- 註冊時間
- 2023-5-6
- 精華
- 在線時間
- 小時
- 米币
-
- 最後登錄
- 1970-1-1
|
發表於 2025-1-4 03:25:35
|
顯示全部樓層
Sexual Precocity in a 16-Month-Old7 z4 V- ^: R/ c3 F9 p
Boy Induced by Indirect Topical& `, p# H" w( ?4 a6 I' J
Exposure to Testosterone7 K* C0 ]% S% z; t$ W
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
$ a$ Z5 P8 b, K. Zand Kenneth R. Rettig, MD1
/ j M4 F! t, W! AClinical Pediatrics1 m9 c* @; D% O0 k7 L1 v, B
Volume 46 Number 6
* {; Y" `) ~' L6 l" ]July 2007 540-543
+ A6 v# ~) n. B- @9 n1 W© 2007 Sage Publications" g' A# ]; D/ d% g& H: L. K
10.1177/00099228062966513 E0 w9 `; R* j* y3 w7 o
http://clp.sagepub.com
. x) N. W! K0 a4 }3 J; H& ?hosted at
* ^1 O& ^/ F. {% G9 i& N9 F% k) fhttp://online.sagepub.com5 D/ I# m* x+ n5 @" U% e/ }
Precocious puberty in boys, central or peripheral,1 o* G! d/ G! q0 S
is a significant concern for physicians. Central
% d! s& [1 I) G# W* N _precocious puberty (CPP), which is mediated
: P9 j: n- u: \- O! F* G$ I' Xthrough the hypothalamic pituitary gonadal axis, has
7 ~0 Y8 z( k8 N) \a higher incidence of organic central nervous system* s+ D: ^/ s6 B* b9 F7 P
lesions in boys.1,2 Virilization in boys, as manifested* m4 @, j# _* k/ I! G0 L/ t! q
by enlargement of the penis, development of pubic
; G8 l8 e9 ]6 V5 U/ A7 ]hair, and facial acne without enlargement of testi-: t# l+ V! W" Y2 h% K) [* h5 j7 d
cles, suggests peripheral or pseudopuberty.1-3 We# Q6 M+ l. \7 D9 W# F
report a 16-month-old boy who presented with the
+ j! K( [1 p: P1 F# P" |enlargement of the phallus and pubic hair develop-# ?* ]1 P/ r5 E; ~
ment without testicular enlargement, which was due. b& j! K8 e. s6 K/ q _1 C
to the unintentional exposure to androgen gel used by3 l8 V8 c$ R& f/ p0 }1 E, `
the father. The family initially concealed this infor-% W1 m7 q9 N6 g
mation, resulting in an extensive work-up for this6 A1 f) V. x, I1 I1 ?
child. Given the widespread and easy availability of, y3 _ W' P ^/ \/ R
testosterone gel and cream, we believe this is proba-! y" o/ l2 s: v6 N' c0 w5 P
bly more common than the rare case report in the) Q8 ~; B3 W+ S( A* g( O
literature.4
0 S% a' S" V& u- T8 h XPatient Report
4 r) w0 g- ]; Z" RA 16-month-old white child was referred to the: o% z1 [' C9 ^2 G
endocrine clinic by his pediatrician with the concern" a: Y8 }+ }) M
of early sexual development. His mother noticed9 a+ P/ W, F( G" K5 L
light colored pubic hair development when he was
- i- R+ l, d2 |# W/ w' q4 ?From the 1Division of Pediatric Endocrinology, 2University of; Q5 J% x. L) e( m3 y7 ?
South Alabama Medical Center, Mobile, Alabama.
8 U) e( ^' Y$ OAddress correspondence to: Samar K. Bhowmick, MD, FACE,
( W- J, O- B& s( h8 ~Professor of Pediatrics, University of South Alabama, College of5 T+ s+ ~( {4 I# r! C- P, R2 Z
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;9 Q# O% }( H0 n- Y4 @
e-mail: [email protected].+ |* ?7 S( |- z8 L. @. t! x
about 6 to 7 months old, which progressively became
$ r# W) J% S& H5 l: H0 W! Rdarker. She was also concerned about the enlarge-, k+ B8 n: ~/ G; _& s5 E
ment of his penis and frequent erections. The child9 X8 m; F( x4 F9 R4 c; {2 h
was the product of a full-term normal delivery, with
8 n+ G3 n# A1 H( a7 N- [5 |a birth weight of 7 lb 14 oz, and birth length of
2 t6 [) b1 ?1 Q1 e& j; y% _% Y* }' s20 inches. He was breast-fed throughout the first year
; x9 \, V9 g' m1 Vof life and was still receiving breast milk along with7 z' `6 ?% r: s" W
solid food. He had no hospitalizations or surgery,
8 @8 |+ T' o! c. ^! land his psychosocial and psychomotor development
* A2 T" F# T0 Z. ]3 u; w2 Lwas age appropriate.
