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Sexual Precocity in a 16-Month-Old
# q: x5 v/ o9 M; R- VBoy Induced by Indirect Topical
7 c1 N t2 r# S' RExposure to Testosterone" G9 d/ g1 d" d+ N) B; N" Y$ G
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
9 M% f7 f) j" A0 q% n$ |" f& R# Land Kenneth R. Rettig, MD1
# P, Z8 T) W- u. {4 QClinical Pediatrics9 K9 N) E/ a3 V# D, L# Q
Volume 46 Number 6 W: l' P( U* O- x) z) A% m1 N
July 2007 540-543
6 i# P- |# f( ^© 2007 Sage Publications
5 I! `# @4 F. O) u# x; p' ?10.1177/0009922806296651; A) k( Y2 R A; x8 X6 Y' v
http://clp.sagepub.com: G- w: _3 d- j5 M. [9 h& K3 j
hosted at
' P/ ^$ w" r$ X/ o, ^7 c) qhttp://online.sagepub.com r7 H/ ]7 w/ X) K+ \
Precocious puberty in boys, central or peripheral,
( b$ E3 I3 q. Z O6 F1 A/ K7 zis a significant concern for physicians. Central
4 G& N$ f( ]" m; bprecocious puberty (CPP), which is mediated# ~! \0 P5 Q6 K7 [. Q' k7 N
through the hypothalamic pituitary gonadal axis, has6 J, y5 {7 u. n5 o7 B* R3 S& i
a higher incidence of organic central nervous system' @4 f4 B1 G: U- r
lesions in boys.1,2 Virilization in boys, as manifested) j) b& w9 X, h
by enlargement of the penis, development of pubic% d. M. Z9 u& ~: _7 o
hair, and facial acne without enlargement of testi-3 c! c0 `+ _) U" T1 V5 t
cles, suggests peripheral or pseudopuberty.1-3 We
6 T/ w" G, T# |4 _$ }report a 16-month-old boy who presented with the; s" J7 d* A. W; P1 f
enlargement of the phallus and pubic hair develop-
n# o9 N9 l; Cment without testicular enlargement, which was due, ~: v2 B9 ~7 w4 M7 @
to the unintentional exposure to androgen gel used by
" `4 ^" v& N% Ethe father. The family initially concealed this infor-
( Q7 g/ w3 b2 C7 P7 xmation, resulting in an extensive work-up for this
$ p- w9 X" _ X, V1 q4 schild. Given the widespread and easy availability of( k4 j* q" X6 V6 E
testosterone gel and cream, we believe this is proba-& S2 e5 a+ x" Q: H6 Z
bly more common than the rare case report in the
" h1 r, s# g5 ]6 q% s" H. ^; uliterature.4
/ n3 \; o- @$ }Patient Report+ Q9 Z' c- Z" i
A 16-month-old white child was referred to the1 S+ q2 M) r" R' a$ ^3 q
endocrine clinic by his pediatrician with the concern
8 v, j* O3 u* _# B L: a7 Cof early sexual development. His mother noticed
[6 [( c4 m1 P9 E0 \( B6 d. }1 elight colored pubic hair development when he was2 u! d2 A+ o3 K. w; [8 w) L
From the 1Division of Pediatric Endocrinology, 2University of. [( G8 ^2 F8 S6 O9 G6 J* x& j
South Alabama Medical Center, Mobile, Alabama.9 z! p$ d, M/ `
Address correspondence to: Samar K. Bhowmick, MD, FACE,
1 [9 D: |/ O8 g" }4 s6 M; y' sProfessor of Pediatrics, University of South Alabama, College of" k! s% n1 m9 }& y+ }
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;% B, B, R; r* g- S) L2 l
e-mail: [email protected].
8 b& x0 O8 P# I6 u# w/ A2 u* tabout 6 to 7 months old, which progressively became
' `. I \- ]* Ddarker. She was also concerned about the enlarge-
8 M- G. M/ K2 c' e1 Y hment of his penis and frequent erections. The child
4 p V h* w7 r7 Y- r4 N" Q. Nwas the product of a full-term normal delivery, with
& `; ?4 c$ s Ca birth weight of 7 lb 14 oz, and birth length of8 y& d- Q D- K1 ~/ e( R
20 inches. He was breast-fed throughout the first year, e! _ N( f/ g) I, a
of life and was still receiving breast milk along with
7 B3 \, O& n- D) `4 ]( N1 D1 Bsolid food. He had no hospitalizations or surgery,
: }9 [# d1 O3 `& L& K2 K& {and his psychosocial and psychomotor development4 h0 f# {0 Y, A8 z/ j. M r
was age appropriate.
