- 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
( `, n) W0 H2 U! W2 X0 L! F- c- RBoy Induced by Indirect Topical5 E+ O& W- b0 G* q: A' M
Exposure to Testosterone) B- c* _$ v2 m# I, p, ]
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2* u; z4 \$ M9 |4 g! c2 `5 `, p
and Kenneth R. Rettig, MD1
( |( X7 ~* ~3 qClinical Pediatrics8 g% @ a% Q5 L9 |6 b
Volume 46 Number 6* x4 E4 O" `, [- H
July 2007 540-543
, X$ l5 f" Y( f: ]/ ^- K$ r© 2007 Sage Publications! F. X! o$ z7 H+ s1 O; P, |4 o
10.1177/0009922806296651
6 l. L9 N6 B6 O' J6 l# yhttp://clp.sagepub.com
; j) a' I8 t) v# t+ @hosted at
- X ]2 k6 H9 Y v* c, h) ohttp://online.sagepub.com; q; Z; _4 H% q0 S* _- t! c
Precocious puberty in boys, central or peripheral,) }" x- v E! S3 S z
is a significant concern for physicians. Central
8 w2 `2 R5 s2 a- pprecocious puberty (CPP), which is mediated6 Q B. G; g4 r9 T' ]5 M% H4 A
through the hypothalamic pituitary gonadal axis, has! ]: g& c* E4 D" R
a higher incidence of organic central nervous system
" ]" Q9 M2 H7 ?% p# \. {- Q% g/ E% Tlesions in boys.1,2 Virilization in boys, as manifested2 s" W: s+ b! o
by enlargement of the penis, development of pubic
! ]& P, ?1 h6 c% M5 n- Khair, and facial acne without enlargement of testi-* E3 q- Y4 H- t3 G+ ` ~! ^
cles, suggests peripheral or pseudopuberty.1-3 We
! k& }6 {4 q' e9 t6 W! S5 m( j6 Creport a 16-month-old boy who presented with the
: S& N- \" x. E: q( Wenlargement of the phallus and pubic hair develop-" V7 \ k' y E( G
ment without testicular enlargement, which was due4 j8 ] \& P6 A
to the unintentional exposure to androgen gel used by! w+ w) Y7 s" ]& ]
the father. The family initially concealed this infor-. H1 K8 `9 S) b% Y& O$ I- U
mation, resulting in an extensive work-up for this
! K& U: q2 n9 ~child. Given the widespread and easy availability of$ U3 W- X1 u5 T) F
testosterone gel and cream, we believe this is proba-
4 A2 |' z0 ~# B: B! V; g: }bly more common than the rare case report in the
n* ?3 |: c# d" g. s+ S) b/ ?literature.4/ G G/ m' y0 s/ K% h3 J( v
Patient Report& n5 I# |" O) J8 Q% B% V2 J: J
A 16-month-old white child was referred to the, U7 j0 G( d/ M% G) [
endocrine clinic by his pediatrician with the concern
: }6 `1 N1 y3 S0 \of early sexual development. His mother noticed3 w, _# f/ |3 {: u, V5 b
light colored pubic hair development when he was6 U5 y1 \, r; n/ w d' R, z
From the 1Division of Pediatric Endocrinology, 2University of8 C* F) I$ S n1 {
South Alabama Medical Center, Mobile, Alabama.: x; S( I7 i" U
Address correspondence to: Samar K. Bhowmick, MD, FACE,
% L$ [# F- K$ V* y* @3 a$ B0 p5 I IProfessor of Pediatrics, University of South Alabama, College of
* f; P4 P8 Q% g% o6 I8 u+ |0 w: g2 BMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
