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is a significant concern for physicians. Central
' n+ y/ G; f4 U! }5 X; Xprecocious puberty (CPP), which is mediated
; m, T+ N+ y8 e4 othrough the hypothalamic pituitary gonadal axis, has+ q2 v0 u% K: V8 m- P$ p: M1 ^
a higher incidence of organic central nervous system
9 ^( t1 M/ G$ `9 _; Hlesions in boys.1,2 Virilization in boys, as manifested6 O" `2 m$ ?& J. X* }
by enlargement of the penis, development of pubic
: d" C2 p6 r5 |0 @/ a3 s$ Uhair, and facial acne without enlargement of testi-
! ~# ~# V* e' Q8 R& ~$ W# C: s3 ?4 U3 |cles, suggests peripheral or pseudopuberty.1-3 We
" \2 a# f, b% E" ^6 Preport a 16-month-old boy who presented with the
( ~/ f6 `% w+ V" L! kenlargement of the phallus and pubic hair develop-/ z. E- l" F/ ^! L) M/ B- H6 ^
ment without testicular enlargement, which was due2 y- e" Y# C) u3 |! b: I1 j3 k0 G
to the unintentional exposure to androgen gel used by
: i- P# y9 O% N' O; i8 |* }the father. The family initially concealed this infor-$ |1 ] e0 k8 s
mation, resulting in an extensive work-up for this
6 w+ ?( s) K/ C9 {child. Given the widespread and easy availability of
) G4 e9 g& N T* ^testosterone gel and cream, we believe this is proba-7 H+ _6 W2 |8 o) P
bly more common than the rare case report in the: B9 [% ]! z' I
literature.4
3 Q4 }- N! o; ~Patient Report1 C! s# u5 t$ W/ _
A 16-month-old white child was referred to the2 T4 ~" g. y) g# T. |7 h0 T& O
endocrine clinic by his pediatrician with the concern
! a: K; F6 Z+ \& D& ~/ A, rof early sexual development. His mother noticed
8 D! |# h% h* e: H- klight colored pubic hair development when he was$ s& a& I0 w! l5 r6 Q
From the 1Division of Pediatric Endocrinology, 2University of# C1 s0 o, d5 O3 l
South Alabama Medical Center, Mobile, Alabama.' \* l+ |6 S1 E9 X: \* m8 ^ b
Address correspondence to: Samar K. Bhowmick, MD, FACE,
* A' ?& n8 w8 Q/ FProfessor of Pediatrics, University of South Alabama, College of8 ~' e2 h6 V0 X: P4 T/ f* H
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;' N, o$ ^" P. z: u* k! N
e-mail: [email protected]./ M& i. f- ` ~
about 6 to 7 months old, which progressively became4 ^$ T2 U9 R" r9 A/ X+ i
darker. She was also concerned about the enlarge-+ a Z- j( q2 t$ A2 O6 E$ r: X
ment of his penis and frequent erections. The child
$ \) s$ ~2 Z) E0 K9 V! {+ i3 j# vwas the product of a full-term normal delivery, with5 t) k9 b ~" ^% A3 ^: Q9 B$ ^
a birth weight of 7 lb 14 oz, and birth length of$ X7 }+ p, f2 t- Y/ v. v8 g/ K7 P9 {$ W6 J
20 inches. He was breast-fed throughout the first year: V0 Y0 P0 |2 M, L
of life and was still receiving breast milk along with! `$ M( X H; [% r. w
solid food. He had no hospitalizations or surgery,
2 O# w9 G$ ^1 V9 aand his psychosocial and psychomotor development
* n6 U1 ~4 V$ o1 Bwas age appropriate.
" [+ D, g, S6 M( U! ^The family history was remarkable for the father,8 g4 P" ]5 N4 }5 a* N& P
who was diagnosed with hypothyroidism at age 16,8 h2 Z: n1 j0 p! p, j+ d" h
which was treated with thyroxine. The father’s
: C' E$ B( S" c9 vheight was 6 feet, and he went through a somewhat
1 V- K! i3 o4 ?4 _early puberty and had stopped growing by age 14.' ?5 G- o. m$ o8 d1 ^7 c4 |
The father denied taking any other medication. The
: B8 k) }! s# D, y( Nchild’s mother was in good health. Her menarche" a( m* k5 Y! R- \5 i$ G- m H
was at 11 years of age, and her height was at 5 feet
! j2 a" D/ L1 K& _1 I3 J& I5 inches. There was no other family history of pre-
9 ]7 I4 J! L5 k3 ]+ pcocious sexual development in the first-degree rela-
" Y! k8 H# @! R0 K9 mtives. There were no siblings.