# |7 q5 K. [# C2 s. y4 x% qThe family history was remarkable for the father,
, X" j6 Z* c" w& C% M$ vwho was diagnosed with hypothyroidism at age 16,& k: i$ y; \( P: r. H
which was treated with thyroxine. The father’s
7 T6 {+ d, f$ i. O' Dheight was 6 feet, and he went through a somewhat+ s8 F( D. E, y; w3 [ U; ^& |
early puberty and had stopped growing by age 14.6 G: d% V% ]- v4 H
The father denied taking any other medication. The9 l y" `3 W. F4 n
child’s mother was in good health. Her menarche
9 \* K) c9 v8 {4 T a# Pwas at 11 years of age, and her height was at 5 feet
) o6 y4 x/ H. w6 e) n' S' l z5 inches. There was no other family history of pre-, }3 y* ~8 X" x+ A
cocious sexual development in the first-degree rela-
- ^) Z3 I# H4 M. J* ^tives. There were no siblings.
, F, s. i: Z0 yPhysical Examination! D! l8 q4 A8 c* K8 b. g
The physical examination revealed a very active,& x0 P O$ y- I+ D I0 S9 g8 ^! {6 ?
playful, and healthy boy. The vital signs documented
9 [# S) G2 f, r+ m8 E4 ba blood pressure of 85/50 mm Hg, his length was
' @. \+ I2 E; Z- \3 _9 o90 cm (>97th percentile), and his weight was 14.4 kg
+ o3 Y2 q. R2 j7 k# M# G(also >97th percentile). The observed yearly growth
4 X( Q7 e4 z# N# lvelocity was 30 cm (12 inches). The examination of& F7 q5 F0 s2 |/ L) K' y9 m0 a8 z: b
the neck revealed no thyroid enlargement.* z2 s" V6 ^& D# b
The genitourinary examination was remarkable for
4 S7 C8 _# m/ S/ genlargement of the penis, with a stretched length of
! C9 U' Q) r( ], Q, X4 z/ s8 cm and a width of 2 cm. The glans penis was very well
& i( c2 `0 @# C; B9 S) Kdeveloped. The pubic hair was Tanner II, mostly around
: k0 C6 N! [- c: Z) x4 d4 s540
; y5 I$ _4 f: T, i% \' Sat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from% Q" v9 y; m* J+ x
the base of the phallus and was dark and curled. The
& A4 L2 S+ k0 T/ { Ltesticular volume was prepubertal at 2 mL each.
1 Z4 d( r" o8 B8 UThe skin was moist and smooth and somewhat
" u1 F- V( Y# [8 Joily. No axillary hair was noted. There were no }7 S8 K: u( E( t& i6 C- Z
abnormal skin pigmentations or café-au-lait spots.
! q, W7 n$ `$ j" x4 LNeurologic evaluation showed deep tendon reflex 2+/ ^! \4 B- Q2 U" f# E0 c/ A1 h& g
bilateral and symmetrical. There was no suggestion
. K+ t$ M/ X9 H7 E, Z- O, j7 P, }of papilledema.
) D( ^- ?/ |2 ~3 P/ O0 |5 RLaboratory Evaluation
& y, i+ U# U) r) p6 y) M; BThe bone age was consistent with 28 months by" `* K/ ?& f2 _( d1 Y! r
using the standard of Greulich and Pyle at a chrono-
1 [0 k+ l, d ^2 mlogic age of 16 months (advanced).5 Chromosomal
3 ~& d6 j$ O5 j. G) ]3 V4 {2 {karyotype was 46XY. The thyroid function test9 k0 B! h& ]( W% l7 m7 j
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
5 a: |, V$ _$ W) Z' @lating hormone level was 1.3 µIU/mL (both normal)./ D1 b5 Q' B1 \, U; t8 B4 i* [5 b
The concentrations of serum electrolytes, blood, w# R: H( q. u% W/ g. ?5 r
urea nitrogen, creatinine, and calcium all were" N% R; t: p9 l$ B; d6 ?
