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Sexual Precocity in a 16-Month-Old% ]- l; ?0 r# G& @8 I
Boy Induced by Indirect Topical% L3 k D+ Q! D1 |* Z/ ~3 R
Exposure to Testosterone
8 H1 c' P2 |) h( M6 ESamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2" c! [2 O# w. L
and Kenneth R. Rettig, MD1
" m4 g9 T; ?3 N- _ x3 p8 {" [" NClinical Pediatrics
- Z: l ~, j! b0 V6 QVolume 46 Number 6- h7 b5 ]! ? m7 s
July 2007 540-543
* t6 Q3 Y8 H- v: j& y. u© 2007 Sage Publications
0 D' c7 G3 |, S8 K+ j10.1177/00099228062966511 U' O7 Z$ U4 m% T, A' d( B
http://clp.sagepub.com
' `; G% }8 G; o- Z, S9 ?' }- Ihosted at- \, i$ [ a+ }* T
http://online.sagepub.com {7 S8 ?* O; I* W
Precocious puberty in boys, central or peripheral,* V/ q) L. _. T- I; y/ r
is a significant concern for physicians. Central( Q. Y. U8 k% L& _- R- _5 T% [
precocious puberty (CPP), which is mediated
e" c9 N- V6 z! K) A6 M+ y0 Q3 wthrough the hypothalamic pituitary gonadal axis, has
8 {3 z9 C0 x; |$ q4 ma higher incidence of organic central nervous system5 c9 U6 }8 V6 d5 f/ `
lesions in boys.1,2 Virilization in boys, as manifested
" ?' G$ d! o" Mby enlargement of the penis, development of pubic: h' V7 s; i/ D6 x1 Y
hair, and facial acne without enlargement of testi-( Q! j0 {3 ?% B- o/ T
cles, suggests peripheral or pseudopuberty.1-3 We7 H( R+ D6 H& A# r, l l- \7 X
report a 16-month-old boy who presented with the, S1 h% G! s* J
enlargement of the phallus and pubic hair develop-
' n; W0 p2 b0 ?& ~) x% l( |+ tment without testicular enlargement, which was due
5 v5 n$ \6 p7 Vto the unintentional exposure to androgen gel used by
( x! b _. E- j* Xthe father. The family initially concealed this infor-* `2 j( ^# n# m# N4 M. R
mation, resulting in an extensive work-up for this( z% s6 ^1 E. [" s T) \
child. Given the widespread and easy availability of0 `3 _+ L/ D2 |' r8 v8 |* `" e
testosterone gel and cream, we believe this is proba-
' F% @% Z: y: @ qbly more common than the rare case report in the
& y5 V/ B, _: k6 g- I5 R4 Pliterature.4
& L) C- Y4 z& }6 ]( K5 lPatient Report q, a. m2 Z: @
A 16-month-old white child was referred to the4 e0 r" Z% o& j& d; e
endocrine clinic by his pediatrician with the concern' i* N4 h J1 c
of early sexual development. His mother noticed
) Q c9 C) t- v% vlight colored pubic hair development when he was0 {6 ?! w) f! `4 `6 m
From the 1Division of Pediatric Endocrinology, 2University of
# x9 r! @; T/ @! ]South Alabama Medical Center, Mobile, Alabama.
, k' o: j' [* b7 p u9 LAddress correspondence to: Samar K. Bhowmick, MD, FACE,
, L# z4 T4 y& n IProfessor of Pediatrics, University of South Alabama, College of
. n9 s) G/ D, K% Y6 lMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
" E }- T) s5 G- Je-mail: [email protected].9 a! I" m( \1 m' @& u+ x N, G
about 6 to 7 months old, which progressively became% s- r2 y' |' M/ D1 f. x
darker. She was also concerned about the enlarge-
- x# [6 \" p$ }# ~5 s. t1 Cment of his penis and frequent erections. The child. A" h$ z% v |) E4 N% j- p
was the product of a full-term normal delivery, with
) v `9 u5 S% c, q& |a birth weight of 7 lb 14 oz, and birth length of
# [- o2 d9 D* w, Q20 inches. He was breast-fed throughout the first year+ d8 l! Q) E: ~. c4 u
of life and was still receiving breast milk along with
% _) P# W) z* O. B1 p& {6 Psolid food. He had no hospitalizations or surgery,; ?3 Z) \8 u. Z7 {3 L
and his psychosocial and psychomotor development
( m* Q6 n, t9 g3 l# q/ f# J* ?7 Cwas age appropriate.
