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Sexual Precocity in a 16-Month-Old7 {* d# |/ P7 Z! n
Boy Induced by Indirect Topical
( p8 n9 a1 d9 R* s bExposure to Testosterone. D6 y+ A. y7 X; s2 X
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2$ m/ m1 R: X1 q' y) f0 K
and Kenneth R. Rettig, MD1
, _' ^6 [% V1 M! U/ S7 [ [Clinical Pediatrics. v; b2 H' z! ~: R, M
Volume 46 Number 6
. P9 K$ x3 I2 C3 Q0 NJuly 2007 540-543- Q9 T8 C0 ^0 v4 G; i
© 2007 Sage Publications! K- f( E( e _7 D9 i
10.1177/0009922806296651( K; L$ |/ B- u+ n9 A+ e' y/ u& f, n
http://clp.sagepub.com$ x% H3 M2 Y' R2 A9 g: n; l
hosted at
( m. P: x1 x) q" e s: Mhttp://online.sagepub.com
# U5 \/ j5 |: n. S/ uPrecocious puberty in boys, central or peripheral,
% t2 c P7 _- {' @7 q" F; Ois a significant concern for physicians. Central
, |# _( L# Q7 v$ r3 U! |% Jprecocious puberty (CPP), which is mediated
( k6 _3 @ i3 o" c8 G$ bthrough the hypothalamic pituitary gonadal axis, has% [1 O" ]4 e% H) Q5 B
a higher incidence of organic central nervous system2 ^* w1 f, }3 z5 r8 y
lesions in boys.1,2 Virilization in boys, as manifested6 v0 \5 C" {$ |2 ~6 s
by enlargement of the penis, development of pubic0 n* f' y) L( v7 p
hair, and facial acne without enlargement of testi-7 i& k5 T# P8 b
cles, suggests peripheral or pseudopuberty.1-3 We; }5 x0 ]7 w9 c- B: d- b5 ]! ]
report a 16-month-old boy who presented with the' [( H4 p c! n, F' _3 j3 X
enlargement of the phallus and pubic hair develop-
: l7 E2 e( V+ y4 u9 w# Bment without testicular enlargement, which was due
0 U- w, b# u6 @" V( [2 Eto the unintentional exposure to androgen gel used by
' S7 m& j0 ~" u+ o. ~0 k |the father. The family initially concealed this infor-8 n! T+ c9 K+ z8 J
mation, resulting in an extensive work-up for this4 r E6 V1 W- A& q/ N6 ~! Z
child. Given the widespread and easy availability of
6 \' B# k( j; N d, k( jtestosterone gel and cream, we believe this is proba-5 ^: o8 _) i9 g; K9 G; G1 a
bly more common than the rare case report in the
9 [9 |; c: o, ~5 I; H2 \literature.4
& C5 M: l+ [( bPatient Report2 U# K) d, [5 v( P6 A z7 {% I$ w
A 16-month-old white child was referred to the
* s* _/ \# x; U2 h2 [- V& i Pendocrine clinic by his pediatrician with the concern
6 W3 P, K# w8 z* Y! S( I# ?* Dof early sexual development. His mother noticed- y, N8 F u3 I" \& u& E- v
light colored pubic hair development when he was
5 O2 }5 `9 V! ~/ EFrom the 1Division of Pediatric Endocrinology, 2University of
" N) j# M3 }& `' k1 qSouth Alabama Medical Center, Mobile, Alabama.
z; F4 c, l$ J0 N5 w' y7 HAddress correspondence to: Samar K. Bhowmick, MD, FACE, e' Y; H4 H* M4 G- A- p1 H) w
Professor of Pediatrics, University of South Alabama, College of
# {$ B/ p1 E6 w3 c1 i+ dMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;! H* w: k6 C' C2 C
e-mail: [email protected]. H$ _/ k5 c7 f8 M9 w- X
about 6 to 7 months old, which progressively became
8 M& r/ C6 Q% b; ~+ a- _# ?3 xdarker. She was also concerned about the enlarge-
( `* [( k& y8 \* ^6 A5 N% {6 M/ k2 lment of his penis and frequent erections. The child
5 P; |. a- F; Owas the product of a full-term normal delivery, with% j. k, a6 P3 F- t0 C! @
a birth weight of 7 lb 14 oz, and birth length of
- S9 d* c9 {. h1 C20 inches. He was breast-fed throughout the first year
/ Y0 D9 b5 m X' V( @: d0 g/ bof life and was still receiving breast milk along with
' v8 }" l0 | j4 U0 e) w5 Esolid food. He had no hospitalizations or surgery,4 q9 p+ C$ P8 T* J
