- 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. f# e4 p+ ~! d# e {& W" m( R% v r% u
Boy Induced by Indirect Topical# S. H/ M5 F8 X. Z) U4 W
Exposure to Testosterone
' q/ o/ }& {" V8 @3 K, jSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
! ?. I$ `7 ~7 aand Kenneth R. Rettig, MD1
; T+ h6 j9 y }' x1 D: {# E# ~5 ]$ w, |Clinical Pediatrics% ?3 i: `+ f/ L* W4 z
Volume 46 Number 6
; M) ]0 U( O; E% {/ ]July 2007 540-543' u" y, R; @/ M W/ u! T: M
© 2007 Sage Publications
k' a) l% }* O8 s9 m10.1177/0009922806296651
- |2 E" N8 j4 D5 `( y5 [http://clp.sagepub.com) y0 V- @% s9 {9 m4 p
hosted at. L1 ^! u/ J: H+ n7 B/ W- Z2 C. O
http://online.sagepub.com
# N! p( `- S( e% U+ D$ R6 vPrecocious puberty in boys, central or peripheral,! B l2 N3 O0 e3 Z
is a significant concern for physicians. Central6 J' Y- m6 d. n" D/ {3 Y. \
precocious puberty (CPP), which is mediated
# ^( E8 J* Z h& Y8 dthrough the hypothalamic pituitary gonadal axis, has
( {: r0 z c0 e2 ]- _% B3 }, xa higher incidence of organic central nervous system' u. r) N( C. _- A7 V
lesions in boys.1,2 Virilization in boys, as manifested$ K5 L3 a/ [7 @6 Z0 A. s
by enlargement of the penis, development of pubic/ q: X0 Y% u3 D: m( \6 h7 c
hair, and facial acne without enlargement of testi-
8 |" T" W5 b5 B2 w( Y& j, [! ]cles, suggests peripheral or pseudopuberty.1-3 We
) r$ s' J! H0 j- \( J: ureport a 16-month-old boy who presented with the
1 m1 m3 A9 d' F% l" k: Xenlargement of the phallus and pubic hair develop-; a7 p) [- {$ z) e
ment without testicular enlargement, which was due# X% r: T; H; ^! S& C
to the unintentional exposure to androgen gel used by
$ H, d) y* |; V/ jthe father. The family initially concealed this infor-
1 ]0 w+ ~1 H% k; Gmation, resulting in an extensive work-up for this* v) x& F3 e& p4 {' x7 R$ t
child. Given the widespread and easy availability of
$ r; V, a$ R1 V8 O: gtestosterone gel and cream, we believe this is proba-; K! E5 Z' r# o7 z- T/ K
bly more common than the rare case report in the7 l8 Q/ R) f, ]2 f
literature.4+ `; y2 h6 m" T% @/ Z
Patient Report
7 d' `! b9 H rA 16-month-old white child was referred to the6 `7 ]# m7 K( ~6 P! H d B/ C% K
endocrine clinic by his pediatrician with the concern# N/ o2 U# a9 Y9 L$ c- K
of early sexual development. His mother noticed9 x5 f/ p* }6 a& ]. C' p8 j
light colored pubic hair development when he was
* D9 P' l& ^% Q4 B4 YFrom the 1Division of Pediatric Endocrinology, 2University of$ w) ^2 q! y( D V: `
South Alabama Medical Center, Mobile, Alabama.
0 d9 ]' i. m( R7 |% J" cAddress correspondence to: Samar K. Bhowmick, MD, FACE, D+ M* T2 G+ u) a Q' \
Professor of Pediatrics, University of South Alabama, College of* i5 |( a4 C9 z$ K6 ~% T: C
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
' I; ?! A6 T4 u6 Z. Y' Ke-mail: [email protected].. Q& i: g: F- ]# a7 H9 ^
about 6 to 7 months old, which progressively became
8 L0 G& V! \" s: T! {' _4 z6 j, v8 Xdarker. She was also concerned about the enlarge-
+ m9 |9 [$ G" [9 |1 j" Pment of his penis and frequent erections. The child3 q% }( u3 t* w0 m+ S& k) g0 p
was the product of a full-term normal delivery, with
* e3 E) \4 ^& ~7 U( h& ~) b6 O0 ?a birth weight of 7 lb 14 oz, and birth length of
8 B5 e4 ?- m' A$ |+ i- D; i3 i* y20 inches. He was breast-fed throughout the first year& \2 h% J4 R+ R( Y4 G5 d
of life and was still receiving breast milk along with( n2 s# i) w1 u3 v' S
solid food. He had no hospitalizations or surgery,
0 c1 r* C% h* u& ^$ iand his psychosocial and psychomotor development
R+ K$ z7 U. _- J: Dwas age appropriate.
