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Sexual Precocity in a 16-Month-Old
; d( u" @! I" B/ PBoy Induced by Indirect Topical
/ R+ V- B1 ^1 h3 o9 B$ U$ wExposure to Testosterone5 Z1 p; B: d+ c m; _6 y/ X
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
+ T h( T, K- R3 A4 T9 Tand Kenneth R. Rettig, MD13 g; E( B4 h" t$ V/ z4 W( y$ P% v% \
Clinical Pediatrics
7 l7 q* ]9 h+ Q- x# O" _4 bVolume 46 Number 6
+ B, @ \2 r, j. Z1 u2 _0 YJuly 2007 540-5434 y% R. c9 o: r9 Y+ }# c& q
© 2007 Sage Publications1 w& \" n) x6 a( ? }' C1 |( a9 e
10.1177/0009922806296651$ n- ~+ s$ x2 f+ e
http://clp.sagepub.com1 p! ^" [( O( @
hosted at
4 C# m/ e6 K( G# K K# F9 E& e X! C- dhttp://online.sagepub.com
4 D( q0 ^: F _3 Z) a4 w: t9 FPrecocious puberty in boys, central or peripheral,5 q: h: Z0 K% ~, O8 D+ a8 d
is a significant concern for physicians. Central
4 k( a+ J! A" w0 Gprecocious puberty (CPP), which is mediated
+ t% `. |, Z& H& b0 x# q8 S0 bthrough the hypothalamic pituitary gonadal axis, has
6 Q. L& g' e" Y8 h. ]7 [' t% aa higher incidence of organic central nervous system
5 `, ]3 I0 ]2 F4 i. ylesions in boys.1,2 Virilization in boys, as manifested; w' p* h: J- k
by enlargement of the penis, development of pubic. U# K" W0 Y2 g! }& k b
hair, and facial acne without enlargement of testi-0 ~: U# `2 X0 k, [; S
cles, suggests peripheral or pseudopuberty.1-3 We
+ |0 K; E, Q; R, Areport a 16-month-old boy who presented with the! }' T/ h/ |: V
enlargement of the phallus and pubic hair develop-; f7 Q/ G/ ?+ M" \8 |" g! r
ment without testicular enlargement, which was due! V( |7 Y; q4 H8 z
to the unintentional exposure to androgen gel used by
1 G3 P* h/ y2 G2 R' R; mthe father. The family initially concealed this infor-8 f" S, b2 m( \0 }" v
mation, resulting in an extensive work-up for this
3 X9 U7 G$ T+ r9 c6 ichild. Given the widespread and easy availability of
7 s$ o. ~. O1 X. n: }testosterone gel and cream, we believe this is proba-1 g, @9 M3 g; }; h
bly more common than the rare case report in the$ T; k% e, J4 M$ }
literature.4' q: |" ?! ]" k+ O0 p- J f
Patient Report( ]3 {& n1 s: A; h7 V
A 16-month-old white child was referred to the, q! Y9 R( r/ Z5 D
endocrine clinic by his pediatrician with the concern
3 I3 J$ w& i k8 N3 Uof early sexual development. His mother noticed) d# B! n2 u X5 F
light colored pubic hair development when he was/ z/ |7 x _! z- _. V
From the 1Division of Pediatric Endocrinology, 2University of
, l0 I j& B- k: cSouth Alabama Medical Center, Mobile, Alabama.
% D8 s# h8 s4 X+ d( q( cAddress correspondence to: Samar K. Bhowmick, MD, FACE,$ `: \; ~0 \8 E c; K
Professor of Pediatrics, University of South Alabama, College of' z" J, u! E. b: Z4 j2 X& ~! Z
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
3 {, s( l, I: }, fe-mail: [email protected].
