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Sexual Precocity in a 16-Month-Old* g9 h& o0 a$ F1 r/ E
Boy Induced by Indirect Topical3 ?9 z! l( l' R) E
Exposure to Testosterone6 G* z: G+ k* n# R1 e) W% a) ?9 @
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,28 h& O2 q* i- |9 B, t# \4 t& X
and Kenneth R. Rettig, MD1, O# {1 c! ?5 H' W
Clinical Pediatrics
! k; F9 R" D( A3 ]1 `Volume 46 Number 6
1 h) j; }; T$ Y- V8 }/ F1 U) _July 2007 540-543! z7 Q3 U8 y* q& E/ ?% X
© 2007 Sage Publications8 t) C2 Y2 r1 U: ~' s) i
10.1177/0009922806296651! w' t# z5 o/ W6 q% e$ O
http://clp.sagepub.com N& T5 p. {* Q* y- J
hosted at; @$ z- N3 M/ B* q4 u
http://online.sagepub.com
; k0 q$ _ H" ^" W' Z" KPrecocious puberty in boys, central or peripheral,3 w7 W7 q! N8 V! b& z V4 V( Y# H
is a significant concern for physicians. Central. l: \' _2 }0 F' F" M
precocious puberty (CPP), which is mediated! J1 e8 h. O: p: @3 [; W
through the hypothalamic pituitary gonadal axis, has! _8 H5 F3 F6 k2 I* k
a higher incidence of organic central nervous system
) w$ P1 A/ o0 d1 a% y. M U) Clesions in boys.1,2 Virilization in boys, as manifested
) Z1 `) I& J2 j3 q2 X& H5 u2 X, dby enlargement of the penis, development of pubic" {5 w" p6 A# O' ~
hair, and facial acne without enlargement of testi-" i# K- z/ f5 B! G. k
cles, suggests peripheral or pseudopuberty.1-3 We+ W. M# g2 D; T5 S0 l# b' P
report a 16-month-old boy who presented with the8 H: e/ ?% x4 o5 S
enlargement of the phallus and pubic hair develop-5 `7 |! C H* o4 C8 X' n2 n
ment without testicular enlargement, which was due
. [! [# p# s( W$ {' Fto the unintentional exposure to androgen gel used by
9 \ G- C9 _; m& w" Pthe father. The family initially concealed this infor-
5 e }7 E2 L1 Z% k5 U8 i0 U% smation, resulting in an extensive work-up for this+ p$ o3 C2 }; @! V$ }6 \% S9 X
child. Given the widespread and easy availability of
! u( I3 @# x8 ]5 j: Ttestosterone gel and cream, we believe this is proba-. R: C0 W$ f3 G/ E
bly more common than the rare case report in the, N& O2 [ M6 m+ E: u; n
literature.4/ _( T3 r) j5 U& l
Patient Report7 T, b0 ^& ~1 ~' i
A 16-month-old white child was referred to the5 R! w7 S$ [9 @" p
endocrine clinic by his pediatrician with the concern1 r3 H- u4 `* `6 L5 G
of early sexual development. His mother noticed* s# ^5 v) W O6 w, q4 t
light colored pubic hair development when he was6 a0 E: ]+ M+ V" R7 `
From the 1Division of Pediatric Endocrinology, 2University of
9 R$ s0 Z* {. K# ^ CSouth Alabama Medical Center, Mobile, Alabama.; y& G# Y t5 `* u7 R' \
Address correspondence to: Samar K. Bhowmick, MD, FACE,
' @7 T/ `+ p* \Professor of Pediatrics, University of South Alabama, College of, ^" V( Z4 ~7 B0 r$ M; U
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
, w* M# }" L* @* j3 U2 E; le-mail: [email protected].