and his psychosocial and psychomotor development
8 Q# ~2 Q# T8 Z; f% }6 }was age appropriate.
. y) ]5 y: O( |/ |4 l4 FThe family history was remarkable for the father,3 y; v& Y, V" V
who was diagnosed with hypothyroidism at age 16,& `( p$ x! t. H' b1 Q6 x L
which was treated with thyroxine. The father’s r3 Q/ Y" c' ^/ f g/ F1 x4 y
height was 6 feet, and he went through a somewhat/ V( X# W$ d" ]* s+ C2 B- S3 J: h! V
early puberty and had stopped growing by age 14.
+ W% M: Q# L! p% N# }" x- gThe father denied taking any other medication. The
B/ n" B% q$ d# z* S/ Y9 W0 N8 ychild’s mother was in good health. Her menarche4 s& i# N. v4 m, q# C" X
was at 11 years of age, and her height was at 5 feet: \* y8 g$ M9 ]6 l
5 inches. There was no other family history of pre-
0 j2 R3 |( h3 k; N+ Scocious sexual development in the first-degree rela-+ k) t2 A7 h" D; E% F0 M2 R
tives. There were no siblings.0 T0 ?/ p' |1 r" V3 {! z
Physical Examination+ @) u% l) }' c/ W% N. I7 s# Q
The physical examination revealed a very active,6 e7 |+ H, r+ T3 _: M4 w* \0 B9 Z
playful, and healthy boy. The vital signs documented
" r) b- m$ q* c2 ra blood pressure of 85/50 mm Hg, his length was4 w# u, @/ n5 B: o' `; \
90 cm (>97th percentile), and his weight was 14.4 kg
2 ~- z9 r# s7 e4 O* y(also >97th percentile). The observed yearly growth$ }& ]" O* S! E9 U7 G4 J0 L
velocity was 30 cm (12 inches). The examination of
" V% x7 Y& K) B& Ethe neck revealed no thyroid enlargement.* v |2 m2 X* B( ~4 }, q
The genitourinary examination was remarkable for
# M# } \" A C: A: ~enlargement of the penis, with a stretched length of1 O. J) Y: ^1 D4 K4 O5 A2 B
8 cm and a width of 2 cm. The glans penis was very well7 k8 b$ F g$ i! a: U- V, @" e
developed. The pubic hair was Tanner II, mostly around+ Q; Q9 a" x3 J% f% Q+ `; e2 w# g" P
540
" x$ a% O8 |: i* |0 z' p& j; R0 Iat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
' T1 l! X' F2 \8 fthe base of the phallus and was dark and curled. The9 k; Z; u+ h$ Q" {7 t
testicular volume was prepubertal at 2 mL each.7 B/ h8 g1 W# D" X; i) T, f6 p
The skin was moist and smooth and somewhat
D0 P* O8 g, B. goily. No axillary hair was noted. There were no5 W, U+ E* d' m
abnormal skin pigmentations or café-au-lait spots.
* { i% U0 e1 U5 C1 R" N ~. g% f& xNeurologic evaluation showed deep tendon reflex 2+4 _* M3 A+ s. f8 a. h. x( D
bilateral and symmetrical. There was no suggestion
: W, E: ~/ w% R* Y' k/ }8 q+ R* \of papilledema. P& H. Z0 @" R* c( `0 s3 Q0 ^
Laboratory Evaluation
7 U& q) [9 r) K8 ]5 I3 CThe bone age was consistent with 28 months by
/ Z% {9 p: f z- F5 pusing the standard of Greulich and Pyle at a chrono-8 K6 `# Q z6 H5 M4 k, }6 T
logic age of 16 months (advanced).5 Chromosomal
4 G- |% I3 c4 w( v# p# h7 lkaryotype was 46XY. The thyroid function test
3 R7 P; P% K0 {5 F) Eshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
; g, K+ @% V, G% b3 xlating hormone level was 1.3 µIU/mL (both normal).
