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Sexual Precocity in a 16-Month-Old
0 N- |/ S( e |5 `- P. _Boy Induced by Indirect Topical
* T0 M P) q Y6 D& E k+ {Exposure to Testosterone5 r0 m4 m, W( L7 Q* u
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
5 S9 w* [0 J0 r& yand Kenneth R. Rettig, MD1- A( w: p& D7 n% c+ W; |7 M
Clinical Pediatrics
U- n- i0 N/ ]8 W' f: R7 rVolume 46 Number 6
4 K% h/ o$ ]3 [; \July 2007 540-543
/ Z" U" C' K6 L7 |8 v& t© 2007 Sage Publications, r1 l: M6 w& _" x: H
10.1177/00099228062966517 H" P& e* f7 ^8 x( c* ?+ J
http://clp.sagepub.com) F g. @; w% @' D& e- U* b, @) t7 z
hosted at
+ B) z& \, w8 `5 q: }6 @- q; Vhttp://online.sagepub.com
6 x, v; E" h" y, Q) k, _. P* IPrecocious puberty in boys, central or peripheral,
# ?9 Y0 T3 K5 d! Z# n Mis a significant concern for physicians. Central8 x! H' H* n3 q% u4 S, m
precocious puberty (CPP), which is mediated
1 ?3 m5 }0 s% _: `. d4 ?through the hypothalamic pituitary gonadal axis, has3 d, W; d$ B$ {. b! E
a higher incidence of organic central nervous system
" i- e! w$ Y# @lesions in boys.1,2 Virilization in boys, as manifested
0 l% M0 _7 c& C7 qby enlargement of the penis, development of pubic5 w# [ W9 e) Z% r+ o3 q3 j
hair, and facial acne without enlargement of testi-
) g* S( L, r6 h8 c' d% xcles, suggests peripheral or pseudopuberty.1-3 We
# h$ o f* k2 ?5 e2 d% Mreport a 16-month-old boy who presented with the2 [5 ~2 z& f- _% b
enlargement of the phallus and pubic hair develop-
8 Q* i5 A. V; J. q- V H* N% i, Mment without testicular enlargement, which was due
% f9 D. ^0 R- \* [8 E/ hto the unintentional exposure to androgen gel used by( o: _/ e+ H; l
the father. The family initially concealed this infor-& y% |" u1 \8 |' k B, E
mation, resulting in an extensive work-up for this1 t" w# S. L; u+ a
child. Given the widespread and easy availability of
. [0 |8 L8 o! `( T4 G" }* T }( ltestosterone gel and cream, we believe this is proba-% J# F% m1 M) J9 P. ~ p! b" ?
bly more common than the rare case report in the
3 c6 d+ d7 x. W) D2 Bliterature.4
3 H8 ]; w5 a6 X: ?Patient Report2 n9 O! v# v j ^/ `
A 16-month-old white child was referred to the+ h. |/ S* \& f/ h) g
endocrine clinic by his pediatrician with the concern
- z0 l& G; U; U9 tof early sexual development. His mother noticed
/ o( e9 }% v6 i+ Xlight colored pubic hair development when he was
$ ]8 ~9 p( }) f- d) \6 n8 gFrom the 1Division of Pediatric Endocrinology, 2University of) s1 L3 [& g! G/ F* `& S
South Alabama Medical Center, Mobile, Alabama.8 _; a7 d R+ Z7 }# H; ~# B) V# C
Address correspondence to: Samar K. Bhowmick, MD, FACE,; ?& _9 V5 j% h1 ?0 n
Professor of Pediatrics, University of South Alabama, College of9 `' m8 X' [ b2 i. H# d; ]* v
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;# m2 K7 c* b- W( R# S- x" E4 m, q5 Z
e-mail: [email protected].+ I+ {! w/ |: O. N" R
about 6 to 7 months old, which progressively became
7 i E5 A* T$ K! Qdarker. She was also concerned about the enlarge-4 T7 E. N3 Y5 n8 ~
ment of his penis and frequent erections. The child- n) \* H' [* b& Z" i0 M5 J
was the product of a full-term normal delivery, with