, I: o- W0 n) l# Qabout 6 to 7 months old, which progressively became
- l: ]- g$ D/ O! v Z8 ddarker. She was also concerned about the enlarge-
, V/ ~( V& [) W& w8 Ament of his penis and frequent erections. The child. y" q8 ~# M9 C( w* `
was the product of a full-term normal delivery, with
; d# p6 d6 I6 z' z ga birth weight of 7 lb 14 oz, and birth length of
4 ^$ \" M7 n+ f- k, B20 inches. He was breast-fed throughout the first year
) J3 R% C3 @( G" G7 S i9 yof life and was still receiving breast milk along with
" `: [! t/ u7 _4 q3 G" E5 N) esolid food. He had no hospitalizations or surgery,
& M( {# b* s& w$ y, a1 w3 X5 c7 _and his psychosocial and psychomotor development) \, V9 e& E7 l
was age appropriate.3 g' {& f4 B( s' u2 K b$ J- y( i' t
The family history was remarkable for the father,
, W# ?9 X$ }$ S, [' Z8 }- d* ywho was diagnosed with hypothyroidism at age 16,) `+ Q; s( Y7 k1 o, H" {$ h
which was treated with thyroxine. The father’s- H- r/ c7 U# M& S9 N
height was 6 feet, and he went through a somewhat8 |$ K- e* v' \# y. [
early puberty and had stopped growing by age 14.
2 f9 u# x- m" P8 mThe father denied taking any other medication. The& h( l( \% d( Q! I2 C, c
child’s mother was in good health. Her menarche
) s, ]; W& X; P! P/ lwas at 11 years of age, and her height was at 5 feet
3 H8 g' t) }! E$ M6 e) S7 w, q3 V5 inches. There was no other family history of pre-
+ w# A0 D/ D+ S/ n. ycocious sexual development in the first-degree rela-
w3 _9 {$ g4 xtives. There were no siblings.$ ^+ o6 x( C+ `: B
Physical Examination6 \, P: G3 x9 Q) Q# v3 n' t
The physical examination revealed a very active,5 ]! Z1 u+ J$ `' v7 {
playful, and healthy boy. The vital signs documented
% ^+ F0 ?0 ?: za blood pressure of 85/50 mm Hg, his length was: i! C' R5 s' S3 y2 S4 Y6 C/ R
90 cm (>97th percentile), and his weight was 14.4 kg
" c$ i1 k1 X+ I( w9 }2 Q(also >97th percentile). The observed yearly growth. y5 G" m! b9 L9 [$ U
velocity was 30 cm (12 inches). The examination of
! E8 v2 w/ D% T6 ? X9 Lthe neck revealed no thyroid enlargement.% ?5 x' u$ v* F5 z# z+ U9 E
The genitourinary examination was remarkable for
& ]6 K+ a" o3 k4 P3 ]2 o9 {enlargement of the penis, with a stretched length of4 w( [( Y' O3 }* n- P
8 cm and a width of 2 cm. The glans penis was very well
' ?+ \8 C* {4 ?6 Fdeveloped. The pubic hair was Tanner II, mostly around1 ?0 v- _3 a7 P) R4 x5 G- q
540( c$ _5 k* h9 L! t7 p' C g
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the base of the phallus and was dark and curled. The
$ `7 G# F; I) U0 B. C# w, Qtesticular volume was prepubertal at 2 mL each.
8 a( d( W% X" O- H) @+ X3 u6 [The skin was moist and smooth and somewhat
) f% R, I: b- x8 k* O! hoily. No axillary hair was noted. There were no
_9 }! S5 Z5 h, e- Habnormal skin pigmentations or café-au-lait spots.! Q m# ^" H' V% a- X
Neurologic evaluation showed deep tendon reflex 2+
& ]2 m1 l% l! i4 y2 p- X5 m5 P8 _! kbilateral and symmetrical. There was no suggestion' l. K. \1 U. \2 Z- l
