- 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' M- l B" x/ G/ f! ~+ e) d
Boy Induced by Indirect Topical* a$ J3 q' L j3 d. m+ L$ m5 G
Exposure to Testosterone; q# {* R/ I2 W" W& a# X4 m
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
* M& @/ m& j H7 F# sand Kenneth R. Rettig, MD1
9 t$ Q5 e! G" B: JClinical Pediatrics
% T4 t6 y: f a* I$ \4 m% gVolume 46 Number 6+ R3 x% L: P- {* a6 G& z/ H
July 2007 540-543
4 E! t$ Z+ E: Q I7 E1 M© 2007 Sage Publications% y! w, }" j/ |. D8 d
10.1177/0009922806296651
. h/ U K( X6 O* G. d1 r3 Fhttp://clp.sagepub.com
; B9 ~# H6 d0 a8 \9 i O# `! Dhosted at
, [ m7 n* V) E% Vhttp://online.sagepub.com0 Z: C$ k' I. V& i1 J$ q, f. Y# C
Precocious puberty in boys, central or peripheral,
6 M. ]0 |& J$ Pis a significant concern for physicians. Central
* |6 n/ ~! K8 L( Q) Mprecocious puberty (CPP), which is mediated
$ Y7 [9 `# i) t0 l+ P( q) g4 S( Athrough the hypothalamic pituitary gonadal axis, has# Y- x& j Y# J
a higher incidence of organic central nervous system" e$ V9 Z0 \" A5 m/ G* n8 P: n( r
lesions in boys.1,2 Virilization in boys, as manifested
& H; ?2 V2 P; B) N1 b+ V2 Cby enlargement of the penis, development of pubic
: i$ B% k1 u2 O/ X: }hair, and facial acne without enlargement of testi-
6 Y5 N) y0 W0 y( b" H: i: ccles, suggests peripheral or pseudopuberty.1-3 We- Z, r+ g# e b$ n
report a 16-month-old boy who presented with the! j8 P: L+ r6 k, B) F1 _
enlargement of the phallus and pubic hair develop-
, k" H9 `& n Y/ q7 ]; Rment without testicular enlargement, which was due7 ~# z! B& ]3 t. E8 V9 a
to the unintentional exposure to androgen gel used by
3 R3 o; ~5 f d% j, u Qthe father. The family initially concealed this infor-: q& r" ~ H. [+ _; @3 h, J H; h- n
mation, resulting in an extensive work-up for this
: r! S% _3 q1 x2 u* Schild. Given the widespread and easy availability of
8 ]3 j2 h0 l! E1 [) atestosterone gel and cream, we believe this is proba-0 q4 A% V' }+ k; K
bly more common than the rare case report in the, {) c* J2 X% Y6 M1 j. \
literature.4
5 J% b/ D; B$ qPatient Report! m" F8 t- H4 T+ E* i6 B9 R; |
A 16-month-old white child was referred to the' [: }; b7 w- ^9 n0 s- O0 y
endocrine clinic by his pediatrician with the concern- y5 l9 o G) \: Z6 d( c# ? E
of early sexual development. His mother noticed5 k, U" O/ W+ K
light colored pubic hair development when he was
+ T+ \7 e- g7 i! j9 EFrom the 1Division of Pediatric Endocrinology, 2University of' p% x- `, \9 O9 r! l% M; h7 N2 P
South Alabama Medical Center, Mobile, Alabama.( r, `8 q0 y6 Z" C, K. L
Address correspondence to: Samar K. Bhowmick, MD, FACE,( f9 y5 g5 [) F3 I
Professor of Pediatrics, University of South Alabama, College of9 z! c( _9 g1 x1 {* M8 S* N8 s* A
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;! b* z( W& \9 s
e-mail: [email protected].
) Z' `; ]% p. u9 o) Z1 ^2 @; labout 6 to 7 months old, which progressively became
& V/ o/ C2 t- Zdarker. She was also concerned about the enlarge-
3 |' N) `; E1 o* a$ U" B7 ~- N9 Fment of his penis and frequent erections. The child
1 E* @- A; \8 p Xwas the product of a full-term normal delivery, with
# J( ]6 b; ]1 N+ J. |. ka birth weight of 7 lb 14 oz, and birth length of8 g) G) h: L3 w& N1 C- ]& Y, F5 f8 i6 t
20 inches. He was breast-fed throughout the first year
" R# y0 u$ u( ~; {* |of life and was still receiving breast milk along with
. X/ k9 V- U" G* \1 q5 Gsolid food. He had no hospitalizations or surgery,$ `& z0 |+ w% e
and his psychosocial and psychomotor development n! k8 y% X( U2 }: x
was age appropriate.