; t( G' Q% n9 |) ~a birth weight of 7 lb 14 oz, and birth length of
7 [% A0 s8 a! y20 inches. He was breast-fed throughout the first year
; J1 q ]' N8 S# w9 w5 C* a* zof life and was still receiving breast milk along with9 n) A6 U W5 V0 j/ U3 |! _
solid food. He had no hospitalizations or surgery,
! s+ A+ M5 K9 ]/ z+ nand his psychosocial and psychomotor development( K) _ Y# Q, q
was age appropriate.0 s7 o8 k0 ^! W# R' Y
The family history was remarkable for the father,
% m( {% H7 [6 cwho was diagnosed with hypothyroidism at age 16,+ S0 n+ L4 [: Y) [) c) x/ g
which was treated with thyroxine. The father’s
* Q3 a; m! D; w8 S7 xheight was 6 feet, and he went through a somewhat u# K) }4 K0 \. P$ m
early puberty and had stopped growing by age 14.# k) `0 i3 k0 G
The father denied taking any other medication. The
, E+ j/ V; `9 }child’s mother was in good health. Her menarche! Y0 m; K9 P+ k" ?9 S) h1 |
was at 11 years of age, and her height was at 5 feet
9 u6 o [! Z+ T& X4 H- W5 inches. There was no other family history of pre-
5 G* i1 {* Q. K& Y6 P8 scocious sexual development in the first-degree rela-
' D: S" D) P+ ]tives. There were no siblings.
! [2 k$ N1 S6 T y$ b) zPhysical Examination
' T& i2 U% o" R% nThe physical examination revealed a very active,
, o! o; n; Y0 N6 P& f6 Jplayful, and healthy boy. The vital signs documented- ^2 B/ S$ m2 D6 _! d; u3 p
a blood pressure of 85/50 mm Hg, his length was" W- {5 `4 _, V3 \3 H4 B/ D
90 cm (>97th percentile), and his weight was 14.4 kg$ W# x$ e C0 L/ j
(also >97th percentile). The observed yearly growth6 a6 u( f. O K! l/ k
velocity was 30 cm (12 inches). The examination of
4 B* |- g S/ Kthe neck revealed no thyroid enlargement.
" _ ~, y% I; [& B2 n4 K8 g' pThe genitourinary examination was remarkable for
: j) a2 l! }& g+ nenlargement of the penis, with a stretched length of" H5 n# N. D# u
8 cm and a width of 2 cm. The glans penis was very well
! j( Y. U K; ideveloped. The pubic hair was Tanner II, mostly around
, }( U1 [- a1 Z$ ^540$ A8 [" p4 N$ o* |( H3 T
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
, C& X$ K& V Pthe base of the phallus and was dark and curled. The
" a, m* Q. ~( B9 d* Atesticular volume was prepubertal at 2 mL each. Z i( N1 _4 M
The skin was moist and smooth and somewhat
! R+ C% F6 }3 p) J+ ~oily. No axillary hair was noted. There were no
9 |# [: X; B, P1 yabnormal skin pigmentations or café-au-lait spots.# P# z8 f4 u5 k& L
Neurologic evaluation showed deep tendon reflex 2+/ F; T2 E. N x( A. U
bilateral and symmetrical. There was no suggestion
6 H# H o8 C) {8 yof papilledema.
/ B. ~; O% i0 |. l" i) L( fLaboratory Evaluation
0 u) E7 w3 |# a Z( pThe bone age was consistent with 28 months by
( _2 _9 i3 a P, ^, d) c! i. rusing the standard of Greulich and Pyle at a chrono-8 ~( s' o* I* X! O3 X
logic age of 16 months (advanced).5 Chromosomal% m# s! `; J$ }; F1 o& P9 i: e) Y
karyotype was 46XY. The thyroid function test& V( A+ P+ X" o0 J& [2 F; s g
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
2 v/ ^2 Y0 Y$ O' C8 q M1 Ylating hormone level was 1.3 µIU/mL (both normal).