of papilledema.( d7 F5 C0 w3 Z( N8 \
Laboratory Evaluation
- S, u4 x O. `% v oThe bone age was consistent with 28 months by
" d. ^8 a# H# @4 r9 }2 ousing the standard of Greulich and Pyle at a chrono-
5 z0 c/ v: ^1 \8 Elogic age of 16 months (advanced).5 Chromosomal
/ j& E! L$ v. z. u4 ]1 m2 h- N, xkaryotype was 46XY. The thyroid function test
7 M# ^6 V, a+ J$ Dshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
5 J' L! z- j( z3 L; klating hormone level was 1.3 µIU/mL (both normal).
+ Z- y2 H- J% BThe concentrations of serum electrolytes, blood
" G( l6 k( f) i. ?0 O N; R4 @) m0 Aurea nitrogen, creatinine, and calcium all were
4 [9 t% Z# f" A1 Wwithin normal range for his age. The concentration4 T3 R ~, G# T4 }
of serum 17-hydroxyprogesterone was 16 ng/dL
" c$ B1 ?, v: G3 ](normal, 3 to 90 ng/dL), androstenedione was 20
" l- j) l. H* i0 o, T# png/dL (normal, 18 to 80 ng/dL), dehydroepiandros-! V5 @* R7 a) k5 l7 R) S( x
terone was 38 ng/dL (normal, 50 to 760 ng/dL),; C) t0 [# l* q
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
% ~$ Z4 b1 c& v- F49ng/dL), 11-desoxycortisol (specific compound S)
- L H) b) s, [6 D& |was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
2 U" E1 M. ^& |# D# \1 G% \ ?tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
$ q" t- A! Q* Gtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
- E3 P% b( Y( u3 R+ W7 S. c7 Pand β-human chorionic gonadotropin was less than" ^) b/ H: A# P: Q a& L9 s
5 mIU/mL (normal <5 mIU/mL). Serum follicular. U J! }3 @; X; D5 K6 D, |
stimulating hormone and leuteinizing hormone
# B9 P: k7 C3 [( c2 W3 w0 aconcentrations were less than 0.05 mIU/mL. i' O5 Q8 y9 G% e' E
(prepubertal).! E8 A7 n" r9 s8 s1 C; \
The parents were notified about the laboratory
5 c! d; Z; L" @results and were informed that all of the tests were
# @" D7 u# }: cnormal except the testosterone level was high. The
! x2 N7 X& @7 e" @7 {5 D( t( U/ Nfollow-up visit was arranged within a few weeks to
6 b3 o- Y4 ~. ?" u- f9 L) Nobtain testicular and abdominal sonograms; how-* _ {7 i/ k3 O$ H3 F$ B1 c
ever, the family did not return for 4 months.+ `& W* |* Z4 [
Physical examination at this time revealed that the' {' P6 P3 e* |1 j' h4 B' m' A
child had grown 2.5 cm in 4 months and had gained
4 e- M, Q% x, u2 s3 m& W: ?8 q% H2 kg of weight. Physical examination remained
9 I$ E1 ?. y/ H6 m+ ~unchanged. Surprisingly, the pubic hair almost com-- n0 |$ Q' z/ v
pletely disappeared except for a few vellous hairs at
. a& D5 D B0 v! W7 T, g0 _the base of the phallus. Testicular volume was still 2
& e6 F5 f+ p! K4 _ @mL, and the size of the penis remained unchanged.
/ j8 l7 |# n) I# K( Y/ jThe mother also said that the boy was no longer hav-& i3 z# u5 }- C( p4 H
ing frequent erections.9 K, b7 S/ V$ ~
Both parents were again questioned about use of5 ^( G+ G, _/ p# t* g5 q7 @4 ~
any ointment/creams that they may have applied to
0 U3 B, p2 N8 Ithe child’s skin. This time the father admitted the9 u/ d8 q5 Q- c+ f
Topical Testosterone Exposure / Bhowmick et al 541
3 C# Z, c1 D4 x N( e( Buse of testosterone gel twice daily that he was apply-0 z2 F% ]5 A v; ~1 v
ing over his own shoulders, chest, and back area for
7 u) n8 b4 D% M5 c C6 Xa year. The father also revealed he was embarrassed
# q: U' D% B7 U* \to disclose that he was using a testosterone gel pre-& W! p, |7 q! {/ T" E
scribed by his family physician for decreased libido- ^# R0 L1 c+ z0 U" l1 a r
secondary to depression.' r( }5 B, q3 m" {5 T
The child slept in the same bed with parents.0 E3 T/ I9 s; M% D( R. y$ m
The father would hug the baby and hold him on his
0 a, m f; w: v& d( ]# Z& Pchest for a considerable period of time, causing sig-
" B' o) H, ]# G. jnificant bare skin contact between baby and father.