$ v3 c* M" C: YPhysical Examination
( C6 _! ?) w7 g6 W7 j H1 q8 {The physical examination revealed a very active,
% u% c8 l# r! ^playful, and healthy boy. The vital signs documented# n$ A& Y1 B( r6 ]$ W
a blood pressure of 85/50 mm Hg, his length was7 W- y& y! p, p, H- v4 I2 ` Q6 F
90 cm (>97th percentile), and his weight was 14.4 kg
' v) l: m [9 f5 `0 r& K(also >97th percentile). The observed yearly growth
4 @% w2 L, W8 Q" _# _) Lvelocity was 30 cm (12 inches). The examination of5 Y) I' C0 q; \* B- M$ g
the neck revealed no thyroid enlargement.8 W+ w/ U. ]9 H) o+ R8 |
The genitourinary examination was remarkable for
# E- ?; e: M& z- b8 A3 X. Cenlargement of the penis, with a stretched length of& L: k7 {# m3 X9 E6 a6 T+ i7 ^
8 cm and a width of 2 cm. The glans penis was very well8 R' V- G1 _' I) A$ ?
developed. The pubic hair was Tanner II, mostly around
6 F3 H `; e, h; P7 ?540
' [) @+ d9 C) l% aat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from1 p. h2 w s, v5 |9 g! X
the base of the phallus and was dark and curled. The
4 M9 z% e" L8 v2 w0 C7 W& ntesticular volume was prepubertal at 2 mL each.. |8 x, l0 Z( e* ^9 V2 g! B* ^
The skin was moist and smooth and somewhat
n( p2 Q- T' L8 ?* Moily. No axillary hair was noted. There were no
y& a" n) A# J. m% f. E- y$ I! K! E0 Labnormal skin pigmentations or café-au-lait spots.
1 H3 J% q2 W8 l. `5 m, INeurologic evaluation showed deep tendon reflex 2+# O' G1 s- Y, i, C1 S9 p
bilateral and symmetrical. There was no suggestion
" b+ x' f e4 _' }4 ~* E& c9 K, Xof papilledema.
1 p" o) W' s3 iLaboratory Evaluation
+ ?2 _; \+ J f4 n" \+ R- ?The bone age was consistent with 28 months by' U' S1 A$ o% _1 R8 Y/ H: X) B
using the standard of Greulich and Pyle at a chrono-3 X% g" l f& t, K) B) L' H
logic age of 16 months (advanced).5 Chromosomal3 h- s3 O% A$ D
karyotype was 46XY. The thyroid function test8 [# |6 Y b/ l% j
showed a free T4 of 1.69 ng/dL, and thyroid stimu-7 z% A; ^6 [6 [. T
lating hormone level was 1.3 µIU/mL (both normal)." g. C7 x" u2 H
The concentrations of serum electrolytes, blood9 D0 v5 o' ~0 @
urea nitrogen, creatinine, and calcium all were- k; T O. V9 h s" P
within normal range for his age. The concentration
$ d6 R [# V0 _) Q$ T G$ g- a5 Dof serum 17-hydroxyprogesterone was 16 ng/dL6 A b+ i3 X/ {5 l4 B/ ~5 D$ T2 T
(normal, 3 to 90 ng/dL), androstenedione was 20
3 ?1 P' Z) v! V2 L# _9 w* Sng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-0 p' o) V* o! y' @0 ^6 B
terone was 38 ng/dL (normal, 50 to 760 ng/dL),. B, g9 N7 k7 a8 ]* T8 v3 T, d
desoxycorticosterone was 4.3 ng/dL (normal, 7 to9 c* Z# {7 e7 S" ?& T c A7 H7 _; j
49ng/dL), 11-desoxycortisol (specific compound S)3 T6 y. \2 e/ O0 v
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-0 y3 r. T" A, H, Z
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total- a# V, d1 Y: a) J1 b
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),: B% _" [; w# M
and β-human chorionic gonadotropin was less than1 U A3 E% Y; {- t7 @, b
5 mIU/mL (normal <5 mIU/mL). Serum follicular
8 q" k% a. R+ | b# ostimulating hormone and leuteinizing hormone: p1 k8 l8 D3 x3 m
concentrations were less than 0.05 mIU/mL8 Y" S; t7 O- w s8 c
(prepubertal).
