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Sexual Precocity in a 16-Month-Old
, g# o8 Q) W! W6 YBoy Induced by Indirect Topical# l- ?' x) c* G( a7 w8 g% \) F i
Exposure to Testosterone
' x5 d2 Q" u! \Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2& T0 f+ q3 ]& C; u- f
and Kenneth R. Rettig, MD1# s+ H" s' I: Y: F/ f# L
Clinical Pediatrics( Z. }& f, }$ Q6 @ t8 _
Volume 46 Number 6
% T- m' J6 n7 QJuly 2007 540-543: K: c! A6 M5 B) L% L
© 2007 Sage Publications
0 M9 A8 i- O5 n: m6 \6 [ a10.1177/00099228062966517 v" S, x& P: R4 u( H& J6 L' z
http://clp.sagepub.com( M# _4 [/ j; d- m, y1 V
hosted at
" T9 l/ L& G. q: U6 `http://online.sagepub.com$ E* `' F# L" d# \: H9 }
Precocious puberty in boys, central or peripheral,8 U' D: u3 M8 H9 x' N
is a significant concern for physicians. Central6 w: h6 h* F8 f8 B
precocious puberty (CPP), which is mediated/ E1 @. S$ i# n/ E) h3 V# ]& A
through the hypothalamic pituitary gonadal axis, has: F! s, x: t5 i0 o# S% Q
a higher incidence of organic central nervous system
) c! B# T8 S6 b3 @, ]1 z- Vlesions in boys.1,2 Virilization in boys, as manifested
H) ] m) W# n% {8 nby enlargement of the penis, development of pubic- d& P) s9 g4 S o
hair, and facial acne without enlargement of testi-! u+ b. L/ L2 D) w
cles, suggests peripheral or pseudopuberty.1-3 We4 j2 u# k( U6 d [5 \& M, f" H
report a 16-month-old boy who presented with the
( k% i. G( L* X. N# V1 z6 Xenlargement of the phallus and pubic hair develop-9 @& S; o: U- J) a. _- O4 H
ment without testicular enlargement, which was due
% A9 d0 n8 ?( \1 q' ato the unintentional exposure to androgen gel used by
5 P) m/ W" ~! p: Z: _/ } Vthe father. The family initially concealed this infor-/ _& J; I: x# o2 q7 O) o0 d. }5 X
mation, resulting in an extensive work-up for this
; S; c# _1 n" N. h- o% K" nchild. Given the widespread and easy availability of
# P9 E; u9 p/ ntestosterone gel and cream, we believe this is proba-2 R( K C9 {, L! R, _' a! E1 ?
bly more common than the rare case report in the
E. r6 g% F* t, |+ nliterature.4( l/ J7 V% b, R
Patient Report
7 j/ e5 N/ E1 y* ~% R3 u; eA 16-month-old white child was referred to the
& Y$ _. b8 W9 {+ [endocrine clinic by his pediatrician with the concern/ E5 R$ L3 v' n' J, r9 d
of early sexual development. His mother noticed
& {: C. D: u) U" {9 ilight colored pubic hair development when he was. P7 R4 f3 g! q5 J; u
From the 1Division of Pediatric Endocrinology, 2University of2 d5 W. C) s' u/ C
South Alabama Medical Center, Mobile, Alabama.
. v3 F+ N/ P6 I8 ~) SAddress correspondence to: Samar K. Bhowmick, MD, FACE,/ y% l& r+ {% U6 Z
Professor of Pediatrics, University of South Alabama, College of
. |" O0 }1 J# [( BMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
2 W' e( [$ y6 e$ J, w3 E0 Ie-mail: [email protected].5 M1 b. }# j$ \
about 6 to 7 months old, which progressively became
8 R5 s( L7 o+ Y% A' F% Tdarker. She was also concerned about the enlarge-
n! \6 k0 ^' \. O. `! w, Q4 Xment of his penis and frequent erections. The child- ]# p- J+ j T
was the product of a full-term normal delivery, with
- X' k) h& E' o) s( }7 \* Ra birth weight of 7 lb 14 oz, and birth length of
- n- G% O* }8 d# p/ {1 s) w20 inches. He was breast-fed throughout the first year5 N% ]. p- d+ S( ~- V! [
of life and was still receiving breast milk along with$ q' ^8 B' }7 R- b
solid food. He had no hospitalizations or surgery,) J, f6 x1 y. k3 P; X+ H
and his psychosocial and psychomotor development% l" y2 A' Y% C! t( U
was age appropriate.