! g5 L/ V3 Y. t2 I8 |The father also admitted that after the phone call,
/ U, m h: k H1 y5 vwhen he learned the testosterone level in the baby
- e8 T* B7 O$ t' j% Y4 ~was high, he then read the product information/ a( W% I, M! D8 P& A$ J: {
packet and concluded that it was most likely the rea-
$ a) s6 w% w. Y. d2 C& f, |son for the child’s virilization. At that time, they
; Q# z$ `: R; d! [% n2 ^: Fdecided to put the baby in a separate bed, and the5 V* j( x8 D% C L- F" I
father was not hugging him with bare skin and had
@' H* M* G; Fbeen using protective clothing. A repeat testosterone" t4 u+ L/ _! P2 E% R) G R
test was ordered, but the family did not go to the1 L. K' F; m% _ P9 X
laboratory to obtain the test.$ v5 c6 B$ y% G V) b
Discussion
4 A6 O+ Y( K) v |) ?# }Precocious puberty in boys is defined as secondary- O9 B E, u G
sexual development before 9 years of age.1,4
- S }" k3 X' W2 x+ Z$ TPrecocious puberty is termed as central (true) when
. ^7 p; B1 d& T1 r. W9 u5 B" d: g0 Eit is caused by the premature activation of hypo-
7 J2 @5 K% E, `8 }( a2 zthalamic pituitary gonadal axis. CPP is more com-
( ]; o% T/ ^& {mon in girls than in boys.1,3 Most boys with CPP
1 @- W5 f) p5 Omay have a central nervous system lesion that is; H: L, a Z( h, L( s0 d% J
responsible for the early activation of the hypothal-% |! e, W8 A+ D8 y. N9 \. J8 v
amic pituitary gonadal axis.1-3 Thus, greater empha-$ c8 I4 H* k, b/ }8 x. {$ g
sis has been given to neuroradiologic imaging in
4 a3 E( \6 T/ [boys with precocious puberty. In addition to viril-5 J1 x7 w+ |0 f8 a! }
ization, the clinical hallmark of CPP is the symmet-) x5 `( {5 ?' p& R: N! J
rical testicular growth secondary to stimulation by4 E: U5 f8 o+ v& g+ p8 A% c
gonadotropins.1,3
8 {5 D, F) |0 v8 K @7 wGonadotropin-independent peripheral preco-
" F+ Z! }/ ?. b, x' s0 ?cious puberty in boys also results from inappropriate- o, M4 ?6 \& C2 A
androgenic stimulation from either endogenous or
; [0 W( J& H# \; Yexogenous sources, nonpituitary gonadotropin stim-
1 _6 N6 j/ D( z: [3 tulation, and rare activating mutations.3 Virilizing9 c6 n9 A- J% G. e3 @
congenital adrenal hyperplasia producing excessive
5 [+ b ~2 a% v1 _adrenal androgens is a common cause of precocious
4 i: m7 ]" |1 [) _puberty in boys.3,4+ `6 M1 o, ]* D" h" [% ^ ~; |
The most common form of congenital adrenal: ?, E, E+ {% N4 x4 P- P3 z
hyperplasia is the 21-hydroxylase enzyme deficiency.