, s6 A# J4 V+ y Q: e2 nThe parents were notified about the laboratory* d# }' ` i. G' j, \/ x
results and were informed that all of the tests were
9 S: ^/ r- g" O5 I) W9 R3 ]0 W. p- cnormal except the testosterone level was high. The. a) N. Y, t, |% _6 Z3 _
follow-up visit was arranged within a few weeks to4 V2 J8 [! u% T8 ~$ v
obtain testicular and abdominal sonograms; how-
% D3 {" h$ o% Q, lever, the family did not return for 4 months.' _) M# I, W; |" W$ u
Physical examination at this time revealed that the. i0 {3 ^& B' d& m
child had grown 2.5 cm in 4 months and had gained5 q8 g& R( O8 g1 ]. Q1 ?
2 kg of weight. Physical examination remained% {- k- g( s6 F$ v( h+ B9 h# n
unchanged. Surprisingly, the pubic hair almost com-
$ ]2 _9 R. K2 n( n$ Wpletely disappeared except for a few vellous hairs at9 N1 `! f2 L* l8 }& f4 z% q
the base of the phallus. Testicular volume was still 2. Y1 G- \0 G# p- l: K( D2 {
mL, and the size of the penis remained unchanged.
: E9 p/ ^; f3 ]2 S1 W7 F( y8 t# fThe mother also said that the boy was no longer hav-
+ r5 b. i9 c$ k* g Q/ y. ?ing frequent erections.* m1 h2 G0 A. G" r' @6 o8 k/ V
Both parents were again questioned about use of
. t& ?8 T% Q5 F' M, r/ \3 U( ?any ointment/creams that they may have applied to
$ X* }' _( }7 y1 V( vthe child’s skin. This time the father admitted the/ {" Q/ b5 N x9 V1 a p( O
Topical Testosterone Exposure / Bhowmick et al 541" v. Y% t$ w9 T
use of testosterone gel twice daily that he was apply-1 I* Z8 t8 ^8 E; f' U, |0 G
ing over his own shoulders, chest, and back area for
1 P' A7 m O8 U9 n& W3 M* Da year. The father also revealed he was embarrassed
# P! Q9 W% W b6 d: k9 Rto disclose that he was using a testosterone gel pre-9 E0 K4 n1 p$ E) Z7 ]
scribed by his family physician for decreased libido1 _: g# y; L [. \6 J9 d
secondary to depression.
2 y! O0 X2 ?# ^0 T4 XThe child slept in the same bed with parents.# z" h$ A( Q! t
The father would hug the baby and hold him on his
' s z, [4 N" d* S5 n# z: T( ~' |chest for a considerable period of time, causing sig-0 o( L6 i" `+ H+ g+ m( `7 `4 o
nificant bare skin contact between baby and father.% g+ _, l+ b" `8 U1 y( V, V
The father also admitted that after the phone call,
7 _) m! `, N( c5 _# N6 f: L8 k2 d$ v* k$ Dwhen he learned the testosterone level in the baby
! U/ |( B/ t! k& U3 C: Uwas high, he then read the product information
; H; I# ^% _5 ^2 _1 _3 v1 b9 v0 qpacket and concluded that it was most likely the rea-# C$ b( `3 a) i9 q4 a b
son for the child’s virilization. At that time, they1 T4 }& x& P! T& z# t8 ~
decided to put the baby in a separate bed, and the
/ o' y7 f% }4 w) u: i# }; hfather was not hugging him with bare skin and had
2 j4 e9 ]; H2 Gbeen using protective clothing. A repeat testosterone, B; A m! d3 x, D% N4 n
test was ordered, but the family did not go to the M0 J0 N$ O* W
laboratory to obtain the test.