within normal range for his age. The concentration
7 P" d" n$ j" G; e3 a# _0 U0 n. U& _of serum 17-hydroxyprogesterone was 16 ng/dL
& L7 g6 E. V! U2 o% J% t(normal, 3 to 90 ng/dL), androstenedione was 20 v0 s5 f2 B/ g( D
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
( ?: g, P; s5 V$ z& ~7 S5 F! F$ jterone was 38 ng/dL (normal, 50 to 760 ng/dL),
. ]0 {# [% {2 `" `- Y% Cdesoxycorticosterone was 4.3 ng/dL (normal, 7 to- O: W* {1 p' R2 k" C5 S
49ng/dL), 11-desoxycortisol (specific compound S)
. R/ J; b. @8 u/ T7 [was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
+ o, T6 k8 h$ ~3 t* l/ M! u$ g8 ytisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
: T5 @3 ]% |5 n, R4 y" b4 {testosterone was 60 ng/dL (normal <3 to 10 ng/dL),8 |6 `, g7 f/ E, i' @
and β-human chorionic gonadotropin was less than
: o- z: T/ Z5 u& B' B5 mIU/mL (normal <5 mIU/mL). Serum follicular
5 _ |* ^: l5 S& W: ustimulating hormone and leuteinizing hormone
) f: w* z. |* V( _concentrations were less than 0.05 mIU/mL
" ?$ u" j& @; V% V9 j(prepubertal).8 H7 L; J1 s* z5 y) Y
The parents were notified about the laboratory# ^! U# s2 n& C; x" }' K& j
results and were informed that all of the tests were. @& u4 F& M! ~
normal except the testosterone level was high. The
9 G0 |! K# O2 n7 Wfollow-up visit was arranged within a few weeks to
& v- b/ u9 _- d) L1 hobtain testicular and abdominal sonograms; how-* H1 [8 q6 b# d9 G/ c( C. [
ever, the family did not return for 4 months.
1 ]! B/ K- V4 H" x' \Physical examination at this time revealed that the6 H5 B$ A) Q( q+ L/ r! S* t8 H3 S( N
child had grown 2.5 cm in 4 months and had gained" T+ v4 R0 ~. W
2 kg of weight. Physical examination remained
' o8 |* Q5 \( Nunchanged. Surprisingly, the pubic hair almost com-
6 z1 N) k, {' d* A# Bpletely disappeared except for a few vellous hairs at' H5 t. G' O( g6 F! \0 m
the base of the phallus. Testicular volume was still 2
- t L2 C% l a" m( LmL, and the size of the penis remained unchanged.
) k+ B5 r# o6 }* ^The mother also said that the boy was no longer hav-
3 G B5 b- g) |$ jing frequent erections.
% ^% M5 S( Q w# VBoth parents were again questioned about use of
( i( W- O; L, _2 ?4 Z! i) Yany ointment/creams that they may have applied to
: ^+ L: J+ K; n0 Y% ^- {the child’s skin. This time the father admitted the
& a. t- Y8 | E4 ~/ V8 h& mTopical Testosterone Exposure / Bhowmick et al 541; H% V% x6 k' S3 n
use of testosterone gel twice daily that he was apply-
% {/ x% J# U& @- I( Eing over his own shoulders, chest, and back area for$ O& @; E% w$ U0 D( Z2 |" M
a year. The father also revealed he was embarrassed
% }( f5 s+ T6 V; |: pto disclose that he was using a testosterone gel pre-
/ M# Z9 `3 k7 r& ]5 w% _. iscribed by his family physician for decreased libido
+ B5 r! T0 A3 E3 B; |secondary to depression., R. l2 y4 ?2 P# q/ v, s8 ^% j
The child slept in the same bed with parents.
% u$ _; T7 V( F% j/ \+ bThe father would hug the baby and hold him on his
' m% s ~# [; @* A# {chest for a considerable period of time, causing sig-. @7 t2 {% v+ o$ T4 O
nificant bare skin contact between baby and father.
