged period of time.
' n. ?$ \$ N% I6 hAlthough the bone age was advanced at the time of$ s; D0 {* ^( F4 \; ]$ i- \
diagnosis, the child had a normal growth velocity at! \$ C# u. b7 Z) y+ m; H% q W3 J
the follow-up visit. It is hoped that his final adult
. U3 H' G% Y% Cheight will not be affected.
5 B( S! G/ k9 g8 \8 nAlthough rarely reported, the widespread avail-
' H# `* U i; y7 L: `, kability of androgen products in our society may& ?% n$ c" n6 g/ O9 f. t
indeed cause more virilization in male or female
- k( j& t1 ]; Z0 }$ a8 ychildren than one would realize. Exposure to andro-) w5 p ]1 p) R W Z* q
gen products must be considered and specific ques- Q. e( Q6 B2 _( C6 G( t& q
tioning about the use of a testosterone product or
. _0 W) E6 N; c" K! W: Rgel should be asked of the family members during
C# z' v7 d |6 uthe evaluation of any children who present with vir-3 K9 R2 }. d; i5 {$ q* X# e
ilization or peripheral precocious puberty. The diag-
! T' F; c ^0 l6 ^8 J1 E0 T( Xnosis can be established by just a few tests and by# F4 s; N; D) |
appropriate history. The inability to obtain such a
2 T& ~8 E# P. Jhistory, or failure to ask the specific questions, may
. ]% z) p4 L8 b0 P& u7 lresult in extensive, unnecessary, and expensive
' v8 r1 E* V# y4 ?7 w( t! ~investigation. The primary care physician should be# J7 e8 {; M5 Y0 z
aware of this fact, because most of these children: n% k- r4 J4 I, K
may initially present in their practice. The Physicians’2 p+ Q2 v; m6 T3 f" M, s3 g8 l6 B
Desk Reference and package insert should also put a
w5 m- w' \4 Y) f; U: Zwarning about the virilizing effect on a male or& z# e# ~6 C5 K7 x1 x+ W* i# T
female child who might come in contact with some-' ?, n6 }) v0 m5 v+ ~' m$ ~6 n
one using any of these products.
K3 J% [; ^" z ZReferences5 Z' r$ I9 u3 C, H
1. Styne DM. The testes: disorder of sexual differentiation
' e. Q3 r2 Y9 |and puberty in the male. In: Sperling MA, ed. Pediatric1 A5 o6 p; s' o
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
2 y8 O$ w; `2 N1 K* }2002: 565-628.
* V; ~) I/ B+ q U2 w6 g2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious6 w' {9 b) F* T# v; n! e
puberty in children with tumours of the suprasellar pineal' q. J+ p$ y; E6 r, P. E
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
! ]& S% d( L0 }. E9 hTopical Testosterone Exposure / Bhowmick et al 543
$ I: n; u$ R, b# {; E5 X1 mareas: organic central precocious puberty. Acta Paediatr.
5 ?) Y* p5 A/ M" D% Q. {3 l0 R2001;90:751-756.6 F3 Y. O, b D+ ~% v/ \5 u( _
3. Lee PA. Puberty and its disorders. In: Lifshitz F, ed.* r1 x0 Q" z7 C
Pediatric Endocrinology. 4th ed. New York, NY: Marcel
# i! H/ U" A9 S% K5 @$ N9 yDekker Inc; 2003:211-238.
. z+ v9 [ C1 S1 b4. Yu YM, Punyasavatsu N, Elder D, D’Ercole AJ. Sexual
% E" \/ u2 t; m( {; }5 @development in a two-year-old boy induced by topical
1 G) D, _; X- K$ Sexposure to testosterone. Pediatrics. 1999;104:e23.1 ]8 K5 W, O$ l6 b' g
5. Greulich WW, Pyle SI, eds. Radiographic Atlas of. C) O1 c N& M1 o; P. o9 w6 j% z
Skeletal Development of the Hand and Wrist. 2nd ed.- N8 S+ h9 V' E) M: H+ w
Stanford, CA: Stanford University Press; 1959.
3 t9 M3 r( g( _6 G- z6. Physicians’ Desk Reference. Androgel 1% testosterone,
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