- 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
; E9 H, Y4 r' L# ?Boy Induced by Indirect Topical
; o( \: P% ^ q) } jExposure to Testosterone
0 U! M' _8 L' n6 t @$ y5 @Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
& l. {; J( O: R2 d/ i$ Jand Kenneth R. Rettig, MD1
8 e* b! I) Y: ]' sClinical Pediatrics
4 ^4 l/ I9 h/ t, h8 p4 FVolume 46 Number 65 ^% R) S% o4 c, v
July 2007 540-543
, g) y/ `& ]2 n G( P* [© 2007 Sage Publications$ L* V" g" U f
10.1177/0009922806296651
6 E% ]6 K0 m A+ ]http://clp.sagepub.com
, l8 s! u' x2 m, _7 g9 |hosted at
; L0 \; O5 i4 C' p5 g$ Phttp://online.sagepub.com! B) i0 |. v' ?0 N# }4 m9 j% `
Precocious puberty in boys, central or peripheral,
! W# L5 P! i! w: P2 S6 z4 ~7 u+ kis a significant concern for physicians. Central
0 [7 e6 m; Q) w8 ?0 e# ?2 vprecocious puberty (CPP), which is mediated
, \9 ~$ M8 M1 e7 Mthrough the hypothalamic pituitary gonadal axis, has1 {9 h1 ?1 b0 c/ {% d8 T) J8 `
a higher incidence of organic central nervous system
3 m8 b2 Z' J5 P& ?1 j+ llesions in boys.1,2 Virilization in boys, as manifested
0 a# u3 f# a& i5 R3 @) W* dby enlargement of the penis, development of pubic
6 _# J2 o- u+ g) i% yhair, and facial acne without enlargement of testi-
4 X- z& ]3 ~* r% n0 O1 S# fcles, suggests peripheral or pseudopuberty.1-3 We
4 ]' b1 i; h$ G5 d$ K4 Nreport a 16-month-old boy who presented with the
/ L- F; P) {0 j, P6 b) {enlargement of the phallus and pubic hair develop-
( {# w9 w' g0 G& o6 M6 }ment without testicular enlargement, which was due
6 V2 `( [; d! D/ a6 ~9 E3 ?/ Eto the unintentional exposure to androgen gel used by
6 F0 }4 V; `& d( I& |the father. The family initially concealed this infor-
$ c3 I c7 e/ C' hmation, resulting in an extensive work-up for this
7 I: }$ m# s9 O5 ^9 Kchild. Given the widespread and easy availability of
, _2 Y- U3 j2 @$ Q7 ?- \testosterone gel and cream, we believe this is proba-
. C; c; m7 Z; N- p8 q8 d7 p7 Mbly more common than the rare case report in the5 X1 P+ ~/ F: E' G1 `- G
literature.4
6 a/ D+ n" P2 e' ^! S( ?4 D9 d7 a4 |Patient Report
. P# A. a% F1 N+ _: E" lA 16-month-old white child was referred to the
2 U& E+ P: o# l$ L' P- E- C8 [3 Cendocrine clinic by his pediatrician with the concern
- K; G* L/ `; H+ g0 {; fof early sexual development. His mother noticed
7 D" J& h7 T/ ?1 r# Plight colored pubic hair development when he was `3 ^" U' n& B9 P9 j9 _
From the 1Division of Pediatric Endocrinology, 2University of
/ Y3 G. `5 Y" J. K6 k+ OSouth Alabama Medical Center, Mobile, Alabama.
2 K. x/ a! W6 t3 `% I5 eAddress correspondence to: Samar K. Bhowmick, MD, FACE,0 I/ }8 K8 ?2 f4 G# W9 t0 u( o
Professor of Pediatrics, University of South Alabama, College of
1 w2 C5 }/ x7 c% g% @/ F9 z# o, jMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;/ j) R* C+ n( D4 s
e-mail: [email protected].4 W$ l$ w5 }, ^
about 6 to 7 months old, which progressively became! ]* D, c5 s0 e8 ^& |
darker. She was also concerned about the enlarge-
% }# B' C- L) S" W, w( Kment of his penis and frequent erections. The child
" ]7 Y, k( L+ s. `: ?was the product of a full-term normal delivery, with
5 C% }2 b E9 F& Pa birth weight of 7 lb 14 oz, and birth length of
6 A2 Q' Q/ r/ N9 |20 inches. He was breast-fed throughout the first year; s: w: c6 [5 R2 V: Q! V
of life and was still receiving breast milk along with2 p6 T5 B6 O3 U0 Y% T8 y
solid food. He had no hospitalizations or surgery,
% b: a/ |7 N, [and his psychosocial and psychomotor development
, D+ o5 K* J* S- c; o0 fwas age appropriate.
