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Sexual Precocity in a 16-Month-Old+ B8 [% C% K! J v1 s: C2 y
Boy Induced by Indirect Topical7 a1 h4 b+ C) M
Exposure to Testosterone* z' M: T, q) H/ b6 F/ D
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
" k$ ^( z& y3 a: Cand Kenneth R. Rettig, MD1+ E7 n4 B& N _/ `
Clinical Pediatrics
0 W. n9 A E# \% I& i( t' \Volume 46 Number 6
$ y0 p5 r( i" b3 a# \6 TJuly 2007 540-543
1 w0 a4 E! a8 e1 F" c9 U0 S* T© 2007 Sage Publications
; B A( X, _ U7 {; F! N: Y10.1177/0009922806296651
/ t( a0 T; y6 B/ A8 S0 I5 [% ]http://clp.sagepub.com+ f' x+ @: E" w8 ?
hosted at
4 x: J! A/ U, S9 Khttp://online.sagepub.com
+ t/ \3 c. S- X. oPrecocious puberty in boys, central or peripheral,' { ~4 U8 t9 k( N8 @# z+ @
is a significant concern for physicians. Central
6 v- F; T W& }* h! Yprecocious puberty (CPP), which is mediated6 o) V( s) `% \& \* S; o
through the hypothalamic pituitary gonadal axis, has7 t$ z) J* l- O( h/ ?" }' f$ k
a higher incidence of organic central nervous system4 [8 c. u4 K0 |5 T# Y' R
lesions in boys.1,2 Virilization in boys, as manifested8 `0 r* n+ [) P& j0 F8 }/ a
by enlargement of the penis, development of pubic+ s% [* x0 d8 h, O ~* b2 V
hair, and facial acne without enlargement of testi-) A4 ?) S1 ^; Q0 M: Q% d
cles, suggests peripheral or pseudopuberty.1-3 We% k* _0 O0 D: m9 j' b
report a 16-month-old boy who presented with the
7 o6 {! |' R3 I' P' Zenlargement of the phallus and pubic hair develop-0 @0 j J/ E! W# _
ment without testicular enlargement, which was due
9 }2 D3 @, ]/ j5 Kto the unintentional exposure to androgen gel used by1 Z7 P/ }, U% j
the father. The family initially concealed this infor-
7 P4 V! g1 e- W# z" W6 Hmation, resulting in an extensive work-up for this- J, W- a- [8 R) L+ G7 x
child. Given the widespread and easy availability of1 P Q0 W$ `" S3 j0 l
testosterone gel and cream, we believe this is proba-+ g1 b/ r6 r* Y2 q% } T F$ }
bly more common than the rare case report in the
' h! k9 A0 x8 z1 q1 s9 Cliterature.4" G: P; k0 D# x% e8 B& z9 |
Patient Report
/ x4 |9 ?2 O( E% v/ d. QA 16-month-old white child was referred to the7 }. X. b' b/ C/ [+ K Q
endocrine clinic by his pediatrician with the concern
1 ~2 b5 R1 U' j5 I0 l/ j; t! Oof early sexual development. His mother noticed
! t! K6 A7 T3 x$ h3 j" }light colored pubic hair development when he was
% [: Y# x# R6 e, S7 R v9 m* I. dFrom the 1Division of Pediatric Endocrinology, 2University of
2 K6 B5 J9 J, I; b0 y3 ~South Alabama Medical Center, Mobile, Alabama.) h9 Q$ H* ?$ Z- K# Q. K7 g+ X1 s0 H
Address correspondence to: Samar K. Bhowmick, MD, FACE,
. m" [7 L3 u4 F9 zProfessor of Pediatrics, University of South Alabama, College of# S0 K. I" G+ L
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
1 H! c1 `7 _5 z; W) Y. A6 Z le-mail: [email protected].
2 I, k! ?. l! ^about 6 to 7 months old, which progressively became* S& T; W1 _! U7 j# M% ]& h5 \1 k
darker. She was also concerned about the enlarge-0 k# j. g" m5 {0 P; Y
ment of his penis and frequent erections. The child# w" Q9 y% @8 `* p; a
was the product of a full-term normal delivery, with
4 a; B. X. p K5 v2 }% na birth weight of 7 lb 14 oz, and birth length of
5 d! k& t6 c6 S% q9 l20 inches. He was breast-fed throughout the first year* h4 J1 R9 }9 {- J
of life and was still receiving breast milk along with/ S1 n: k2 N* O! W4 K9 q% j) W0 F
solid food. He had no hospitalizations or surgery,5 Y5 @6 d# J0 i) ?+ {. Q
and his psychosocial and psychomotor development; v2 U, {! r) N/ j* U \3 m( _, H
was age appropriate.
