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is a significant concern for physicians. Central
- t1 A$ ]9 w3 w E1 bprecocious puberty (CPP), which is mediated7 u, C- H9 G5 Z' m
through the hypothalamic pituitary gonadal axis, has+ f/ D% o& D+ ~
a higher incidence of organic central nervous system
- |4 t' A$ z9 k% olesions in boys.1,2 Virilization in boys, as manifested, ]! f' g+ V1 P7 M; C4 o5 a# c- T
by enlargement of the penis, development of pubic& P; f: X2 Q* {
hair, and facial acne without enlargement of testi-
, ]/ {! m$ _4 k5 D& n: U3 P9 Wcles, suggests peripheral or pseudopuberty.1-3 We
/ e% A% V0 Q: g3 u0 M8 T5 r: }( {report a 16-month-old boy who presented with the; x; r; R0 Y0 ?! F8 d$ s- I
enlargement of the phallus and pubic hair develop-/ C5 x; T+ G- q
ment without testicular enlargement, which was due
$ W$ \; @: z. E$ cto the unintentional exposure to androgen gel used by$ S, C8 O, ]. B* z/ r# V
the father. The family initially concealed this infor-; s4 v r. D1 ~6 ?
mation, resulting in an extensive work-up for this, r2 T3 Q/ E& D* A
child. Given the widespread and easy availability of7 s& t5 O% Z& c* U) m1 d* _& h
testosterone gel and cream, we believe this is proba-
; E/ E3 V% j. l1 Ibly more common than the rare case report in the
7 s( N" q0 Y1 b( Y0 F# G1 lliterature.48 B V% G7 B& h
Patient Report; ?: |7 V: k: x! m0 ]
A 16-month-old white child was referred to the6 ~& T. Y" `- c1 ^
endocrine clinic by his pediatrician with the concern! z. ?8 `& [$ u9 s
of early sexual development. His mother noticed
" E/ _% h6 |% `4 klight colored pubic hair development when he was! e3 t' }, Q4 ?$ z
From the 1Division of Pediatric Endocrinology, 2University of$ D4 }6 A! v9 y8 v
South Alabama Medical Center, Mobile, Alabama., X2 `6 k J3 u, C T
Address correspondence to: Samar K. Bhowmick, MD, FACE,
* E: ^% @, i* z N7 WProfessor of Pediatrics, University of South Alabama, College of
; K# P0 u: }" ~' U+ j# Y) ?; uMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;5 W6 A+ [* E5 Y7 L! o, ^
e-mail: [email protected].
n T3 S( o2 nabout 6 to 7 months old, which progressively became5 p- x4 J3 Z7 d% d- m# h; h5 m
darker. She was also concerned about the enlarge-
: ~: ^+ F5 e) Y2 ^" h, W: }6 rment of his penis and frequent erections. The child
* S+ P* Z! p4 {" b2 uwas the product of a full-term normal delivery, with
1 F$ C) U8 R% p+ \& q: J3 |a birth weight of 7 lb 14 oz, and birth length of, J1 I B1 l( i o" C1 H D3 s
20 inches. He was breast-fed throughout the first year j* f7 [- z8 M" `. p4 Z
of life and was still receiving breast milk along with1 M5 r4 |5 J1 h) W0 f- Q
solid food. He had no hospitalizations or surgery,, d9 F9 d, O+ r J8 Z; D' \/ u
and his psychosocial and psychomotor development; c2 i& \8 v6 ?3 H1 U" ]5 @
was age appropriate.
1 c/ w& _7 ` Z$ \1 {The family history was remarkable for the father," B' v6 d: V7 s U
who was diagnosed with hypothyroidism at age 16,
2 H5 d5 P8 j/ }* C- [# dwhich was treated with thyroxine. The father’s
+ V/ D @. _ j; h7 Wheight was 6 feet, and he went through a somewhat3 U! ~/ _5 B9 g! W
early puberty and had stopped growing by age 14.) g! a3 b% g- b+ j" f: F# G! f
The father denied taking any other medication. The& h2 |, y; E+ B4 C# B' J
child’s mother was in good health. Her menarche( I: m5 q. w. r. X3 k5 Y! e
was at 11 years of age, and her height was at 5 feet; D4 |2 v7 X+ M' Q9 w
5 inches. There was no other family history of pre-
# Q3 R6 j* F8 @' X( {cocious sexual development in the first-degree rela-, l' q& S; _/ U
tives. There were no siblings.