" C% W. i5 G; \- A9 x& h0 M. z5 A MThe family history was remarkable for the father,
! J9 S- \! `& P6 ], b' X) W, Wwho was diagnosed with hypothyroidism at age 16,; y0 L1 a* v1 z9 t* _
which was treated with thyroxine. The father’s
2 X" s& Z$ K! k1 ]3 Yheight was 6 feet, and he went through a somewhat
" G0 c( Z$ o; \1 X$ O2 {/ h( X$ e Yearly puberty and had stopped growing by age 14.
) i0 I- d( t7 |/ {: t5 HThe father denied taking any other medication. The
: K; v6 w" r* A+ x9 F, Z+ U8 tchild’s mother was in good health. Her menarche; X5 W- z! m$ ?
was at 11 years of age, and her height was at 5 feet
2 ?/ Y5 N& [9 h( T9 P. {5 inches. There was no other family history of pre-
- a! L' E$ x) J1 n Ecocious sexual development in the first-degree rela-
, F2 q0 m, R1 f! Otives. There were no siblings.7 x( h+ x: N( t9 ], G6 F
Physical Examination
; ~9 m, Y3 T+ {7 _5 N3 Y, kThe physical examination revealed a very active, z; a6 T4 C0 q2 r# G4 a/ e" N
playful, and healthy boy. The vital signs documented' W) _; J% q' G5 U6 A, P% ~, ^
a blood pressure of 85/50 mm Hg, his length was" Y+ K0 d1 R" O4 _, ]
90 cm (>97th percentile), and his weight was 14.4 kg
$ m+ |1 s) Z/ K4 u$ \7 R M8 h7 M6 d(also >97th percentile). The observed yearly growth
$ @2 K2 J" r* K tvelocity was 30 cm (12 inches). The examination of
5 c6 e8 u& o+ i# z# E5 gthe neck revealed no thyroid enlargement.$ Y4 w! \1 E& q1 A, ~
The genitourinary examination was remarkable for
, {- |( R2 n& e! s2 H; Xenlargement of the penis, with a stretched length of
5 R0 m4 g. r# }. F) \$ Z1 V8 cm and a width of 2 cm. The glans penis was very well2 N7 A3 j; Z: I' t* a
developed. The pubic hair was Tanner II, mostly around# \4 ^2 ^* X& u7 g
540
6 E2 ]! J( F2 }+ f2 O+ l4 W: `) oat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from$ Q L" S1 B1 j, _6 B/ r
the base of the phallus and was dark and curled. The
w9 c4 e" o! Rtesticular volume was prepubertal at 2 mL each.
. e+ o6 g( `0 Z/ NThe skin was moist and smooth and somewhat
' C+ Z- w* k* }9 F0 ]1 Soily. No axillary hair was noted. There were no
0 ? H6 E, {/ \' ?abnormal skin pigmentations or café-au-lait spots.
u1 T) y; |! I7 j. d/ F" @Neurologic evaluation showed deep tendon reflex 2+
! {4 G) o/ h- Q r; p1 U" H5 ibilateral and symmetrical. There was no suggestion
& k/ b0 `* v! F" N; @8 h! cof papilledema.