9 _. Q' t! a, l3 j: `$ g n6 FThe family history was remarkable for the father,
1 D& R! r) ?8 }/ e! _) j' bwho was diagnosed with hypothyroidism at age 16,* f. [8 H. \* f2 g
which was treated with thyroxine. The father’s$ ~/ }0 U3 R( X) B! x: Q
height was 6 feet, and he went through a somewhat9 b/ x) Z, k6 w% T, A; F
early puberty and had stopped growing by age 14.: {& w: V" ^6 Q) t$ m
The father denied taking any other medication. The
6 l9 Q. K% {6 H% hchild’s mother was in good health. Her menarche; o+ u, m: Z6 e4 J. d
was at 11 years of age, and her height was at 5 feet* M, y' Q Y$ d! [: a: N
5 inches. There was no other family history of pre-* S; M9 Y S( p* R9 Q" h! Z9 S7 k
cocious sexual development in the first-degree rela-& z+ S. v* \) k2 n0 z; o4 f( j6 ^+ M
tives. There were no siblings.
# F7 l0 H; l) D. kPhysical Examination% }( U: A( G, }) O' Q
The physical examination revealed a very active,
# ] @' _. z7 e F+ M6 t& }5 n# {! pplayful, and healthy boy. The vital signs documented1 V" }+ {4 r+ L8 b( _6 l, X" T
a blood pressure of 85/50 mm Hg, his length was
& t4 x3 t, I9 p90 cm (>97th percentile), and his weight was 14.4 kg
& J/ ^$ N. `" a1 X0 Y& h(also >97th percentile). The observed yearly growth
5 d( Z8 T1 e6 n4 b* X* E: Dvelocity was 30 cm (12 inches). The examination of
* V/ _( O8 \( r6 P1 ^. j% `- ithe neck revealed no thyroid enlargement.
U' h7 e( W4 A$ ]+ @$ TThe genitourinary examination was remarkable for( S, _% {* f# w
enlargement of the penis, with a stretched length of
0 _, ~9 ~# A8 v% F) o- x' ?7 [8 cm and a width of 2 cm. The glans penis was very well
; ]7 z. I! t6 D0 ]9 }developed. The pubic hair was Tanner II, mostly around' e* D4 \- V& P3 }
540
( O2 E5 y+ G3 N: E; k* sat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from" d& E) B& x5 |; n3 n
the base of the phallus and was dark and curled. The
9 z7 y/ v4 Y, }testicular volume was prepubertal at 2 mL each.
# A, t9 N2 |1 e3 SThe skin was moist and smooth and somewhat
: |0 r1 A% @; B5 Hoily. No axillary hair was noted. There were no
: O! J) q/ T, @& i% c ^abnormal skin pigmentations or café-au-lait spots.: ^3 y; e1 u( A& s9 Q
Neurologic evaluation showed deep tendon reflex 2+
4 d( u6 Q$ u l6 v5 T, V: `bilateral and symmetrical. There was no suggestion
% V5 w( C' U. D' e* p7 u( aof papilledema.
