- 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-Old& z$ ]6 x7 G5 b7 Q: X- v2 W
Boy Induced by Indirect Topical, v8 i$ Q" _" b6 g% O {8 R' s
Exposure to Testosterone
: q1 w0 @; O* i* Q4 b! s) d. FSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,21 [/ k8 c1 \( q1 M4 E' b H
and Kenneth R. Rettig, MD1
$ o- R" A8 y: Y& ~* T9 [Clinical Pediatrics! \ ` B# f7 P+ k& P! u& e9 J( P
Volume 46 Number 69 Z( N/ v0 I$ c0 d1 t: N# T: Z
July 2007 540-543
: Y3 T# R* d7 Z+ A© 2007 Sage Publications
7 E+ J, x. F& f7 N1 d4 d9 K' ?10.1177/0009922806296651/ U* T% U- p( P J3 o& v$ [% i
http://clp.sagepub.com
. O# w* Z+ Z0 D8 a/ C, ~/ x6 b0 yhosted at
K7 F4 Y7 T/ C/ M& Ihttp://online.sagepub.com5 J- S; A& N3 P
Precocious puberty in boys, central or peripheral,9 _/ D! ^9 J# d' _( r; t
is a significant concern for physicians. Central! S" |$ |' ]2 j$ s9 q2 l3 Y
precocious puberty (CPP), which is mediated+ m" Z+ A7 z" G4 T
through the hypothalamic pituitary gonadal axis, has
7 c$ f" J x- B9 R9 @" |. R: v+ W8 _a higher incidence of organic central nervous system
7 r0 Q$ c) r/ i6 ?+ C5 m. Rlesions in boys.1,2 Virilization in boys, as manifested
" ]7 \! l8 h) R; m' U. Hby enlargement of the penis, development of pubic
$ \. H6 w9 u4 h; `% Yhair, and facial acne without enlargement of testi-
* Z9 z6 u. u$ lcles, suggests peripheral or pseudopuberty.1-3 We5 h4 x' e# Z- {
report a 16-month-old boy who presented with the
n, Q, c$ \# Z w( yenlargement of the phallus and pubic hair develop- r$ @; ^% z; Y% _; z
ment without testicular enlargement, which was due2 w6 |1 C; S1 @9 m5 o e3 D
to the unintentional exposure to androgen gel used by& A' i8 V" p: c
the father. The family initially concealed this infor-
$ j) F" O, i( K$ s0 M% _. u! hmation, resulting in an extensive work-up for this
0 V. Z* X7 ^' J$ A3 e _child. Given the widespread and easy availability of! J( }" y2 f' z% O
testosterone gel and cream, we believe this is proba-6 D( L; j: Z+ b" T- L5 U, K' I x5 [
bly more common than the rare case report in the
1 A4 v2 A, Z: _" aliterature.4( z/ |0 `: d* Z s" V9 E
Patient Report
" Q, P' C& Z+ O" M( LA 16-month-old white child was referred to the/ a0 {4 @7 x/ n( K0 V" c
endocrine clinic by his pediatrician with the concern
3 h9 L8 |; a; H/ |' rof early sexual development. His mother noticed
# N8 W9 T4 Z: _3 k, D$ ]light colored pubic hair development when he was3 p* C( P! H5 N' e) r; j/ ?9 c: c
From the 1Division of Pediatric Endocrinology, 2University of: |7 ^: n; @. E9 l# d# C- i; m
South Alabama Medical Center, Mobile, Alabama.
4 x( z1 D+ Y; e$ \& P0 w( NAddress correspondence to: Samar K. Bhowmick, MD, FACE,7 T5 E% Y# s1 l! }+ Q' Q% A
Professor of Pediatrics, University of South Alabama, College of. N; y8 Q7 K8 F5 g7 ]2 p) X
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
8 ?+ c% E9 _* d9 q' S( ^" Ce-mail: [email protected].& }! @% S3 R- j# U" F
about 6 to 7 months old, which progressively became
( B1 W- f) O5 bdarker. She was also concerned about the enlarge-9 l. K/ h% w3 I9 E7 J
ment of his penis and frequent erections. The child& a( D- [! |9 ]+ v" t" p
was the product of a full-term normal delivery, with
L' c3 Y/ _. D6 G4 ka birth weight of 7 lb 14 oz, and birth length of( _3 e$ F/ R: G* T1 G- ^+ K
20 inches. He was breast-fed throughout the first year
& j$ F+ r7 m* f' c5 ~of life and was still receiving breast milk along with0 k& a. O" W, z) ^: g
solid food. He had no hospitalizations or surgery,0 G* a) Q/ E* t9 h! D( f& \" [
and his psychosocial and psychomotor development' r6 D3 t) z1 P
was age appropriate.
