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is a significant concern for physicians. Central
1 C; [' n; q* h0 l; Vprecocious puberty (CPP), which is mediated4 M1 ]% g+ x2 z/ b3 H. Q/ y
through the hypothalamic pituitary gonadal axis, has9 V: G+ O, c7 ~5 r
a higher incidence of organic central nervous system
6 V6 u/ t4 p" G P: S7 }lesions in boys.1,2 Virilization in boys, as manifested( z3 W/ C. _' P; D; l/ m$ R1 V
by enlargement of the penis, development of pubic9 D$ `* }+ l8 C- d3 A" {2 X' S2 H
hair, and facial acne without enlargement of testi-
# B( V. y- Q5 F% H* Ocles, suggests peripheral or pseudopuberty.1-3 We4 B/ D8 `$ L: T _( |$ D
report a 16-month-old boy who presented with the) ]* M0 j! ]! A% c" }
enlargement of the phallus and pubic hair develop-, m5 _+ j. z, W0 M5 ] }
ment without testicular enlargement, which was due
+ v' w3 T# B% p+ J1 j5 O- i6 K. Rto the unintentional exposure to androgen gel used by
0 c" `5 ~: A5 Q4 q1 }7 U! lthe father. The family initially concealed this infor-+ ~ B0 z3 p( n ^! |2 l$ d+ B
mation, resulting in an extensive work-up for this% z" K3 t0 r) P" Z+ C
child. Given the widespread and easy availability of$ U, U4 F1 d+ n! o. e" |
testosterone gel and cream, we believe this is proba-
' p$ A; x R1 E# s4 j) Sbly more common than the rare case report in the
5 ~, q9 ^, g. ]( M- ]+ zliterature.4
0 _3 X V: @2 \6 i& [5 H3 lPatient Report$ W- F I+ L9 o; j, E, G
A 16-month-old white child was referred to the
# ^& ^" d! d5 Q$ \: A( }3 A/ xendocrine clinic by his pediatrician with the concern
6 r F/ D% `, A( w5 Hof early sexual development. His mother noticed
' L/ g9 S0 ^2 ]" klight colored pubic hair development when he was
0 y2 K6 s# X& w; \9 \+ hFrom the 1Division of Pediatric Endocrinology, 2University of
5 b+ A* ^, r8 O4 ]South Alabama Medical Center, Mobile, Alabama.# w; `+ a. e# }0 _& Q6 c
Address correspondence to: Samar K. Bhowmick, MD, FACE,' u2 h" j/ x/ R# w# v
Professor of Pediatrics, University of South Alabama, College of1 s; B! C6 J& v4 E6 N8 n# Q2 S: e4 R
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;, s- u& s# s. y4 H" f
e-mail: [email protected].
a7 U, t" Z# O: q7 W Q, l5 ]about 6 to 7 months old, which progressively became
( m' y% Z9 e2 Y5 _" }darker. She was also concerned about the enlarge-7 M& Y' K3 c J; e
ment of his penis and frequent erections. The child* y$ Q& L4 j ~* P
was the product of a full-term normal delivery, with9 K: u* y1 Z+ K# X, Z; U! j+ L8 T
a birth weight of 7 lb 14 oz, and birth length of
- R# [9 F& T9 z20 inches. He was breast-fed throughout the first year
2 |5 j; k# `5 l* n: \of life and was still receiving breast milk along with5 V7 {/ E$ L' p% j' G8 n
solid food. He had no hospitalizations or surgery,) v1 m$ Q' V9 v# \6 r; h1 D- R
and his psychosocial and psychomotor development
- T& I3 J% B- E1 m) B! w3 c& p; Bwas age appropriate.! x- P0 |/ M4 _ X6 D1 k% M
The family history was remarkable for the father,) R1 f Z2 e. |' c
who was diagnosed with hypothyroidism at age 16,+ c1 x, b3 h9 l* j- h, V- t
which was treated with thyroxine. The father’s$ F9 N w: h3 `3 [- K. Y5 H4 c/ _$ J
height was 6 feet, and he went through a somewhat! L' j, r! U5 {4 W1 R
early puberty and had stopped growing by age 14.) F5 g# l Q8 S' |2 h
The father denied taking any other medication. The7 P/ |$ y" E* y! D4 n, k2 @
child’s mother was in good health. Her menarche1 ] M) @5 d' Q1 ]2 ]% y0 q
was at 11 years of age, and her height was at 5 feet1 O2 ]5 X5 _7 O! b: ^4 [0 M) X
5 inches. There was no other family history of pre-" G. a* W" L# D) U$ F
cocious sexual development in the first-degree rela-
. `- M& {# Z& E! i& `tives. There were no siblings.) G- ]6 ^/ f0 ?' N9 ~% ~' h, U
Physical Examination; j9 c! _' I2 n# y
The physical examination revealed a very active,: ^! q. b1 }8 K; L4 |; K' X
playful, and healthy boy. The vital signs documented! d; e% N I# E" r, y
a blood pressure of 85/50 mm Hg, his length was
/ @4 T$ q1 p& \% P, y90 cm (>97th percentile), and his weight was 14.4 kg
. o. B M$ f# x) S# [7 c(also >97th percentile). The observed yearly growth3 [ w! [9 o' U" z
velocity was 30 cm (12 inches). The examination of7 P! q$ X4 e; Y& q
the neck revealed no thyroid enlargement.