2 J" Y; \* J/ x3 pPhysical Examination Z4 O4 ~0 s& d" E5 H
The physical examination revealed a very active,% l% H! V& `$ m$ U% V
playful, and healthy boy. The vital signs documented Z P! y4 d' i" Q1 I( Q0 D$ W
a blood pressure of 85/50 mm Hg, his length was
2 f( k4 d% t, Z90 cm (>97th percentile), and his weight was 14.4 kg S9 L" X/ C' |4 p0 B( A/ _% g
(also >97th percentile). The observed yearly growth+ a/ g$ c8 n, e7 w1 i9 M2 F
velocity was 30 cm (12 inches). The examination of0 X0 i- N7 ~$ [. @
the neck revealed no thyroid enlargement.
' `- n: l ^! W/ x& Q1 `( lThe genitourinary examination was remarkable for
. k# w6 C4 h0 D9 @+ T2 }" P |enlargement of the penis, with a stretched length of) `" H7 Z# _- B) a) P& ~6 {# ?8 R
8 cm and a width of 2 cm. The glans penis was very well
" {, h. H3 u" Edeveloped. The pubic hair was Tanner II, mostly around
7 Y6 ] U4 N8 G P2 Z; [540* G$ F: c' G/ {2 |! Y! f4 g$ O
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
5 R# l6 H' m0 e# j8 Ythe base of the phallus and was dark and curled. The1 S3 u6 c6 Y! a! I/ S$ o
testicular volume was prepubertal at 2 mL each.
. u k) T' w' p% j- D+ n4 u5 o' xThe skin was moist and smooth and somewhat" p. z2 A' ]4 N/ J" V( L% S# f
oily. No axillary hair was noted. There were no9 T ^" ]3 m7 I o$ f
abnormal skin pigmentations or café-au-lait spots.2 O k, y; |4 i1 K0 x$ I8 Y
Neurologic evaluation showed deep tendon reflex 2+
+ S0 Q$ Z0 s5 g8 Nbilateral and symmetrical. There was no suggestion, l4 e. z7 E; ?
of papilledema.3 L9 G( L( M& n! B$ v; Y. r5 {
Laboratory Evaluation. q- H$ b" i" L
The bone age was consistent with 28 months by
p e4 E) s+ z: e+ jusing the standard of Greulich and Pyle at a chrono-4 k% ~* Y& _4 a+ v6 k9 s3 a
logic age of 16 months (advanced).5 Chromosomal! _9 i! p7 ~: j5 g0 ^ J- I
karyotype was 46XY. The thyroid function test
, C$ j) N6 y$ j6 i2 lshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
& U% d3 [$ Q, s5 t. xlating hormone level was 1.3 µIU/mL (both normal).7 l4 z1 {) C9 z8 k. H5 }1 e$ \
The concentrations of serum electrolytes, blood, p8 g6 g" r2 |- I
urea nitrogen, creatinine, and calcium all were
4 R, O- R/ |9 c+ F/ qwithin normal range for his age. The concentration) v9 l' i7 @5 J$ ^' M6 }! d
of serum 17-hydroxyprogesterone was 16 ng/dL
2 ]3 {" ~* L7 U(normal, 3 to 90 ng/dL), androstenedione was 20; U" G; |) @. Y$ U# O
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
i' I/ t! n! n( o2 o5 H. {( {" ?9 dterone was 38 ng/dL (normal, 50 to 760 ng/dL),0 o0 @/ e! {/ p3 |1 _
desoxycorticosterone was 4.3 ng/dL (normal, 7 to, g. f& c* F ~3 G0 v
49ng/dL), 11-desoxycortisol (specific compound S)
6 `: l5 k' L' P, ~2 T0 U) ]! F6 ?5 zwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-* u% B4 ^. f+ O( o3 n+ r
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
5 S( @# A" ]1 D. M& e. t! Otestosterone was 60 ng/dL (normal <3 to 10 ng/dL),$ r( M3 u6 k/ i3 s O; R+ k( b
and β-human chorionic gonadotropin was less than
# J f- C5 [+ A. J5 mIU/mL (normal <5 mIU/mL). Serum follicular
0 {8 I$ }7 z8 u$ astimulating hormone and leuteinizing hormone
* y" L5 C+ u0 B% i" econcentrations were less than 0.05 mIU/mL3 ^( ~7 a. W# g. B- b
(prepubertal).