* x! J/ u' f: {* q q$ k1 GDiscussion
5 M& p( q) P3 f) O1 }( D' kPrecocious puberty in boys is defined as secondary/ M) e: h/ h' W5 i% }* W
sexual development before 9 years of age.1,4
5 Y% n( n9 ~ {' {2 o+ P7 W$ XPrecocious puberty is termed as central (true) when
4 W. ]9 @! ~* Z2 [5 `4 {it is caused by the premature activation of hypo-
, g8 n% m0 E3 P/ t# v, Uthalamic pituitary gonadal axis. CPP is more com-
& P, h# N/ t" {mon in girls than in boys.1,3 Most boys with CPP9 s5 U9 s) Z: u4 ^7 V
may have a central nervous system lesion that is
6 I P3 N P; o- aresponsible for the early activation of the hypothal-
; t8 g; t7 C5 _; Namic pituitary gonadal axis.1-3 Thus, greater empha-5 z7 z- R2 ] f! v. F
sis has been given to neuroradiologic imaging in
) H9 N, q$ d. x! Q8 B/ j$ sboys with precocious puberty. In addition to viril-, L& a. C' o* I1 z* c; `+ ^
ization, the clinical hallmark of CPP is the symmet-0 p; K! o+ y0 G, t4 B6 @
rical testicular growth secondary to stimulation by/ g" e- N. P6 d3 e
gonadotropins.1,3# l4 \7 K/ Z; M8 E" v
Gonadotropin-independent peripheral preco-
) T' c d6 X4 l& z/ f. G4 c, F/ e; Acious puberty in boys also results from inappropriate
0 T2 I# |+ L; s3 kandrogenic stimulation from either endogenous or$ P6 N, u0 i5 ]2 A4 L4 |+ [
exogenous sources, nonpituitary gonadotropin stim-# c( s$ n5 k3 c
ulation, and rare activating mutations.3 Virilizing7 Q B* }2 J5 X0 C. m
congenital adrenal hyperplasia producing excessive
, ^4 z/ \4 n* i; M; g# radrenal androgens is a common cause of precocious
) x I* R) o3 q, ~3 Zpuberty in boys.3,45 n' S9 X$ L3 q" X$ Q
The most common form of congenital adrenal; Y$ V" t/ Z7 ~, G9 F3 P. c
hyperplasia is the 21-hydroxylase enzyme deficiency.! d$ { A/ B! \5 {. |8 b, m- y% a
The 11-β hydroxylase deficiency may also result in
) x! b) q6 {) O0 { F3 H- W) R- o+ kexcessive adrenal androgen production, and rarely,
' y7 n Y; H- Van adrenal tumor may also cause adrenal androgen
" H; y' N' S4 ~' s" T' H3 ]$ Rexcess.1,3: @! b( @' J7 {8 }
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
% R" b E% F& N/ l# W* w; u542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
+ K+ H+ O) z2 a3 I q5 x! xA unique entity of male-limited gonadotropin-+ m3 n5 P* f, V# Q7 [1 C# [
independent precocious puberty, which is also known
; @* k- j3 W6 U+ j! M( tas testotoxicosis, may cause precocious puberty at a3 W0 Z' \3 O6 b7 a1 C" @
very young age. The physical findings in these boys
7 @+ { g( f6 I; R, w3 bwith this disorder are full pubertal development,
/ z- D0 u3 s0 k" O5 T, W* iincluding bilateral testicular growth, similar to boys
2 }5 J8 U6 G% L0 L% dwith CPP. The gonadotropin levels in this disorder
* l0 b/ t& B8 D/ o3 Zare suppressed to prepubertal levels and do not show
- e9 C! @! v5 upubertal response of gonadotropin after gonadotropin-2 \# q' T6 t6 l6 P
releasing hormone stimulation. This is a sex-linked
# {: H. q! P6 N' _( Sautosomal dominant disorder that affects only" S+ y( N3 N! e* o% [- X, w( ~
males; therefore, other male members of the family. y4 B y+ u- F' z% i
may have similar precocious puberty.3
+ m8 P8 X, q: |In our patient, physical examination was incon-
( N& u" \& i( Z5 O8 asistent with true precocious puberty since his testi-; N" r7 i5 F/ P) o
cles were prepubertal in size. However, testotoxicosis
2 \3 n3 z+ t: ]. J f. owas in the differential diagnosis because his father7 [! A- _& v2 W* f# N3 H9 B2 N
started puberty somewhat early, and occasionally,
3 r% _) t7 n) X: Y7 e" N5 Ztesticular enlargement is not that evident in the. B9 j. K1 A+ I$ P: M* P
beginning of this process.1 In the absence of a neg-
# S; l( z" |$ z7 Jative initial history of androgen exposure, our
( h) o3 V- w7 r2 _5 ?biggest concern was virilizing adrenal hyperplasia,9 Q6 _0 U0 r( P
either 21-hydroxylase deficiency or 11-β hydroxylase! t! T' \3 i2 n
deficiency. Those diagnoses were excluded by find-: E+ }; l! v6 ^
ing the normal level of adrenal steroids.3 A3 {& R0 L% w i, J6 J# E) e
The diagnosis of exogenous androgens was strongly
% v. l9 T1 X8 X4 x' |: esuspected in a follow-up visit after 4 months because$ K0 h7 x) W' t: |5 \
the physical examination revealed the complete disap-' V1 @6 g7 _! e4 J" ^9 Q
pearance of pubic hair, normal growth velocity, and+ m7 Y6 o N+ H1 j6 S0 `2 N7 {
decreased erections. The father admitted using a testos-7 J) G |* n: ]/ N s9 C
terone gel, which he concealed at first visit. He was: Y G$ \0 o3 G) n0 h, d! n
using it rather frequently, twice a day. The Physicians’7 H" f. `; o8 t# G! H
Desk Reference, or package insert of this product, gel or
! Y! ?( I0 ^- w( l) f. b8 dcream, cautions about dermal testosterone transfer to; b. q/ E9 l i2 Z2 M- h# ?+ z
unprotected females through direct skin exposure.