h. i4 d3 _. X% pThe concentrations of serum electrolytes, blood0 N3 U {% g7 D+ x6 l7 m5 s
urea nitrogen, creatinine, and calcium all were s( M" u) O6 T
within normal range for his age. The concentration
% F- Z7 |- f1 Sof serum 17-hydroxyprogesterone was 16 ng/dL
& \8 ~9 y+ P5 X" S7 ?: M(normal, 3 to 90 ng/dL), androstenedione was 20
2 B+ u9 Q8 d6 D- l8 O7 A9 W7 B9 Cng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-1 E' j# l, Y. V) B. K
terone was 38 ng/dL (normal, 50 to 760 ng/dL),# I2 ]7 G; u' \* d
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
' S8 e4 o9 v4 X" }. ^( Q" {49ng/dL), 11-desoxycortisol (specific compound S)
0 D1 A. g7 l: F) [/ Q$ q6 u3 x5 b$ ~# Xwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-- t# |) {, P+ h2 B, i$ d: e
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
( `5 K* a& k' c) q2 Otestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
' s& |- C: j' j& x1 Jand β-human chorionic gonadotropin was less than: ~0 L. W T: I9 D) l: p
5 mIU/mL (normal <5 mIU/mL). Serum follicular
# Y& I7 h8 }7 Z6 h/ a, Y6 D4 I2 Zstimulating hormone and leuteinizing hormone
$ c/ m0 z! r! a0 g, x* Qconcentrations were less than 0.05 mIU/mL
, i+ R: f2 H7 H+ F4 N/ W; p' o8 y. o(prepubertal).5 ^7 J2 M( D- a8 G3 q
The parents were notified about the laboratory, k5 B" f9 N2 K: F7 Z0 y
results and were informed that all of the tests were# ~# Y+ t* o2 M
normal except the testosterone level was high. The+ j. q1 X& E1 T: [8 C, B
follow-up visit was arranged within a few weeks to
8 S S% x+ I( p! f( z, Q: `obtain testicular and abdominal sonograms; how-
! y; s# r' Z% c& k1 n/ cever, the family did not return for 4 months.
5 ]# U3 @9 ^: D$ u/ I9 S1 mPhysical examination at this time revealed that the
! y4 J( G' Z: Z. b, {child had grown 2.5 cm in 4 months and had gained
& q2 S4 M6 h( g6 v }2 kg of weight. Physical examination remained+ D% ^% b5 z, |+ Y# |: v
unchanged. Surprisingly, the pubic hair almost com-* B0 j6 i& y% x s4 X* n7 k9 B/ G
pletely disappeared except for a few vellous hairs at* ?1 o& `! b$ U, y& S5 D4 I
the base of the phallus. Testicular volume was still 2
0 z* i* z. Z ^+ B$ K- g" hmL, and the size of the penis remained unchanged.% w% k/ r0 C1 r' b; x
The mother also said that the boy was no longer hav-
. c+ `6 W6 L" C# Ming frequent erections.
, M, `( v4 Z. V' u: xBoth parents were again questioned about use of0 I, z2 Q% R9 B8 J/ a; S: c7 M
any ointment/creams that they may have applied to
7 V% R0 T: x) d9 w+ y" Kthe child’s skin. This time the father admitted the( L, l. n G" a1 W. f
Topical Testosterone Exposure / Bhowmick et al 541
# Z" ^0 ?7 W; W9 w- A! G2 [. wuse of testosterone gel twice daily that he was apply-2 q- C; Q6 x- B8 `, Y( j& ]
ing over his own shoulders, chest, and back area for5 s: S$ I% E4 }
a year. The father also revealed he was embarrassed0 N9 R' m3 r$ S$ V9 e
to disclose that he was using a testosterone gel pre-
8 l$ u$ _& g- ]% ?& ?/ n6 d4 G) Nscribed by his family physician for decreased libido) L& b& Q* H) e- S, c* @, v
secondary to depression.
& c" j" @1 u( r9 ^! I- GThe child slept in the same bed with parents.
