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Sexual Precocity in a 16-Month-Old
I) l, P; i2 i2 W4 O* wBoy Induced by Indirect Topical
2 _3 v; y4 z" `( ~" c- z: Z4 pExposure to Testosterone. ?& q4 J5 f# Z! Y
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
& J/ z/ w8 Q; C( q, h/ M' y m8 d+ n# Hand Kenneth R. Rettig, MD1' G% m3 c) v: r9 }" ]+ t
Clinical Pediatrics
$ s" X5 f2 s9 v# d4 x) FVolume 46 Number 65 O: l) A' _" W; h
July 2007 540-543
6 R* p( |, {( R1 x! o- V5 l) @© 2007 Sage Publications
6 @3 g$ ^5 B9 F% {! m. ~$ f10.1177/0009922806296651
7 V3 ^, a8 S# h6 |( @http://clp.sagepub.com
' Y" l; t! t- v0 S0 whosted at
$ J! S: k7 B% l/ S! Bhttp://online.sagepub.com
" S( I9 h$ L. w+ s+ b3 j0 M2 TPrecocious puberty in boys, central or peripheral,: F& M/ X, } E. X4 _
is a significant concern for physicians. Central; O2 m0 e# m! z1 ~" m
precocious puberty (CPP), which is mediated! M$ Y/ g. r2 u j2 h+ w4 E
through the hypothalamic pituitary gonadal axis, has0 E5 f+ p& @- C* I0 R, \
a higher incidence of organic central nervous system
b& |/ @# _# r# |( X1 Llesions in boys.1,2 Virilization in boys, as manifested
! B# x5 @( W8 S$ h# u: Tby enlargement of the penis, development of pubic4 z& |% |' x( G0 ~- L) A2 j
hair, and facial acne without enlargement of testi-2 `6 q; B0 f0 \
cles, suggests peripheral or pseudopuberty.1-3 We
1 B9 G+ ^, V! Y( Treport a 16-month-old boy who presented with the- t; b* o' T R6 m
enlargement of the phallus and pubic hair develop-8 z. j2 A: s2 R5 w: }; M
ment without testicular enlargement, which was due
$ s" s' m( ^0 k2 }to the unintentional exposure to androgen gel used by
" N; Y; ^. e4 w# c/ pthe father. The family initially concealed this infor-
: d/ {9 m+ A; ~- Y B' W& e( Bmation, resulting in an extensive work-up for this' w9 B( f- t! A, {
child. Given the widespread and easy availability of( Z' W. g5 t# \) \. n
testosterone gel and cream, we believe this is proba-
, O" Q0 @- U7 U: Wbly more common than the rare case report in the
; c1 I! G+ E5 z5 [/ E" Nliterature.4
. A( H2 z$ W% _" y, O8 _# Y; Y3 pPatient Report
1 Y5 _6 O3 G2 @: d$ T7 sA 16-month-old white child was referred to the
' u+ c7 v. q% j6 g- rendocrine clinic by his pediatrician with the concern* Z6 ?& ^8 r( y# ~5 O0 s8 y
of early sexual development. His mother noticed% o; y- M* A, t" U
light colored pubic hair development when he was# W5 y8 |# p6 z1 n8 Y( T
From the 1Division of Pediatric Endocrinology, 2University of
' H8 {- X! L. m" S3 c% ASouth Alabama Medical Center, Mobile, Alabama.
9 Z" I! s* Y5 K/ b2 h# w) hAddress correspondence to: Samar K. Bhowmick, MD, FACE,3 D) t% \) t1 I% s5 R
Professor of Pediatrics, University of South Alabama, College of$ g% X$ D' F- u% n2 O- J3 E
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;% O6 }; R( p& k- P, R
e-mail: [email protected].
