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Sexual Precocity in a 16-Month-Old
( \& U- U; K3 zBoy Induced by Indirect Topical! d: ?7 e4 v0 k; J3 L% \( _7 w! b% L2 }
Exposure to Testosterone6 O* k+ @1 V; u3 |/ e. q% Q3 h6 K
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
; T% R# A5 r# A; ?$ cand Kenneth R. Rettig, MD1
$ C6 W$ l" Q8 oClinical Pediatrics# h# ]# c. E: G8 U" B/ x* M3 O: e
Volume 46 Number 6
# j9 B# `& G$ g' sJuly 2007 540-543
" m$ N: F' x: ?% W( p8 i7 i© 2007 Sage Publications
' I& g: \7 E9 X2 a, C% \, z10.1177/0009922806296651# R- |8 q7 P* Q" o' H
http://clp.sagepub.com+ p$ F( l: d/ S- h. P: D5 O5 G
hosted at
7 M2 v9 Z! i2 a K1 O' Fhttp://online.sagepub.com, j7 a* T% u# ]% H+ C0 Q1 \- _
Precocious puberty in boys, central or peripheral,, ~ }; M0 u+ l& V, g* J! `. ]1 B
is a significant concern for physicians. Central
3 Z# w* O" y# f; K7 Jprecocious puberty (CPP), which is mediated4 y( ]% }' g0 h% J" h
through the hypothalamic pituitary gonadal axis, has! W& @6 ^. l) W' ~2 i6 d6 G
a higher incidence of organic central nervous system& H& x* d8 P4 m5 z
lesions in boys.1,2 Virilization in boys, as manifested+ G2 ^" {) G( ^, f
by enlargement of the penis, development of pubic
% E: R( I- ]9 ]" k8 U' Y: K" ?hair, and facial acne without enlargement of testi-& o* e( g/ Y" F3 j( A, k
cles, suggests peripheral or pseudopuberty.1-3 We! Q) l1 ?6 G+ D) ^ X1 x
report a 16-month-old boy who presented with the7 x" s3 {8 _' q* C% `1 }
enlargement of the phallus and pubic hair develop-
/ l) l# v7 b4 \8 [' M" Bment without testicular enlargement, which was due2 c# y7 ?' @1 e/ w1 v. ^$ o! f
to the unintentional exposure to androgen gel used by
- ~7 a( i# h8 ]9 I5 gthe father. The family initially concealed this infor-
* w+ z# I! O; @9 d4 i9 e cmation, resulting in an extensive work-up for this
3 {+ a: {( Q. U& c# k% D: A/ gchild. Given the widespread and easy availability of
, @) X) P& Z; v+ u# o8 Xtestosterone gel and cream, we believe this is proba-9 ]6 h; V" e. s
bly more common than the rare case report in the
9 p# F3 S$ T5 J1 D+ M4 t) Eliterature.4# B, q/ Z8 c j! s
Patient Report: X) R8 A! A) T& K7 g% d4 b
A 16-month-old white child was referred to the9 C8 X; x( l1 H: t3 z& ], `+ R& D- `
endocrine clinic by his pediatrician with the concern
3 u/ r2 |5 w: |4 gof early sexual development. His mother noticed
9 u0 l9 J+ {7 k( m! E3 c) Y+ y& d- xlight colored pubic hair development when he was2 d; h7 W2 a/ E0 v
From the 1Division of Pediatric Endocrinology, 2University of
6 g" h6 M# h" i' @5 ~- y: u- ^& KSouth Alabama Medical Center, Mobile, Alabama.+ [! ^2 c( R: z; @, p7 z7 k
Address correspondence to: Samar K. Bhowmick, MD, FACE,- K9 e0 e* U& I. P, J% f$ e
Professor of Pediatrics, University of South Alabama, College of
I& Z8 \ B! X9 K2 c6 E/ bMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;3 u9 Q y+ {* U7 u: P
e-mail: [email protected].- }% E2 ]9 N8 D' @/ I/ r
about 6 to 7 months old, which progressively became& C: j/ b! Z: V$ A+ w
darker. She was also concerned about the enlarge-+ a- i, M8 C* c4 K
ment of his penis and frequent erections. The child( G* n9 C& E* r$ I+ m
was the product of a full-term normal delivery, with
