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Sexual Precocity in a 16-Month-Old
4 V* \$ b6 J( h! B& O, ?4 i* zBoy Induced by Indirect Topical, A( {$ I7 h* P
Exposure to Testosterone
5 v: |. p5 ~8 qSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
( P/ G5 K$ u& b! J& d, gand Kenneth R. Rettig, MD1
0 q' N ^- F; w- g) UClinical Pediatrics
1 P4 L6 {6 E D* GVolume 46 Number 6
* O2 |0 a7 W( }0 v% }July 2007 540-543
' Q$ z4 |0 }( \ D9 ^, d© 2007 Sage Publications, d% N% B$ N' E g
10.1177/00099228062966513 j/ M, z( n7 u) x
http://clp.sagepub.com0 v% k. K2 `8 v# I9 X3 p+ Q& K
hosted at9 i6 z. _4 }' R" f. {$ s0 ]. V4 Y
http://online.sagepub.com
) K Y, {( V3 Z' Z) I% aPrecocious puberty in boys, central or peripheral,
8 R2 t" S) p2 m- R% his a significant concern for physicians. Central, O) L: u. w7 Q
precocious puberty (CPP), which is mediated
% ~+ D, Y& E1 c6 X! pthrough the hypothalamic pituitary gonadal axis, has
1 z `( P2 B8 Z1 G5 V! Ka higher incidence of organic central nervous system
0 q* F+ j, P2 c6 tlesions in boys.1,2 Virilization in boys, as manifested
; |( A/ @# n' ]5 Gby enlargement of the penis, development of pubic5 Q( _- R) x! ]+ [
hair, and facial acne without enlargement of testi-
* m* B, |0 f8 X% S& A8 M% S9 _cles, suggests peripheral or pseudopuberty.1-3 We
$ b7 j. l9 W2 a0 K4 T) areport a 16-month-old boy who presented with the
; g' |7 v1 z* s: v8 K1 Fenlargement of the phallus and pubic hair develop-
; W9 `" w1 |6 u0 Q% ^4 {: @% l; m5 vment without testicular enlargement, which was due# } U4 |/ _ z8 Y/ j
to the unintentional exposure to androgen gel used by
$ r. r4 o9 C# b `. othe father. The family initially concealed this infor-
& C% J3 R U7 ~% Dmation, resulting in an extensive work-up for this6 n* Y6 `% T& I" O
child. Given the widespread and easy availability of
( M. f* d% R. {: _testosterone gel and cream, we believe this is proba-5 s# ~6 ^; T+ p4 K' b1 {0 f* L
bly more common than the rare case report in the
! v) ?9 b$ d. d0 ?6 D# mliterature.4
$ G( q6 g% ?% b8 y+ K- ?Patient Report" o. c, x$ l8 s v' P1 A
A 16-month-old white child was referred to the7 H! |9 i8 Q7 v, }/ J# H
endocrine clinic by his pediatrician with the concern
# Z4 t# y; \6 B6 T- y! yof early sexual development. His mother noticed
, Y6 s: {$ H" u, G' b% {; h' Clight colored pubic hair development when he was7 n) p6 `9 P. t* f. q# c* Q/ c
From the 1Division of Pediatric Endocrinology, 2University of: Y3 A) r- ]" W* m0 F
South Alabama Medical Center, Mobile, Alabama.
0 h1 t9 u% m8 t+ pAddress correspondence to: Samar K. Bhowmick, MD, FACE,
1 e! K0 w4 x5 f( Y% ~/ qProfessor of Pediatrics, University of South Alabama, College of- t" W( Q( |% O
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
) M9 o( f' m7 s/ ne-mail: [email protected].
