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Sexual Precocity in a 16-Month-Old* ~; s0 m) f3 a2 N
Boy Induced by Indirect Topical8 _$ S0 b3 z1 @: R3 P' s+ K3 T
Exposure to Testosterone1 r& S5 x# f* C8 k' \; l
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
& p! L/ V' B. e) q; qand Kenneth R. Rettig, MD1
" I3 u& \4 w- i; a }Clinical Pediatrics5 ?6 n/ J" X& d3 e, b9 h8 D
Volume 46 Number 6$ w7 N: T5 r0 N& a) @, r* i% X
July 2007 540-543# o+ V2 W+ |9 B8 q; Y
© 2007 Sage Publications
: S4 Q6 [2 f, b) u10.1177/0009922806296651
) `! g$ r; P) O: f% u' A) Zhttp://clp.sagepub.com0 l0 H. C) u+ V) k; Z/ s+ u# o4 X
hosted at
, B& k: g+ Q% `4 ~5 P1 w) @http://online.sagepub.com; K! g a+ K- c) D' D: e$ ?
Precocious puberty in boys, central or peripheral,
( |4 F [$ K. B. U' xis a significant concern for physicians. Central+ F# w. B$ _, L% w6 K: n: Y
precocious puberty (CPP), which is mediated1 C1 V8 t1 V/ M7 k& F! ?( N
through the hypothalamic pituitary gonadal axis, has
; R; Q0 A8 G+ z& R7 Ia higher incidence of organic central nervous system
, L2 Y2 `7 [3 v8 N! A4 I3 Q4 p6 Ylesions in boys.1,2 Virilization in boys, as manifested2 Z/ Q/ ^& ~% M2 R' z8 C
by enlargement of the penis, development of pubic
1 V! O. {, ]/ _5 K5 t% E5 }* s/ lhair, and facial acne without enlargement of testi-
, X9 K3 D, I( c7 x" M dcles, suggests peripheral or pseudopuberty.1-3 We9 Z, Z9 V: [0 f, d1 d( D
report a 16-month-old boy who presented with the$ _ k0 A# }; x1 N2 c8 }! e$ P5 N
enlargement of the phallus and pubic hair develop-% K1 u0 c( `# [2 p! k9 c
ment without testicular enlargement, which was due
* K, T" [: ]6 [to the unintentional exposure to androgen gel used by
. i0 H3 @# n5 c ~6 t; m" d& b+ f cthe father. The family initially concealed this infor-; B7 I# A8 ^# Z
mation, resulting in an extensive work-up for this
0 V& Z5 v. u0 T! `$ U( J8 ^' Y, v$ Hchild. Given the widespread and easy availability of
B" W* p$ z6 o' R$ ptestosterone gel and cream, we believe this is proba- d2 B' j2 U8 K1 U
bly more common than the rare case report in the
% O" D( T& n" b6 `$ S3 qliterature.4
% h9 Y1 F3 |0 L/ t* F! M9 nPatient Report
. }2 Q9 S: u7 O0 T, s2 UA 16-month-old white child was referred to the
' S O6 c/ L6 n3 x$ q( R% P# sendocrine clinic by his pediatrician with the concern3 J+ T+ U3 X+ J1 ]1 L
of early sexual development. His mother noticed( i0 p! z& ~6 M' x- E) n+ n: k
light colored pubic hair development when he was
4 G3 J! w& s: _' F4 CFrom the 1Division of Pediatric Endocrinology, 2University of" K8 s I3 D7 ?6 \3 H
South Alabama Medical Center, Mobile, Alabama.
" r9 h9 @1 R: v6 B, hAddress correspondence to: Samar K. Bhowmick, MD, FACE,
: ]( K& n8 }/ \3 WProfessor of Pediatrics, University of South Alabama, College of
7 e# p) ^1 i5 n1 E+ U$ X7 V+ jMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;( C' V( R) _, J6 E8 n5 i7 c
e-mail: [email protected].