& o9 A% U$ E, k0 v6 K; iThe family history was remarkable for the father,
+ C0 ~- K" C% k% l' \who was diagnosed with hypothyroidism at age 16,
# V- t2 t {3 a5 u$ V) Kwhich was treated with thyroxine. The father’s" M( K' ]' p& f1 y# x+ m/ u8 v
height was 6 feet, and he went through a somewhat
o$ t( ]/ U2 H1 a" dearly puberty and had stopped growing by age 14.
: A+ I4 k3 D" g9 tThe father denied taking any other medication. The2 k! J: D. ~) {0 l. w1 c" [
child’s mother was in good health. Her menarche" q5 K, w; j. V( H& N% k
was at 11 years of age, and her height was at 5 feet" U8 ~4 b' K' V- V7 E
5 inches. There was no other family history of pre-
. B# j( f& l0 `1 Scocious sexual development in the first-degree rela-
: \' e7 |' Q* u" V9 gtives. There were no siblings.
: t; J5 l/ q S; N! EPhysical Examination) |# s5 H- h( S; D' X
The physical examination revealed a very active,' c- ~6 W6 W0 L
playful, and healthy boy. The vital signs documented* n$ ~/ a* u. z# M
a blood pressure of 85/50 mm Hg, his length was9 R# A7 U+ v4 G/ @& N
90 cm (>97th percentile), and his weight was 14.4 kg
: N; R/ w% Q; C& M7 ^(also >97th percentile). The observed yearly growth! V9 q$ u5 C, ~- e+ ~* ?3 \
velocity was 30 cm (12 inches). The examination of
, ~5 O( ^+ v% V% lthe neck revealed no thyroid enlargement.
. A3 Q5 ~) j% Y6 yThe genitourinary examination was remarkable for& m" K; R1 R1 \7 u6 ^! F P
enlargement of the penis, with a stretched length of: L, H" Y; _$ w. d) X
8 cm and a width of 2 cm. The glans penis was very well$ Z/ O/ c" e3 f$ ~$ J
developed. The pubic hair was Tanner II, mostly around+ a; k- [- j' q
540
) I7 ?4 A" E+ f; J3 D$ Gat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
5 }+ M- x f& k( O; @the base of the phallus and was dark and curled. The
7 O9 t/ _& T% q8 z3 ktesticular volume was prepubertal at 2 mL each.
# R5 Z1 i- K( W; h' SThe skin was moist and smooth and somewhat- E) h" x" n* K
oily. No axillary hair was noted. There were no
( H9 W: `6 ]4 W6 H: u3 }& [/ \& zabnormal skin pigmentations or café-au-lait spots.
( v a6 ^4 ?% n+ xNeurologic evaluation showed deep tendon reflex 2+5 `' v% t1 N o- _1 B
bilateral and symmetrical. There was no suggestion
5 Y: F; q2 M. V$ @of papilledema., y4 E% g7 |- l, b5 o# O8 u X8 h
Laboratory Evaluation
7 {. Q3 s0 {' Q7 e$ v, N8 n" N% X3 NThe bone age was consistent with 28 months by
