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Sexual Precocity in a 16-Month-Old
" P2 h2 }7 c! _# I2 }5 \" S% D' W0 lBoy Induced by Indirect Topical
) z% s! ^6 _+ u! c+ E5 j( d8 ZExposure to Testosterone
) |, k M/ {9 e# t* [7 S- ]4 ?Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
, H1 w5 Y3 H1 \( x8 nand Kenneth R. Rettig, MD1# P" d/ ?4 F% D; s3 q, W6 E; u
Clinical Pediatrics
+ P" z" d( t+ c, f/ g% G; k( z2 bVolume 46 Number 6# S Q* _5 G9 s, ~9 J( Z) t- Q- {
July 2007 540-543
# N! E4 Z5 i! u8 _5 T© 2007 Sage Publications6 @1 P2 o: N) r; u3 j+ J' E) R; }6 m# ^
10.1177/0009922806296651$ N* F3 T# M2 u0 G% E I
http://clp.sagepub.com, f. g( n! [1 i# G. \! ~. j
hosted at3 H9 U# j3 v+ g0 L/ A
http://online.sagepub.com, S7 f o2 q. k3 O( K# r# P
Precocious puberty in boys, central or peripheral,) h, c2 y4 e0 k6 R8 J
is a significant concern for physicians. Central
0 w2 J8 r) C/ Q" E/ y4 cprecocious puberty (CPP), which is mediated5 y4 X& [1 p/ Z7 g
through the hypothalamic pituitary gonadal axis, has
; {8 ^5 E) l6 [6 }& va higher incidence of organic central nervous system
. ~, M% i/ i% n- i5 e$ klesions in boys.1,2 Virilization in boys, as manifested
: q; A) s L/ H. J J# P% ?( lby enlargement of the penis, development of pubic6 t0 G3 |' J! Y/ `; f1 Q9 H
hair, and facial acne without enlargement of testi-3 P' U1 F5 D/ s$ R
cles, suggests peripheral or pseudopuberty.1-3 We" T; W! r0 K3 G3 w
report a 16-month-old boy who presented with the w# M6 V) M9 n; p5 ^1 g
enlargement of the phallus and pubic hair develop-
7 f; \2 A5 ]7 N. O5 o6 U5 E0 wment without testicular enlargement, which was due
! C& H8 `( [! ]% pto the unintentional exposure to androgen gel used by( i2 L4 Q, t7 k
the father. The family initially concealed this infor-1 z/ ^! p8 k; ?, I% N
mation, resulting in an extensive work-up for this, Q/ w1 z/ \0 y6 N1 y
child. Given the widespread and easy availability of
; D) x& E$ E9 z# ^+ ?/ U g5 H) @testosterone gel and cream, we believe this is proba-6 j& x. m/ [) ?8 T* t, r( U# b$ |
bly more common than the rare case report in the/ s- n! {* o2 q) B7 R
literature.4
: U& l! P4 [! Q3 G. f- EPatient Report2 J. x& l/ i0 r/ b/ f
A 16-month-old white child was referred to the
% R' f! G3 K+ G7 L% nendocrine clinic by his pediatrician with the concern
, W% o9 ?6 d' g, |! s% i: eof early sexual development. His mother noticed+ y2 L* e1 k( ^
light colored pubic hair development when he was
/ M8 x. t5 C, q$ H- v% D) ~From the 1Division of Pediatric Endocrinology, 2University of
, b* j7 _$ [9 M$ V/ R, ASouth Alabama Medical Center, Mobile, Alabama.
/ E( r$ R* \. [9 oAddress correspondence to: Samar K. Bhowmick, MD, FACE,
; Y& @) D; @# ]2 L# p- n oProfessor of Pediatrics, University of South Alabama, College of
# E9 N; u F" c/ @: {% a8 QMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;+ L( q1 D5 O) V+ z% S
e-mail: [email protected].
