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Sexual Precocity in a 16-Month-Old1 d" A3 }5 L; D! R: u
Boy Induced by Indirect Topical% b4 e3 ^5 R( ~) {9 f! L% S7 x
Exposure to Testosterone5 Z7 {$ N$ A$ f6 K( ]
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2# U- J; I; j# Z
and Kenneth R. Rettig, MD1
% ~8 J3 L% c( _' N1 Q( S T A/ |Clinical Pediatrics; M2 L4 X( X# | Y3 D
Volume 46 Number 64 Y# w( \: c0 W& S, z, z- |
July 2007 540-543
; W! W6 C3 V0 S9 X© 2007 Sage Publications
3 |1 m8 g6 G9 F" h; {10.1177/0009922806296651
; S- Q* I! R) \http://clp.sagepub.com1 r* i+ G, Q! D4 }* U$ f
hosted at
& D) m9 q$ U$ L* D$ Dhttp://online.sagepub.com, m% J/ a w3 Q
Precocious puberty in boys, central or peripheral,( A3 @) i* U& C0 h
is a significant concern for physicians. Central; h' A. \3 A% u
precocious puberty (CPP), which is mediated0 G. u5 H" D+ ?1 p8 b) u% d
through the hypothalamic pituitary gonadal axis, has
5 X& f, M0 I$ l- Ga higher incidence of organic central nervous system
% S7 C0 r6 g- u; Mlesions in boys.1,2 Virilization in boys, as manifested
/ w2 L( V0 w1 ?by enlargement of the penis, development of pubic1 K+ V7 n# d7 G0 R$ u9 z2 o1 g
hair, and facial acne without enlargement of testi-$ k) S" m; G) m$ k
cles, suggests peripheral or pseudopuberty.1-3 We
0 P: V! n: g: k) Z+ qreport a 16-month-old boy who presented with the; f" N5 t% Z4 w4 G2 E! N0 g1 z4 C
enlargement of the phallus and pubic hair develop-# ]2 \& s& O% u3 D# x X% c# Z
ment without testicular enlargement, which was due. p: ^! a1 h1 x1 j
to the unintentional exposure to androgen gel used by6 V& @" t' A3 p5 @- N7 F1 X7 g2 ]
the father. The family initially concealed this infor-) |2 Z8 }. _% ^5 L _& ]$ }
mation, resulting in an extensive work-up for this* K. I; L, n4 }+ W- j
child. Given the widespread and easy availability of! ?5 {& s- ?3 g9 Y7 j4 G; S
testosterone gel and cream, we believe this is proba-
* ]. E3 ?, I y7 Ably more common than the rare case report in the9 }. W+ Z% w2 F* t+ ~) l
literature.4
+ P6 p1 k, \# m8 S6 U5 I6 jPatient Report
* z3 G4 ], J3 `& j( c5 OA 16-month-old white child was referred to the
3 j+ R0 T" t3 z. _, I4 c* iendocrine clinic by his pediatrician with the concern" P0 a& m, x* C% }8 P2 Y; U2 J) |: [
of early sexual development. His mother noticed3 G% D+ e) w& p. E5 F0 e
light colored pubic hair development when he was
7 Y8 b( x; Q5 f. W' x+ x! SFrom the 1Division of Pediatric Endocrinology, 2University of
5 ]- a' B" Q; ~" P3 nSouth Alabama Medical Center, Mobile, Alabama.
9 y' j' ^5 n% a4 a1 \Address correspondence to: Samar K. Bhowmick, MD, FACE,
$ L5 S {4 p& s( p6 Y9 g' ?Professor of Pediatrics, University of South Alabama, College of
& W4 m: n# `9 {5 a- y' IMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
( N6 F* v5 _9 B: ie-mail: [email protected].3 E( s* c# F7 {: C; s9 n
about 6 to 7 months old, which progressively became3 O! z8 R1 x% `% O. j5 A
darker. She was also concerned about the enlarge-( R) J& V% J) }& k) t
ment of his penis and frequent erections. The child$ j# F% _' s1 x
was the product of a full-term normal delivery, with
8 H) ?- m$ l. m6 m' V- ka birth weight of 7 lb 14 oz, and birth length of
) I# }+ u0 x3 y20 inches. He was breast-fed throughout the first year
; v' A# _) j! c: [of life and was still receiving breast milk along with
& ~& h* p/ a1 P) Ksolid food. He had no hospitalizations or surgery,
, Y( B. b- G& xand his psychosocial and psychomotor development
; P% c5 [1 u1 U4 b8 Xwas age appropriate.
