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Sexual Precocity in a 16-Month-Old
& f f; b* g# dBoy Induced by Indirect Topical
* e9 f. S6 \! O. \+ d1 Y; TExposure to Testosterone
j6 B- X3 o0 l( k# C0 b: fSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2/ n' Z6 d* J7 w/ O K# b
and Kenneth R. Rettig, MD1
. X. W6 i+ V0 B( f5 YClinical Pediatrics& k0 j$ |' z+ h! ]6 Y, d5 C
Volume 46 Number 6
) d6 @, K- Y- w. H4 h2 ~8 L, OJuly 2007 540-543
1 ]) `( O. b+ h© 2007 Sage Publications5 p+ y. g5 P* J: s4 d2 u2 D k
10.1177/0009922806296651
* U$ H' Q- v& p' Khttp://clp.sagepub.com7 R6 K- t$ z8 b
hosted at
2 \& {2 |( ?6 {6 E# Jhttp://online.sagepub.com
' _. p8 \, B/ V. w2 PPrecocious puberty in boys, central or peripheral,
' M8 o3 o8 ?. n) \; K+ \# x9 dis a significant concern for physicians. Central1 G9 z3 F/ x! u4 z. s
precocious puberty (CPP), which is mediated; |/ t6 \$ {* X: s7 U; f5 o
through the hypothalamic pituitary gonadal axis, has1 w( m. u1 V0 {: I! X
a higher incidence of organic central nervous system" j0 s& s; x$ W; p
lesions in boys.1,2 Virilization in boys, as manifested
% V5 R! ^- x$ R$ J) h5 _+ ]! Q! Nby enlargement of the penis, development of pubic4 L! s) ?0 c5 y% f$ _3 b- k9 a
hair, and facial acne without enlargement of testi-9 S# t- M& G/ e2 E9 V/ }
cles, suggests peripheral or pseudopuberty.1-3 We
3 m& { D; v; j- Oreport a 16-month-old boy who presented with the: ]) A2 N0 v' g$ P$ R6 W
enlargement of the phallus and pubic hair develop-$ z5 u) s4 e, q1 `+ u$ f6 V
ment without testicular enlargement, which was due
" b% @" L; B; J" c) pto the unintentional exposure to androgen gel used by
5 B# P! d. U% c& t$ U6 _the father. The family initially concealed this infor-
9 f( u D, s0 b% L0 W8 z% u$ X% Imation, resulting in an extensive work-up for this( R+ E* u1 f$ ]9 } c! G
child. Given the widespread and easy availability of
7 ?& w: h* M) {/ R& I I. Ctestosterone gel and cream, we believe this is proba-! p" c2 t6 Q9 V: Q0 H, T9 ?( a
bly more common than the rare case report in the
( @2 ` \6 A& \7 Tliterature.4
3 k% n8 p5 M: x( @Patient Report
1 K0 V. Z- g& i* `( [ h& s1 WA 16-month-old white child was referred to the
5 p- b O+ c2 `1 Uendocrine clinic by his pediatrician with the concern
) [, R9 W: S0 b! f- q& e* Gof early sexual development. His mother noticed' P" D& b/ u8 O% E4 A' b
light colored pubic hair development when he was0 u# k3 Z: z5 f, c5 |" B" F
From the 1Division of Pediatric Endocrinology, 2University of6 P$ @1 o# n1 v
South Alabama Medical Center, Mobile, Alabama.