+ a4 C1 X" x* p. z ^, g0 ?3 q" YThe genitourinary examination was remarkable for0 C$ Y4 E. x! ?% S \" ^
enlargement of the penis, with a stretched length of6 s% x3 R4 D9 R* z8 S( J
8 cm and a width of 2 cm. The glans penis was very well& r9 ^% [% e0 ~( h$ E2 A, r* y
developed. The pubic hair was Tanner II, mostly around/ j+ H* m* h) b- }
5408 w: d2 v, h3 d1 T7 M& g
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
A S/ A$ A, l$ d% _the base of the phallus and was dark and curled. The
% _- h a5 D; |, X7 T. ~testicular volume was prepubertal at 2 mL each.' i8 _ \7 `: s0 k$ F% J
The skin was moist and smooth and somewhat! N8 v8 {8 q* v# y" `+ \
oily. No axillary hair was noted. There were no8 u6 K( Z! U3 q
abnormal skin pigmentations or café-au-lait spots.
: L" L& T z. cNeurologic evaluation showed deep tendon reflex 2+6 N' {9 E* Z A( c. {
bilateral and symmetrical. There was no suggestion
3 H9 f6 X1 P0 s @5 {; Y5 ~of papilledema.
' w: A1 ^! B6 |9 x5 {Laboratory Evaluation
! S( v% C0 y' B: S" S+ J5 eThe bone age was consistent with 28 months by
/ Y& ~( r4 ^4 w# Q* Y Tusing the standard of Greulich and Pyle at a chrono-
7 N2 O1 W! H2 S/ A& x, Elogic age of 16 months (advanced).5 Chromosomal4 ]3 a0 L4 B" p& x
karyotype was 46XY. The thyroid function test4 m7 q: `2 |% P! M5 n2 G
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
( c: g5 T- I& ~0 T! ^1 tlating hormone level was 1.3 µIU/mL (both normal).
& ?1 L5 ^% ^* UThe concentrations of serum electrolytes, blood
! b7 N) y% r6 x" Furea nitrogen, creatinine, and calcium all were
# h' T/ O( l; Y5 fwithin normal range for his age. The concentration
' B& l5 I( S hof serum 17-hydroxyprogesterone was 16 ng/dL
0 f ?( I. N/ I1 F* y(normal, 3 to 90 ng/dL), androstenedione was 20$ V: P3 r. U" g. x+ o
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
. _4 r6 C6 a" Z8 k6 i. Pterone was 38 ng/dL (normal, 50 to 760 ng/dL),
* \. @ X$ ]. m3 kdesoxycorticosterone was 4.3 ng/dL (normal, 7 to3 O. s# }. G+ C; H
49ng/dL), 11-desoxycortisol (specific compound S)- p$ Q6 ~% X+ i( u, c9 f9 a1 u
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
) o! A* N5 I: R5 G' S6 U% @" vtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
: B. i. [9 q% t5 X0 G0 W6 ^testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
% h2 ^; f) o: w5 ~. \- k! Vand β-human chorionic gonadotropin was less than
4 f3 i+ s- j% v9 X4 _5 mIU/mL (normal <5 mIU/mL). Serum follicular' w$ }1 o6 L3 S. a7 F- U
stimulating hormone and leuteinizing hormone6 h0 w+ D4 n% Q" m0 J1 ?0 N
concentrations were less than 0.05 mIU/mL
E4 I1 u1 i( M. ^(prepubertal).+ b; w$ X0 I3 m
The parents were notified about the laboratory
9 {9 @4 t6 f1 \results and were informed that all of the tests were
2 G! K6 B" N8 l6 k' o/ A9 t9 f! {normal except the testosterone level was high. The
