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Sexual Precocity in a 16-Month-Old
3 _9 n# |. U! KBoy Induced by Indirect Topical( x0 U! f# B& c' F( m* L- y
Exposure to Testosterone
4 P) b, b* t3 |% b& X) E4 \Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,28 B. p2 B, L5 H9 r+ _
and Kenneth R. Rettig, MD1$ A- P2 v. \' S8 z5 Y5 G
Clinical Pediatrics
- D* o. ]" n: a# UVolume 46 Number 6; }8 A2 S, |, p7 V' g- B) c
July 2007 540-543
- t5 n" ?3 S; F! x- k% _4 ` F: Y© 2007 Sage Publications
6 |, ?4 O5 d9 |7 U10.1177/0009922806296651
' U& R. O# t0 U3 O/ B" H- @http://clp.sagepub.com i, t y, j1 L" c
hosted at
. \8 R; S1 Y7 Nhttp://online.sagepub.com
4 }7 t4 H, c# ~9 ~6 c0 T/ o% j; L6 ]Precocious puberty in boys, central or peripheral,
8 \4 L1 u. n; p9 Gis a significant concern for physicians. Central& E" q* m0 E @2 i# k1 W" J D4 m! @
precocious puberty (CPP), which is mediated
9 m9 h" o& H1 Ythrough the hypothalamic pituitary gonadal axis, has
7 o( G" H; v6 h- e& y$ U8 O1 Ma higher incidence of organic central nervous system
2 W5 Z% g& @0 Q9 S( \' glesions in boys.1,2 Virilization in boys, as manifested4 b2 S' G1 u/ A8 r. G) v1 U
by enlargement of the penis, development of pubic
8 m4 y. d% [, F# Bhair, and facial acne without enlargement of testi-1 E" I' d3 \% Q/ C0 c
cles, suggests peripheral or pseudopuberty.1-3 We
$ A S* i7 c" N8 p! R: wreport a 16-month-old boy who presented with the" d7 T' | m6 {) [% C* ]
enlargement of the phallus and pubic hair develop-
1 v, }, ~* o# v; W" lment without testicular enlargement, which was due! j6 F7 t0 O$ d2 A! K
to the unintentional exposure to androgen gel used by, @; _/ _8 U- U* n# U3 l( {$ C# R
the father. The family initially concealed this infor-' v& j9 O2 Q# _$ h4 X/ i6 G; J
mation, resulting in an extensive work-up for this
8 P5 A. x* \, M& |5 h9 e8 Z' {child. Given the widespread and easy availability of+ T( f9 y: x; l; }4 u: b$ p* z
testosterone gel and cream, we believe this is proba-3 B0 [) j8 N5 X# I
bly more common than the rare case report in the
+ I* n$ \- f" ?literature.43 ~ @/ h- C; M8 i5 v. Z a9 [8 y
Patient Report
6 N5 N7 _3 E+ BA 16-month-old white child was referred to the
$ O) I# s G& E* C' |! X7 `endocrine clinic by his pediatrician with the concern
# m' k0 l* P/ h$ t+ Yof early sexual development. His mother noticed
" U% D4 h/ I3 u5 ?3 U8 alight colored pubic hair development when he was
2 ?' W; F* B: yFrom the 1Division of Pediatric Endocrinology, 2University of+ e+ r$ D" {( n% h
South Alabama Medical Center, Mobile, Alabama.! w" S7 s0 M! T8 i' F- i
Address correspondence to: Samar K. Bhowmick, MD, FACE,
2 B6 M. g2 W" F: y+ _Professor of Pediatrics, University of South Alabama, College of$ a4 Y" m+ d! l4 o
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;. }8 a2 N2 m P6 Y3 ~
e-mail: [email protected].& H6 P) \) i& h
about 6 to 7 months old, which progressively became1 n3 w& w- O9 b' a/ ^1 f
darker. She was also concerned about the enlarge-; I! r7 j& }6 ^ r- ]! z
ment of his penis and frequent erections. The child# ?( A5 \! w9 z( [
was the product of a full-term normal delivery, with; m. P" c* e1 _+ P. q6 S
a birth weight of 7 lb 14 oz, and birth length of
8 P3 |+ V: ?% D3 m6 G20 inches. He was breast-fed throughout the first year3 v8 t6 @; a8 u# Q6 a# _: g
of life and was still receiving breast milk along with/ a/ t& N$ V$ e6 l$ [6 w U2 s
