- 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 03:27:02
|
顯示全部樓層
Sexual Precocity in a 16-Month-Old* C7 O. d5 ]& ?
Boy Induced by Indirect Topical( G$ l* @# Z0 {
Exposure to Testosterone
/ d( O. J; _$ F# I }Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2- W/ G/ ~3 U4 ^5 m0 x
and Kenneth R. Rettig, MD1
' A7 X$ Y# M" N1 W, e& k5 f7 H; IClinical Pediatrics
/ `' k4 E( C% V- e- @Volume 46 Number 6" ~3 \2 U% @ P! v6 O' ~! {3 N1 H- F
July 2007 540-543
' K0 `9 l3 d5 S© 2007 Sage Publications- ?+ N1 V: i# r; c) `& Y8 V
10.1177/00099228062966511 I4 K$ U) Y0 P0 D% Q" X
http://clp.sagepub.com; U G9 T& A% o4 x M; e
hosted at& {: J: E6 J) ]% J+ b
http://online.sagepub.com) C7 X& s. A* `" w) U' p1 b
Precocious puberty in boys, central or peripheral,; U& @$ R$ N8 F( s: z
is a significant concern for physicians. Central
7 O1 e& }$ l8 U; Wprecocious puberty (CPP), which is mediated+ f/ k. e( Z! d3 g0 v9 `
through the hypothalamic pituitary gonadal axis, has& T: D/ T4 J2 d3 k
a higher incidence of organic central nervous system6 y3 I1 R9 K& T3 A. C6 O2 Y% R& i% W
lesions in boys.1,2 Virilization in boys, as manifested5 ^$ [, j- W/ U
by enlargement of the penis, development of pubic
* j0 q6 j( @ x/ v4 ~; e1 yhair, and facial acne without enlargement of testi-
8 b0 @# _' n; M/ ucles, suggests peripheral or pseudopuberty.1-3 We% w6 N% f* M" P3 \( U( P$ q
report a 16-month-old boy who presented with the
0 E r; g" p* i; Y6 q" Y8 e0 @5 {* I& uenlargement of the phallus and pubic hair develop-) g, e' F: H7 n, ?
ment without testicular enlargement, which was due
1 J3 z5 [. ^# d! P7 w. ]to the unintentional exposure to androgen gel used by
; b3 j7 y# U; c! }the father. The family initially concealed this infor-, T. i# C4 O _- ~9 `
mation, resulting in an extensive work-up for this) K" F" n$ m) c$ I- A @# e: j3 l& G
child. Given the widespread and easy availability of
9 Q2 {% t) [- h5 B( Rtestosterone gel and cream, we believe this is proba-
+ Q1 x q! r" K; i* z+ z }2 tbly more common than the rare case report in the) d* R+ m2 ]9 O
literature.4
) i+ _ D6 F2 ~; |+ l6 KPatient Report
2 v4 Q$ ^6 F3 \( m* oA 16-month-old white child was referred to the
* [9 Y+ @8 ^0 y8 Mendocrine clinic by his pediatrician with the concern
# b( \8 T- [. Jof early sexual development. His mother noticed5 _! I! e& K; }7 {. `+ k6 f& X
light colored pubic hair development when he was
) h1 S) w9 P) R) x3 L; k# EFrom the 1Division of Pediatric Endocrinology, 2University of* p, d$ ~) j2 y& ^+ C
South Alabama Medical Center, Mobile, Alabama." J+ n% w7 | b3 d; k" [# d
Address correspondence to: Samar K. Bhowmick, MD, FACE,
" }/ ?( {1 a: Q* R: L& u6 n1 |Professor of Pediatrics, University of South Alabama, College of
1 A/ T2 q$ ?# W5 F0 MMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;! B) V u' w6 m% v
e-mail: [email protected].