- `0 n, L' }: {2 iThe family history was remarkable for the father,0 z, E2 S# J/ p* l& V
who was diagnosed with hypothyroidism at age 16,
! W- ~( y; E2 s8 j* N$ jwhich was treated with thyroxine. The father’s! H8 C/ {8 Y+ s
height was 6 feet, and he went through a somewhat u* i# e- o* ^, h" V
early puberty and had stopped growing by age 14./ e- U$ y% \" u5 z# p; m
The father denied taking any other medication. The
0 o" v' |9 g- c5 O* nchild’s mother was in good health. Her menarche
3 O4 i5 {* r" h: H: T6 f! `2 s+ pwas at 11 years of age, and her height was at 5 feet
) Z( ~) r% P7 ?, f" P" Z9 |5 inches. There was no other family history of pre-( T. |/ ^. I" C, C- | V; L
cocious sexual development in the first-degree rela-+ o5 @' D0 |: G `! b( a
tives. There were no siblings.
. g% R4 k W1 K) U" w# v, X# vPhysical Examination1 q' {# [% l, O) r7 u6 ?
The physical examination revealed a very active,
' q" X$ ?7 m0 [7 [, t Jplayful, and healthy boy. The vital signs documented
( U% T& E! T. V1 {6 ga blood pressure of 85/50 mm Hg, his length was
% N7 G z( ]* M- ~( U( q5 g4 |4 K1 D90 cm (>97th percentile), and his weight was 14.4 kg
. i1 z2 x- L8 \& q4 Q- ~; J' k! B(also >97th percentile). The observed yearly growth% X3 Y% a+ b) n, m
velocity was 30 cm (12 inches). The examination of
: o7 b% `/ X8 h6 f: r/ C+ d8 F5 T' @the neck revealed no thyroid enlargement.+ B3 [- m1 z Y/ u: V7 J
The genitourinary examination was remarkable for4 f& n; V5 T0 i% K8 E* A( K
enlargement of the penis, with a stretched length of7 H; I: s/ k5 w) M
8 cm and a width of 2 cm. The glans penis was very well
6 a' r/ z. Q E$ }developed. The pubic hair was Tanner II, mostly around
# S* v# F# A) n540
! n% x6 c2 i' Y# _3 ^, s% lat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from: T# p P: w/ a5 J+ F
the base of the phallus and was dark and curled. The
9 n' g& }1 P+ E, h2 v. A; Ntesticular volume was prepubertal at 2 mL each.
! C9 |7 s7 ]7 e: W. _; ^0 r$ |3 SThe skin was moist and smooth and somewhat3 M; [8 H# r- B O
oily. No axillary hair was noted. There were no9 P- v6 D& l# ?
abnormal skin pigmentations or café-au-lait spots.+ @/ Y, n: S5 B! d9 }; b
Neurologic evaluation showed deep tendon reflex 2+) X( C2 Z. P, }- \: F
bilateral and symmetrical. There was no suggestion
! q: e4 s) `* y& {of papilledema.