solid food. He had no hospitalizations or surgery,1 V5 t! \! `5 Y' O7 s
and his psychosocial and psychomotor development0 l% b3 n0 c: Y2 t+ B1 N3 Q
was age appropriate.4 m$ v9 l, j; z S
The family history was remarkable for the father,* I8 H8 [5 ?' V$ D# C
who was diagnosed with hypothyroidism at age 16,: K( L. z6 R. H1 A8 S V
which was treated with thyroxine. The father’s
' _( u, v* s& M9 [" R" v- Qheight was 6 feet, and he went through a somewhat! }2 ?: l5 G! S" n
early puberty and had stopped growing by age 14.# v- V" e+ o8 C8 H- n( c
The father denied taking any other medication. The9 |. v8 m) s7 u ]1 O8 W
child’s mother was in good health. Her menarche
4 o& m! H2 t+ ]4 K9 Uwas at 11 years of age, and her height was at 5 feet/ n$ A5 m; @9 y
5 inches. There was no other family history of pre-" y: r [+ ~6 j" K
cocious sexual development in the first-degree rela-
/ N3 z' q) K) ^ |) H6 Ttives. There were no siblings.1 ?6 I% S; U, b7 `6 Q
Physical Examination3 U( O, S7 T. ~6 H
The physical examination revealed a very active,
. q# W. r* [ ^$ H; wplayful, and healthy boy. The vital signs documented
+ U2 m* L; |7 Ia blood pressure of 85/50 mm Hg, his length was
8 W# p- w, S- Q6 ^90 cm (>97th percentile), and his weight was 14.4 kg
$ S/ t) T+ X1 ] g! {(also >97th percentile). The observed yearly growth% @5 }$ P! P& ]0 ~
velocity was 30 cm (12 inches). The examination of( t8 S( [2 t6 P0 `- ]% ` e
the neck revealed no thyroid enlargement.
9 }, f0 X q" }$ sThe genitourinary examination was remarkable for7 M8 a1 \8 K+ c8 |& @% x2 M1 }
enlargement of the penis, with a stretched length of6 ^- T( y+ f9 V
8 cm and a width of 2 cm. The glans penis was very well4 G2 K1 C* H0 e! ^
developed. The pubic hair was Tanner II, mostly around8 u$ Q/ g X0 j6 L b
540% X/ G( c8 y; E/ ]1 T# w" x
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the base of the phallus and was dark and curled. The2 m; u# ~1 W/ n" u$ u% O/ o
testicular volume was prepubertal at 2 mL each.2 ^% O9 u9 C: T, _, ^1 c
The skin was moist and smooth and somewhat) k5 L& q; H0 V" r7 U5 `1 C- x
oily. No axillary hair was noted. There were no
z1 @- p9 `3 R: [4 L! E; Aabnormal skin pigmentations or café-au-lait spots.
( g% d0 b4 w4 r+ NNeurologic evaluation showed deep tendon reflex 2+6 ?* ~ ^( z. f0 X6 Y1 i2 Z1 w
bilateral and symmetrical. There was no suggestion
$ Y, J' W1 l$ L; [3 D) f6 q( pof papilledema.
6 w2 W# V- Z& Q2 i' z& O. wLaboratory Evaluation l" W- l6 a* R: A
The bone age was consistent with 28 months by
. W% U. H) L) ]) |/ Cusing the standard of Greulich and Pyle at a chrono-3 H/ Z y: b6 N4 g9 n# ^2 y
logic age of 16 months (advanced).5 Chromosomal
+ F) o$ y6 |. l4 ]- F# {karyotype was 46XY. The thyroid function test
6 S( m! O Q1 i9 K$ d9 n" Zshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
8 x& ? U4 t; N$ `- [$ R! Elating hormone level was 1.3 µIU/mL (both normal)., E+ c; S' w5 \0 a9 W7 s$ W
The concentrations of serum electrolytes, blood9 d/ O% }/ e% b
urea nitrogen, creatinine, and calcium all were
. v! F: U/ W9 E1 S: C7 rwithin normal range for his age. The concentration7 \; C% s% t$ @0 L2 W
of serum 17-hydroxyprogesterone was 16 ng/dL
& G% M m2 k, y" z, f/ K+ F(normal, 3 to 90 ng/dL), androstenedione was 20- M) k( W' K0 ~' e4 |/ h- e
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-. I' Q5 _/ @' U( ^% ?