3 `8 e" B! ] V7 X8 \# s- O8 }The family history was remarkable for the father,
7 ^" u, d4 y* w) I0 d- V' iwho was diagnosed with hypothyroidism at age 16,' k2 K0 U8 u4 n3 j5 L
which was treated with thyroxine. The father’s
6 i8 H) Y3 D+ B: J7 V1 F% n9 vheight was 6 feet, and he went through a somewhat
& _: S: K* j' d$ n. hearly puberty and had stopped growing by age 14.$ s; k& g; H2 C0 n& |) z! L
The father denied taking any other medication. The
( R! U% K' |. m% Qchild’s mother was in good health. Her menarche
6 W8 c( A5 Z' q1 Kwas at 11 years of age, and her height was at 5 feet1 z( ^- X% R+ \
5 inches. There was no other family history of pre-6 _/ _/ |, F; A) r# {7 ] H
cocious sexual development in the first-degree rela-
1 Y! F' q5 {+ `/ etives. There were no siblings.+ [. x I ^+ g
Physical Examination1 k$ `; T+ b) y$ D1 a
The physical examination revealed a very active,
& e- |% |* s( i+ M% J$ dplayful, and healthy boy. The vital signs documented; H4 y1 @: `: E$ O9 {
a blood pressure of 85/50 mm Hg, his length was( D8 V3 g% M3 @+ A$ ?' i( b1 A3 a
90 cm (>97th percentile), and his weight was 14.4 kg
& `- a& m5 M% Y1 K* b' J& T(also >97th percentile). The observed yearly growth
6 G8 i' g) Q7 g T: d: N# H. ivelocity was 30 cm (12 inches). The examination of' z8 s& m: T# O9 ?9 n
the neck revealed no thyroid enlargement.
) j7 m: m$ _1 ]& @% R* n, N3 d- }% X: v% zThe genitourinary examination was remarkable for( T- b; U6 B! y( D. _
enlargement of the penis, with a stretched length of" g b- Z8 X0 O4 X
8 cm and a width of 2 cm. The glans penis was very well& n5 r8 `- z; y. A! A
developed. The pubic hair was Tanner II, mostly around8 h# f$ r5 {9 B; t4 U; N
540! ~# ]8 Z( Y' b
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from9 E, t, E) ? p
the base of the phallus and was dark and curled. The: ]) f; a. m" q3 `: ]6 v
testicular volume was prepubertal at 2 mL each.
* {5 K8 o8 E6 p/ B1 WThe skin was moist and smooth and somewhat
- U: m3 r& G. i6 U; Koily. No axillary hair was noted. There were no
7 u( F4 c' T i. j- G5 y2 }abnormal skin pigmentations or café-au-lait spots.8 z8 \ n) N8 V3 L* D) Y2 R
Neurologic evaluation showed deep tendon reflex 2+
! T' |9 I# d+ p6 {/ Tbilateral and symmetrical. There was no suggestion
5 ~/ [' e3 F) u) {7 p3 C) bof papilledema.