5 }" K) b N, u$ E/ x" dabout 6 to 7 months old, which progressively became
9 @6 ~, A Y2 ^! q Adarker. She was also concerned about the enlarge-
# W7 h9 A3 O5 fment of his penis and frequent erections. The child
) I* c9 ~$ Q0 b( d/ _! _was the product of a full-term normal delivery, with
/ J2 a/ H) ^) P4 Y) d/ ^a birth weight of 7 lb 14 oz, and birth length of
: P4 z. L% s4 \20 inches. He was breast-fed throughout the first year
- w6 J( p( V" P k2 a; n4 v9 iof life and was still receiving breast milk along with& E) X0 P! `* x. _" |
solid food. He had no hospitalizations or surgery,/ l9 @5 L( A7 ]4 G+ _9 B% V# J
and his psychosocial and psychomotor development: _, }' a4 ~ }9 k
was age appropriate.' S$ F8 U0 K# p, R. l% [
The family history was remarkable for the father,4 @( S: i @' @) q2 Z, l
who was diagnosed with hypothyroidism at age 16,
, C* F# i$ T# q8 }! P7 j5 Iwhich was treated with thyroxine. The father’s
3 {. Q+ |) D' Q3 y1 z- Z mheight was 6 feet, and he went through a somewhat( R* l3 t, b$ Y
early puberty and had stopped growing by age 14.( g( l" [( T8 N6 V+ J' q- b
The father denied taking any other medication. The5 q3 I" L" R; z+ J8 M1 A- _
child’s mother was in good health. Her menarche3 I ^+ G f4 T
was at 11 years of age, and her height was at 5 feet! Q0 A7 {! l5 m' f
5 inches. There was no other family history of pre-3 ?6 _+ c# F7 z0 n
cocious sexual development in the first-degree rela-
+ B: c* D s# R C- Atives. There were no siblings.4 M, w4 T# O1 s: f
Physical Examination# j6 [9 c# Z# `0 T) |5 G$ W0 `/ S4 E
The physical examination revealed a very active,7 x+ F# i# B! A( D; O( @
playful, and healthy boy. The vital signs documented
, I' V+ k) i. ka blood pressure of 85/50 mm Hg, his length was; m, B }* g. ?1 e$ w/ s; q
90 cm (>97th percentile), and his weight was 14.4 kg
0 H3 i! z7 p2 g+ K1 @6 n(also >97th percentile). The observed yearly growth
" h2 m4 u. S" G: hvelocity was 30 cm (12 inches). The examination of+ p9 J1 I: p7 t/ H4 i
the neck revealed no thyroid enlargement.5 |5 \; y' T, T
The genitourinary examination was remarkable for' S. D3 Y" ?% g
enlargement of the penis, with a stretched length of
2 U% D8 g( {9 N2 d8 k8 cm and a width of 2 cm. The glans penis was very well
4 p* R3 R5 b8 B9 kdeveloped. The pubic hair was Tanner II, mostly around) B- f7 t5 p2 f9 N. N, L
540
: _5 o0 I; Q1 S$ t! C# a1 A2 E k. iat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from% B2 w0 T+ _7 r
the base of the phallus and was dark and curled. The
6 J: u) Y' l6 G0 n: ]$ ^! ttesticular volume was prepubertal at 2 mL each.2 q; Y% b& P' b: g% w' Q
The skin was moist and smooth and somewhat
. H+ Y+ I9 u. L# f0 C# }2 hoily. No axillary hair was noted. There were no, C* O1 Z* s3 D4 s
abnormal skin pigmentations or café-au-lait spots." T3 l6 L* k! \. K% T
Neurologic evaluation showed deep tendon reflex 2+
9 F' K( ]; \ c/ y( P8 sbilateral and symmetrical. There was no suggestion4 I+ k) H# N" D1 H6 B
of papilledema.
% V/ P" `& R( M/ k: H9 n. bLaboratory Evaluation
Q# p0 }" ~4 C- G1 s5 n) C2 \: qThe bone age was consistent with 28 months by
3 x' P* t. R' f& Wusing the standard of Greulich and Pyle at a chrono-) B% V' i/ L! T! c9 y
logic age of 16 months (advanced).5 Chromosomal
# C/ y; ?2 \# e; h4 {. N1 Y4 L; Ckaryotype was 46XY. The thyroid function test) N6 j0 C& X2 M) g( t2 `0 N
showed a free T4 of 1.69 ng/dL, and thyroid stimu-# i6 I" C/ q h! Y/ m% f
lating hormone level was 1.3 µIU/mL (both normal).