1 P5 R$ s3 T) g0 {) v+ s. d! fThe concentrations of serum electrolytes, blood! k- a4 p8 C# p# R% E
urea nitrogen, creatinine, and calcium all were2 @* A' e8 l6 Y6 j2 z" ^
within normal range for his age. The concentration6 b, P M: W+ ^
of serum 17-hydroxyprogesterone was 16 ng/dL. _+ m" C+ r6 z! g# \1 K
(normal, 3 to 90 ng/dL), androstenedione was 20
4 J3 u+ ?4 G( a6 E0 Y) k: Ung/dL (normal, 18 to 80 ng/dL), dehydroepiandros-) n2 R" z. k/ W A$ J1 [
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
) E% p7 t* |3 G2 Adesoxycorticosterone was 4.3 ng/dL (normal, 7 to
& ~9 D4 _4 w% K: T+ S/ _49ng/dL), 11-desoxycortisol (specific compound S)
( J' y5 E4 Z' Y, `was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-1 z6 R( X" k2 }( k$ d L
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
% ?/ W; D/ Q+ t* U( l, P! [testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
5 |! ~) c* d; j9 hand β-human chorionic gonadotropin was less than1 r* Z( ]' @, i1 s. i5 F8 b9 ?
5 mIU/mL (normal <5 mIU/mL). Serum follicular
! U5 G" O) ]) i& Y& v7 l4 W9 {stimulating hormone and leuteinizing hormone
, L9 u) o3 \8 {2 x, _4 z w! Econcentrations were less than 0.05 mIU/mL- P) q0 S: c7 k
(prepubertal).
2 c+ {* ~6 q4 E3 g% OThe parents were notified about the laboratory
* o9 j5 t) Q' e( i! E. U8 ]results and were informed that all of the tests were
' C8 R0 X$ \; ]# N' ^* r0 j/ ^normal except the testosterone level was high. The$ \& Q6 n2 W$ `) F. b/ P
follow-up visit was arranged within a few weeks to
6 A$ w, L5 L/ nobtain testicular and abdominal sonograms; how-' {5 l; T) {. a; x5 P
ever, the family did not return for 4 months.
- D9 j0 R, G# \Physical examination at this time revealed that the
0 @5 l/ q2 p& G% A+ dchild had grown 2.5 cm in 4 months and had gained
& i7 e3 J' s5 u; x5 U! O2 kg of weight. Physical examination remained" T7 h' U" [# u; V9 M
unchanged. Surprisingly, the pubic hair almost com-& G2 y7 J1 z9 s5 X
pletely disappeared except for a few vellous hairs at
; Q, R: a3 h6 q _) Tthe base of the phallus. Testicular volume was still 2% W, J! ]4 I Z8 o" p, N
mL, and the size of the penis remained unchanged.3 m3 |$ S% _8 f" P* _: Y
The mother also said that the boy was no longer hav-: o, l' S" ]2 u/ d
ing frequent erections.5 k2 g1 E+ J2 g, s
Both parents were again questioned about use of0 } T0 v& m! Q5 o4 x; v* V; d
any ointment/creams that they may have applied to. a/ t( D, ~* T @$ P
the child’s skin. This time the father admitted the
7 d) G6 E% B; O' s& d z: PTopical Testosterone Exposure / Bhowmick et al 541
e# u* p) H* E$ f$ Q2 _use of testosterone gel twice daily that he was apply-, ^" Y- a, W, V8 j+ T
ing over his own shoulders, chest, and back area for
$ u R5 p+ R7 r3 ra year. The father also revealed he was embarrassed }7 `5 G% p2 P, j2 ]* q8 X
to disclose that he was using a testosterone gel pre-- D& \" }! ?& `; B m
scribed by his family physician for decreased libido
8 ]1 B8 @* u% d+ E* l" {- @secondary to depression.4 s9 u3 l! p& Y" n0 U
The child slept in the same bed with parents.# z: ?4 V, c$ n* O7 A. O, W: g
The father would hug the baby and hold him on his
8 c+ V9 e- }# \6 bchest for a considerable period of time, causing sig-
& v$ d# j$ X& [8 n; C0 Gnificant bare skin contact between baby and father.