0 c" m' r) h1 Busing the standard of Greulich and Pyle at a chrono-
* F8 u+ X8 F+ I; Mlogic age of 16 months (advanced).5 Chromosomal5 Q! ]1 x B, Y
karyotype was 46XY. The thyroid function test
; l' W: l7 D2 mshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
5 E6 t# c4 W! F* U7 k8 Dlating hormone level was 1.3 µIU/mL (both normal).
0 m& h I8 q3 ?" @' \* H4 SThe concentrations of serum electrolytes, blood6 r4 R6 @; F) ?. B* \; l
urea nitrogen, creatinine, and calcium all were! u" M2 P9 p; h; \
within normal range for his age. The concentration5 F" e6 V% w. h. u( T4 c
of serum 17-hydroxyprogesterone was 16 ng/dL
. D. Z# i0 ?3 Z: F0 t( U(normal, 3 to 90 ng/dL), androstenedione was 20 [1 N' O! ~) m. R! D
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-: n$ W" t! L7 \- R
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
5 ~7 Y! f. d+ D7 v% Tdesoxycorticosterone was 4.3 ng/dL (normal, 7 to9 O1 h# ]5 u* H4 i1 L
49ng/dL), 11-desoxycortisol (specific compound S)2 K R. i' _ F/ F; K" c% J
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
8 S6 M6 N. O* h: a; h& v" Z: {tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
\* z$ F; e S: Xtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
' e! T! I, v) ^$ b; @' j$ oand β-human chorionic gonadotropin was less than! o2 F4 b- b* u2 E1 t2 c5 R
5 mIU/mL (normal <5 mIU/mL). Serum follicular
S/ f% O1 \; k3 G3 }2 o; hstimulating hormone and leuteinizing hormone6 L8 t8 O8 A; ?
concentrations were less than 0.05 mIU/mL
$ ?2 S6 B5 M3 U M(prepubertal).
& F) s5 m. S6 C, cThe parents were notified about the laboratory& O8 d/ C9 I' e; m: m. y. ]
results and were informed that all of the tests were2 q j/ m/ [) a* @# P# `) {, s
normal except the testosterone level was high. The M9 @7 ^+ n+ p2 G: x
follow-up visit was arranged within a few weeks to
/ G, s( C" m# e, Cobtain testicular and abdominal sonograms; how-6 {0 L9 @- _; [, R- P1 k& X6 C
ever, the family did not return for 4 months.2 E* `+ C' R- k' a
Physical examination at this time revealed that the
% M* G( G2 r/ Ychild had grown 2.5 cm in 4 months and had gained6 x ~2 i# D7 u8 {3 f. [# a
2 kg of weight. Physical examination remained8 @0 a3 g |# j7 F, z& d, y( u
unchanged. Surprisingly, the pubic hair almost com-1 a* v9 }2 \* H+ O. L( |- W
pletely disappeared except for a few vellous hairs at) [+ F4 u" [2 G/ p& m3 H( U
the base of the phallus. Testicular volume was still 2# s0 m, e. j* ~$ F/ V
mL, and the size of the penis remained unchanged.
- t0 }) X/ o# k3 |: YThe mother also said that the boy was no longer hav-
% `. z5 L, } ^$ jing frequent erections.
, O) ]: q& y" R* a5 [$ L9 K' _, _Both parents were again questioned about use of K/ k, W1 U: ~+ i4 j( }
any ointment/creams that they may have applied to
! m# d Q9 Y8 h2 a" sthe child’s skin. This time the father admitted the& ?" { g7 w F! A5 k
Topical Testosterone Exposure / Bhowmick et al 541
% v: W0 U' V) P- `; \' C) Ause of testosterone gel twice daily that he was apply-
- B/ I' T6 U: i3 k6 [8 L, _ing over his own shoulders, chest, and back area for
0 R3 I( b, O+ P2 o/ Ga year. The father also revealed he was embarrassed
) W* A& ~! ]! y. f6 R+ k9 N% Uto disclose that he was using a testosterone gel pre-
8 r4 o7 R5 F5 U) [9 Xscribed by his family physician for decreased libido
9 s4 n- ~* Q0 B" o3 H1 n. N' k# gsecondary to depression.7 c2 h- r: f( u0 [' g% ?# }
The child slept in the same bed with parents.
, Z: X& A1 j7 L- ?& D5 A: J3 UThe father would hug the baby and hold him on his
0 o/ O9 Q$ j. m0 g" schest for a considerable period of time, causing sig-
8 n6 }; G& r1 m% h' h5 k: X+ ~* \% nnificant bare skin contact between baby and father.