J- w" k% I( r1 J' M% d+ oabout 6 to 7 months old, which progressively became
* q" Q* s: w! A5 w) h# ndarker. She was also concerned about the enlarge-4 E; O* d0 q$ `/ x! b M! G
ment of his penis and frequent erections. The child
0 y1 @" ~8 l7 O0 N# Rwas the product of a full-term normal delivery, with, o1 L$ M- h7 S& i
a birth weight of 7 lb 14 oz, and birth length of
* N9 n' E$ O% o4 o20 inches. He was breast-fed throughout the first year
& Y0 N1 w8 }1 s/ ]: t! P; H8 ? Aof life and was still receiving breast milk along with( w+ n" i7 w' H+ A! B5 ^6 a) z
solid food. He had no hospitalizations or surgery,! o! C; _! l) d5 B, R
and his psychosocial and psychomotor development
5 G' k1 o z( w& Y1 Pwas age appropriate.9 d, H# j @8 v/ @% \% U% D
The family history was remarkable for the father," `7 _/ N- v- {# ?% L, i
who was diagnosed with hypothyroidism at age 16, F7 p7 ]% P& q% T. u3 \6 L
which was treated with thyroxine. The father’s4 U- T( k- C( ?. }
height was 6 feet, and he went through a somewhat
% O1 k! |& |8 O8 c3 Y! {early puberty and had stopped growing by age 14.
|: b0 S0 o- x3 ]The father denied taking any other medication. The
, {7 m9 ?5 u# p$ jchild’s mother was in good health. Her menarche
* c$ `, ]# r. }3 k/ W# {was at 11 years of age, and her height was at 5 feet
* Y I0 C' T7 t! X/ u4 U5 inches. There was no other family history of pre-
+ T/ u4 l5 b' Y \$ Ycocious sexual development in the first-degree rela- H/ s! j1 e% A, ]# w5 b' b
tives. There were no siblings.
1 G* H. O4 `+ R+ j+ vPhysical Examination
6 S. u l- P' Z; yThe physical examination revealed a very active,
! X3 m% `; x5 |6 m) ]/ d- pplayful, and healthy boy. The vital signs documented+ L8 \. _' Z9 {
a blood pressure of 85/50 mm Hg, his length was
2 [1 F" l( R0 [- }4 J6 u% N90 cm (>97th percentile), and his weight was 14.4 kg+ u$ I) p0 u8 z {7 E0 x1 C
(also >97th percentile). The observed yearly growth
1 j% s# m! U7 S! o( v/ d$ Hvelocity was 30 cm (12 inches). The examination of
5 W" W& u! y# Q C. @7 @; A; jthe neck revealed no thyroid enlargement.
' y+ V% f8 ^+ Y, Z! X" H( j/ N4 f6 gThe genitourinary examination was remarkable for. l8 `3 C$ ]( f" h
enlargement of the penis, with a stretched length of$ ~1 ~& o$ [6 e8 F+ N5 B
8 cm and a width of 2 cm. The glans penis was very well/ I9 E4 }4 v( q1 \; x
developed. The pubic hair was Tanner II, mostly around1 H; B$ R4 w' q3 U
540, F. t9 v# H/ H1 T. G& ]( O
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
. g+ f" }& T9 c$ D5 z8 l7 tthe base of the phallus and was dark and curled. The
) L7 \* h' Z" q- Htesticular volume was prepubertal at 2 mL each.
5 P, {- ^8 G0 Z& ^0 b6 jThe skin was moist and smooth and somewhat2 A, S" r3 o! @. Q1 Q
oily. No axillary hair was noted. There were no
/ B/ B4 m) D ?+ J* R" oabnormal skin pigmentations or café-au-lait spots.
$ Q. | G( p. [4 _3 WNeurologic evaluation showed deep tendon reflex 2+, L% V# ^% i) O. a: j- {
bilateral and symmetrical. There was no suggestion
5 B x$ I7 V0 L+ ?of papilledema.
" N+ \( v) ]1 W3 a1 t tLaboratory Evaluation
c5 e1 P; D3 M8 O- r; z' hThe bone age was consistent with 28 months by
2 v7 }- K8 E4 d1 Gusing the standard of Greulich and Pyle at a chrono-
6 {( W8 |) G! O/ G) \logic age of 16 months (advanced).5 Chromosomal7 I$ l7 Y0 {- P+ q3 o. ^
karyotype was 46XY. The thyroid function test
$ x' e, ^& ]- c4 q4 K+ dshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
- h% P( Y% R" b1 d/ y9 O) m1 ulating hormone level was 1.3 µIU/mL (both normal).