# U) K4 L/ J) x+ `6 PThe father also admitted that after the phone call,4 K p+ Z& n/ B, P# ~
when he learned the testosterone level in the baby
+ z* ]1 O: W. ?% q! @* }was high, he then read the product information3 s% c. h: M' Y: H' f- u5 t
packet and concluded that it was most likely the rea-
% o8 A3 Y+ W8 m+ kson for the child’s virilization. At that time, they$ H/ A2 x h, ?
decided to put the baby in a separate bed, and the, @$ S8 \/ o& J# Y" L5 y# @% X
father was not hugging him with bare skin and had1 y$ j+ c4 ~( r5 G, ?
been using protective clothing. A repeat testosterone
' O# @1 B0 Z' {8 P( \, Utest was ordered, but the family did not go to the
0 `% J/ y# D6 h% T: x: Rlaboratory to obtain the test. `4 k$ j# o+ d& _. P+ T
Discussion
6 P: J4 B; M3 a. FPrecocious puberty in boys is defined as secondary% M9 e5 w7 l( a" A
sexual development before 9 years of age.1,4$ }' ?9 v0 N; m* R
Precocious puberty is termed as central (true) when
7 C9 |7 i6 Z2 @5 pit is caused by the premature activation of hypo-8 V7 Z/ Z2 c5 d; x
thalamic pituitary gonadal axis. CPP is more com-6 Z7 w3 l9 h4 U$ n1 z6 j/ K
mon in girls than in boys.1,3 Most boys with CPP
3 U2 E0 V" P0 umay have a central nervous system lesion that is% P; r: o e1 I: f
responsible for the early activation of the hypothal-
0 W; e- X3 ? iamic pituitary gonadal axis.1-3 Thus, greater empha-
3 M3 J, @7 @. {1 l* T( z5 Ysis has been given to neuroradiologic imaging in. o. G! _: t4 [7 a
boys with precocious puberty. In addition to viril-
" n; B5 L. a4 E" p- Z1 Rization, the clinical hallmark of CPP is the symmet-
. P5 {! v% ~; W* [rical testicular growth secondary to stimulation by8 Q+ [3 A" e5 L" ^" b: T
gonadotropins.1,3
$ @: C/ P8 I( z8 {3 ~% O7 A3 v& sGonadotropin-independent peripheral preco-2 w: x% u& l1 J
cious puberty in boys also results from inappropriate; r; @* u8 }. u, F: ^% Y: A: i1 j
androgenic stimulation from either endogenous or
3 j! z1 i/ e% W- Y8 X! n! [exogenous sources, nonpituitary gonadotropin stim-+ Y E& b8 R. a* x2 {
ulation, and rare activating mutations.3 Virilizing
0 a7 `- w' m2 ycongenital adrenal hyperplasia producing excessive
# e# Y) M) R) j# M& J6 badrenal androgens is a common cause of precocious
/ i2 G# v( J8 o: fpuberty in boys.3,4% o8 B+ v: Z# p
The most common form of congenital adrenal1 S6 u' d7 y" y1 ?; S8 ?4 T
hyperplasia is the 21-hydroxylase enzyme deficiency.. K" g! O: e1 N
The 11-β hydroxylase deficiency may also result in6 Q7 |% D9 O, e2 |' ]
excessive adrenal androgen production, and rarely,
. U: O% I: H, h4 k van adrenal tumor may also cause adrenal androgen& a4 a3 u5 x; c3 u2 [
excess.1,3
% ?7 ?' J4 r* Jat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
% |$ p0 E8 o' N; d9 N- B. }" k542 Clinical Pediatrics / Vol. 46, No. 6, July 20077 @" P4 l3 n+ q8 i5 M/ D' b
A unique entity of male-limited gonadotropin-, y5 d& i, {. l
independent precocious puberty, which is also known
7 E( M' P" A3 m8 Y' \0 l# C. b( Sas testotoxicosis, may cause precocious puberty at a
4 }5 R) e9 K4 u8 Avery young age. The physical findings in these boys! ?6 D# c G9 q) [
with this disorder are full pubertal development,
' Z1 e1 a$ K& M$ n# Y/ d) Aincluding bilateral testicular growth, similar to boys2 H$ D: B ?6 {8 E$ k" Z8 s+ B s