# x# ?7 ^, |" G' f' ^5 Q' cfollow-up visit was arranged within a few weeks to. ^7 ]; |& s$ s2 Q k% z# y1 T
obtain testicular and abdominal sonograms; how-
. M, v5 G. A( D, [/ Tever, the family did not return for 4 months.$ L% y; |: `% U: J6 o; F3 l
Physical examination at this time revealed that the' Q& {- g; o; U0 j" y0 V: o: t
child had grown 2.5 cm in 4 months and had gained
; b* R# A) R; ]& M* [3 q2 kg of weight. Physical examination remained) c# @0 }1 O; V- V
unchanged. Surprisingly, the pubic hair almost com-9 r% F# a. ^. i/ i$ a7 B9 I9 ]
pletely disappeared except for a few vellous hairs at
3 X0 X1 k1 O5 Wthe base of the phallus. Testicular volume was still 2
' K: T+ L0 L( x' ]mL, and the size of the penis remained unchanged. E( m0 L9 M4 U; ^# V
The mother also said that the boy was no longer hav-
) h2 \& m- K) C Y, Sing frequent erections.
6 D4 i# X4 Q" nBoth parents were again questioned about use of. {6 C" U( W) H, M5 Y" L
any ointment/creams that they may have applied to
7 \ E& r# N4 H& S4 R- Pthe child’s skin. This time the father admitted the: p/ S7 h1 m- s r( H" G: S( R
Topical Testosterone Exposure / Bhowmick et al 5410 t( d' O" e! H* R
use of testosterone gel twice daily that he was apply-
5 M* t# X; }5 T, p' t' Bing over his own shoulders, chest, and back area for, X! e+ z( Z9 Q; ^ I
a year. The father also revealed he was embarrassed0 F5 Z5 t, R' b& z
to disclose that he was using a testosterone gel pre-
% C$ W/ q) V' [5 N7 {9 Jscribed by his family physician for decreased libido
3 l0 }: W9 a. c% b) Gsecondary to depression.* C% q6 n+ X1 w e
The child slept in the same bed with parents.6 t& ]) A9 h$ `! b' x
The father would hug the baby and hold him on his
8 W0 J6 X1 I4 m3 a0 E9 @chest for a considerable period of time, causing sig-
3 J* d9 ]: o; @! i* q$ Dnificant bare skin contact between baby and father.' r, T! i P% Q' _
The father also admitted that after the phone call,
& N6 o. ]3 y+ q- O1 ?# Ywhen he learned the testosterone level in the baby
- C1 `" [% T1 r( P; l0 ?6 K9 K* _was high, he then read the product information+ l; {( b, I# E/ J+ D" y. E
packet and concluded that it was most likely the rea-/ V" G/ X; s8 g, J7 f. k! C
son for the child’s virilization. At that time, they
, U X* ^2 I# |decided to put the baby in a separate bed, and the8 m9 ?8 g! [0 W/ a- k: j
father was not hugging him with bare skin and had, c, @) Q5 c P8 ~; a7 a" J' y
been using protective clothing. A repeat testosterone% Z1 R. j" _' R( @; C
test was ordered, but the family did not go to the
' K) r5 f+ s! d5 ]; }laboratory to obtain the test.2 g6 I% P3 b( D. i6 y F4 x" y$ i
Discussion1 g9 A* L1 q4 k1 I
Precocious puberty in boys is defined as secondary
2 v* j1 i' I a, v( Xsexual development before 9 years of age.1,4% ?0 Z& C6 t+ R9 v( G% _
Precocious puberty is termed as central (true) when
2 `+ n6 |5 {4 ]2 C5 l( Rit is caused by the premature activation of hypo-6 s! R0 h' W$ x& [6 q2 _. h. i0 l3 ?