% v) |6 d: o l0 tSerum testosterone level was found to be 2 times the
2 j$ ?. K3 R1 `& J; L4 [baseline value in those females who were exposed to
, I& T' J! J$ U" Y) Jeven 15 minutes of direct skin contact with their male5 d& _+ E' G8 o! _
partners.6 However, when a shirt covered the applica-* h2 Z; D3 E: ]3 q( _/ t0 k
tion site, this testosterone transfer was prevented.: q1 f" `8 n, a* M+ n
Our patient’s testosterone level was 60 ng/mL,7 [) }1 E2 o$ w) g4 N- h" N
which was clearly high. Some studies suggest that
: f; [2 R4 A& m T( P( Edermal conversion of testosterone to dihydrotestos-/ Y5 V) u: y1 b' Q- ~$ M
terone, which is a more potent metabolite, is more
4 W9 R- g4 s; E0 P N: ]active in young children exposed to testosterone
# j( i; N0 L( Gexogenously7; however, we did not measure a dihy-
9 H5 s; g! j; w* X3 ]4 h5 zdrotestosterone level in our patient. In addition to
: G( [" r; e; {9 C6 ]; Evirilization, exposure to exogenous testosterone in
# X r: U& `+ x9 {! V7 o$ n% F! u: Jchildren results in an increase in growth velocity and; b$ e% K$ L! a J7 X
advanced bone age, as seen in our patient.% m$ A) w" Y1 `" X$ m& s7 d
The long-term effect of androgen exposure during" s* @0 v( m" V
early childhood on pubertal development and final
( K7 E K) q, Y* \- G, `adult height are not fully known and always remain
! v3 T2 `, O5 H4 S# Y" }a concern. Children treated with short-term testos-. i- G2 Y! S7 f5 f; `" l8 d
terone injection or topical androgen may exhibit some
! W* G7 n# M4 z+ }acceleration of the skeletal maturation; however, after' _" ]8 n' }+ ^3 ~
cessation of treatment, the rate of bone maturation
# b, D+ d+ V2 B" d; Z) `decelerates and gradually returns to normal.8,9
, e* x, k a* R/ mThere are conflicting reports and controversy/ T/ K3 E% w9 q9 F: ^7 o, W
over the effect of early androgen exposure on adult
2 ?0 }* Q& \1 }6 Ipenile length.10,11 Some reports suggest subnormal* w+ R6 n! K$ a! U$ _& p$ Y. A# `$ p
adult penile length, apparently because of downreg-& y! r# Q: r4 W5 O& ?! n
ulation of androgen receptor number.10,12 However,
+ d7 x0 c- ^3 X4 |/ C0 OSutherland et al13 did not find a correlation between
0 m! I* n0 |, i* [0 q% A8 rchildhood testosterone exposure and reduced adult
9 P9 U6 U" k/ F! f! W4 t# @penile length in clinical studies./ i0 u! Z$ N2 F: D& t
Nonetheless, we do not believe our patient is3 k3 k# F2 N+ v, f, C! q R
going to experience any of the untoward effects from
5 r# _* T+ b' q+ U$ {. z! P* m! qtestosterone exposure as mentioned earlier because; T# S1 V5 x+ n. F3 a$ I( ]
the exposure was not for a prolonged period of time.( Z$ N1 {: C; F" e3 W* b
Although the bone age was advanced at the time of
/ J2 q! I# m f; W% z/ j1 Cdiagnosis, the child had a normal growth velocity at
+ P$ C \& e1 w) Ythe follow-up visit. It is hoped that his final adult
% N/ M# D1 i5 d2 G5 aheight will not be affected.4 R- q n5 a- j* I
Although rarely reported, the widespread avail-
0 J5 p: b2 Z1 C1 ?7 Xability of androgen products in our society may3 S, S0 Q+ x; d9 P) U