! M; @7 O0 p6 F% @" VLaboratory Evaluation
+ }( S0 q6 z* Y6 sThe bone age was consistent with 28 months by
# R1 [- A3 t5 @) Xusing the standard of Greulich and Pyle at a chrono-' h- n+ @6 m( E) ?+ d
logic age of 16 months (advanced).5 Chromosomal5 k J1 \' e7 }' Z
karyotype was 46XY. The thyroid function test, r0 U( D0 ]. r6 v! ]
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
2 v- \5 v5 ^3 J& ^/ m6 y. Qlating hormone level was 1.3 µIU/mL (both normal).$ r' X# g5 S: H. F+ ~+ d- e# g
The concentrations of serum electrolytes, blood
8 S& F' Z( r" G) H$ A7 ]urea nitrogen, creatinine, and calcium all were
) E& I! ~4 X+ Bwithin normal range for his age. The concentration" }# ^- U, c' a" O8 ~$ e& C
of serum 17-hydroxyprogesterone was 16 ng/dL2 F0 [! f5 `/ x# Z
(normal, 3 to 90 ng/dL), androstenedione was 208 ]5 X+ S# `% D4 C( @
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-3 S6 k; F3 Y' r) w) b$ F
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
# o" X2 c$ T' y2 Udesoxycorticosterone was 4.3 ng/dL (normal, 7 to
' s! `; }7 m& M49ng/dL), 11-desoxycortisol (specific compound S)
. z2 s7 V0 q2 w1 Vwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
$ N1 L7 n }; Q# C+ K* c. u2 Wtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
" ~2 Q- p+ z& ?/ n# _3 W1 ~testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
5 Z" p& e$ U& M4 V/ Gand β-human chorionic gonadotropin was less than
9 M" _: u, j$ O/ k- d5 mIU/mL (normal <5 mIU/mL). Serum follicular
% f7 I) o- z, C2 G& r3 c6 astimulating hormone and leuteinizing hormone, P# F& E$ W" S/ P; b% u/ a
concentrations were less than 0.05 mIU/mL
& z1 g/ j& v( P& d' z! X(prepubertal).$ w/ m+ ` d: s
The parents were notified about the laboratory& \5 b9 a- y- i/ U# Y% k
results and were informed that all of the tests were I/ A2 k3 S- \1 s5 y$ P# s
normal except the testosterone level was high. The
0 s, o. d$ |9 G3 m" ~7 E4 pfollow-up visit was arranged within a few weeks to
4 w# C+ D) O& `5 ?3 u1 g: x- \obtain testicular and abdominal sonograms; how-# J* m5 U5 r5 t+ k) Y) \5 I; Y
ever, the family did not return for 4 months.5 l0 G6 c0 {) _
Physical examination at this time revealed that the0 X7 M* V" d2 x/ }8 x
child had grown 2.5 cm in 4 months and had gained4 Z4 r9 f P7 |! ~# M& E/ `+ d4 ]
2 kg of weight. Physical examination remained
: ^8 E6 ?$ h6 S/ k5 H6 qunchanged. Surprisingly, the pubic hair almost com-/ y3 t* G r& m1 i0 V
pletely disappeared except for a few vellous hairs at
3 E9 |# c5 x8 z5 _, b( p, t* Lthe base of the phallus. Testicular volume was still 2# S, M# ?6 Z8 E2 \# m& P1 s+ P
mL, and the size of the penis remained unchanged.* d. P# q4 {* L7 l2 d3 Z* S
The mother also said that the boy was no longer hav-7 f# c% ?2 H" k' G- y5 @
ing frequent erections.; i' v, d* Z: J# D: E
Both parents were again questioned about use of
+ Q) ^* ~! W4 J3 f* X- Jany ointment/creams that they may have applied to
, O$ o/ W5 O; [' x; ^the child’s skin. This time the father admitted the8 w7 s& o- o4 W
Topical Testosterone Exposure / Bhowmick et al 541/ D. S% `: C7 g7 V
use of testosterone gel twice daily that he was apply-
& ]9 m8 H1 J9 }' ]2 E- _% ]/ P7 S0 _& iing over his own shoulders, chest, and back area for
# l: e" a% K+ m0 ^' @2 \) Wa year. The father also revealed he was embarrassed
/ H. _4 [% o) l3 Z8 a! g6 t4 zto disclose that he was using a testosterone gel pre-$ T: r9 v9 `& N$ Z2 ^, P3 `4 O
scribed by his family physician for decreased libido
" F# r6 I$ F9 B% ~6 K4 Zsecondary to depression.! l3 B' H. E, v- N
The child slept in the same bed with parents.
" K p5 C' c( s3 `9 DThe father would hug the baby and hold him on his
" @& ]0 m3 N8 Vchest for a considerable period of time, causing sig-/ S! j* L2 P" h2 _
nificant bare skin contact between baby and father.