* k% l7 P- U# z9 Y* ~7 z% |The family history was remarkable for the father,
: c/ ^1 Y5 B1 g2 @1 jwho was diagnosed with hypothyroidism at age 16,/ k6 \: G& A; z: d( S, l3 e8 z
which was treated with thyroxine. The father’s% M% \' z9 h5 `( Z
height was 6 feet, and he went through a somewhat
) z( M9 G$ O2 k8 A" p# ?: n! U$ [early puberty and had stopped growing by age 14.' Y# @" C0 e; |" [* f. U# N& E$ v3 s
The father denied taking any other medication. The* _! e( h0 v5 j
child’s mother was in good health. Her menarche
9 i# C/ k/ o8 V7 ^6 Twas at 11 years of age, and her height was at 5 feet
C4 g$ S! @/ Z: D9 J; E5 inches. There was no other family history of pre-
4 R+ H, D* O; }cocious sexual development in the first-degree rela-
' b; p/ W: m5 u& a5 e1 y8 {tives. There were no siblings.
7 Q8 ]# B/ F( K9 N+ `. APhysical Examination' A0 [9 d8 S1 C- I. a
The physical examination revealed a very active,
% d) b! T, U5 m7 \6 o' G/ wplayful, and healthy boy. The vital signs documented
- I" j5 V& [! J na blood pressure of 85/50 mm Hg, his length was# v8 H4 |( V2 m# c& @: S; E
90 cm (>97th percentile), and his weight was 14.4 kg
) P o K/ I2 p/ v/ ?5 J( ?(also >97th percentile). The observed yearly growth( J- o8 i2 f. ]* I/ Y: v
velocity was 30 cm (12 inches). The examination of
- |4 F: V* }3 b C, z" ]" Jthe neck revealed no thyroid enlargement.
: J9 j/ s$ D% QThe genitourinary examination was remarkable for
2 V+ W4 W2 g- c3 _enlargement of the penis, with a stretched length of- u% N! y6 l) Z- p8 e4 M7 ~
8 cm and a width of 2 cm. The glans penis was very well( C3 a: m0 B8 B |8 N' @ ^
developed. The pubic hair was Tanner II, mostly around
* Q, T1 p* i/ Q$ k* t540) \" b& k, b! t. r: f
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from4 j' g+ g2 z& x2 L1 H
the base of the phallus and was dark and curled. The7 M( I4 h7 t5 P: O- P( Q* s6 F4 q, z
testicular volume was prepubertal at 2 mL each.7 I: W2 l9 j0 g. R
The skin was moist and smooth and somewhat
' H. g8 i! x3 V! b# roily. No axillary hair was noted. There were no
9 [1 h2 ]9 z+ j [8 y' H mabnormal skin pigmentations or café-au-lait spots." p+ c8 F" D1 @5 X% b& |9 r
Neurologic evaluation showed deep tendon reflex 2+
3 F. `. z, e, p) n- j6 h* h9 Gbilateral and symmetrical. There was no suggestion
. w8 K9 q4 V) H/ G0 B1 [of papilledema.
[* y6 ~5 \3 g& q& h. {5 O" lLaboratory Evaluation
! t! Z% L+ _# V+ e$ X) ^+ ]The bone age was consistent with 28 months by: k9 ?* d. R2 R# h5 C; [
using the standard of Greulich and Pyle at a chrono-0 M9 c3 d8 O$ q/ g
logic age of 16 months (advanced).5 Chromosomal# R7 ^: F( t# E& g% P, R
karyotype was 46XY. The thyroid function test
6 O& m4 x# C5 a, b% z$ dshowed a free T4 of 1.69 ng/dL, and thyroid stimu-6 }9 g; }7 P; |: F! A/ i+ i1 H
lating hormone level was 1.3 µIU/mL (both normal).
