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is a significant concern for physicians. Central
; R3 k, y: t$ ? hprecocious puberty (CPP), which is mediated
# l d% m+ X( Z4 l. Nthrough the hypothalamic pituitary gonadal axis, has
) o' z1 v# n; Ta higher incidence of organic central nervous system
9 d T+ J3 g, t* U9 `& t% ^lesions in boys.1,2 Virilization in boys, as manifested
& S+ K' ~& i5 {1 H9 v+ k% A: bby enlargement of the penis, development of pubic& w7 R) E% J" z. O, b* l: `
hair, and facial acne without enlargement of testi-8 T3 }* n1 O! r# @6 `# G
cles, suggests peripheral or pseudopuberty.1-3 We
3 D7 n% O4 l8 w" d* |* y. t A3 Oreport a 16-month-old boy who presented with the! [) ] _% U0 T+ {: n- O
enlargement of the phallus and pubic hair develop-( t8 T+ d7 Y+ A0 h u7 I7 ?
ment without testicular enlargement, which was due
2 M7 u6 p- Z0 ]3 Wto the unintentional exposure to androgen gel used by2 o& s; t7 y: a$ g% G$ r: L
the father. The family initially concealed this infor-' v2 m/ Q+ u& L% M3 I8 s, G. @: f
mation, resulting in an extensive work-up for this7 `/ x6 x3 ~3 k; f8 ^/ c% t. t
child. Given the widespread and easy availability of0 r" Q% `2 K. I( h. Z
testosterone gel and cream, we believe this is proba-9 {) v' O8 N; `$ t8 C# i5 y% ^
bly more common than the rare case report in the2 q* O# S4 {6 o" p1 {# O" x
literature.4' J' |. H$ a5 F
Patient Report
0 j+ S( I; E% C3 }: A' mA 16-month-old white child was referred to the/ {% g) f4 Z5 Y3 K6 q0 W5 a9 W, k
endocrine clinic by his pediatrician with the concern" g% d; @ {% N* O. R! S
of early sexual development. His mother noticed
$ a6 K! a1 W/ l! Klight colored pubic hair development when he was+ c1 I$ w C' e/ z/ ~
From the 1Division of Pediatric Endocrinology, 2University of
, W: K6 } l: ^" s& ISouth Alabama Medical Center, Mobile, Alabama.
0 ?7 e1 p) Q: x! Y) V yAddress correspondence to: Samar K. Bhowmick, MD, FACE,: E! G8 e/ ]/ d9 @, W5 n
Professor of Pediatrics, University of South Alabama, College of
, r ^* L4 _5 f# MMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;) q7 H1 J1 @4 t7 j! A3 n
e-mail: [email protected].
5 ?5 y* k5 W- Zabout 6 to 7 months old, which progressively became
. o* J$ P0 M. K6 T7 xdarker. She was also concerned about the enlarge-
; \. D+ r5 S! e* g/ P( Y/ Vment of his penis and frequent erections. The child
+ U, w9 m" O* a$ g. G* j( }was the product of a full-term normal delivery, with7 E" g7 A! N1 ?$ z$ U; D7 o) u
a birth weight of 7 lb 14 oz, and birth length of& F- ? S: q4 H* S/ v5 N0 o5 o$ u
20 inches. He was breast-fed throughout the first year& _9 `: \. e; }
of life and was still receiving breast milk along with' k; E5 Q: y$ _& P" }- V
solid food. He had no hospitalizations or surgery,
% x4 Z$ T% k2 W0 Eand his psychosocial and psychomotor development
- h7 r; G7 \: F0 owas age appropriate.
) H/ ^' r B, l, v. n7 t9 oThe family history was remarkable for the father," Q9 k8 E+ d/ _+ `
who was diagnosed with hypothyroidism at age 16,$ ^" P9 {. l1 p" \
which was treated with thyroxine. The father’s* u2 R& K$ V2 }/ A! |( {
height was 6 feet, and he went through a somewhat
8 \3 ^; a) O, x8 qearly puberty and had stopped growing by age 14.0 A" ?. B* W) U c; d$ [
The father denied taking any other medication. The
/ C( O* c" z8 y) y- B2 W9 Achild’s mother was in good health. Her menarche0 ]( {- M& _. e" ^# C. |
was at 11 years of age, and her height was at 5 feet# e( G, e5 w) K4 H7 S _
5 inches. There was no other family history of pre-
[' s7 o6 {5 B m( i/ C Bcocious sexual development in the first-degree rela-
/ Z8 Y' [, d9 F) B. z( Itives. There were no siblings.