/ O: z" e$ q* u, o4 ~& e# k# ZThe concentrations of serum electrolytes, blood
/ _- ?5 T# e" N( Wurea nitrogen, creatinine, and calcium all were8 }8 K5 I1 {( o7 r/ w
within normal range for his age. The concentration
( p. I" C0 _. H3 lof serum 17-hydroxyprogesterone was 16 ng/dL/ m$ R% j7 W' @* F7 w0 s: V
(normal, 3 to 90 ng/dL), androstenedione was 20; n# U. Q! g' {! M, v+ U
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-1 D: W* d2 h7 l& r# J
terone was 38 ng/dL (normal, 50 to 760 ng/dL),6 a$ L' k( J3 u; i
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
. v. n4 l. Z* {# u& I49ng/dL), 11-desoxycortisol (specific compound S)+ H8 H2 t, W" G9 A- |/ \
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-; W& V& b& L, C1 r; f) V
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total6 S5 [3 x& a7 f/ } B% ]
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),& z8 Q! A& L) {& j
and β-human chorionic gonadotropin was less than
\& U% w6 N* @. J' I5 mIU/mL (normal <5 mIU/mL). Serum follicular
4 s9 l2 T1 o' Q9 \7 jstimulating hormone and leuteinizing hormone# n/ s) k- |/ w4 W) A5 |
concentrations were less than 0.05 mIU/mL
: g/ i$ A- Y2 V) h/ k2 t(prepubertal).' B6 x1 k" E5 ^: r. e+ t! v6 G( f6 v
The parents were notified about the laboratory5 V# _& a/ T, V3 m& F
results and were informed that all of the tests were
3 n! p, i9 g6 snormal except the testosterone level was high. The6 n: E8 _9 u! c: b6 ~# ^, F/ f; f
follow-up visit was arranged within a few weeks to0 {; ~+ f1 M, n8 \, r0 q3 N; m
obtain testicular and abdominal sonograms; how-# T$ n7 S2 J8 E7 Y% `7 A
ever, the family did not return for 4 months.
% X- C' V4 K9 x# \. @- aPhysical examination at this time revealed that the+ i# c. Q- _" d/ b
child had grown 2.5 cm in 4 months and had gained
7 ^* x, g$ ]% E: x4 ]% ?) l2 kg of weight. Physical examination remained
1 g% {: I, P8 eunchanged. Surprisingly, the pubic hair almost com-
; e7 \" F8 i ]5 A2 P/ s& wpletely disappeared except for a few vellous hairs at
- I' s0 u! [4 D& rthe base of the phallus. Testicular volume was still 21 f; D, ^/ r# R8 y% I
mL, and the size of the penis remained unchanged.- Z9 D+ A+ S, a+ y4 v$ ]. r
The mother also said that the boy was no longer hav-
$ ?3 v: H6 d* L/ oing frequent erections.
! ]% ?( m2 ]1 Q; T+ SBoth parents were again questioned about use of( R5 U8 e7 U/ j+ l# [
any ointment/creams that they may have applied to+ ?# q; @* |7 `4 _% n
the child’s skin. This time the father admitted the
# O; l: o8 Z% z% K/ a1 K1 O& c( F& nTopical Testosterone Exposure / Bhowmick et al 541
5 }8 r( b/ o, Tuse of testosterone gel twice daily that he was apply-9 j) p0 }7 y8 Z# c" \; M
ing over his own shoulders, chest, and back area for
( Z/ T+ M! W- j$ J$ c; n; \* p& da year. The father also revealed he was embarrassed. t( S3 N H6 o6 t* y" P7 w
to disclose that he was using a testosterone gel pre-* R% `! }5 ]9 @# l$ C
scribed by his family physician for decreased libido. g; X; D5 |! d* c
secondary to depression.