( E: [/ f6 f8 `0 vThe father also admitted that after the phone call,
c' W. w; F+ n1 M8 J- uwhen he learned the testosterone level in the baby2 _$ {/ t/ Y$ |( x2 y! V( v+ Q' W
was high, he then read the product information, n1 }, A7 b0 M6 ?+ o8 V
packet and concluded that it was most likely the rea-0 {( b8 b' d4 V( h9 ~
son for the child’s virilization. At that time, they
. y6 M0 c4 m% N4 J7 a2 J* [: Kdecided to put the baby in a separate bed, and the
! F x' S% P" nfather was not hugging him with bare skin and had/ i: [' k" W g8 V9 w+ \% \
been using protective clothing. A repeat testosterone
8 w! }; e* e4 f# wtest was ordered, but the family did not go to the
4 L( o3 G4 O( C9 x! F* Wlaboratory to obtain the test./ o7 m) o) h s
Discussion/ k* ~+ \) ~: u; q/ {
Precocious puberty in boys is defined as secondary/ l6 ^! O& G. c6 q
sexual development before 9 years of age.1,4( ]% Y8 H; ^; w7 |2 @
Precocious puberty is termed as central (true) when
: z/ f& P2 {' }it is caused by the premature activation of hypo-$ U. @+ G) y/ r% q( {+ z2 s: U/ `' ]
thalamic pituitary gonadal axis. CPP is more com-
+ p& X# f) H2 q& E. Z' [4 Amon in girls than in boys.1,3 Most boys with CPP
+ ?, T2 M) }4 J6 x8 f2 u5 D" amay have a central nervous system lesion that is6 i1 `6 P. U1 S! q$ z3 ]
responsible for the early activation of the hypothal-; K- G$ p* i" z* b: b1 A/ ?3 ~9 r
amic pituitary gonadal axis.1-3 Thus, greater empha-2 H/ R5 {* Q% g0 L& V
sis has been given to neuroradiologic imaging in
! j a& U5 J& {, [boys with precocious puberty. In addition to viril-
, ^& O- z* E1 T$ s$ Nization, the clinical hallmark of CPP is the symmet-
7 i+ H* l/ k& e$ A- C) Trical testicular growth secondary to stimulation by- G. k9 o' ]( w
gonadotropins.1,3$ G8 V9 Z \& ^3 l
Gonadotropin-independent peripheral preco-
. Y- S+ ^9 u( ?0 E4 q. U1 q" M Ncious puberty in boys also results from inappropriate
1 `% a0 {! h$ y/ n0 n0 Gandrogenic stimulation from either endogenous or
( t5 M5 D+ r. x7 w! {: `exogenous sources, nonpituitary gonadotropin stim-
2 N6 s' J9 p Z/ _" pulation, and rare activating mutations.3 Virilizing
% O" U' X$ O# p' O4 q! y) W# Xcongenital adrenal hyperplasia producing excessive
2 `, P0 y( o' y j! X. o% cadrenal androgens is a common cause of precocious
. i5 D M! i3 l( d9 ipuberty in boys.3,44 I' ~+ F1 z2 ~
The most common form of congenital adrenal* i) C W1 Z. l+ W3 G# B' ~; h
hyperplasia is the 21-hydroxylase enzyme deficiency.' s; L! ?8 }$ B7 A7 h
The 11-β hydroxylase deficiency may also result in/ v. Z2 t t! V3 C% [
excessive adrenal androgen production, and rarely,
8 s. h3 d( Y6 u8 n) ?an adrenal tumor may also cause adrenal androgen
5 `7 p4 X- u3 q( Bexcess.1,34 ?2 U w2 p' D8 f
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
U5 f/ K. j6 p# c( ?* k5 \9 S1 j& O. V542 Clinical Pediatrics / Vol. 46, No. 6, July 20079 l# k2 r' E* i4 L
A unique entity of male-limited gonadotropin-
( W8 v0 {- ?3 b+ `6 Oindependent precocious puberty, which is also known: [* K) ?, n# i* t3 Z
as testotoxicosis, may cause precocious puberty at a/ o4 f# R6 h+ }8 J4 M7 e0 ?