8 {7 E o' {7 x' ?about 6 to 7 months old, which progressively became
8 d7 _" \9 Z7 u% t8 i$ w; m5 udarker. She was also concerned about the enlarge-, l! V: f1 {5 R; n6 k* T
ment of his penis and frequent erections. The child
, _6 g S. q: n4 uwas the product of a full-term normal delivery, with$ C6 y6 J. v. {1 g5 X
a birth weight of 7 lb 14 oz, and birth length of/ I1 y I/ m0 H) y! W1 ~
20 inches. He was breast-fed throughout the first year8 d* `+ l H/ X& a( `( ^/ e
of life and was still receiving breast milk along with
# \, [6 ~, L; I' esolid food. He had no hospitalizations or surgery,
- T" _* t) |* w/ i. W' {and his psychosocial and psychomotor development. L) c, G6 m" v! `, R
was age appropriate.0 ]$ v* t- P& H1 W$ m$ P
The family history was remarkable for the father,5 @0 ~) {' i( P9 e4 d4 [% F
who was diagnosed with hypothyroidism at age 16,+ S2 }: K4 Y7 X& A7 p& O8 q
which was treated with thyroxine. The father’s: h1 y4 W% A3 T: a$ B* q
height was 6 feet, and he went through a somewhat% t/ n2 X# i/ X5 m
early puberty and had stopped growing by age 14.- l6 b2 Z+ L4 L* `8 G5 _
The father denied taking any other medication. The4 w0 Y( ~4 @8 O: @# j% z
child’s mother was in good health. Her menarche
' m$ f' ]/ y, [9 d: O1 fwas at 11 years of age, and her height was at 5 feet
y, O( U& I: W% s; G$ e0 ~5 inches. There was no other family history of pre-% a& ~- m" q+ _& s4 E1 v; {8 z
cocious sexual development in the first-degree rela-
. A& C& \9 Z: ttives. There were no siblings.
1 C- K9 v5 T M. d" V" NPhysical Examination
% z+ r- j+ G- U1 BThe physical examination revealed a very active,
; I, c8 |" t( Z. Gplayful, and healthy boy. The vital signs documented
" b8 {. X+ V6 a {a blood pressure of 85/50 mm Hg, his length was
2 ]& L% i% |. m90 cm (>97th percentile), and his weight was 14.4 kg7 I) F# F' x1 w& S# c# j
(also >97th percentile). The observed yearly growth( ]+ ^% ]* v) y% ?0 E9 R% q
velocity was 30 cm (12 inches). The examination of
- q! F8 M8 e+ r& P5 }the neck revealed no thyroid enlargement.8 J4 b9 Z2 P9 ~
The genitourinary examination was remarkable for \# [% l. |8 c& B
enlargement of the penis, with a stretched length of4 N$ B9 X9 e7 V( E l# e$ t/ x
8 cm and a width of 2 cm. The glans penis was very well
1 e/ ~" X0 j, _0 q: t, P: Qdeveloped. The pubic hair was Tanner II, mostly around
- q9 ~0 F+ {" f% j2 |; u. E) e540
0 U5 G) w( B$ E8 [ R3 eat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from m# M2 e& W1 D( M8 g7 h
the base of the phallus and was dark and curled. The B9 Y+ C/ w% O3 D" \ r; `0 H
testicular volume was prepubertal at 2 mL each.4 Z+ ]5 g, N, z+ O+ H" ~( B
The skin was moist and smooth and somewhat) e" I* d# r. J% G; q9 s% }& I
oily. No axillary hair was noted. There were no3 Z+ J, P4 }( N( H
abnormal skin pigmentations or café-au-lait spots.% R$ ^( g) ~: I9 S& a! v
Neurologic evaluation showed deep tendon reflex 2+
. i! s3 F8 w5 C8 W0 b+ Y: M% Ubilateral and symmetrical. There was no suggestion, j% U" I( c! K" h% H! Y
of papilledema.7 i. N% C5 j; L; ~4 j( w# `( x
Laboratory Evaluation
, |4 k5 {# U' w- g0 [The bone age was consistent with 28 months by/ h2 @* p3 o* V# [- m5 f% X
using the standard of Greulich and Pyle at a chrono-
1 _" G5 r1 G8 l4 i' |/ Plogic age of 16 months (advanced).5 Chromosomal
' b3 ~' s/ Y) y/ Ukaryotype was 46XY. The thyroid function test' U J- U2 M" V+ s
showed a free T4 of 1.69 ng/dL, and thyroid stimu- i" f4 H5 s$ V H& k7 E1 j
lating hormone level was 1.3 µIU/mL (both normal).