4 U; q' \' P' S, Qabout 6 to 7 months old, which progressively became
! K/ I% E: O9 d$ |, R J1 Pdarker. She was also concerned about the enlarge-
: w# {$ j1 v5 D* I8 o8 h% m' jment of his penis and frequent erections. The child& |: H' c3 |) p9 ~7 l
was the product of a full-term normal delivery, with
) {8 V' f" V+ {/ V" ]) B9 ~2 k& ha birth weight of 7 lb 14 oz, and birth length of
. M [5 B5 X6 o, S' x0 o7 V20 inches. He was breast-fed throughout the first year
4 c: h, b. e7 Fof life and was still receiving breast milk along with
2 `( b! |0 ^6 R% [: R" vsolid food. He had no hospitalizations or surgery,
' M; u5 }8 G" a; Iand his psychosocial and psychomotor development! Z/ P: t. ^! h
was age appropriate.3 D: L) X y3 K& _( N1 z; A* j/ d
The family history was remarkable for the father,
2 c, A& ?5 S$ e# J3 uwho was diagnosed with hypothyroidism at age 16,
- B& u' b/ i7 D& nwhich was treated with thyroxine. The father’s# V8 V1 b8 a. S+ r0 d9 e2 i
height was 6 feet, and he went through a somewhat
- u$ [- a) |' Q) B4 q/ q6 F: learly puberty and had stopped growing by age 14.7 Q1 U6 {. {# ]7 e
The father denied taking any other medication. The. H: w5 r- Z3 u' h; H
child’s mother was in good health. Her menarche
% k7 F1 m4 A0 ^, t. {* twas at 11 years of age, and her height was at 5 feet
, e$ ?( B6 [- }0 [5 g5 inches. There was no other family history of pre-
% {1 G3 Y/ V7 c; R# qcocious sexual development in the first-degree rela-9 C ^4 w7 }0 x4 N# }, @
tives. There were no siblings.
5 [; ~* Y8 B$ _9 D8 V- W s* ePhysical Examination
* {9 x7 M n x( q% [" mThe physical examination revealed a very active,4 ~( l0 v) Q' `7 |( A& g
playful, and healthy boy. The vital signs documented
) q4 F1 K6 y; T: ]. j- Ma blood pressure of 85/50 mm Hg, his length was0 u6 E! Z# n/ m! j
90 cm (>97th percentile), and his weight was 14.4 kg% M& w3 Z/ B* _. }: E) L) K1 z5 D
(also >97th percentile). The observed yearly growth9 Q8 g/ F# z6 R+ ]- w7 p# p
velocity was 30 cm (12 inches). The examination of* B' |, z5 k' s8 q
the neck revealed no thyroid enlargement.2 Y* v, d8 C" ?
The genitourinary examination was remarkable for
3 u) I- q5 y; Cenlargement of the penis, with a stretched length of8 F% O( f4 ]$ y8 {# ~* T
8 cm and a width of 2 cm. The glans penis was very well
6 \8 y* i6 b4 V: Edeveloped. The pubic hair was Tanner II, mostly around+ ]' @2 H% [# n# ~% ]$ |' \
540# b R2 T9 j) j* Q4 |( f1 `$ W
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from+ f. i6 K: u, A% A3 t
the base of the phallus and was dark and curled. The5 E7 ]5 t4 Z/ u
testicular volume was prepubertal at 2 mL each.
0 A2 @! O% K" U% u6 I" gThe skin was moist and smooth and somewhat
1 ~" g3 S2 @- p4 V/ P/ q% ^ xoily. No axillary hair was noted. There were no' u: \8 w4 K8 x0 i- n; y8 i1 B
abnormal skin pigmentations or café-au-lait spots.