2 V2 ~$ l, U: DThe father also admitted that after the phone call,
( l( [- P; }) Q9 i: _* ~2 \8 t% Jwhen he learned the testosterone level in the baby
* K; ^5 @+ o" i7 ?9 a* _$ R7 f0 G# Gwas high, he then read the product information. [. h3 z4 H l1 @
packet and concluded that it was most likely the rea-+ O3 M' \- w+ Z% K
son for the child’s virilization. At that time, they! t, h2 t h$ G
decided to put the baby in a separate bed, and the
# |- ?" S+ J: o# mfather was not hugging him with bare skin and had
* J6 I% v+ q; m# _been using protective clothing. A repeat testosterone
/ R8 k8 C1 R2 j5 btest was ordered, but the family did not go to the
) z. t& d! P! x! t& q6 v blaboratory to obtain the test.% G) l$ B- s: `8 R$ f
Discussion2 F. Y" E4 m5 ^# v
Precocious puberty in boys is defined as secondary% a# T+ i( ?. h1 h4 b5 \" ~3 X
sexual development before 9 years of age.1,4
& q( Q& i: `- d# V2 WPrecocious puberty is termed as central (true) when
, i y' V9 u! ]it is caused by the premature activation of hypo-5 a" `" U7 i1 Y
thalamic pituitary gonadal axis. CPP is more com-
- k& }% K& q8 g2 O$ [mon in girls than in boys.1,3 Most boys with CPP
# R, @; ^# S: W. m |! zmay have a central nervous system lesion that is |1 E1 h' }8 j3 d5 I; Q
responsible for the early activation of the hypothal-
- V: C Z2 ^ S5 {$ Lamic pituitary gonadal axis.1-3 Thus, greater empha-- E, {3 C( `; J" q" I* p- {2 D
sis has been given to neuroradiologic imaging in
1 _! e" S f8 P6 c$ c" A" s' N# Iboys with precocious puberty. In addition to viril-
5 [+ U3 r& A8 G. S q7 I1 sization, the clinical hallmark of CPP is the symmet-
J+ M V! g) O; d1 L/ Crical testicular growth secondary to stimulation by
0 L1 v- \- z. D3 R# Z4 p8 j$ _gonadotropins.1,39 H7 e5 r0 }5 Q% g! r1 |( t
Gonadotropin-independent peripheral preco-
) N, T" H& Z( \* _; o. tcious puberty in boys also results from inappropriate3 S4 k7 _) y# g O6 b
androgenic stimulation from either endogenous or8 y7 C/ n F H' a' j( _& s( H8 n x
exogenous sources, nonpituitary gonadotropin stim-2 d& X A' n/ a- z) W
ulation, and rare activating mutations.3 Virilizing( F. H3 O+ J! K2 {+ w
congenital adrenal hyperplasia producing excessive
; Q5 J& A) e3 Nadrenal androgens is a common cause of precocious
9 |" D- ~5 ^$ C! P0 a- [puberty in boys.3,4! w' u; J- H; N( r! k0 H) t1 |
The most common form of congenital adrenal
# K/ m" A( j& _; n' V# n7 a2 W' ]hyperplasia is the 21-hydroxylase enzyme deficiency.
; P$ Y2 r9 j6 }* \The 11-β hydroxylase deficiency may also result in8 n5 p* t) O( g. s' g/ E% C8 V
excessive adrenal androgen production, and rarely,
) P6 x- \. G, B/ v. Tan adrenal tumor may also cause adrenal androgen
3 \* ]7 R1 q: Q; A5 q2 O, ~excess.1,3
3 H) M7 v! M! L, Tat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
3 M3 e/ [4 e* z9 n$ _& \9 b542 Clinical Pediatrics / Vol. 46, No. 6, July 20071 A# x; `3 s$ |* S9 h5 i
A unique entity of male-limited gonadotropin-! v6 |# C! C! y6 ]0 b4 v
independent precocious puberty, which is also known
4 H w# r6 V* C( f! Jas testotoxicosis, may cause precocious puberty at a4 C9 g; Z3 p& ]$ u" H
very young age. The physical findings in these boys
5 ^+ U% B) ~% Qwith this disorder are full pubertal development,3 I8 h8 f" B/ j- N( [
including bilateral testicular growth, similar to boys
, }3 P, q, g' o0 Q0 H( L% i8 {with CPP. The gonadotropin levels in this disorder5 h0 u% B# W1 _; ?