4 u1 K$ F0 b8 W0 XThe child slept in the same bed with parents.! A9 l6 K( u4 W' ]8 S0 s5 ~' n }( ]
The father would hug the baby and hold him on his
& e2 t2 w4 c/ E1 _8 `chest for a considerable period of time, causing sig-4 Y) e5 C$ v4 H% \
nificant bare skin contact between baby and father.3 ^4 N7 W% t& r2 C4 Y# W, |
The father also admitted that after the phone call,# z1 q) u7 q! @8 D
when he learned the testosterone level in the baby' ]2 M# {2 p8 u& j
was high, he then read the product information/ Z- K1 a1 {6 B; l" {- ~
packet and concluded that it was most likely the rea-, j& h4 ^( d. c3 x6 B
son for the child’s virilization. At that time, they
% K) U Z2 ?$ V. a7 G7 l+ K( cdecided to put the baby in a separate bed, and the5 f5 @: ]0 O: m1 n6 R" Y% ` U
father was not hugging him with bare skin and had) _+ e+ P% p+ T" \- `- o# t
been using protective clothing. A repeat testosterone
* a' N* J2 p0 U0 x R0 j' \test was ordered, but the family did not go to the) q/ o! a% H/ V3 Y
laboratory to obtain the test.
' [( R5 o; T1 M5 y) HDiscussion0 q5 @! B: o. I b7 i: k9 v
Precocious puberty in boys is defined as secondary
0 v8 m0 P; ^3 i5 ysexual development before 9 years of age.1,4' w$ X3 ~ o$ e
Precocious puberty is termed as central (true) when
! Z7 ^- a: f6 s K5 t$ u, [it is caused by the premature activation of hypo-; p$ _% D- e: d% G F$ p) V# ^
thalamic pituitary gonadal axis. CPP is more com-
) E( n# V) [& ^7 C0 n, n6 ~2 \mon in girls than in boys.1,3 Most boys with CPP
6 S3 _: E8 E4 ^( \& umay have a central nervous system lesion that is
% V3 g( N$ I# Presponsible for the early activation of the hypothal-
2 N- c1 p& {% k+ ~3 Z' k" eamic pituitary gonadal axis.1-3 Thus, greater empha-6 p" L8 n8 t, k2 V
sis has been given to neuroradiologic imaging in
5 F( ~: Z2 [, qboys with precocious puberty. In addition to viril-
) e5 O% Y5 s% b+ H: L1 S" b, xization, the clinical hallmark of CPP is the symmet-+ }) ^" x% `/ s a C: _8 ~! R
rical testicular growth secondary to stimulation by
1 f! j6 ~6 x5 dgonadotropins.1,3
' v4 F6 x6 n% W. OGonadotropin-independent peripheral preco-
; R4 m, W, p; n$ Q+ Z( @cious puberty in boys also results from inappropriate
' a8 Y) \, n. L7 H& qandrogenic stimulation from either endogenous or
/ T! w) x8 x$ i6 M9 m8 w: kexogenous sources, nonpituitary gonadotropin stim-
& W) s6 ]/ r7 ?5 L; Q, f6 Z k9 oulation, and rare activating mutations.3 Virilizing
: c1 }1 ?! f/ T. B, s, Hcongenital adrenal hyperplasia producing excessive9 V# _6 H0 X+ x
adrenal androgens is a common cause of precocious/ U, E6 b1 |6 i0 t
puberty in boys.3,4
+ V: j9 z) G! `1 Y2 _4 i4 PThe most common form of congenital adrenal8 \/ w/ h. g5 {
hyperplasia is the 21-hydroxylase enzyme deficiency.; ? `& K( C1 M1 b" u
The 11-β hydroxylase deficiency may also result in! [1 Z- l5 }0 P+ c( a7 G
excessive adrenal androgen production, and rarely,
1 d9 n; L3 b9 B( a0 T% nan adrenal tumor may also cause adrenal androgen) H/ G2 p2 @$ Y! s
excess.1,3
0 F2 O3 @8 f8 p" t! N$ O6 z9 O9 q1 Wat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from# D5 U' c1 i. e
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
4 p4 P7 O9 U3 c" n* v8 x. G! `A unique entity of male-limited gonadotropin-2 H% ?; }0 M w
independent precocious puberty, which is also known
d+ a# `% v" R* |' O3 V( h1 Kas testotoxicosis, may cause precocious puberty at a! K& b- k4 [6 W& M" I4 Z6 W
very young age. The physical findings in these boys: x* z! F8 ^' G, O$ S* ?# I0 W ~
with this disorder are full pubertal development,
- g6 C- T1 k3 y9 gincluding bilateral testicular growth, similar to boys
. C6 {* {6 Y% D# ?; `0 Kwith CPP. The gonadotropin levels in this disorder
/ H3 _- v# T; n) ~* Hare suppressed to prepubertal levels and do not show
/ h- X3 M: g3 K/ X3 m+ E; `pubertal response of gonadotropin after gonadotropin-9 j% V9 U8 m5 s
releasing hormone stimulation. This is a sex-linked
0 P6 a ~; o" K/ Eautosomal dominant disorder that affects only
7 |" ]% b' h/ V& B/ ^9 H6 Smales; therefore, other male members of the family w3 N/ |8 i3 }: X
may have similar precocious puberty.3+ c1 n- A/ Y# ?5 S( f
In our patient, physical examination was incon- E' L# D& O4 \" f+ N' j6 ?