; ?% i4 B2 M! B0 GLaboratory Evaluation! _ o$ ?$ P1 x4 {8 o1 h" U" q
The bone age was consistent with 28 months by
8 u8 t& n: w- Y2 U1 S- ~" tusing the standard of Greulich and Pyle at a chrono-7 ^* Y; L/ k% {! D5 A
logic age of 16 months (advanced).5 Chromosomal
+ U6 f _9 @6 A! V/ Xkaryotype was 46XY. The thyroid function test5 e% c! |& \2 k8 V; S
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
$ v ]/ e( L7 K g( Blating hormone level was 1.3 µIU/mL (both normal).0 M, V8 f3 q% N9 l5 d
The concentrations of serum electrolytes, blood, V* H6 M# t% G7 |% v
urea nitrogen, creatinine, and calcium all were2 o" ]3 O0 {) _, U! e
within normal range for his age. The concentration
( ]( E/ I$ X$ ^of serum 17-hydroxyprogesterone was 16 ng/dL
! x# c+ t( P5 g _(normal, 3 to 90 ng/dL), androstenedione was 203 A8 v/ E/ ~/ N0 p; G
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
4 T5 {3 n, t' e- C/ E/ kterone was 38 ng/dL (normal, 50 to 760 ng/dL),8 c# ^. `% r+ ~* F7 D% m' e+ t
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
/ M: O9 j+ }& g7 f+ v49ng/dL), 11-desoxycortisol (specific compound S)9 k) p, V# O4 E1 G6 g3 G3 C
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
3 e! u# M& A0 n6 i& |+ C' K. Vtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
M" i. c! p5 d$ K/ L" R# [testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
& D6 u% X1 ^: eand β-human chorionic gonadotropin was less than* y6 ^! n" ]6 B+ v
5 mIU/mL (normal <5 mIU/mL). Serum follicular6 V8 u9 l9 Q( I3 v& y
stimulating hormone and leuteinizing hormone8 v* F- _7 c' K/ z- {
concentrations were less than 0.05 mIU/mL( K! S1 A7 |! L: f: u3 K
(prepubertal).
& ^6 N8 R! _: g: t. hThe parents were notified about the laboratory
7 W! o9 [2 A/ I Jresults and were informed that all of the tests were
/ R. c' E2 u3 _$ l/ F" |normal except the testosterone level was high. The: r7 e% ^& a& k
follow-up visit was arranged within a few weeks to4 H8 p) u; {/ z. c
obtain testicular and abdominal sonograms; how-$ A/ u8 i6 q. q, I
ever, the family did not return for 4 months.: a9 I9 U, \0 i& g! M! d7 u) I2 B
Physical examination at this time revealed that the& Z/ R1 {( s+ |2 K2 C! D
child had grown 2.5 cm in 4 months and had gained) k1 ]$ n1 W! l% z+ ]8 q9 T
2 kg of weight. Physical examination remained0 s+ I" n4 Y; V& q
unchanged. Surprisingly, the pubic hair almost com-
! n% P( I% @- V3 t" q& H/ Ppletely disappeared except for a few vellous hairs at
$ H' O& A3 H3 `- rthe base of the phallus. Testicular volume was still 20 A3 d5 V3 P. y, J. w8 I9 o1 ~
mL, and the size of the penis remained unchanged.( ~$ D$ _7 V" a* Z! p
The mother also said that the boy was no longer hav-% ~ y$ F* V6 K, t; g
ing frequent erections.
" d1 T4 o0 B$ T2 b0 u% ZBoth parents were again questioned about use of' [3 m3 B- [) [' n# Q
any ointment/creams that they may have applied to
) v# i: z% t8 w. x! a2 B+ ~the child’s skin. This time the father admitted the" V( T$ I0 Q" ]8 T; J& L
Topical Testosterone Exposure / Bhowmick et al 5415 `) Z1 R. {( \/ \5 u3 `% v2 }
use of testosterone gel twice daily that he was apply-
! v, B) B2 B3 g6 ?4 Iing over his own shoulders, chest, and back area for1 c: ^; I7 r- h6 v
a year. The father also revealed he was embarrassed
. X. T+ W0 d9 x, M6 J+ q8 F0 A# a' {to disclose that he was using a testosterone gel pre-
* C8 ~- Z% G- L& K% e' gscribed by his family physician for decreased libido; G6 J3 x- M- k( x# c
secondary to depression.
4 q# P! \* C% w) pThe child slept in the same bed with parents.
$ S, H" m# ~) x; ~% FThe father would hug the baby and hold him on his
6 C2 h H( _0 o) D5 ?9 vchest for a considerable period of time, causing sig-
& o, ^5 X5 n! X+ K/ |nificant bare skin contact between baby and father.