- b- ]0 X2 j, g8 t3 ^' J# zNeurologic evaluation showed deep tendon reflex 2+
# w9 j1 d1 J9 }' ]8 ~bilateral and symmetrical. There was no suggestion
6 O* G3 R4 V( w$ H* y. |' G( Q: d/ {+ _of papilledema.
5 S2 S; R2 l4 k6 x% MLaboratory Evaluation
! |) L" c/ {: U- ]0 T) zThe bone age was consistent with 28 months by
6 |0 T2 ]/ c7 k) `using the standard of Greulich and Pyle at a chrono-' O7 }4 |/ B" L+ `# x: [+ u
logic age of 16 months (advanced).5 Chromosomal
. X. k, |; N4 ^2 v1 {( t! X& l. V( Ikaryotype was 46XY. The thyroid function test
+ a4 n8 @* \6 Fshowed a free T4 of 1.69 ng/dL, and thyroid stimu-# {+ l' g3 K; o& a
lating hormone level was 1.3 µIU/mL (both normal)., a, I+ ^1 P; N, D1 D! Y% P
The concentrations of serum electrolytes, blood4 z+ y. d+ q, X
urea nitrogen, creatinine, and calcium all were
4 Q! t5 x9 h V# P% a; S; O$ T. bwithin normal range for his age. The concentration1 d) s! l6 o" v* M5 H& V5 y% [
of serum 17-hydroxyprogesterone was 16 ng/dL
7 S' z* t. ^2 Y5 z(normal, 3 to 90 ng/dL), androstenedione was 20: w- h* @& G& @
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-. U& z( _, E3 ~4 V/ U8 }- ^0 W0 _ l
terone was 38 ng/dL (normal, 50 to 760 ng/dL),/ G; }1 M5 B+ M- T2 U8 M" T2 N" E
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
: l+ q, [' s! r' u6 v f: u49ng/dL), 11-desoxycortisol (specific compound S)/ s- h, [& U0 n1 |
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
! T4 I# b( S# o* A: }: {tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total' p- {0 Z# Z% S8 r( a/ e
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
' W; j% B5 P$ |" e, s, L/ Iand β-human chorionic gonadotropin was less than
+ o- A& K5 F9 R' G9 Y5 mIU/mL (normal <5 mIU/mL). Serum follicular* {6 \ S% ~7 [7 I4 W& `4 d5 M3 G
stimulating hormone and leuteinizing hormone
6 c% u- B- j1 Y, Rconcentrations were less than 0.05 mIU/mL% z4 ^* _2 ?/ f4 \
(prepubertal).% R% z6 r! r" J
The parents were notified about the laboratory
' G. U: c9 V7 Wresults and were informed that all of the tests were
9 k$ P9 H6 U$ z. C; Enormal except the testosterone level was high. The$ C; ?% h: R% l6 p1 T, m w
follow-up visit was arranged within a few weeks to
$ s$ j# z5 f; |3 n# Oobtain testicular and abdominal sonograms; how-
7 t+ x7 |+ s, a- d! Kever, the family did not return for 4 months.
' ?: I, w+ c- P& g4 g& EPhysical examination at this time revealed that the# k7 t) F f. |
child had grown 2.5 cm in 4 months and had gained
' @; X8 u6 I( H9 E& A2 kg of weight. Physical examination remained# Q- A2 J! o/ k, o& O
unchanged. Surprisingly, the pubic hair almost com-( R- X/ f+ ]) i |; N- I3 d* y* D, F8 D
pletely disappeared except for a few vellous hairs at
3 F5 [# T" l) Vthe base of the phallus. Testicular volume was still 2
8 ?4 J; o8 a; bmL, and the size of the penis remained unchanged.' g, U5 J8 S/ P) w* P! S
The mother also said that the boy was no longer hav-
2 w8 C/ o) _8 |; wing frequent erections., ^* y" `0 G R; z, m' ]: C( J
Both parents were again questioned about use of
. f# I2 E3 ~) `# C4 M8 Zany ointment/creams that they may have applied to( `6 ~' H9 j% b
the child’s skin. This time the father admitted the+ Y7 F; j" A6 o* D( l" u. s* p2 f/ ~
Topical Testosterone Exposure / Bhowmick et al 541
0 E8 ~" x Q9 ^$ t3 Zuse of testosterone gel twice daily that he was apply-
/ B" ^2 C0 y. ]ing over his own shoulders, chest, and back area for$ N& `% X: H: @4 [0 M4 d
a year. The father also revealed he was embarrassed
$ @: ?. Q; r1 Z1 [to disclose that he was using a testosterone gel pre-: n8 W3 M, W* V* l
scribed by his family physician for decreased libido% @3 d) d2 \. o3 Y
secondary to depression.