: E$ K4 _6 `" k) Uabout 6 to 7 months old, which progressively became7 @4 T/ B7 u) c, J9 l: r; j: X
darker. She was also concerned about the enlarge-$ {' v3 M/ n+ K5 O5 p7 f5 {
ment of his penis and frequent erections. The child
: s. G G; n4 Z# D6 |2 fwas the product of a full-term normal delivery, with
- m+ U% G, z) q- L5 r7 xa birth weight of 7 lb 14 oz, and birth length of. e; X8 o7 k8 C& F, q/ Q
20 inches. He was breast-fed throughout the first year% j- }1 h. s' [5 A
of life and was still receiving breast milk along with& ?" A4 i! d. U3 H* y$ [+ S; _
solid food. He had no hospitalizations or surgery,
- }: e# e$ {1 Jand his psychosocial and psychomotor development, ?/ z2 Y' K8 R. |/ N$ b
was age appropriate.9 [1 N1 c6 L% ]
The family history was remarkable for the father,
~5 Z- D, i* j, o: G9 @: ^who was diagnosed with hypothyroidism at age 16,
1 c) y/ L" K. b6 g' Qwhich was treated with thyroxine. The father’s
% l4 {- u* j) \' Lheight was 6 feet, and he went through a somewhat6 ^/ i3 w/ N6 _# T5 X
early puberty and had stopped growing by age 14.5 H! \7 s% E8 m0 i8 t }
The father denied taking any other medication. The
9 V8 P+ n' R$ u: q Rchild’s mother was in good health. Her menarche
( @6 ]) E- o' A" h8 Lwas at 11 years of age, and her height was at 5 feet
9 ~5 T6 [$ W% Z) \, N5 inches. There was no other family history of pre-
" E$ u* }+ R3 R) Fcocious sexual development in the first-degree rela-8 H7 K* M1 q+ L4 f8 J( [! r
tives. There were no siblings.
( H# v; q& y2 nPhysical Examination: i) h" X, u% F; f
The physical examination revealed a very active,
2 d' I8 \: a2 _" ]0 Nplayful, and healthy boy. The vital signs documented! O; G `+ e1 V5 `. b4 s1 ~
a blood pressure of 85/50 mm Hg, his length was6 E% I' t* M! Y3 `6 _ V9 V
90 cm (>97th percentile), and his weight was 14.4 kg
# e/ T5 @7 N# a, S(also >97th percentile). The observed yearly growth
, D+ h1 \3 A( n& K4 C6 M+ f' g1 cvelocity was 30 cm (12 inches). The examination of
2 A5 ^3 G) l: Z7 Z/ Z5 a0 Kthe neck revealed no thyroid enlargement.
0 { e) M3 t) ?) j' \9 lThe genitourinary examination was remarkable for$ u3 o* h( j- g E$ T3 E
enlargement of the penis, with a stretched length of
* P E" d! [# I$ O- X" n) w8 cm and a width of 2 cm. The glans penis was very well* y4 q+ N6 ^- J6 k5 L
developed. The pubic hair was Tanner II, mostly around3 i3 n3 m* j$ ]) P' |+ |8 s
540
( ?6 f5 _& }6 tat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from, r) m' |$ R6 h# a
the base of the phallus and was dark and curled. The' q: M- N; Z8 m& }$ ]
testicular volume was prepubertal at 2 mL each., c5 k0 e% p' E/ y
The skin was moist and smooth and somewhat; j. y8 g5 @6 V3 p# Q, P
oily. No axillary hair was noted. There were no
$ Q. u, p* v, a- eabnormal skin pigmentations or café-au-lait spots.1 R- B) V/ s# K: U
Neurologic evaluation showed deep tendon reflex 2+2 {. V+ m. {8 a6 H5 Z, J% N
bilateral and symmetrical. There was no suggestion
: E2 y; `* V' g; r+ H. h& E4 kof papilledema.0 U; ]& N# g4 R3 Y
Laboratory Evaluation
7 s+ E2 }! K/ i& A+ BThe bone age was consistent with 28 months by5 m+ @9 z6 \" F" E. A# c; g" v
using the standard of Greulich and Pyle at a chrono-
6 \# v! U* o G+ Xlogic age of 16 months (advanced).5 Chromosomal6 H% F: G K9 G9 m
karyotype was 46XY. The thyroid function test J0 K; D4 k! c! ~! k K
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
7 W) R, u2 z' e- Hlating hormone level was 1.3 µIU/mL (both normal).5 G# p1 _# E7 z
The concentrations of serum electrolytes, blood
6 v9 d7 D4 Q- [urea nitrogen, creatinine, and calcium all were
: U, `( z) T4 j' s( twithin normal range for his age. The concentration
- a5 ], Q1 m) {' `of serum 17-hydroxyprogesterone was 16 ng/dL1 ?: H' [' [$ p& B6 `- N! ~; }' c
(normal, 3 to 90 ng/dL), androstenedione was 20: _* w$ M- Z; U( v- Q S
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-8 c2 }. W8 z# i, a `0 W' q! O G2 N; O
terone was 38 ng/dL (normal, 50 to 760 ng/dL),0 g( Z0 Z$ }) `9 m" }) ~
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
- X q" |' ]) }" b6 \7 L49ng/dL), 11-desoxycortisol (specific compound S). D0 u' N) V" S* h
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
( P3 T5 X0 X, u0 ?! [tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
: E) A* g2 w0 q+ b* utestosterone was 60 ng/dL (normal <3 to 10 ng/dL),0 v) H, M, H( B' D+ E+ C) M
and β-human chorionic gonadotropin was less than
7 W Z( ^7 _, k) o; \4 n5 mIU/mL (normal <5 mIU/mL). Serum follicular
3 X* `" w6 M( u% d8 tstimulating hormone and leuteinizing hormone
* r k% @% c1 B7 M6 iconcentrations were less than 0.05 mIU/mL
) c: f/ F3 Y! t7 }, {' g5 @9 {(prepubertal).