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
]0 M( w$ t2 ]! ^+ D% j+ ]3 Bdesoxycorticosterone was 4.3 ng/dL (normal, 7 to. ?* u! @) `) N$ Y
49ng/dL), 11-desoxycortisol (specific compound S)
# Y! a- z+ w! ^. u- e& K3 Dwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
" @5 @4 B0 ~" _tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total3 r, _& N7 ~) ~2 C
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),! p" v5 k7 c. ^. l
and β-human chorionic gonadotropin was less than
1 W% |) ^" L/ @) L6 X V# N+ q5 mIU/mL (normal <5 mIU/mL). Serum follicular# j5 f' ~% }, _2 b0 B, ^- L/ y0 R
stimulating hormone and leuteinizing hormone+ q j Y' w* i$ I6 A, [
concentrations were less than 0.05 mIU/mL
7 j; { C9 W7 C, e. V(prepubertal).; u' \6 l/ o/ V6 y5 B
The parents were notified about the laboratory0 e' {% H+ M& J2 M
results and were informed that all of the tests were2 t0 G0 @4 p4 a' C: f
normal except the testosterone level was high. The! M6 d- J$ ^6 x$ W' z) ?
follow-up visit was arranged within a few weeks to M; r" z q9 U; n2 [2 I" ^1 y
obtain testicular and abdominal sonograms; how-+ P9 Z$ [8 Y( [ O7 X: M* i
ever, the family did not return for 4 months.9 J% r* l5 S8 H
Physical examination at this time revealed that the& H- t5 T, @9 I1 w% Q$ e
child had grown 2.5 cm in 4 months and had gained" Z& J& s$ R% P8 _* [
2 kg of weight. Physical examination remained
, A$ M3 ]3 O- r/ v/ N7 o! ? Lunchanged. Surprisingly, the pubic hair almost com-
( q: \) q) E4 J9 E) R. ypletely disappeared except for a few vellous hairs at
9 F/ I' Q( }7 E/ qthe base of the phallus. Testicular volume was still 2
8 H+ ~( [$ X5 W5 d3 [6 H6 HmL, and the size of the penis remained unchanged.
8 w/ z0 h, D: t& r& \- [The mother also said that the boy was no longer hav-
9 W4 F8 `& ?; o) v% L3 F5 }ing frequent erections.
1 o& x& G |: G; vBoth parents were again questioned about use of
* U B1 [4 Z+ r' c" u) h5 u3 lany ointment/creams that they may have applied to8 b+ o: i6 }* Q7 z. g9 s
the child’s skin. This time the father admitted the
, A* ?3 K5 |$ {* n# ~Topical Testosterone Exposure / Bhowmick et al 5412 H5 X4 J' `' ` ?
use of testosterone gel twice daily that he was apply-
' `3 N1 D' p) d* ~1 q8 P% E. Ving over his own shoulders, chest, and back area for7 B" m, r4 p! u! u
a year. The father also revealed he was embarrassed U3 v0 k; Q! J
to disclose that he was using a testosterone gel pre-: U% M/ q; N7 T% j" `' \
scribed by his family physician for decreased libido# E; V: T* M( ` i; o
secondary to depression.
/ s" Q4 c8 k( J$ v7 xThe child slept in the same bed with parents." m) M7 B& {( b7 T4 d6 p
The father would hug the baby and hold him on his
" K7 e! ~, Z schest for a considerable period of time, causing sig-, E) q6 I/ e p1 g2 v: l
nificant bare skin contact between baby and father.