' K3 [4 ^: p0 [" ?! H* |0 mLaboratory Evaluation: K/ P; Z; ?9 I3 G+ W4 k
The bone age was consistent with 28 months by
$ V3 W' x9 K- n* C9 dusing the standard of Greulich and Pyle at a chrono-
5 q- J$ n( @" G; T! alogic age of 16 months (advanced).5 Chromosomal! Z6 m* I) N1 a1 W! X" e
karyotype was 46XY. The thyroid function test
/ j+ u' X* c! u! W! H0 ?showed a free T4 of 1.69 ng/dL, and thyroid stimu-* ?5 O4 b. Q5 a+ I: `; o+ j
lating hormone level was 1.3 µIU/mL (both normal).4 D( c, V& Z: i7 _
The concentrations of serum electrolytes, blood/ j) u. o3 J: o
urea nitrogen, creatinine, and calcium all were
, Q: i* ?% }7 h- u, [within normal range for his age. The concentration! I# d0 _8 \, [3 B
of serum 17-hydroxyprogesterone was 16 ng/dL
8 I" p7 Y+ I e, J(normal, 3 to 90 ng/dL), androstenedione was 202 a0 |( D2 s+ L2 o: h
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-$ A1 S1 [" R) n) {$ O1 ]
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
4 U n t8 H" ^. k! i3 B5 t- ddesoxycorticosterone was 4.3 ng/dL (normal, 7 to
% q& q+ X& r+ d# P6 t7 E0 O49ng/dL), 11-desoxycortisol (specific compound S)3 F, S2 Z+ K: w# _% h; g/ f
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-, t+ [/ D+ G8 ?) K. v3 {" m; `
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total a: v) V6 T- t
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),) b4 t0 v0 |7 O6 i
and β-human chorionic gonadotropin was less than& ]) r+ Q! z' z3 O
5 mIU/mL (normal <5 mIU/mL). Serum follicular
! r9 h& c$ Z5 S+ ~9 x! wstimulating hormone and leuteinizing hormone
2 L4 E l! ~4 d$ yconcentrations were less than 0.05 mIU/mL& K; ^5 U2 p( o2 n; ~- _
(prepubertal).
3 f+ \& O( ?* i- M0 s- z, LThe parents were notified about the laboratory: J3 {$ L5 |4 _1 k/ p4 ~
results and were informed that all of the tests were- u: k, X+ j0 k1 T& q
normal except the testosterone level was high. The
, x% O5 w! O: S0 m6 O* o( r# Dfollow-up visit was arranged within a few weeks to
: K* @+ F4 A9 U3 E9 F! \obtain testicular and abdominal sonograms; how-* J% X- ^8 v8 V7 x
ever, the family did not return for 4 months.
0 u Q' X3 P' v3 M% h! jPhysical examination at this time revealed that the
; f5 a9 L" A3 X$ \- ?2 a/ [0 Wchild had grown 2.5 cm in 4 months and had gained
* t& }8 B" R2 m7 L- s2 }2 kg of weight. Physical examination remained! R" \6 w0 O+ A" F9 E* j
unchanged. Surprisingly, the pubic hair almost com-9 p* `' }) u2 Y0 f; e* }" {
pletely disappeared except for a few vellous hairs at$ ?* U7 u2 t- V" ^
the base of the phallus. Testicular volume was still 2. W* |$ D+ I! s3 o( d* }0 L
mL, and the size of the penis remained unchanged.
& S' Y- f* R5 k7 a, ]: J+ V6 `The mother also said that the boy was no longer hav-3 X% ]. F* i4 {6 Y5 d1 q" f) G
ing frequent erections.
! @- @: r/ k6 }% ABoth parents were again questioned about use of
9 o3 p( w$ C/ Dany ointment/creams that they may have applied to% `/ t; S( s+ U( b- m, s- `( H0 F
the child’s skin. This time the father admitted the
! k8 A: ?1 C6 w; j2 Z( Z( nTopical Testosterone Exposure / Bhowmick et al 541
2 }, X: L0 ?. }use of testosterone gel twice daily that he was apply-
2 ?& d; j( p9 r2 Ring over his own shoulders, chest, and back area for
7 Z; W2 Q0 o8 Z! o" Xa year. The father also revealed he was embarrassed* ?" ^) }6 m1 P* }% ` Q5 M0 l5 i
to disclose that he was using a testosterone gel pre-( h" [ G5 z* F
scribed by his family physician for decreased libido- H4 \4 L$ q$ F( f+ A7 o- f
secondary to depression.