" w7 t! e/ ^! V' ~( pThe concentrations of serum electrolytes, blood
* Q( j+ t' e/ \, rurea nitrogen, creatinine, and calcium all were/ T. Y+ P a* p* a9 n& d
within normal range for his age. The concentration- y, i* {9 S5 q! l. S" p
of serum 17-hydroxyprogesterone was 16 ng/dL
8 d" t$ Y! R. {" H(normal, 3 to 90 ng/dL), androstenedione was 20
/ j& ]! R# F7 ?2 ?3 dng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-& u* U. @; Z! v7 {+ n
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
# Y+ H: e; a2 K7 ~! v% Xdesoxycorticosterone was 4.3 ng/dL (normal, 7 to9 S @ G9 |2 @, A: Q* h
49ng/dL), 11-desoxycortisol (specific compound S)
/ C/ ^, E2 k' e) Q/ Mwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-. o% C4 h9 n, g6 \% q
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total4 T* n( d1 y3 X; E. c! `; i
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
' k0 W4 i' Q" w* u/ S2 ^and β-human chorionic gonadotropin was less than
6 P( t5 y( h) d8 L5 mIU/mL (normal <5 mIU/mL). Serum follicular
- V! h0 X4 L% Kstimulating hormone and leuteinizing hormone g1 m- G+ _; o
concentrations were less than 0.05 mIU/mL4 F, Y9 O' Y( w) t6 `2 s$ G+ a
(prepubertal).
7 U) F' K$ U2 l: |1 aThe parents were notified about the laboratory
5 z$ S( v! {: yresults and were informed that all of the tests were$ T) r9 k$ V0 y' r% T" m
normal except the testosterone level was high. The# Q- `0 q. U% @4 w6 p4 t0 q/ Y
follow-up visit was arranged within a few weeks to
7 h! s/ w( |7 ^- ]0 @- wobtain testicular and abdominal sonograms; how-
" S4 u+ C4 [2 b9 I. r" m- Kever, the family did not return for 4 months.
" Y1 k( A# s: X" C' E2 }Physical examination at this time revealed that the6 r% y$ B2 L1 d+ C( J
child had grown 2.5 cm in 4 months and had gained
$ R+ Z9 v; s6 E4 I2 Y" ]" k- q2 F+ I7 K2 kg of weight. Physical examination remained
. b/ H, c7 \% R* Vunchanged. Surprisingly, the pubic hair almost com-
$ v$ v) L8 C6 g1 Q/ D* R4 ?pletely disappeared except for a few vellous hairs at
( V4 S1 W- {/ c; p X1 Qthe base of the phallus. Testicular volume was still 2) _0 K$ k5 E' W% [* f- D
mL, and the size of the penis remained unchanged.( A/ O- P3 {& T- S: p4 W
The mother also said that the boy was no longer hav-
8 E" b4 ?/ M! |8 z& D' H Ming frequent erections.1 _2 \ X1 i+ e5 q* | f1 q
Both parents were again questioned about use of. J9 m8 B' ], K
any ointment/creams that they may have applied to5 j& ?3 y f! p& ]9 a
the child’s skin. This time the father admitted the
4 k6 b- h' F3 m/ f* w' cTopical Testosterone Exposure / Bhowmick et al 541& c" Z# z9 K+ w% a
use of testosterone gel twice daily that he was apply-
5 o3 p9 f2 r$ ]1 ~8 p; jing over his own shoulders, chest, and back area for5 f# |) C2 Y+ t) @* i
a year. The father also revealed he was embarrassed
: q8 }& `8 M& p& D1 Mto disclose that he was using a testosterone gel pre-2 a5 M2 l3 D2 @/ V. y% o
scribed by his family physician for decreased libido
2 D3 f4 z' O9 F! i1 Msecondary to depression., w8 F# A7 P8 d9 c! N) J
The child slept in the same bed with parents.* I, | T. ]6 u% }3 u* a
The father would hug the baby and hold him on his- ^. t6 d3 N/ t7 _9 I: M: y
chest for a considerable period of time, causing sig-5 u$ y* L" r( s. _; g8 H* b
nificant bare skin contact between baby and father.