sistent with true precocious puberty since his testi-
* B! s# X6 I, T5 J9 `+ n8 z2 y+ Acles were prepubertal in size. However, testotoxicosis
F! b l+ E; X7 W6 Hwas in the differential diagnosis because his father) m% m2 t' L0 {( T$ o
started puberty somewhat early, and occasionally,/ e# H: d1 E' [+ Z! V3 S9 B( e( o; M
testicular enlargement is not that evident in the
' t# `6 l U+ r4 Q# cbeginning of this process.1 In the absence of a neg-
: C) R' T; j4 ]ative initial history of androgen exposure, our" ^9 y2 J( Z& G3 L3 s$ s) n: x
biggest concern was virilizing adrenal hyperplasia,+ M5 Y4 R0 K$ K' v3 h$ H
either 21-hydroxylase deficiency or 11-β hydroxylase9 P% `, w+ J ?3 V. u7 k$ b J
deficiency. Those diagnoses were excluded by find-
8 H5 Y1 G g9 xing the normal level of adrenal steroids.
! E7 p3 R4 X3 {* Y1 hThe diagnosis of exogenous androgens was strongly, j$ B8 @: {: G3 C/ a2 ]! J
suspected in a follow-up visit after 4 months because1 g: x8 ?+ E6 [) |
the physical examination revealed the complete disap-6 ]2 [1 f) t6 f
pearance of pubic hair, normal growth velocity, and
5 X6 P! `" I; c4 M3 ddecreased erections. The father admitted using a testos-( d- w; w0 }' B- n" V: x5 c
terone gel, which he concealed at first visit. He was
8 m& Y2 y! V# i& ^! d3 Z1 }( Kusing it rather frequently, twice a day. The Physicians’" \- [5 f; l* ]; r
Desk Reference, or package insert of this product, gel or5 ?4 x( D+ U' U7 r, A/ u
cream, cautions about dermal testosterone transfer to
6 e3 i$ Y5 k; K: I( q0 ^unprotected females through direct skin exposure., c2 ]! R' N+ b5 W
Serum testosterone level was found to be 2 times the
6 r6 F z, @+ @. c$ P) Xbaseline value in those females who were exposed to
9 t& f: O% ` n7 Z4 Jeven 15 minutes of direct skin contact with their male1 b0 z- Z. x: e6 a( K# ]) P2 T3 M
partners.6 However, when a shirt covered the applica-
! W" N z# u' Q7 ~" F. wtion site, this testosterone transfer was prevented.
b# h1 r, U. U' L0 O; M, ]Our patient’s testosterone level was 60 ng/mL,# p {' u# \# l
which was clearly high. Some studies suggest that7 X( |) S1 C3 @# v# C6 A- x. C2 _
dermal conversion of testosterone to dihydrotestos-
, t# Q4 u, {) vterone, which is a more potent metabolite, is more" e( q) U6 F8 e, k4 y: T$ f
active in young children exposed to testosterone" q$ L2 P1 D/ r4 Q2 V" j* Q9 }/ B5 u$ r
exogenously7; however, we did not measure a dihy-% D9 s2 Q6 Q2 _5 \+ ]1 W+ E
drotestosterone level in our patient. In addition to
/ L* }# |2 E9 ~' k5 Q' Jvirilization, exposure to exogenous testosterone in8 D2 M* t6 d( v
children results in an increase in growth velocity and4 f5 E7 S. C: q( B
advanced bone age, as seen in our patient.
