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Sexual Precocity in a 16-Month-Old+ ?4 [# e. ?3 c8 i
Boy Induced by Indirect Topical6 d- P" A: y5 Y0 ]" N8 l A! r
Exposure to Testosterone5 T& }7 F# q) Q1 l* X' Y9 d
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
" d1 ], D4 F2 Q% x( p6 W; M5 o+ n! Fand Kenneth R. Rettig, MD1
& V: S* n1 I6 u/ i% p# oClinical Pediatrics0 m6 v; m c+ m' @4 i; b2 m/ o: }
Volume 46 Number 61 @% [. R4 t: H( `$ u
July 2007 540-5431 l% B1 P3 p5 E( _% { D% N% X
© 2007 Sage Publications i, X9 C$ M0 k+ W# w7 N( o
10.1177/0009922806296651. b1 j( @) Z7 K( i: z) ?+ Q
http://clp.sagepub.com
J! x# W3 q7 D7 W3 s; O- \hosted at
" a* q4 x$ V$ f: \" @http://online.sagepub.com: q1 I2 \4 [& T( H& Z! O4 [$ p
Precocious puberty in boys, central or peripheral,
; [+ B0 V& d$ L9 ~is a significant concern for physicians. Central5 v8 ~3 i) i* G2 _# d9 |* j
precocious puberty (CPP), which is mediated' W6 c! p1 H, j0 v
through the hypothalamic pituitary gonadal axis, has
$ \. q" D% S h6 ga higher incidence of organic central nervous system0 L$ K! l7 q; \! T# R
lesions in boys.1,2 Virilization in boys, as manifested7 _9 R( e2 a! _
by enlargement of the penis, development of pubic
]; o' S& i! ~, r& p# V$ l$ u9 }5 mhair, and facial acne without enlargement of testi-/ `+ J, ~1 l R& K2 ?, A, D
cles, suggests peripheral or pseudopuberty.1-3 We
6 e0 K$ j, q, P$ n1 E' M* a! \report a 16-month-old boy who presented with the
* O% X( v: r1 F U1 Denlargement of the phallus and pubic hair develop-* e: ?7 a$ o2 n4 Z" S l
ment without testicular enlargement, which was due! K7 ?; w) g; Q& A( `9 R0 s% q
to the unintentional exposure to androgen gel used by7 t2 B* u6 Q1 k( s4 w4 ^
the father. The family initially concealed this infor-3 q1 N+ C$ c# S! `
mation, resulting in an extensive work-up for this
1 c* b) Q+ o8 m0 A/ w( N& ]child. Given the widespread and easy availability of# ?. D( f. j+ C0 H3 o- @2 G+ M, ]
testosterone gel and cream, we believe this is proba-
" |$ Y, s2 y4 @- g( F4 o" T; o; rbly more common than the rare case report in the3 J6 c4 f; f/ t3 ^
literature.47 S8 v6 l% ~( k
Patient Report- X/ D" I) Z* @* y
A 16-month-old white child was referred to the
$ y4 ?- y& o% ]. [3 K/ ^endocrine clinic by his pediatrician with the concern' \2 ?+ w7 o% u2 W
of early sexual development. His mother noticed7 ~% E0 t. s k* c( h& u9 s
light colored pubic hair development when he was$ h3 U, I0 z) I" Q" |# r% Z& l: V: Q
From the 1Division of Pediatric Endocrinology, 2University of9 W' q8 a0 U4 s3 L/ Y* _' j
South Alabama Medical Center, Mobile, Alabama.
; P2 I; X% S m# jAddress correspondence to: Samar K. Bhowmick, MD, FACE,
, P( k9 B. x( n$ H; R% `Professor of Pediatrics, University of South Alabama, College of
0 l4 [8 }6 Z; V- P* oMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;/ l: j" Z6 C6 l @0 X
e-mail: [email protected].