9 a7 W0 V4 A4 u- Q0 N0 [Laboratory Evaluation
% T8 M& ]8 V* T. J9 nThe bone age was consistent with 28 months by
8 Y# n m( G- P) h. I" w8 Lusing the standard of Greulich and Pyle at a chrono-
) }% r, [' R" s5 p( s, Z6 Klogic age of 16 months (advanced).5 Chromosomal
5 d' t6 S2 C# O% y* pkaryotype was 46XY. The thyroid function test
' p, t; r7 L! z; a0 U' nshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
# @* H+ M1 [8 |* O9 L5 clating hormone level was 1.3 µIU/mL (both normal).
* v9 @ x W# C# |3 yThe concentrations of serum electrolytes, blood: E: u% y, x- @: _) K3 c0 W
urea nitrogen, creatinine, and calcium all were
5 C3 b; c; I/ M8 Vwithin normal range for his age. The concentration
* S, h; l# n. R# Xof serum 17-hydroxyprogesterone was 16 ng/dL0 z2 D& B, `& L9 }
(normal, 3 to 90 ng/dL), androstenedione was 20. l+ p. G7 g7 ^' v% R6 ?9 G% m' m
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-5 `3 D8 x' a" D; F% ] f
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
' k' o6 s7 c: @3 `, ^desoxycorticosterone was 4.3 ng/dL (normal, 7 to
$ n" M# V1 u" z4 M h; y& h49ng/dL), 11-desoxycortisol (specific compound S)% A, C( M; _) S6 `1 b! k- \
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
) D# v" j3 h: o0 Y$ }tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
6 f, q9 p& y" U4 s5 i: {( }testosterone was 60 ng/dL (normal <3 to 10 ng/dL),8 H0 Q0 J- D# b, n
and β-human chorionic gonadotropin was less than1 Z# p r; S" w1 y/ M4 P3 U0 `2 Z
5 mIU/mL (normal <5 mIU/mL). Serum follicular
% C9 i1 q% b9 x3 x6 d* fstimulating hormone and leuteinizing hormone
{4 o- @$ j+ @1 A5 F4 zconcentrations were less than 0.05 mIU/mL7 g: Q& \% U; U1 u. s! T9 {0 `3 P
(prepubertal).
# y! r+ m$ ?0 V* D# q/ i' H L& MThe parents were notified about the laboratory; {; |7 X' L+ j! @5 b8 `
results and were informed that all of the tests were
+ R+ ]+ F/ h, |normal except the testosterone level was high. The; o7 U& f% B+ F4 R5 Z: ~
follow-up visit was arranged within a few weeks to
0 Y s5 O) N i; f, i, w! jobtain testicular and abdominal sonograms; how-5 m* ` Q: _$ B) h8 P' U1 e% q
ever, the family did not return for 4 months.& |7 p) C- U/ L- }7 u
Physical examination at this time revealed that the; E& Z6 S) N) x* M; \3 b
child had grown 2.5 cm in 4 months and had gained7 ~* W9 Y( e% ?5 t) B8 S
2 kg of weight. Physical examination remained
$ S" Z$ w! w8 Y* Runchanged. Surprisingly, the pubic hair almost com-% E9 V3 {5 C" P
pletely disappeared except for a few vellous hairs at
+ r5 F9 T Y) l$ B7 g5 Hthe base of the phallus. Testicular volume was still 29 B! M6 M% u- j+ ^3 L. G5 H
mL, and the size of the penis remained unchanged.; T( s8 B h+ N D% c' ]) ^
The mother also said that the boy was no longer hav-
' U& w, m1 @9 R ]1 ?ing frequent erections.
, K4 w6 a9 H2 W- Z# y# JBoth parents were again questioned about use of/ P! N3 {0 n% w @" [/ s4 k. Q* P
any ointment/creams that they may have applied to# H6 p2 _2 u: R2 s, o5 z
the child’s skin. This time the father admitted the
9 j6 l2 i, q- `' ^$ o0 |1 k @Topical Testosterone Exposure / Bhowmick et al 541
i0 O& q4 C0 Y6 h1 S2 {! e* kuse of testosterone gel twice daily that he was apply-
" Q6 l' x6 @* m x3 y3 g% \ing over his own shoulders, chest, and back area for
% }. M' `5 R! r- ]# y+ Oa year. The father also revealed he was embarrassed
8 i5 k ~- L0 v; r( j6 ]4 uto disclose that he was using a testosterone gel pre-
4 l& a, g6 F* ~! j+ ?scribed by his family physician for decreased libido
9 {. h4 ?. l+ l! L" q8 n* U7 Rsecondary to depression.
- a0 V0 b' z5 _# g1 g% \; UThe child slept in the same bed with parents.' T( u5 [( ]6 H8 Y' ?* O
The father would hug the baby and hold him on his
0 H1 N2 a1 j. f8 S2 n5 @5 Dchest for a considerable period of time, causing sig-/ e0 s! Q: r" `3 N$ L& ?) R7 v4 l
nificant bare skin contact between baby and father.