5 e7 ]5 b, E" _, `2 o/ ~3 Qa birth weight of 7 lb 14 oz, and birth length of% Y$ {+ F) k2 |+ W4 l2 f* B' E
20 inches. He was breast-fed throughout the first year5 {0 i! q) a7 z; P( R/ z
of life and was still receiving breast milk along with
% z1 \, Y w7 Q8 P& G. s& X; u! tsolid food. He had no hospitalizations or surgery,# @2 I( s% D$ c' ?$ I9 ^- h3 {
and his psychosocial and psychomotor development
4 r) {6 t' T( |, D; H" B. Awas age appropriate.# H! [ W, w% i- |: T9 U
The family history was remarkable for the father,( B% o+ i1 e0 m
who was diagnosed with hypothyroidism at age 16,
7 _: F# O( @8 { c# A. ^/ bwhich was treated with thyroxine. The father’s
6 {0 `1 w$ E6 y8 y% s0 u) Fheight was 6 feet, and he went through a somewhat q: w' K" V: \7 ^. n. D1 Q5 V
early puberty and had stopped growing by age 14.+ e9 g: d& p& b# z
The father denied taking any other medication. The, q Y, ~, u$ ~0 r: H0 V
child’s mother was in good health. Her menarche
& [9 ~- D) W t/ kwas at 11 years of age, and her height was at 5 feet
+ A8 U) A* f( K, ^5 inches. There was no other family history of pre-. t, F4 n$ N4 T3 Z, Y
cocious sexual development in the first-degree rela-
" ^( S: }0 N2 z- u( g, M" Btives. There were no siblings.
" j5 y0 E2 o# S& T: APhysical Examination7 \7 s2 z* {6 m7 ?6 w
The physical examination revealed a very active,/ h/ r7 Y# r& `1 f# K4 \
playful, and healthy boy. The vital signs documented9 M9 d7 h; Y, Y. X/ h7 B
a blood pressure of 85/50 mm Hg, his length was/ R L0 }" D8 M7 e; e0 w4 X
90 cm (>97th percentile), and his weight was 14.4 kg8 v9 @3 r5 }7 ~% P* x
(also >97th percentile). The observed yearly growth. U5 E7 \- @; L* {8 B. t
velocity was 30 cm (12 inches). The examination of. L% L. i& w1 j* {" O m
the neck revealed no thyroid enlargement.) w G0 @) f$ X W8 _! \5 o, U. M1 J
The genitourinary examination was remarkable for
0 G t, F3 |% ^$ Genlargement of the penis, with a stretched length of Z0 h+ k: E( R9 ^# y2 V2 O# }
8 cm and a width of 2 cm. The glans penis was very well
) K# B0 C* M, I7 C sdeveloped. The pubic hair was Tanner II, mostly around6 D) E- E4 U+ {$ P
540
: Y' I" S' J9 i9 p; V3 Lat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from& h5 t+ f8 }" \) ~7 j' l `
the base of the phallus and was dark and curled. The) Y% g8 }( u" G, ]! [, o8 G4 c
testicular volume was prepubertal at 2 mL each.
( u5 S/ x3 R) }7 V' jThe skin was moist and smooth and somewhat
3 D" G$ U, M. f7 `% c8 I, A9 toily. No axillary hair was noted. There were no
! J3 R! o- R5 q+ U( @abnormal skin pigmentations or café-au-lait spots.6 L4 I: y# i- g
Neurologic evaluation showed deep tendon reflex 2+
$ B; u1 K7 ~; U; ?4 l2 R5 qbilateral and symmetrical. There was no suggestion) S9 T4 Z( F! X
of papilledema. w) X- U- d1 B! L" Z& j, Z
Laboratory Evaluation
; M J/ |' R5 bThe bone age was consistent with 28 months by
3 U: | j) `2 o8 \& @5 @ @+ eusing the standard of Greulich and Pyle at a chrono-
# z- \( @& F' J, Flogic age of 16 months (advanced).5 Chromosomal
$ m9 P1 x: @5 mkaryotype was 46XY. The thyroid function test7 H$ f9 m+ ]! w9 e2 H
showed a free T4 of 1.69 ng/dL, and thyroid stimu-, G3 Y0 a, {( V, H8 }; k7 j7 R6 C
lating hormone level was 1.3 µIU/mL (both normal).