4 e% r. g* Y9 ]- s8 [ {7 s* I. OThe family history was remarkable for the father,
2 e* U3 Y2 W2 c) d: k6 Fwho was diagnosed with hypothyroidism at age 16,& I7 O9 j8 M. \" k+ d/ }
which was treated with thyroxine. The father’s8 T+ e: u8 w( H/ y$ y3 u
height was 6 feet, and he went through a somewhat
* r! L7 S- @) {% i5 w$ b' Oearly puberty and had stopped growing by age 14.
0 D% B7 d) ~" C2 W5 h1 k% x, `4 ]The father denied taking any other medication. The
& |( x6 v+ D: ~5 ]: v! ochild’s mother was in good health. Her menarche+ B: X- m5 r6 H. ~: ?5 E5 D4 n
was at 11 years of age, and her height was at 5 feet
" {) ^3 k+ O; [+ J1 S5 inches. There was no other family history of pre-
. K6 w' a0 \, u) t+ rcocious sexual development in the first-degree rela-8 E2 I2 _4 s& O8 y5 Y2 O4 A
tives. There were no siblings., G$ c! k. R- C5 r5 S5 D
Physical Examination' i; Z* K3 y$ S6 e
The physical examination revealed a very active,
( z0 O' E% V. y8 s" h: S* Nplayful, and healthy boy. The vital signs documented
$ G! }8 _- ]4 Da blood pressure of 85/50 mm Hg, his length was `- P D5 x0 S* _5 i* P
90 cm (>97th percentile), and his weight was 14.4 kg9 h- d( A6 m+ l$ s, N" V3 ]
(also >97th percentile). The observed yearly growth% Q$ J% \7 Z( v, h& B. B0 x
velocity was 30 cm (12 inches). The examination of
5 x- E8 ~" {1 zthe neck revealed no thyroid enlargement.4 G$ V! Q3 q6 p+ K6 w+ q
The genitourinary examination was remarkable for
/ o: n ?* O4 M* W) {( N2 S1 x% Xenlargement of the penis, with a stretched length of
3 Q1 ?& Z8 I* K1 [$ z9 N A8 {8 cm and a width of 2 cm. The glans penis was very well
- ?; M% R! T! U2 @developed. The pubic hair was Tanner II, mostly around
' t0 G) O" l( r1 r$ H. }, p540
8 ]3 Z L" B$ fat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from0 y, F5 }& I; W( ^
the base of the phallus and was dark and curled. The, ?/ Q0 ]8 v( n- e
testicular volume was prepubertal at 2 mL each.
A g6 n! {( x( JThe skin was moist and smooth and somewhat$ j5 q# A% J) y+ U1 V8 X: z
oily. No axillary hair was noted. There were no
! s. D" u/ o5 V! sabnormal skin pigmentations or café-au-lait spots.! A$ c7 }& ~7 l* Z. }/ i
Neurologic evaluation showed deep tendon reflex 2+
( B6 q1 \4 q5 n$ u$ ~" ]bilateral and symmetrical. There was no suggestion
, {6 y- l3 P1 W) bof papilledema.