( |2 G* s/ g& e! t) ], EThe family history was remarkable for the father,
9 S% `: d! \$ c. C1 {% ewho was diagnosed with hypothyroidism at age 16,8 f" W7 @% D; B* T% h3 b: z
which was treated with thyroxine. The father’s
- e" Y$ Q* m3 c* Q5 g( I" Z. \height was 6 feet, and he went through a somewhat6 { |9 {1 y/ ^ y/ C; l
early puberty and had stopped growing by age 14.
" V8 R0 ?; ~- q" O) g O7 ]The father denied taking any other medication. The5 S) h5 @. {5 o8 V- d b
child’s mother was in good health. Her menarche
1 \4 v* v; { p: F5 Ewas at 11 years of age, and her height was at 5 feet0 z8 X) p: Q* ~
5 inches. There was no other family history of pre-
8 o. B& U% O7 V) f* r+ ecocious sexual development in the first-degree rela-0 |) X* L. S# i t: V, l
tives. There were no siblings. @1 G1 L8 F& i; w4 S" d
Physical Examination
& }+ R7 n2 Q/ c( J3 S' A8 `) M2 @, sThe physical examination revealed a very active,0 @% i, a0 q3 \' u
playful, and healthy boy. The vital signs documented
( z9 f3 r( Z! I9 l" {5 ga blood pressure of 85/50 mm Hg, his length was
& T1 D7 M# [1 i5 E4 y% }6 G90 cm (>97th percentile), and his weight was 14.4 kg9 E! t& N, O/ l# ?. b
(also >97th percentile). The observed yearly growth
m5 Z* I+ \1 b! c# ~velocity was 30 cm (12 inches). The examination of- }' Z9 |4 C& V: N
the neck revealed no thyroid enlargement.3 X1 N5 a. G% Z2 B7 M. l9 @
The genitourinary examination was remarkable for# C/ Y. e4 k; l: l
enlargement of the penis, with a stretched length of: A' H9 ]: ^% c3 }5 W
8 cm and a width of 2 cm. The glans penis was very well6 b% p9 c1 ]5 m1 ?) d: {
developed. The pubic hair was Tanner II, mostly around
* `% @ Q( d2 I u% U* _* k% b5409 m$ V3 a9 M" r# O
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from- _" u% g9 d) y0 D, `+ H8 {# {1 g
the base of the phallus and was dark and curled. The
# G" {- C1 U4 \2 i4 rtesticular volume was prepubertal at 2 mL each.$ r/ x1 I; D" t, b7 c! I
The skin was moist and smooth and somewhat
: ]$ J* ?9 L/ P5 E2 F# ^oily. No axillary hair was noted. There were no
) `3 N) W% i# x+ L- h" Rabnormal skin pigmentations or café-au-lait spots.! p) D9 R( C' p- @
Neurologic evaluation showed deep tendon reflex 2+) H7 U& Y7 p* Z: n$ g0 r* F
bilateral and symmetrical. There was no suggestion
7 O- }* ^- G7 k2 d7 d# D. i, |0 mof papilledema.7 n# F0 c- e& y+ [: F N4 u
Laboratory Evaluation' i6 W. |+ e, P1 t/ u
The bone age was consistent with 28 months by6 A) y' e0 W+ M% E
using the standard of Greulich and Pyle at a chrono-3 q. U7 U& w3 I1 l1 Z
logic age of 16 months (advanced).5 Chromosomal- |( l: F6 I# _- c5 J
karyotype was 46XY. The thyroid function test. V' c: S d- \) T: n+ s
showed a free T4 of 1.69 ng/dL, and thyroid stimu-7 o# p0 \0 A" a& D6 p
lating hormone level was 1.3 µIU/mL (both normal).