/ Z" n/ |9 b" `/ G- O7 iThe parents were notified about the laboratory
& F( M6 x& G7 G3 w9 T6 z1 Q3 R( presults and were informed that all of the tests were4 h/ j% S# g( @8 |! \2 m& N
normal except the testosterone level was high. The9 d) v$ m6 ]" u3 B2 _( p3 P) h* Z
follow-up visit was arranged within a few weeks to
% I7 f' R6 ]/ Y# Sobtain testicular and abdominal sonograms; how-- w: o" `9 O# t* R; }8 i/ _! y
ever, the family did not return for 4 months.
9 K5 }9 M4 d5 K# L: e5 u1 T( pPhysical examination at this time revealed that the. A+ a$ q/ o! |4 r7 V3 m% X
child had grown 2.5 cm in 4 months and had gained
+ X5 c; ?3 D' A. K1 O7 C2 kg of weight. Physical examination remained3 m- _3 D1 W* F' P1 r2 [
unchanged. Surprisingly, the pubic hair almost com-$ K7 q; J" X _6 M
pletely disappeared except for a few vellous hairs at5 @6 I/ _3 W4 Y. }" I# g4 Y) }: [
the base of the phallus. Testicular volume was still 26 l+ e: H: f: D% N; ]7 s% G
mL, and the size of the penis remained unchanged.6 g- L5 H* q3 R' a# k; y
The mother also said that the boy was no longer hav-9 I& u8 A3 S5 x5 M; h- z9 E) m
ing frequent erections.* D, K. M# Z% N7 @4 t
Both parents were again questioned about use of
' c S+ A7 X3 H5 K9 |any ointment/creams that they may have applied to
2 _/ b j' x/ d. Uthe child’s skin. This time the father admitted the
+ S$ Q C: M/ u! T( |Topical Testosterone Exposure / Bhowmick et al 5411 e$ C) ]/ M+ a5 M! F
use of testosterone gel twice daily that he was apply-' ~! A2 {. b6 K$ O0 }; k" P
ing over his own shoulders, chest, and back area for
3 m/ R: X' G# A: @a year. The father also revealed he was embarrassed; c a/ Y$ S$ f. n1 W
to disclose that he was using a testosterone gel pre-9 g5 O: b8 \, H4 f2 B+ D' I+ f
scribed by his family physician for decreased libido
8 H: C/ [; f% j0 L* D; D9 W" psecondary to depression.
1 J% p! m3 {" A( q/ d1 F" d$ V7 o, a. TThe child slept in the same bed with parents.5 Y& t! _' L+ x% J5 x5 b) y
The father would hug the baby and hold him on his* \# g1 ^; X4 \ |! v
chest for a considerable period of time, causing sig-
/ B5 g$ j5 }: D% ]# \nificant bare skin contact between baby and father.
1 D5 }, N# v# m* V# ^, R1 TThe father also admitted that after the phone call,
: D" Y* m+ Z! R0 V: i7 iwhen he learned the testosterone level in the baby
6 e3 v; Q2 V6 _' x+ A5 Zwas high, he then read the product information
" a4 L! E- [% D" v* m" Y1 i9 E% `1 Ppacket and concluded that it was most likely the rea-
/ y% y( l& y) x3 w. `' L% Rson for the child’s virilization. At that time, they% M5 \- c+ \6 a" j2 c( I
decided to put the baby in a separate bed, and the
! M6 {7 }) I, }4 n# zfather was not hugging him with bare skin and had1 G; W$ m- \/ O
been using protective clothing. A repeat testosterone
, d6 S! ?/ K/ O0 c; E5 o. w3 Ftest was ordered, but the family did not go to the
/ Y9 f! E7 R# Klaboratory to obtain the test.