$ f& _7 T; I' f# w8 L+ fLaboratory Evaluation) C; M- h5 Y; L$ n. X9 H
The bone age was consistent with 28 months by: ]3 p; P: V9 T
using the standard of Greulich and Pyle at a chrono-
+ Q. D' g+ Z; ]$ \! q' _logic age of 16 months (advanced).5 Chromosomal
: d1 X- f' \1 S- e" y) Okaryotype was 46XY. The thyroid function test& G6 q% E1 D; Y0 `
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
% v- n. C/ }5 G( z6 ~lating hormone level was 1.3 µIU/mL (both normal).5 z4 r# d4 F7 f) g* c9 b
The concentrations of serum electrolytes, blood9 F: R. U% ^: N2 ~
urea nitrogen, creatinine, and calcium all were a1 J: P% U2 Y& E1 S" W6 _
within normal range for his age. The concentration& Y( q" b+ h- {" P# _6 j
of serum 17-hydroxyprogesterone was 16 ng/dL
8 ^* M. J" {, c* P' V3 N(normal, 3 to 90 ng/dL), androstenedione was 20" V. q/ h( H7 v4 p
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-; D8 x7 ~' l, w
terone was 38 ng/dL (normal, 50 to 760 ng/dL),) x* s# @7 Q5 u- b
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
{ e* J+ ` b6 r: O+ O' Y4 r4 v49ng/dL), 11-desoxycortisol (specific compound S)
, b5 z2 u) n2 p$ p' w% [2 Rwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
2 m) G' R' b9 ?% H7 V! e8 u) v" jtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total4 h% M/ N) w2 }1 O7 B( }
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),; y w$ f# A. T) u, _8 L7 ~
and β-human chorionic gonadotropin was less than
# B2 K" |; i! c5 O5 mIU/mL (normal <5 mIU/mL). Serum follicular
1 p7 @) M* s8 U, ?stimulating hormone and leuteinizing hormone- J% Y3 b* |! J' z8 j
concentrations were less than 0.05 mIU/mL& _) Q* t0 I {% y$ h' V, i
(prepubertal).$ k5 B3 H6 J, a( \
The parents were notified about the laboratory
: h5 f" P/ v9 Y* f* ?* dresults and were informed that all of the tests were
- S2 m, ^, u _normal except the testosterone level was high. The
0 r, B! V. g+ T, a# ffollow-up visit was arranged within a few weeks to
+ O' v' X' `! ]obtain testicular and abdominal sonograms; how-
, q4 d: V( w* _7 Sever, the family did not return for 4 months.* d' ]; M ^! q0 s) R
Physical examination at this time revealed that the0 R% N4 a8 j- g! ]5 _+ d
child had grown 2.5 cm in 4 months and had gained
0 B8 I/ Z' T! @; j2 kg of weight. Physical examination remained T4 ]7 `- o7 I% W3 v
unchanged. Surprisingly, the pubic hair almost com-
6 |) U9 |; l# g: @0 zpletely disappeared except for a few vellous hairs at
. Q0 Q8 }! z g# [/ [9 r3 _the base of the phallus. Testicular volume was still 2
, e8 D. S5 D8 a: s4 O9 c8 W* e" CmL, and the size of the penis remained unchanged.: ]* h* r5 _# s+ c
The mother also said that the boy was no longer hav-
$ S- Z% P5 P1 E+ j5 Q) Iing frequent erections.) b: d: k( P. j& j0 X0 T" e
Both parents were again questioned about use of1 `% a! h( Q% h7 L; m
any ointment/creams that they may have applied to; k, B- C0 O& D
the child’s skin. This time the father admitted the
# w: b% ^: R7 n; R- j9 nTopical Testosterone Exposure / Bhowmick et al 541/ j' G6 { C4 x5 @0 W1 v
use of testosterone gel twice daily that he was apply-2 d: x6 Q& d2 b: G6 d2 g, L8 |
ing over his own shoulders, chest, and back area for
" \" m9 b, g; a2 p" Y N1 B+ Ma year. The father also revealed he was embarrassed
) c8 e. ~$ v9 ]to disclose that he was using a testosterone gel pre-' c7 p! E. o5 w
scribed by his family physician for decreased libido
* G X: M6 o4 ^( p3 rsecondary to depression.
$ J5 m6 A, d: ^& \) r8 ` s- @The child slept in the same bed with parents.
, ~9 J* y2 o- F eThe father would hug the baby and hold him on his; L+ ]$ _! S. u; Q0 S
chest for a considerable period of time, causing sig-
7 C7 ~9 ^$ a j9 _nificant bare skin contact between baby and father.
$ y" Q/ d$ m& D& pThe father also admitted that after the phone call,
- P1 I- R( K1 I! F$ t V7 }when he learned the testosterone level in the baby1 T( V' s0 p1 H
was high, he then read the product information3 {7 x( z0 g& ]; H0 r: e% a
packet and concluded that it was most likely the rea-1 t! B4 U8 r. v* A* {/ R! @9 K
son for the child’s virilization. At that time, they1 W) q, }; V8 z9 Y4 f
decided to put the baby in a separate bed, and the
+ X$ t9 O# {( G6 N8 K9 w6 ]father was not hugging him with bare skin and had( l2 s; ?( A$ }* H5 z7 }
been using protective clothing. A repeat testosterone
# j" B: p6 m3 r. y* ytest was ordered, but the family did not go to the
! H0 H$ u+ r: J' ~# a* dlaboratory to obtain the test.