5 I" u4 d+ G( ?) r; ?4 K/ `The father also admitted that after the phone call,1 u: w. P( X7 R3 ?% x# |
when he learned the testosterone level in the baby" v8 j' \; H+ Y$ H
was high, he then read the product information9 f( [8 g9 Z) H& R
packet and concluded that it was most likely the rea-
5 q8 M4 s+ V0 }$ G9 H, W# T; [# qson for the child’s virilization. At that time, they' U/ o. u# M, j* ^% V$ Q# T
decided to put the baby in a separate bed, and the0 Y x' o3 f: n/ Q0 h7 M7 g/ q
father was not hugging him with bare skin and had
% r6 ]( @; a5 j& z: z2 Kbeen using protective clothing. A repeat testosterone
7 K6 D. s: |- o0 `" btest was ordered, but the family did not go to the9 m! g# a a# u; w t3 p
laboratory to obtain the test.% A# W$ K0 C) l" A7 s5 H3 q
Discussion
2 E- ?+ Z( ?; H: ]Precocious puberty in boys is defined as secondary9 { F+ X: L. t$ ~# J- A
sexual development before 9 years of age.1,4
( t& t' l+ i" S: rPrecocious puberty is termed as central (true) when
' B1 d$ y, G& P9 Zit is caused by the premature activation of hypo-
3 R" ?' m; |: hthalamic pituitary gonadal axis. CPP is more com-
5 ~' X. z" r$ d+ U$ J' zmon in girls than in boys.1,3 Most boys with CPP/ j& m* S' q& M, c9 ^
may have a central nervous system lesion that is
2 J1 T1 z1 U* k' o) w3 tresponsible for the early activation of the hypothal-
0 M" W' I3 }! E d! w- Q5 S9 [amic pituitary gonadal axis.1-3 Thus, greater empha-4 c3 h! h7 U: E5 \/ }0 M
sis has been given to neuroradiologic imaging in+ ~: L, j- r3 C2 S, h. c' c
boys with precocious puberty. In addition to viril-( |8 H+ ^/ g1 l! i |1 X+ {7 R- k. L7 `
ization, the clinical hallmark of CPP is the symmet-) S2 H5 `. { W0 q' A0 H) E
rical testicular growth secondary to stimulation by; W# @8 O, j( X. E4 [: Z
gonadotropins.1,33 m- k$ r8 Z% p* Y ~$ }" M
Gonadotropin-independent peripheral preco-
: e, _6 X2 Z$ M& ?cious puberty in boys also results from inappropriate
4 o/ T' _% Y& g$ H/ A$ F, z7 V t8 [androgenic stimulation from either endogenous or
" i$ T E% T; p! Fexogenous sources, nonpituitary gonadotropin stim-" C% |8 o8 r. C1 C. S' M9 I
ulation, and rare activating mutations.3 Virilizing s0 z' w2 U! l9 P" O
congenital adrenal hyperplasia producing excessive
% Y: g) Q/ ]) P. sadrenal androgens is a common cause of precocious
0 S/ G+ m; D( d% S$ ypuberty in boys.3,4
9 A" K+ X* @( e0 N; uThe most common form of congenital adrenal
Z3 z3 B) |. O& A: Rhyperplasia is the 21-hydroxylase enzyme deficiency.