$ J& I* P/ i+ G! h4 B9 a1 IThe concentrations of serum electrolytes, blood
/ L/ s$ J$ N( D/ l- Curea nitrogen, creatinine, and calcium all were
( }9 ~& z/ A [) U% t) \( Uwithin normal range for his age. The concentration9 P& v3 Q, s) z- w6 O
of serum 17-hydroxyprogesterone was 16 ng/dL& d! \2 w: P/ \; o+ L0 o
(normal, 3 to 90 ng/dL), androstenedione was 20. S& i2 [, c( u. C% s
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
1 ~% [- U& o! ^: J; b7 h t, b7 mterone was 38 ng/dL (normal, 50 to 760 ng/dL),, F) ~9 U/ s9 K
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
3 R* R# H. ?* T49ng/dL), 11-desoxycortisol (specific compound S)% n4 Q# Q% K+ J( d( i& R9 p# u( ^$ v
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
0 n1 p9 ?" ?0 U! otisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
; y) @! g- j& D: n% Utestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
! F+ y5 m$ K* X$ ?% x0 [and β-human chorionic gonadotropin was less than
! H+ w% Q3 G, W: u5 mIU/mL (normal <5 mIU/mL). Serum follicular( K1 m p3 S6 X7 r, K$ Z
stimulating hormone and leuteinizing hormone
/ J9 \' Q- w2 _: k; yconcentrations were less than 0.05 mIU/mL# t l) ~# U# K$ I; t
(prepubertal).7 _+ K$ y# O) t7 m" Q$ D& [3 g
The parents were notified about the laboratory
0 V% D1 g- I- B+ `7 Rresults and were informed that all of the tests were
# ^* L- D: p" F; jnormal except the testosterone level was high. The( i# K% R; e+ x x
follow-up visit was arranged within a few weeks to+ `, @ F! x) a t
obtain testicular and abdominal sonograms; how-. `4 M3 G+ ]% R
ever, the family did not return for 4 months.! X* V I2 F/ [, i7 s& @
Physical examination at this time revealed that the
+ j3 a3 a, s& F, u# ]7 }' d" `child had grown 2.5 cm in 4 months and had gained
% R! D. B) _9 V- E7 O2 kg of weight. Physical examination remained
& _, P* U* D C# X$ `% C2 t Uunchanged. Surprisingly, the pubic hair almost com-, m% Q3 M' L( D3 _! L/ E9 r
pletely disappeared except for a few vellous hairs at8 c" ^2 C" J9 \/ O( [
the base of the phallus. Testicular volume was still 2% D5 x' ?6 Y8 {) d
mL, and the size of the penis remained unchanged.! j- i' q8 X! D1 X
The mother also said that the boy was no longer hav-: t! |# D# k8 }0 d7 c8 Q% ^& A: d
ing frequent erections.
7 U) t, `5 f! r: f% ?Both parents were again questioned about use of) W1 u% U" M/ F: ^* u' f1 S# j
any ointment/creams that they may have applied to
8 Y0 p `) i3 `: s5 R/ ~. hthe child’s skin. This time the father admitted the4 {8 K: a, [5 A# ^, T& ?
Topical Testosterone Exposure / Bhowmick et al 541+ Y" Z" K8 g% i1 s
use of testosterone gel twice daily that he was apply-* K7 l/ }8 M; R4 a0 Y+ [
ing over his own shoulders, chest, and back area for+ D8 D# d0 B* S L. k2 ?- O
a year. The father also revealed he was embarrassed
3 k; w+ k' H) _' h/ ?1 K# u Zto disclose that he was using a testosterone gel pre-
+ i1 H7 i Y" Z! {8 Uscribed by his family physician for decreased libido: A3 o4 h0 Y! X) M9 `
secondary to depression.% y3 l5 A1 Q; V" p2 O" i: g0 G
The child slept in the same bed with parents.