% J0 f0 _! n7 r3 L5 eThe concentrations of serum electrolytes, blood
, i. g% U( m5 _& Uurea nitrogen, creatinine, and calcium all were+ N6 W7 R' T* c3 F% u) N/ a
within normal range for his age. The concentration
7 S# j, r' C! U" j# @" S1 g# Eof serum 17-hydroxyprogesterone was 16 ng/dL: ]1 q6 J- x* _6 K' ]* J _
(normal, 3 to 90 ng/dL), androstenedione was 20
) Y% f. j5 l2 V2 R f1 p9 Ung/dL (normal, 18 to 80 ng/dL), dehydroepiandros-+ p$ @7 @6 }# ~
terone was 38 ng/dL (normal, 50 to 760 ng/dL),7 o! w2 }0 y4 v: d5 a8 ^7 ]+ i
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
# [9 H5 c4 n. v49ng/dL), 11-desoxycortisol (specific compound S)
6 C9 B- L: h6 a4 }/ g; E) dwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-, G- ?9 ~: h% }8 W
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total# y% E! C' l0 r0 ~5 e3 O
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
* V7 `5 y( J, l+ x) ?and β-human chorionic gonadotropin was less than
# }1 e: Q/ q5 ~ g5 mIU/mL (normal <5 mIU/mL). Serum follicular3 ^' Z# n/ u! j6 ~+ I8 t
stimulating hormone and leuteinizing hormone
" S) \8 s! y3 zconcentrations were less than 0.05 mIU/mL
& v" v! _! z4 w5 H. z( w(prepubertal).
( c' E5 q' M, s7 _. bThe parents were notified about the laboratory
. l% k5 I( K7 u; s( o+ qresults and were informed that all of the tests were
9 E2 U& M1 I; n9 ?! l, Knormal except the testosterone level was high. The* C2 R. d$ ?' X' P6 p" e
follow-up visit was arranged within a few weeks to
3 V9 A$ d' h7 R' E& q4 }obtain testicular and abdominal sonograms; how-2 @! B1 y( q) K; y! [
ever, the family did not return for 4 months.) Q( l5 a# E7 U! ~
Physical examination at this time revealed that the$ `' K6 g, O7 o3 U1 l
child had grown 2.5 cm in 4 months and had gained
8 u. B6 h! a9 [" ?: ?2 kg of weight. Physical examination remained* f$ B/ ^9 z: u/ ]* ]. f
unchanged. Surprisingly, the pubic hair almost com-
6 S+ K# l2 O. K- |6 j- v- ]pletely disappeared except for a few vellous hairs at+ }$ p: P; P7 X
the base of the phallus. Testicular volume was still 2/ | r. B! a6 y; ?. K( a
mL, and the size of the penis remained unchanged.- g( ]2 i$ P6 u! D) C4 E- A6 |# ^
The mother also said that the boy was no longer hav-) ^3 f4 @) V) w( z$ ~
ing frequent erections.
0 g" G) M! S t( W( }7 ~Both parents were again questioned about use of" K: [% O2 p" _# e; }
any ointment/creams that they may have applied to; D% Z1 t# G* w8 S' o
the child’s skin. This time the father admitted the+ \8 h2 V1 j" d
Topical Testosterone Exposure / Bhowmick et al 5410 ~5 W P8 W5 D* H
use of testosterone gel twice daily that he was apply-0 C3 q0 [$ I9 s- F$ f, v) m
ing over his own shoulders, chest, and back area for$ {6 k2 a e; x& f. P1 c& ?) T
a year. The father also revealed he was embarrassed. c* p) U% d: V' I* u/ x, Z: ?$ O
to disclose that he was using a testosterone gel pre-
# Q0 Z" ]. _9 o/ l1 Wscribed by his family physician for decreased libido) ^+ ]; R9 T9 o7 s) W" z0 Y8 Z
secondary to depression.
" m1 \. I5 u s/ YThe child slept in the same bed with parents.
0 v0 X( h. c* h5 `. I+ S* X$ Z! ]- l/ ZThe father would hug the baby and hold him on his6 W3 J: e7 k6 y/ t3 D
chest for a considerable period of time, causing sig-* h" X# O* N3 w0 ]6 V# N: x' Y
nificant bare skin contact between baby and father.