6 v4 q* f' g5 k% I1 Y. y! \Discussion6 B1 X- n- Y% [$ b1 {, o! m: }
Precocious puberty in boys is defined as secondary
/ |7 F- ?7 x) K1 m n" U, [sexual development before 9 years of age.1,4
# X2 F: t' r0 d/ mPrecocious puberty is termed as central (true) when7 L& g1 E" K1 q% _
it is caused by the premature activation of hypo-
0 j+ v- C1 _ kthalamic pituitary gonadal axis. CPP is more com-
/ F1 w8 R, D U$ d. c5 s ]2 {: Bmon in girls than in boys.1,3 Most boys with CPP8 G% M0 P, G6 {# T: U: a
may have a central nervous system lesion that is$ b& e* z. w. F% K/ R/ S9 s
responsible for the early activation of the hypothal-6 X) L# Y5 S t/ {
amic pituitary gonadal axis.1-3 Thus, greater empha-
3 o5 f; J3 b% V- L' Gsis has been given to neuroradiologic imaging in+ M- ^( `& [# ]5 H% q9 |; Q0 c( Z: G
boys with precocious puberty. In addition to viril-& c; l$ |: L1 l0 U# X" s
ization, the clinical hallmark of CPP is the symmet-5 D1 I. c, [# y. e! T/ N
rical testicular growth secondary to stimulation by
5 [" k k A+ \% Z( A* pgonadotropins.1,3
8 {1 j( l" y$ |6 k$ N& {Gonadotropin-independent peripheral preco-5 n( X7 ~ y" N' ]0 C4 d
cious puberty in boys also results from inappropriate$ f, P8 J9 i! p' e. d5 ?2 i
androgenic stimulation from either endogenous or
; _( u: |: _, u7 i2 r% mexogenous sources, nonpituitary gonadotropin stim-
& u7 T& A* k2 a& W5 E" [( r6 H$ f) ]# vulation, and rare activating mutations.3 Virilizing
7 N! d+ V. K$ b* F7 U z+ C5 ccongenital adrenal hyperplasia producing excessive) C, @" s0 \/ S7 K# x" P% K6 H
adrenal androgens is a common cause of precocious
0 L- |# D0 r. Bpuberty in boys.3,4# s6 T. C& X3 f. i$ l
The most common form of congenital adrenal
' ~2 }/ _/ q T& W3 U( ^& c1 n% bhyperplasia is the 21-hydroxylase enzyme deficiency.5 t# A1 x- t0 C. ~
The 11-β hydroxylase deficiency may also result in; M) E2 D% [: _. {6 h$ L- V
excessive adrenal androgen production, and rarely,
* A& g. N% m7 u E7 ean adrenal tumor may also cause adrenal androgen' c# O# j1 F5 k6 z' m' ~5 t
excess.1,3
, f* V0 W9 J1 R$ g% C6 E. \at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
$ C! d+ a5 A! D9 `' | `* m. @542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
- P3 v& O( c8 }% \* z; lA unique entity of male-limited gonadotropin-; [2 y7 J1 e0 \% i' V# s/ t* f
independent precocious puberty, which is also known+ P0 k6 D; Q1 g5 W$ m" C8 Q$ Z9 E" k
as testotoxicosis, may cause precocious puberty at a
( r2 {+ z8 q+ `3 X0 Qvery young age. The physical findings in these boys
% n$ N; A" J Pwith this disorder are full pubertal development,
+ X' W/ D" L8 E" j0 e$ v- Oincluding bilateral testicular growth, similar to boys8 ~- V5 D: x6 M% X
with CPP. The gonadotropin levels in this disorder
+ z, G' ^ i' k5 Y7 a$ L1 V1 D+ ]& rare suppressed to prepubertal levels and do not show
# R( u/ ?2 X' K2 l' {. {pubertal response of gonadotropin after gonadotropin-3 r7 }# V2 x/ d% b' u# [$ O
releasing hormone stimulation. This is a sex-linked' @3 R! _9 D( g3 w1 k1 P
autosomal dominant disorder that affects only7 W- z4 t7 M! ~ e, M" P
males; therefore, other male members of the family: Q+ @; M+ c# y7 m5 t
may have similar precocious puberty.3
& W6 R/ n! O) C* M4 x [" g& dIn our patient, physical examination was incon-
- M, e# D p" Z+ b) V& R5 l% {sistent with true precocious puberty since his testi-. M& Q3 j6 t" O
cles were prepubertal in size. However, testotoxicosis0 n7 n4 ^2 ~8 Y# {
was in the differential diagnosis because his father
6 L- s0 }* S" E6 @started puberty somewhat early, and occasionally,. \' \2 ]( ~8 Z2 y M; |