2 w9 c u3 Q" z; m7 T1 LAddress correspondence to: Samar K. Bhowmick, MD, FACE,3 L" o- l8 H8 T! [/ k
Professor of Pediatrics, University of South Alabama, College of
. b8 M3 u/ e% F. @" IMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
+ ?$ q) G3 A! ~& k9 q) he-mail: [email protected]./ M' }5 S0 k) n8 Q) V3 Y
about 6 to 7 months old, which progressively became C: ~3 J6 n% w, G* z( h
darker. She was also concerned about the enlarge-# I( C0 b. k a. \
ment of his penis and frequent erections. The child% a9 L3 T P9 U# B2 f" }! M
was the product of a full-term normal delivery, with, g9 w; v8 f7 @+ N6 R! U
a birth weight of 7 lb 14 oz, and birth length of
2 d A2 A p8 O6 a. c! o+ X( O8 B: {20 inches. He was breast-fed throughout the first year
& Z8 O8 z- m u$ ]+ ` b0 W1 G* y7 fof life and was still receiving breast milk along with
! B. ?( Z n) r1 u1 |1 { c; Xsolid food. He had no hospitalizations or surgery,8 e" a- ^# g+ K& T' c N0 ^; S
and his psychosocial and psychomotor development+ S& g$ N* z7 P0 S7 Y" u& \
was age appropriate.! |: Z5 Z% @" |; Z6 A% y
The family history was remarkable for the father,2 h/ O/ z1 ? E# y% `' @+ M. s
who was diagnosed with hypothyroidism at age 16,
) ~4 o5 r& g0 |. C# rwhich was treated with thyroxine. The father’s3 E$ S' U( a4 E/ Y* G7 t: e
height was 6 feet, and he went through a somewhat S; c1 T" f5 i! W7 e6 Q
early puberty and had stopped growing by age 14./ d9 J. p+ f1 X, c2 G
The father denied taking any other medication. The1 O8 U: ^& j( m) r
child’s mother was in good health. Her menarche) {* h& o }- u4 _* Y
was at 11 years of age, and her height was at 5 feet m" W7 U. ^) F' B. F
5 inches. There was no other family history of pre-; f5 x$ ^' U# Z0 i, t4 y& q$ ]
cocious sexual development in the first-degree rela-
) R& g# O e" F# ?2 utives. There were no siblings.
3 K% B! K7 ]! S9 q0 A' `/ XPhysical Examination
, |" @" _! t# |+ j+ M$ pThe physical examination revealed a very active,$ z: W+ M$ o8 Y" l, ^$ X b
playful, and healthy boy. The vital signs documented' O; k0 {* o. X8 A( l
a blood pressure of 85/50 mm Hg, his length was
1 z( D+ s- E; ^3 _90 cm (>97th percentile), and his weight was 14.4 kg9 H+ [: @5 Y+ X2 F: J1 d( ?
(also >97th percentile). The observed yearly growth
) `6 x- R, L1 X5 h- a$ qvelocity was 30 cm (12 inches). The examination of
& V4 }# W: R zthe neck revealed no thyroid enlargement.9 |9 F# W4 U0 g
The genitourinary examination was remarkable for8 ]6 E$ t3 [ s
enlargement of the penis, with a stretched length of$ `* n9 c8 k3 D% [1 g
8 cm and a width of 2 cm. The glans penis was very well/ N- v# |' [- N. D% {
developed. The pubic hair was Tanner II, mostly around
3 K) i, m6 G8 ~5 U( ?9 f$ B3 j. A0 |540% d, P$ g. v0 x& m8 N3 C/ I
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from" g) g# b6 F A% F" U1 X3 a2 ^
the base of the phallus and was dark and curled. The5 s3 T9 T3 k9 w7 o
testicular volume was prepubertal at 2 mL each., z1 U0 w; j) P9 J% V" T
The skin was moist and smooth and somewhat# {8 [ l! X/ K+ Q
oily. No axillary hair was noted. There were no6 e: J' C4 w' s6 R
abnormal skin pigmentations or café-au-lait spots.4 F: E( `/ a: r9 T8 Z% `; {
Neurologic evaluation showed deep tendon reflex 2+1 J/ K8 m5 j" |& |' z' C. X! E# z! b
bilateral and symmetrical. There was no suggestion& a/ ~; P' D9 p" n
of papilledema.- U; k4 q& e' q6 Y
Laboratory Evaluation
7 q1 t2 R; y: i% LThe bone age was consistent with 28 months by
# }) e0 m( L' ~. j1 vusing the standard of Greulich and Pyle at a chrono- O0 k; @ |+ I7 O; ]3 n9 o. `
logic age of 16 months (advanced).5 Chromosomal3 W! M: J+ k5 G1 D4 o5 m* w
karyotype was 46XY. The thyroid function test
& f9 ?" \! T2 w" X7 nshowed a free T4 of 1.69 ng/dL, and thyroid stimu-& b% G w" n' t6 I1 X# M
lating hormone level was 1.3 µIU/mL (both normal).