3 h% l3 d% {) @5 CThe father also admitted that after the phone call,% p( p( [7 Z: L- X3 H* I' k
when he learned the testosterone level in the baby4 Q) b5 @1 r- o6 Y! L
was high, he then read the product information" h: b* Z8 n% m% q* k2 y" g
packet and concluded that it was most likely the rea- e$ G1 t4 a6 i) r. Y7 T: N
son for the child’s virilization. At that time, they& y) c" |+ m! b4 h
decided to put the baby in a separate bed, and the
' ]$ U& f& B4 Q; n$ _5 A3 dfather was not hugging him with bare skin and had1 S% g0 m8 I; p2 v" Z. y1 X
been using protective clothing. A repeat testosterone
6 t% B5 D, j6 [* o. P: v, ~test was ordered, but the family did not go to the3 [& K6 P3 t8 _' R( o
laboratory to obtain the test.
3 i* V4 g6 d* E/ {4 @# J) ]Discussion$ _0 v8 _ \4 ~3 ]4 i6 T3 o
Precocious puberty in boys is defined as secondary
8 C2 d7 ~1 a) G1 ?3 y6 P% |1 Csexual development before 9 years of age.1,4' \; H7 L' f* F- Q4 Y1 T3 f
Precocious puberty is termed as central (true) when
% x. t7 |( |6 o o' e, M pit is caused by the premature activation of hypo-4 ]: F3 Q- t3 A1 f2 t4 N; {
thalamic pituitary gonadal axis. CPP is more com-
) ~0 z u9 z" D: smon in girls than in boys.1,3 Most boys with CPP8 S7 q% J* R# p0 D
may have a central nervous system lesion that is
. v% u( a6 C8 H. [& B- M/ wresponsible for the early activation of the hypothal-" h0 ~& V; _/ i
amic pituitary gonadal axis.1-3 Thus, greater empha-. V- F' }" c$ d) e( Q9 i
sis has been given to neuroradiologic imaging in
" k4 C8 Z `& ^: b, `1 Jboys with precocious puberty. In addition to viril-$ t& I/ a6 c2 W1 T
ization, the clinical hallmark of CPP is the symmet-
2 a8 p$ b6 @& ?9 s) l0 q: K( grical testicular growth secondary to stimulation by D( O7 B7 T s$ a; m# t# T3 F
gonadotropins.1,3
8 O6 T# F( v7 q) gGonadotropin-independent peripheral preco-
/ o$ }/ j0 ]$ p3 s' scious puberty in boys also results from inappropriate. n! N- C6 f* o
androgenic stimulation from either endogenous or
+ {8 D9 Z" U6 J8 bexogenous sources, nonpituitary gonadotropin stim-
/ Z) P' p& A$ nulation, and rare activating mutations.3 Virilizing$ ~& t, s7 E' l2 c% M
congenital adrenal hyperplasia producing excessive
; S6 p& x: I$ L; N( d0 ^! R7 [adrenal androgens is a common cause of precocious. R2 l0 p$ ?) p+ f) J. K
puberty in boys.3,4
- f0 X' j3 G3 N" h F/ JThe most common form of congenital adrenal
% y. p8 |& ?) m! ~ thyperplasia is the 21-hydroxylase enzyme deficiency.' j& }9 Q1 P6 s! v9 O: O4 [
The 11-β hydroxylase deficiency may also result in4 D! Q( h! ^+ n2 [' O
excessive adrenal androgen production, and rarely,& P3 G9 n$ Y! \+ P9 z1 g# C+ ]
an adrenal tumor may also cause adrenal androgen
" `( T1 r+ B! f- Z' i5 e- Q. [excess.1,3- `1 f# X: O" j7 T& L, y: V
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
: W; g8 I- X! p' m+ M9 x8 _3 v542 Clinical Pediatrics / Vol. 46, No. 6, July 20076 j# j- L# j( j
A unique entity of male-limited gonadotropin-4 K B8 a+ E+ l, h' x
independent precocious puberty, which is also known6 p' i. g* w( L7 A( V
as testotoxicosis, may cause precocious puberty at a
* v- }# F$ x, R. A2 p, v- c lvery young age. The physical findings in these boys, b+ l! L2 r2 G- r8 o& J5 S- r
with this disorder are full pubertal development,7 E1 L- B" b& k, o8 j# ?