% x9 R! q. s- x# U; K( m( [1 u5 ]The parents were notified about the laboratory
# f; j+ e- o. U0 h; gresults and were informed that all of the tests were. k* a+ b2 B) M
normal except the testosterone level was high. The9 Q8 m# g+ `5 k% r0 |% e, Y
follow-up visit was arranged within a few weeks to
7 P- h* O8 Z5 F% |% n ]% Cobtain testicular and abdominal sonograms; how-' K* `* d8 {" p4 Y
ever, the family did not return for 4 months." q5 l1 l5 r) U& c' n
Physical examination at this time revealed that the
! B: J9 e. b/ j. D4 x8 lchild had grown 2.5 cm in 4 months and had gained
# [/ X x1 u8 ?2 P2 kg of weight. Physical examination remained
/ t" v l1 G: M# H! I, H; tunchanged. Surprisingly, the pubic hair almost com-/ U* i2 n0 R5 y+ U1 l8 n
pletely disappeared except for a few vellous hairs at
! a# B8 x+ E' |3 g& ~& D7 Ithe base of the phallus. Testicular volume was still 26 Z; h) Z% I, o* w+ {! W$ z
mL, and the size of the penis remained unchanged.
2 x- `# U; c2 y" _6 |; fThe mother also said that the boy was no longer hav-- p1 Q& u+ Z% O# I. E, i
ing frequent erections.
' C* | N+ M6 P" S) F7 U+ g- UBoth parents were again questioned about use of9 i& T! d, c! o- R+ K8 E0 S, A$ m
any ointment/creams that they may have applied to
" g" S3 p- `1 W4 ]/ `* e( a- Hthe child’s skin. This time the father admitted the
0 e( ^+ l! E/ E) A0 z8 _Topical Testosterone Exposure / Bhowmick et al 541/ c7 R# s% L6 G0 Z0 y3 b) `) S
use of testosterone gel twice daily that he was apply-7 C+ _" l( Y2 T- r% Y
ing over his own shoulders, chest, and back area for5 U' i \, ~, h7 p0 Q6 E! R& s
a year. The father also revealed he was embarrassed
" D( L* _3 O$ X3 Z0 D% b9 O4 qto disclose that he was using a testosterone gel pre-0 h1 y5 F7 z/ G2 U* c
scribed by his family physician for decreased libido
. O7 I5 v" U* csecondary to depression.' [9 |& d& T/ s1 l: v
The child slept in the same bed with parents.6 B" o* }- X3 Y% h: f' ?! R
The father would hug the baby and hold him on his, _+ t+ _3 e! J
chest for a considerable period of time, causing sig- U ?8 |9 Y4 }3 m8 q7 t
nificant bare skin contact between baby and father.