4 C6 G& O0 R. O3 s9 z! qe-mail: [email protected].
( W# ~- F; R! i8 E1 l( N3 gabout 6 to 7 months old, which progressively became2 l4 q* h# A( e- z
darker. She was also concerned about the enlarge-
3 T. o1 z" X: z! L# Sment of his penis and frequent erections. The child- ` d. o) V+ D6 j1 J! Z
was the product of a full-term normal delivery, with) i: j$ H+ M3 N; |" x
a birth weight of 7 lb 14 oz, and birth length of
9 `0 f, x, P0 w- G+ x0 D8 o+ Y20 inches. He was breast-fed throughout the first year
- G+ ?0 \/ E+ e# g) U% ]% Qof life and was still receiving breast milk along with- C$ E/ }3 W2 s- a2 O {6 U" u
solid food. He had no hospitalizations or surgery,4 w( A. W7 I8 J2 e) L4 \2 ]4 q
and his psychosocial and psychomotor development2 b \) a; V4 L' V
was age appropriate., ~; m/ z2 N" v& F7 A* {
The family history was remarkable for the father,5 j% W3 @ H# G0 [5 O7 R1 m7 a
who was diagnosed with hypothyroidism at age 16,
6 i2 |) h3 N$ I5 h9 f; R# g& Gwhich was treated with thyroxine. The father’s7 j; v1 P* Z9 }+ Y
height was 6 feet, and he went through a somewhat
) C3 G% |- n+ P* Q& [: X, Wearly puberty and had stopped growing by age 14.
" ^7 Z o7 Q- B; z4 P! \- |The father denied taking any other medication. The
7 L: |9 L9 n! Gchild’s mother was in good health. Her menarche2 d( w p) g( L/ H5 e
was at 11 years of age, and her height was at 5 feet
5 W1 K# \7 Y( K% L; e2 Z6 C5 inches. There was no other family history of pre-
8 n/ Z. O b" U) a1 ~" @cocious sexual development in the first-degree rela-
' X( a, A2 ]# q* X0 [. d* wtives. There were no siblings./ |- @0 a( V4 u1 A* z) Y3 P0 O: W9 S A
Physical Examination, A7 [: J- Z3 V+ i% c/ v" J! q4 B
The physical examination revealed a very active,
# U# n7 Q$ K2 M+ z/ Eplayful, and healthy boy. The vital signs documented
9 O" S+ S `+ Ga blood pressure of 85/50 mm Hg, his length was ~* h+ d/ N" x( k0 z
90 cm (>97th percentile), and his weight was 14.4 kg1 ?& P# R. j1 v0 x: m
(also >97th percentile). The observed yearly growth
6 I6 p7 G$ a! s/ J0 x g9 bvelocity was 30 cm (12 inches). The examination of
) k6 a7 \, [( [5 w& w1 Ethe neck revealed no thyroid enlargement.
' ]: D2 h l$ z+ x" q9 ^9 F0 b1 iThe genitourinary examination was remarkable for9 ]' e5 F* m. h& X3 L: C
enlargement of the penis, with a stretched length of- g5 w$ o4 x2 Y: a8 d$ e
8 cm and a width of 2 cm. The glans penis was very well$ Q- |7 x g# K ~5 y- G
developed. The pubic hair was Tanner II, mostly around! r, X% x- w/ l2 J
540
, |* l. |5 T7 ^. l+ rat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from O* H5 y4 s+ W9 x- c/ A+ T
the base of the phallus and was dark and curled. The
2 D% N0 u9 ?6 S9 U, a0 C1 rtesticular volume was prepubertal at 2 mL each.( |. v* A& V7 a; ~# g
The skin was moist and smooth and somewhat0 W. F, N, f( k" g# P2 N7 A/ v9 z
oily. No axillary hair was noted. There were no
, G9 H p _/ _ }, ^' e5 babnormal skin pigmentations or café-au-lait spots.
! S" e. T. a3 U2 DNeurologic evaluation showed deep tendon reflex 2+
* \0 t) I3 k6 W, M9 Z! y- Z6 wbilateral and symmetrical. There was no suggestion
1 [; u: M6 ~# l+ d1 p Vof papilledema.
5 l6 t/ M2 T: V3 D* vLaboratory Evaluation
4 u9 L( g. C5 u: e/ a+ ^The bone age was consistent with 28 months by2 c5 ]6 O# W2 ^- ~% Z7 u0 `