# A9 P% \' z: }3 tThe long-term effect of androgen exposure during
7 r' U' V: r3 W5 r8 Y* Searly childhood on pubertal development and final. A M( }1 g5 E# e% t" n$ @6 [
adult height are not fully known and always remain' I* s. ]) N5 a% R( f2 V# A, y( P
a concern. Children treated with short-term testos-
: C3 i+ G6 l+ Lterone injection or topical androgen may exhibit some
* A1 l6 \7 @, p# s) \acceleration of the skeletal maturation; however, after5 \. @1 ^& X, X8 y: X/ K& p
cessation of treatment, the rate of bone maturation
$ ?7 Z3 J1 t, a8 Q" \decelerates and gradually returns to normal.8,9
* e$ R8 C, C& jThere are conflicting reports and controversy
. ], h6 N1 Q# K+ n7 B5 U4 }* wover the effect of early androgen exposure on adult& s0 }8 Q8 {$ K+ A0 A2 O
penile length.10,11 Some reports suggest subnormal
0 n& b+ a. p2 s( B% Zadult penile length, apparently because of downreg-0 O4 w& T% ]+ p7 `- L+ D2 x
ulation of androgen receptor number.10,12 However,
3 J1 K* \, ^5 F2 P& e! K( ZSutherland et al13 did not find a correlation between6 N7 L% y% ]! J$ b* k2 n
childhood testosterone exposure and reduced adult
G6 m( M& u( Kpenile length in clinical studies.
- D0 Q, R D6 ]. x+ pNonetheless, we do not believe our patient is
5 S8 f/ x2 L- Y5 t7 sgoing to experience any of the untoward effects from2 ~) z7 w1 e, G
testosterone exposure as mentioned earlier because
9 V8 o+ O5 B& {0 @the exposure was not for a prolonged period of time.
l f+ M. I9 {Although the bone age was advanced at the time of! ?* q" Z3 P* T4 j2 S9 _
diagnosis, the child had a normal growth velocity at" R; Z A" {3 ?/ h. W: R! W9 b& {1 C
the follow-up visit. It is hoped that his final adult
f1 ]& H7 @7 \1 Z8 ^5 X+ Zheight will not be affected.6 P0 t# t3 m# m l
Although rarely reported, the widespread avail-5 _% C( D1 t- ~; I9 U1 u: W: a4 N! ~
ability of androgen products in our society may
3 s+ A6 l7 u6 |4 ~indeed cause more virilization in male or female8 b/ y6 A% g! o/ N# Q
children than one would realize. Exposure to andro-1 m- h) ]5 y: U$ D/ {
gen products must be considered and specific ques-
8 y F: @ B, K. rtioning about the use of a testosterone product or8 W+ T6 p- E! P/ }1 O+ c6 R$ b
gel should be asked of the family members during
) j- e& r9 \8 S3 X. Tthe evaluation of any children who present with vir-
3 R4 P7 j* A: V& _& V3 Kilization or peripheral precocious puberty. The diag-) T, p e$ P7 A; p# n8 a/ I
nosis can be established by just a few tests and by" a& _3 D5 M1 d/ V3 D! i0 x
appropriate history. The inability to obtain such a! X' m6 O! {' K+ J" N
history, or failure to ask the specific questions, may
% `3 b% E+ }+ m2 bresult in extensive, unnecessary, and expensive
2 i8 ? j, D' U: S5 \investigation. The primary care physician should be2 [6 Y& u6 U/ t0 O1 n1 h
aware of this fact, because most of these children
! \2 A/ ^( _6 P. A0 e! [, v* m: zmay initially present in their practice. The Physicians’9 H- \: G2 D4 X& T# B; H
Desk Reference and package insert should also put a) _, F5 W4 B- Q( e" G
warning about the virilizing effect on a male or. T) Q" X6 X6 j: K: [9 M5 K1 a
female child who might come in contact with some-
& O3 X* M1 I; q. cone using any of these products.! z; B9 J7 t7 o; p8 g6 {" m
References4 d9 a6 f1 F& V: z" _
1. Styne DM. The testes: disorder of sexual differentiation' z9 q3 \ ?& m4 p1 ~- H
and puberty in the male. In: Sperling MA, ed. Pediatric
: w7 F" b# ?1 V; Y4 l( qEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
7 V: Z- A3 v! `2002: 565-628.
4 a: z9 U x. j+ }2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
! x+ b; e3 Q8 W5 jpuberty in children with tumours of the suprasellar pineal |
|