% T2 N' Z, x& yThe concentrations of serum electrolytes, blood# H! ^% \; A- j6 B9 h' u
urea nitrogen, creatinine, and calcium all were
$ U1 S" H7 f0 ]within normal range for his age. The concentration
8 {8 ^; Q, K1 @$ l R9 vof serum 17-hydroxyprogesterone was 16 ng/dL, d5 H* k: k. R2 p4 m+ k
(normal, 3 to 90 ng/dL), androstenedione was 20( Y4 O \8 a* `. z( V4 I
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
8 ], k) t! C- Y: m: zterone was 38 ng/dL (normal, 50 to 760 ng/dL),% }* t# j2 m% ]" i6 V- D
desoxycorticosterone was 4.3 ng/dL (normal, 7 to. N- @, d; T/ S. [- a
49ng/dL), 11-desoxycortisol (specific compound S)
" a" _5 J0 J/ c% ]was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
; ?) Q \, N6 n" Q4 B3 {tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total$ D: N1 F- b8 z; y+ S' I$ X: H# o
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),. Y1 ^9 X/ l9 K5 `
and β-human chorionic gonadotropin was less than! ]1 Q. I! `( [! {3 K/ H' \
5 mIU/mL (normal <5 mIU/mL). Serum follicular- w5 {9 m) I# G" r
stimulating hormone and leuteinizing hormone
( [% I9 F* f: C$ S# R9 econcentrations were less than 0.05 mIU/mL
5 O! m l; ]- w# f(prepubertal).
0 \. _7 t* ?2 \- p" j& tThe parents were notified about the laboratory& o. U. b7 I# U% h
results and were informed that all of the tests were4 o, M2 K! k% `7 z' T! R' Y) I
normal except the testosterone level was high. The
& Q( M* @: C, L. Lfollow-up visit was arranged within a few weeks to7 j" s* r% w# S8 G% ?* b
obtain testicular and abdominal sonograms; how-
# g6 x1 p+ H2 ?! [* W" |ever, the family did not return for 4 months.
* a3 t% g, s" |4 z/ k i( WPhysical examination at this time revealed that the
" p/ J% K/ @( {( z7 lchild had grown 2.5 cm in 4 months and had gained+ W9 b" X1 x% V+ j+ ^5 V
2 kg of weight. Physical examination remained
# r# ^, `* y) A' S% Y. Zunchanged. Surprisingly, the pubic hair almost com-
* x# _! u5 s8 U) }0 ^3 Upletely disappeared except for a few vellous hairs at. Q, V$ o) K0 K$ l" C3 |
the base of the phallus. Testicular volume was still 2
3 L2 Q: B1 X/ N# LmL, and the size of the penis remained unchanged.
; g" N& V6 m$ z' S* d! YThe mother also said that the boy was no longer hav-3 s& z: P! {2 V9 M0 A W' a( l
ing frequent erections. z7 C+ z( B5 r$ G! i) V
Both parents were again questioned about use of
8 \8 V2 i, Z+ H2 [, eany ointment/creams that they may have applied to
z9 \4 G& b+ xthe child’s skin. This time the father admitted the' W: a& K+ a- n& H: T3 ?
Topical Testosterone Exposure / Bhowmick et al 541) G9 e4 ?: y# I, C% D
use of testosterone gel twice daily that he was apply-" R$ O) K) O; ]1 o$ N
ing over his own shoulders, chest, and back area for# P( f% ~% M+ c8 i7 w
a year. The father also revealed he was embarrassed
+ N3 G3 X: }- d+ ]to disclose that he was using a testosterone gel pre-
9 s( q1 L5 Y8 w- E. U; |scribed by his family physician for decreased libido1 V# M6 V& j+ k4 j* S: I8 I
secondary to depression.- ^) L P% P6 s) R# {
The child slept in the same bed with parents.4 ^4 M5 K; M# f c) v) {" E
The father would hug the baby and hold him on his
; z1 d# f5 ?1 z5 k/ m" Wchest for a considerable period of time, causing sig-
5 l1 D6 A8 H) z c! v7 Q# lnificant bare skin contact between baby and father.+ b) B& ]8 V% A" P9 \9 e
The father also admitted that after the phone call,* }' r4 j" j) }# |: ^+ i& T
when he learned the testosterone level in the baby' R3 c: l3 p& X8 ]2 @
was high, he then read the product information: b: U# N O/ K% ]* I/ I
packet and concluded that it was most likely the rea-+ |* o; H p( B. C
son for the child’s virilization. At that time, they
! E7 |, Q3 Z/ z$ o! `1 I2 K. mdecided to put the baby in a separate bed, and the n) |0 u" v3 f1 L; h' N
father was not hugging him with bare skin and had; N: n6 R0 c& M+ a0 h
been using protective clothing. A repeat testosterone
$ x. N" z3 r [5 Q! ]& l: N4 @7 U( t. Wtest was ordered, but the family did not go to the: [' B: J- O, b: o
laboratory to obtain the test.