( C( L/ Y5 l9 L9 D/ {* lThe concentrations of serum electrolytes, blood
" V; @& H5 v2 q9 ourea nitrogen, creatinine, and calcium all were
) K s, D/ s" R6 bwithin normal range for his age. The concentration4 {% u- ^$ k# D" F
of serum 17-hydroxyprogesterone was 16 ng/dL8 G& j% z5 z8 \! P" t
(normal, 3 to 90 ng/dL), androstenedione was 20! L% @$ A, c% |6 K5 }$ ^
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-: b- | A/ X! t# D. A$ h) E0 p
terone was 38 ng/dL (normal, 50 to 760 ng/dL),; e# B- y. f9 v
desoxycorticosterone was 4.3 ng/dL (normal, 7 to/ t9 t _# w& T; s
49ng/dL), 11-desoxycortisol (specific compound S)
6 ?3 C5 ]: o0 d: C" gwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-. g5 y( @6 W6 @
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
4 G) _+ M& o: R) a6 z2 F* rtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),# ~8 s# w. Z& \* {1 o
and β-human chorionic gonadotropin was less than
1 p% H8 D. N H; `, E/ ? c% C( v5 mIU/mL (normal <5 mIU/mL). Serum follicular& C. P5 ~4 Q0 d7 O4 l3 l* w2 o
stimulating hormone and leuteinizing hormone% f6 }9 H. R: Q' p5 ^
concentrations were less than 0.05 mIU/mL& g8 E/ _5 n$ O5 ^* [5 \ a
(prepubertal).
# D% |. f' j0 B' C9 K; CThe parents were notified about the laboratory% P& I# N; @# {
results and were informed that all of the tests were: j h- o0 }9 G o, K! T# v
normal except the testosterone level was high. The
0 h% z5 j8 l* efollow-up visit was arranged within a few weeks to
1 `1 y7 g$ a# Y( x* uobtain testicular and abdominal sonograms; how-
6 m q% ^ G/ v7 T4 [ever, the family did not return for 4 months.
- I) F1 ~2 h3 ^' v, l, R; ?& |Physical examination at this time revealed that the
* p% N0 [% z# @9 k# U4 fchild had grown 2.5 cm in 4 months and had gained# a+ S' I( x: Q- ?9 i8 ~
2 kg of weight. Physical examination remained
7 }. o" j6 x: m$ X) t. o1 I3 dunchanged. Surprisingly, the pubic hair almost com-7 t7 R& f0 Q! O/ S# ^& m/ T
pletely disappeared except for a few vellous hairs at
2 F2 Q! I* m2 k! ithe base of the phallus. Testicular volume was still 2
4 R5 P, i% z _4 ?# g2 TmL, and the size of the penis remained unchanged.
1 S9 ~9 D G3 \) `( X6 O& BThe mother also said that the boy was no longer hav-4 J" u9 o& o0 F6 d, {
ing frequent erections.3 s6 b# n K3 P( v' |, H0 w! y' v9 {
Both parents were again questioned about use of
6 q2 V+ K2 h5 [8 d qany ointment/creams that they may have applied to
/ j& f9 d1 |4 Y, C4 Vthe child’s skin. This time the father admitted the
: d+ ?; q, [: DTopical Testosterone Exposure / Bhowmick et al 541
) N( n5 Q5 V7 W0 Kuse of testosterone gel twice daily that he was apply-4 m9 Y" W" `& {: |/ i ]: t
ing over his own shoulders, chest, and back area for" T& y1 h$ S/ p( ~
a year. The father also revealed he was embarrassed
* n& f: d0 A' `to disclose that he was using a testosterone gel pre-( g6 X- C" i0 s6 v1 {
scribed by his family physician for decreased libido
/ |2 h/ g" ]- D+ D/ o; Zsecondary to depression.