( N- ?: ~) \/ X7 s" d Wabout 6 to 7 months old, which progressively became
3 U* Y7 i' m+ w; ^& ldarker. She was also concerned about the enlarge-" |& B' }( b5 e( s
ment of his penis and frequent erections. The child
5 `( e$ v& Z4 @% r2 b1 K5 i, `was the product of a full-term normal delivery, with. n, q8 M" J0 A' R0 Q! q9 A
a birth weight of 7 lb 14 oz, and birth length of
- ]( m% {" N* g! ?. P20 inches. He was breast-fed throughout the first year5 h1 H3 }" Z' D1 i: B4 Z3 v
of life and was still receiving breast milk along with- ?; f) N! |6 G; }. c% W6 k. C
solid food. He had no hospitalizations or surgery,) K. \' f! l; ~ _% g0 C
and his psychosocial and psychomotor development- G% C4 l7 S# i" s, [
was age appropriate.; \# B3 Z* N2 M1 @" S* S+ t3 o
The family history was remarkable for the father,
) S( }; P( F& @0 F/ dwho was diagnosed with hypothyroidism at age 16,
$ }; f. i; x e3 p) e. ?. n: gwhich was treated with thyroxine. The father’s
9 i* ^1 x/ O) e/ T0 Bheight was 6 feet, and he went through a somewhat; F+ o- @! U) O$ ?" Y, ^8 }0 r
early puberty and had stopped growing by age 14.
: a! X+ Y0 C z+ }1 i- eThe father denied taking any other medication. The
% E, O( S! I# ?' q' n( V: ?child’s mother was in good health. Her menarche
. \0 P! X r! a! Ywas at 11 years of age, and her height was at 5 feet
4 E0 c- Y$ n2 \* E6 n. e5 inches. There was no other family history of pre-( J1 H# k3 }" [* z8 y5 q l
cocious sexual development in the first-degree rela-
9 H( x. E' s9 A& p, b; c% Z' Ltives. There were no siblings.
& l" x) M9 \4 w( V% hPhysical Examination
; E4 Q, I1 J) F/ GThe physical examination revealed a very active,
: k4 l$ H5 M6 _( X& s: dplayful, and healthy boy. The vital signs documented
) ?$ o- U. n+ [( Y7 D$ Da blood pressure of 85/50 mm Hg, his length was
! t2 L$ u; X, g0 g90 cm (>97th percentile), and his weight was 14.4 kg( O* A& t2 Q+ P$ c% U8 w( r# N5 Z$ h
(also >97th percentile). The observed yearly growth$ k5 E% h8 e" {, d9 r5 L
velocity was 30 cm (12 inches). The examination of
# p3 Q$ R: W4 K) n# |the neck revealed no thyroid enlargement.
7 l K# f3 m3 y6 P, W* ~The genitourinary examination was remarkable for7 G/ ?' S9 Z# |: b
enlargement of the penis, with a stretched length of
9 o" I/ n/ h! z$ i3 `0 Y3 Q3 t8 cm and a width of 2 cm. The glans penis was very well
3 u5 D) k6 T# M5 X |developed. The pubic hair was Tanner II, mostly around
/ B- _' W8 c7 X3 D540
* T- P, S0 L5 o* t5 U: Z1 Z( Mat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from( ]+ N, z8 ^7 U1 Z
the base of the phallus and was dark and curled. The
! P+ X# r" b" H1 ntesticular volume was prepubertal at 2 mL each.