thalamic pituitary gonadal axis. CPP is more com-
/ J1 M9 F5 I# @& v# [mon in girls than in boys.1,3 Most boys with CPP
) b( `* w( O3 ]. b1 M( Tmay have a central nervous system lesion that is$ C* M* z: h+ ^4 u9 J5 x
responsible for the early activation of the hypothal-
9 F' F/ e" |) b1 _amic pituitary gonadal axis.1-3 Thus, greater empha-, h; ?% ~( X7 ]1 ]" f% N5 m
sis has been given to neuroradiologic imaging in. ^7 q6 x: n: s/ k; j
boys with precocious puberty. In addition to viril-+ W& A: f9 S' f* b
ization, the clinical hallmark of CPP is the symmet-3 W/ r% x; \ i0 L: o+ ?
rical testicular growth secondary to stimulation by
; w& X! v6 C" @% i( X$ b) Xgonadotropins.1,33 K! \8 j, x8 O+ O+ t6 e2 l
Gonadotropin-independent peripheral preco-2 U! \) r$ B2 z! {- n
cious puberty in boys also results from inappropriate' u. J7 _- y5 C3 @0 ~5 w
androgenic stimulation from either endogenous or
( t2 }3 _6 g) F: c8 Dexogenous sources, nonpituitary gonadotropin stim-- u, ^6 M+ j8 G9 @; [$ J
ulation, and rare activating mutations.3 Virilizing" S8 n ^: T1 h) F. f# j4 q
congenital adrenal hyperplasia producing excessive" `, [) a1 }- V& X- f" k/ l2 }/ p0 z
adrenal androgens is a common cause of precocious) e5 O0 i3 r' u( H0 f* ^4 G% c% ?- Q
puberty in boys.3,4! i0 ~3 O' E; y& ?0 k6 |
The most common form of congenital adrenal! G2 ]" i5 O9 Z; W# f: A
hyperplasia is the 21-hydroxylase enzyme deficiency.( ?. k- \3 m* r5 y$ b0 p/ l9 |
The 11-β hydroxylase deficiency may also result in- R4 L4 j1 n, i$ u, M. l3 r
excessive adrenal androgen production, and rarely,
6 `( a- D# c" M, z1 L6 B( Zan adrenal tumor may also cause adrenal androgen
o5 h. J! ]1 w* W, Hexcess.1,3* N/ ~0 d) _; U I+ q! E4 D& G) g
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from* b- o1 Y# x2 e; g
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007& s4 ~. U1 Q- A
A unique entity of male-limited gonadotropin-1 q* g" y% a' y
independent precocious puberty, which is also known( A$ b% u M+ K! x5 S8 j
as testotoxicosis, may cause precocious puberty at a- c1 ^; v* P$ O
very young age. The physical findings in these boys, Q% O, s( b- c, ^1 n
with this disorder are full pubertal development,
* n/ E. Q" F( V0 y9 fincluding bilateral testicular growth, similar to boys8 L; x/ f# D* u& X
with CPP. The gonadotropin levels in this disorder
- p' s6 |- D+ z" ^are suppressed to prepubertal levels and do not show% `4 r; e) P6 }& j% f% s8 D
pubertal response of gonadotropin after gonadotropin-
: o9 x; R( H5 k- d0 treleasing hormone stimulation. This is a sex-linked6 ?' u6 M* d1 Z1 }
autosomal dominant disorder that affects only
" Y* x7 X# R2 p7 E0 c u2 g. Dmales; therefore, other male members of the family9 j. d+ g {8 @
may have similar precocious puberty.3
0 S% T+ I/ y7 o+ {) iIn our patient, physical examination was incon-; ~, Y+ F# P; |: Q- o
sistent with true precocious puberty since his testi-
! t; ~! K9 K. X! Q- ?cles were prepubertal in size. However, testotoxicosis
1 b9 Z& T; Z+ O) r3 p, Mwas in the differential diagnosis because his father
$ l1 c( p+ X& ^3 l8 P- |* Wstarted puberty somewhat early, and occasionally,
. x: }( h! f. Q5 |- Xtesticular enlargement is not that evident in the' K. z) r$ m, K3 N1 k; O; Q4 F& @
beginning of this process.1 In the absence of a neg-
- e# ^9 C' |& U3 r$ v2 native initial history of androgen exposure, our
1 A* t3 O: ]( ~3 v5 Y5 cbiggest concern was virilizing adrenal hyperplasia,
7 I! G) x+ s+ leither 21-hydroxylase deficiency or 11-β hydroxylase
' l4 N, N+ D% y: f" y% tdeficiency. Those diagnoses were excluded by find-
$ ]0 C3 E' O- v5 k6 h; \* r! Aing the normal level of adrenal steroids.2 e; ]4 _0 b$ _: A5 z; n$ T4 T
The diagnosis of exogenous androgens was strongly' _" \$ ^- f. a4 P! r" a) v5 h
suspected in a follow-up visit after 4 months because
, f5 _% Y4 M1 p$ `2 `, mthe physical examination revealed the complete disap-
. q$ u4 L% j) u# l5 V& f) c8 T# Q; Ppearance of pubic hair, normal growth velocity, and! F9 R% k6 ^ a3 Y: m. v
decreased erections. The father admitted using a testos- N' r) q7 V2 d) j
terone gel, which he concealed at first visit. He was0 n0 H$ W5 T: d# o2 A" W
using it rather frequently, twice a day. The Physicians’
4 Q, Z8 k% { EDesk Reference, or package insert of this product, gel or& l* C3 @) t2 |# B8 ^. I
cream, cautions about dermal testosterone transfer to
* h p1 L1 f) _1 H4 `. O4 X4 M7 W' {unprotected females through direct skin exposure.