with CPP. The gonadotropin levels in this disorder
( x$ y8 g9 v$ _; Bare suppressed to prepubertal levels and do not show
: g* z! Z) U2 J2 W v6 V. {7 Zpubertal response of gonadotropin after gonadotropin-
# ^5 s( _% e3 |, K6 z$ kreleasing hormone stimulation. This is a sex-linked1 [: ]9 F3 d( i9 |) e9 m; ]4 v
autosomal dominant disorder that affects only
" c) F* A4 U. @males; therefore, other male members of the family+ _; ]9 d7 d1 N; n+ |5 u
may have similar precocious puberty.3
- H. b& v& T+ p" t+ g. m! YIn our patient, physical examination was incon-) d6 I9 i& r1 A# f
sistent with true precocious puberty since his testi-
" n7 |% v6 ]8 A X& J. ?cles were prepubertal in size. However, testotoxicosis
7 k5 c- B" I8 L) K2 Fwas in the differential diagnosis because his father
0 r$ B0 v) r3 j* U& sstarted puberty somewhat early, and occasionally,
3 d, r+ [( a+ C' y' I5 n5 rtesticular enlargement is not that evident in the
/ h9 d7 [6 g! W& t ybeginning of this process.1 In the absence of a neg-) g' r; U, g, g
ative initial history of androgen exposure, our0 x; c* g0 p2 T/ }0 i$ c; o7 h) Y9 K
biggest concern was virilizing adrenal hyperplasia,0 }, s0 ?( _! X# N p8 p
either 21-hydroxylase deficiency or 11-β hydroxylase
! p4 j; I0 Q* p6 k6 K+ {deficiency. Those diagnoses were excluded by find-
8 ^ P2 {5 W# s$ J% K( Ting the normal level of adrenal steroids.6 L. H% O3 u, k/ Y/ |) O9 d2 N
The diagnosis of exogenous androgens was strongly
) T8 y2 D! n& i' Y0 jsuspected in a follow-up visit after 4 months because/ _, N; c1 S' q) |* ^
the physical examination revealed the complete disap-7 M7 w5 F+ l5 F
pearance of pubic hair, normal growth velocity, and8 b3 Y! @" y; w8 N2 v4 h3 ^0 `
decreased erections. The father admitted using a testos-
& U* g! Q6 P2 b4 g' bterone gel, which he concealed at first visit. He was
0 T1 S6 K' X, T1 X# K# ^& }using it rather frequently, twice a day. The Physicians’( x* r# L" F1 n- x" A8 M2 d
Desk Reference, or package insert of this product, gel or
6 Q3 ]! }4 X7 s8 D* h+ `cream, cautions about dermal testosterone transfer to
+ Z0 E5 O$ ~) G0 Gunprotected females through direct skin exposure.
- _( v. Y: y3 F) [! l3 TSerum testosterone level was found to be 2 times the
# I& }& D. O8 ?4 L" J& j+ dbaseline value in those females who were exposed to
1 w& N& p) D, S4 veven 15 minutes of direct skin contact with their male3 m/ P) l6 \" V8 u c& n/ e; u& l
partners.6 However, when a shirt covered the applica-
# F5 g- e; ~7 L7 r) y+ gtion site, this testosterone transfer was prevented." X3 @/ d! n" y4 Y% G) f% @0 c
Our patient’s testosterone level was 60 ng/mL,6 P/ H& V$ {/ r! x E; k1 v
which was clearly high. Some studies suggest that
4 a( M' Z0 E9 ~3 T- L: edermal conversion of testosterone to dihydrotestos-9 ?, b' ?9 ^' a9 I# ^) E
terone, which is a more potent metabolite, is more; g8 l+ P/ ~5 Y3 s
active in young children exposed to testosterone; z3 r6 f$ A3 M, Z
exogenously7; however, we did not measure a dihy-
5 C" V, ^* ]8 U7 O- u$ hdrotestosterone level in our patient. In addition to
" o8 c* G6 D6 J9 Y% X3 p/ Q6 p( Yvirilization, exposure to exogenous testosterone in
/ u1 n( @# A$ Q, q+ q' I/ m4 jchildren results in an increase in growth velocity and
& f' j3 H0 g* B# u6 e# f- qadvanced bone age, as seen in our patient.