' ?, h, W$ Y# B0 U& M5 ~/ [$ DThe father also admitted that after the phone call,
" E$ \0 n) C% bwhen he learned the testosterone level in the baby0 B# w4 f* d0 R- Y9 Y
was high, he then read the product information
6 f3 P3 H/ w9 Kpacket and concluded that it was most likely the rea-
7 p8 g* R: R2 l' bson for the child’s virilization. At that time, they
8 G- l9 a& ]! d3 [! Cdecided to put the baby in a separate bed, and the
3 N$ p: t5 k3 d3 q3 bfather was not hugging him with bare skin and had" D$ Z9 j7 \, f$ [; u, t
been using protective clothing. A repeat testosterone1 N. u; y- }6 g6 u7 o W
test was ordered, but the family did not go to the1 w* m) |1 Q+ N( R
laboratory to obtain the test.
! ^& g1 J9 s( w0 f H; _Discussion2 z* G Y/ N3 _; e- P" y& y5 q
Precocious puberty in boys is defined as secondary6 x5 v7 W+ {4 }
sexual development before 9 years of age.1,4$ F0 M2 B7 p' Z7 h& \$ q
Precocious puberty is termed as central (true) when
3 s/ C3 C4 k$ x0 C, Cit is caused by the premature activation of hypo-
# {- F( o& C" u% T2 A, Athalamic pituitary gonadal axis. CPP is more com-( d( y/ U, V5 J
mon in girls than in boys.1,3 Most boys with CPP
. n# k5 [) `+ |' ?" k# Bmay have a central nervous system lesion that is6 f7 ?4 n4 z9 ~7 z
responsible for the early activation of the hypothal-
8 E' P9 ^/ Q& Q- M/ hamic pituitary gonadal axis.1-3 Thus, greater empha-
) a# t6 I6 s5 z& X0 [sis has been given to neuroradiologic imaging in
$ {7 \! _! [* r9 d( z! Hboys with precocious puberty. In addition to viril-
) T- s. O) T& y9 t& n8 e# xization, the clinical hallmark of CPP is the symmet-
+ \2 T: B9 ?+ }rical testicular growth secondary to stimulation by. I" t ]/ L+ | d# R4 H, F. @3 s
gonadotropins.1,30 ~0 N+ _9 J# i! }. p9 ~
Gonadotropin-independent peripheral preco-
) Z- l- [- O) u% Z% ]* B7 \cious puberty in boys also results from inappropriate+ c2 z; b) g7 m! S
androgenic stimulation from either endogenous or
X. `: i4 z& c' R4 Y) n: q; Texogenous sources, nonpituitary gonadotropin stim-+ }" q' C1 D$ y7 q: o4 s
ulation, and rare activating mutations.3 Virilizing
" ^& n% `3 y/ L3 k$ r4 z# t; fcongenital adrenal hyperplasia producing excessive
; c1 M0 E9 z# ?. Qadrenal androgens is a common cause of precocious
6 f$ i W+ `% L' B3 s8 l/ Y/ upuberty in boys.3,4
. ?. d% e3 g" z7 l4 c ZThe most common form of congenital adrenal
+ V) _& M( T* d, ~8 Q& D _5 thyperplasia is the 21-hydroxylase enzyme deficiency.
+ G4 Q9 w4 T0 }' G$ JThe 11-β hydroxylase deficiency may also result in
1 R; M! O( L. `' Oexcessive adrenal androgen production, and rarely,
3 t, P+ u6 H3 F% qan adrenal tumor may also cause adrenal androgen" \; C5 A+ n) f' U2 x" J( v* U
excess.1,3
0 a2 G4 i8 N2 s. @- {5 \at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from8 p' v) A! l( W# z( `3 K/ P2 P
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007: p( R9 Y, f! L7 F4 d' b* i
A unique entity of male-limited gonadotropin-1 r: S& P6 ~/ F+ [1 m2 @
independent precocious puberty, which is also known
5 ?' _) R" i3 o/ z2 H; @as testotoxicosis, may cause precocious puberty at a
3 |6 a- P5 d0 ]4 Q! Tvery young age. The physical findings in these boys, e# Z* {5 x9 \( j+ c0 _; _
with this disorder are full pubertal development,
; ^) `" h7 I5 A% S( Y/ |including bilateral testicular growth, similar to boys# X7 n1 h( @' ^
with CPP. The gonadotropin levels in this disorder! I* @1 Y, @3 }9 \6 X. o
are suppressed to prepubertal levels and do not show- {) z( }7 D+ r$ s