# [/ D4 D; f/ @7 v kThe 11-β hydroxylase deficiency may also result in& c& R- c) q- P( o, J
excessive adrenal androgen production, and rarely,' I0 u7 W! X1 f6 K( F
an adrenal tumor may also cause adrenal androgen0 n5 p; B# Z/ s! \/ p. }; n/ ]' E( W/ }
excess.1,35 {) r2 Y1 ~! ]7 t/ ^+ D0 k! h5 [
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
8 c5 `5 |' s) h- c; B) x8 Q3 N& v542 Clinical Pediatrics / Vol. 46, No. 6, July 2007; Q6 a, Z9 B2 {1 q3 t
A unique entity of male-limited gonadotropin-; x! T0 G: |+ T4 v7 a$ q. u
independent precocious puberty, which is also known! X; V% I/ x9 N! m7 G& C
as testotoxicosis, may cause precocious puberty at a+ n2 Q4 K! R( u" o4 j! J( \0 G) B
very young age. The physical findings in these boys% N3 z. f! d/ u& }
with this disorder are full pubertal development,9 R7 B- ?5 y0 i8 _
including bilateral testicular growth, similar to boys
' ~+ a6 T6 e8 T! X, P5 v" y4 ]2 uwith CPP. The gonadotropin levels in this disorder3 A6 q% c. F( H: \; i" _% Q
are suppressed to prepubertal levels and do not show& h ?# @" W2 w
pubertal response of gonadotropin after gonadotropin-
8 q/ |9 v! V" T3 b( t# ?" @releasing hormone stimulation. This is a sex-linked4 M* e0 e3 i# K" A& _' v! r5 r- _
autosomal dominant disorder that affects only
$ r, z. V) q9 r- P' g/ I# o5 @& M7 Umales; therefore, other male members of the family4 Y2 A1 R K- x
may have similar precocious puberty.3( ?: D+ q+ _6 j+ S k8 C
In our patient, physical examination was incon-
% a! \) R' F" j, E1 Nsistent with true precocious puberty since his testi-
7 T$ e' N5 _3 M5 ^. Fcles were prepubertal in size. However, testotoxicosis
; ~1 E8 ?1 e' x5 ^8 z% _was in the differential diagnosis because his father" H3 E9 S* s( _; X
started puberty somewhat early, and occasionally,; T# i% A4 j; ]$ S' u
testicular enlargement is not that evident in the
. @7 `0 B& T7 g2 lbeginning of this process.1 In the absence of a neg-7 q( B/ \' |/ V) f% h( i
ative initial history of androgen exposure, our
( y, U" F% H4 ]. u$ H* n8 v; ^1 ]biggest concern was virilizing adrenal hyperplasia,4 ^) x Y8 z" ~
either 21-hydroxylase deficiency or 11-β hydroxylase7 Y: ^* q G) H) E
deficiency. Those diagnoses were excluded by find-: f i# E' _. L7 M! T' t2 F- _
ing the normal level of adrenal steroids." r( R; q, j4 _7 z" |$ x6 _3 _
The diagnosis of exogenous androgens was strongly
`# k8 M9 K. u v* {; Ysuspected in a follow-up visit after 4 months because0 O7 `7 [7 I7 {% G. _
the physical examination revealed the complete disap-
o7 p2 H0 W2 Npearance of pubic hair, normal growth velocity, and* x; H" b* |3 k6 |
decreased erections. The father admitted using a testos-
6 I; {- H# h9 f; [terone gel, which he concealed at first visit. He was
4 w+ C/ I" e! A( H2 d; A7 {1 E5 u- tusing it rather frequently, twice a day. The Physicians’0 L" X* b* D- A% D6 I6 y- u
Desk Reference, or package insert of this product, gel or( I# w( K0 W( w
cream, cautions about dermal testosterone transfer to
( ^% R3 R `' k$ n9 Cunprotected females through direct skin exposure.* W5 v- u! q) y# Z" f3 o. g
Serum testosterone level was found to be 2 times the
- R% x; e. [$ G, \9 T, Dbaseline value in those females who were exposed to t) G9 r9 ]1 o4 t+ V" h
even 15 minutes of direct skin contact with their male/ E3 @" `7 S. M4 s7 Q: e ]6 L7 _
partners.6 However, when a shirt covered the applica-8 }2 O1 u8 ^% D. b ]
tion site, this testosterone transfer was prevented.4 S$ i4 A% g: Q. v- y& d: Q
Our patient’s testosterone level was 60 ng/mL, C- }( Z# d% y6 [
which was clearly high. Some studies suggest that
Q2 p+ G- x! y0 c' Qdermal conversion of testosterone to dihydrotestos-
- [; A- a) u7 t$ Yterone, which is a more potent metabolite, is more
+ v. M' f1 J1 K* Jactive in young children exposed to testosterone
8 D" j& T4 A% E: [exogenously7; however, we did not measure a dihy-7 v9 C' f- S8 i2 q% X
drotestosterone level in our patient. In addition to