( J! T2 {3 U5 U' o% dThe child slept in the same bed with parents.6 g& \9 `9 Y6 V/ o" k# B
The father would hug the baby and hold him on his
7 ~% O. ~7 W/ F: _: j8 m- Dchest for a considerable period of time, causing sig-
: m6 ~/ |8 G4 a9 s% Cnificant bare skin contact between baby and father.3 w( q! R% f0 }3 m4 \* n
The father also admitted that after the phone call,
^2 _* Q. |5 Q) d. C* `/ wwhen he learned the testosterone level in the baby
- t- |( U$ ]" W) u4 ^" j$ n1 f% ~was high, he then read the product information3 _% x3 K/ s. E- V% k3 T
packet and concluded that it was most likely the rea-. K1 z% A; y. X# [) r1 ~8 P
son for the child’s virilization. At that time, they7 y( e; ^. K v
decided to put the baby in a separate bed, and the
6 `& C4 M* \" efather was not hugging him with bare skin and had4 \$ U' z9 n7 o
been using protective clothing. A repeat testosterone
% l1 I$ M9 V& Ttest was ordered, but the family did not go to the& R% m/ J" O( C4 ~, X, ?8 G' Y5 p( a
laboratory to obtain the test.
2 J: ]& c6 i$ ]; }+ l- A& `Discussion
9 t$ j# v( Y6 u/ z3 fPrecocious puberty in boys is defined as secondary {" v+ {6 ]) T: X) q
sexual development before 9 years of age.1,4. X" \( H7 e, ^! R! D# c& {
Precocious puberty is termed as central (true) when
( m7 H% w$ F* H8 ]- G- yit is caused by the premature activation of hypo-9 k4 o9 D: p: }4 i
thalamic pituitary gonadal axis. CPP is more com-
; U* A. J2 L; B% c! {8 hmon in girls than in boys.1,3 Most boys with CPP$ b. w/ h {4 A4 T
may have a central nervous system lesion that is
. k9 `# _8 C3 M* ?- Jresponsible for the early activation of the hypothal-
, a1 l k! N) p2 \- Hamic pituitary gonadal axis.1-3 Thus, greater empha-1 W1 L$ B- Z4 D% o
sis has been given to neuroradiologic imaging in
/ [1 S6 p: z& N1 C Z, E4 jboys with precocious puberty. In addition to viril-
' X R$ n2 G1 J- y" aization, the clinical hallmark of CPP is the symmet-; m t6 p! i9 U9 u* N
rical testicular growth secondary to stimulation by6 P, P3 D4 ]9 G) o# z* x+ l6 ?
gonadotropins.1,3
; S# u6 i- g N6 j7 Z; u) IGonadotropin-independent peripheral preco-4 K @% ^. u( r8 _ u" F
cious puberty in boys also results from inappropriate' e2 d$ B( N3 p. L' M5 Q
androgenic stimulation from either endogenous or
/ ?0 Q+ S* d. Z8 _7 ~2 cexogenous sources, nonpituitary gonadotropin stim-
: j+ O3 T* A0 a# gulation, and rare activating mutations.3 Virilizing3 |6 S2 e3 Z- A( m3 C/ V7 p! c
congenital adrenal hyperplasia producing excessive
( z+ z0 S; }9 ~: {/ c& d, o6 y7 Yadrenal androgens is a common cause of precocious
# f+ g0 y d* l8 S8 \: |puberty in boys.3,4
5 W3 Z- S/ i! U2 ^The most common form of congenital adrenal8 e0 W$ d' @2 f" Q
hyperplasia is the 21-hydroxylase enzyme deficiency.' r; z$ K9 t7 J6 q
The 11-β hydroxylase deficiency may also result in
0 l& t+ t& v! L6 D# a# Mexcessive adrenal androgen production, and rarely,
+ Y# {6 r e8 D. Xan adrenal tumor may also cause adrenal androgen
' _( y4 ^2 s# W3 T2 V. H$ \excess.1,3
/ g9 f; ]" K S% z7 sat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
! L8 Q9 Z4 N6 Z/ m( {542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
* w6 Q( u* O& |: C% i2 ^A unique entity of male-limited gonadotropin-
% P$ t. {: T8 g3 \" l/ cindependent precocious puberty, which is also known. ?- l, K) ~! A
as testotoxicosis, may cause precocious puberty at a
" M% t* Q$ t7 t+ ?, U9 V* Jvery young age. The physical findings in these boys