$ k, C" V4 @5 k, K y) kThe father would hug the baby and hold him on his
1 i( V3 F4 B2 j* [2 {; |chest for a considerable period of time, causing sig-2 `& @- l9 w& n" D
nificant bare skin contact between baby and father.1 m1 p# N( r2 [, _
The father also admitted that after the phone call,
% V0 p0 e8 R1 H: w% {% Iwhen he learned the testosterone level in the baby
2 ~( H3 I0 R$ h( wwas high, he then read the product information
. B) F+ T/ g* opacket and concluded that it was most likely the rea-
9 W, M2 a, w0 k8 c' V- u1 sson for the child’s virilization. At that time, they
" _- e5 ]8 k4 P2 sdecided to put the baby in a separate bed, and the
3 r' i$ W4 n8 P' ofather was not hugging him with bare skin and had+ _4 V% ?" j2 z! S* b3 V, c% k
been using protective clothing. A repeat testosterone
" j1 V! @. r5 q; y7 o5 Ltest was ordered, but the family did not go to the
! d M5 E9 Q& S- plaboratory to obtain the test.
5 V6 ~$ h; o3 t+ I/ ~Discussion/ b- j2 @4 ~4 r0 D9 Q) {# k
Precocious puberty in boys is defined as secondary
3 ~) y" v- A asexual development before 9 years of age.1,4
$ ?" X0 l3 S0 d" T, {Precocious puberty is termed as central (true) when) ^0 L; j6 @0 Y; e0 A/ q. @5 X
it is caused by the premature activation of hypo-
$ G9 D* {: c9 _8 Fthalamic pituitary gonadal axis. CPP is more com-4 W; d/ B* y* F+ J
mon in girls than in boys.1,3 Most boys with CPP
. t- J. f( f, D+ i% h& Wmay have a central nervous system lesion that is
2 u; a- M! o% S/ C! i! _' I& v; @responsible for the early activation of the hypothal-
! n& N) M5 H @amic pituitary gonadal axis.1-3 Thus, greater empha-
* H; Z: ^2 c$ D; Ysis has been given to neuroradiologic imaging in! _9 Y- J1 N* ?- P4 ]
boys with precocious puberty. In addition to viril-
& q; n0 y0 z3 Y6 ]0 g. Kization, the clinical hallmark of CPP is the symmet-
- U1 w. X' O9 q6 ]rical testicular growth secondary to stimulation by; a9 R7 t, ]/ W) p3 ^+ K- `+ Q3 {
gonadotropins.1,3' N8 h/ L! W) q8 c; u, p
Gonadotropin-independent peripheral preco-! N) m# c* f* }8 A- Q j
cious puberty in boys also results from inappropriate1 r$ }7 ]) C9 m9 J. ~) ]
androgenic stimulation from either endogenous or
2 a6 ]) t8 P$ Bexogenous sources, nonpituitary gonadotropin stim-, O. D/ R! t* e, l
ulation, and rare activating mutations.3 Virilizing
# h! ]/ g+ t1 N- Dcongenital adrenal hyperplasia producing excessive
- a/ i( ~$ c) x& f0 X9 Jadrenal androgens is a common cause of precocious
0 _( M1 G; _5 Y6 z7 \puberty in boys.3,4
* b. u6 |1 Y1 Q7 ^' wThe most common form of congenital adrenal: G* r: R D! X$ Q5 u5 S! @- R3 w
hyperplasia is the 21-hydroxylase enzyme deficiency. j& D1 |- k, |' d
The 11-β hydroxylase deficiency may also result in
: y5 l1 \+ t% c: yexcessive adrenal androgen production, and rarely,
$ C5 d0 ^6 Y) l8 A: Nan adrenal tumor may also cause adrenal androgen
; n3 H& B/ T/ Z4 Z* l: Sexcess.1,3
$ ^* c2 v- z" I8 {! w* z' uat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from G7 p9 z+ n/ v" ?1 ?, J
542 Clinical Pediatrics / Vol. 46, No. 6, July 20074 I1 c$ {6 |2 W8 |2 W7 y
A unique entity of male-limited gonadotropin-
, Z0 [% [: c8 |% w: A F# Sindependent precocious puberty, which is also known5 b. f* z. m7 _1 D
as testotoxicosis, may cause precocious puberty at a* Z* w: g* E. p! X3 q
very young age. The physical findings in these boys
' N8 I* e" T* _7 f. m; Iwith this disorder are full pubertal development,
+ P- K, l8 c$ f1 d/ eincluding bilateral testicular growth, similar to boys