very young age. The physical findings in these boys
- F( H$ o' } w& U* G8 w# _with this disorder are full pubertal development,
! H6 a; |2 z% e$ n* B3 ?including bilateral testicular growth, similar to boys8 P+ x& U" X& i5 w2 Y/ k
with CPP. The gonadotropin levels in this disorder
, t: } ~4 ?9 f* w9 nare suppressed to prepubertal levels and do not show
& y' s' Q2 H( r8 ?3 ?/ ^pubertal response of gonadotropin after gonadotropin-
2 |& l4 G, |, l+ } M6 H! ~+ Y Z) Ereleasing hormone stimulation. This is a sex-linked
R0 K/ X3 D6 h, X/ m2 kautosomal dominant disorder that affects only# Q6 K/ @, G, [* v" A5 \
males; therefore, other male members of the family
8 w. P# V1 J% Zmay have similar precocious puberty.3/ e7 {& Q/ I4 ^
In our patient, physical examination was incon-1 ]/ i/ j# o0 R2 D3 H
sistent with true precocious puberty since his testi-3 h1 ]- ^8 o3 u% C/ G( v
cles were prepubertal in size. However, testotoxicosis
, \0 r% ~. N+ T, `: L3 bwas in the differential diagnosis because his father
0 k) h. ]- i l4 N. j+ ^started puberty somewhat early, and occasionally,
5 L0 h/ a0 x- i3 Etesticular enlargement is not that evident in the
2 z$ y' |( s" l' x' C/ M' i) j! s9 Ibeginning of this process.1 In the absence of a neg-
: Z# R, z3 b( ]) Y; c" B. K7 Kative initial history of androgen exposure, our; r6 C* x! x( N4 S
biggest concern was virilizing adrenal hyperplasia,
& }9 L: H) h! teither 21-hydroxylase deficiency or 11-β hydroxylase/ t- `+ k# c# B( o
deficiency. Those diagnoses were excluded by find-
/ d2 l) \$ `5 F3 d# ding the normal level of adrenal steroids.
$ B% c% J& B3 [3 nThe diagnosis of exogenous androgens was strongly
9 ]5 z' E' N: \: s0 R& d- F$ Vsuspected in a follow-up visit after 4 months because0 w- }9 C. N( x b
the physical examination revealed the complete disap-+ B Y( a9 Z ^( }7 h( R% @
pearance of pubic hair, normal growth velocity, and
7 U4 o5 w8 M6 L) F& hdecreased erections. The father admitted using a testos-$ U: z, d, ~; f3 s* u9 U
terone gel, which he concealed at first visit. He was9 [2 r/ Z, e) Y5 V
using it rather frequently, twice a day. The Physicians’0 w; e' o% y# A% h4 U8 F, }* X
Desk Reference, or package insert of this product, gel or
" H1 ]5 P1 B) s$ j' ^ L" Y* ncream, cautions about dermal testosterone transfer to. \3 @% c3 F; f* q* }5 z
unprotected females through direct skin exposure.
6 c5 x+ ]1 ?% [4 M* \: oSerum testosterone level was found to be 2 times the6 j' y5 l- L R1 t- }' J5 i
baseline value in those females who were exposed to
0 D- l& t2 _9 Z; L' ^2 Ceven 15 minutes of direct skin contact with their male/ M4 }* A2 |9 G# z( C0 X- Z
partners.6 However, when a shirt covered the applica-
( s7 I( |( [9 L+ H' A. f; ] ?3 Ition site, this testosterone transfer was prevented./ n! y7 O {" ^, z: |
Our patient’s testosterone level was 60 ng/mL,8 |5 Q$ x. X6 c k* J0 q
which was clearly high. Some studies suggest that
' b9 J1 a" s3 D' U$ Cdermal conversion of testosterone to dihydrotestos-4 m. k2 u2 u$ c) ~6 T9 y
terone, which is a more potent metabolite, is more
5 m$ V5 p% V/ |0 [& ^ n9 F8 Yactive in young children exposed to testosterone" B! k8 n* n( I9 k$ S
exogenously7; however, we did not measure a dihy-1 E* q4 [0 B& {/ l3 T
drotestosterone level in our patient. In addition to; J& H' k$ T; O. ?" M6 G8 t
virilization, exposure to exogenous testosterone in! i+ b$ l1 N0 F/ m6 D7 {
children results in an increase in growth velocity and5 Z ~3 c" C% s! H& j
advanced bone age, as seen in our patient., ^9 U: d" p! Q
The long-term effect of androgen exposure during, R2 P, v6 S- I. \& f0 u7 A3 D