& j4 L& Y2 {& m2 G4 Y) J9 ]7 w: VThe family history was remarkable for the father,
. X. r% h, y$ xwho was diagnosed with hypothyroidism at age 16,
, [. a- I$ t$ W, E; k0 Qwhich was treated with thyroxine. The father’s. P. @+ |; d! b* Z6 `+ Z- v
height was 6 feet, and he went through a somewhat
! `" Z6 F6 A" v$ ?7 x2 Nearly puberty and had stopped growing by age 14.( M6 j0 F( I4 l5 Z) w
The father denied taking any other medication. The
; D" T |5 p! Q7 ^/ Bchild’s mother was in good health. Her menarche ^# _' \/ _5 C# W$ h; V) g
was at 11 years of age, and her height was at 5 feet9 ^1 h8 h4 q) H; E6 |/ M
5 inches. There was no other family history of pre-
7 O& s4 _! A: a% c, V3 |) ?cocious sexual development in the first-degree rela-
5 S% k2 q9 d$ m# V( r- V) otives. There were no siblings.2 `0 @9 E5 o% m$ _! K
Physical Examination
+ |" _! Q0 _( Q+ h8 J+ B ^The physical examination revealed a very active,; }. w4 i) [3 C8 }/ ?2 \
playful, and healthy boy. The vital signs documented* A0 V1 P) R( o q
a blood pressure of 85/50 mm Hg, his length was3 Y3 h8 ~3 l# ~& t$ ?5 I8 X4 J: D8 D1 k
90 cm (>97th percentile), and his weight was 14.4 kg+ ]2 y: \8 f6 ?+ k! l2 K+ w1 q) U R
(also >97th percentile). The observed yearly growth
`% k' Z2 N* Qvelocity was 30 cm (12 inches). The examination of
& E; x4 k- S6 j: @the neck revealed no thyroid enlargement.
5 i1 @2 {' W0 K8 GThe genitourinary examination was remarkable for& |0 J0 l4 y0 l
enlargement of the penis, with a stretched length of
/ P7 y) m( N% O9 v% g7 t8 cm and a width of 2 cm. The glans penis was very well
7 F1 ]: S) d" _4 jdeveloped. The pubic hair was Tanner II, mostly around0 n( o% Z1 w9 A- Y+ V5 m5 o
540% l O: i+ Z# t8 p3 n
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
" {! I( g1 j. m3 K% ~# ?the base of the phallus and was dark and curled. The) M" T. G7 w& K* o; S- t6 |( Z
testicular volume was prepubertal at 2 mL each.
! R3 q3 ~" U9 D+ S5 @The skin was moist and smooth and somewhat, E; p7 [" N* m+ K
oily. No axillary hair was noted. There were no
% s9 J9 `9 S" q' xabnormal skin pigmentations or café-au-lait spots.0 s2 T( K( }. D5 \* ^$ T* f: v, Z
Neurologic evaluation showed deep tendon reflex 2+2 \; ~" e: L0 X2 K, v
bilateral and symmetrical. There was no suggestion
* Y: ~1 S" {2 ~3 Wof papilledema.