including bilateral testicular growth, similar to boys( k1 z- T+ ~) O" }
with CPP. The gonadotropin levels in this disorder
& [6 U6 K' ?2 V1 }4 xare suppressed to prepubertal levels and do not show+ M, u4 t t( K
pubertal response of gonadotropin after gonadotropin-
( `- Q1 E3 R; i/ P. J! n5 Vreleasing hormone stimulation. This is a sex-linked
2 P4 h. K3 c1 |% w6 Q4 `1 F9 Gautosomal dominant disorder that affects only
4 m8 V. O d/ c: T- Emales; therefore, other male members of the family6 `! v1 J, d: A% n j& o; y
may have similar precocious puberty.3
. j# s, _" @: `6 L, ^ GIn our patient, physical examination was incon-$ _" i% s) |% s' j' C: H: c/ \
sistent with true precocious puberty since his testi-
' V% s; D w+ tcles were prepubertal in size. However, testotoxicosis
7 @+ K2 ?1 @8 y3 R# qwas in the differential diagnosis because his father/ l* c5 `, c V- w$ s7 I
started puberty somewhat early, and occasionally,% B) q0 f( x, u. q# Z a7 w
testicular enlargement is not that evident in the
2 Z I+ N+ n( V& Y a. Z$ Ebeginning of this process.1 In the absence of a neg-+ ?$ Z3 L+ J. ]6 J# A
ative initial history of androgen exposure, our
' c0 R; G! _, F' T" {biggest concern was virilizing adrenal hyperplasia, Z- L9 j" C7 p, X
either 21-hydroxylase deficiency or 11-β hydroxylase, z0 l/ z. j8 ?7 k
deficiency. Those diagnoses were excluded by find-: I' q/ p3 V* C- ]+ d
ing the normal level of adrenal steroids.
% R' {3 w q. MThe diagnosis of exogenous androgens was strongly, m3 a7 ~: j- V4 r# o/ n
suspected in a follow-up visit after 4 months because
( ]7 u. |2 |$ ?$ i4 u% nthe physical examination revealed the complete disap-
A' g9 u* L) z" {. I' upearance of pubic hair, normal growth velocity, and3 v$ x, ?" @' K8 X) V0 {) u
decreased erections. The father admitted using a testos-) { t4 ^% Q! h3 u/ j
terone gel, which he concealed at first visit. He was
4 @1 g. K! h% t; g Q( ^using it rather frequently, twice a day. The Physicians’- w x& c8 I. b
Desk Reference, or package insert of this product, gel or
) U4 Q5 d4 s! L# g, Z3 ccream, cautions about dermal testosterone transfer to
, N5 E( E2 j3 y5 z; Xunprotected females through direct skin exposure.* T1 G$ V8 E9 {/ P( E, G5 X( q
Serum testosterone level was found to be 2 times the* f6 _' B1 B' v- n; C. q
baseline value in those females who were exposed to/ c; m+ {$ q, y' f. o
even 15 minutes of direct skin contact with their male
1 A8 T9 P# ?1 y& w9 R: K+ ?partners.6 However, when a shirt covered the applica-' B+ W. U0 s+ O: z- H0 \' X
tion site, this testosterone transfer was prevented.
" i0 e X# n8 C( ]9 j% K2 _0 POur patient’s testosterone level was 60 ng/mL,5 m* K, A' g9 L5 q0 O4 Z$ {
which was clearly high. Some studies suggest that
, ]5 M8 N! P: ]/ \6 Gdermal conversion of testosterone to dihydrotestos-
& l ^+ ~, ~& a9 G V& z; H mterone, which is a more potent metabolite, is more0 x5 @" Y$ a3 k) w ?