early childhood on pubertal development and final
6 D9 }- I: {, j5 [- [0 Kadult height are not fully known and always remain
% C" @: x" f) @& F+ ?# da concern. Children treated with short-term testos-3 m5 q0 `) f/ F. m T2 W' [! H5 a
terone injection or topical androgen may exhibit some
/ t+ a$ O* D( X4 ^: s1 macceleration of the skeletal maturation; however, after+ A: o8 L' S3 Y5 A3 l3 b/ i, L
cessation of treatment, the rate of bone maturation
7 Q( }" S0 q3 e3 W6 q `/ Ddecelerates and gradually returns to normal.8,9 ?9 r& O. l, v
There are conflicting reports and controversy4 i$ A" P5 c5 D" r" ^9 E0 @
over the effect of early androgen exposure on adult$ l3 m. V3 I4 L
penile length.10,11 Some reports suggest subnormal
) i+ Q7 [$ A' j, Iadult penile length, apparently because of downreg-
y* R' ^6 g, w6 rulation of androgen receptor number.10,12 However,3 ~# d8 {0 `1 ]& z8 h6 h, ^
Sutherland et al13 did not find a correlation between
9 v; u# o3 X- q% _* Bchildhood testosterone exposure and reduced adult
# S; z" d% ^7 g7 y0 j- Upenile length in clinical studies.
! v5 o9 @6 K+ r2 \Nonetheless, we do not believe our patient is1 U% P* R5 f& q- g7 y
going to experience any of the untoward effects from
6 x* ?) e0 o" D4 r" E6 j, {. mtestosterone exposure as mentioned earlier because+ f8 A% y- d; [8 l
the exposure was not for a prolonged period of time.
) u# m K! M7 h) a+ NAlthough the bone age was advanced at the time of" |2 H' L/ P G, M
diagnosis, the child had a normal growth velocity at
1 i* D' m- }. j7 Bthe follow-up visit. It is hoped that his final adult
; o$ {9 Y' C4 a) {height will not be affected.. ]5 B2 g0 i1 |7 j F) b2 g: z( `9 D
Although rarely reported, the widespread avail-
2 l+ U& `3 s; N# yability of androgen products in our society may
1 o; [+ F5 Y$ \2 Gindeed cause more virilization in male or female8 L+ V! ^6 C! y& B) b9 I& i1 f
children than one would realize. Exposure to andro-
/ P" `% A6 l7 Ogen products must be considered and specific ques-
- p/ a( R$ p+ F: S* [tioning about the use of a testosterone product or
1 N, u5 N8 T; ~5 A4 hgel should be asked of the family members during( r+ ]4 ?4 [0 [1 v: I0 j" Y
the evaluation of any children who present with vir-% [, J/ C, r7 ~, y4 D; G
ilization or peripheral precocious puberty. The diag-# O8 ^% W1 ]' e( b" P: Y
nosis can be established by just a few tests and by- w. U: M/ N' J: z& f
appropriate history. The inability to obtain such a
# ~+ u2 V! x& |history, or failure to ask the specific questions, may
" m. }( p; b z+ E: Uresult in extensive, unnecessary, and expensive3 J+ L7 `/ J9 {: E. x
investigation. The primary care physician should be- o( I; z" N- ^4 W* g' R- c
aware of this fact, because most of these children8 h3 P" [' o9 f
may initially present in their practice. The Physicians’
6 Y( S6 Y# X- C3 `4 tDesk Reference and package insert should also put a
& n4 Q! _( O; X5 m, X/ lwarning about the virilizing effect on a male or
$ S, ?& w8 T, H! X$ ufemale child who might come in contact with some-
5 e& c, }3 v3 q2 p. y+ J+ J. }one using any of these products.
- j& W6 c1 L( }4 pReferences+ ~2 h o6 j( S* q- A
1. Styne DM. The testes: disorder of sexual differentiation) C4 O% I# _5 x. ^# ^/ P' f: w# n
and puberty in the male. In: Sperling MA, ed. Pediatric
$ J6 J0 [0 p; WEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;; L2 G) r9 M6 d" `" L
2002: 565-628.& P6 W5 [1 X* ]* N2 v% \
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
9 y/ u7 F8 ] V$ a% Mpuberty in children with tumours of the suprasellar pineal |
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