/ _) m" d; n3 S- `5 rSerum testosterone level was found to be 2 times the
8 U, \7 _$ q. y: ]8 ]4 o' lbaseline value in those females who were exposed to' {/ E) e0 `# s( N0 C
even 15 minutes of direct skin contact with their male7 ]$ n$ `/ T0 U4 q) I. {1 s
partners.6 However, when a shirt covered the applica-. i8 l0 v$ n) B
tion site, this testosterone transfer was prevented.) j2 ?7 g6 W2 D! w `
Our patient’s testosterone level was 60 ng/mL,9 q; h* W$ }3 { W* p
which was clearly high. Some studies suggest that
1 e5 Q1 X t; v2 Pdermal conversion of testosterone to dihydrotestos-
o0 p. e0 x, |; {3 w. wterone, which is a more potent metabolite, is more
) h4 [: r, A- eactive in young children exposed to testosterone
F$ i3 `) u# f3 I! R$ Iexogenously7; however, we did not measure a dihy-3 Y f: q; g8 l2 H$ X
drotestosterone level in our patient. In addition to r5 M+ Q+ F1 l
virilization, exposure to exogenous testosterone in) ?4 c! u" m; h+ I2 J2 T! }
children results in an increase in growth velocity and
, L0 F) W! J- L. @! j/ J9 ~advanced bone age, as seen in our patient.5 ^. |$ h+ q/ Z. b% a$ ^) a
The long-term effect of androgen exposure during8 ?" w" }) F, K
early childhood on pubertal development and final5 I/ s2 i3 c* N# K' |
adult height are not fully known and always remain
) E+ U; ~+ o4 s4 A5 i( t0 G7 ~a concern. Children treated with short-term testos-
/ M1 f1 z; b# f+ ^. s: A- fterone injection or topical androgen may exhibit some. o' c, t/ a$ d5 j4 ~3 o' D
acceleration of the skeletal maturation; however, after# b) u" V/ @7 l2 W q
cessation of treatment, the rate of bone maturation: C8 U' d; e/ h2 k# ?
decelerates and gradually returns to normal.8,9) z$ e$ N; R: W, r. s
There are conflicting reports and controversy
5 a/ }" j5 n! M9 ~& hover the effect of early androgen exposure on adult
l s# `5 z2 B( ?' R) Openile length.10,11 Some reports suggest subnormal: o$ r0 ~; U! E# [ a
adult penile length, apparently because of downreg-
; g# I" E$ `' e+ A: q; rulation of androgen receptor number.10,12 However,
* m# _ g$ C. U: N: m9 }" xSutherland et al13 did not find a correlation between
) h6 ?) L2 Z" u+ w |+ c3 Cchildhood testosterone exposure and reduced adult
) `3 `: M% a$ d# c8 ppenile length in clinical studies.8 B8 O, ?6 [8 h1 l* h1 v
Nonetheless, we do not believe our patient is
4 n; t* O" [; ^) s( o/ zgoing to experience any of the untoward effects from
+ W$ R* g0 X, D, ^testosterone exposure as mentioned earlier because
8 f- h/ q/ l2 J4 ]' ]7 rthe exposure was not for a prolonged period of time.
! n/ T* J+ B, r3 QAlthough the bone age was advanced at the time of
: P6 d$ F3 l7 e/ s( @. q4 i* q: udiagnosis, the child had a normal growth velocity at4 P1 [3 Y8 N" `7 V
the follow-up visit. It is hoped that his final adult) X( A0 P) o& s# j- e T
height will not be affected.