/ Q5 s7 G. y, vThe 11-β hydroxylase deficiency may also result in
+ M; x. g, @2 Z, Y5 E7 {3 @2 K& S7 ^excessive adrenal androgen production, and rarely,' _- ?4 U% z( O' i
an adrenal tumor may also cause adrenal androgen# T1 z7 N, ]- J5 ^9 l: B
excess.1,3
6 U G& ] u* x* y3 Rat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from1 u6 p- D$ ?- `( P' Z8 h* u
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
$ T9 u9 z: r+ P) a( ^A unique entity of male-limited gonadotropin-
8 V( b F. K: x9 ^; Mindependent precocious puberty, which is also known8 `. V9 J* G S P9 D9 F( j
as testotoxicosis, may cause precocious puberty at a' z, l) I/ l5 o0 F6 s
very young age. The physical findings in these boys; `# g1 E$ {4 `4 b+ J; ~
with this disorder are full pubertal development,
" h# Q Q2 i9 ^including bilateral testicular growth, similar to boys
; N- J7 i9 E- \! r9 e, S7 g5 |with CPP. The gonadotropin levels in this disorder i4 ~7 J! Y$ G5 A
are suppressed to prepubertal levels and do not show
( p: S) g! v, x Q2 Vpubertal response of gonadotropin after gonadotropin-: f6 ^: P2 E/ Q4 O( R
releasing hormone stimulation. This is a sex-linked
1 W. x; ?. k- d* |& ^autosomal dominant disorder that affects only
- c+ W* d; A) \6 {2 Y6 `/ ?males; therefore, other male members of the family$ P+ C5 w3 }7 }3 e/ K) ~5 O
may have similar precocious puberty.35 q4 I0 K/ S( }% u
In our patient, physical examination was incon-
! Y G& ^8 Q" U( Gsistent with true precocious puberty since his testi-
2 a8 e1 V8 V: I" Acles were prepubertal in size. However, testotoxicosis
9 e5 w+ n/ I8 ~was in the differential diagnosis because his father
1 ^! ]* g5 k. f( Y* Zstarted puberty somewhat early, and occasionally,
* }. o( K ]& Z5 s' utesticular enlargement is not that evident in the; U* I. a$ `! P$ O3 E; ?% U- ?
beginning of this process.1 In the absence of a neg-! H0 p0 B/ r* k2 e
ative initial history of androgen exposure, our
3 t$ p9 w) u/ ]1 l6 j* `. c: ~" G# ?" [biggest concern was virilizing adrenal hyperplasia,
. s7 k! x) m+ v" b. Ieither 21-hydroxylase deficiency or 11-β hydroxylase
" @! u, w$ I) sdeficiency. Those diagnoses were excluded by find-3 _1 R+ S9 I/ c9 v& h Y9 Y3 V
ing the normal level of adrenal steroids.8 [, F, R4 q _3 `, G6 a% n
The diagnosis of exogenous androgens was strongly
$ G2 a' }& U6 ^7 S. s9 h& q3 esuspected in a follow-up visit after 4 months because: W* P9 W- |( U' @' P+ j/ l
the physical examination revealed the complete disap-
% w% v! `4 c- S1 npearance of pubic hair, normal growth velocity, and, m$ r4 T7 s( D( \7 r; y! _
decreased erections. The father admitted using a testos-5 t; ~: e) e/ K" I( u/ k
terone gel, which he concealed at first visit. He was# I7 o$ [& S, _- t6 c: d
using it rather frequently, twice a day. The Physicians’
5 U/ _7 r. n i( y2 z a& M( TDesk Reference, or package insert of this product, gel or+ f! ^( }2 l1 @) C
cream, cautions about dermal testosterone transfer to8 K2 }, v2 H1 _- o4 Z" P
unprotected females through direct skin exposure.+ K: T! I# I$ x* d! M
Serum testosterone level was found to be 2 times the
9 q! E; w7 s- y4 y: w, \baseline value in those females who were exposed to( N* X5 g3 N9 q q9 m5 }+ ^" u
even 15 minutes of direct skin contact with their male
3 t0 }* r1 M) j8 h, Epartners.6 However, when a shirt covered the applica-
! i9 C% V9 s: R* K& q0 ition site, this testosterone transfer was prevented.7 \+ F- N1 v |' s( g
Our patient’s testosterone level was 60 ng/mL,6 y9 y( [& ^& G/ H, g) _1 D& G/ a
which was clearly high. Some studies suggest that
* W, i( Q4 M3 X; ]1 ldermal conversion of testosterone to dihydrotestos- l3 c0 q$ L, @$ }2 z
terone, which is a more potent metabolite, is more
; {" O! n+ U/ u3 Wactive in young children exposed to testosterone
# U4 N i* C2 {" aexogenously7; however, we did not measure a dihy-! z. y+ O! O# B" Q3 g, k
drotestosterone level in our patient. In addition to5 G' ?' X1 x3 I. z' k* q