3 S x8 s; H+ e/ ?- eDiscussion2 `! X9 S1 c# M' k3 n
Precocious puberty in boys is defined as secondary
& |" c" Y8 h# N( n2 Z( J/ tsexual development before 9 years of age.1,48 M. n2 d% u6 t+ z) j- C8 S& b
Precocious puberty is termed as central (true) when
* K, j0 ^& J3 Z& u& @it is caused by the premature activation of hypo-7 Q+ C' B9 M4 Q8 M/ D; {3 c
thalamic pituitary gonadal axis. CPP is more com-. I j, c* v0 u/ }
mon in girls than in boys.1,3 Most boys with CPP* Z. C" j2 }' T! C2 E
may have a central nervous system lesion that is+ t2 V. I* k8 B; \. \: h" N
responsible for the early activation of the hypothal-
- q; u; \4 T4 o- C9 Jamic pituitary gonadal axis.1-3 Thus, greater empha-
$ c' W C" L. [& Z2 i9 e' u7 Z* ^sis has been given to neuroradiologic imaging in
6 W* i) Q n2 d$ ^( kboys with precocious puberty. In addition to viril-
4 @+ x& {6 q- m2 R5 Dization, the clinical hallmark of CPP is the symmet-" i1 Y/ ^- c' E; d T7 V6 n( }9 V
rical testicular growth secondary to stimulation by
# U3 W: l( x1 e+ ^+ A1 l0 C+ @$ igonadotropins.1,34 B2 p4 ]& I8 A
Gonadotropin-independent peripheral preco-6 X8 O$ m) t" A8 @+ M8 \
cious puberty in boys also results from inappropriate2 M, O' {) G' B: m8 ?9 [
androgenic stimulation from either endogenous or
# K& Q7 F4 Z; F2 W* \- _& t! gexogenous sources, nonpituitary gonadotropin stim-% z3 u8 n+ R) w+ D( X/ o
ulation, and rare activating mutations.3 Virilizing
# h% c! t) D/ E) |, X5 P- Ocongenital adrenal hyperplasia producing excessive
" _% X: i2 ^" W* H o6 F; {; y/ Jadrenal androgens is a common cause of precocious: F, R( ^8 P/ L* a! a
puberty in boys.3,4/ A& g9 i7 y) j- G" k8 f
The most common form of congenital adrenal& Y, l( r2 H$ b2 _. z
hyperplasia is the 21-hydroxylase enzyme deficiency.
& [' s6 R" ?9 L( W+ R1 ~The 11-β hydroxylase deficiency may also result in+ F* W8 K5 `- V J- I2 t
excessive adrenal androgen production, and rarely,0 E; H" O! X& C# h9 F
an adrenal tumor may also cause adrenal androgen* E1 \ L F# L& t: \
excess.1,3
1 ]7 w" O* z$ L. h# G$ Uat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from" q$ P3 d4 k: Z% y
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
: q: g: y1 H5 P4 N. sA unique entity of male-limited gonadotropin-
$ i% C: j& _, \& Cindependent precocious puberty, which is also known( Y8 D4 V2 _( R0 Z6 W! b' `
as testotoxicosis, may cause precocious puberty at a9 }. R8 ^1 m6 E. H0 n9 F$ j; b
very young age. The physical findings in these boys
* R# H0 B6 N0 e( |6 y: X3 J& wwith this disorder are full pubertal development,
R% X) F7 {7 H# R" Vincluding bilateral testicular growth, similar to boys! }$ }3 ]1 N. c. E. C4 g& M7 C
with CPP. The gonadotropin levels in this disorder% I' \0 B+ f4 i7 ~8 z
are suppressed to prepubertal levels and do not show
0 O6 Q/ v2 n8 q0 D4 {+ @pubertal response of gonadotropin after gonadotropin-. L% a- K; ~% Y" @5 J
releasing hormone stimulation. This is a sex-linked0 O* x1 T3 Y( t0 _
autosomal dominant disorder that affects only
6 _/ n# H+ J. C" B1 F5 }# x* Ymales; therefore, other male members of the family
3 J) P, w, J$ w4 e4 c3 omay have similar precocious puberty.3& d1 ^6 d+ e+ C" A2 x
In our patient, physical examination was incon-6 I) j1 g: X/ H8 i- e1 [
sistent with true precocious puberty since his testi-
( v1 H; W! i/ b7 v7 w% [cles were prepubertal in size. However, testotoxicosis
# K" R1 G3 S1 twas in the differential diagnosis because his father5 c! o2 t- ]* m
started puberty somewhat early, and occasionally,
% z% W- c3 ^/ Q1 Otesticular enlargement is not that evident in the& p+ Q/ R U0 s2 ]) i9 [/ w
beginning of this process.1 In the absence of a neg-8 u# l7 {4 \0 z/ S
ative initial history of androgen exposure, our
# B) _5 Z3 j: n5 W4 E- U2 z. ibiggest concern was virilizing adrenal hyperplasia,
v* ]- X4 W% I5 Q) Aeither 21-hydroxylase deficiency or 11-β hydroxylase$ n- n7 O4 S' @) N
deficiency. Those diagnoses were excluded by find-+ O: w" h2 e) Y# j
ing the normal level of adrenal steroids.6 G' |: w$ L: l* m
The diagnosis of exogenous androgens was strongly. O. Q% _6 K" ^* Q
suspected in a follow-up visit after 4 months because
! l. P7 F8 k1 {the physical examination revealed the complete disap-
: K+ V# Z* o5 [ _/ ^5 [pearance of pubic hair, normal growth velocity, and
: U+ ^- b, S9 x& d/ ^decreased erections. The father admitted using a testos-
9 g' S' J4 j9 [terone gel, which he concealed at first visit. He was
; t$ S' B, g" Rusing it rather frequently, twice a day. The Physicians’
5 v7 ]/ s% E1 mDesk Reference, or package insert of this product, gel or$ i2 R+ i$ K: K; Q
cream, cautions about dermal testosterone transfer to% ?6 i: d% Z; q' j: B5 T
unprotected females through direct skin exposure.