. K5 m3 ~, y( A$ TThe father would hug the baby and hold him on his
* Z& H$ h( p3 R# Z" nchest for a considerable period of time, causing sig-) h0 v9 H7 Y( _3 `8 T2 c
nificant bare skin contact between baby and father.1 T. ?- \! q. l0 h. E& n$ v
The father also admitted that after the phone call,
) G. x5 f) S) E' i& ^when he learned the testosterone level in the baby4 |' X5 G4 z( f: u* F
was high, he then read the product information
" }' i6 ^2 a8 K8 l# j& Ypacket and concluded that it was most likely the rea-/ _ K7 r$ k& V* m
son for the child’s virilization. At that time, they) h' W0 l- o" |( K$ R/ i
decided to put the baby in a separate bed, and the1 U& H# E! b! S' e5 R6 U
father was not hugging him with bare skin and had
; [$ v. F. i$ Y6 V% ?; ]/ V! kbeen using protective clothing. A repeat testosterone
% V; e0 r3 Y+ ?4 Atest was ordered, but the family did not go to the6 ~% G6 ?+ R6 t. R! ?! Y) O
laboratory to obtain the test.
$ f3 k; R1 P, w/ o- B- Q0 gDiscussion0 F9 T. Z$ h, q
Precocious puberty in boys is defined as secondary( w0 n2 \- K8 m$ f
sexual development before 9 years of age.1,43 z! T7 {* k' m) q `- [7 U
Precocious puberty is termed as central (true) when
% t" u1 x; @ p: s, q& h5 ]1 Xit is caused by the premature activation of hypo-
6 U) J8 z7 W) y+ lthalamic pituitary gonadal axis. CPP is more com-4 H) w1 q! e, J3 N6 z# Y
mon in girls than in boys.1,3 Most boys with CPP
7 C: y! G5 z4 v7 dmay have a central nervous system lesion that is* ?/ {6 B' Q! n
responsible for the early activation of the hypothal-% X# W7 K: C5 a; n6 M( F3 |, m
amic pituitary gonadal axis.1-3 Thus, greater empha-& T7 Y" l1 l& U4 f. X5 ?
sis has been given to neuroradiologic imaging in6 F3 I, H5 B0 U; A
boys with precocious puberty. In addition to viril-
7 F5 f1 c7 G3 h I: b7 H8 Jization, the clinical hallmark of CPP is the symmet-
1 ^. f5 N: o' G0 Mrical testicular growth secondary to stimulation by* P+ w) C1 \; ]- D% A5 B
gonadotropins.1,3
6 D* t2 c- r, T' ]; s8 S- iGonadotropin-independent peripheral preco-
+ B8 b7 g6 C4 L4 N: L: Acious puberty in boys also results from inappropriate
& T& r! c: Z' l1 z pandrogenic stimulation from either endogenous or6 i7 K) K# F8 n/ S
exogenous sources, nonpituitary gonadotropin stim-
/ J( w# z" t' L6 v2 |2 Dulation, and rare activating mutations.3 Virilizing
3 n! n/ D) v2 u$ U" ]congenital adrenal hyperplasia producing excessive
$ o& z( ~; o/ Y; zadrenal androgens is a common cause of precocious+ | k7 a: Q" o3 T2 u- U2 _; L6 A1 |
puberty in boys.3,4
) k* J0 j; o* o) XThe most common form of congenital adrenal( A- d, J% f: N# `# C, Z( P
hyperplasia is the 21-hydroxylase enzyme deficiency.6 i: }5 h' e/ K9 u9 a o' A
The 11-β hydroxylase deficiency may also result in
8 k$ m& k) B) C6 m6 B; texcessive adrenal androgen production, and rarely,
2 [0 v8 u8 x s) d* j) k' G Man adrenal tumor may also cause adrenal androgen/ L# s& u' u3 j3 y
excess.1,3) X* t' S K( N, C. N( r
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from# s; E7 c6 E6 A( X
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
$ j7 {6 l( s' \! pA unique entity of male-limited gonadotropin-
`7 r; [! `4 c1 Q, G* Lindependent precocious puberty, which is also known
+ g* y4 }6 x# r) x) \2 {1 |as testotoxicosis, may cause precocious puberty at a
- C; _% C& h0 I8 `) Pvery young age. The physical findings in these boys7 n% ?6 x% ]- w