' K' _7 m- V* _% r4 _The skin was moist and smooth and somewhat& M; E/ `6 `) X6 U
oily. No axillary hair was noted. There were no
! {# F- T/ d( t/ d8 }" B8 Dabnormal skin pigmentations or café-au-lait spots.- k/ O, O8 H1 h; k
Neurologic evaluation showed deep tendon reflex 2+- |" I* v Y- Q: \
bilateral and symmetrical. There was no suggestion
1 S4 F' l% P- j9 xof papilledema.; J" o9 ?0 e# \4 p
Laboratory Evaluation$ e, S# A8 \2 A! X4 {! y( K
The bone age was consistent with 28 months by
. N! L9 |$ |& \5 P3 kusing the standard of Greulich and Pyle at a chrono-" J, X! B- A) A1 N
logic age of 16 months (advanced).5 Chromosomal
6 ]4 Z" v3 F: x6 }karyotype was 46XY. The thyroid function test
; S/ P0 g, U% Q( zshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
4 I& S* O( C3 H" n, S. ilating hormone level was 1.3 µIU/mL (both normal)." g- ?/ i( K$ K2 ~9 c
The concentrations of serum electrolytes, blood$ B% D0 r0 o& Z6 n" X, N) o
urea nitrogen, creatinine, and calcium all were7 }9 d" ~+ l' ^1 U( k+ }! y, J
within normal range for his age. The concentration
6 o" z1 _3 ^1 w [of serum 17-hydroxyprogesterone was 16 ng/dL( A% O+ q" a, F/ u" V o! V( i/ Z
(normal, 3 to 90 ng/dL), androstenedione was 20% s1 v3 p' \( o- w9 k
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
4 O9 f; u, k/ Y! m+ z2 R. s1 K( Yterone was 38 ng/dL (normal, 50 to 760 ng/dL),
/ q5 @7 ]1 g% L/ Z, e# X2 ^: ]desoxycorticosterone was 4.3 ng/dL (normal, 7 to% G6 b. Y2 d1 _5 [. y: B
49ng/dL), 11-desoxycortisol (specific compound S)' J- ^! L! ]( t; O; y8 p7 F6 X+ u
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
# C' ]5 G9 M. u" \tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
% U! j( ?7 Q5 A& h: Ctestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
# o. j& x% ~0 Nand β-human chorionic gonadotropin was less than# t9 u9 ]" R; ]1 b# S; q
5 mIU/mL (normal <5 mIU/mL). Serum follicular) H/ [8 Z, T" x9 u/ w/ h
stimulating hormone and leuteinizing hormone
. [! h5 E, Z( {5 f K" gconcentrations were less than 0.05 mIU/mL' b% f, \6 F0 p% g
(prepubertal).
( z2 M1 A% H x8 R/ [The parents were notified about the laboratory
6 r( J3 p9 N( Fresults and were informed that all of the tests were" G5 L3 n/ A, u6 Z5 P$ d
normal except the testosterone level was high. The9 ~; m4 Q) s+ w3 d3 U+ o' [
follow-up visit was arranged within a few weeks to
% B" o3 @% C3 i. f: t3 ^) r0 |obtain testicular and abdominal sonograms; how-; T" V4 ^* V4 o' K7 Q
ever, the family did not return for 4 months.
6 L# q% }4 f% Y! j- D$ UPhysical examination at this time revealed that the: I8 M1 z+ ~5 ~$ t9 s1 a
child had grown 2.5 cm in 4 months and had gained
# h6 D8 J; D$ d7 L! L2 kg of weight. Physical examination remained
' B% v Y, N, t6 a7 i! _unchanged. Surprisingly, the pubic hair almost com-
/ U8 D" @6 D: F- X; U7 Ipletely disappeared except for a few vellous hairs at2 R4 H! R9 l# s4 c+ @" n( A
the base of the phallus. Testicular volume was still 2
0 d( Z% z# z$ T, T: h mmL, and the size of the penis remained unchanged.3 v* y9 h: `: M$ ?& r
The mother also said that the boy was no longer hav-( }' [7 G Y! f( ]3 r% K- o w' Y
ing frequent erections.0 p0 G" S" K/ I l7 ?+ D; m: g5 F% C
Both parents were again questioned about use of
& l) |* P$ {4 Cany ointment/creams that they may have applied to- v& ?0 b- ]' m8 Y. p
the child’s skin. This time the father admitted the
: l6 v. y2 Q+ W+ ]+ F9 YTopical Testosterone Exposure / Bhowmick et al 5412 M( d4 a- H! D' Z' g+ C1 f
use of testosterone gel twice daily that he was apply-
^3 X8 R& ]9 R( F* iing over his own shoulders, chest, and back area for
( m7 [8 {7 i* R8 L" Aa year. The father also revealed he was embarrassed
4 y& b6 f, ~# v& Dto disclose that he was using a testosterone gel pre-
9 K$ F' i: H( | }# ~scribed by his family physician for decreased libido
( e# b+ n/ a( b; o. ^: a1 W- n8 zsecondary to depression.