3 [3 F) j/ @% [+ E) i9 uThe father also admitted that after the phone call,
5 C2 m) l1 f0 h- Q6 K7 n4 E2 Awhen he learned the testosterone level in the baby
* Y: {7 E$ o6 T1 ?9 R+ D4 kwas high, he then read the product information
( T( ~6 F$ r6 H2 Spacket and concluded that it was most likely the rea-' C7 W! @4 n7 g, o* v% [ N7 z+ G
son for the child’s virilization. At that time, they# U, s5 X) W; b% o% J" Z
decided to put the baby in a separate bed, and the
( D3 X' E* N" O8 ]- Q3 Sfather was not hugging him with bare skin and had) e- d c+ ~: \3 Z3 l. T" Y ~
been using protective clothing. A repeat testosterone) g1 a+ L/ k% f+ @) c
test was ordered, but the family did not go to the
* \0 o* [' D/ o% b! G0 R/ J3 P0 A7 a1 wlaboratory to obtain the test.
7 ~/ p7 I! h5 L) k5 t3 [Discussion( Q( k. t. ]' {& W8 u) E
Precocious puberty in boys is defined as secondary
, }/ }3 W3 x0 P2 D. {: isexual development before 9 years of age.1,4
& P' ~$ H# d4 a+ ]# }Precocious puberty is termed as central (true) when& V4 P0 ^ P8 e$ r7 \0 ?- f5 [0 @
it is caused by the premature activation of hypo-
0 l$ ^$ A! k% Bthalamic pituitary gonadal axis. CPP is more com-
, N* Y, ]" ]( t$ @. k" hmon in girls than in boys.1,3 Most boys with CPP0 N1 Q& M( S8 n% U+ H( [
may have a central nervous system lesion that is) b/ M# P6 s3 e, z+ A. U
responsible for the early activation of the hypothal-
: M( V* y4 j6 |" f% uamic pituitary gonadal axis.1-3 Thus, greater empha-( E4 K! q/ A5 {2 h: @8 Y
sis has been given to neuroradiologic imaging in$ w& `5 O( W8 u7 t9 Y' t
boys with precocious puberty. In addition to viril-
9 s+ [8 `$ M; J6 E) ~: r% Lization, the clinical hallmark of CPP is the symmet-
- {( j: P. H- {6 T, yrical testicular growth secondary to stimulation by
8 T+ B7 g+ B, N9 Z( ], Pgonadotropins.1,36 m( p# r4 y% P7 S2 n/ p4 M
Gonadotropin-independent peripheral preco-
0 C3 _ o8 G& p) g3 x" b3 Jcious puberty in boys also results from inappropriate7 p0 s8 q( r2 M. e5 e7 X" p
androgenic stimulation from either endogenous or8 d/ e* f' Q- w( _3 B3 ]0 ]7 E
exogenous sources, nonpituitary gonadotropin stim-1 A9 ?& E ?+ C/ E/ d8 c
ulation, and rare activating mutations.3 Virilizing
/ W$ Q2 }* y9 U+ L' m7 `. N- pcongenital adrenal hyperplasia producing excessive
% g9 V0 s) q& cadrenal androgens is a common cause of precocious
+ m, k1 G" h I" Q, l, D5 qpuberty in boys.3,4) |; I2 p' `: h8 V- E
The most common form of congenital adrenal
- k% }/ T0 s/ i$ R6 Shyperplasia is the 21-hydroxylase enzyme deficiency.