: A3 A7 F L6 Y% q& oThe father also admitted that after the phone call,
% ^$ A' }: {' \7 K% U$ P# Ewhen he learned the testosterone level in the baby
4 n2 |% C- Z8 \6 H/ Zwas high, he then read the product information
2 y7 j0 A5 y3 ?# k6 i+ Z) j) npacket and concluded that it was most likely the rea-+ y1 p; e, ?8 V) d7 R: _& K3 f
son for the child’s virilization. At that time, they
( S! c; h# J4 m3 U& P, e1 vdecided to put the baby in a separate bed, and the* C/ f2 C* c3 z- x7 K" _2 I
father was not hugging him with bare skin and had
4 Q9 ]+ I# s5 }been using protective clothing. A repeat testosterone
- Z3 E1 [9 _; d* |2 y/ t5 utest was ordered, but the family did not go to the V( n3 B7 J) B9 p: x
laboratory to obtain the test.
9 O1 p) r! {9 IDiscussion( C8 J. C3 B( }3 j
Precocious puberty in boys is defined as secondary3 f, I8 u" i1 c8 a
sexual development before 9 years of age.1,4
1 P6 }3 _- e% |; V+ M8 L: jPrecocious puberty is termed as central (true) when
3 L; y0 p+ m/ j* k9 }& |1 N4 h1 ]it is caused by the premature activation of hypo-4 G4 F, ~% q( ^( g+ E0 I
thalamic pituitary gonadal axis. CPP is more com-' u( X( L% A! O+ _( n' @! k3 V) o
mon in girls than in boys.1,3 Most boys with CPP
& g, T) t: k6 x0 Fmay have a central nervous system lesion that is
* L$ A: H6 j# l+ xresponsible for the early activation of the hypothal-5 k; q" Z& f: X% D+ O+ M0 O/ }
amic pituitary gonadal axis.1-3 Thus, greater empha-( \7 G' ]0 m( I4 y- ^6 J' K
sis has been given to neuroradiologic imaging in
. t3 A8 K O# Cboys with precocious puberty. In addition to viril-
7 |. S3 A7 J$ B- E% dization, the clinical hallmark of CPP is the symmet-
3 \4 M/ d$ \* N+ erical testicular growth secondary to stimulation by
8 b6 K$ s! q$ G6 [; @gonadotropins.1,3
g% S6 W* F) Q( p |( h" GGonadotropin-independent peripheral preco-
* v0 J8 O' h0 f( @# Ocious puberty in boys also results from inappropriate: Q0 J' i* l+ m2 D, C/ [ H
androgenic stimulation from either endogenous or0 a8 c( R1 q- {2 a
exogenous sources, nonpituitary gonadotropin stim-# P, b, m+ p9 w* I) H
ulation, and rare activating mutations.3 Virilizing
4 g. e( f/ `/ J. `4 \, o, vcongenital adrenal hyperplasia producing excessive
! i3 f/ B( D$ e7 @: E& X/ Padrenal androgens is a common cause of precocious
+ T9 B' w$ ]0 }5 L# M* upuberty in boys.3,40 h! y5 j; e. k* q3 p& o" c
The most common form of congenital adrenal! H( k% }- S3 @) V
hyperplasia is the 21-hydroxylase enzyme deficiency.
, [$ u+ S1 m! ]5 s) |. ~1 gThe 11-β hydroxylase deficiency may also result in: E6 L/ L5 l" K
excessive adrenal androgen production, and rarely,
4 g2 ]! J6 |. i5 v* n- jan adrenal tumor may also cause adrenal androgen& L7 m7 S$ r6 Y
excess.1,35 ?1 L" j7 w9 `, v) q+ _% U
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542 Clinical Pediatrics / Vol. 46, No. 6, July 2007: ^) f3 o$ Y: e5 X1 K5 f5 R; ?