, ~; l K4 A1 ^# s0 A7 qPhysical Examination
7 a- {9 I& C8 m8 KThe physical examination revealed a very active,8 L, K+ P% _5 |' x, _+ Z, r/ I
playful, and healthy boy. The vital signs documented
2 D. j) u: B$ t8 ^6 }, Wa blood pressure of 85/50 mm Hg, his length was. k8 ?+ f7 Y0 i D
90 cm (>97th percentile), and his weight was 14.4 kg4 ^, J" t8 K- b* q- D, g" X. X$ G7 N+ \6 E
(also >97th percentile). The observed yearly growth
$ }+ b/ X+ z: i# |7 Yvelocity was 30 cm (12 inches). The examination of/ n t9 U' z- v5 B0 Z# w$ d
the neck revealed no thyroid enlargement. p" ?& ~0 W, s
The genitourinary examination was remarkable for
p# l* }2 w0 @' x! e' benlargement of the penis, with a stretched length of. _% U! V* A6 o+ m# W1 l
8 cm and a width of 2 cm. The glans penis was very well& E+ Q: k" L( h3 f+ U9 v1 x O
developed. The pubic hair was Tanner II, mostly around
, u1 V8 d$ @( x# v1 T' d+ J0 f540 O: v, m: l5 c) k5 w5 T
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
! ^! x* [; k# t \the base of the phallus and was dark and curled. The
- s& h0 R- n: E' l6 ztesticular volume was prepubertal at 2 mL each.
, H* ^- O9 ~5 @8 D; W0 J& h, Z5 ~The skin was moist and smooth and somewhat8 L* y2 w. |/ i j
oily. No axillary hair was noted. There were no, C* E9 H3 |2 d0 x4 `
abnormal skin pigmentations or café-au-lait spots.' M* F5 A& [2 S0 F5 ^
Neurologic evaluation showed deep tendon reflex 2+$ m* ~' R" Y+ r: X/ P
bilateral and symmetrical. There was no suggestion
/ a, ?: e* ~8 R! c y! qof papilledema./ ^' ~ v" U) c1 Y3 I7 x* T
Laboratory Evaluation8 H8 g0 ]5 S4 r8 q+ ^7 T1 p" R
The bone age was consistent with 28 months by6 a2 {; E( ]' O$ t) _4 n; |" ]/ t
using the standard of Greulich and Pyle at a chrono-" Z' q/ d0 u) I* L X6 u
logic age of 16 months (advanced).5 Chromosomal
! ~7 s" k7 o T f# ykaryotype was 46XY. The thyroid function test# I8 M8 d1 Z9 n& b* v& t. H
showed a free T4 of 1.69 ng/dL, and thyroid stimu-7 r5 y1 E0 j8 e1 ~- Q! P3 q2 s" `( b
lating hormone level was 1.3 µIU/mL (both normal).9 M4 m" H: q @% Y# E1 t
The concentrations of serum electrolytes, blood3 j- z" j( J) T2 J# P5 {
urea nitrogen, creatinine, and calcium all were# D" J- q- U0 }
within normal range for his age. The concentration
, t7 l$ N3 v$ S2 m- g" _+ rof serum 17-hydroxyprogesterone was 16 ng/dL0 M X& p, T1 e7 u) X, N$ c1 z, w
(normal, 3 to 90 ng/dL), androstenedione was 20" V# p0 L, B- _
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-! C8 W& i3 x4 F' z/ ?# X* y
terone was 38 ng/dL (normal, 50 to 760 ng/dL),( ?2 |4 V; t; R! g
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
p! a7 v, u0 E4 V, @49ng/dL), 11-desoxycortisol (specific compound S)$ h7 w9 z5 s) |- q5 L& e
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
7 d) s5 c. n. Q0 [tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
" B7 E+ C* e6 o7 L6 c6 [+ q! @testosterone was 60 ng/dL (normal <3 to 10 ng/dL),& |( C5 A& l8 d/ U+ w! O1 m
and β-human chorionic gonadotropin was less than
* i1 ?; B- B0 B m1 K4 L5 mIU/mL (normal <5 mIU/mL). Serum follicular
( k9 y) l3 A+ r( Nstimulating hormone and leuteinizing hormone) ^6 ~! K3 w; N3 b; S! d; p* U$ K) a
concentrations were less than 0.05 mIU/mL$ H8 q7 |2 r( m7 i( a7 I4 V% ?3 K
(prepubertal).9 X% V+ ]& d" A! s+ D2 K8 K3 q- J
The parents were notified about the laboratory