: U) i9 f, t+ d. H* C0 g8 pabout 6 to 7 months old, which progressively became# v1 ?% {' X# N" X
darker. She was also concerned about the enlarge-
5 f7 Y( d/ c8 V5 x- xment of his penis and frequent erections. The child. m4 E/ R9 c8 w
was the product of a full-term normal delivery, with9 k! ]! X; G& ?: Y8 r0 V# W
a birth weight of 7 lb 14 oz, and birth length of' L) {1 p$ j$ I: w& _
20 inches. He was breast-fed throughout the first year, F( z2 T- ?! r! n, Q" q
of life and was still receiving breast milk along with
3 H! o6 c: c. }0 j( K! W3 q$ L) D+ Rsolid food. He had no hospitalizations or surgery,# ?$ o$ [2 V( n, h
and his psychosocial and psychomotor development% l# b2 w3 E, y
was age appropriate.; N" d# r" e+ a& l* l, z% }% q
The family history was remarkable for the father,
8 @& g6 N! ~: ?3 Ewho was diagnosed with hypothyroidism at age 16,% ~$ r$ P/ F+ V$ l/ l
which was treated with thyroxine. The father’s0 a" J; q% [: K& ?
height was 6 feet, and he went through a somewhat5 L5 Y, W0 [( W( `3 K
early puberty and had stopped growing by age 14.
; M9 d! e' [1 e+ o, aThe father denied taking any other medication. The
. B% q/ }$ w& \child’s mother was in good health. Her menarche6 E+ s: K7 g8 u, ~2 ~
was at 11 years of age, and her height was at 5 feet1 q$ r3 |" v' W, T9 i
5 inches. There was no other family history of pre-
, V: o: W8 U7 T! b$ J4 j6 S/ Hcocious sexual development in the first-degree rela-
/ O. u7 b: d5 p9 Atives. There were no siblings.' `. U3 D3 i9 U
Physical Examination
# ]# R1 s9 v" E/ D4 [+ \The physical examination revealed a very active,
6 c* O9 K) i) H2 o# {; M- ~/ Mplayful, and healthy boy. The vital signs documented
, p! [' q V7 d, M) E, |a blood pressure of 85/50 mm Hg, his length was1 ^( |$ v: ^1 L" w
90 cm (>97th percentile), and his weight was 14.4 kg
q, `8 o: }! [# z(also >97th percentile). The observed yearly growth0 l2 H* E- B* I) j
velocity was 30 cm (12 inches). The examination of
* G- u Q2 F7 c% i( } wthe neck revealed no thyroid enlargement.1 v: w. N! L; K4 |3 N
The genitourinary examination was remarkable for
$ S* S W- a9 z: p2 Q, ^, [enlargement of the penis, with a stretched length of5 r7 z& E8 @3 D; ?# }3 Q
8 cm and a width of 2 cm. The glans penis was very well& i& R" \9 a& T+ w1 J% \3 w8 T" Q
developed. The pubic hair was Tanner II, mostly around
- O2 r/ E; `8 \1 [/ N. Y540; [ p4 e( N V9 p! c6 p
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from: G. Y/ c8 G& {) v5 e7 c
the base of the phallus and was dark and curled. The
9 v! S* r+ i. O7 b% Wtesticular volume was prepubertal at 2 mL each.: `! W6 k! F2 m3 ^% ~; u, @8 X
The skin was moist and smooth and somewhat. y$ ^1 W, T- y+ f6 N. @
oily. No axillary hair was noted. There were no
' h+ N$ j% P2 Kabnormal skin pigmentations or café-au-lait spots.0 S* s2 m2 Y# f
Neurologic evaluation showed deep tendon reflex 2+
5 D v9 p4 c n; l; |6 O* ybilateral and symmetrical. There was no suggestion T# D- W9 M% e; x
of papilledema.0 ]0 y7 s( W8 W3 F+ \
Laboratory Evaluation
/ x' v4 i/ N \$ k) h3 t& m+ BThe bone age was consistent with 28 months by
' `( V m6 ]8 i- |using the standard of Greulich and Pyle at a chrono-
( C( n( Z* a: n) @# v( z" flogic age of 16 months (advanced).5 Chromosomal- e$ x0 w* O, t& R
karyotype was 46XY. The thyroid function test
7 C& x/ w5 L# v0 _" }showed a free T4 of 1.69 ng/dL, and thyroid stimu-5 D0 [: H" g# a' v4 O/ @ m; Q
lating hormone level was 1.3 µIU/mL (both normal).