using the standard of Greulich and Pyle at a chrono-) |! W4 ^# h% }
logic age of 16 months (advanced).5 Chromosomal
) L" y) K; P4 ~karyotype was 46XY. The thyroid function test
' H; `% f P2 V4 Nshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
2 V" w5 w, s3 q4 xlating hormone level was 1.3 µIU/mL (both normal).
8 s, O/ O- M$ m3 P6 a# V, N7 NThe concentrations of serum electrolytes, blood
9 d8 g# Y, c2 g! x- z) M9 |7 \urea nitrogen, creatinine, and calcium all were7 P6 z4 Z1 D$ {5 F
within normal range for his age. The concentration# y/ j6 `8 ]& }4 ^% e/ q
of serum 17-hydroxyprogesterone was 16 ng/dL( w3 m {& G! Y6 C' c! w$ D
(normal, 3 to 90 ng/dL), androstenedione was 20
% `- }% m# Y2 r& o/ f( B6 ~ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
! @* }: F; O! v7 mterone was 38 ng/dL (normal, 50 to 760 ng/dL),- D" n: ^; b E* E6 C
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
! j9 X6 s" g0 _- |2 H n( k K49ng/dL), 11-desoxycortisol (specific compound S)0 b* m- f% C- S- |4 [( @
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
! A: `# O( ]/ A- Itisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
, S5 R8 N* E. Jtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),' [! p# n1 y8 V, Z& v* {7 k
and β-human chorionic gonadotropin was less than" h _' |! Y7 y
5 mIU/mL (normal <5 mIU/mL). Serum follicular8 O% m6 x8 f3 o$ Y! D$ j. `
stimulating hormone and leuteinizing hormone4 t! F6 t7 E4 y: z0 x9 s, p3 O8 Z' p
concentrations were less than 0.05 mIU/mL( O: J6 X4 ^ M' F* m' }5 g& e
(prepubertal).$ v- n. @- z/ h4 `
The parents were notified about the laboratory
8 B8 k. u: k) C/ ^- V8 C; uresults and were informed that all of the tests were7 F1 e: D( }+ B5 }, t
normal except the testosterone level was high. The3 P& k2 G# O7 t7 B
follow-up visit was arranged within a few weeks to2 b* w1 z# j2 O2 S
obtain testicular and abdominal sonograms; how-
* R) o. b* S; a3 oever, the family did not return for 4 months." J' N4 }3 n. f: B- r m
Physical examination at this time revealed that the
7 k- I% K: c3 B% s. e; \) S/ Fchild had grown 2.5 cm in 4 months and had gained
6 r$ }0 L+ q) N: F2 kg of weight. Physical examination remained
9 g! e- L2 u6 l" R& y- \2 Q5 gunchanged. Surprisingly, the pubic hair almost com-. ~1 W# o8 v6 J4 @/ c0 n2 h, ?
pletely disappeared except for a few vellous hairs at
& R. X. v' T: othe base of the phallus. Testicular volume was still 2- T/ t) p: [/ k) X2 @+ H
mL, and the size of the penis remained unchanged.4 I& Z3 V9 I5 a; Z* K
The mother also said that the boy was no longer hav-) i* A8 z/ u8 M/ J
ing frequent erections.
. O: v5 U2 L w8 R' N" l$ a2 `Both parents were again questioned about use of
, C1 d+ p/ w* C1 ~* v4 F% t* Gany ointment/creams that they may have applied to
9 t- n- j- b; t% j- s! d3 }the child’s skin. This time the father admitted the
7 _9 m- a: w; j. VTopical Testosterone Exposure / Bhowmick et al 541
, O) k* s1 n1 y% Buse of testosterone gel twice daily that he was apply-
) F0 w" n7 Z( D/ T2 m, ]ing over his own shoulders, chest, and back area for( v/ U+ m/ n2 J+ Q P
a year. The father also revealed he was embarrassed
1 A8 X# r7 {- x+ ]2 }to disclose that he was using a testosterone gel pre-( Q# `: L& ~( ~4 {! V0 E7 V
scribed by his family physician for decreased libido
5 Q! E. Y& R6 J* l5 ]: ^secondary to depression.
4 B) q, k5 Q/ P5 JThe child slept in the same bed with parents.# p. b2 @5 f2 C
The father would hug the baby and hold him on his
; A* t( d, h9 p2 K; l5 [8 K; R1 Rchest for a considerable period of time, causing sig-
- x% k e* P- Z, {" x; Vnificant bare skin contact between baby and father.