* x. i, X- K- ?# Z. iDiscussion
2 T- `' f) }6 lPrecocious puberty in boys is defined as secondary4 R. H: ~# c2 [" ^/ }; Q
sexual development before 9 years of age.1,4
6 v1 G' V, h4 P; QPrecocious puberty is termed as central (true) when8 H/ I) j, R6 N' O' A
it is caused by the premature activation of hypo-
! r2 Q) T0 g5 U0 Fthalamic pituitary gonadal axis. CPP is more com-
+ N, ^* N( E5 F& @ mmon in girls than in boys.1,3 Most boys with CPP
# S1 ^- y& q/ V% y& Mmay have a central nervous system lesion that is
- `* L" o9 q, F uresponsible for the early activation of the hypothal-3 z7 }4 F4 r7 j
amic pituitary gonadal axis.1-3 Thus, greater empha-) P% \' j, M5 t: F
sis has been given to neuroradiologic imaging in
' f) l# {$ j" |. {7 {9 {boys with precocious puberty. In addition to viril-: ?7 f! G0 m/ c/ @$ \: b. n7 ]
ization, the clinical hallmark of CPP is the symmet-" }4 r9 s _6 q0 R9 c# h- X! w
rical testicular growth secondary to stimulation by1 c* s7 {4 `* ]; w! g0 j/ ]6 E. P
gonadotropins.1,3+ E0 S4 G0 J) ]! T3 X+ \9 C
Gonadotropin-independent peripheral preco-
g' S9 G- o# @% ?% |cious puberty in boys also results from inappropriate
* r# p2 I0 `. s- R7 k8 d9 I; @ gandrogenic stimulation from either endogenous or
% ]5 n/ l7 Z, N0 Lexogenous sources, nonpituitary gonadotropin stim-
- w1 ~( S. r) _. {ulation, and rare activating mutations.3 Virilizing7 T4 \( M t' `* F; g0 Z" [+ K
congenital adrenal hyperplasia producing excessive6 F: g' H1 g" D, o7 l9 f
adrenal androgens is a common cause of precocious
0 O( \( T/ b1 x' s: S# _; Bpuberty in boys.3,4: X' P- v0 e' z. V: |- I
The most common form of congenital adrenal
( z) N' y7 h1 Y5 I, [hyperplasia is the 21-hydroxylase enzyme deficiency." t! i( O/ V6 Q* ?! S9 n
The 11-β hydroxylase deficiency may also result in
/ z2 E5 ~( P$ D' \excessive adrenal androgen production, and rarely,
+ C7 Z8 I7 J( A) ?3 H, B/ Yan adrenal tumor may also cause adrenal androgen
6 s W! [- S8 s) Qexcess.1,3
- ~: a4 o; q: x" M) Q' Mat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
, I' V1 U9 l5 c& x4 `! A542 Clinical Pediatrics / Vol. 46, No. 6, July 2007" E) c3 s. i( i: v) b* r
A unique entity of male-limited gonadotropin-7 Y+ F# k' _ P7 _/ b
independent precocious puberty, which is also known: t. y \9 k- Y7 c0 t P' ^( S( X
as testotoxicosis, may cause precocious puberty at a; _/ k, j3 _; |+ i1 q
very young age. The physical findings in these boys2 O0 o4 _2 t+ k
with this disorder are full pubertal development,- a; i3 s! z' O/ _, C3 P( E( f# {" R
including bilateral testicular growth, similar to boys
: F+ M8 R# V+ Qwith CPP. The gonadotropin levels in this disorder/ @* L a+ M* y) k0 S/ w6 ]9 j
are suppressed to prepubertal levels and do not show
2 F1 }" @! D Xpubertal response of gonadotropin after gonadotropin-+ s) L& W- q' k9 o
releasing hormone stimulation. This is a sex-linked
, T, r3 _" l% m, W; a& g& iautosomal dominant disorder that affects only