pubertal response of gonadotropin after gonadotropin-
& |, z0 f- i5 e9 H/ s6 A9 r \5 Vreleasing hormone stimulation. This is a sex-linked+ u% R7 {& k* h6 i2 z
autosomal dominant disorder that affects only
: l! X# A3 _' j+ p$ [males; therefore, other male members of the family
+ W' N: g3 ]3 umay have similar precocious puberty.32 n% r5 P, j. U4 ?( C) z6 y
In our patient, physical examination was incon-
( }' C' a9 T4 Wsistent with true precocious puberty since his testi-- {3 y& d- ?8 D! W) s( A1 M
cles were prepubertal in size. However, testotoxicosis
, G5 H) I3 R: X1 @, l# q$ }" Wwas in the differential diagnosis because his father
8 b: j0 ^" [* t/ Z [+ u5 {7 j8 Zstarted puberty somewhat early, and occasionally,& A6 N) m4 a- ^8 f
testicular enlargement is not that evident in the
& I0 ]* E1 f. k0 i3 _5 _beginning of this process.1 In the absence of a neg-; H8 | c) M8 D2 y
ative initial history of androgen exposure, our6 H m- }0 a, R2 r1 {
biggest concern was virilizing adrenal hyperplasia,
" p$ D% e& o: V/ veither 21-hydroxylase deficiency or 11-β hydroxylase
7 f4 @) T% z. w. @1 m2 ldeficiency. Those diagnoses were excluded by find-, `( r" }- F! H/ T2 k
ing the normal level of adrenal steroids.
& U0 [. \. Y: E; d5 @The diagnosis of exogenous androgens was strongly% ]$ }0 s0 f" }% N4 D: s# L
suspected in a follow-up visit after 4 months because
. ]4 w! \" Y7 ~+ ~9 F$ }the physical examination revealed the complete disap-' I5 k8 V9 h7 `6 K7 t
pearance of pubic hair, normal growth velocity, and1 h3 I! F5 q8 p+ K0 V5 y$ }
decreased erections. The father admitted using a testos-
/ R3 H0 l) L/ v1 K }terone gel, which he concealed at first visit. He was8 z. p: {0 }) |# t
using it rather frequently, twice a day. The Physicians’
; X6 N! x$ {& o, |Desk Reference, or package insert of this product, gel or
% B& H H6 j- E4 a' bcream, cautions about dermal testosterone transfer to0 F' C4 w& r* H3 J- @2 f
unprotected females through direct skin exposure.
+ H' V/ k- T4 w5 s! YSerum testosterone level was found to be 2 times the C1 A8 p/ j3 W* i) X, ?
baseline value in those females who were exposed to
$ O9 y* n. d* T9 Q2 feven 15 minutes of direct skin contact with their male! e) u2 e" }- W; }* R5 M. Z
partners.6 However, when a shirt covered the applica-
6 k. R* q) n5 I1 u6 D7 x+ ation site, this testosterone transfer was prevented.
5 [( Z2 \7 E! `/ A$ f7 U9 hOur patient’s testosterone level was 60 ng/mL,/ k+ g# y% u. K1 |6 L
which was clearly high. Some studies suggest that% ?& i( i3 V0 g! a2 ^9 J* l
dermal conversion of testosterone to dihydrotestos-" T; y3 }. m& k# ]! y9 b
terone, which is a more potent metabolite, is more# |; c _9 [/ A; @& R# o
active in young children exposed to testosterone- m+ j* j$ S5 @( ], F7 v" H
exogenously7; however, we did not measure a dihy-. Z; ^2 O5 {+ `4 d/ y
drotestosterone level in our patient. In addition to9 X4 Q0 }5 w# d& L& h
virilization, exposure to exogenous testosterone in) a/ e5 c4 E% o% C
children results in an increase in growth velocity and9 C) f6 e. G! P8 W7 T" v& Q
advanced bone age, as seen in our patient.% ~% q. O+ X. m
The long-term effect of androgen exposure during
' L2 U" J" }" c2 o3 g7 w$ Hearly childhood on pubertal development and final) O( s/ }6 X C1 L$ x
adult height are not fully known and always remain; C3 u) Q* \6 e4 j* }& t
a concern. Children treated with short-term testos-