testicular enlargement is not that evident in the
% S0 E0 n- N0 ^$ bbeginning of this process.1 In the absence of a neg-
- t. `0 K* b0 tative initial history of androgen exposure, our
1 q9 Q3 A, R: ?- j/ lbiggest concern was virilizing adrenal hyperplasia,
K( }5 e5 k1 h( L- geither 21-hydroxylase deficiency or 11-β hydroxylase
1 \2 q$ O/ Y/ \0 `0 i4 vdeficiency. Those diagnoses were excluded by find-
5 {" H+ N7 v2 H! r2 Wing the normal level of adrenal steroids.0 O( p6 h* d- I! |0 E. q
The diagnosis of exogenous androgens was strongly
. _2 L; B" O' Bsuspected in a follow-up visit after 4 months because' c% H5 n* F: Y5 W
the physical examination revealed the complete disap-
, e2 B! G5 j; O! d2 b/ B+ s* zpearance of pubic hair, normal growth velocity, and+ z* i& M2 w2 o* f2 }
decreased erections. The father admitted using a testos-
. n Q! j7 q, Aterone gel, which he concealed at first visit. He was* g* J4 t- s' q
using it rather frequently, twice a day. The Physicians’
% N8 R6 O' q) gDesk Reference, or package insert of this product, gel or
2 }1 N3 t! W2 }cream, cautions about dermal testosterone transfer to+ c* ?5 r2 E7 G) `& G# U/ ]
unprotected females through direct skin exposure.1 i2 h! u& F' G5 s' F& E
Serum testosterone level was found to be 2 times the% h* f, ]' k! K3 N Y
baseline value in those females who were exposed to
, V& _ z7 a' ?2 w# Zeven 15 minutes of direct skin contact with their male
$ ?, T5 H5 R2 U; F! R( @+ y7 S9 `partners.6 However, when a shirt covered the applica-6 P$ D5 X/ |4 C
tion site, this testosterone transfer was prevented.
+ X, I1 n8 w3 T; v- d% ZOur patient’s testosterone level was 60 ng/mL,/ A9 E2 \ r) F* y! f4 P
which was clearly high. Some studies suggest that
$ ~" r$ w; t6 k& ^% K4 e1 Sdermal conversion of testosterone to dihydrotestos-# J, y" b" Y& a' E3 X
terone, which is a more potent metabolite, is more0 M. {4 N: ?7 J, @6 d; l
active in young children exposed to testosterone
6 o: c L0 Y. _5 L: u1 l! @# aexogenously7; however, we did not measure a dihy-
, B2 ~2 x5 Q. t s$ Q6 Zdrotestosterone level in our patient. In addition to
* Z$ w; T9 G- K0 `virilization, exposure to exogenous testosterone in4 E( T; w: m, Z. r
children results in an increase in growth velocity and: H7 \7 @7 T; @, }6 ^
advanced bone age, as seen in our patient.9 |, \! `/ z ~9 q8 w) u/ \
The long-term effect of androgen exposure during6 \0 \% j0 t6 }2 d. B
early childhood on pubertal development and final# D8 R! I# H, @' Z% ?) p9 o/ P
adult height are not fully known and always remain$ s0 s" O% d* Z/ D' J, h' P& |
a concern. Children treated with short-term testos-
* w5 e; E0 F% {4 S1 Pterone injection or topical androgen may exhibit some
1 X: n6 z- w: W5 N3 D# Lacceleration of the skeletal maturation; however, after4 l4 E* S( d# q! z" q
cessation of treatment, the rate of bone maturation
( n, n% {1 b) ldecelerates and gradually returns to normal.8,91 A, c+ {6 g7 Y5 G+ w
There are conflicting reports and controversy
- y7 {" Z, G5 B1 t5 q0 i1 hover the effect of early androgen exposure on adult
) ]$ T* N6 K. J# {3 N( f, Tpenile length.10,11 Some reports suggest subnormal. }1 U' R7 a8 a) y8 X( [
adult penile length, apparently because of downreg-! U- G+ }# j s2 \, {
ulation of androgen receptor number.10,12 However,
! y0 w9 z3 G2 {& \/ W' p# nSutherland et al13 did not find a correlation between# z2 E" a& g9 M% s0 l. v3 y
childhood testosterone exposure and reduced adult, B" @! Z; X& j' F& e# H( ]
penile length in clinical studies.