1 B( h! J) B3 C% h) G) UThe child slept in the same bed with parents.
0 d: y4 \% V" n$ W' @The father would hug the baby and hold him on his
. j8 J; G' b% r) k( ochest for a considerable period of time, causing sig-
* A, W# U6 h a! B7 H' ^# k& d+ c' lnificant bare skin contact between baby and father., G6 [ F9 M$ q3 h2 l
The father also admitted that after the phone call,( r- `+ Q6 S! \
when he learned the testosterone level in the baby+ c+ {3 [8 f: P0 [4 H1 @# L
was high, he then read the product information* B+ ]( b( z }1 P
packet and concluded that it was most likely the rea-5 ? \4 w' `; s8 ~( `$ G$ c2 m
son for the child’s virilization. At that time, they9 I* ?6 _; f$ \, g
decided to put the baby in a separate bed, and the
/ p3 A$ n7 r; C: Gfather was not hugging him with bare skin and had
- d+ q% { H) d4 gbeen using protective clothing. A repeat testosterone4 Z% m' a0 l1 A4 `' z' `
test was ordered, but the family did not go to the9 z9 o& [$ X6 p9 Q# E C
laboratory to obtain the test.
( U% X/ p: @: P4 w$ J9 ]Discussion
$ N* `/ I$ W% E$ T% nPrecocious puberty in boys is defined as secondary
' v/ |# p$ F" i/ L2 p9 a1 r( Wsexual development before 9 years of age.1,4
0 p% m. C4 |$ fPrecocious puberty is termed as central (true) when7 ^. `' B& e: a. @& n: v
it is caused by the premature activation of hypo-2 n0 I8 n0 w+ E$ A, {& q1 ]# h( e
thalamic pituitary gonadal axis. CPP is more com-! v- v( e: A- W! ?+ W
mon in girls than in boys.1,3 Most boys with CPP" ?1 u/ K+ |# l) |* b% y- ^
may have a central nervous system lesion that is, }5 T" r8 _* d
responsible for the early activation of the hypothal-
9 {: G d- C( }8 s8 @amic pituitary gonadal axis.1-3 Thus, greater empha-) R2 j: U6 V- K% g2 w7 F
sis has been given to neuroradiologic imaging in
+ ? A# B& g) O6 n5 r; r% Lboys with precocious puberty. In addition to viril-% q Y* p5 R0 D* t+ j
ization, the clinical hallmark of CPP is the symmet-5 F: `/ H' I% v6 s
rical testicular growth secondary to stimulation by# ?- A F8 } G8 a/ c
gonadotropins.1,3
/ a6 t1 r- f; q6 MGonadotropin-independent peripheral preco-
* I2 n8 ~( P# V `" B" N: {' Ucious puberty in boys also results from inappropriate7 ~5 ^6 o8 x$ a1 B% D+ o
androgenic stimulation from either endogenous or1 _% h0 o1 `6 Z9 a9 B
exogenous sources, nonpituitary gonadotropin stim-
7 }( t+ M# l! sulation, and rare activating mutations.3 Virilizing) _7 C( Q8 J! j" V
congenital adrenal hyperplasia producing excessive
% L, S; q" Y3 S1 z$ ?adrenal androgens is a common cause of precocious9 z) X& S& w% C t7 l0 Z9 v, a) V
puberty in boys.3,4
4 l b! g" C0 |( @7 m$ BThe most common form of congenital adrenal. i, s1 D- p; ]1 q. O9 {8 R; M
hyperplasia is the 21-hydroxylase enzyme deficiency.
. C% `" r0 o( i8 T, h. HThe 11-β hydroxylase deficiency may also result in
3 f) |0 \" q+ E+ K) Jexcessive adrenal androgen production, and rarely,
4 M8 J. t# _# A# { o$ V, Uan adrenal tumor may also cause adrenal androgen: P" w6 e( f }- c
excess.1,3
9 V' }% ^& w% s% H% T- v5 Zat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
, }; ^0 I% z) l5 m& L, h542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
# u/ A5 w8 \4 V4 p' PA unique entity of male-limited gonadotropin-5 g. n' }6 f* L9 h
independent precocious puberty, which is also known
0 b2 S! U* Z8 x0 m% i+ [7 e3 W$ h8 Oas testotoxicosis, may cause precocious puberty at a
: V/ J" N8 I9 X, kvery young age. The physical findings in these boys6 E2 F7 ~* u8 N3 N3 M: Q( \