3 K+ G. b1 N' ^5 F" g) tmales; therefore, other male members of the family* Z/ c. c- Y, i: ~- V
may have similar precocious puberty.3
8 `* K& T" `0 {In our patient, physical examination was incon-
5 n5 P! J$ e/ R7 esistent with true precocious puberty since his testi-
& B- }" f7 L9 P' J# tcles were prepubertal in size. However, testotoxicosis2 w) \; _! l: v2 W
was in the differential diagnosis because his father
, n5 S& ]- r* A. ^started puberty somewhat early, and occasionally,: S2 i6 |; i2 D' z" S9 L
testicular enlargement is not that evident in the
6 v& x4 i; \0 c. }1 F1 \: jbeginning of this process.1 In the absence of a neg-
: L S4 `9 d# a h: Y. Mative initial history of androgen exposure, our$ C, k( ?; Q* k. n+ w% h4 b, j
biggest concern was virilizing adrenal hyperplasia,, G" x" r, E0 I- ?4 O
either 21-hydroxylase deficiency or 11-β hydroxylase7 d, r" ^+ x# ~9 l1 ~
deficiency. Those diagnoses were excluded by find-' C, p* F; ^1 `) @
ing the normal level of adrenal steroids. W1 a2 ?; F- U- l* H1 H9 @
The diagnosis of exogenous androgens was strongly
4 h4 g7 Y8 q b4 V: R M8 esuspected in a follow-up visit after 4 months because% y$ J- w! ~/ N
the physical examination revealed the complete disap-
; e1 Y6 }# c) K7 Z$ l5 U" `; r! Zpearance of pubic hair, normal growth velocity, and
! U, |3 t& W$ y3 t7 E8 U2 W8 |. Cdecreased erections. The father admitted using a testos-
3 x) O/ Y. |* _2 u3 _terone gel, which he concealed at first visit. He was% }9 d$ V6 V& G: Q4 ]
using it rather frequently, twice a day. The Physicians’1 ?9 j' B+ [( q1 g- U8 g! b
Desk Reference, or package insert of this product, gel or" f* K* ^7 L: O; k/ ?/ ^
cream, cautions about dermal testosterone transfer to( X8 y& F5 ^# i& {& m0 `- ? y
unprotected females through direct skin exposure.
& x+ a' e) z% w& q8 oSerum testosterone level was found to be 2 times the+ n; r# N% J6 s5 D* }. [# O. q
baseline value in those females who were exposed to
0 c0 m% E/ D* S0 l. xeven 15 minutes of direct skin contact with their male9 z- u; b8 t7 }0 S4 i5 y- e# |4 w5 o
partners.6 However, when a shirt covered the applica-
, v p9 O& k& m5 Ction site, this testosterone transfer was prevented.
' j, ^0 _2 D* Z, D- d, ^) H. XOur patient’s testosterone level was 60 ng/mL,9 M7 e8 ^7 Y) \, \! x6 h2 F6 V
which was clearly high. Some studies suggest that
2 \! \9 D3 {' v1 w* K8 jdermal conversion of testosterone to dihydrotestos-) v! T/ t1 R1 ]+ K8 |
terone, which is a more potent metabolite, is more d( \ ~; o p
active in young children exposed to testosterone* I; F. _; L. e% n
exogenously7; however, we did not measure a dihy-+ ^, I( _1 A8 |" t5 l
drotestosterone level in our patient. In addition to l& V8 e6 d+ M1 j$ ?
virilization, exposure to exogenous testosterone in" v; n5 A8 a3 d0 N w/ l" g( d
children results in an increase in growth velocity and/ a* c6 s- c9 [. l& C
advanced bone age, as seen in our patient.