5 c. M! O3 r! j$ G* |. yThe concentrations of serum electrolytes, blood& ]6 h$ E, P. C; p. T. f
urea nitrogen, creatinine, and calcium all were0 X( ?$ k3 a: ~9 h$ O! R; v
within normal range for his age. The concentration
8 F6 ], w3 U4 p! |of serum 17-hydroxyprogesterone was 16 ng/dL
- [5 ?+ U7 F$ i% c(normal, 3 to 90 ng/dL), androstenedione was 20
1 N) h) S, \7 s. X3 U W7 wng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
( C0 B' I8 o8 b F4 u! Z8 v: \" @terone was 38 ng/dL (normal, 50 to 760 ng/dL),
7 ^# N- t7 D- o) Tdesoxycorticosterone was 4.3 ng/dL (normal, 7 to/ b: k% v7 s7 ~# Q+ h
49ng/dL), 11-desoxycortisol (specific compound S)* q( x u# e1 s
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
, Y* }) q9 G& o$ ?tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total1 C% n. Q6 P' }* s) B: m
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
/ P7 I+ u2 _0 Y+ E5 E" C( I# yand β-human chorionic gonadotropin was less than
5 K& _ |8 d5 a& U0 D6 u8 r5 mIU/mL (normal <5 mIU/mL). Serum follicular
2 i8 ]: [1 ~, i# c! A4 Ystimulating hormone and leuteinizing hormone; U T1 u( z3 c6 Y+ G
concentrations were less than 0.05 mIU/mL
- U* m# [- Q! s" @: e/ m(prepubertal).
9 ]. [: h( ?" y! }. X; TThe parents were notified about the laboratory
' T: E/ \$ l: [' Y! f K1 o: s- vresults and were informed that all of the tests were0 P% Y. d$ O) _3 T' P$ x
normal except the testosterone level was high. The
& j% a0 t) X Z: mfollow-up visit was arranged within a few weeks to4 z8 @- k z4 l! ]# Q0 D9 W) ?
obtain testicular and abdominal sonograms; how-7 @3 W* ]0 k- b- g0 U( D: T) w
ever, the family did not return for 4 months.
1 J& `0 F% y6 a+ E% N s: }Physical examination at this time revealed that the
1 v$ B' k! m5 j8 `child had grown 2.5 cm in 4 months and had gained" X* e5 o( h* B f! J
2 kg of weight. Physical examination remained
! ~# ^: i8 F" t/ z7 iunchanged. Surprisingly, the pubic hair almost com-
3 W% V) X2 N" j4 npletely disappeared except for a few vellous hairs at
% ~! y# S$ m5 X- {5 ]the base of the phallus. Testicular volume was still 2
$ r3 |* Q7 T: M+ Y8 MmL, and the size of the penis remained unchanged.7 _- ^: G+ Z8 m. V6 K* H P