$ b6 t' s8 n: b! WThe child slept in the same bed with parents.' J: W3 X9 Z, z& O z( c* d% `0 q2 B
The father would hug the baby and hold him on his, }+ i: n. n& y0 q
chest for a considerable period of time, causing sig-
8 i; {1 e0 Y6 } q- e: m" fnificant bare skin contact between baby and father.$ i" o4 u, B5 n7 z
The father also admitted that after the phone call,
4 j5 b$ p% i) z& A6 y. u% U5 R5 ]when he learned the testosterone level in the baby
0 i+ A- C8 L: k6 ?( U5 Y8 }" Cwas high, he then read the product information9 Z9 \4 U+ x: @% e9 g) t# I
packet and concluded that it was most likely the rea-
[3 ]2 [% M' b; p6 Yson for the child’s virilization. At that time, they
u+ R6 I1 D* b+ \+ ]( Xdecided to put the baby in a separate bed, and the# q2 N5 o! h) v1 c0 D
father was not hugging him with bare skin and had8 [6 N7 w# y3 d7 @3 K
been using protective clothing. A repeat testosterone* J5 G8 ~" k- E$ I; l/ N& n0 G6 ]
test was ordered, but the family did not go to the
% l8 |8 s, ]1 V! B4 G0 U1 {0 Zlaboratory to obtain the test.6 H) b4 F1 b% Z' s- N) C* a: O* _' U
Discussion1 d+ D4 R$ Q' R
Precocious puberty in boys is defined as secondary8 v2 e8 l4 t! p" q
sexual development before 9 years of age.1,4
; w0 k% [) R/ t; Z% t& R( ePrecocious puberty is termed as central (true) when
3 O2 X/ W3 Z8 E! P" n- _it is caused by the premature activation of hypo-0 b6 T# b3 |/ A. e) K9 ^9 r, u( Y$ }
thalamic pituitary gonadal axis. CPP is more com-: i3 C* W1 W" m5 U, l4 o
mon in girls than in boys.1,3 Most boys with CPP
+ D3 { n* c% x( Smay have a central nervous system lesion that is
+ c& W" {" Q% {6 R# {+ Jresponsible for the early activation of the hypothal-
0 P' [% C& {4 @amic pituitary gonadal axis.1-3 Thus, greater empha-
& s. h5 K" h& H+ g# B% F) W% z3 ksis has been given to neuroradiologic imaging in, z5 Y6 D0 }7 U- d1 V: N
boys with precocious puberty. In addition to viril-5 d x- j. B# @- |3 l
ization, the clinical hallmark of CPP is the symmet-
2 k. Q1 }% q+ b8 |' Y! Crical testicular growth secondary to stimulation by
/ |* n( h2 b% v, Dgonadotropins.1,3
* w u! R4 d" L; ]/ b, y, E) SGonadotropin-independent peripheral preco-6 t( {* i2 Y" m- V
cious puberty in boys also results from inappropriate
8 X H1 k+ A# g% d2 Randrogenic stimulation from either endogenous or
& P, i& n1 A1 h9 L2 Vexogenous sources, nonpituitary gonadotropin stim-
; [% _7 E" M9 S9 v9 n+ S* wulation, and rare activating mutations.3 Virilizing
" r! I y" K6 d( J. B# Bcongenital adrenal hyperplasia producing excessive9 X- }( P& a1 J5 ]& M) A+ V5 l. l) E
adrenal androgens is a common cause of precocious1 E% {5 C; s1 l( y
puberty in boys.3,4
5 F8 C% _% D& A# z, v0 M/ GThe most common form of congenital adrenal3 ]# E2 k0 `6 u& L3 D6 r j
hyperplasia is the 21-hydroxylase enzyme deficiency.! [$ I% q7 q* N: C! g, g E
The 11-β hydroxylase deficiency may also result in
. M+ V5 S& L& I# M. ?# vexcessive adrenal androgen production, and rarely,0 R* I! @' Q" N2 [# w- x1 s# c$ N( r
an adrenal tumor may also cause adrenal androgen6 j; E+ g0 l5 |- U5 l4 O
excess.1,3
: S1 E- U/ {/ G% [at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
. W) N% H! O3 S) T- y: [542 Clinical Pediatrics / Vol. 46, No. 6, July 20074 V$ g: G8 ~0 r; y
A unique entity of male-limited gonadotropin-
) t; f' F' h0 Findependent precocious puberty, which is also known' u7 A0 Y! g1 |: j* ^4 o& A
as testotoxicosis, may cause precocious puberty at a
x! b3 [* \9 Mvery young age. The physical findings in these boys% M: _* q- ?: l9 F
with this disorder are full pubertal development,
6 |/ z7 U( a! F& ^4 S5 oincluding bilateral testicular growth, similar to boys, s3 H* L9 v! Z; W5 j3 N
with CPP. The gonadotropin levels in this disorder
* Q& { u+ h# Q$ N9 e4 j& aare suppressed to prepubertal levels and do not show
0 Z6 m* a# m. w9 E1 ipubertal response of gonadotropin after gonadotropin-# v: B$ e: x: } h- d
releasing hormone stimulation. This is a sex-linked
& C8 h$ d% S8 F- s0 W# Xautosomal dominant disorder that affects only' A0 P, O2 o: t' `- X/ K