B, m! x! U" MThe concentrations of serum electrolytes, blood Z4 `+ Z3 [3 S5 l3 g' Y$ O
urea nitrogen, creatinine, and calcium all were
3 a" c7 t9 [' y: [# twithin normal range for his age. The concentration4 B% _8 x" d2 Z6 y- F
of serum 17-hydroxyprogesterone was 16 ng/dL; P" J$ W a* x
(normal, 3 to 90 ng/dL), androstenedione was 203 d4 u. z A4 w5 y: F. i# A
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-% {0 z {; j! c
terone was 38 ng/dL (normal, 50 to 760 ng/dL),4 ~( o) x8 w/ S$ R1 B' J
desoxycorticosterone was 4.3 ng/dL (normal, 7 to& w8 e. X# X3 [, \/ H; X
49ng/dL), 11-desoxycortisol (specific compound S)( J+ H' Y$ W |. Y* \) T
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
7 [. R4 j0 L: @' Y/ i+ z- @tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
* C! ?0 Z1 p3 C) |$ Dtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),& N( W" v5 E& k, D1 ?
and β-human chorionic gonadotropin was less than: t& q! {3 @" X6 q, I `
5 mIU/mL (normal <5 mIU/mL). Serum follicular
) B4 C3 a5 ]0 I6 _# G4 W1 B' tstimulating hormone and leuteinizing hormone
' k/ g+ T; j4 Q" Y2 }! Tconcentrations were less than 0.05 mIU/mL' ?- m, r7 j7 k+ K7 x1 i0 I! q
(prepubertal).
; M- b8 l& E& K+ R; t- A3 e& ]The parents were notified about the laboratory
5 m, f$ z' y3 j% x( n: dresults and were informed that all of the tests were6 Z% H4 z* f2 C5 |0 s7 g# u
normal except the testosterone level was high. The' X, t; y/ N/ o2 z7 `" g
follow-up visit was arranged within a few weeks to8 S! J" G3 j2 |% g6 ~
obtain testicular and abdominal sonograms; how-9 X& Z3 {# K% |- H4 l
ever, the family did not return for 4 months.
Y9 _% }0 V: Q8 w; f% Z7 P& O- m$ l. iPhysical examination at this time revealed that the
, N0 K: @) n6 e* \, nchild had grown 2.5 cm in 4 months and had gained/ z$ p+ c% z) L( W1 s1 X& m2 Z, l6 A
2 kg of weight. Physical examination remained
, i3 t$ B# c1 H2 k! j$ Gunchanged. Surprisingly, the pubic hair almost com-( B6 J* s8 t9 T& U1 |" @
pletely disappeared except for a few vellous hairs at: v6 w- W% C. H3 v
the base of the phallus. Testicular volume was still 2
8 {$ ^/ h7 [7 v/ h; D* u: r! BmL, and the size of the penis remained unchanged.$ L' B. E5 E! l* s2 X, `
The mother also said that the boy was no longer hav-, n. @6 i, Z+ O: c. n0 X+ g1 k9 d
ing frequent erections.7 Q( H, K5 D) n& P( S& T/ n( F: z" h
Both parents were again questioned about use of9 P% h4 D6 P+ `" e
any ointment/creams that they may have applied to
4 w& r' @ y" n2 q4 Z- wthe child’s skin. This time the father admitted the
% X8 D/ W9 i2 `$ k) h0 ITopical Testosterone Exposure / Bhowmick et al 5415 z P g; T5 \7 C
use of testosterone gel twice daily that he was apply-, R3 h5 O% W" ?9 @" O3 ^
ing over his own shoulders, chest, and back area for
0 M3 Y# \0 R; ?( xa year. The father also revealed he was embarrassed
% ^! l# c6 P" ?! Qto disclose that he was using a testosterone gel pre-
! u- y8 u8 f8 z' mscribed by his family physician for decreased libido
/ ?$ @6 @5 J7 asecondary to depression.
8 E6 u8 K! S0 i9 G( YThe child slept in the same bed with parents.5 d: Z% g/ c$ d2 A w( j
The father would hug the baby and hold him on his) n$ w' e1 c- [6 h
chest for a considerable period of time, causing sig-; p6 `1 u4 b X3 d% A
nificant bare skin contact between baby and father.