8 A( e) E% N# `5 Q, F% I" ^6 ?The child slept in the same bed with parents. l8 M: V" d$ R. e2 F- L' ^
The father would hug the baby and hold him on his
! j7 |( M2 T s3 ?. T% u% e3 `chest for a considerable period of time, causing sig-; G# d. l G2 W( U) }
nificant bare skin contact between baby and father.8 P) q: U, G6 y+ `7 [
The father also admitted that after the phone call,: P# H% f2 t) _1 r# y) \% w
when he learned the testosterone level in the baby, P9 I! ~' x/ L) l
was high, he then read the product information0 K/ D# b/ O3 B( R) P
packet and concluded that it was most likely the rea-, {# }- D* ^/ H1 M4 Y/ C
son for the child’s virilization. At that time, they
, Q3 [4 Z6 J; x# f" Jdecided to put the baby in a separate bed, and the
3 e z: w8 o: M' A& M6 afather was not hugging him with bare skin and had
1 P F& v5 y# D/ \- h3 dbeen using protective clothing. A repeat testosterone# G. E) I1 ~: X1 c4 z
test was ordered, but the family did not go to the
9 j: f2 Z. `, l) x# I6 y% w; ~laboratory to obtain the test.
6 m* ^9 c* d; r; K% a" [9 {3 DDiscussion) e! [8 Y; t, i [4 W( c9 H
Precocious puberty in boys is defined as secondary; f2 }0 P3 f" m# Y$ g
sexual development before 9 years of age.1,4
) ~) a8 D L+ B) wPrecocious puberty is termed as central (true) when2 I' V. X" k; G# |2 u
it is caused by the premature activation of hypo-
1 t6 g8 u) |' _1 k5 Othalamic pituitary gonadal axis. CPP is more com-
0 {& r& f: M9 y4 ], Nmon in girls than in boys.1,3 Most boys with CPP @; O( D k; z0 K
may have a central nervous system lesion that is
0 j( ?( j- H; e& ^responsible for the early activation of the hypothal-6 W+ x1 y3 B1 A$ S9 F; ^5 j" D6 e
amic pituitary gonadal axis.1-3 Thus, greater empha-2 O. {: L. `3 J) T% J
sis has been given to neuroradiologic imaging in
2 x7 p; Q _8 j" K/ Oboys with precocious puberty. In addition to viril-5 L- m. d& R! X# v8 u
ization, the clinical hallmark of CPP is the symmet-; k# v9 D2 }, q4 ]
rical testicular growth secondary to stimulation by0 G" i( v; p, F* d7 H
gonadotropins.1,3
/ K. I6 {; ~; c# C1 ^4 \Gonadotropin-independent peripheral preco-
% f9 v8 n+ d* x( m2 C) Mcious puberty in boys also results from inappropriate2 j$ O1 ^. [- r8 }# p3 }. V2 i
androgenic stimulation from either endogenous or
; d* e0 x+ B9 G* w) ?) [exogenous sources, nonpituitary gonadotropin stim-
( R3 w7 v8 Y2 G% Q" b. Bulation, and rare activating mutations.3 Virilizing/ G) F0 {$ z, `5 C2 j( x* T. _
congenital adrenal hyperplasia producing excessive
/ \3 _: r. c3 |adrenal androgens is a common cause of precocious
. G' O: Q K5 d. ]# Hpuberty in boys.3,4
! W* ^4 k! e3 J% N; d$ V& sThe most common form of congenital adrenal
|9 z# I/ u' `/ B+ J% \hyperplasia is the 21-hydroxylase enzyme deficiency.* H# t/ H" }5 Q! D% Q
The 11-β hydroxylase deficiency may also result in
' L u- W2 N. J. E, }8 xexcessive adrenal androgen production, and rarely,
: ^! e) M" A, |. Van adrenal tumor may also cause adrenal androgen( k8 c2 |+ j" o' U6 u
excess.1,3
, X' Q, }9 \6 l. a fat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from, D$ i7 t" v6 }; _8 m
542 Clinical Pediatrics / Vol. 46, No. 6, July 20074 F2 F4 I9 F, a; P
A unique entity of male-limited gonadotropin-" X; Z& d" g2 P9 I' t3 X
independent precocious puberty, which is also known
% A1 Y, j/ x3 a0 [as testotoxicosis, may cause precocious puberty at a
' _4 `+ m: H5 c! N; V( k" Yvery young age. The physical findings in these boys
. i: i3 x# A8 f+ dwith this disorder are full pubertal development,