5 z8 B8 Y- d+ _, h- }4 H* M7 SLaboratory Evaluation k: Z# \ _8 I9 a2 ?! e
The bone age was consistent with 28 months by
9 F$ Q7 O/ M1 U. G9 _using the standard of Greulich and Pyle at a chrono-+ M" |& }' |8 B
logic age of 16 months (advanced).5 Chromosomal, q; G4 a( O8 ?2 H" N/ a- o
karyotype was 46XY. The thyroid function test+ m. }3 T8 [& o1 d
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
% f- f2 D2 F k2 Klating hormone level was 1.3 µIU/mL (both normal).. z5 G* E$ o! m
The concentrations of serum electrolytes, blood! _& ~/ S- [+ o" ]8 {
urea nitrogen, creatinine, and calcium all were
& I5 Z$ n3 W9 O, m# Xwithin normal range for his age. The concentration- U! S% ^* H' O" `7 E+ L
of serum 17-hydroxyprogesterone was 16 ng/dL
( @: t/ G4 r& u: n, `(normal, 3 to 90 ng/dL), androstenedione was 202 y: l; E3 `! B {% i
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
; \- j( M4 F2 h% y' w: m( X7 f5 [& @8 Fterone was 38 ng/dL (normal, 50 to 760 ng/dL),
/ m! w& b, d! ?* d% T! a0 R) d0 D# Fdesoxycorticosterone was 4.3 ng/dL (normal, 7 to
; E- F5 Z2 \0 L4 V# f" L! N49ng/dL), 11-desoxycortisol (specific compound S)7 _0 I5 b1 I0 W, y# D+ Q; g
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
2 k& ^( f( `. ?# Htisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total. }' z7 X+ U; s* ^1 \# {
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
/ d9 ]* t2 M3 s7 yand β-human chorionic gonadotropin was less than
. p U& e6 s" ~& B( W5 mIU/mL (normal <5 mIU/mL). Serum follicular4 W+ ]& M2 D% @
stimulating hormone and leuteinizing hormone
% A+ Q2 Z0 v8 ]. y) @1 fconcentrations were less than 0.05 mIU/mL
/ M3 z; q5 M, ? v(prepubertal).
; a( p- z! Q7 c0 C& uThe parents were notified about the laboratory
5 j, \9 U* |1 C' q8 ?results and were informed that all of the tests were3 i+ E7 e, U& P: z/ W* x0 k
normal except the testosterone level was high. The( b4 a( Z9 Y1 [0 U( x4 X; Z
follow-up visit was arranged within a few weeks to
4 `! [5 p6 B2 m: x4 \; wobtain testicular and abdominal sonograms; how-
% l( Y5 A! P; ^ever, the family did not return for 4 months." @7 k, }8 W. y, `% s0 w3 L6 i1 l
Physical examination at this time revealed that the
0 d L+ N5 l$ U$ a- Echild had grown 2.5 cm in 4 months and had gained
$ U: J1 w% d" M0 }! g2 kg of weight. Physical examination remained
2 f- s* k9 ?4 u' N/ A) Bunchanged. Surprisingly, the pubic hair almost com-! t' u& {2 }+ h9 d: f
pletely disappeared except for a few vellous hairs at
0 M* q/ x) x g6 ^; B }: x- e. g) Hthe base of the phallus. Testicular volume was still 2, a5 r+ _: w. V# s
mL, and the size of the penis remained unchanged.
1 B+ [5 f7 F) Z5 U3 i/ j UThe mother also said that the boy was no longer hav-
$ Y" \" a2 R1 S. y; I U: Zing frequent erections.
: N* N) v, p0 w: ~Both parents were again questioned about use of- h5 @: ]# p$ h- E" d; w
any ointment/creams that they may have applied to
7 w! \- b4 k6 M9 o" m* S# z4 Jthe child’s skin. This time the father admitted the
8 C- q2 }8 x% [% wTopical Testosterone Exposure / Bhowmick et al 541/ A) o4 \" c* U
use of testosterone gel twice daily that he was apply-
8 r) l+ C. T! }+ ^- N7 d6 Ting over his own shoulders, chest, and back area for2 H# U& n3 N, u/ l8 @
a year. The father also revealed he was embarrassed
# c$ I0 {: L' b7 F' [6 m1 ?to disclose that he was using a testosterone gel pre-, T- j) p2 E" g8 h2 q. w3 O" |
scribed by his family physician for decreased libido
" b5 ~' x% p8 D/ }& \7 B( V5 B" ysecondary to depression. [3 Z+ p, I7 W& K4 q
The child slept in the same bed with parents.
# @8 ?: r3 `8 N: `! t' T1 iThe father would hug the baby and hold him on his
" W/ w7 I+ M, Y! ?6 \; i) Rchest for a considerable period of time, causing sig-" [3 B" L3 R1 j8 |
nificant bare skin contact between baby and father.