' i2 F6 k+ e- X* ^- R2 Z, ?/ ^Serum testosterone level was found to be 2 times the
, p" ?7 o; p: L" U" P: Lbaseline value in those females who were exposed to& |; G5 X0 i5 X+ i' a- ?
even 15 minutes of direct skin contact with their male
$ r1 ?* ]- x8 {: g% W; jpartners.6 However, when a shirt covered the applica-
2 f: e D9 X6 g2 E: ftion site, this testosterone transfer was prevented.
; q9 @% k& `# q* }! z5 lOur patient’s testosterone level was 60 ng/mL,6 R1 F9 e! {* _! H
which was clearly high. Some studies suggest that/ z' z- ^8 O% h1 M6 S# U! S* R
dermal conversion of testosterone to dihydrotestos-' n+ X, S7 v* [, x/ K& s+ x
terone, which is a more potent metabolite, is more9 x+ N% T# z& {
active in young children exposed to testosterone
' {$ l: e" j1 `2 H( zexogenously7; however, we did not measure a dihy-6 X& I/ V8 V! ]% C& w* b1 \
drotestosterone level in our patient. In addition to5 Q' P. L. `5 V, S0 F. Q
virilization, exposure to exogenous testosterone in) {" j/ t" R9 A& [$ I; O8 h) {
children results in an increase in growth velocity and; L* \" o6 \. v& k1 Q1 Z. ]
advanced bone age, as seen in our patient.
, A8 p" l( {, c4 H" P% lThe long-term effect of androgen exposure during
2 L, k' K9 Y* d/ f/ m) Yearly childhood on pubertal development and final; l1 V0 w1 u0 t
adult height are not fully known and always remain. L4 h- T* f' w( }$ R
a concern. Children treated with short-term testos-
- J* M# Y+ |) oterone injection or topical androgen may exhibit some
1 x5 k0 }- w, E* N aacceleration of the skeletal maturation; however, after
9 ~7 K2 y' O) _7 M9 @cessation of treatment, the rate of bone maturation9 {/ t( {; `/ I0 w
decelerates and gradually returns to normal.8,9+ U5 M5 K% S; [
There are conflicting reports and controversy
: \/ ^( B5 H6 K* u8 w4 uover the effect of early androgen exposure on adult/ Y/ \) Q* M5 n- [
penile length.10,11 Some reports suggest subnormal
/ w% E9 N# h4 m" ?$ Hadult penile length, apparently because of downreg-
9 T X" \/ B8 A: M( P$ Yulation of androgen receptor number.10,12 However,
$ B7 m6 l3 A/ j5 h O6 NSutherland et al13 did not find a correlation between& \9 z3 |/ T0 }1 r$ K& I2 g
childhood testosterone exposure and reduced adult
Z+ K5 H- ^- jpenile length in clinical studies.