7 q: d8 e: q6 p# u7 z/ qThe father also admitted that after the phone call,
7 }3 p/ _# e' z( Zwhen he learned the testosterone level in the baby e2 S9 h$ ]. b" d
was high, he then read the product information6 k3 J4 o# K, S' @! j
packet and concluded that it was most likely the rea-
) L' u# d0 h+ fson for the child’s virilization. At that time, they
/ P' T1 |5 a s% rdecided to put the baby in a separate bed, and the0 L5 @4 S2 V# D$ }% Z2 D
father was not hugging him with bare skin and had! M+ U, m6 h2 Z* L: R
been using protective clothing. A repeat testosterone
$ |# t s3 Y ?" E' U8 s c$ Z4 Gtest was ordered, but the family did not go to the1 ? m5 A7 @, r5 K; ^8 {
laboratory to obtain the test.
3 X; M6 i5 b9 Q+ aDiscussion' p& N0 H) Q2 K, c
Precocious puberty in boys is defined as secondary
+ G% a, }# o! _" @" j) msexual development before 9 years of age.1,40 t6 |# O I" F1 W( J* Y) L2 _9 z
Precocious puberty is termed as central (true) when$ ^1 i" H- [2 \1 k- y
it is caused by the premature activation of hypo-
1 |& T6 h4 B3 z4 b. |; {thalamic pituitary gonadal axis. CPP is more com-( p- w" `5 D6 `0 ~* f& I& R5 P
mon in girls than in boys.1,3 Most boys with CPP5 h6 }& w1 m0 Z# ~3 {
may have a central nervous system lesion that is
( `1 X. v9 x. r9 t) {responsible for the early activation of the hypothal-; \6 `0 |' M; c U4 j
amic pituitary gonadal axis.1-3 Thus, greater empha-( g4 Y# Y( T9 E: V
sis has been given to neuroradiologic imaging in
! L# O. }1 q3 C, J3 w+ [boys with precocious puberty. In addition to viril-/ o0 n7 w4 r3 \. c6 l# y
ization, the clinical hallmark of CPP is the symmet-0 V" e# b2 S2 w+ Z0 z
rical testicular growth secondary to stimulation by; W+ f, R' Q/ [0 S |! h+ b
gonadotropins.1,33 m6 |9 v+ D# V* a5 o8 T
Gonadotropin-independent peripheral preco-9 V+ ?$ `& v& A' F+ F6 q
cious puberty in boys also results from inappropriate
: ]4 `& z+ Q/ J! J7 I8 T$ }+ ^androgenic stimulation from either endogenous or" _6 V# z) R# \& t- Q/ [/ X- r. V
exogenous sources, nonpituitary gonadotropin stim-
6 ~. E6 G7 R0 j/ y6 l$ ]# Culation, and rare activating mutations.3 Virilizing/ {7 `5 y! q) i; Y
congenital adrenal hyperplasia producing excessive* b' k6 v" f1 b* R6 E8 i1 C
adrenal androgens is a common cause of precocious+ j+ v7 O5 H; ]4 q6 j% k
puberty in boys.3,4& J( M4 Y9 b9 S% |: i
The most common form of congenital adrenal+ |- ]0 n8 R0 x/ O4 K% p' Y1 k8 e
hyperplasia is the 21-hydroxylase enzyme deficiency.