- C% Y7 ~ X( Y9 gincluding bilateral testicular growth, similar to boys) g8 M/ @' X6 ?2 c
with CPP. The gonadotropin levels in this disorder, |1 W2 v o Q9 o( |
are suppressed to prepubertal levels and do not show& Z5 Z/ ]0 L' o4 `2 e, t! K% K
pubertal response of gonadotropin after gonadotropin-/ a9 s( ?( x# N+ _ A. O# T, C) c% N
releasing hormone stimulation. This is a sex-linked9 c5 o, a: }$ O+ w% I3 t" p
autosomal dominant disorder that affects only% x u# Z1 `+ i* x, [& u( d
males; therefore, other male members of the family
" s; K v& Y3 w, r b# rmay have similar precocious puberty.3
2 R4 _3 W) L2 L7 v ]In our patient, physical examination was incon-7 f( E6 J# M: Z; s( g: N. ]. L
sistent with true precocious puberty since his testi-
- _+ Y) r! ~& e, acles were prepubertal in size. However, testotoxicosis; j- m; u5 s/ I1 q3 x. b
was in the differential diagnosis because his father
5 Z( S @, o% h2 hstarted puberty somewhat early, and occasionally,% ^0 H2 T6 z0 q, V# C! c# I
testicular enlargement is not that evident in the, ~; L9 n) I3 x; F/ v
beginning of this process.1 In the absence of a neg-( a* |, _0 L2 @2 V# t
ative initial history of androgen exposure, our& O8 o$ q: |/ C2 H, b; C
biggest concern was virilizing adrenal hyperplasia,2 z' m; n* ]0 b4 N
either 21-hydroxylase deficiency or 11-β hydroxylase* e) ?: `, N( D! S7 r9 v9 r6 \8 c
deficiency. Those diagnoses were excluded by find-
, R0 ^, S) M2 N9 [ Zing the normal level of adrenal steroids.# a, e, ]8 r! ]/ f; {( G
The diagnosis of exogenous androgens was strongly
+ v3 B# M: e( Y1 Rsuspected in a follow-up visit after 4 months because( G' v w9 b7 @' q
the physical examination revealed the complete disap-5 d# V% F% e) C5 x9 ^
pearance of pubic hair, normal growth velocity, and
0 Q/ Y* |: y0 _( Udecreased erections. The father admitted using a testos-8 F, i( ~, ^/ \, {( ]6 A3 K7 M/ j
terone gel, which he concealed at first visit. He was/ l; [* m! X% d
using it rather frequently, twice a day. The Physicians’
2 e& r7 H1 n S0 ~8 q, b, sDesk Reference, or package insert of this product, gel or
( f4 B/ ?) _1 o" x: [cream, cautions about dermal testosterone transfer to
) V# R& d; j: {$ p( ]5 Runprotected females through direct skin exposure.
+ E2 c. {. q1 z" Q, J; HSerum testosterone level was found to be 2 times the
8 `! O+ V q8 G7 O7 bbaseline value in those females who were exposed to: a! r0 Z- G' d: V4 @' ]/ n0 U
even 15 minutes of direct skin contact with their male) M5 Y8 S4 S! Q0 g3 n/ F# c. f
partners.6 However, when a shirt covered the applica-" ~' b0 a y; `6 c
tion site, this testosterone transfer was prevented.% ~& y) w/ U- R: u* q3 H5 p+ X
Our patient’s testosterone level was 60 ng/mL,- t, D) P; B6 U# }2 g* W9 a" `
which was clearly high. Some studies suggest that
- p1 r" v; t0 X' q7 G4 r. Tdermal conversion of testosterone to dihydrotestos-: X( N% e7 e n- ?' P
terone, which is a more potent metabolite, is more
" d$ _$ ]* Q; h$ zactive in young children exposed to testosterone7 `$ c, V& e8 K- Z3 b8 G( ^& c
exogenously7; however, we did not measure a dihy-3 s z4 D- Z- A9 Z, q" z
drotestosterone level in our patient. In addition to
7 {# u2 t$ i/ a- Uvirilization, exposure to exogenous testosterone in
2 }; \* V* }- V( T/ d. mchildren results in an increase in growth velocity and) |8 j+ P4 }6 q& m1 I$ g- W* R
advanced bone age, as seen in our patient.6 C u4 w; J' e% p
The long-term effect of androgen exposure during$ [0 _3 F! D% w; @- ~# |
early childhood on pubertal development and final: j; m* y6 z, f* B+ o* j4 N