* I: }' r% p Y! Z7 T8 O) }with CPP. The gonadotropin levels in this disorder
4 c. ?& p1 [9 ?are suppressed to prepubertal levels and do not show7 E# b% f* W9 a
pubertal response of gonadotropin after gonadotropin-
: Y" ~7 p5 {/ t- X C7 p% treleasing hormone stimulation. This is a sex-linked
# h$ F* U9 F; U* I/ v! sautosomal dominant disorder that affects only7 k* f) C% c v( q1 \
males; therefore, other male members of the family6 D/ r7 X# u$ |& j' @/ `
may have similar precocious puberty.3! B: Q! z! v- ?- E' c) n
In our patient, physical examination was incon-
1 K9 [0 g9 p' k4 S# o' I8 i S1 fsistent with true precocious puberty since his testi-+ |4 }& W4 B7 T! `( c, @" a
cles were prepubertal in size. However, testotoxicosis
z+ u$ J, f9 ` swas in the differential diagnosis because his father3 P$ m4 j" f- C& l$ p
started puberty somewhat early, and occasionally,- |9 f) b+ H3 k6 u8 k
testicular enlargement is not that evident in the; W/ E$ j9 }0 {5 k+ K
beginning of this process.1 In the absence of a neg-
# M3 V' S! k1 |# ^- kative initial history of androgen exposure, our
( F+ T, O6 C: n' F* x) K. n4 [/ @biggest concern was virilizing adrenal hyperplasia,
- `7 O/ @1 H) }/ G. o: |9 Peither 21-hydroxylase deficiency or 11-β hydroxylase
8 V! Y! R% b& Tdeficiency. Those diagnoses were excluded by find-
" A6 R: O4 s. A8 S# D% Eing the normal level of adrenal steroids.
9 ~( F/ |5 c, OThe diagnosis of exogenous androgens was strongly
2 z$ m/ p$ I2 H9 Bsuspected in a follow-up visit after 4 months because
3 Z5 U7 R( q% Nthe physical examination revealed the complete disap-
3 o$ A2 O2 h, P! y8 M9 X1 Rpearance of pubic hair, normal growth velocity, and M% {8 E, l7 u$ H% Y' h
decreased erections. The father admitted using a testos-' \8 m. N# ~/ h" n" v' V, [1 ^
terone gel, which he concealed at first visit. He was! V( l+ Y: \0 X* ], Z8 L" a
using it rather frequently, twice a day. The Physicians’6 T; n, H+ a7 m
Desk Reference, or package insert of this product, gel or' g: J- _0 h: _3 t
cream, cautions about dermal testosterone transfer to
* R" Q/ I1 R8 junprotected females through direct skin exposure.. P. @1 f- j6 F2 P% Q! v
Serum testosterone level was found to be 2 times the
, E* k8 F8 p3 `. R7 |8 k9 T% q' Y8 obaseline value in those females who were exposed to$ f/ [4 [# ?2 M; r
even 15 minutes of direct skin contact with their male
0 f, E% ~* b4 }/ \2 t" e9 Fpartners.6 However, when a shirt covered the applica-
( Q3 D; I3 v& B+ ption site, this testosterone transfer was prevented.# }8 w4 K! j" b: d- q9 z
Our patient’s testosterone level was 60 ng/mL,8 }8 ?( |5 x& a# k/ L: c4 q
which was clearly high. Some studies suggest that
! |; H; K9 T$ S, c: |dermal conversion of testosterone to dihydrotestos-
0 S1 Y O2 I" p qterone, which is a more potent metabolite, is more
; W, b e. r3 b8 K9 iactive in young children exposed to testosterone# N& P0 U' M' e+ G
exogenously7; however, we did not measure a dihy-
" L8 x( L1 v+ Z1 B0 t5 l1 `drotestosterone level in our patient. In addition to- e: u0 ~2 H5 j9 O
virilization, exposure to exogenous testosterone in8 V0 T+ Q5 h7 }, v5 c/ @: f& ~1 [! k6 {
children results in an increase in growth velocity and) |- w" s) d# M8 F
advanced bone age, as seen in our patient.. E$ ^% [. U9 h: j- q
The long-term effect of androgen exposure during' F8 N' }& D2 P/ W( ]* I
early childhood on pubertal development and final
, I; ?0 G$ m. O3 badult height are not fully known and always remain