+ E, A: R9 s7 [+ J' Iwith this disorder are full pubertal development,! H' k, {$ v0 Z
including bilateral testicular growth, similar to boys, @0 X& C: |& O: I) T
with CPP. The gonadotropin levels in this disorder
% F9 @0 g; ^6 p9 W' j7 ^, e3 fare suppressed to prepubertal levels and do not show8 e1 } B, T. N( E) H
pubertal response of gonadotropin after gonadotropin-8 Z, p- H! J6 L0 s7 l: Q, I" [1 f
releasing hormone stimulation. This is a sex-linked
. s0 O6 D; @* sautosomal dominant disorder that affects only
; ^( \$ ?& u4 ]# f( Wmales; therefore, other male members of the family
. c( d/ {6 P p/ Ymay have similar precocious puberty.3
% b i' x* A" K9 WIn our patient, physical examination was incon-
" [# _6 t2 |- u* r2 h7 _* v7 s( \2 Esistent with true precocious puberty since his testi-
5 V+ P W" f& w- rcles were prepubertal in size. However, testotoxicosis. L8 [, O6 h1 S: O+ I9 }1 _) F9 j
was in the differential diagnosis because his father
3 Y+ X$ L% ~6 O: sstarted puberty somewhat early, and occasionally,+ p5 v1 U. y) {; B3 K2 r
testicular enlargement is not that evident in the
4 @$ u% _, [# W$ g0 z. v4 ]beginning of this process.1 In the absence of a neg-
" C/ I" ]) t4 X3 x( H2 M2 sative initial history of androgen exposure, our8 Y H. `; b1 [/ p5 ]7 o
biggest concern was virilizing adrenal hyperplasia,
( }6 q! E) W8 l7 seither 21-hydroxylase deficiency or 11-β hydroxylase+ u. W3 J; N" x' N+ n2 }
deficiency. Those diagnoses were excluded by find-
1 P( T: d! W# ping the normal level of adrenal steroids.
4 h4 |9 z& R6 P1 h/ x/ l$ gThe diagnosis of exogenous androgens was strongly
5 B9 h% [ G# z* j7 A H+ m) _suspected in a follow-up visit after 4 months because
, P/ V n( k( Hthe physical examination revealed the complete disap-4 e C1 @) R7 @
pearance of pubic hair, normal growth velocity, and* L6 O/ L5 z6 n* a( v
decreased erections. The father admitted using a testos-. @' K% i K' ~9 O
terone gel, which he concealed at first visit. He was' _; s/ m2 D7 p$ M8 x# P! h$ J2 j
using it rather frequently, twice a day. The Physicians’ S6 k& j3 h2 l+ H& _
Desk Reference, or package insert of this product, gel or% |& i! L5 ~/ @- R& Q; c2 H
cream, cautions about dermal testosterone transfer to+ u' x$ x+ d/ t6 l
unprotected females through direct skin exposure. Z2 ]" }" V, ~" ]) Y* }
Serum testosterone level was found to be 2 times the5 |! k. S" Q0 [$ l- [
baseline value in those females who were exposed to
" U+ e g8 x. k" qeven 15 minutes of direct skin contact with their male
, l$ Z. a( s" X8 Tpartners.6 However, when a shirt covered the applica-+ s% {& S: \0 b' B$ Q. q" k+ z& X
tion site, this testosterone transfer was prevented.
; s3 o8 v0 }( G/ S5 j8 nOur patient’s testosterone level was 60 ng/mL,% P$ d( Z+ F9 m! t V" }
which was clearly high. Some studies suggest that
7 d6 ]! E5 m3 |2 B3 G% D' |dermal conversion of testosterone to dihydrotestos-6 O/ K' c! G6 Q9 |: ?
terone, which is a more potent metabolite, is more
, f3 ~9 g" o; U: O# ?active in young children exposed to testosterone
& ]: d; e8 [% v& lexogenously7; however, we did not measure a dihy-& ^4 d3 |, K8 T* n% {
drotestosterone level in our patient. In addition to7 O& d! Q, ^' n, k" t( V g
virilization, exposure to exogenous testosterone in& p% C9 J9 E* r; {5 K; {5 v, l
children results in an increase in growth velocity and
+ M1 X4 N+ B( Q4 L" qadvanced bone age, as seen in our patient.