The mother also said that the boy was no longer hav-
2 P% s, g; `0 u0 h J; |ing frequent erections.
) f7 X/ S. @$ p. F' ]Both parents were again questioned about use of
9 I& n7 L0 o$ N( q o# X/ E# g1 Kany ointment/creams that they may have applied to# ]4 w3 t, T* V# P" i1 h
the child’s skin. This time the father admitted the. s7 |9 S4 F1 A8 V* t
Topical Testosterone Exposure / Bhowmick et al 541
8 b) j4 s+ B) j% {use of testosterone gel twice daily that he was apply-
" a+ J3 ~' X g& s3 eing over his own shoulders, chest, and back area for
/ R% ^) C l5 J4 o- P' Ua year. The father also revealed he was embarrassed
1 N2 G; [! ~* Z9 Oto disclose that he was using a testosterone gel pre-% H$ S+ w9 G0 }7 E
scribed by his family physician for decreased libido
6 L) X1 x' d" z* H6 R N0 J" csecondary to depression.( r; @6 @( ?8 o8 W" ~5 }
The child slept in the same bed with parents.7 B. b) g5 o$ M
The father would hug the baby and hold him on his/ a. u$ s& T( u4 I0 I% v! o
chest for a considerable period of time, causing sig-
9 V6 A# {5 n2 P Anificant bare skin contact between baby and father.
. `$ T8 L7 | ^' A0 e/ OThe father also admitted that after the phone call,. J5 n% o# e( a
when he learned the testosterone level in the baby4 r) ]* C5 @4 r) s( D$ j
was high, he then read the product information1 L4 M- g" ~; E$ j3 ~
packet and concluded that it was most likely the rea-) D% O; e" ^ I1 G
son for the child’s virilization. At that time, they
& A( t6 W& ]' ?, T, z' |1 `decided to put the baby in a separate bed, and the. [' o# w0 ?2 ^' ]/ c; V( C3 D
father was not hugging him with bare skin and had
* X8 n/ @# O3 _, v! xbeen using protective clothing. A repeat testosterone) C' [9 x$ s' x! N& E: g. K0 G
test was ordered, but the family did not go to the& t% w9 A; h" T+ q
laboratory to obtain the test.
! z7 p% g2 m' g2 b% HDiscussion
4 r/ k4 b; g/ K- P1 g, h) iPrecocious puberty in boys is defined as secondary% z! W1 e' H, b/ }
sexual development before 9 years of age.1,4
5 n1 } q4 x: H+ M7 _Precocious puberty is termed as central (true) when6 B2 y3 _( q& a1 Y+ \0 L
it is caused by the premature activation of hypo-) d4 p/ k! K* B# H# ~ t, Y
thalamic pituitary gonadal axis. CPP is more com- q; y( ^( a2 r+ w
mon in girls than in boys.1,3 Most boys with CPP1 U/ I3 e1 O/ y$ h1 @" x# F
may have a central nervous system lesion that is" O9 Z+ \( N* ]( d' ]6 H+ p
responsible for the early activation of the hypothal-+ y( T4 v0 U1 X! F1 y
amic pituitary gonadal axis.1-3 Thus, greater empha-
4 Q; ~$ y* ?8 A* Lsis has been given to neuroradiologic imaging in; }, z: U7 J. p# ^5 a; z" ~4 e
boys with precocious puberty. In addition to viril-- B+ ?7 e; |. L/ |
ization, the clinical hallmark of CPP is the symmet-
7 {- g7 n" [; _7 ?) h; q5 Hrical testicular growth secondary to stimulation by
1 g; R+ r4 T. O1 @! @gonadotropins.1,3: ^1 X# [2 y8 O! h0 b) f
Gonadotropin-independent peripheral preco-
3 b( j0 U9 d; w2 Wcious puberty in boys also results from inappropriate
3 r* Y/ G0 A! e t: N3 q- _androgenic stimulation from either endogenous or
7 R8 V- n( k4 M2 U0 X! aexogenous sources, nonpituitary gonadotropin stim-" O6 K2 H2 m+ [5 {
ulation, and rare activating mutations.3 Virilizing
' x. @( Q) A1 S8 Acongenital adrenal hyperplasia producing excessive1 ?$ n, Z. e+ C7 v
adrenal androgens is a common cause of precocious
" ]% @1 Q& m8 Apuberty in boys.3,44 u( F4 y) a% N0 ~$ k6 x S
The most common form of congenital adrenal
. S* m% K2 S( r# J# Y7 h: lhyperplasia is the 21-hydroxylase enzyme deficiency.