4 Z" f7 ~0 b4 S1 K! m0 ~1 `* zThe father also admitted that after the phone call,
/ P& e0 Y: h) ?5 xwhen he learned the testosterone level in the baby# l, U* [* |% R- s' i. R ~$ q
was high, he then read the product information J- h; I9 ~: @; c1 L- S' r
packet and concluded that it was most likely the rea-. D8 A( u: K' K+ q7 C# ~# Y
son for the child’s virilization. At that time, they
4 m, ^& g% J# {- Pdecided to put the baby in a separate bed, and the$ c& X6 i0 I# y" ^( m4 j
father was not hugging him with bare skin and had/ x1 K) P$ J- M8 T
been using protective clothing. A repeat testosterone6 T# S5 Q0 p. e& q6 s
test was ordered, but the family did not go to the2 V& `& J3 K& z& t/ M) v* ]
laboratory to obtain the test.# T+ j% H4 l! T6 I% m" {* d3 x
Discussion
0 t3 L# D/ y+ B$ Q, O$ f! Z# P) QPrecocious puberty in boys is defined as secondary2 m5 y+ E2 X& X/ b6 d& |
sexual development before 9 years of age.1,4# {/ l4 N2 ~/ A5 S
Precocious puberty is termed as central (true) when( y2 v6 M4 C- h
it is caused by the premature activation of hypo-
/ v0 [3 P! r& ?6 W4 C9 j8 Hthalamic pituitary gonadal axis. CPP is more com-) F1 R7 E5 E9 ^2 R$ W
mon in girls than in boys.1,3 Most boys with CPP
0 L4 H2 J$ Y/ G! gmay have a central nervous system lesion that is
$ o: l9 D6 ?* N/ W. gresponsible for the early activation of the hypothal-, O6 p1 D1 Y% [: d$ o. E
amic pituitary gonadal axis.1-3 Thus, greater empha-
( ?+ i0 Y3 d1 H' O$ ]7 `% x2 [sis has been given to neuroradiologic imaging in
+ y/ O* i/ N) }3 W; Tboys with precocious puberty. In addition to viril-
: S- R1 @: c: b2 C1 U! wization, the clinical hallmark of CPP is the symmet-
; X J5 G6 R- Rrical testicular growth secondary to stimulation by
3 c J3 Q! K/ t; |! E& ?' O4 `gonadotropins.1,3
2 x; |: h+ y/ VGonadotropin-independent peripheral preco-4 q* B l9 S% H i# B9 C
cious puberty in boys also results from inappropriate
# n4 k O6 r8 `( i/ q) Q: Q- randrogenic stimulation from either endogenous or
% ?4 G- p9 ]6 p1 i( A3 iexogenous sources, nonpituitary gonadotropin stim-+ J$ X* _0 U N/ x& A) H* K$ F, n
ulation, and rare activating mutations.3 Virilizing
9 O ? i, Y& }$ `/ @! u4 m( Vcongenital adrenal hyperplasia producing excessive
: w' \5 J+ m1 R6 H- J/ jadrenal androgens is a common cause of precocious
6 j6 F2 a7 ~- G. _. i Hpuberty in boys.3,4# W& z' k, v& H" v' c
The most common form of congenital adrenal
- f; n7 `* x/ H$ f! P# `4 p1 Ohyperplasia is the 21-hydroxylase enzyme deficiency." W! J0 i0 q4 q4 D6 ^6 \' i0 Z
The 11-β hydroxylase deficiency may also result in) F$ E. x4 J) I
excessive adrenal androgen production, and rarely,- b8 ?; t1 M* p
an adrenal tumor may also cause adrenal androgen
: v1 C: ]/ h' a$ N0 fexcess.1,39 Z5 V0 }. P% u% f6 h; C# r
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from& S6 L: C0 ]7 }6 h3 L5 H
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
/ `2 d9 D0 k* m: SA unique entity of male-limited gonadotropin-
0 B3 j" l. s t7 }+ Mindependent precocious puberty, which is also known! p0 d9 c3 t9 z9 m! z- n
as testotoxicosis, may cause precocious puberty at a
4 L. E% W: x4 V0 K0 b7 ^3 h) \very young age. The physical findings in these boys" ?7 Z3 l4 O K7 I; n
with this disorder are full pubertal development,