indeed cause more virilization in male or female# S. \4 b" Q* \" Q
children than one would realize. Exposure to andro-2 M$ {( D8 I6 |4 S
gen products must be considered and specific ques-
5 G- L5 m( I% S* _tioning about the use of a testosterone product or* T4 u2 |( w# T/ n/ J. S7 o2 t) k
gel should be asked of the family members during
, k `& i+ w8 k( \7 `" `the evaluation of any children who present with vir-) v6 o! B- s8 Z! Y: [ R+ B$ N' k
ilization or peripheral precocious puberty. The diag-
" m' U% W3 E @7 X4 f1 Mnosis can be established by just a few tests and by- ]& V4 v' ^) k7 ^
appropriate history. The inability to obtain such a. |9 f7 T% w" u ^; [
history, or failure to ask the specific questions, may1 a! z" T Z. X
result in extensive, unnecessary, and expensive
" y& a9 G, ?$ B( Dinvestigation. The primary care physician should be9 q3 Q9 F/ d/ o7 C6 C% [
aware of this fact, because most of these children/ H9 y# a& |: d& u8 x* Z H
may initially present in their practice. The Physicians’
! B6 L3 H% j1 X' J3 w- }6 n5 LDesk Reference and package insert should also put a! ?; B+ n8 n9 N7 @5 Y( x9 \
warning about the virilizing effect on a male or
% P7 ^- J$ X2 ifemale child who might come in contact with some-
, Z( j8 o! w: e. J+ zone using any of these products.0 g `+ S8 T! r" w
References$ k+ d$ ?- v, {5 Y# N; ?
1. Styne DM. The testes: disorder of sexual differentiation
+ K# |; Z9 ^0 S2 R. j$ Wand puberty in the male. In: Sperling MA, ed. Pediatric& Z/ I- C. x+ A7 o4 u1 [# H& C: B
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
% @/ I5 ]' T( E6 t3 R) k: e8 ~2002: 565-628.) [+ x8 |8 V! [' P
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
7 n' z! ~2 }) f) `% g/ [7 R5 Dpuberty in children with tumours of the suprasellar pineal
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areas: organic central precocious puberty. Acta Paediatr.& @! F: a3 Q# v
2001;90:751-756./ y" w9 u- B h& n6 o) M# d
3. Lee PA. Puberty and its disorders. In: Lifshitz F, ed.) W. x( j7 [6 x% ~, Y! i( I$ K( L
Pediatric Endocrinology. 4th ed. New York, NY: Marcel1 b# @1 j' B1 h- ?1 H# i' |
Dekker Inc; 2003:211-238.
( S, g/ p+ {+ N5 k9 L) n) l: z4. Yu YM, Punyasavatsu N, Elder D, D’Ercole AJ. Sexual! }" H9 u# G' g. B# y$ q* Q
development in a two-year-old boy induced by topical/ n) a! w4 k2 z
exposure to testosterone. Pediatrics. 1999;104:e23.' O8 H' G) M. @+ w
5. Greulich WW, Pyle SI, eds. Radiographic Atlas of# e# x: v, J! A, i( D' E
Skeletal Development of the Hand and Wrist. 2nd ed.+ C2 _8 _3 x+ V
Stanford, CA: Stanford University Press; 1959.
3 }8 d' X* F8 E& ~. ?6. Physicians’ Desk Reference. Androgel 1% testosterone,) L/ [6 @3 ]5 u ~ @4 V% O
Unimed Pharmaceutical Inc. Montvale, NJ: Medical- v7 A6 ]- M2 E6 w6 b
Economics Company, Inc; 2004:3239-3241.
* x) U& n' w6 \- b+ w4 D7. Klugo RC, Cerny JC. Response of micropenis to topical7 J+ {7 c3 R. J9 S
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