R9 e$ S6 H- A3 r. wThe 11-β hydroxylase deficiency may also result in
8 Z3 P0 Z& o8 D' jexcessive adrenal androgen production, and rarely,
) ]0 f2 h {& a) `# h% f3 Ban adrenal tumor may also cause adrenal androgen
: O I" s( C1 i$ bexcess.1,3- }2 N0 \% [/ `9 O+ O' a! Q) M8 Z
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from( k! o0 y) O# H
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
8 T! @! U# U7 d* X1 c# DA unique entity of male-limited gonadotropin-
9 @$ B" p- R U* _5 A5 oindependent precocious puberty, which is also known
4 N; Q$ y2 S/ `& u* {as testotoxicosis, may cause precocious puberty at a6 q% O' t0 k" j) c# `8 L
very young age. The physical findings in these boys$ H e+ c, w0 H" v
with this disorder are full pubertal development,
# U) p4 Q2 C. |including bilateral testicular growth, similar to boys; t2 r5 Z6 k9 y4 F5 {
with CPP. The gonadotropin levels in this disorder! r; U3 Y" v8 G
are suppressed to prepubertal levels and do not show
6 D5 q" ]/ \# R1 U/ t( npubertal response of gonadotropin after gonadotropin-
0 c5 s: }( J4 i; X$ z- g; S: ]& Greleasing hormone stimulation. This is a sex-linked X* e1 `5 `3 f7 u! W# z7 D
autosomal dominant disorder that affects only6 L# L! z! R3 ?; p
males; therefore, other male members of the family U9 y) j% v: A' U: S' h
may have similar precocious puberty.3) E; \! t' h& ~1 k0 j. [( c; \& ~& \
In our patient, physical examination was incon-' B$ A) D2 h9 Y y* \0 Y
sistent with true precocious puberty since his testi-1 T$ ~! q3 v5 Z; j; i# {
cles were prepubertal in size. However, testotoxicosis
( M" ^$ c- o! l5 _6 P3 r5 C+ j$ kwas in the differential diagnosis because his father
, |4 J3 i! f5 w3 U0 y3 astarted puberty somewhat early, and occasionally,
* Z; D6 Z1 b* { X6 A6 Ytesticular enlargement is not that evident in the& b e& g2 c( J: L+ V7 E% V
beginning of this process.1 In the absence of a neg-! F. K1 j/ g. |
ative initial history of androgen exposure, our" G v! y) o2 X1 q4 J/ L
biggest concern was virilizing adrenal hyperplasia,1 t/ P% u0 l1 |
either 21-hydroxylase deficiency or 11-β hydroxylase) J3 o2 D* I# o: c
deficiency. Those diagnoses were excluded by find-
( c- D5 J4 k$ W# ging the normal level of adrenal steroids.
+ ^# T/ n& b6 p! {) ]6 ]% d; X3 BThe diagnosis of exogenous androgens was strongly; o3 J4 x/ O7 [$ [* B3 O) {
suspected in a follow-up visit after 4 months because2 D( I. G' c3 h
the physical examination revealed the complete disap-
$ R- B5 U7 a7 o' s! l3 B I* ]' cpearance of pubic hair, normal growth velocity, and
4 g7 B4 y" S/ Tdecreased erections. The father admitted using a testos-6 q+ X& ]8 N, N2 i4 Z
terone gel, which he concealed at first visit. He was. N# T3 o4 ~6 C$ v# T$ x* Z
using it rather frequently, twice a day. The Physicians’" u1 c2 X$ c, q/ u t
Desk Reference, or package insert of this product, gel or/ S, Q8 l) o- U
cream, cautions about dermal testosterone transfer to
% G! }' s; H& K& Ounprotected females through direct skin exposure.
& V, e4 E9 C+ \. YSerum testosterone level was found to be 2 times the
: m" v7 P$ k$ |6 q- L |baseline value in those females who were exposed to# ^; f/ A% X2 v) V& U) e4 x
even 15 minutes of direct skin contact with their male
! q+ k4 c9 ]% O) k" M, {partners.6 However, when a shirt covered the applica-# t/ l$ d- G X
tion site, this testosterone transfer was prevented.
3 E; ?8 p4 Y4 B; hOur patient’s testosterone level was 60 ng/mL,
; y) H" a7 w/ `( y8 O0 j2 b3 wwhich was clearly high. Some studies suggest that
3 \3 c! e: V5 ^0 Edermal conversion of testosterone to dihydrotestos-
9 w/ p/ Y2 _, U4 ~$ R! [$ r. dterone, which is a more potent metabolite, is more. J8 I4 L1 k) V! X9 l( S; T
active in young children exposed to testosterone
4 q) `( ]+ |+ m0 `, y6 z# d4 Xexogenously7; however, we did not measure a dihy-
& r0 }% R: D( F' s) [drotestosterone level in our patient. In addition to3 e- z5 C/ P% D0 o
virilization, exposure to exogenous testosterone in- A) Y5 D, C" D" `4 Z0 s9 P
children results in an increase in growth velocity and4 M9 s# D. b* a9 o
advanced bone age, as seen in our patient.