+ [5 K5 M D. a2 w5 {The long-term effect of androgen exposure during4 y8 D% K N7 @' j
early childhood on pubertal development and final4 |6 I7 Y% u; j4 Z+ J
adult height are not fully known and always remain
, B5 l H1 `! ma concern. Children treated with short-term testos-
9 A7 _9 \. b3 Bterone injection or topical androgen may exhibit some
& t& p& c4 s+ v( ?; hacceleration of the skeletal maturation; however, after
+ z( m6 ~' D% y N/ O: @4 Xcessation of treatment, the rate of bone maturation- e1 f& j5 `& Z% _$ O
decelerates and gradually returns to normal.8,91 o5 \; v! \' A6 _1 U4 N2 N
There are conflicting reports and controversy
+ l4 s4 Q8 h/ r3 v( ?over the effect of early androgen exposure on adult# A, p/ r# B: Q0 \2 T3 S. {
penile length.10,11 Some reports suggest subnormal5 }8 {+ z9 ?! }. A3 T
adult penile length, apparently because of downreg-: v. v/ c( f" n: p) }
ulation of androgen receptor number.10,12 However,
7 d8 m& u# e7 E% M2 S3 c7 m8 MSutherland et al13 did not find a correlation between. C" |" \" W3 e2 x
childhood testosterone exposure and reduced adult0 Y2 E" U/ ?$ m* R
penile length in clinical studies." L% U" C% i7 Y! `
Nonetheless, we do not believe our patient is- ^/ Y- I6 [6 o9 S. {% b& ]! t/ v
going to experience any of the untoward effects from1 d$ g# g9 Y1 v; J4 Y* V3 D
testosterone exposure as mentioned earlier because3 o( F. Z! M4 N( R L
the exposure was not for a prolonged period of time." p, T: U; G7 ^5 t3 B" |( `
Although the bone age was advanced at the time of
) `! S b- u9 Mdiagnosis, the child had a normal growth velocity at3 Y, E8 a: y" d: x# t
the follow-up visit. It is hoped that his final adult4 A) @7 _3 B) S, s' s" a. F
height will not be affected.
; [$ @( `8 J2 z/ `Although rarely reported, the widespread avail-
& N, @3 L, U8 e9 Z* J+ N$ ]ability of androgen products in our society may0 i; b4 A" h, }6 F
indeed cause more virilization in male or female; F' S: i( [9 ~1 u9 H
children than one would realize. Exposure to andro-' h) w4 X6 G6 z0 L; ~, W& \& r
gen products must be considered and specific ques-
% J0 r2 O$ A4 a1 `tioning about the use of a testosterone product or- u- Q: _9 D1 }4 p9 ~
gel should be asked of the family members during
1 y# i$ b) ^' zthe evaluation of any children who present with vir-
7 C+ h+ t+ e) M9 K8 q6 T1 E( bilization or peripheral precocious puberty. The diag-
, z$ o* K( W& a8 T8 u- x/ Wnosis can be established by just a few tests and by
+ I) X* S( T5 h$ ^4 ^appropriate history. The inability to obtain such a
2 `# j- J& ~* e" c& [0 Lhistory, or failure to ask the specific questions, may
/ w) y4 a5 @% ]. P, ^result in extensive, unnecessary, and expensive
1 c: \ [8 q' k: U R& x* N/ Oinvestigation. The primary care physician should be I7 c8 p& A6 q+ s: W
aware of this fact, because most of these children
" K! G" S* q* _" e$ p! Mmay initially present in their practice. The Physicians’, n" W# p; r8 \2 [
Desk Reference and package insert should also put a
4 {( u! R, |! Z0 _/ Owarning about the virilizing effect on a male or' u, f0 X2 B _% H0 @+ R6 \3 K; p
female child who might come in contact with some-- b) y5 }2 [5 |
one using any of these products.8 [ M) I1 d+ s2 k
References. A9 J2 @) Z) b& f! {
1. Styne DM. The testes: disorder of sexual differentiation1 R/ I: M' r6 d! B6 K
and puberty in the male. In: Sperling MA, ed. Pediatric4 `' A8 v9 f' t8 S
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;, g2 o6 \" c2 J, j* Z3 \
2002: 565-628. ~ M7 p$ R( `
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious: i9 i4 W% |% P% m; @
puberty in children with tumours of the suprasellar pineal |
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