t- ]1 t& `9 f% _* E2 Mincluding bilateral testicular growth, similar to boys
5 x5 ^7 r, C- t- K7 c1 p( \# Qwith CPP. The gonadotropin levels in this disorder% c) Q. e9 m( ]+ \& p. ]9 Y4 v
are suppressed to prepubertal levels and do not show
( ^( ~8 K! z* A$ ?pubertal response of gonadotropin after gonadotropin-* n. Q: A+ K& M$ Q4 Q
releasing hormone stimulation. This is a sex-linked3 h/ x" v9 `, p9 H
autosomal dominant disorder that affects only* O4 e9 R2 u3 f+ y0 E
males; therefore, other male members of the family
9 S9 s3 y: t4 S) Wmay have similar precocious puberty.3 ^' t" @+ j- p: l
In our patient, physical examination was incon-1 k0 j" j" r) U. J- {
sistent with true precocious puberty since his testi-+ |# K4 H; g, a# H, J0 }
cles were prepubertal in size. However, testotoxicosis
! u. m+ G1 g2 _" ^6 v* cwas in the differential diagnosis because his father% |4 W5 m0 j9 ^% t! j) L! s! [9 @% z
started puberty somewhat early, and occasionally,
; Z+ H+ B- r* D9 Z; w+ j+ h; Otesticular enlargement is not that evident in the
" x9 E& i3 G( Y9 ybeginning of this process.1 In the absence of a neg-4 i; l7 r4 X) [' I
ative initial history of androgen exposure, our! ~) B& R( B" C/ _/ V9 ^
biggest concern was virilizing adrenal hyperplasia,2 W% ?2 d' K) s5 v1 O
either 21-hydroxylase deficiency or 11-β hydroxylase
# Q3 C0 S2 L) V9 edeficiency. Those diagnoses were excluded by find-
0 A3 R4 m2 Q! Ting the normal level of adrenal steroids.
; O) D6 C8 w& Q i" M7 UThe diagnosis of exogenous androgens was strongly
' U$ S8 I; A; b+ N6 {suspected in a follow-up visit after 4 months because
& e2 q9 r {8 r0 f1 gthe physical examination revealed the complete disap-3 c: _1 { d/ H( q7 @
pearance of pubic hair, normal growth velocity, and) A. l6 [3 o$ L5 K" b9 t
decreased erections. The father admitted using a testos-* J9 L% o5 }. ^
terone gel, which he concealed at first visit. He was" e% M/ d1 H, K* e3 {
using it rather frequently, twice a day. The Physicians’
1 ]; E5 d/ ^7 x; M; lDesk Reference, or package insert of this product, gel or
% x) ?$ h S( dcream, cautions about dermal testosterone transfer to
: E, }% L* J9 v" a# }, b6 Q. r. eunprotected females through direct skin exposure.1 O2 P% a- y2 v) r
Serum testosterone level was found to be 2 times the4 ^1 `9 S! {$ E( H1 Z
baseline value in those females who were exposed to# h/ M A' c' b4 y3 p& b
even 15 minutes of direct skin contact with their male$ O- ~1 _* D' ?, D1 W
partners.6 However, when a shirt covered the applica-2 o A" k. w' O0 l
tion site, this testosterone transfer was prevented.# {, ~9 U' v( z1 Y, T
Our patient’s testosterone level was 60 ng/mL,
6 \3 O" t C' }$ \6 hwhich was clearly high. Some studies suggest that, J% Q% Q8 h1 {* K" c
dermal conversion of testosterone to dihydrotestos-. h& t2 K$ b) @/ i. r. O
terone, which is a more potent metabolite, is more" `- O1 ~# J' J
active in young children exposed to testosterone
. `) z# T. x4 V5 {, [4 a0 x O3 iexogenously7; however, we did not measure a dihy-! {+ {' I: m$ w9 p% o3 D
drotestosterone level in our patient. In addition to
# R' q9 j- {3 n5 X* ?& Gvirilization, exposure to exogenous testosterone in
" p9 b _( O$ ]5 p. fchildren results in an increase in growth velocity and# d1 k; P" ^- d
advanced bone age, as seen in our patient.