# D9 K, ? w# K& T) P* yThe father also admitted that after the phone call,
+ w3 s( A, g D6 ?when he learned the testosterone level in the baby
$ A6 ^2 F" q0 L" h" T# owas high, he then read the product information# s+ R8 P, U0 l8 J' ]& s
packet and concluded that it was most likely the rea-" \$ e% {: _3 _/ p" j' T( s
son for the child’s virilization. At that time, they# _* l( D4 c& a0 }' O/ `
decided to put the baby in a separate bed, and the: m; @7 m! R1 x1 Z4 |* A
father was not hugging him with bare skin and had1 c. S. E* p- c7 N0 F
been using protective clothing. A repeat testosterone
1 ~, E3 _! {/ xtest was ordered, but the family did not go to the T. i0 ^7 b) _. A) u+ h3 ~! S
laboratory to obtain the test.3 |" ~/ a8 b0 O( S
Discussion
1 x$ u `6 y% |. y% c' w. tPrecocious puberty in boys is defined as secondary3 f0 ^# L* [5 E1 v- z
sexual development before 9 years of age.1,4
3 G+ w0 X" r/ jPrecocious puberty is termed as central (true) when
% A) G2 }& | b6 i3 qit is caused by the premature activation of hypo-* J6 `5 ~! i6 P9 u
thalamic pituitary gonadal axis. CPP is more com-; `& l1 ?$ H7 n- o( D/ w
mon in girls than in boys.1,3 Most boys with CPP( `3 b' N5 a* u$ @( \% G
may have a central nervous system lesion that is
: z6 b4 D/ d* z+ sresponsible for the early activation of the hypothal-1 F2 p1 y" M# o0 c8 e+ W
amic pituitary gonadal axis.1-3 Thus, greater empha-
, a: h1 l- d4 Bsis has been given to neuroradiologic imaging in
I2 X& r* v8 t ~/ _boys with precocious puberty. In addition to viril-
% M- @! i3 [3 o. u' t3 b$ q8 vization, the clinical hallmark of CPP is the symmet-
5 F3 t5 ^# f0 w3 t& Q) |: Jrical testicular growth secondary to stimulation by, K1 O# T1 X8 D# n) Y
gonadotropins.1,3; [( H) ~, Q; O& E2 @6 W
Gonadotropin-independent peripheral preco-
^7 ~* |+ _) j% n% t+ F( ?% [" p) ^cious puberty in boys also results from inappropriate0 P! _4 R: G! e/ ]3 g
androgenic stimulation from either endogenous or+ u' l$ c3 G0 b6 {4 q# R2 y
exogenous sources, nonpituitary gonadotropin stim-
* U( d- b/ e6 q% ?8 aulation, and rare activating mutations.3 Virilizing- i0 ^3 S! \! @2 B* T: K
congenital adrenal hyperplasia producing excessive
# @3 x c/ t' x2 t! ~, R: qadrenal androgens is a common cause of precocious
, ?. g) z0 ?- O0 G2 d, bpuberty in boys.3,4) o2 d6 b+ ?+ h! a2 w- u) a
The most common form of congenital adrenal. X) X. X7 a1 G @, @& x3 e
hyperplasia is the 21-hydroxylase enzyme deficiency.
6 }; O$ m2 M# O$ t; oThe 11-β hydroxylase deficiency may also result in
+ D) t0 m- x/ C0 s$ h& W) xexcessive adrenal androgen production, and rarely,. s, o- m8 L) l# @
an adrenal tumor may also cause adrenal androgen' G. a# K4 |) a& e$ D9 V# ?