A unique entity of male-limited gonadotropin-. E$ X5 @0 J! y+ ~5 M) @5 T
independent precocious puberty, which is also known
' b0 G* N. v0 y# j: r1 J1 Has testotoxicosis, may cause precocious puberty at a
( H( n3 `- N# w# q3 T* Overy young age. The physical findings in these boys8 b" t: G& j# u0 l C4 B
with this disorder are full pubertal development,9 K5 ?1 g7 w2 r2 a0 Y; T2 e( H
including bilateral testicular growth, similar to boys) U! Z& {& t! U7 `5 L! F
with CPP. The gonadotropin levels in this disorder& K1 D. F5 m w/ L
are suppressed to prepubertal levels and do not show
# ?. A( k7 `( Y2 J# }* spubertal response of gonadotropin after gonadotropin-, l2 M7 {0 j9 h$ N, v2 i9 e
releasing hormone stimulation. This is a sex-linked: {& N4 l# W( f1 F, b
autosomal dominant disorder that affects only9 y; ^! q O8 E7 I ?! N
males; therefore, other male members of the family
/ ^0 @! Q8 q k4 T( Tmay have similar precocious puberty.3
l) r8 t/ l: T+ C) \) MIn our patient, physical examination was incon-
# S5 Y1 N* _- p$ Lsistent with true precocious puberty since his testi-- ~, {0 j1 b& w9 q. b
cles were prepubertal in size. However, testotoxicosis
) e5 V n+ z7 n/ h5 kwas in the differential diagnosis because his father
# X/ d6 y( _$ Ystarted puberty somewhat early, and occasionally,
8 }7 q7 `: v$ U, Ktesticular enlargement is not that evident in the
: R6 i& L: H6 mbeginning of this process.1 In the absence of a neg-) o( K! C% E0 y2 @/ |
ative initial history of androgen exposure, our
& |6 \- D/ J) Ubiggest concern was virilizing adrenal hyperplasia,
8 d: @) `; V9 ]) Weither 21-hydroxylase deficiency or 11-β hydroxylase% L! @) B5 ~6 N$ q% T
deficiency. Those diagnoses were excluded by find-1 C) u" y0 `6 E+ F
ing the normal level of adrenal steroids.
! {5 z& b0 S( T) r+ m+ rThe diagnosis of exogenous androgens was strongly
: B2 b" x& d9 P! n6 A4 rsuspected in a follow-up visit after 4 months because( T9 V' ~" N: q: T: Q1 K
the physical examination revealed the complete disap-8 I6 G7 f5 T. a* x
pearance of pubic hair, normal growth velocity, and
" W! [! P9 a# E" R" ^. Gdecreased erections. The father admitted using a testos-/ Z0 i7 S/ L1 S" N$ G8 I: d4 ?) k
terone gel, which he concealed at first visit. He was, m2 c* ^+ d$ B. h
using it rather frequently, twice a day. The Physicians’- N$ _4 `. w, Z
Desk Reference, or package insert of this product, gel or0 A4 \, X2 Y$ i F# h
cream, cautions about dermal testosterone transfer to, `" c1 e [6 P; J2 a; O
unprotected females through direct skin exposure.
s; l. K( P) }6 g# \( sSerum testosterone level was found to be 2 times the
" T$ e- U' f* ]8 kbaseline value in those females who were exposed to5 q' R+ g, a3 k
even 15 minutes of direct skin contact with their male- [9 B) I. j" ] e( b
partners.6 However, when a shirt covered the applica-: p1 G+ T; U5 }% U, U
tion site, this testosterone transfer was prevented.
0 V# N4 [; X" UOur patient’s testosterone level was 60 ng/mL,2 q% G; h: |: I& C. n& m
which was clearly high. Some studies suggest that
9 c0 P* W9 g9 k- T3 B- b3 \dermal conversion of testosterone to dihydrotestos-- A9 k( U }/ [+ K
terone, which is a more potent metabolite, is more; ^! D. C1 l5 S
active in young children exposed to testosterone
. F* O$ {$ b, y; ~7 Q4 qexogenously7; however, we did not measure a dihy-
8 m I+ U- x0 |drotestosterone level in our patient. In addition to1 K8 l4 v+ C9 a7 Y
virilization, exposure to exogenous testosterone in
# V4 I! J) Y4 o( v1 ^8 n. A9 ^# ?1 mchildren results in an increase in growth velocity and
0 k6 \& s: E3 ~1 F% Z" cadvanced bone age, as seen in our patient.6 _8 R0 b. k" |& d6 `% W* O& Y& m
The long-term effect of androgen exposure during4 \' Y$ v$ c9 B' Q