with this disorder are full pubertal development,
) g9 u5 g. q, I) _including bilateral testicular growth, similar to boys
6 B! L( H% J+ ]4 `1 S3 g% Swith CPP. The gonadotropin levels in this disorder
3 W/ [, F0 f# B b8 Y1 o) ]2 U2 xare suppressed to prepubertal levels and do not show+ p N& k: n6 E; s/ n
pubertal response of gonadotropin after gonadotropin-
8 |( o& J. ^9 j3 {' I7 H8 }/ dreleasing hormone stimulation. This is a sex-linked
% b1 D3 w3 ?, s# W0 yautosomal dominant disorder that affects only
9 I, Q9 \& ]3 P" |& \ a* kmales; therefore, other male members of the family
8 P7 Q: c3 Z" z2 U* j$ umay have similar precocious puberty.3
( U3 |3 \2 q% i! U m. G1 rIn our patient, physical examination was incon-& O0 `+ I, [1 b
sistent with true precocious puberty since his testi-0 X5 a/ ^. ?' t- e& B! y$ o) f
cles were prepubertal in size. However, testotoxicosis
: K( ~: q0 }$ [" Q# p: ewas in the differential diagnosis because his father
0 |* @ W1 z5 c, u) L8 ystarted puberty somewhat early, and occasionally,# R( }, |7 S1 O9 B" K0 d6 W
testicular enlargement is not that evident in the
$ P4 F! n8 e! Z* m3 k. \beginning of this process.1 In the absence of a neg-
6 s, K6 o! [2 d6 V# Z2 Xative initial history of androgen exposure, our
( \+ }! [ G$ B" u: Fbiggest concern was virilizing adrenal hyperplasia,
! W& N2 S, }/ Y/ ~ V! yeither 21-hydroxylase deficiency or 11-β hydroxylase
" a+ g5 M1 c9 ^. s3 E Vdeficiency. Those diagnoses were excluded by find-
5 e: B2 H3 S" H7 k) K" @6 @ing the normal level of adrenal steroids.
* O! _; q. K' j) xThe diagnosis of exogenous androgens was strongly
4 a8 H+ D7 H1 q6 s: fsuspected in a follow-up visit after 4 months because$ x" G$ h5 L \/ {: w- O1 k2 X/ W
the physical examination revealed the complete disap-' D, N. z0 N% e5 W; j( x) G
pearance of pubic hair, normal growth velocity, and
. W, z' |# ?0 q$ T) R/ Ydecreased erections. The father admitted using a testos-9 w* U$ a9 U! J {
terone gel, which he concealed at first visit. He was: ]+ e" U* P% p% j6 z" A9 V- @* Q( G
using it rather frequently, twice a day. The Physicians’0 V; V2 p; Y" i2 M2 z
Desk Reference, or package insert of this product, gel or
# @0 s; i; h* s% x* e& pcream, cautions about dermal testosterone transfer to- q+ g- L' c& |. l* [
unprotected females through direct skin exposure.% Y' i3 ^1 O1 n
Serum testosterone level was found to be 2 times the1 |! _5 n( B7 G9 _2 L
baseline value in those females who were exposed to! M p1 L& O+ v2 V7 l' d
even 15 minutes of direct skin contact with their male
! H: a4 q2 {' |9 Cpartners.6 However, when a shirt covered the applica-
3 c# p; H k: j1 gtion site, this testosterone transfer was prevented.
1 S7 ~: Y' {' f7 k p- u0 jOur patient’s testosterone level was 60 ng/mL,% e, X( K4 O* n
which was clearly high. Some studies suggest that
. f1 {( k/ f, ]6 |dermal conversion of testosterone to dihydrotestos-
9 U* _: f [7 E, Z4 |terone, which is a more potent metabolite, is more
9 j( {, Z6 }: h/ p% kactive in young children exposed to testosterone6 _3 d- z5 x% c. d& I6 j" N
exogenously7; however, we did not measure a dihy-
K `. `& i/ G0 Y, n: ]drotestosterone level in our patient. In addition to1 g" z9 n4 b# g. X! m
virilization, exposure to exogenous testosterone in4 C% ]( B4 [5 s. B: ?4 G/ O! [
children results in an increase in growth velocity and5 o. p" S% B" |- z7 y# H4 p, c$ @
advanced bone age, as seen in our patient.