excess.1,3
2 z, H7 c7 |0 M# x; {at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
( a5 g+ Z0 U" ^% C9 s! S542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
1 B0 _& ^* n. d% nA unique entity of male-limited gonadotropin-+ e5 F& R# ]% l2 t3 d, w) F: ]
independent precocious puberty, which is also known( y: M8 \7 t, i+ L( {
as testotoxicosis, may cause precocious puberty at a
* A! Q. G8 E+ i0 T# o) Avery young age. The physical findings in these boys4 U3 U& t! }1 r) w
with this disorder are full pubertal development,. K0 ~- i! q- H' _. Z, q7 w# Q8 X% b
including bilateral testicular growth, similar to boys' ]1 q+ h* e+ ]3 w2 R
with CPP. The gonadotropin levels in this disorder
( @8 o0 ?& Y" o5 Pare suppressed to prepubertal levels and do not show
& q x1 K2 P6 o/ j& Jpubertal response of gonadotropin after gonadotropin-; [1 i7 w; l0 \! |
releasing hormone stimulation. This is a sex-linked
* I* r& f1 M$ mautosomal dominant disorder that affects only
, L, \3 B! u+ o1 W' `2 S5 Pmales; therefore, other male members of the family
- {2 K; S; u) [* y7 E1 Emay have similar precocious puberty.3
1 ? n$ x' T, N& B, vIn our patient, physical examination was incon-
1 O6 d% O" {0 d5 C' ssistent with true precocious puberty since his testi-
/ p2 V6 _9 T7 t1 z+ tcles were prepubertal in size. However, testotoxicosis
. h/ X+ p7 M" [4 Uwas in the differential diagnosis because his father& H7 h) }+ h& \" N q' `
started puberty somewhat early, and occasionally,/ U: R! H, s# x; C
testicular enlargement is not that evident in the& \- L: ?$ |" K2 f
beginning of this process.1 In the absence of a neg-. M/ Z4 M5 ]5 D
ative initial history of androgen exposure, our) V+ S% t4 O; _2 s0 t* l
biggest concern was virilizing adrenal hyperplasia,* @1 `) s! {+ C$ b
either 21-hydroxylase deficiency or 11-β hydroxylase% z; |9 q" u: R* n
deficiency. Those diagnoses were excluded by find-; L- y5 z; V& N& S, X# k
ing the normal level of adrenal steroids./ M2 o+ A- @& {; S0 o
The diagnosis of exogenous androgens was strongly& m9 m8 B1 ?4 t2 J7 G
suspected in a follow-up visit after 4 months because3 K' B8 V0 Y+ ?; \; I- G
the physical examination revealed the complete disap-
# D3 `1 N0 ]6 g) Z, f' q: ?3 Wpearance of pubic hair, normal growth velocity, and
/ X5 c% @$ S5 B0 N) rdecreased erections. The father admitted using a testos-
6 ~9 ^' j5 [; ? ~4 ]terone gel, which he concealed at first visit. He was |9 W" I6 L( N+ O4 _ ]
using it rather frequently, twice a day. The Physicians’3 w& e# d' s- D) d; a" j) m1 V
Desk Reference, or package insert of this product, gel or
6 [- m, p; S, }) h5 S. L a& n, Rcream, cautions about dermal testosterone transfer to
. R8 H! l+ j3 } L* {& K. sunprotected females through direct skin exposure.6 A8 O- r% h& Z" x8 @
Serum testosterone level was found to be 2 times the
* h! v) p. ~; r2 g1 J/ fbaseline value in those females who were exposed to
+ `7 _) f) e3 L+ q1 j" o( |even 15 minutes of direct skin contact with their male/ m( c+ P; ?8 p/ I# P# k" a" r
partners.6 However, when a shirt covered the applica-. E/ K. V0 z$ X( r6 B0 v
tion site, this testosterone transfer was prevented.3 e# ~) k' Z/ G& v1 R/ n! ^- d' W
Our patient’s testosterone level was 60 ng/mL,2 v! O; Y$ N/ U9 {% d* A" p
which was clearly high. Some studies suggest that" O1 a0 i4 V1 f# ~
dermal conversion of testosterone to dihydrotestos-
# W5 F& D a Rterone, which is a more potent metabolite, is more" O0 V3 `6 Y3 e" Q8 T% t3 Q
active in young children exposed to testosterone# C' g% K" i. u, d- _# O
exogenously7; however, we did not measure a dihy-
, e$ s( t5 F7 B" S; r& idrotestosterone level in our patient. In addition to
& L, \: c4 x& L. L7 A \+ jvirilization, exposure to exogenous testosterone in
( ]8 V- X, a. X. X1 ^: W4 Q# w" xchildren results in an increase in growth velocity and
. e5 _' J' M9 ^( e* Padvanced bone age, as seen in our patient.