0 S- y* v% f7 g0 j kresults and were informed that all of the tests were6 g' i; J U1 }0 u2 I
normal except the testosterone level was high. The
( R2 Y5 }( D" g3 ~6 _! m7 C# nfollow-up visit was arranged within a few weeks to
1 f" v" G3 g0 mobtain testicular and abdominal sonograms; how-
/ n5 z( d7 i6 u' ?ever, the family did not return for 4 months.# k; g! T0 X) e
Physical examination at this time revealed that the
) }, H, @( I) v) q6 wchild had grown 2.5 cm in 4 months and had gained
$ N T4 D" ^; S- F D1 u2 kg of weight. Physical examination remained
9 x/ l' J) [' A6 I* N% Z/ kunchanged. Surprisingly, the pubic hair almost com-
0 e1 K E3 J& j8 e9 k" Ypletely disappeared except for a few vellous hairs at
# ], F @3 l% W. p* jthe base of the phallus. Testicular volume was still 20 i; L3 ~/ c, w2 E
mL, and the size of the penis remained unchanged./ Z1 z$ v8 _7 j, G% d
The mother also said that the boy was no longer hav-7 e2 x8 f0 d) ~( E
ing frequent erections.8 j1 L* ?+ F/ I! N& y3 ? p4 U# h: n
Both parents were again questioned about use of' a& U. v p6 x9 }" O
any ointment/creams that they may have applied to
# [( X( U6 j3 Bthe child’s skin. This time the father admitted the7 G4 Z. t: E, b
Topical Testosterone Exposure / Bhowmick et al 541
5 h8 o0 K! V k8 @1 C5 \use of testosterone gel twice daily that he was apply-
P3 z' c6 N, U% ] I# S# zing over his own shoulders, chest, and back area for: D' h2 i! f0 Q9 b
a year. The father also revealed he was embarrassed
8 I% b! H+ s" d) _to disclose that he was using a testosterone gel pre-
! g1 g. L" F* pscribed by his family physician for decreased libido; [5 S' y, D9 X, u" F6 |/ p! k) c
secondary to depression.
# t3 L& i4 Z& i* MThe child slept in the same bed with parents.
9 n7 T# K" {+ b9 B) ?1 c. Z+ xThe father would hug the baby and hold him on his
* U) ~9 Z" ^, n- ~/ a' kchest for a considerable period of time, causing sig-
# X( l. o. Q% Fnificant bare skin contact between baby and father.
, T* G* r. Z, M) w* E: ^3 KThe father also admitted that after the phone call,
# f) W- i8 [0 ]0 e, r7 L4 B- x) Awhen he learned the testosterone level in the baby8 K; `, y: P. d/ z( `, s+ i0 o
was high, he then read the product information6 Y8 j6 ?. S, V# U( G
packet and concluded that it was most likely the rea-
# {7 l; R% C) @' j) N4 ?son for the child’s virilization. At that time, they
) b. s; ?, g7 V5 J- O( Kdecided to put the baby in a separate bed, and the' X& K; I% N& c7 p" o% ?& a- `* w
father was not hugging him with bare skin and had7 G2 }/ _. M2 h2 l( Y! E$ R5 C
been using protective clothing. A repeat testosterone
* q9 B9 S" W7 Z; qtest was ordered, but the family did not go to the
& n1 }/ _0 s5 [: d$ elaboratory to obtain the test.8 \8 F8 S4 A3 D2 t3 Y$ |) `
Discussion# v- J- i. `! F4 a( A
Precocious puberty in boys is defined as secondary( w- f m0 S) m. V5 ~0 B- @
sexual development before 9 years of age.1,41 u) h* v7 \7 k& S) I/ Y N' Q3 U1 h$ P m
Precocious puberty is termed as central (true) when
: J" B) W- a; A8 mit is caused by the premature activation of hypo-
. a5 s* ]' @" ]& Rthalamic pituitary gonadal axis. CPP is more com-8 I4 h# P; t1 h( C2 |
mon in girls than in boys.1,3 Most boys with CPP
7 Y: s2 e4 ?' k! R: z7 |8 t; Rmay have a central nervous system lesion that is
$ s! ~: G1 y, F' t. vresponsible for the early activation of the hypothal-7 n* U0 r1 X1 t. a