! Q- ~% H, H9 P H( }, q( V1 GThe long-term effect of androgen exposure during
6 M7 D5 z- S- c' Y& x1 ]early childhood on pubertal development and final- A. u& ^+ c* a, ^5 ?- H7 E
adult height are not fully known and always remain
- @& r( k6 q8 \' H) D& Y4 Pa concern. Children treated with short-term testos-
! d5 @. {% z$ J# H' qterone injection or topical androgen may exhibit some
: r2 t) o5 F7 T( }8 k- G% O$ Gacceleration of the skeletal maturation; however, after
8 t, o( \1 [) C( j mcessation of treatment, the rate of bone maturation
2 @# ]8 W6 b9 _( i+ j: K8 {6 _decelerates and gradually returns to normal.8,9
' M1 U6 X% g0 X6 p' z, M/ LThere are conflicting reports and controversy
+ {& L$ ]' A6 V, b2 h& Uover the effect of early androgen exposure on adult
& i+ V( ?. t o- G2 Jpenile length.10,11 Some reports suggest subnormal
% N. @ ~1 X5 [adult penile length, apparently because of downreg-5 v3 e& e$ ^; _$ {. v5 O( j5 X
ulation of androgen receptor number.10,12 However,
+ t. `3 e0 {4 j$ tSutherland et al13 did not find a correlation between1 ]! ]" G- ^. F/ d) z
childhood testosterone exposure and reduced adult0 P1 i* D0 a: w! C0 B: a
penile length in clinical studies.
) R. o* q+ l3 D& g- nNonetheless, we do not believe our patient is
9 b! N2 l+ p C- \) P) {going to experience any of the untoward effects from
9 B# i' C) s7 y7 n6 `3 |testosterone exposure as mentioned earlier because% X$ q' W3 B, y3 _% U1 M/ y
the exposure was not for a prolonged period of time.
8 t7 d" T" \0 ~6 ~, R `1 GAlthough the bone age was advanced at the time of
+ X% p. y; S! R% m& z4 L6 ydiagnosis, the child had a normal growth velocity at
' n: } @" q1 j: E; `6 M( z0 Qthe follow-up visit. It is hoped that his final adult4 S* E; R% T6 s' S0 Q9 z3 _7 R' l+ g
height will not be affected.
3 b* ~8 s! [. ^% b) QAlthough rarely reported, the widespread avail-
8 a) B$ I- S3 pability of androgen products in our society may+ Q+ e2 R* d) l1 q$ ~* X
indeed cause more virilization in male or female
9 ]! d' K# u7 P; k b) [4 i jchildren than one would realize. Exposure to andro-$ @$ r* Y) U+ H, S, z
gen products must be considered and specific ques-/ L, z4 H9 b. \; }; E
tioning about the use of a testosterone product or _8 v: F3 C* ~ ?
gel should be asked of the family members during
: r# R3 r P* Xthe evaluation of any children who present with vir-
; X Z+ @# R1 }$ F( y) dilization or peripheral precocious puberty. The diag-( T7 `! N* G9 x
nosis can be established by just a few tests and by" C3 W# ~2 C- s4 H+ J: E1 g. z$ C
appropriate history. The inability to obtain such a* P( F2 A- {% T& m
history, or failure to ask the specific questions, may3 b) e: x7 A+ }$ ~8 Z" e5 t F
result in extensive, unnecessary, and expensive7 b/ u! K( v2 F7 @) X# z
investigation. The primary care physician should be4 P# \3 L" B7 a, i5 R
aware of this fact, because most of these children
, t1 f2 w( [: [3 L7 M3 z# Kmay initially present in their practice. The Physicians’6 W9 c! D+ j' S/ V: U1 g( |; t
Desk Reference and package insert should also put a% ^# h# e! i: E Z5 ?) ~ @" k
warning about the virilizing effect on a male or/ i: B8 i2 D- Z6 z
female child who might come in contact with some-
$ }9 ?4 E) m3 U$ y5 z2 gone using any of these products.
* ]8 S5 R; _* g0 \: iReferences4 Q5 a ?, a6 ]: l3 |, h5 J+ c
1. Styne DM. The testes: disorder of sexual differentiation
& D( B' D; u9 band puberty in the male. In: Sperling MA, ed. Pediatric( X3 P! z, b1 j: \. q
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;; Q: v) i' H1 R g L( p. B$ b
2002: 565-628.: s4 H+ `2 W( J) ]( N I
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
: m; ?4 z$ X. \# b$ m7 N1 E; ]9 ^puberty in children with tumours of the suprasellar pineal |
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