* c i" v9 n s+ }# b0 R6 UThe long-term effect of androgen exposure during
) ~7 H4 x. U% `3 Z. uearly childhood on pubertal development and final6 u) j6 H& J" ?
adult height are not fully known and always remain0 H' z& k+ E1 M6 R/ t
a concern. Children treated with short-term testos-* i O' f" O+ v# e; u9 Z9 E0 {; k: F
terone injection or topical androgen may exhibit some3 }4 Y5 ~9 P6 U! { T
acceleration of the skeletal maturation; however, after. Y; @# W2 A- A0 \
cessation of treatment, the rate of bone maturation1 \; h, u# N' B
decelerates and gradually returns to normal.8,9% W6 \; t y! Y p8 P$ X7 T g
There are conflicting reports and controversy/ J( \( r3 `7 D. n/ [
over the effect of early androgen exposure on adult
; _$ I4 I0 C" E6 @) [4 xpenile length.10,11 Some reports suggest subnormal" u# l) O- @* ^, [* H
adult penile length, apparently because of downreg-
/ @, n8 S+ x' Rulation of androgen receptor number.10,12 However,
* Z* M, I M3 b+ hSutherland et al13 did not find a correlation between
4 _& ]' d* l" V- d# h2 Nchildhood testosterone exposure and reduced adult- h/ L8 Q( |4 B5 d* g1 D
penile length in clinical studies.
" b/ I3 d/ U, I6 P! i% l6 XNonetheless, we do not believe our patient is
/ W* k+ p5 H' F3 z8 W) M, n4 \$ lgoing to experience any of the untoward effects from5 o0 O! \4 P" `$ S/ d
testosterone exposure as mentioned earlier because( y8 R. n, ^( Z
the exposure was not for a prolonged period of time.3 l7 q1 |) J' ^% e4 i! G4 F6 m
Although the bone age was advanced at the time of6 u* R/ \: E; f' P+ I1 o) S
diagnosis, the child had a normal growth velocity at
5 d" J( T- g; ^; q1 dthe follow-up visit. It is hoped that his final adult
; d6 P# W( `, o( d5 u, `5 P% g/ I$ K sheight will not be affected.* _ o8 X( G3 n* Q
Although rarely reported, the widespread avail-' ]& d+ Y4 Z; Q; P- s( u6 y; W
ability of androgen products in our society may0 p+ F7 p1 [* J; D. X7 q3 m
indeed cause more virilization in male or female
" U5 B0 F# g+ ^2 B0 `children than one would realize. Exposure to andro-/ E- D$ ~4 G6 ^+ ?5 {% C1 ?
gen products must be considered and specific ques-
- n: \, X1 W# Z; gtioning about the use of a testosterone product or
/ C3 k/ L! w A+ Kgel should be asked of the family members during1 {3 @# k0 K+ Q0 k
the evaluation of any children who present with vir-1 h$ V8 {: ~1 l l8 e% H% p% S' ^% j
ilization or peripheral precocious puberty. The diag-
8 N0 I6 @) Y! K+ N& {$ Tnosis can be established by just a few tests and by, g# i! Y/ H) Z) ?
appropriate history. The inability to obtain such a0 _) t4 v* |# v, R
history, or failure to ask the specific questions, may5 |: u( J7 P* f' Z$ j- ]) J
result in extensive, unnecessary, and expensive" ^; p k, Y. w/ X- O* p7 ^
investigation. The primary care physician should be, L. K( z* E U
aware of this fact, because most of these children; q* Z& J1 \8 K ~
may initially present in their practice. The Physicians’
& Z( }2 V9 ?3 e2 o- }" v/ m" ~: TDesk Reference and package insert should also put a
0 X& d) e- Q. x/ @: w3 {7 Ywarning about the virilizing effect on a male or
# |2 L. C" U! ^' |* _7 Zfemale child who might come in contact with some-
' \, K2 }% ~& p+ A' q, U7 aone using any of these products.' M6 G4 Z: `1 v5 u5 q
References
0 T! z* X2 H! X3 @9 s4 S; o1 k1. Styne DM. The testes: disorder of sexual differentiation
2 x7 ]( L3 Q- e+ e! x. o+ b& D; \* Land puberty in the male. In: Sperling MA, ed. Pediatric
$ h$ X. b; ]! ?3 D7 g3 `7 FEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
) ?8 g2 \3 l- _# [5 J2002: 565-628.
2 D* x6 Y" ^8 p/ L3 Y- F2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious# U, _( ]0 O3 _4 t: R3 M# w
puberty in children with tumours of the suprasellar pineal |
|