; h- m' o0 c! J& {1 i; X' WNonetheless, we do not believe our patient is6 y' m* f2 c- L! d6 W) o: x. E
going to experience any of the untoward effects from
: a% b% V) T" r/ \0 ptestosterone exposure as mentioned earlier because6 Q( ]0 s3 m5 w x0 Y! L
the exposure was not for a prolonged period of time.) k$ z- Y0 u& p
Although the bone age was advanced at the time of4 Y* `# z8 d4 c
diagnosis, the child had a normal growth velocity at8 F. v I( N. \. X; n+ @% U
the follow-up visit. It is hoped that his final adult
0 B! B. W# [1 ]% D; s5 hheight will not be affected.
; S1 y$ ?# Q* n3 T7 o5 G& nAlthough rarely reported, the widespread avail-! ~5 S3 e3 A: Z8 _- c
ability of androgen products in our society may
# h1 I/ l8 @' I% T/ Q* i$ ?indeed cause more virilization in male or female
& P$ z) `3 K2 `children than one would realize. Exposure to andro-
* N9 o4 ^1 w1 P3 Tgen products must be considered and specific ques-3 q5 M: Q# J$ |" A5 _4 \
tioning about the use of a testosterone product or
4 T5 X8 t! C" H4 P9 i6 G( Y* Xgel should be asked of the family members during7 S% ~) s' Z" M# t7 x5 _5 a
the evaluation of any children who present with vir-
3 C4 Q4 D+ b3 x1 B9 I* \% z* dilization or peripheral precocious puberty. The diag-
6 a* N% @; K* N5 W/ ?8 Lnosis can be established by just a few tests and by
\1 u- T& p( v9 q/ I0 x+ \appropriate history. The inability to obtain such a9 S o- [5 M! q$ Y1 W# y6 d0 w
history, or failure to ask the specific questions, may6 `* Y. b* N- g6 ~' ?) V' A4 L! N
result in extensive, unnecessary, and expensive% P* Q$ A' e' N4 t
investigation. The primary care physician should be0 g9 s- C+ z- G" Q
aware of this fact, because most of these children2 x% ]) z1 Y. N$ Y
may initially present in their practice. The Physicians’6 e& P5 C2 E3 w+ c" W! z
Desk Reference and package insert should also put a
+ X" w; [4 d$ F3 d, {warning about the virilizing effect on a male or' T0 s4 ?& Y* G/ ?" E# {
female child who might come in contact with some-. a% h3 i" W& o8 k k* F. w+ @9 T
one using any of these products.
# r3 o4 H4 b( v3 a$ |6 `References4 ]3 p$ r% X9 {- i8 V& |
1. Styne DM. The testes: disorder of sexual differentiation
3 i$ b5 ~$ f5 y' {and puberty in the male. In: Sperling MA, ed. Pediatric
% j" ~- k. k9 A& ?# D1 kEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
6 H3 x+ L0 ~; h+ f8 z2002: 565-628.
9 V+ E% c; G1 @$ _2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
+ K# e8 X; D+ a1 G6 a# k& zpuberty in children with tumours of the suprasellar pineal. Q3 T7 {4 z3 f: m2 @
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from9 y9 p* k: k- p+ s3 \' O
Topical Testosterone Exposure / Bhowmick et al 543
) C/ @; S; E1 ^6 aareas: organic central precocious puberty. Acta Paediatr./ v6 q( t b! p1 L$ b/ c
2001;90:751-756.
. t: C/ m" T$ I4 K9 h3. Lee PA. Puberty and its disorders. In: Lifshitz F, ed.
3 l x6 {# V) G/ d; g0 X& S' Z% I7 ~4 wPediatric Endocrinology. 4th ed. New York, NY: Marcel
" j H) _6 e- O2 f$ fDekker Inc; 2003:211-238.
6 w9 B3 Q$ t: d0 D7 [0 D4. Yu YM, Punyasavatsu N, Elder D, D’Ercole AJ. Sexual' {0 d6 e; m- e+ i5 t+ h" O
development in a two-year-old boy induced by topical
8 M V! \ d' D: Q! J) Kexposure to testosterone. Pediatrics. 1999;104:e23.! }/ g1 v' o; q, S6 {6 T# w
5. Greulich WW, Pyle SI, eds. Radiographic Atlas of
" Z4 ]" g9 T$ T# y4 U4 F1 _Skeletal Development of the Hand and Wrist. 2nd ed.4 z! j( z& L) e/ J8 y3 ^
Stanford, CA: Stanford University Press; 1959.7 y2 P7 F% T9 h3 k9 ~
6. Physicians’ Desk Reference. Androgel 1% testosterone,. l" C, r Y2 d$ Y9 F
Unimed Pharmaceutical Inc. Montvale, NJ: Medical% j( g. F: p$ o- |2 N j! r
Economics Company, Inc; 2004:3239-3241.2 H4 z- b+ {# \+ l; _
7. Klugo RC, Cerny JC. Response of micropenis to topical/ g4 ]/ H& y- T. P3 H5 Z% C. B
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