: [ @4 H. v: [1 _1 _* @0 SThe 11-β hydroxylase deficiency may also result in
' ~& |, Y H" D$ H+ qexcessive adrenal androgen production, and rarely,
/ X/ _4 O5 I' X* u. c, {3 \an adrenal tumor may also cause adrenal androgen, |/ K5 \: N% B4 U! M
excess.1,3' k6 s6 \9 n Z
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from |- v5 g8 f3 t5 l. b1 f+ z
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007. [. b3 s& H# \8 [/ M2 N! V* ^
A unique entity of male-limited gonadotropin-
7 n3 y# {+ M* _- `: @independent precocious puberty, which is also known% z. x4 W* F1 Q+ q
as testotoxicosis, may cause precocious puberty at a
5 w. X3 c% }6 f# fvery young age. The physical findings in these boys
, p, \$ j7 k$ M4 G4 X1 N" Xwith this disorder are full pubertal development,9 |; F8 {0 I" R. y
including bilateral testicular growth, similar to boys) [! _/ f1 j" |. ~# y- w; s* w/ d
with CPP. The gonadotropin levels in this disorder6 n: W) j! A z
are suppressed to prepubertal levels and do not show
, q- W( D& d- q' M) q5 A& w/ r+ npubertal response of gonadotropin after gonadotropin-3 r! m+ D6 E, v4 E- |
releasing hormone stimulation. This is a sex-linked
" h- W# z- G9 c7 v9 Hautosomal dominant disorder that affects only
+ G" g5 j4 m3 q/ i: p& Ymales; therefore, other male members of the family& @8 r$ V$ c5 [7 V- T" B& m. L
may have similar precocious puberty.3
6 R A2 [1 a: e' |: ^2 |- ~& jIn our patient, physical examination was incon- `) K+ C$ h: F8 a. m
sistent with true precocious puberty since his testi-
1 f* `2 k8 f* {5 }! v# Xcles were prepubertal in size. However, testotoxicosis" V* R6 S) j) E U( y1 [
was in the differential diagnosis because his father. b: A: _+ x8 d! y
started puberty somewhat early, and occasionally,
' z6 f2 k y1 o1 Ytesticular enlargement is not that evident in the1 N9 y" T0 P# l" N; j
beginning of this process.1 In the absence of a neg-! t& M T' L9 l5 Z5 `8 t; [, ~
ative initial history of androgen exposure, our3 d5 w8 A: D: Q5 F/ j, T. ^* K
biggest concern was virilizing adrenal hyperplasia,+ u/ K( f: u' R# i) q6 @
either 21-hydroxylase deficiency or 11-β hydroxylase0 i7 ?' c/ t$ ]/ O4 c
deficiency. Those diagnoses were excluded by find-# e m8 h' [$ u7 ^
ing the normal level of adrenal steroids.
) y+ J$ @8 ^# aThe diagnosis of exogenous androgens was strongly
% C% ?0 X# v2 n/ c. N( Lsuspected in a follow-up visit after 4 months because
( E7 X5 T/ f7 o+ G5 H0 Fthe physical examination revealed the complete disap-
8 ?: D: h: u4 W# b4 a' Rpearance of pubic hair, normal growth velocity, and c3 a [* Q" Q% G/ G2 ?7 w' _
decreased erections. The father admitted using a testos-
. U$ ~0 ^( w2 Z6 b7 ]terone gel, which he concealed at first visit. He was& P w& T) G% ~' h8 Y5 {
using it rather frequently, twice a day. The Physicians’6 x! N( `" {7 l
Desk Reference, or package insert of this product, gel or
3 U( P* J3 h* n+ S" H( a: j9 h& kcream, cautions about dermal testosterone transfer to
$ m! n4 J! E) {* y% eunprotected females through direct skin exposure.
/ {1 B% \6 Q2 z0 NSerum testosterone level was found to be 2 times the
; `5 q; `. ~% W. A8 P5 b' D6 { Pbaseline value in those females who were exposed to1 p( P* n; X% E, q1 w2 d1 b; b
even 15 minutes of direct skin contact with their male1 t, V W8 _0 e6 {" ~
partners.6 However, when a shirt covered the applica-5 ], ~3 ^% V( Z
tion site, this testosterone transfer was prevented., x/ {- J: c9 r6 O3 W
Our patient’s testosterone level was 60 ng/mL,
! d% e: @( J w8 lwhich was clearly high. Some studies suggest that% f. x- c2 C& _- P/ M
dermal conversion of testosterone to dihydrotestos-
3 u7 L* e; d' v/ H' c% }0 i; s' [terone, which is a more potent metabolite, is more
4 L* q* H% E' ~2 [active in young children exposed to testosterone, y. P% E( P5 } |) o7 [
exogenously7; however, we did not measure a dihy-) N/ \4 ?. b) t5 u9 f
drotestosterone level in our patient. In addition to f2 H, J3 B7 D; q a3 R
virilization, exposure to exogenous testosterone in
$ D5 _! J' ?8 A8 Hchildren results in an increase in growth velocity and
+ O4 T0 F& D6 K4 X* J8 c& z1 ^$ iadvanced bone age, as seen in our patient.1 d) U H! s, D
The long-term effect of androgen exposure during& G" a+ i9 i1 f& R! N
early childhood on pubertal development and final
. w9 ~" y5 f$ t- Padult height are not fully known and always remain
* T6 _7 H+ z5 X+ f$ o0 o8 C1 ka concern. Children treated with short-term testos-: u: m/ C7 f) ]. w
terone injection or topical androgen may exhibit some
& g4 ~+ t8 [( |, g$ [7 bacceleration of the skeletal maturation; however, after
* Z9 {( l G L _7 u# P+ E) hcessation of treatment, the rate of bone maturation
) [0 J* D: z. k6 Y6 Z& q$ m" Udecelerates and gradually returns to normal.8,9. m6 g& W2 w9 c! ?5 M3 t
There are conflicting reports and controversy, q1 J V7 |( i/ J' h
over the effect of early androgen exposure on adult* |, u" H4 L' k% d
penile length.10,11 Some reports suggest subnormal
5 ~. w. k: a) n N& Fadult penile length, apparently because of downreg-
% j3 O" ~& Q$ `6 `4 X a5 Q( c3 ~ulation of androgen receptor number.10,12 However,
# c( a0 Y% t3 i! m# K9 xSutherland et al13 did not find a correlation between* ~* s- x+ w8 u* p. i: Y" w
childhood testosterone exposure and reduced adult$ M5 s6 z; k, X9 `
penile length in clinical studies.