" C+ t9 F: s3 X( v1 E4 `9 C3 nThe father also admitted that after the phone call,
$ _6 Q; t+ C* b" m0 s8 Cwhen he learned the testosterone level in the baby
8 ~$ z# H/ o- M7 U: W/ E, Zwas high, he then read the product information
. u' {: C0 f+ H2 G tpacket and concluded that it was most likely the rea-
! @2 w0 | o7 A0 E3 v: Rson for the child’s virilization. At that time, they' j8 u M0 T9 |' F; ^9 k/ B
decided to put the baby in a separate bed, and the
# r j" A! r% Vfather was not hugging him with bare skin and had+ q- @7 }' F9 l- d* l
been using protective clothing. A repeat testosterone3 v: ]' N1 o: X$ h7 p5 b2 r6 r
test was ordered, but the family did not go to the8 P' Y4 b$ e5 Z
laboratory to obtain the test.% n i; V" B5 M
Discussion
$ i6 D, S- T0 ~Precocious puberty in boys is defined as secondary" w1 Q3 s0 j& [, `) i. J. N
sexual development before 9 years of age.1,4
9 P3 T" q' }1 t6 J: c/ e# H$ W9 ~4 PPrecocious puberty is termed as central (true) when8 k/ [- \- D: ? m8 I' Y1 T9 S \
it is caused by the premature activation of hypo-* \4 y4 U1 J$ s3 X; a# K `
thalamic pituitary gonadal axis. CPP is more com-( b1 f4 `' \! r* i! k; D7 ~
mon in girls than in boys.1,3 Most boys with CPP% } b8 y8 r! R- t# r2 r
may have a central nervous system lesion that is4 N1 j7 S) _; @3 y' E3 q4 \
responsible for the early activation of the hypothal-( o! _. j& ?' w9 Q- h- n! y
amic pituitary gonadal axis.1-3 Thus, greater empha-; A$ r! h* Q" B: ~
sis has been given to neuroradiologic imaging in" D# p4 b+ o- o7 H3 C& M+ A
boys with precocious puberty. In addition to viril-6 k& ]" `/ f7 c! R: I
ization, the clinical hallmark of CPP is the symmet-5 }; i M& Y! a- X5 O* I5 s; P
rical testicular growth secondary to stimulation by- S. C* r2 N0 n" V6 z1 g
gonadotropins.1,3
6 c1 v, x4 S3 |5 a( ~2 ?1 Y1 SGonadotropin-independent peripheral preco-
& v# i* z0 i( v9 h K* C& F; ocious puberty in boys also results from inappropriate# _" y' w( A8 _
androgenic stimulation from either endogenous or
0 l7 V6 A/ }9 x3 l# u1 |9 xexogenous sources, nonpituitary gonadotropin stim-
- d; x3 n0 I* U* F2 S9 Q! fulation, and rare activating mutations.3 Virilizing
$ v; ?2 X; k4 ^$ _& ]3 y, l$ ?congenital adrenal hyperplasia producing excessive/ P3 |8 k6 p/ K c# x) y
adrenal androgens is a common cause of precocious9 h% \8 H _0 V; p
puberty in boys.3,4
" ?9 m+ n# b5 m/ t$ fThe most common form of congenital adrenal
4 q% W. q9 {. e x E, D4 ehyperplasia is the 21-hydroxylase enzyme deficiency.' J+ r4 f i& b5 q; E+ T$ \5 Z7 u! n
The 11-β hydroxylase deficiency may also result in
+ }4 f* z3 ^. M4 q( O1 rexcessive adrenal androgen production, and rarely," c8 ?1 [% h! \; n/ B) @: k/ l" l
an adrenal tumor may also cause adrenal androgen" r; k* ^4 b+ Q- \# ~. ?5 l
excess.1,35 Y/ Z9 x8 E) n) [* {1 a4 s
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
5 M+ g* I5 [8 C4 i542 Clinical Pediatrics / Vol. 46, No. 6, July 20078 m. Q0 B7 x9 ^7 d {' w. Z" H4 y6 ]
A unique entity of male-limited gonadotropin-
$ N/ t5 y5 _% z8 i' vindependent precocious puberty, which is also known- l! Z) K4 v+ E9 l5 J
as testotoxicosis, may cause precocious puberty at a
" W1 g8 B7 f- f4 a3 E; `/ O8 qvery young age. The physical findings in these boys
. M$ U& Y, V( h3 a. a: ?with this disorder are full pubertal development,