virilization, exposure to exogenous testosterone in
% d' a: Q' h, lchildren results in an increase in growth velocity and V# e) v% O: ?- a0 X
advanced bone age, as seen in our patient.5 l/ i5 M% C+ D) b! ]# B4 }% v
The long-term effect of androgen exposure during
! I) W6 w0 b; s3 `' j: ]early childhood on pubertal development and final% K! A: j$ |, i% S" ~
adult height are not fully known and always remain
$ x: w. l9 {4 n- w: n% V9 D/ Y& H; Ba concern. Children treated with short-term testos-
0 \% @2 e/ M9 M4 G+ u3 rterone injection or topical androgen may exhibit some* W% J8 d' P$ M' m- S z8 ^; U( u
acceleration of the skeletal maturation; however, after
2 |/ G1 l5 E, R Q. n4 ycessation of treatment, the rate of bone maturation
2 ?4 T: L2 P9 o: {; Kdecelerates and gradually returns to normal.8,9
! c1 K1 o+ m. E3 U+ L2 M) K% pThere are conflicting reports and controversy7 S; r+ {! O$ l- l
over the effect of early androgen exposure on adult
3 D0 j$ ~$ w! h3 u9 T/ tpenile length.10,11 Some reports suggest subnormal
, `$ f! J6 Y/ y( Xadult penile length, apparently because of downreg-5 y0 g. B2 i) V/ k* K2 @
ulation of androgen receptor number.10,12 However,
* v1 h: T6 [7 \# c5 wSutherland et al13 did not find a correlation between, r& k( ?8 j, I
childhood testosterone exposure and reduced adult2 H( g6 l- l* o8 N& A! {
penile length in clinical studies.3 |6 n' m b. _: v" j; v
Nonetheless, we do not believe our patient is( ^, y$ Z/ l/ k7 ~( H
going to experience any of the untoward effects from$ \5 E9 C6 T8 Z2 B1 l
testosterone exposure as mentioned earlier because
& d) Y. b0 P |5 g( K, I9 Zthe exposure was not for a prolonged period of time.6 t: f, b7 u$ }3 t+ D8 ~! V
Although the bone age was advanced at the time of
3 `* X; v- c2 u; @1 F* N, q J. Fdiagnosis, the child had a normal growth velocity at% h0 J5 p" X5 g( \
the follow-up visit. It is hoped that his final adult
3 j( P8 C) ^# {* I; M. r% [/ Pheight will not be affected.
. D4 v5 d3 \( P1 ~. F. ^5 QAlthough rarely reported, the widespread avail-
; p( y, F+ H1 y6 Z6 K Q+ Zability of androgen products in our society may' R; `' g b7 ?# ?
indeed cause more virilization in male or female, K2 u, P" h( w8 }) Y+ S6 i
children than one would realize. Exposure to andro-( d! @3 C: Q! e2 c; i# C2 X; o
gen products must be considered and specific ques-
( B* w- ? [" [tioning about the use of a testosterone product or
( q/ g% y8 v4 m2 Q8 Qgel should be asked of the family members during
: Q+ G& p' f; D, G- vthe evaluation of any children who present with vir-
- R0 F* ^+ q% u$ v6 ]4 G2 Zilization or peripheral precocious puberty. The diag-( R* w. W( P6 A3 b: d( h/ t
nosis can be established by just a few tests and by4 q, D' ~& Z8 s2 |% H P) y6 l
appropriate history. The inability to obtain such a
! Z |5 F% a$ T+ chistory, or failure to ask the specific questions, may
" a" k+ u4 {' k6 N' [ gresult in extensive, unnecessary, and expensive
7 [7 g1 o- H1 h8 r' P, B3 Ginvestigation. The primary care physician should be- {6 M! N& ]$ H b% d
aware of this fact, because most of these children
: `. ^4 v# x0 ? qmay initially present in their practice. The Physicians’
. |( w/ h: w3 t6 ?' E [6 o1 wDesk Reference and package insert should also put a
- z6 k6 W( e1 y- T# {' Lwarning about the virilizing effect on a male or: i' \: y! X2 q, g: `- Y
female child who might come in contact with some-
$ s+ X" E* Q" o: Aone using any of these products.& I c/ m* B) S/ F9 A: }- l* a& L
References1 I4 q$ U6 f4 A3 |* I$ J" p, E, V G, k
1. Styne DM. The testes: disorder of sexual differentiation
* C: C3 L& I% q, T% l; Sand puberty in the male. In: Sperling MA, ed. Pediatric% T! W! Y( B" c
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
$ G) q$ K4 t% o# G0 p2002: 565-628.) o, J- r$ D/ x3 `
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
+ b+ m3 h5 I$ [2 E* c, Z7 q' Dpuberty in children with tumours of the suprasellar pineal |
|