; D) p P9 `' `' b0 UThe 11-β hydroxylase deficiency may also result in2 }5 A9 }' P' ~4 }
excessive adrenal androgen production, and rarely,
9 O' d$ j& R3 ]an adrenal tumor may also cause adrenal androgen) O+ k7 F: U8 c9 p& \# U$ x4 ]
excess.1,3
( ^- a' p* t8 T3 Gat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
- j- O4 A3 S, Q. v9 F542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
7 V& J8 w5 ?, ^0 U% S" w7 HA unique entity of male-limited gonadotropin-9 w* x7 G$ f( V: M
independent precocious puberty, which is also known; V& Z, H% z/ E2 b9 f3 j: n
as testotoxicosis, may cause precocious puberty at a
$ R: P- [7 H3 |% I1 Uvery young age. The physical findings in these boys3 N j* |; C6 ^- Z, C* U4 j' W
with this disorder are full pubertal development,
$ |8 N4 r5 P) F5 Q: Iincluding bilateral testicular growth, similar to boys
/ x+ _% G. l: f4 Jwith CPP. The gonadotropin levels in this disorder' C% U1 }! R4 v) j: ?) V, Y
are suppressed to prepubertal levels and do not show& _1 Q5 d. t; z, }4 P
pubertal response of gonadotropin after gonadotropin-9 x6 e: F0 H J" r
releasing hormone stimulation. This is a sex-linked, N$ S2 y- L. {
autosomal dominant disorder that affects only
! B% s4 r; p; W0 V0 Hmales; therefore, other male members of the family) H) O' \8 P: p
may have similar precocious puberty.37 r, P6 ?# A0 T% Y# h: O0 n
In our patient, physical examination was incon-
, M8 Q1 w% u# W) @3 @2 a2 a% f2 Isistent with true precocious puberty since his testi-
5 y7 D) p! ^& F# Pcles were prepubertal in size. However, testotoxicosis" I3 F5 r# O, M% U8 v" ~! D, O0 x2 h' G
was in the differential diagnosis because his father! @0 `' a6 }9 v# W! V
started puberty somewhat early, and occasionally,0 U5 |. Z" g. W
testicular enlargement is not that evident in the8 M$ N+ f" G; T" C
beginning of this process.1 In the absence of a neg-' ^) s5 B1 Q% a
ative initial history of androgen exposure, our
+ R& v9 O) s1 W: L+ Qbiggest concern was virilizing adrenal hyperplasia,
/ c2 v' C1 q) s0 q9 V+ G! oeither 21-hydroxylase deficiency or 11-β hydroxylase
2 a& g7 S. N3 S6 I4 Wdeficiency. Those diagnoses were excluded by find-
9 W u* ~9 E# K1 Xing the normal level of adrenal steroids." V! {# q6 ]7 j) X
The diagnosis of exogenous androgens was strongly' r/ T4 _9 R: P- [ `1 h
suspected in a follow-up visit after 4 months because
" N, v& S- E4 Z" N: dthe physical examination revealed the complete disap-0 l- y1 z$ n6 X7 P' I$ h0 g
pearance of pubic hair, normal growth velocity, and6 u) {5 |, O0 T+ H( z/ H$ Y9 U |0 Z
decreased erections. The father admitted using a testos-
) K# J& v( J+ B. |0 \! P$ O; xterone gel, which he concealed at first visit. He was
& l" n$ j% \8 C, s. n" Vusing it rather frequently, twice a day. The Physicians’9 m. W$ I6 J6 l/ s( X
Desk Reference, or package insert of this product, gel or
0 }! `0 c9 f6 ?( p/ I" r7 kcream, cautions about dermal testosterone transfer to
; p1 x; v8 ^7 e2 i. }unprotected females through direct skin exposure.
& k v& K2 o. z$ v+ LSerum testosterone level was found to be 2 times the& s l0 I0 {( T5 A- Q1 _$ R! x' f8 C: W
baseline value in those females who were exposed to% g- N. w0 \7 {
even 15 minutes of direct skin contact with their male
3 c2 Y) w0 c: _partners.6 However, when a shirt covered the applica-- f$ F: L, H" S8 M" H2 M6 l
tion site, this testosterone transfer was prevented.
6 q) S" y' f& L! L- ]! d4 [Our patient’s testosterone level was 60 ng/mL,! p1 \& R$ ~9 H& v! O
which was clearly high. Some studies suggest that
* c0 @- {8 g% ^4 O) ]dermal conversion of testosterone to dihydrotestos-* `- P8 \7 P! I) h
terone, which is a more potent metabolite, is more
- B3 Q- }+ ~9 f4 eactive in young children exposed to testosterone
+ F" h' n' k& y5 c! _1 e$ c( G! Hexogenously7; however, we did not measure a dihy-6 `7 s) u% u$ q. y% V) `% P
drotestosterone level in our patient. In addition to
i3 M" d7 C" x4 vvirilization, exposure to exogenous testosterone in( g2 `9 A, K% d
children results in an increase in growth velocity and* A; o' \8 ?( r4 c F: }
advanced bone age, as seen in our patient.. l, @. M2 w5 R! U
The long-term effect of androgen exposure during7 E. ~6 y2 s, V8 ]& m4 \
early childhood on pubertal development and final
" g- ?5 ?8 R0 M1 P# oadult height are not fully known and always remain
3 _- ]( {' `* z5 Y k: Da concern. Children treated with short-term testos-
6 \/ E3 ~% n m- Uterone injection or topical androgen may exhibit some& }+ s8 j' ^) \
acceleration of the skeletal maturation; however, after
8 U) E: n l- ~# d' H' m! j7 icessation of treatment, the rate of bone maturation
9 ^ O. r" C7 p' R1 Zdecelerates and gradually returns to normal.8,9
0 t+ E, l. H JThere are conflicting reports and controversy
7 O. ?4 E; ]+ _, s2 Q8 nover the effect of early androgen exposure on adult; C0 O2 ~' V+ Q
penile length.10,11 Some reports suggest subnormal
. o/ {( W5 L5 f/ F3 Radult penile length, apparently because of downreg-1 }% v, M6 E! X
ulation of androgen receptor number.10,12 However,
$ L$ o& Y7 j6 S8 J, n7 G. tSutherland et al13 did not find a correlation between3 Z: d7 t( z! T$ U! G
childhood testosterone exposure and reduced adult3 E8 \ X* ~8 m" A2 u
penile length in clinical studies.