- W5 b+ l0 g5 t- cNonetheless, we do not believe our patient is7 j+ _, d( X9 {4 b* F% F
going to experience any of the untoward effects from% f9 F1 f3 |9 e1 r1 a5 I0 R
testosterone exposure as mentioned earlier because
- `& l& I+ J; P& a. j0 cthe exposure was not for a prolonged period of time.9 e8 G8 m1 C* A5 N+ Q& ^
Although the bone age was advanced at the time of
. v( s8 f$ B4 Y' Odiagnosis, the child had a normal growth velocity at+ @5 A9 R0 L3 V0 v/ o
the follow-up visit. It is hoped that his final adult
6 W+ [! T/ V$ K1 `) o4 ^height will not be affected.: ]4 B' f( X5 B. n4 }
Although rarely reported, the widespread avail-
3 E- {. v h6 }ability of androgen products in our society may5 y2 F; p3 b0 N
indeed cause more virilization in male or female
! \1 f K. z# L3 ychildren than one would realize. Exposure to andro-
( _, E( j3 ]* u) L/ N( }gen products must be considered and specific ques-/ h; x( |3 T) ?9 X5 O5 o
tioning about the use of a testosterone product or
3 B& f' d+ D9 S2 y/ V; Agel should be asked of the family members during
% c7 h5 O' ` Z) v4 Z4 X) O) othe evaluation of any children who present with vir-2 Z9 |$ s5 }% w
ilization or peripheral precocious puberty. The diag-8 Z; Z* v5 `, r9 t5 O9 T2 _
nosis can be established by just a few tests and by z1 G$ y; \! a
appropriate history. The inability to obtain such a
' E/ x; x( ?, e0 k' mhistory, or failure to ask the specific questions, may
. W' x4 L/ m+ ~( _8 kresult in extensive, unnecessary, and expensive: I+ j/ ~& N1 b" D
investigation. The primary care physician should be+ h. s# |9 U3 Z- R
aware of this fact, because most of these children
$ g0 I; B6 V+ A" s. P% y2 ymay initially present in their practice. The Physicians’
+ N, ^! k( _. w( h5 l: \1 g4 ZDesk Reference and package insert should also put a0 T, ~. h6 k( ?4 A1 |
warning about the virilizing effect on a male or6 S) x+ \3 t( ]' H: F) n; x
female child who might come in contact with some-
" w" F. @ ^# k8 I6 gone using any of these products./ e. G1 ~' _% ^% c
References6 V: E7 p' w# H3 m" i' |
1. Styne DM. The testes: disorder of sexual differentiation/ k6 i0 o0 {9 f" f
and puberty in the male. In: Sperling MA, ed. Pediatric
/ d" W1 A& A2 _Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;- Q0 Q+ t! i k8 S5 w! m5 B( U6 u4 v. |
2002: 565-628.
G' R! f0 ]7 ~& s+ i% a* E2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious: j- l* c5 a0 ^7 ], O5 z8 B
puberty in children with tumours of the suprasellar pineal |
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