males; therefore, other male members of the family
" r- k0 Q8 _9 ^( C: E( B* U" T" X8 g+ r: Wmay have similar precocious puberty.32 \# X. `9 g* @
In our patient, physical examination was incon-
& G% k- o% w' f' gsistent with true precocious puberty since his testi-/ A, ?4 y' H! P! Y2 O- T+ q
cles were prepubertal in size. However, testotoxicosis
6 B- M5 o# D1 L: ^ g* A* G" `was in the differential diagnosis because his father( Q/ M* {/ G6 j) m1 G! i
started puberty somewhat early, and occasionally,
6 ]0 H: K- [# e8 }testicular enlargement is not that evident in the
' f0 Y- o: `+ A4 ]beginning of this process.1 In the absence of a neg-
6 w- S) B% z/ P0 B/ ^ ?( gative initial history of androgen exposure, our
/ m5 g* A9 _) zbiggest concern was virilizing adrenal hyperplasia,
- q" z" z# K) W8 g9 t! xeither 21-hydroxylase deficiency or 11-β hydroxylase
B( g# G3 s2 ^1 \ Fdeficiency. Those diagnoses were excluded by find-
z/ Q' W8 u) zing the normal level of adrenal steroids.
8 v+ s! h9 `& Q5 K9 b" Z+ S; yThe diagnosis of exogenous androgens was strongly
: q- O% V1 Z7 G+ Tsuspected in a follow-up visit after 4 months because" w: K. Y" w6 ^: K% I
the physical examination revealed the complete disap-( i( b0 i- x. V3 c3 H. F
pearance of pubic hair, normal growth velocity, and% Q- J% d7 i6 N' n8 _/ u
decreased erections. The father admitted using a testos-
/ i S* }! _' oterone gel, which he concealed at first visit. He was
7 I! H2 s# _) N* I2 rusing it rather frequently, twice a day. The Physicians’
- j' d3 ~5 m$ y# \Desk Reference, or package insert of this product, gel or7 g9 `2 [* h8 u2 Q* J x6 g% m6 ]
cream, cautions about dermal testosterone transfer to3 {# g( S$ {$ _: x7 ~6 K1 z( a
unprotected females through direct skin exposure.% c( w. F' \- M' x( R& c- r4 R
Serum testosterone level was found to be 2 times the
8 I% A- ]; e0 e# S j( S! T& wbaseline value in those females who were exposed to9 a& n0 ?5 F& I8 p# V" @2 F' ]: q
even 15 minutes of direct skin contact with their male
# f1 L0 ?1 R% mpartners.6 However, when a shirt covered the applica-8 [7 {0 a* b: t( g
tion site, this testosterone transfer was prevented.) u# s/ j& K: q: h$ o+ M& L
Our patient’s testosterone level was 60 ng/mL,) j- r. i! s1 R. m6 G! _
which was clearly high. Some studies suggest that3 M* }; _1 p( C" |7 F
dermal conversion of testosterone to dihydrotestos-; J9 k' v* \+ y* Q4 @. j) d) j
terone, which is a more potent metabolite, is more" d* V; S+ e4 N. ~# {$ n5 a' v
active in young children exposed to testosterone' Y8 l1 v& G7 `
exogenously7; however, we did not measure a dihy-
: o( u% z5 @# d$ x7 e; y0 ]drotestosterone level in our patient. In addition to" Z1 n3 c$ j; _! |6 j
virilization, exposure to exogenous testosterone in
5 l% Q0 q- M- k9 \" |children results in an increase in growth velocity and
0 U7 H4 \( `0 r& r& |advanced bone age, as seen in our patient.2 ~6 V) N! w, v$ S
The long-term effect of androgen exposure during8 {. {* \! H3 t; m1 B8 f
early childhood on pubertal development and final" {- h: G5 {0 c0 O- r& O
adult height are not fully known and always remain
. |: p4 I d8 @% E1 F8 Na concern. Children treated with short-term testos-
/ [$ [( s o4 d% }3 G# aterone injection or topical androgen may exhibit some) H8 s- T- t" N
acceleration of the skeletal maturation; however, after
3 r9 \0 M5 r; g" ?* {cessation of treatment, the rate of bone maturation$ y) B0 z* b! |- ]- p
decelerates and gradually returns to normal.8,9
2 [( H* h. Q8 I+ rThere are conflicting reports and controversy3 \& b' j, T [3 r. g1 l/ p9 c: c
over the effect of early androgen exposure on adult) ?; K4 e' V/ v9 v
penile length.10,11 Some reports suggest subnormal* X0 I* s( V) {# F
adult penile length, apparently because of downreg-! M) z+ Y- }. ?: O9 B3 x! F
ulation of androgen receptor number.10,12 However,
3 I( I& Q9 G5 H H3 SSutherland et al13 did not find a correlation between
2 ~. N m4 A. \" W/ s+ e/ zchildhood testosterone exposure and reduced adult z2 t/ @1 T; x1 p, p
penile length in clinical studies.