with this disorder are full pubertal development,
3 h4 L) Q/ Y, s: t d) Lincluding bilateral testicular growth, similar to boys
' _7 y5 i* M8 _9 Awith CPP. The gonadotropin levels in this disorder# f! f. i7 n3 ^6 C
are suppressed to prepubertal levels and do not show
7 r+ l8 w! F& |$ M, Q7 B. @: \1 jpubertal response of gonadotropin after gonadotropin-
) a" ^) }5 E0 hreleasing hormone stimulation. This is a sex-linked
6 Y( T$ q4 _* h% }autosomal dominant disorder that affects only
* ]/ ~6 p! h) ~. p; \" f3 N7 q6 {males; therefore, other male members of the family
. r; ]3 ^! _2 k* r& Rmay have similar precocious puberty.3
@8 `! r5 V( f: G ?! HIn our patient, physical examination was incon-% l- k K4 L0 l9 T' Z2 [7 q
sistent with true precocious puberty since his testi-+ v) h. E6 [* q% F& ]
cles were prepubertal in size. However, testotoxicosis( v( Y- h1 r- Y% l: h! J2 S$ s
was in the differential diagnosis because his father" y. t0 M9 K x" f% N* M* |- i) D8 r
started puberty somewhat early, and occasionally,
w$ l2 [ K% K! R* Otesticular enlargement is not that evident in the4 j* J2 z. m& T, Q
beginning of this process.1 In the absence of a neg-0 l' c% p+ ]+ O% o
ative initial history of androgen exposure, our
$ T& N5 b1 |' r3 c+ X5 w) Nbiggest concern was virilizing adrenal hyperplasia,5 w; j4 i3 ?7 n
either 21-hydroxylase deficiency or 11-β hydroxylase
5 d& t6 G6 q" ?$ D+ i# Z. Zdeficiency. Those diagnoses were excluded by find-8 S# N- \8 i* o: x- Q
ing the normal level of adrenal steroids.
) w2 ^8 B& i, p9 c; Y) dThe diagnosis of exogenous androgens was strongly: s3 f5 L! q6 g/ v. d0 _
suspected in a follow-up visit after 4 months because
# r6 J, P( `# X( o/ E0 \2 sthe physical examination revealed the complete disap-- r! ]' j9 D h& i I
pearance of pubic hair, normal growth velocity, and/ T2 n9 y$ f6 B* W5 L! |& y
decreased erections. The father admitted using a testos-
{+ ~9 R3 t. X* Q: [& l. Dterone gel, which he concealed at first visit. He was
3 d: x- l# Q# H) T1 p) c9 [" ~" Tusing it rather frequently, twice a day. The Physicians’
- f& u4 i7 a [1 U" [6 W$ yDesk Reference, or package insert of this product, gel or
7 w# c/ P% ~3 j7 N+ H# Scream, cautions about dermal testosterone transfer to; T" [& U, K ~. v7 } U; z7 s( H
unprotected females through direct skin exposure.& D0 t5 F) `6 R; q7 F* e9 I
Serum testosterone level was found to be 2 times the5 j( y, I4 ]& ]8 R9 Y" O
baseline value in those females who were exposed to! z8 o% F2 d5 x: `, h' T
even 15 minutes of direct skin contact with their male3 ~) X" D* K7 ]3 Z; ^0 s4 F# q
partners.6 However, when a shirt covered the applica-
' \4 r6 s$ I, I8 E$ Ftion site, this testosterone transfer was prevented.
) B ]! W3 w7 {! X* xOur patient’s testosterone level was 60 ng/mL,( E0 l) n! v9 o L3 \# r1 z, t
which was clearly high. Some studies suggest that4 c) b) I( u! T ^! x. q k" D
dermal conversion of testosterone to dihydrotestos-! [, b# _/ n. X; u9 D
terone, which is a more potent metabolite, is more" D: s$ C" x( S2 i
active in young children exposed to testosterone
?! d' N7 j4 X3 m4 a; r, B, }exogenously7; however, we did not measure a dihy-- W t( n% [) M/ B) g5 f
drotestosterone level in our patient. In addition to
6 p1 s( G' L4 y0 i( m' a& C- ~virilization, exposure to exogenous testosterone in; w8 X. v b1 p5 p! d( b3 i
children results in an increase in growth velocity and
' F2 Z x3 k! R: h, Z2 |3 kadvanced bone age, as seen in our patient.