: H d) `& u+ o" i$ r/ q/ [% F* K+ iincluding bilateral testicular growth, similar to boys1 y. Q" }$ h, _; f* a
with CPP. The gonadotropin levels in this disorder; H5 M' D5 q/ v# G9 c" `; O! j# y
are suppressed to prepubertal levels and do not show
% l) C- Q( e7 @+ z2 U# n5 W: fpubertal response of gonadotropin after gonadotropin-
- ~( K* W% Y+ A) f7 f* hreleasing hormone stimulation. This is a sex-linked- _5 Y3 A. C% N, J/ k
autosomal dominant disorder that affects only( D8 ^" z: F) ~# u! W, U. s
males; therefore, other male members of the family' o6 c" e! r t; s' @
may have similar precocious puberty.3
6 {, M& D8 B# dIn our patient, physical examination was incon-
& D; v/ \6 E. V5 Y! Isistent with true precocious puberty since his testi-" N, V) S" o& M f
cles were prepubertal in size. However, testotoxicosis
5 Q7 L- A5 i1 k- C4 ?, y! k! ~was in the differential diagnosis because his father
; Z+ G% S0 j/ \4 X: S3 mstarted puberty somewhat early, and occasionally,
7 T( E5 {$ f2 M4 S' ?0 S1 F; ntesticular enlargement is not that evident in the9 I# |: a$ A9 ~3 A
beginning of this process.1 In the absence of a neg-1 l- {/ K& u' u' Z! N6 a* t
ative initial history of androgen exposure, our
6 v0 X% ^9 O5 _" S& ?biggest concern was virilizing adrenal hyperplasia,5 E1 B+ T. r% P/ p
either 21-hydroxylase deficiency or 11-β hydroxylase
# O$ g; O0 h2 W' m9 U) B1 P. Rdeficiency. Those diagnoses were excluded by find-
8 G0 o* j. A' K( M+ L# Ping the normal level of adrenal steroids.8 N- B @( ]9 I/ ^" [' \. p
The diagnosis of exogenous androgens was strongly. ^+ X( ^, u; P
suspected in a follow-up visit after 4 months because
/ k( o. p: N) p; Othe physical examination revealed the complete disap-: Y. \$ I7 O6 p8 [
pearance of pubic hair, normal growth velocity, and: V' D+ Z. b! O( R
decreased erections. The father admitted using a testos-
3 `/ z) c5 f) t7 z: q: _& P. \terone gel, which he concealed at first visit. He was
" [$ ~% W* d0 a1 q. Gusing it rather frequently, twice a day. The Physicians’+ m2 k. w2 h# t; x6 U
Desk Reference, or package insert of this product, gel or
0 z3 V5 g: y/ v4 Q/ K& X& l- Jcream, cautions about dermal testosterone transfer to
; G- y& a/ \8 runprotected females through direct skin exposure.
, ?) x$ s' v, L6 `& D3 ZSerum testosterone level was found to be 2 times the
, M6 W/ }5 B% [6 F5 sbaseline value in those females who were exposed to7 }3 ~. N1 ?$ W! \
even 15 minutes of direct skin contact with their male- G* [8 v9 V9 V/ C7 |: x$ z
partners.6 However, when a shirt covered the applica-1 p \1 O1 [( |3 b% f% G5 j
tion site, this testosterone transfer was prevented./ G/ [9 i d; u0 j, h
Our patient’s testosterone level was 60 ng/mL,
$ ]* E! r* D3 l; J% y5 [1 X% vwhich was clearly high. Some studies suggest that
9 w; v, z+ t' E& _3 B+ ~dermal conversion of testosterone to dihydrotestos-
( t9 ]9 c" Y7 D& Hterone, which is a more potent metabolite, is more
% j3 o8 U8 |& q; Lactive in young children exposed to testosterone2 p* R2 J4 l$ h3 r( _# ^2 G
exogenously7; however, we did not measure a dihy-8 @( L4 h& b! Y' Q4 I4 g
drotestosterone level in our patient. In addition to
" |6 k: c' y0 K% O9 Avirilization, exposure to exogenous testosterone in
# i6 p. T j! a' t$ achildren results in an increase in growth velocity and
1 l% A4 x! y8 vadvanced bone age, as seen in our patient.