9 J3 \2 U6 V. @) `$ xThe long-term effect of androgen exposure during
; ]0 H/ T6 G9 G+ j$ K: i+ l. D6 bearly childhood on pubertal development and final
9 D9 V0 _# J( b7 m2 Q: iadult height are not fully known and always remain5 O8 D$ d# O( O2 r1 |1 J
a concern. Children treated with short-term testos-
" } {8 m+ j) Bterone injection or topical androgen may exhibit some
, n7 ]- Q/ S2 c$ A5 ~acceleration of the skeletal maturation; however, after
2 D* M$ ^/ q, @+ j* X0 O& _" j Scessation of treatment, the rate of bone maturation% u% @+ w8 J- F; u; E6 a
decelerates and gradually returns to normal.8,9
6 c9 F$ ^ Y) C$ YThere are conflicting reports and controversy
8 h! |* e6 O0 J `( A2 g9 Wover the effect of early androgen exposure on adult3 D7 b7 x+ i) q1 I1 @* i
penile length.10,11 Some reports suggest subnormal
+ E' M$ k/ r) P zadult penile length, apparently because of downreg-6 T, q8 R5 k' N) T
ulation of androgen receptor number.10,12 However,
) A, X8 b& q# P. }4 f( z) Q# FSutherland et al13 did not find a correlation between" U+ ~1 m$ ?; Z2 E" p
childhood testosterone exposure and reduced adult
$ p- K! x5 q( O) i* R* H, Qpenile length in clinical studies.
# c$ l; n8 s7 B5 aNonetheless, we do not believe our patient is
$ X. H7 F' W5 G7 Y" T0 fgoing to experience any of the untoward effects from+ G+ u- Q/ I' P$ u
testosterone exposure as mentioned earlier because
, |/ ]# Q Q& M, Ythe exposure was not for a prolonged period of time." \; Q' H* R% r6 r4 @. G( ?
Although the bone age was advanced at the time of2 k, j4 D$ ^; S% o
diagnosis, the child had a normal growth velocity at
9 X8 B; q$ P' Y1 ^# ^1 j5 @the follow-up visit. It is hoped that his final adult& T' ?) K5 ^+ K0 Z8 _* K, W; S# D6 e
height will not be affected.
5 A+ Z3 q! l* yAlthough rarely reported, the widespread avail-
0 B1 R- I4 C. H7 |# R* ~6 uability of androgen products in our society may- ~6 M8 b! h4 e) O
indeed cause more virilization in male or female, L7 T) F$ a' j3 C; G# s6 V
children than one would realize. Exposure to andro-( @ U, A! Y/ t9 [+ U3 [
gen products must be considered and specific ques-
1 f# O" p8 @0 s% n% g' V3 Ztioning about the use of a testosterone product or
, {9 a: Y5 c/ q4 T, v& bgel should be asked of the family members during, i) ]. _: s+ _: @4 D
the evaluation of any children who present with vir-
# d) Z* S* s2 C6 C4 }+ h( nilization or peripheral precocious puberty. The diag-
1 {& ^- r+ X( hnosis can be established by just a few tests and by
! O- R- @( o- i7 L7 V0 K4 r3 \appropriate history. The inability to obtain such a. o! q( Y, m5 l$ W# A& e6 M
history, or failure to ask the specific questions, may
" i& w z3 y7 P7 I7 X- E6 R: jresult in extensive, unnecessary, and expensive, `8 `0 r9 T: q' i! M: g
investigation. The primary care physician should be0 k/ |; N' `8 L2 [
aware of this fact, because most of these children8 a+ t: w. X. n" g0 W; z
may initially present in their practice. The Physicians’
2 R. M$ a& h8 p5 ^# XDesk Reference and package insert should also put a
# R0 Y. ~/ z" q; ~% Qwarning about the virilizing effect on a male or, k% ~' Q( |3 I! ^1 o- ?$ l, \
female child who might come in contact with some-+ `2 P1 h7 F6 E. F
one using any of these products.
% a1 P& F. j& p! ~$ \References4 L& E. u a7 q; n( ]1 y7 C+ E
1. Styne DM. The testes: disorder of sexual differentiation
8 @# e) W' w4 A4 sand puberty in the male. In: Sperling MA, ed. Pediatric6 V# C1 G8 E% N( U
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
2 `- T4 R2 x6 {1 Y2002: 565-628./ f8 y: F1 t+ K1 u' x
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious, G( m4 M" g# t4 N
puberty in children with tumours of the suprasellar pineal |
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