7 b- o- v0 U: X; E' b7 ONonetheless, we do not believe our patient is, @* Z+ l" T/ T
going to experience any of the untoward effects from7 B2 J1 `3 y5 A
testosterone exposure as mentioned earlier because+ L2 Q7 L1 i. D: ^
the exposure was not for a prolonged period of time.
) ]$ ~" i- D) {4 qAlthough the bone age was advanced at the time of/ M% r4 y7 N' k! B* w
diagnosis, the child had a normal growth velocity at; w# m% C- t% _6 J$ O
the follow-up visit. It is hoped that his final adult
' B. H1 F3 Z0 gheight will not be affected.5 s+ @9 r, E5 N( A% a
Although rarely reported, the widespread avail-. t- g1 E: U* Z9 J: O; H, ^# `0 p
ability of androgen products in our society may
6 z* a1 L( Y. Q* Q! [- xindeed cause more virilization in male or female# _7 H. a& F9 w, \1 z1 E
children than one would realize. Exposure to andro-
2 `6 e+ I$ E% L7 ^+ K: u7 s2 ^gen products must be considered and specific ques-5 I; ~! R% Y0 W
tioning about the use of a testosterone product or2 h/ d) {) }5 i( t
gel should be asked of the family members during
+ \; z" Z" X9 dthe evaluation of any children who present with vir-9 C- ^' z& \8 V R0 N
ilization or peripheral precocious puberty. The diag-
1 z( d3 t8 f; inosis can be established by just a few tests and by
9 x* G5 i1 B$ e9 Z2 Lappropriate history. The inability to obtain such a5 |# ?9 T3 P- ]' E/ L
history, or failure to ask the specific questions, may* Y, W- d/ ?' I5 ~: w- x! b/ J% c5 \
result in extensive, unnecessary, and expensive0 o. D4 t! C$ k" J+ o) k
investigation. The primary care physician should be
! ^7 \/ w6 N$ B) B, Uaware of this fact, because most of these children
! ^3 \" h" z! @5 }may initially present in their practice. The Physicians’0 \+ L, H% v9 }
Desk Reference and package insert should also put a( u0 E, {: M+ }" L* {5 B2 d
warning about the virilizing effect on a male or
' a# H1 V' n! h1 T3 v$ W1 n* o5 s2 Cfemale child who might come in contact with some-
( B# a* e& H# w0 m" ^5 Eone using any of these products.6 v$ M# Y) Z! p7 _0 K
References
, j0 A* c5 ^0 K4 F1. Styne DM. The testes: disorder of sexual differentiation
/ g4 S1 m9 k) {and puberty in the male. In: Sperling MA, ed. Pediatric
/ Q5 c9 C: z! g( p6 h$ gEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
/ \9 z K* r& i a8 q$ p r& \2002: 565-628.$ |3 g. U; a! v2 Y2 `8 i9 R0 P" e* V2 Y
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious; v) `) [8 d( m+ w1 F" Z: _
puberty in children with tumours of the suprasellar pineal |
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