amic pituitary gonadal axis.1-3 Thus, greater empha-
, @& Q; h( X; c3 _sis has been given to neuroradiologic imaging in3 f8 n7 T j( o$ v
boys with precocious puberty. In addition to viril-
" x. l+ ~# a. a; ^/ `! e0 y. Uization, the clinical hallmark of CPP is the symmet-
$ k' F! n* U) U. V$ Z) {0 o0 Srical testicular growth secondary to stimulation by6 j3 S# t0 O6 l8 Y) g1 q
gonadotropins.1,3
% C" B0 b2 \( @Gonadotropin-independent peripheral preco-- q- [0 B1 U2 V9 {- N* T0 h8 q
cious puberty in boys also results from inappropriate! [& O. S! S G* q ~. r
androgenic stimulation from either endogenous or
$ D; d3 u+ F9 q8 y, L gexogenous sources, nonpituitary gonadotropin stim-
C: V9 H! C. j2 }' A* O; Julation, and rare activating mutations.3 Virilizing
0 W0 ]; G! ]7 d: w( ycongenital adrenal hyperplasia producing excessive) T _( K& O& `0 w* I" s2 H
adrenal androgens is a common cause of precocious; m* p: L4 y. Y% H: o5 _
puberty in boys.3,4
0 _) z8 g' {+ b# b/ j+ LThe most common form of congenital adrenal9 ? d1 k& @. A+ t6 W" z
hyperplasia is the 21-hydroxylase enzyme deficiency.* l- d: h- ?% _+ _2 C1 o$ N
The 11-β hydroxylase deficiency may also result in
$ Q! a' E; y! ^7 F2 u7 Kexcessive adrenal androgen production, and rarely,/ `( N4 |% Z, R y+ K- C- @
an adrenal tumor may also cause adrenal androgen# ^# N7 d" { \. U; [
excess.1,3
+ u3 }6 U' c- C. m1 r" Kat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
9 h" u: N4 O4 o V: \542 Clinical Pediatrics / Vol. 46, No. 6, July 20078 |* t4 M' B4 Z% \) B
A unique entity of male-limited gonadotropin-
0 x5 \) h: `' hindependent precocious puberty, which is also known
/ w, c4 \0 V0 v& I- L4 K: w4 t! Kas testotoxicosis, may cause precocious puberty at a# ~/ s% N1 }/ P0 M/ v
very young age. The physical findings in these boys
( q3 }; R F2 }! I$ N% q) }with this disorder are full pubertal development,& b( l. k0 m% A/ }+ Y7 o
including bilateral testicular growth, similar to boys- }5 y8 ?+ r1 j" ?
with CPP. The gonadotropin levels in this disorder
' L, @' ~* l& @are suppressed to prepubertal levels and do not show* W6 v5 N. A4 V# x5 p9 Q
pubertal response of gonadotropin after gonadotropin-
! {' b: C# \; qreleasing hormone stimulation. This is a sex-linked+ E4 j% J' s2 [6 E( O- S# v) x8 h
autosomal dominant disorder that affects only1 e' ? Y" i& B+ ]
males; therefore, other male members of the family0 P P0 K3 m& l/ a' T
may have similar precocious puberty.3% v" O F } w2 L% D( d4 k2 t
In our patient, physical examination was incon-
% I& u& f( R& M/ n) i+ a+ C& K* dsistent with true precocious puberty since his testi-" ^1 D7 |6 D- |* m2 r3 Y
cles were prepubertal in size. However, testotoxicosis% X! i) M9 [0 G. x# R# G
was in the differential diagnosis because his father/ V+ U" z2 i& f* t8 r) S
started puberty somewhat early, and occasionally,1 ?7 f) p; H( i5 N' V1 J+ B
testicular enlargement is not that evident in the
& L+ v( ]) z7 o2 y$ {beginning of this process.1 In the absence of a neg-
7 _% L" ?% o$ z# {ative initial history of androgen exposure, our0 T, x. |/ L& S6 l& f. I" |
biggest concern was virilizing adrenal hyperplasia,
9 p! G, K' H- y7 I) q% R. ueither 21-hydroxylase deficiency or 11-β hydroxylase2 Y1 h6 C8 H7 l( A. s9 J
deficiency. Those diagnoses were excluded by find-* F) t& i, f; b; P' k& w' a
ing the normal level of adrenal steroids.* v$ [* o4 T7 n; _3 q: G