+ H j$ m0 D! Y: U4 ?+ SThe long-term effect of androgen exposure during
! R3 @$ A/ X _early childhood on pubertal development and final% ]" q0 Y b6 d/ T7 u
adult height are not fully known and always remain
$ {! b6 }$ q- s* ha concern. Children treated with short-term testos-7 P+ ~! J% s& ?5 |# x
terone injection or topical androgen may exhibit some
$ s* X8 L# h" wacceleration of the skeletal maturation; however, after
+ A- P6 ^- e2 h5 f2 y! {, @& Pcessation of treatment, the rate of bone maturation4 Q( w" O& I2 z
decelerates and gradually returns to normal.8,98 N9 D) }. z5 {& n) f7 l
There are conflicting reports and controversy
& P1 M4 i' P2 R% fover the effect of early androgen exposure on adult
( l: B3 Q0 C8 ?0 apenile length.10,11 Some reports suggest subnormal' b) a* ?$ |5 L" q) U
adult penile length, apparently because of downreg-
) ^. S* V% X& u( Kulation of androgen receptor number.10,12 However,$ I( J1 E8 C9 g4 g$ ]
Sutherland et al13 did not find a correlation between0 n6 Q! c. j- |' x/ J. [
childhood testosterone exposure and reduced adult
. y6 K+ B3 Q9 npenile length in clinical studies.
& I) u9 g- n; C- a8 t* vNonetheless, we do not believe our patient is
4 a: j4 h8 g( R, |' ?going to experience any of the untoward effects from- M2 X2 u6 j1 u5 a! N2 Z& E- |' g1 ~) T/ G
testosterone exposure as mentioned earlier because
' g) A9 U! E& K/ k3 Wthe exposure was not for a prolonged period of time.
( h/ u2 a! I. l. |Although the bone age was advanced at the time of* L* t W. [9 G% ?
diagnosis, the child had a normal growth velocity at
; }7 j2 w V, [/ B1 ?the follow-up visit. It is hoped that his final adult
R' m7 \. {5 d" t0 F3 k; A/ G! J* \height will not be affected.3 e, b& u) x' ^; C3 o
Although rarely reported, the widespread avail-
- P' s2 n+ ^8 a* ?( J) C7 t" qability of androgen products in our society may7 n2 s, q( b& E8 i
indeed cause more virilization in male or female
+ x4 `5 s- d6 K: U7 Xchildren than one would realize. Exposure to andro-
* o3 s7 d0 C2 Y9 v% |4 _1 vgen products must be considered and specific ques-9 _; i( M- a# { K1 ]4 n$ I5 j* o
tioning about the use of a testosterone product or
; [+ L) D' P6 K' A% |- N3 wgel should be asked of the family members during
+ P E: ]6 l, H6 f5 E, c$ Rthe evaluation of any children who present with vir-. k/ Z9 U3 N% z; j% A/ Y; P
ilization or peripheral precocious puberty. The diag-
- \# |' \0 X0 P" p; a$ w5 P1 e& Jnosis can be established by just a few tests and by3 t) Y& m# b" C! J1 ]: q
appropriate history. The inability to obtain such a/ [* O! @1 A+ X, G/ u
history, or failure to ask the specific questions, may+ a3 W& T$ S8 o7 Y
result in extensive, unnecessary, and expensive8 q7 F8 i) y P1 a- w. a4 Z+ X8 e
investigation. The primary care physician should be% t. B* Q# n `+ M
aware of this fact, because most of these children2 Q6 q& h" d) [3 O. |( }7 M2 D
may initially present in their practice. The Physicians’
( G+ i" b. _8 r, E# F% D0 \Desk Reference and package insert should also put a
: ]9 \1 g* C% Jwarning about the virilizing effect on a male or
* Y- T& |9 r( D- qfemale child who might come in contact with some-' p3 ]$ ]7 l' L2 `4 N: u3 B4 _
one using any of these products.
. o& V, a* s2 c4 iReferences: A/ S+ E& c9 x$ `6 w
1. Styne DM. The testes: disorder of sexual differentiation
1 g k, O7 P0 y9 w* tand puberty in the male. In: Sperling MA, ed. Pediatric
: q. T+ R. Y. AEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;. I% R$ f* @9 i
2002: 565-628.
, V0 g& d2 g7 K4 u2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
3 ]6 R8 l2 `- h( y, z! P1 u& q8 Apuberty in children with tumours of the suprasellar pineal |
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