: V( @8 o# c2 S, ]The long-term effect of androgen exposure during
# ?$ i- ~. W5 E$ a! Fearly childhood on pubertal development and final
; J; |) w/ z2 N" R" r6 Yadult height are not fully known and always remain
- U6 S' E V* T) H7 } ?/ pa concern. Children treated with short-term testos-. A5 K! i: H- f7 Q1 ~" F
terone injection or topical androgen may exhibit some
/ M X* \$ F, A% Wacceleration of the skeletal maturation; however, after6 k- f* c6 i# {* s+ n: T
cessation of treatment, the rate of bone maturation
4 \3 ]. Y% {7 V6 Zdecelerates and gradually returns to normal.8,9' s; n& M4 X! J: m, Y7 F
There are conflicting reports and controversy8 C% g7 x, j9 o, k% M1 V' z
over the effect of early androgen exposure on adult
) z1 v! u6 h, ]- i9 Ypenile length.10,11 Some reports suggest subnormal
1 C; O3 {+ k# c/ n! I: d {adult penile length, apparently because of downreg-
2 U) L/ }" e- h5 Xulation of androgen receptor number.10,12 However,, U7 b1 P0 _5 z" @
Sutherland et al13 did not find a correlation between5 v. q6 k* X. ^
childhood testosterone exposure and reduced adult. D8 w! ~* h# D+ a8 _2 {- ~
penile length in clinical studies.
4 H! U! V1 B; f! CNonetheless, we do not believe our patient is
3 w7 h( N0 Y3 {1 H% x. \& rgoing to experience any of the untoward effects from9 g1 |9 O. ~: ^
testosterone exposure as mentioned earlier because' `. S9 U1 }, [0 d; t+ F
the exposure was not for a prolonged period of time.! [( U2 l. K7 D+ _4 b% I
Although the bone age was advanced at the time of/ k. A7 J9 k$ _
diagnosis, the child had a normal growth velocity at! U6 v) }& F3 s9 x: |
the follow-up visit. It is hoped that his final adult% @1 p8 k. k7 T0 R' p
height will not be affected.
e f1 ]% W7 @: L; l; W @Although rarely reported, the widespread avail-
! A6 z: B+ U' Gability of androgen products in our society may
3 ~( v, N! W, Y* v1 F! k' Q/ ?indeed cause more virilization in male or female
% T3 @. o9 O, Y0 Qchildren than one would realize. Exposure to andro-4 A, Z; L: R4 \0 i
gen products must be considered and specific ques-
- w9 A% n9 N c% v/ Rtioning about the use of a testosterone product or: n3 c9 S7 i8 z* @0 f; y
gel should be asked of the family members during
& k; k% {/ A& U7 w' e" Othe evaluation of any children who present with vir-
6 c o( @5 j" R5 S. J( N) G, Eilization or peripheral precocious puberty. The diag-+ S6 @8 j, x+ [ Z. C5 k( k
nosis can be established by just a few tests and by4 l$ {) L- k/ G9 u4 V2 y0 e
appropriate history. The inability to obtain such a
) d' V" n" c( g4 uhistory, or failure to ask the specific questions, may& ], k* Z* E+ b' ^+ [, O
result in extensive, unnecessary, and expensive
; f0 B7 R. X9 E5 qinvestigation. The primary care physician should be
5 ^6 J, v$ p% e. r% qaware of this fact, because most of these children
' T7 O w6 n/ E- X& M# A6 v* H) jmay initially present in their practice. The Physicians’9 ^( H2 K) B) m8 d ^* L( [7 E( @
Desk Reference and package insert should also put a
/ L5 h* H1 h! ^5 C. E- M" Pwarning about the virilizing effect on a male or
# r; e* b3 z& d5 b/ [( M% _3 S0 Ofemale child who might come in contact with some-
% Q3 `8 X6 T5 J' U* [ Y( None using any of these products.
: R6 H: ]& b G( iReferences: `5 f% g$ p3 y2 v5 k$ s5 L" C
1. Styne DM. The testes: disorder of sexual differentiation0 B( P5 v- C/ e& s& Z3 M7 a
and puberty in the male. In: Sperling MA, ed. Pediatric. I: ~: K! V' f) ~( X
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
3 ~( m# b3 X! |1 _* F, L1 y! d2002: 565-628.# U2 ^) ~2 M+ C0 F9 h* n. q
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious( W7 n* N# Y4 t/ t+ z8 @
puberty in children with tumours of the suprasellar pineal |
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