$ T" w* u$ y" n7 M" p9 `The father also admitted that after the phone call,
# s, S, Q" o) z0 S8 Awhen he learned the testosterone level in the baby7 f) U0 ~, v; _! D2 d* q" h; i
was high, he then read the product information3 e' Y6 e; J0 D) Y0 V
packet and concluded that it was most likely the rea-
4 p8 o3 R6 Q& {2 @son for the child’s virilization. At that time, they
/ ^, F' ]# ^ u) O2 Z2 ]2 @7 F- ydecided to put the baby in a separate bed, and the j% ], \1 \6 z# V" ]! ]( c& d
father was not hugging him with bare skin and had
& l) p$ L3 I& {* b# W Kbeen using protective clothing. A repeat testosterone& {: f, f2 {- r- D9 `9 [* [& u
test was ordered, but the family did not go to the
. }' b w, \2 \9 |. Z/ ^8 K6 Slaboratory to obtain the test.% \4 Y( t# ]6 ] ?; g
Discussion! Q! F/ o4 H" t% u
Precocious puberty in boys is defined as secondary
; ]) ?& K) ^# {, E( asexual development before 9 years of age.1,4
' b* D! R/ p8 w' `+ }- NPrecocious puberty is termed as central (true) when
/ M( q2 z+ L: j; a* vit is caused by the premature activation of hypo-
; E: I$ p& o' ^! cthalamic pituitary gonadal axis. CPP is more com-- H6 ^) u% Z. y% U L3 z
mon in girls than in boys.1,3 Most boys with CPP
. | g' q5 }) e `may have a central nervous system lesion that is z4 v! |1 Y, w! i) H
responsible for the early activation of the hypothal-
% q) F8 H5 w! ~2 gamic pituitary gonadal axis.1-3 Thus, greater empha-
! M" v3 [) T: [( F+ \sis has been given to neuroradiologic imaging in% r5 u4 L/ U C: N. J- K8 d
boys with precocious puberty. In addition to viril-
6 F, k/ J H2 Q. `6 x$ jization, the clinical hallmark of CPP is the symmet-& `' N- V2 e6 U% ]( O% k" Z+ `+ {8 j
rical testicular growth secondary to stimulation by
8 T. r4 j' k' T5 y( `! B1 m% zgonadotropins.1,3" ~, ]7 r9 o6 y1 e2 N
Gonadotropin-independent peripheral preco-
) H! c5 o4 A& T+ zcious puberty in boys also results from inappropriate
+ m$ o0 p9 w. ^androgenic stimulation from either endogenous or
9 {1 r/ ?. ~6 T: H9 f/ @4 [2 Qexogenous sources, nonpituitary gonadotropin stim-
' |9 |) E6 k* ^$ culation, and rare activating mutations.3 Virilizing/ w. o) Q. x0 M2 N9 I. i5 G9 \. T
congenital adrenal hyperplasia producing excessive5 B" d9 s. L5 J, B( ^
adrenal androgens is a common cause of precocious
8 d/ a5 t8 Q, S1 Fpuberty in boys.3,42 | D/ q8 U3 e3 S- H9 y3 o& @
The most common form of congenital adrenal
/ k! M/ f z( P, O2 c4 V5 Yhyperplasia is the 21-hydroxylase enzyme deficiency.