. Q6 P: m' d! D0 L6 r& ?Nonetheless, we do not believe our patient is
; x1 |9 e8 M* n3 C: `going to experience any of the untoward effects from9 E3 |8 @% ]( O5 D, V/ c3 ]1 ?
testosterone exposure as mentioned earlier because% |% {* i. {8 W: ?
the exposure was not for a prolonged period of time.: Z4 Y; F3 ?' T- g7 n6 W% _
Although the bone age was advanced at the time of9 R3 ]- d( q/ R& ^5 O& u" c
diagnosis, the child had a normal growth velocity at
" q' T5 L% ]' u3 `the follow-up visit. It is hoped that his final adult
7 D5 ]3 Y9 y! I J! hheight will not be affected.
1 I8 j6 G; }0 b1 u( xAlthough rarely reported, the widespread avail-
& z3 e2 S7 T; B# Kability of androgen products in our society may. \ R1 M9 e: w$ q3 [* j0 O
indeed cause more virilization in male or female
1 Y8 i" [+ z/ echildren than one would realize. Exposure to andro-0 l0 `3 A( e5 y0 |8 \/ i. d# W
gen products must be considered and specific ques-
) H% R }" \# O8 S9 \1 G' h. [$ mtioning about the use of a testosterone product or
2 Y2 D' W: B+ r( R+ cgel should be asked of the family members during4 f4 R3 T' J; f% A
the evaluation of any children who present with vir-; \# Q3 n- V0 |2 ~9 w
ilization or peripheral precocious puberty. The diag-1 b' u5 R$ O$ D4 C5 i' m
nosis can be established by just a few tests and by
/ f( L8 k- m. F( ^appropriate history. The inability to obtain such a
: K" O# r- ~2 qhistory, or failure to ask the specific questions, may
0 A D2 n. M3 N. k6 hresult in extensive, unnecessary, and expensive
( |$ N; V4 t# i v) a7 @; _* `* Jinvestigation. The primary care physician should be( G# y9 K/ S, ~4 w1 n, d% ]- q
aware of this fact, because most of these children
$ w0 x$ n+ y! z \4 ]may initially present in their practice. The Physicians’
9 c) i4 E; I& j" v, A; N& x8 EDesk Reference and package insert should also put a
6 f9 k, F% t! F- G. Lwarning about the virilizing effect on a male or
o+ }: c; h# K L# {female child who might come in contact with some-! r, z. Z. A B: ^% K; q+ k
one using any of these products.
1 T& L% ?$ p* ?! L: o9 M: w1 FReferences
& ~" c( j0 B& M5 R% y7 y9 V1. Styne DM. The testes: disorder of sexual differentiation
^$ G+ n; N7 ]and puberty in the male. In: Sperling MA, ed. Pediatric. f( r! C4 ~( a! z& Z& J7 K
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
. u! Z/ s% P- y7 l, K' G2002: 565-628.2 Z6 r, d) Y. A7 j
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious5 A7 G* T- G* n+ m! W' @
puberty in children with tumours of the suprasellar pineal |
|