6 ]7 V: d( C) S. y3 `- g- U- g9 gThe long-term effect of androgen exposure during6 Z2 K- q- {6 L# z
early childhood on pubertal development and final7 H Q( ?! @6 l! ?9 d( V
adult height are not fully known and always remain
1 M# j0 e0 T0 g+ w. x4 Ua concern. Children treated with short-term testos-
- C! y% Q$ g, x& aterone injection or topical androgen may exhibit some# A8 Y$ |: N9 c' T
acceleration of the skeletal maturation; however, after
/ I- u2 i& k% r. W& ycessation of treatment, the rate of bone maturation
6 ]6 k) B7 d1 o& a- c7 n6 ddecelerates and gradually returns to normal.8,9
( t, v7 }1 W( [: b5 I4 j% hThere are conflicting reports and controversy- @5 d% [- y+ {, \, I
over the effect of early androgen exposure on adult
) E+ o0 v/ W. Y3 Z% fpenile length.10,11 Some reports suggest subnormal
" }4 }. A" \+ G2 l" eadult penile length, apparently because of downreg-
1 ?+ y, X$ g. _4 J6 ^ulation of androgen receptor number.10,12 However,
) x v$ F6 F' m$ @2 Z- [. NSutherland et al13 did not find a correlation between# C$ a W& D. f! N: o4 v% O \
childhood testosterone exposure and reduced adult
@! A4 Q1 J# h# r1 c9 I/ F j6 openile length in clinical studies.
. a' ~3 t" P* T' m# T0 sNonetheless, we do not believe our patient is
% `& S. J% @% k8 pgoing to experience any of the untoward effects from Z" y# V! g0 X( R' B
testosterone exposure as mentioned earlier because
' S; X x* G! D# @+ Rthe exposure was not for a prolonged period of time.+ A7 p0 D5 c8 j, Q ]$ C; i
Although the bone age was advanced at the time of
6 T x* t( H9 I" ~; }diagnosis, the child had a normal growth velocity at" O9 W r# L P7 m! P4 B& ~* h
the follow-up visit. It is hoped that his final adult
" y/ }( V% ]# O# S6 D# {height will not be affected.$ G: O F$ `; b4 p1 Z; Q
Although rarely reported, the widespread avail-% n6 h* |0 [9 K; G4 B- t/ z
ability of androgen products in our society may
( m! @# s5 c; f mindeed cause more virilization in male or female
( c! B- V; N6 X% o8 }+ Gchildren than one would realize. Exposure to andro-
( b$ G2 w8 v6 a6 d9 {gen products must be considered and specific ques-8 b! z+ o z1 k4 B2 B3 i
tioning about the use of a testosterone product or/ m, U2 ~% n, q
gel should be asked of the family members during
3 P: |* Y6 y' r# [/ j3 }the evaluation of any children who present with vir-, }6 V. d+ p \# {
ilization or peripheral precocious puberty. The diag-' w8 v! U% n" j0 v3 I
nosis can be established by just a few tests and by
2 ~) }$ m5 H. m% Iappropriate history. The inability to obtain such a
4 u1 I% T1 B3 R: t" Q3 xhistory, or failure to ask the specific questions, may- K. @1 h' o# b' U( |
result in extensive, unnecessary, and expensive
# q& ^, y* i# \investigation. The primary care physician should be( @7 Z4 ?) Z( ~2 S: ~
aware of this fact, because most of these children. F4 c) `/ b T
may initially present in their practice. The Physicians’
. a4 ?/ k4 a5 Y( Q* PDesk Reference and package insert should also put a1 Q3 b3 O; \9 C9 P. U
warning about the virilizing effect on a male or
% D, C8 H8 H9 y% \" I L8 p' bfemale child who might come in contact with some-
. G1 f3 B* y H W* f- V6 _4 sone using any of these products." ^$ Y* z1 X/ N- [& F+ E$ @* v
References
$ @, H( j0 ?* ]( E1. Styne DM. The testes: disorder of sexual differentiation
% R) C7 s# E# ~4 pand puberty in the male. In: Sperling MA, ed. Pediatric, C9 T2 T0 \( {' X2 U/ a
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
% y7 j- D9 [8 j U- y4 g# g2002: 565-628.& {4 o4 G; G6 E* O
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
% s/ X$ N% R8 epuberty in children with tumours of the suprasellar pineal |
|