early childhood on pubertal development and final$ t$ Z- `7 ~' j5 C" G/ v
adult height are not fully known and always remain
, ], t2 }; g7 d" b/ z* ~4 Ha concern. Children treated with short-term testos-( G+ g" N) W+ |5 w1 Q
terone injection or topical androgen may exhibit some; m" U- c- F' B( }/ k) @3 C
acceleration of the skeletal maturation; however, after
" g1 x0 ^" \& |+ t& s( r1 Hcessation of treatment, the rate of bone maturation: v: J6 Y- W7 U+ q
decelerates and gradually returns to normal.8,97 g# n& F# ^8 K/ d, t# q
There are conflicting reports and controversy! B9 ?$ _4 e- ]5 K! {8 f# p; Z6 ^
over the effect of early androgen exposure on adult
( f/ z9 [ ?! G5 I1 s ?4 y5 h' Apenile length.10,11 Some reports suggest subnormal
" Y6 ~ K& J7 z+ }adult penile length, apparently because of downreg-
) E9 o" \ O, r* _- o% A5 J, W8 Bulation of androgen receptor number.10,12 However,
# A" a% b* [( c0 U& O8 E) eSutherland et al13 did not find a correlation between8 N( F" J2 s/ L. w
childhood testosterone exposure and reduced adult
( n6 P3 y. S, [2 ypenile length in clinical studies.: O5 }# `. ], [2 [) X
Nonetheless, we do not believe our patient is4 `1 y) i9 O0 c" ~
going to experience any of the untoward effects from
' {+ s0 ]7 \+ F) j* F, Dtestosterone exposure as mentioned earlier because
4 |6 B- q* N( m m" X6 dthe exposure was not for a prolonged period of time.
! k8 H, c) A1 K! i; }1 LAlthough the bone age was advanced at the time of
+ u3 E+ n1 c: L* V$ v# idiagnosis, the child had a normal growth velocity at
, `$ q6 U/ H- G# l/ D- S3 t- J+ z* Kthe follow-up visit. It is hoped that his final adult+ c( N' t( X9 C% w0 m
height will not be affected.
; \/ K% g+ |' e, t- ~) u4 ~Although rarely reported, the widespread avail-
' Q* w1 c5 f. ?# ]# O! d- H, xability of androgen products in our society may6 e3 m* C/ |, x! K
indeed cause more virilization in male or female
s5 Y- A. r( l4 Schildren than one would realize. Exposure to andro-0 R. X' m6 r$ M0 A* m" [
gen products must be considered and specific ques-" r6 k8 k# ^. i; l
tioning about the use of a testosterone product or) }' ^& O9 r [! i0 ^/ t5 ^8 q1 R2 X
gel should be asked of the family members during
4 O: l. O0 Q9 m5 ythe evaluation of any children who present with vir-* d6 v1 S* [7 ^. `. b! l8 \' d9 g- ~
ilization or peripheral precocious puberty. The diag-5 J/ w+ [+ e7 A9 [+ F ^$ [% Y: p/ C
nosis can be established by just a few tests and by
( C7 i" D1 P3 |8 O' h3 S! vappropriate history. The inability to obtain such a. C: K0 R# D q" s
history, or failure to ask the specific questions, may
! Q L' ]/ B7 z O/ j7 `8 iresult in extensive, unnecessary, and expensive
" Y0 x% n! a+ Z8 Yinvestigation. The primary care physician should be
+ H5 ^% y- x+ F5 G% N( Qaware of this fact, because most of these children
$ U4 [1 R* U( k9 a0 Cmay initially present in their practice. The Physicians’7 s. v5 z# f! {5 y
Desk Reference and package insert should also put a
) f5 h8 d/ @5 \warning about the virilizing effect on a male or
% {4 P* j5 L, ^female child who might come in contact with some-/ ?- `' [9 }# s
one using any of these products.
( a& i3 k) _. M1 h2 Q/ pReferences! D( ?& x5 s; z v
1. Styne DM. The testes: disorder of sexual differentiation
2 _/ j @* M1 [9 s5 N( Z5 Xand puberty in the male. In: Sperling MA, ed. Pediatric
$ I! K! D, d9 A3 J; _+ n1 d$ |Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;! B2 K, T2 W% q. l( @, D
2002: 565-628.
& a! b B8 Z/ i) s7 G( x2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
( r8 M' M3 |& [4 `puberty in children with tumours of the suprasellar pineal |
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