% R1 x+ x7 D4 M& y! d% Cterone injection or topical androgen may exhibit some3 @8 D: N3 Q/ U- w( [ i( r
acceleration of the skeletal maturation; however, after% k5 G9 V9 _+ P4 |( |1 a8 s( E* M
cessation of treatment, the rate of bone maturation ]+ Z4 K7 \1 R7 ~- ^: m
decelerates and gradually returns to normal.8,9
; M9 d0 ]/ L! L3 n. y0 {: uThere are conflicting reports and controversy: Y: e% e) [6 X7 c, s
over the effect of early androgen exposure on adult1 i0 H9 }9 ]9 B. h+ r
penile length.10,11 Some reports suggest subnormal
% ~0 Z* N' C5 ^* R# Fadult penile length, apparently because of downreg-
* R" V9 g4 C# F& Gulation of androgen receptor number.10,12 However,8 Z# R* A, l7 M
Sutherland et al13 did not find a correlation between
3 c+ J" [/ w0 lchildhood testosterone exposure and reduced adult5 |) i0 s7 \% c. R+ Z
penile length in clinical studies.. X3 q1 n- C, L# ^) f' }
Nonetheless, we do not believe our patient is8 a! l( S, r0 a( g4 n
going to experience any of the untoward effects from: T0 d% M7 s4 u6 c0 H5 |8 S
testosterone exposure as mentioned earlier because
( \$ t6 }4 f9 ]7 b: q y' @' Mthe exposure was not for a prolonged period of time./ f* z& B- i) g
Although the bone age was advanced at the time of* R1 y4 K# X$ ? j% ^# J
diagnosis, the child had a normal growth velocity at
! ^/ Q3 @/ a+ p1 g* L3 Q% Uthe follow-up visit. It is hoped that his final adult6 }4 V8 x3 k0 l* c9 o9 M
height will not be affected.
4 q% }6 l; b3 a# G) w& ^* lAlthough rarely reported, the widespread avail-# T2 S w4 [. p5 x/ K
ability of androgen products in our society may
! X9 e# m; y- L4 v1 H- X$ rindeed cause more virilization in male or female
( X: e, g/ p# k% g# ~3 N$ v5 Gchildren than one would realize. Exposure to andro-
# z1 c# c6 T& H0 j8 Pgen products must be considered and specific ques-( P4 I/ x' P. C, ]9 m6 o; Q
tioning about the use of a testosterone product or+ W: e$ K5 |7 C( O" g, w- U9 C
gel should be asked of the family members during
9 q: \1 ^/ J0 n2 z; R: Ithe evaluation of any children who present with vir-
# c0 P% v+ u5 r6 j! j1 |; Nilization or peripheral precocious puberty. The diag-) k; H! h% ~8 ]4 }0 R. o/ r/ l! N
nosis can be established by just a few tests and by
. ~. l8 b2 f1 b- q$ z) A! p+ Xappropriate history. The inability to obtain such a4 Y* Y( x0 }0 Z5 r, R3 n
history, or failure to ask the specific questions, may, q) @5 V/ l, h+ A0 l* p& Q
result in extensive, unnecessary, and expensive
Z: z# K" A' w# Einvestigation. The primary care physician should be
% }4 K3 `( v/ s# ]7 naware of this fact, because most of these children, ~5 c" m/ _, b0 [
may initially present in their practice. The Physicians’
5 e3 a" z: E( `0 ^, ZDesk Reference and package insert should also put a& }8 r' s5 [& o }' U; x. s
warning about the virilizing effect on a male or5 Q) H; |# D; {5 Z1 g
female child who might come in contact with some-8 f/ L8 w/ f/ o) J* Q8 Q, K2 S
one using any of these products.
* f9 Y9 K% ~6 m% A8 ?References% z0 C$ F' U, k
1. Styne DM. The testes: disorder of sexual differentiation
% k6 s, A' _. Q( D' X) G0 m4 g& dand puberty in the male. In: Sperling MA, ed. Pediatric
. Y C6 s/ I* ?6 f0 N3 n$ JEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;1 S0 m) E# O* s( A5 E2 x
2002: 565-628.& p; N' D, x; c0 \
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
4 ~; z: }7 x5 x6 |& Q' X+ rpuberty in children with tumours of the suprasellar pineal |
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