The diagnosis of exogenous androgens was strongly9 U0 T* R# z2 }
suspected in a follow-up visit after 4 months because ^9 B0 a& v7 h( z7 A
the physical examination revealed the complete disap- H4 W8 V/ `$ s, C: N0 j/ ?& g
pearance of pubic hair, normal growth velocity, and( k7 b( R& R& P6 o9 Y
decreased erections. The father admitted using a testos- F% @& ~0 M5 M" I' A" a( X" f0 q
terone gel, which he concealed at first visit. He was3 ` u7 t& F( C3 m+ M3 e5 O
using it rather frequently, twice a day. The Physicians’7 G8 m) o) ]& `/ i( r# l
Desk Reference, or package insert of this product, gel or
) _' ]3 _0 W6 Q8 x' D& Acream, cautions about dermal testosterone transfer to
! Y' c+ D+ d+ J4 {. h. J% V$ `unprotected females through direct skin exposure.
( S2 a& ]3 G$ B! b. Y" \0 ESerum testosterone level was found to be 2 times the) p& @! Y6 F5 t
baseline value in those females who were exposed to
) \1 H' o) A& P/ N7 W# Teven 15 minutes of direct skin contact with their male7 W' m. Q# s( |/ j$ t: a
partners.6 However, when a shirt covered the applica-
9 f1 `/ P* m6 ~- x3 Ntion site, this testosterone transfer was prevented.
3 g% |9 U% q0 C4 V! W$ A# lOur patient’s testosterone level was 60 ng/mL,
. Q; I% [$ a2 K ~# T2 Fwhich was clearly high. Some studies suggest that
" {" x. [% v* m% Qdermal conversion of testosterone to dihydrotestos-
5 m( ]5 @) {, A9 `( u/ ~2 ~9 z: lterone, which is a more potent metabolite, is more& X5 l% z/ ]' d
active in young children exposed to testosterone
* W/ k4 @* u2 y' q/ A. T/ Vexogenously7; however, we did not measure a dihy-
. G, ?& j# e2 c+ w( H( m& @. q, w1 Adrotestosterone level in our patient. In addition to
! m' O9 W5 J' K" @+ n! C4 u. ^$ q( {virilization, exposure to exogenous testosterone in
& v0 \% ?8 a- I: Dchildren results in an increase in growth velocity and8 h o4 \) u$ D! N! }
advanced bone age, as seen in our patient.
% ~( b- ]7 V0 e1 a% g; TThe long-term effect of androgen exposure during
3 \$ J* Z6 a. ^( d* i3 @8 e& p% cearly childhood on pubertal development and final
! m: l2 a, e' g0 L; |( g% t* [$ w' jadult height are not fully known and always remain
: F; G) G L5 D; {a concern. Children treated with short-term testos-) f* \" S* |3 v, W
terone injection or topical androgen may exhibit some
0 ], e- D: r1 Q* Cacceleration of the skeletal maturation; however, after
" ~3 v7 V5 w3 scessation of treatment, the rate of bone maturation+ d6 ?7 X4 Z, ^4 Q( C8 G& r
decelerates and gradually returns to normal.8,9
5 {* g" s$ s9 G# P4 A" o( V+ hThere are conflicting reports and controversy
, j& P) W* N4 O7 I8 Rover the effect of early androgen exposure on adult* c4 ?) U7 h( j; ?- e
penile length.10,11 Some reports suggest subnormal
5 |/ x9 f9 d, I/ V, c; L& J$ d( hadult penile length, apparently because of downreg-
9 n; n& @0 M g+ _ulation of androgen receptor number.10,12 However,$ _+ j; t% r+ b
Sutherland et al13 did not find a correlation between0 q, Z& Z% @" ?0 I/ u. x
childhood testosterone exposure and reduced adult
e6 H) l" `; L6 n; j! bpenile length in clinical studies.4 I# T0 c. S v5 d1 m* I8 G4 f! |
Nonetheless, we do not believe our patient is
k4 c% I9 B0 w+ b8 Jgoing to experience any of the untoward effects from5 I3 N$ B- B/ E9 P f( ]
testosterone exposure as mentioned earlier because" k5 Q1 w7 Q3 P2 \* X/ a
the exposure was not for a prolonged period of time.