; o7 n$ Y3 `9 ~$ ]; O! tvirilization, exposure to exogenous testosterone in2 p8 ]( ^% L" p+ \
children results in an increase in growth velocity and
# b G1 L( @3 j( Wadvanced bone age, as seen in our patient. P1 |4 o0 W9 {
The long-term effect of androgen exposure during
6 `& s, f+ w( h5 }8 Z% g& q* kearly childhood on pubertal development and final
k2 h- @8 s" kadult height are not fully known and always remain- H% B) ~% k; m/ A( |- U
a concern. Children treated with short-term testos-
/ A+ ~6 V E5 Y2 B# Tterone injection or topical androgen may exhibit some
: [: t- L* r0 Tacceleration of the skeletal maturation; however, after8 a& r0 z" S. U8 j5 R
cessation of treatment, the rate of bone maturation% e( V. k; x/ P2 l+ K
decelerates and gradually returns to normal.8,9; Q) e' J8 E" d* K' ?4 `- t
There are conflicting reports and controversy2 R8 Y4 c0 F' M, S8 ?3 e
over the effect of early androgen exposure on adult* j& p M# O8 N' R' [- o: }
penile length.10,11 Some reports suggest subnormal. _( s( P& V9 z2 U+ Z
adult penile length, apparently because of downreg-) ^1 x6 G+ t; P. J7 a
ulation of androgen receptor number.10,12 However, N# Z% L2 B _. W
Sutherland et al13 did not find a correlation between; e% ?5 A8 [; m0 v" |, W# b- h
childhood testosterone exposure and reduced adult
: |$ [4 y1 n) V" `penile length in clinical studies.2 `+ P9 ~+ R! w/ s1 n
Nonetheless, we do not believe our patient is: L m0 N- [* T: m* `# ?
going to experience any of the untoward effects from
# [5 W( g# ?3 f, ]/ ?8 F: s U) M* }testosterone exposure as mentioned earlier because
. T% I' m+ a$ q6 cthe exposure was not for a prolonged period of time.
9 N% l2 u4 I, `+ r# b/ FAlthough the bone age was advanced at the time of
) r* H7 Y1 D, D9 Idiagnosis, the child had a normal growth velocity at- o) e6 O5 m# y( y e& q* t- q
the follow-up visit. It is hoped that his final adult
& c7 O+ B& V1 B, A$ pheight will not be affected.
$ o4 ]* D0 O1 E) h* WAlthough rarely reported, the widespread avail-) V8 z5 k; A( D& [ S
ability of androgen products in our society may
# j: A" g" [, X5 o* E9 Rindeed cause more virilization in male or female4 v0 {! B8 l o5 U3 e2 s5 C
children than one would realize. Exposure to andro-
2 d9 u8 X# n- y: Lgen products must be considered and specific ques-; f0 G( M; L) r' U- n
tioning about the use of a testosterone product or
1 n% x3 @( i" j7 `8 G2 ^' Mgel should be asked of the family members during
0 s! P' Y) q1 V# [# v, Tthe evaluation of any children who present with vir-5 a% S- J+ N6 ~+ x2 X9 u3 _
ilization or peripheral precocious puberty. The diag-
5 A i4 g% U& r9 m+ [1 J0 }nosis can be established by just a few tests and by
) g; }' @- I& |" q8 w* H+ Q2 eappropriate history. The inability to obtain such a K$ c. Y; j5 w6 Q# a3 m
history, or failure to ask the specific questions, may1 G! s5 ?- k g) Q: p" B
result in extensive, unnecessary, and expensive: A% {1 r5 p& J# v( p& ~8 h
investigation. The primary care physician should be
4 \5 j; a) P/ D: h5 eaware of this fact, because most of these children5 K5 ?1 V5 q% O% o0 l
may initially present in their practice. The Physicians’
1 }. |( H H* W$ k1 M, ?Desk Reference and package insert should also put a
' p% U+ j% o6 [, [2 P( Twarning about the virilizing effect on a male or n% l- ?% D8 Z8 U. X
female child who might come in contact with some-7 ?8 J. c+ e& ?
one using any of these products.* X: Y+ f3 B2 @* N4 a
References& x; w6 \: |6 w0 K# M/ L( J6 q
1. Styne DM. The testes: disorder of sexual differentiation- W! H" V6 T' ]
and puberty in the male. In: Sperling MA, ed. Pediatric
; H; N5 m6 S2 u+ x p9 r3 H3 Y" \Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
- J8 ~+ P, g4 b! o2002: 565-628.# F2 L# q2 @9 R
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
5 Z/ l) V1 t& C1 b2 Epuberty in children with tumours of the suprasellar pineal |
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