1 [) F3 m! N' F# |( t! n" H) sa concern. Children treated with short-term testos-* f" C2 U/ U& R) X9 |6 ]# O _
terone injection or topical androgen may exhibit some3 p1 S! G; z0 G7 |
acceleration of the skeletal maturation; however, after
# F3 h1 x/ \( w' Ecessation of treatment, the rate of bone maturation. W% l/ b+ Y! M$ ?- A. Q1 r$ ^; N0 {
decelerates and gradually returns to normal.8,9
- s/ P! a ]" [# e( B: i( K, RThere are conflicting reports and controversy; [# T1 a& e# C) V s/ K
over the effect of early androgen exposure on adult
( t- }* X; ]+ |% ]3 v6 tpenile length.10,11 Some reports suggest subnormal
1 E s {: A6 O+ [& r/ b4 S% r! u& Fadult penile length, apparently because of downreg-
( ?( K& Y( P1 {% s uulation of androgen receptor number.10,12 However,1 }, O' g: M4 j
Sutherland et al13 did not find a correlation between
! J" }6 S1 D' U+ b7 V, {5 ^childhood testosterone exposure and reduced adult
" M, H4 C5 `) b5 G' b( q9 ]penile length in clinical studies.
0 D. n/ o) d# q: s: A7 rNonetheless, we do not believe our patient is
! D- Z) q: c9 @/ V9 h# p- _5 cgoing to experience any of the untoward effects from! J( ~) U- }1 ~" e2 o0 j
testosterone exposure as mentioned earlier because
- X$ b: t+ u; L, o9 P& B3 Rthe exposure was not for a prolonged period of time.
# D) v# y9 o7 UAlthough the bone age was advanced at the time of
9 w3 x' R9 _, A: ldiagnosis, the child had a normal growth velocity at
) S1 E2 h% ^+ B J1 [the follow-up visit. It is hoped that his final adult
" @/ W3 P$ }' ^height will not be affected.
: [( W+ P6 `5 A$ H2 W1 yAlthough rarely reported, the widespread avail-
1 s% x( N0 l8 n; P! m v5 }ability of androgen products in our society may
% J. X9 {* l }3 e% @) Jindeed cause more virilization in male or female0 K3 a, v( ]4 y! d2 W! r: B& ]
children than one would realize. Exposure to andro-7 n; F2 C& L. W* z, P
gen products must be considered and specific ques-
3 x% \" e) y' h4 Y9 `tioning about the use of a testosterone product or
+ _, p! C) c! lgel should be asked of the family members during5 d7 b8 k9 |& ? i1 h M
the evaluation of any children who present with vir-
$ c* p. ~/ U T1 gilization or peripheral precocious puberty. The diag-, L' V8 l% V5 {0 N
nosis can be established by just a few tests and by
, w& |6 U2 g Tappropriate history. The inability to obtain such a
; C9 Q- h2 U+ A: L* w& H- `& Dhistory, or failure to ask the specific questions, may" m8 i1 s1 k, Y$ R7 f; d9 E) y
result in extensive, unnecessary, and expensive
' t# p U6 J4 q( `' sinvestigation. The primary care physician should be
& Q V/ f! f9 N5 P5 x7 kaware of this fact, because most of these children0 `1 O/ |. @% j9 Y N4 O ~" c) M
may initially present in their practice. The Physicians’; U, U& X9 r6 p5 h, I* r: @! B
Desk Reference and package insert should also put a0 }6 p- L. N$ y. N4 t" O
warning about the virilizing effect on a male or$ u- q% d+ }! M* T% p: u: H
female child who might come in contact with some-
Z2 i5 }6 l0 q; I5 tone using any of these products.
( {* G: |. v1 I/ V- Y, nReferences
* Q/ d. n& T* T) H. J) ?1. Styne DM. The testes: disorder of sexual differentiation
& ]$ W I4 }' T9 s) r$ mand puberty in the male. In: Sperling MA, ed. Pediatric$ {/ P2 V* }) ^# r( r
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
: o) m: M' g. m1 \2 }" I2002: 565-628., X! q0 E. @; S. U: Y
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious2 k! I! T$ Z" f( w! \
puberty in children with tumours of the suprasellar pineal |
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