7 g2 h$ a1 M6 A4 A; P' o hAlthough the bone age was advanced at the time of
, f- H4 |7 _6 { Ldiagnosis, the child had a normal growth velocity at
3 F5 X9 l3 F- q; j; _) @the follow-up visit. It is hoped that his final adult
8 P+ t) A' y+ Y/ _/ K5 zheight will not be affected./ A/ U3 E8 M" X! ]) H+ k# ^
Although rarely reported, the widespread avail-
6 U# E/ \6 d/ P6 q/ a+ e, ^% h- tability of androgen products in our society may' t1 {# ~- f2 V* h2 c/ W
indeed cause more virilization in male or female' d! x- m8 G( ]
children than one would realize. Exposure to andro-
; J0 K' v' N& ]0 l+ Z9 Jgen products must be considered and specific ques-
6 I( D. M# F+ w6 e& r! `% {7 Ationing about the use of a testosterone product or- q# g+ m# j+ X8 {2 M
gel should be asked of the family members during
9 Y# ~0 S# |" |3 D% Mthe evaluation of any children who present with vir-& I, P' u8 F" N5 J& s
ilization or peripheral precocious puberty. The diag-
" m4 b8 m, S q5 r/ U r5 [) Z& gnosis can be established by just a few tests and by
1 U# R# x& {1 E1 E2 S2 ~8 H' Fappropriate history. The inability to obtain such a
' t% B) s0 L! y$ d4 Vhistory, or failure to ask the specific questions, may
; a9 M- q7 e2 Yresult in extensive, unnecessary, and expensive ?2 W4 @; Z. E9 i5 B% f6 c
investigation. The primary care physician should be
1 Q2 f8 g6 V0 Q2 r0 Laware of this fact, because most of these children+ _7 @. s7 s& ?- P1 L' z1 C
may initially present in their practice. The Physicians’, w b. L8 M+ k/ o( r
Desk Reference and package insert should also put a7 N: H6 p) |: Y* Z5 j/ I& h
warning about the virilizing effect on a male or' \7 i* s: U# k- t
female child who might come in contact with some-* A% j$ }7 ?+ P. x& t& @9 c1 E
one using any of these products./ f$ i8 g3 l3 Y0 L
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) ]' R2 E7 p; H% r0 ?# l1. Styne DM. The testes: disorder of sexual differentiation& \! W+ `1 F3 n' z
and puberty in the male. In: Sperling MA, ed. Pediatric
; r& V4 f" I5 I, bEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;( N; w3 R3 a+ |# o) ]' `% r6 g3 F
2002: 565-628.; E% b" U' i$ e# S! Y9 x
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
$ U( G4 t/ }8 J4 Upuberty in children with tumours of the suprasellar pineal
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6 A) K4 }2 [% Y2 J+ kareas: organic central precocious puberty. Acta Paediatr. \3 U* z5 x1 E, w6 R
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, N: `: }# v6 N% y5 \6 B0 h3. Lee PA. Puberty and its disorders. In: Lifshitz F, ed.
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- J7 U& X3 l. n4 Q4. Yu YM, Punyasavatsu N, Elder D, D’Ercole AJ. Sexual# O# j# L* e3 I+ U. [& C Q! ^
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8 h2 Q* d( J/ C7 Nexposure to testosterone. Pediatrics. 1999;104:e23.6 @" v5 d6 l0 f( g
5. Greulich WW, Pyle SI, eds. Radiographic Atlas of) X/ n9 a. Z- Y/ `1 R) m
Skeletal Development of the Hand and Wrist. 2nd ed.
0 d# @7 v) Z$ {2 `; ?' c1 uStanford, CA: Stanford University Press; 1959.6 [+ v1 }; p h- G; E5 M- j, h% ]
6. Physicians’ Desk Reference. Androgel 1% testosterone,7 [- \$ O1 u6 J) |: F
Unimed Pharmaceutical Inc. Montvale, NJ: Medical% b; o0 J. N/ o7 f) P
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