7 A7 ~& k0 w' `7 ?5 z& `+ N2 R2 xThe long-term effect of androgen exposure during" b0 Q: L5 v: [( F: ^
early childhood on pubertal development and final
# U$ k1 _" H! B' Vadult height are not fully known and always remain' ^) {8 R. i: I" y! K
a concern. Children treated with short-term testos-
) t+ S! i2 r6 i) U9 \9 ]7 @terone injection or topical androgen may exhibit some# q9 `/ p* H; {" Z3 c! h" c+ u- N
acceleration of the skeletal maturation; however, after
: Q" F4 G! N7 @ @( w0 D! X2 Q3 w, ~cessation of treatment, the rate of bone maturation
. r' ~/ A8 C4 J7 e% X: h8 pdecelerates and gradually returns to normal.8,9
; d3 ^. O: U3 w- q$ F5 m% \2 V+ RThere are conflicting reports and controversy
# y& [' E5 k' ~* I* aover the effect of early androgen exposure on adult* u; O& K/ q: P) Q! B. Z
penile length.10,11 Some reports suggest subnormal; z1 p+ `1 \3 M2 X
adult penile length, apparently because of downreg-
- N+ K- ]+ P- b6 V* |( ]% [ulation of androgen receptor number.10,12 However,+ Q |- _, C3 L( c8 k8 n E5 L* w# q
Sutherland et al13 did not find a correlation between
+ V, ]" j$ ^8 H' kchildhood testosterone exposure and reduced adult
& V& Y2 c8 `9 ]: e/ Ypenile length in clinical studies.6 T! Z/ a( q4 t% u! c. W+ n2 n$ i
Nonetheless, we do not believe our patient is7 i8 I# [, f5 b& Q. L
going to experience any of the untoward effects from
; R- _3 T7 k, c# I7 X' ptestosterone exposure as mentioned earlier because
! t$ L8 ]' o3 y! r: k# N3 Jthe exposure was not for a prolonged period of time.
6 @! j$ P- ~ o3 g& B( rAlthough the bone age was advanced at the time of( E. j0 A8 Q5 d
diagnosis, the child had a normal growth velocity at0 U$ L' G5 f. c/ E
the follow-up visit. It is hoped that his final adult: g0 ~+ k U1 D' ^; B9 v2 S: E* j
height will not be affected.
* v# \/ O* j" }" A! C2 lAlthough rarely reported, the widespread avail-
- l6 d; U. g' c6 {ability of androgen products in our society may1 ~( p2 J$ a& R0 t& Y3 B7 Q# b
indeed cause more virilization in male or female5 H/ ?& @9 G2 w. H
children than one would realize. Exposure to andro-
4 R+ y- R2 E5 g' o% P: e Q( t9 e3 T- Qgen products must be considered and specific ques-
: d0 G) S3 S2 H, g2 _# S5 rtioning about the use of a testosterone product or
; o k# J' P2 ]+ u/ C. Ngel should be asked of the family members during
0 S7 J, I A/ D" o1 }the evaluation of any children who present with vir-% `+ U1 G7 _) P* P
ilization or peripheral precocious puberty. The diag-
4 q7 u$ F% p& a) jnosis can be established by just a few tests and by
: x" C k/ k( o( f ]appropriate history. The inability to obtain such a
. e) N, |% G/ \0 ]2 g8 ahistory, or failure to ask the specific questions, may: g0 H- a, D7 R( R) l' Z9 A
result in extensive, unnecessary, and expensive
' y7 |) ~( W6 _6 s: D8 y) Finvestigation. The primary care physician should be- W0 {+ p( k5 H
aware of this fact, because most of these children5 }$ T5 _' H" k+ `; ^( |7 x. k( o
may initially present in their practice. The Physicians’
- I! {* H2 M$ x- QDesk Reference and package insert should also put a2 c' l- o0 P0 n# m
warning about the virilizing effect on a male or
; z7 n! K! w5 [! g5 zfemale child who might come in contact with some-
7 P# m1 F$ @' a1 Done using any of these products.
q* [+ a5 Z# Y, s( ^References v" N. o7 f+ ?: N( l, q
1. Styne DM. The testes: disorder of sexual differentiation
/ `$ p% \8 d& q7 Xand puberty in the male. In: Sperling MA, ed. Pediatric7 F) R' l2 f1 T0 \# }
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
: ~& _: q8 |* ?3 W3 r4 N2002: 565-628.1 P7 T" h2 L) ~7 J' Q
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
8 [, R9 h5 }' ]/ e, x$ npuberty in children with tumours of the suprasellar pineal |
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