; m% i# t) N2 aThe 11-β hydroxylase deficiency may also result in2 G% m# w* D# L3 @/ T
excessive adrenal androgen production, and rarely,
* c$ ~: F+ p( E+ J- @, Yan adrenal tumor may also cause adrenal androgen' _* U! z$ D! y; ]
excess.1,3 {" {$ E: z$ v
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
% E2 Y0 M9 t- U% J& w: C% ~542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
9 r: {& @, a% r6 |2 sA unique entity of male-limited gonadotropin-
& |3 J0 u: v: a" |3 Pindependent precocious puberty, which is also known
3 \- I9 D$ L. Das testotoxicosis, may cause precocious puberty at a
4 @0 I' R+ J( r3 T3 Every young age. The physical findings in these boys
! `) ?) l7 z y1 g7 E zwith this disorder are full pubertal development,
5 c. L0 L/ {* g+ Iincluding bilateral testicular growth, similar to boys* u/ v: J, h% m
with CPP. The gonadotropin levels in this disorder
* z6 Q! M; Q3 d. S, m. C$ g" xare suppressed to prepubertal levels and do not show1 P1 B' T) G5 {7 O6 O# ~5 O1 J
pubertal response of gonadotropin after gonadotropin-8 O* B$ e4 ^# y( o- y, \& x7 P
releasing hormone stimulation. This is a sex-linked
) q7 S$ l9 t2 Q4 @autosomal dominant disorder that affects only
. x ~* A4 e, Hmales; therefore, other male members of the family
! n* t# \, v7 qmay have similar precocious puberty.3
" f/ g1 b( u/ E, LIn our patient, physical examination was incon-
4 w1 t3 k/ c" Z' a! x0 t* Jsistent with true precocious puberty since his testi-; c' U, A4 j4 p
cles were prepubertal in size. However, testotoxicosis
g" Y' u+ I0 F; `was in the differential diagnosis because his father) b @% J( C1 r/ E) G1 u: ^
started puberty somewhat early, and occasionally,3 k7 u7 R0 F7 G4 p8 X* W/ p/ o0 d
testicular enlargement is not that evident in the
! k: S9 a- W! C n- V7 L8 Gbeginning of this process.1 In the absence of a neg-
( O0 h& x5 L5 r6 E# t; D5 jative initial history of androgen exposure, our2 A: ~" k; k3 q5 e2 r9 L3 {
biggest concern was virilizing adrenal hyperplasia,
1 ^. z7 g0 [0 a6 G4 {either 21-hydroxylase deficiency or 11-β hydroxylase
1 ^6 X5 g0 ~3 [- B* o' D$ |2 ~% ~deficiency. Those diagnoses were excluded by find-1 K7 Z9 q v; _& l
ing the normal level of adrenal steroids.
. y0 H$ b; F# q% o% P- EThe diagnosis of exogenous androgens was strongly
9 h' a. D& E. _7 Y* C" r% R: w1 nsuspected in a follow-up visit after 4 months because; B4 K% g/ |4 n b! \( j
the physical examination revealed the complete disap-
* w8 Z: K! `& fpearance of pubic hair, normal growth velocity, and( B# ^" R& `- T: U
decreased erections. The father admitted using a testos-6 X# j% _: e& x+ b4 U x
terone gel, which he concealed at first visit. He was! Y H0 w) X8 E) x7 ?
using it rather frequently, twice a day. The Physicians’
& q" P8 I# }8 G8 @8 B" P& o# m# |# MDesk Reference, or package insert of this product, gel or& [/ v5 `3 X2 \* x5 A! ?
cream, cautions about dermal testosterone transfer to
7 h* p% E- J( V5 {, eunprotected females through direct skin exposure.7 {0 a5 D, @6 X+ L
Serum testosterone level was found to be 2 times the
2 `( w- [7 C3 F5 R2 l) T/ lbaseline value in those females who were exposed to( m& c/ y) K5 T
even 15 minutes of direct skin contact with their male
2 v: [5 m. U J+ m! t- Spartners.6 However, when a shirt covered the applica- H; G! W4 f- O* q5 W3 W# x% k3 N
tion site, this testosterone transfer was prevented.
3 q% X+ w5 |0 e* n; G4 _+ }6 WOur patient’s testosterone level was 60 ng/mL,
7 b! _; ]. f H! {which was clearly high. Some studies suggest that
/ P" R$ N! ^1 Y3 g' v) h2 Hdermal conversion of testosterone to dihydrotestos-! z$ }- d! l& L* r7 ]
terone, which is a more potent metabolite, is more/ K+ t& E1 s) N% q Z& J* X6 q8 i6 ]
active in young children exposed to testosterone, T5 t: Q8 f) z3 @
exogenously7; however, we did not measure a dihy-
" g) m7 \3 o+ t% b @9 Z5 ddrotestosterone level in our patient. In addition to$ z! C9 F" }2 p2 V0 m/ x
virilization, exposure to exogenous testosterone in
: Y2 Z/ F4 J8 Kchildren results in an increase in growth velocity and
* C$ {! M6 ?* y, iadvanced bone age, as seen in our patient./ v( k$ {9 o" b; S
The long-term effect of androgen exposure during
$ @' X k; c+ B, vearly childhood on pubertal development and final# z3 [3 R8 w; K$ g/ E, J# p' j
adult height are not fully known and always remain2 K6 O. ^, H9 L' S: c0 ~1 _- T
a concern. Children treated with short-term testos-
$ D# r7 f; P! F# jterone injection or topical androgen may exhibit some$ n$ t& _ Q/ H; r' [# G+ U/ W; P
acceleration of the skeletal maturation; however, after
2 y1 }, N/ N& x4 N. Scessation of treatment, the rate of bone maturation
2 D: T$ {+ h1 L {5 Mdecelerates and gradually returns to normal.8,9& k' d: a9 R' H. V: p1 ]
There are conflicting reports and controversy
" f6 a) d9 U; J& r/ U! A! Tover the effect of early androgen exposure on adult9 w8 Q& O5 \: \" F, |7 ^2 }
penile length.10,11 Some reports suggest subnormal
8 f6 Z4 H; f* T* @, }adult penile length, apparently because of downreg-6 _1 L9 f2 R8 v0 e% U6 @
ulation of androgen receptor number.10,12 However,. |: o4 W. B6 i' h/ l
Sutherland et al13 did not find a correlation between: H. e# T3 Q) K5 c6 K* u
childhood testosterone exposure and reduced adult. d. m C1 ]6 g# f2 d: o) p3 E
penile length in clinical studies.