are suppressed to prepubertal levels and do not show
: ?: Y$ t6 _/ \$ D8 @& F! B; xpubertal response of gonadotropin after gonadotropin-
8 ?& T6 o6 e: U1 A$ H! Vreleasing hormone stimulation. This is a sex-linked
/ d* m* Y7 T6 r; Pautosomal dominant disorder that affects only
5 x5 h. s/ p" I* \, C& M- amales; therefore, other male members of the family
& u$ `( V0 \2 y+ v8 kmay have similar precocious puberty.3
" L6 }# S# ] B) ?% {In our patient, physical examination was incon-: b1 ~: I0 W; K' u S
sistent with true precocious puberty since his testi-5 j, {7 ~9 I8 `5 _
cles were prepubertal in size. However, testotoxicosis
3 M2 N% p/ e! ^was in the differential diagnosis because his father3 C* i, K5 c" t9 N8 E
started puberty somewhat early, and occasionally,
1 L9 G ~9 y+ z% r0 jtesticular enlargement is not that evident in the# p8 G+ T$ U) c; p) Z: Y
beginning of this process.1 In the absence of a neg-7 g8 `; X: `4 @3 S2 Z( e( k5 N
ative initial history of androgen exposure, our# m' V8 g; B$ t" x& N" F3 c
biggest concern was virilizing adrenal hyperplasia,
F8 O" T& L2 s: I- H8 a- }+ yeither 21-hydroxylase deficiency or 11-β hydroxylase0 s% y5 F$ J" a4 l! `) h
deficiency. Those diagnoses were excluded by find-6 X8 B5 q, L' C! R
ing the normal level of adrenal steroids.
4 a6 e, L$ a* m/ n- vThe diagnosis of exogenous androgens was strongly
* } e# w9 N( K" ^suspected in a follow-up visit after 4 months because
/ o) p+ j3 I/ k. Pthe physical examination revealed the complete disap-
# d% s- r$ l2 y: B& hpearance of pubic hair, normal growth velocity, and
' |7 u8 {2 F& \9 F4 Y6 j2 q7 ydecreased erections. The father admitted using a testos-
& w% \* ^2 H8 N% r- Hterone gel, which he concealed at first visit. He was
5 k( g1 P g2 ^2 R1 Q7 ^using it rather frequently, twice a day. The Physicians’
) B9 n) e; B: d$ d2 ^$ S4 q+ ^8 }Desk Reference, or package insert of this product, gel or. S& P, v, l* e9 N3 u/ l9 d
cream, cautions about dermal testosterone transfer to! [8 i/ F1 `0 l2 x
unprotected females through direct skin exposure. r5 ?9 o9 ?) @% H8 H8 C' T
Serum testosterone level was found to be 2 times the
( I* ^/ c( H/ s: f* O8 g2 K4 ?baseline value in those females who were exposed to
6 F; P. x+ H2 j+ q- teven 15 minutes of direct skin contact with their male
& P) l* T5 T* [/ jpartners.6 However, when a shirt covered the applica-
3 x, L7 c5 C8 c. f7 Ytion site, this testosterone transfer was prevented.