6 Y9 w0 F% ~; ~3 Q. hAlthough rarely reported, the widespread avail-+ t. t8 N; K9 _: ^
ability of androgen products in our society may
6 A! ?( p" Q/ U a+ Lindeed cause more virilization in male or female9 b% E7 \6 U2 u4 h
children than one would realize. Exposure to andro-
[8 T. b0 H2 R7 C# L. agen products must be considered and specific ques- }0 f% U0 S* q( s* U; }
tioning about the use of a testosterone product or. ~# B& T. J* P0 o. |1 h# e2 r
gel should be asked of the family members during! `7 D" a" h1 I) e/ I- |0 X7 T
the evaluation of any children who present with vir-8 @) R! y" _: Y h- k7 B
ilization or peripheral precocious puberty. The diag-: F" b. o- u4 ^3 v) A
nosis can be established by just a few tests and by
3 ^) d6 `+ \* ^! {! Lappropriate history. The inability to obtain such a
, c7 w5 A' Q, H' f+ A% phistory, or failure to ask the specific questions, may
, j% Q8 J8 p& C- T# O! z, E4 qresult in extensive, unnecessary, and expensive/ y3 p4 Q2 A% b
investigation. The primary care physician should be9 J# B# H9 Q4 x: f/ i2 @
aware of this fact, because most of these children
+ _) d l8 a Q, r# [2 |" g% x" Jmay initially present in their practice. The Physicians’5 B& y2 v+ A7 l' R+ @+ C
Desk Reference and package insert should also put a
3 M8 i0 d3 f' ~% t! twarning about the virilizing effect on a male or' @& J% E# W) `% p8 W ]- A3 [
female child who might come in contact with some-7 C0 q$ b6 X$ T
one using any of these products.
9 h0 ]! w( V4 z+ pReferences
# a; r7 Q2 F( }* T* J: x7 X1. Styne DM. The testes: disorder of sexual differentiation0 w+ X: x9 o5 L8 F2 L
and puberty in the male. In: Sperling MA, ed. Pediatric# t) x0 [4 F2 L8 p& [
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
, F W$ J, l% Y5 v2002: 565-628." x' m, U. Q( V, P9 U
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
0 s+ s* g, b/ A1 Gpuberty in children with tumours of the suprasellar pineal
6 }* h1 y* n( G6 w& `# p9 A& _at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from; D L6 c5 s/ O. D" ]5 F3 }/ U, G
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# W, R2 ~8 J7 h V( Pareas: organic central precocious puberty. Acta Paediatr.. o/ P8 P$ {- e R% E" H
2001;90:751-756.
6 P+ G, `* m+ U; m+ V2 T" l6 \3. Lee PA. Puberty and its disorders. In: Lifshitz F, ed.
( T) S3 M3 X" W& C5 V1 T DPediatric Endocrinology. 4th ed. New York, NY: Marcel [' k5 {3 [+ ?
Dekker Inc; 2003:211-238.
8 V" p; ~$ C# c$ J1 B- ~4. Yu YM, Punyasavatsu N, Elder D, D’Ercole AJ. Sexual
# m# t0 w" ]( b0 Ydevelopment in a two-year-old boy induced by topical e% ^$ v; H7 D7 ]3 J. z$ e
exposure to testosterone. Pediatrics. 1999;104:e23.
3 z% L1 C: q. @+ u9 m5. Greulich WW, Pyle SI, eds. Radiographic Atlas of8 l1 m$ a' j7 ]4 V6 o9 x. G
Skeletal Development of the Hand and Wrist. 2nd ed. X* m+ q5 k' h9 w# s
Stanford, CA: Stanford University Press; 1959.
+ t& W* W( S8 L7 L% b( a6. Physicians’ Desk Reference. Androgel 1% testosterone,2 A% ^( y- p: c) O N
Unimed Pharmaceutical Inc. Montvale, NJ: Medical( I* F7 B& ~) U# j% ]8 n6 [( N6 ~
Economics Company, Inc; 2004:3239-3241.
: [4 e5 P @4 O% ]1 f7. Klugo RC, Cerny JC. Response of micropenis to topical
% n2 p& w% t' J4 z1 mtestosterone and gonadotropin. J Urol. 1978;119:6 V% u- u3 }6 q! Z
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