1 }: I: ^( F- Z; INonetheless, we do not believe our patient is
! Z4 N3 V7 j) W9 |9 xgoing to experience any of the untoward effects from
6 R) k0 Z! n" btestosterone exposure as mentioned earlier because
; X- q0 o9 {; W& rthe exposure was not for a prolonged period of time.0 ~. @0 h; ` h f& h
Although the bone age was advanced at the time of! V" i; L& j$ T1 X3 M
diagnosis, the child had a normal growth velocity at
0 P' G$ f& {- i+ j; P6 S' Cthe follow-up visit. It is hoped that his final adult
+ T d* R# B7 x v0 c3 N' Aheight will not be affected.
" A# N" Y8 `1 A) u0 G1 V8 iAlthough rarely reported, the widespread avail-
# C' E8 U7 X1 W0 O2 D' _% \ability of androgen products in our society may/ s3 S0 Z4 X z
indeed cause more virilization in male or female! O9 N# I: o. H) Z
children than one would realize. Exposure to andro-' J$ H# {0 P5 v" x3 ^
gen products must be considered and specific ques-
' L- [7 f: n# ]8 l0 H% K( vtioning about the use of a testosterone product or
, }; D. s- U' q7 _0 sgel should be asked of the family members during
# ?* g& d& O- p) A* m3 J Bthe evaluation of any children who present with vir-1 {8 l0 M3 w+ M# \- Y ^$ z/ B
ilization or peripheral precocious puberty. The diag-3 Z/ ?$ ] N# b7 ?+ X8 C. R
nosis can be established by just a few tests and by
6 Y7 Y+ ~# d2 Z6 w. K2 \8 Bappropriate history. The inability to obtain such a9 A0 o4 d" M7 s% E
history, or failure to ask the specific questions, may
, Z! F) r2 [. o$ T1 x. A. q0 nresult in extensive, unnecessary, and expensive
. r4 F. y. C, o' L: Q2 j" hinvestigation. The primary care physician should be0 ?' T( J4 [: j2 C+ j" g
aware of this fact, because most of these children
, E& m$ w8 G$ w* \1 N% p. wmay initially present in their practice. The Physicians’$ X% b1 e& p0 y1 `( @
Desk Reference and package insert should also put a$ i' u+ s5 m$ r* r8 z+ ]8 u
warning about the virilizing effect on a male or2 p) }5 n# R* \8 a. q
female child who might come in contact with some-( W7 x2 L1 R% R' I4 l
one using any of these products.
5 K( N q8 W6 V! PReferences
$ ^* r2 f1 b7 q1. Styne DM. The testes: disorder of sexual differentiation
3 E2 R) Q0 X/ Y9 n, X( p7 n; o; X$ band puberty in the male. In: Sperling MA, ed. Pediatric& A: s6 I- N& Q
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders; k, V) J9 J; m+ ?5 b. ~
2002: 565-628.
- s' A6 h* z5 m4 q2 E, ^2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
2 r8 G& H1 Q! n) y/ J% Ipuberty in children with tumours of the suprasellar pineal |
|