active in young children exposed to testosterone4 U# v+ a! t9 Q2 g' k/ `
exogenously7; however, we did not measure a dihy-- ~+ T; C( v, i$ |
drotestosterone level in our patient. In addition to# n, Q7 w1 h# G; h
virilization, exposure to exogenous testosterone in6 a: |' t) V' f- e
children results in an increase in growth velocity and' a, }& h( C6 U1 \
advanced bone age, as seen in our patient.3 t' \& E. B: u9 d" h
The long-term effect of androgen exposure during9 X8 b) B& \. u0 e5 b) f: @
early childhood on pubertal development and final
, B* Q9 I1 U( B! fadult height are not fully known and always remain
5 f7 u) G8 k8 U; m Qa concern. Children treated with short-term testos-0 ^6 J4 o! i K) A& |* d0 H
terone injection or topical androgen may exhibit some6 H% a/ l8 T9 ^" ^- Y
acceleration of the skeletal maturation; however, after }# D1 k% o3 q1 N( C; W8 O
cessation of treatment, the rate of bone maturation
0 v9 w! d" W7 A. F" |0 f6 h. Mdecelerates and gradually returns to normal.8,9
6 [; r) W3 E' ` |" H1 OThere are conflicting reports and controversy) c; f5 w7 C" J5 g$ c) M
over the effect of early androgen exposure on adult$ c% [0 t9 v# q; K
penile length.10,11 Some reports suggest subnormal+ G% i2 o& a1 d: q- i
adult penile length, apparently because of downreg-* A) G' B# I G% }9 ]
ulation of androgen receptor number.10,12 However,( Q$ u( ~; g' Q7 d
Sutherland et al13 did not find a correlation between
' R2 H7 x. I3 B" Q: ^: d0 Tchildhood testosterone exposure and reduced adult& g* [- v/ S/ [+ r/ l4 y3 J
penile length in clinical studies.
7 x4 n h ~- t rNonetheless, we do not believe our patient is$ |- P2 A4 P9 U) [
going to experience any of the untoward effects from
) S) [7 [9 I9 _5 x: e; btestosterone exposure as mentioned earlier because3 W: X' c( m* l$ Y' j3 u1 W
the exposure was not for a prolonged period of time.- U$ Y5 ^/ c- g) F
Although the bone age was advanced at the time of* A& ^. D4 i6 O
diagnosis, the child had a normal growth velocity at
* x O1 a0 ^3 \' L" C, E) jthe follow-up visit. It is hoped that his final adult
1 Z2 m- j, P+ d" vheight will not be affected.7 k- b6 P4 j3 N
Although rarely reported, the widespread avail-6 k) t1 s) E& k$ h- u* h
ability of androgen products in our society may c$ ^, y$ S E: \
indeed cause more virilization in male or female3 p) Y* v4 K+ U! u
children than one would realize. Exposure to andro-
: K/ V) P3 }, Zgen products must be considered and specific ques-
" H4 P2 b9 b3 `- ^. w! R6 j! l: e" `tioning about the use of a testosterone product or
' k8 U9 d- P- Ggel should be asked of the family members during
' I* E3 B8 h4 A4 b' f& nthe evaluation of any children who present with vir-* C, S0 \! c0 y+ W
ilization or peripheral precocious puberty. The diag-
" x+ H2 X0 e- M1 s& |nosis can be established by just a few tests and by
5 ^% ]' @5 ?+ Z2 n9 mappropriate history. The inability to obtain such a2 m# H, j2 P2 }7 |
history, or failure to ask the specific questions, may6 b7 m" z& S- L% X
result in extensive, unnecessary, and expensive
9 ^. q$ M# F! D/ E% }investigation. The primary care physician should be! T; N+ Y; a7 m) r8 Q
aware of this fact, because most of these children
8 P4 r1 E, H# ]& `' L3 imay initially present in their practice. The Physicians’
$ ^, u0 `1 l: k7 J8 j2 vDesk Reference and package insert should also put a
1 z2 f. H8 m' b' dwarning about the virilizing effect on a male or
6 K7 N' i8 }8 ]2 S1 o0 ufemale child who might come in contact with some-: L! e% n9 f6 G H, ^3 h$ u6 M
one using any of these products.0 R1 ]$ i4 w$ L
References
3 v9 f8 J2 `1 I# A% i1. Styne DM. The testes: disorder of sexual differentiation
/ D0 s, `3 Q& h5 F8 u7 Xand puberty in the male. In: Sperling MA, ed. Pediatric
" e) T8 D7 T# i8 C# r' }Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
7 J0 g2 s+ L6 V0 H) i+ k# H+ X2002: 565-628.
$ `) B$ [: Y7 E- H! i: m# ]0 E2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious; L" T' ]1 |0 {: s ?* ~; b4 b
puberty in children with tumours of the suprasellar pineal |
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