1 [, K: U% f1 vOur patient’s testosterone level was 60 ng/mL,
/ k1 V4 d) _& z% ewhich was clearly high. Some studies suggest that9 d1 `% p0 X- |4 ~+ B
dermal conversion of testosterone to dihydrotestos-4 q, @. R$ n) h' R4 Q2 h
terone, which is a more potent metabolite, is more
/ A* P1 b9 Q. G; f! d+ Gactive in young children exposed to testosterone
- S% v, B1 Q; D. l0 i) S4 kexogenously7; however, we did not measure a dihy-" k% ^' M1 [9 J1 P1 s% f
drotestosterone level in our patient. In addition to
5 A- s0 A0 I& H5 S) m' x$ ~$ Dvirilization, exposure to exogenous testosterone in" C' e; ~8 @; h" M
children results in an increase in growth velocity and# w8 `& ]% v0 K- P* N
advanced bone age, as seen in our patient.* H& z% w# R5 Z/ c! B
The long-term effect of androgen exposure during! m6 n" e0 k5 J+ A
early childhood on pubertal development and final) D; x- |# ~) ^3 r
adult height are not fully known and always remain
& e' H9 z9 j( T& R# @, h) [" @# ra concern. Children treated with short-term testos-
' m6 [( A n& j1 y* Gterone injection or topical androgen may exhibit some$ S. f4 T5 K5 P) m
acceleration of the skeletal maturation; however, after
4 K! n# F2 u) Mcessation of treatment, the rate of bone maturation- v$ v; g) O7 S" h7 h- H7 e
decelerates and gradually returns to normal.8,9
( T: ^6 C# ^) u8 }, z9 E. F. v8 l1 ^There are conflicting reports and controversy; p7 V1 l2 ?+ | t$ l( }) R% B
over the effect of early androgen exposure on adult
) `, ~& _. L1 w0 ]) Kpenile length.10,11 Some reports suggest subnormal; I9 l. g: t6 h, ?% N% g
adult penile length, apparently because of downreg-) f+ o" B Q1 K
ulation of androgen receptor number.10,12 However," v6 `1 ]% \5 M6 ^3 v5 f
Sutherland et al13 did not find a correlation between1 C+ T6 h/ r- m4 C
childhood testosterone exposure and reduced adult
1 {6 i' I8 D, ^! k7 W9 O; zpenile length in clinical studies.
' e7 `9 h2 v, e6 qNonetheless, we do not believe our patient is( X k3 |+ [( }; y5 C! ~6 y( N
going to experience any of the untoward effects from
3 g% D5 @5 d, [+ R8 M+ v5 ]& Ctestosterone exposure as mentioned earlier because6 m1 ?5 ^- W( Z p8 m3 O. x
the exposure was not for a prolonged period of time.
( H. [* h9 W. V1 a FAlthough the bone age was advanced at the time of3 a, w1 c8 N3 _. s8 u
diagnosis, the child had a normal growth velocity at" }7 B, W7 h& M& x
the follow-up visit. It is hoped that his final adult7 M: k& l9 S, b d. Y1 ~, t3 _8 m
height will not be affected.
- j& O& f! y4 }. S( _$ CAlthough rarely reported, the widespread avail-
7 {# i7 u) s; B# G1 s/ O: M$ iability of androgen products in our society may& Q$ t/ X% X! v
indeed cause more virilization in male or female
# f- G. M$ b) L2 fchildren than one would realize. Exposure to andro-
- X8 I. Y' _1 p3 L' Ygen products must be considered and specific ques-4 _. i* r8 k3 a' h6 K
tioning about the use of a testosterone product or
: x" a8 O: |5 bgel should be asked of the family members during: c, K5 k! H4 L: z* R/ d& `
the evaluation of any children who present with vir-
1 `* ^# G% Y0 e7 Y# xilization or peripheral precocious puberty. The diag-' [5 w& z6 g4 j& M+ B4 q
nosis can be established by just a few tests and by
! u9 f9 n& D7 u# @/ g: Happropriate history. The inability to obtain such a
* J3 v% ]" ~ G, R+ p- {history, or failure to ask the specific questions, may
& I4 @3 n/ E! f2 L/ R6 q: nresult in extensive, unnecessary, and expensive; C( j# V3 }1 Y8 R, w
investigation. The primary care physician should be+ ]- Y& |3 t: T& E
aware of this fact, because most of these children, N2 e7 g) M* e) f X7 p, ?0 |
may initially present in their practice. The Physicians’
/ h# E$ O4 i/ c I$ f# }Desk Reference and package insert should also put a
% g* e1 n5 J4 }- i* l8 X1 uwarning about the virilizing effect on a male or- O/ q/ I" U8 v7 ~; Q3 |# Q
female child who might come in contact with some-6 _8 \* T1 Y0 H+ X! T
one using any of these products.# n. Q4 W( {7 ]! E+ A
References6 M) w# R4 i- w0 }( H2 c
1. Styne DM. The testes: disorder of sexual differentiation
% L# R5 s1 \/ Cand puberty in the male. In: Sperling MA, ed. Pediatric: p% \9 M$ m/ w- [- c
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;5 M( b& K, s# x, U
2002: 565-628.9 l: L4 s( w; G. @3 ]/ l
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
$ t/ C7 [8 z% } Q4 H0 P5 `5 Epuberty in children with tumours of the suprasellar pineal |
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