, i. j- ~& `8 T9 i+ NNonetheless, we do not believe our patient is
0 U$ h1 a0 z5 Igoing to experience any of the untoward effects from
! K% {- \4 B# q3 o# f- a, xtestosterone exposure as mentioned earlier because3 N# {' q7 t3 C
the exposure was not for a prolonged period of time.
. F; E% O3 V- S# mAlthough the bone age was advanced at the time of& y" H7 } \4 r3 M+ V/ I" t
diagnosis, the child had a normal growth velocity at
; H8 e% }* i9 `5 ? y, V/ C9 l- Jthe follow-up visit. It is hoped that his final adult
: L# o' u, m/ n- [# uheight will not be affected.5 v1 {. N$ s& ~% k# W3 X
Although rarely reported, the widespread avail-
8 H2 M5 \' S" lability of androgen products in our society may
7 C; s- G, x6 Xindeed cause more virilization in male or female
" G8 b* ]( B3 s- m$ _. Jchildren than one would realize. Exposure to andro-
& D, p7 t3 I& c% Sgen products must be considered and specific ques-/ Y1 }$ n2 B( @+ p9 V0 w+ P
tioning about the use of a testosterone product or' ^. a/ G8 X5 c4 c1 b( a
gel should be asked of the family members during7 n' T% ~3 S1 g" @ W! c$ Q% X h; s
the evaluation of any children who present with vir-/ e# E; b. ?/ O" ]5 i, _
ilization or peripheral precocious puberty. The diag-
, A4 i3 ^3 U7 T4 i$ p; q0 knosis can be established by just a few tests and by0 z$ d4 B( ] a$ x5 z. ~' B' C
appropriate history. The inability to obtain such a. D- v' ^- M7 z/ N$ j( W, T4 i
history, or failure to ask the specific questions, may8 X: F: w, _! D7 m) i! V* b
result in extensive, unnecessary, and expensive
( p* h; {4 F! u! u; `, |investigation. The primary care physician should be* `+ [% H( |8 {# [! a; j
aware of this fact, because most of these children* y' G4 @/ W& U( ?0 o. M& b
may initially present in their practice. The Physicians’
6 s( k) v* Q6 y# O8 h: N: e( XDesk Reference and package insert should also put a
: c S: ` f2 x! \ @1 W c0 cwarning about the virilizing effect on a male or' S# j0 k) K$ m4 ^( j
female child who might come in contact with some-# M6 f) [! h/ s# H
one using any of these products.
7 {/ C c& O3 N; C- h% f, kReferences
9 F0 N8 D. u( c0 F" G& D- O1. Styne DM. The testes: disorder of sexual differentiation- e/ Z0 x+ G4 M$ M S1 f V+ u
and puberty in the male. In: Sperling MA, ed. Pediatric: O+ ?* v R0 h/ Q5 e) [, N
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
`8 h* w" ^! l$ S0 i7 |2002: 565-628.4 z* }: _/ C" u- Q8 N- x
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious4 K" O* `- S) k: p3 l
puberty in children with tumours of the suprasellar pineal |
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