' X8 M) k& m5 o2 z0 E% I* WThe long-term effect of androgen exposure during
0 n- C+ j- u, Aearly childhood on pubertal development and final, Z+ u' o( ]6 X
adult height are not fully known and always remain3 N4 I: O" f& c/ h4 b
a concern. Children treated with short-term testos-
* q. }0 j% l+ t7 \5 I, Tterone injection or topical androgen may exhibit some
2 l7 b4 h p) m/ N, b% q0 Qacceleration of the skeletal maturation; however, after" ?, k! t7 F6 V( j
cessation of treatment, the rate of bone maturation
* }7 m p. t# V. j- rdecelerates and gradually returns to normal.8,93 `6 z7 n3 ?' q, H' o" d
There are conflicting reports and controversy% T) p, I. a$ R9 }0 r% {8 o' n
over the effect of early androgen exposure on adult6 e" e8 Q$ K- p
penile length.10,11 Some reports suggest subnormal7 ^9 v+ z+ S) H6 ]) i
adult penile length, apparently because of downreg-
% Y7 E! R& i5 ?: @6 uulation of androgen receptor number.10,12 However,9 ~# Z/ ^; X: ]; c' a/ V0 N1 R
Sutherland et al13 did not find a correlation between9 o9 W6 Y5 J4 U2 x) I D
childhood testosterone exposure and reduced adult+ S y2 r- w: _1 q4 t: r3 P
penile length in clinical studies.% b% v: X/ w8 J9 J+ r q5 v
Nonetheless, we do not believe our patient is
3 R. R! R* C! ?# \) s8 rgoing to experience any of the untoward effects from0 t& K% p) E a" W1 L- m" s
testosterone exposure as mentioned earlier because' Y# R( |' O( @- N8 D, [
the exposure was not for a prolonged period of time.% s0 M* a6 l" l+ t5 s
Although the bone age was advanced at the time of
1 X8 N, Y6 O/ ~$ B/ z+ T9 K4 h1 kdiagnosis, the child had a normal growth velocity at
" M3 k$ f: f- { g' @( A' D, Athe follow-up visit. It is hoped that his final adult
4 o" ~. l, Q! z; X7 j3 Nheight will not be affected., x/ I" D8 i/ x) V$ Z
Although rarely reported, the widespread avail-% x6 q# e" O/ v6 {# Q0 \. S2 n
ability of androgen products in our society may; ^& \* v1 Q/ t7 o6 ~: I
indeed cause more virilization in male or female
3 P h& x- O1 A$ tchildren than one would realize. Exposure to andro-
9 n5 V3 J9 I' }+ f* m& F# agen products must be considered and specific ques-# K# v2 Y% M/ H8 [& S( ^$ p4 W
tioning about the use of a testosterone product or
3 B. w: h5 J3 c. Agel should be asked of the family members during! _- x: y8 ]5 ^8 A- u/ e
the evaluation of any children who present with vir-
( l; L5 X, K M6 lilization or peripheral precocious puberty. The diag-0 D5 w& |% E+ k& |# S9 X8 ~, i
nosis can be established by just a few tests and by
/ m" P/ A; m- I; Q: v8 lappropriate history. The inability to obtain such a
6 K' H2 t0 k& {history, or failure to ask the specific questions, may* n6 c5 |) |- o, y, x% j& J
result in extensive, unnecessary, and expensive# `! t- o1 r" q1 F
investigation. The primary care physician should be( A5 O A2 t, a' W+ ]/ _
aware of this fact, because most of these children9 V' |5 T7 {! K
may initially present in their practice. The Physicians’! l3 H) b. W0 i" \: O/ p
Desk Reference and package insert should also put a+ a5 Q# ]. O) W
warning about the virilizing effect on a male or
6 O- [# K1 W, C/ sfemale child who might come in contact with some-
+ H" b# l7 L. Done using any of these products.- _6 H4 V3 N9 J$ ?/ Z
References
: w3 @ _' c5 t1 @1. Styne DM. The testes: disorder of sexual differentiation8 l/ c- r1 i, Q8 ^( j
and puberty in the male. In: Sperling MA, ed. Pediatric
) F& k) l1 f0 {/ ^+ o0 Z- sEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
4 f7 F" I0 S* F7 T0 c2002: 565-628.8 x3 V3 d7 K0 O! s C v
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
' ~* L' t; [! k) Ipuberty in children with tumours of the suprasellar pineal |
|