adult height are not fully known and always remain
3 z, p4 C$ a9 a/ y5 Ta concern. Children treated with short-term testos-/ ]( n% w2 f0 w) p& Q
terone injection or topical androgen may exhibit some
" k6 A3 A& O: b6 |# sacceleration of the skeletal maturation; however, after, f+ u- {2 d1 {! D8 x2 C8 d
cessation of treatment, the rate of bone maturation
# |; R9 C; _' y4 cdecelerates and gradually returns to normal.8,9& y6 s; H1 i7 ?0 ~* D
There are conflicting reports and controversy
; r1 X3 q, r5 pover the effect of early androgen exposure on adult
6 r3 a! g2 s9 S" W+ r7 spenile length.10,11 Some reports suggest subnormal9 z" h* u& y( t6 `
adult penile length, apparently because of downreg-
4 W+ u# s) V: ?ulation of androgen receptor number.10,12 However,
. S" ^; T0 P, w3 fSutherland et al13 did not find a correlation between) E* J5 ^1 k; p ]' @; z/ J5 r) M
childhood testosterone exposure and reduced adult9 C7 T2 M: a% U+ q, r, V
penile length in clinical studies.3 s4 S/ y; y% f+ a q& D! {
Nonetheless, we do not believe our patient is" @* k* ~9 s Z9 @/ {+ a! ]
going to experience any of the untoward effects from
3 O8 [- k4 c4 A+ vtestosterone exposure as mentioned earlier because
1 Q4 e1 @8 } o8 T8 a% E) u: B7 c {the exposure was not for a prolonged period of time.
7 Y3 L: d8 [7 F9 kAlthough the bone age was advanced at the time of* A& O) F2 Z1 j1 j( p
diagnosis, the child had a normal growth velocity at
8 f2 _8 ^( L5 @the follow-up visit. It is hoped that his final adult
$ v$ U3 ^$ [; X1 R+ xheight will not be affected.
+ g2 w( A. @0 P( O- jAlthough rarely reported, the widespread avail-; D' w+ V4 d H
ability of androgen products in our society may2 F" ]* t i9 m3 g9 `
indeed cause more virilization in male or female
' q3 o) P" ]4 L( C$ h+ A5 wchildren than one would realize. Exposure to andro-$ E& R; f5 H; \" k
gen products must be considered and specific ques-
0 y# @; ]* k$ u* ntioning about the use of a testosterone product or0 l, i: E+ a, Y. V1 y# s2 u% O
gel should be asked of the family members during- N; z q8 y" x
the evaluation of any children who present with vir-% C* z1 \! H# h
ilization or peripheral precocious puberty. The diag-
: ]( J f! |/ K7 H+ Vnosis can be established by just a few tests and by
8 u8 b9 b( F! p' eappropriate history. The inability to obtain such a& z" T2 y( H! d; Y, T p
history, or failure to ask the specific questions, may
+ E O2 m! e6 oresult in extensive, unnecessary, and expensive: d: W6 i6 L6 K
investigation. The primary care physician should be
# I( E7 M. h" U% x/ laware of this fact, because most of these children) t6 O7 O; g% D0 {, m, b$ X
may initially present in their practice. The Physicians’
6 C& a7 ^" m7 h8 ZDesk Reference and package insert should also put a" Y5 E2 n' A( R# \1 r* ~- j y2 x
warning about the virilizing effect on a male or
! c# g! ^6 y s7 N( ?female child who might come in contact with some-5 s; d- d$ b9 T0 _
one using any of these products./ l! b' `: O: W) V7 S
References6 _/ t9 e. \ a" n/ a" p- \
1. Styne DM. The testes: disorder of sexual differentiation' `" c( n" W" t1 `1 A. P9 \
and puberty in the male. In: Sperling MA, ed. Pediatric, V! w( W. G4 n: d6 b/ [
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;9 }' O" \; t9 R: P1 j. k2 p6 k
2002: 565-628.
# n* o; s- C! U; d2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
2 U1 F+ J) J3 P+ Rpuberty in children with tumours of the suprasellar pineal |
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