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Sexual Precocity in a 16-Month-Old
: }$ c, g: a4 d) N4 }Boy Induced by Indirect Topical
, A$ r% H2 r3 j, A q6 dExposure to Testosterone% W0 e( b* k# K- z* R
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
# w, f" q4 W$ W8 wand Kenneth R. Rettig, MD1
6 d. c& j% |. K3 q) Q* T# a jClinical Pediatrics
0 z' C) r; T3 }) aVolume 46 Number 6
* K. C5 A5 X& o2 D% EJuly 2007 540-543
! f* [! ^5 \$ | F© 2007 Sage Publications
b3 I' C, a% v2 q* V10.1177/0009922806296651
, h2 H6 G8 m5 |, r% o+ xhttp://clp.sagepub.com* d: u/ p& x% t: E
hosted at' L' E4 b$ M+ `7 {
http://online.sagepub.com1 y! u1 u! Y( l7 k \
Precocious puberty in boys, central or peripheral,
! t4 r [ N" Z% \/ nis a significant concern for physicians. Central
: z* l/ g& {; jprecocious puberty (CPP), which is mediated5 x3 t4 e+ P* S( t+ A
through the hypothalamic pituitary gonadal axis, has+ W) E& t e% [+ A9 C7 u. h6 U
a higher incidence of organic central nervous system
( _, m. E6 m# u* Dlesions in boys.1,2 Virilization in boys, as manifested
. H8 D% A. ]. E( k2 `by enlargement of the penis, development of pubic
9 s4 }7 a* _4 X" r0 Bhair, and facial acne without enlargement of testi-
4 W3 w3 C3 m( mcles, suggests peripheral or pseudopuberty.1-3 We$ n8 j+ o7 s' L$ w0 E8 Q
report a 16-month-old boy who presented with the
6 @* s4 _- q0 O4 u* G( menlargement of the phallus and pubic hair develop-' I3 `( Z8 N+ [1 H5 P' a
ment without testicular enlargement, which was due. c" W |! d- d; F7 x
to the unintentional exposure to androgen gel used by
# L/ w' T3 j+ y4 w/ f6 S+ a2 vthe father. The family initially concealed this infor-" q0 Z) Q5 v: n* E" w* y
mation, resulting in an extensive work-up for this0 O A! G: l: [8 u2 ]' w8 } G; B+ ~
child. Given the widespread and easy availability of
& O4 \) W/ ~3 v% h( V8 [4 r, Vtestosterone gel and cream, we believe this is proba-: E: C! K, @7 U0 y! R
bly more common than the rare case report in the" T" W5 ~% G% N( r
literature.4
7 }2 J6 g0 i& _) n! g: i( n& p) @; J- bPatient Report
/ a8 P4 k+ r, v( K& bA 16-month-old white child was referred to the0 L) L" @ {8 C9 X0 n
endocrine clinic by his pediatrician with the concern
n3 }! |. Q& M' K& v1 N! Z" n6 u* P0 sof early sexual development. His mother noticed
3 U5 N2 a6 G+ F$ l2 _' mlight colored pubic hair development when he was
' `. J# Q; S' L3 Z9 xFrom the 1Division of Pediatric Endocrinology, 2University of( [9 W% w* F' J: G, ^
South Alabama Medical Center, Mobile, Alabama.
4 `9 K1 e# p2 EAddress correspondence to: Samar K. Bhowmick, MD, FACE,- j8 e3 m/ h2 r& f: ^
Professor of Pediatrics, University of South Alabama, College of$ U. H# P# }7 g* g( z% u! t+ p
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;: f2 R6 z$ u& _$ Z
e-mail: [email protected].
" R' A6 r& w8 G8 }. K/ @about 6 to 7 months old, which progressively became
. j& v6 `2 @: }darker. She was also concerned about the enlarge-( L5 }: _6 A, v7 C# K1 I
ment of his penis and frequent erections. The child
( f2 D& D( m, ywas the product of a full-term normal delivery, with/ B2 ~* f( z2 r; M3 x. u% t6 }3 ~
a birth weight of 7 lb 14 oz, and birth length of
; w% Y1 s4 M! w1 F) X20 inches. He was breast-fed throughout the first year
# ?% ?* z& c" [. p. ~of life and was still receiving breast milk along with
. U- }! p) ]" K/ Ssolid food. He had no hospitalizations or surgery,1 U8 a. Z' }- F; F7 Q0 \3 B
and his psychosocial and psychomotor development0 Z# s, x# f0 }
was age appropriate.
8 a2 K2 \1 E$ q9 Q+ vThe family history was remarkable for the father,
E/ C6 u F/ n# E- o3 Xwho was diagnosed with hypothyroidism at age 16,
_% I4 N% ?1 x) Y5 qwhich was treated with thyroxine. The father’s
a( |1 E t, v% ?- I, s2 K! Wheight was 6 feet, and he went through a somewhat
. H5 s; [( a3 Qearly puberty and had stopped growing by age 14.' |$ \& C5 Z1 F& ?+ Y4 z
The father denied taking any other medication. The
7 s9 A; C* L/ g) ~# Xchild’s mother was in good health. Her menarche
/ g3 B8 J9 l6 dwas at 11 years of age, and her height was at 5 feet
2 P! _) c1 Q& Q7 n5 inches. There was no other family history of pre-) y x6 \& N2 x N2 g
cocious sexual development in the first-degree rela-
2 A5 L/ \ v7 l3 j/ itives. There were no siblings., ~ x( u8 a1 T. d9 L
Physical Examination
. V2 D1 r& \. p+ K# G, nThe physical examination revealed a very active,
0 \4 \3 g8 \ l( \/ [4 H* y8 u; pplayful, and healthy boy. The vital signs documented% b8 k+ X8 v. q
a blood pressure of 85/50 mm Hg, his length was3 c; D# e- S. |1 R: x4 c" T( E
90 cm (>97th percentile), and his weight was 14.4 kg w2 H! u) T9 f, f! E
(also >97th percentile). The observed yearly growth
% ^1 L" ^* Z; b+ I; _. B0 z Fvelocity was 30 cm (12 inches). The examination of2 Z, g8 V. n: h- p+ o% a
the neck revealed no thyroid enlargement.
% P2 ?9 E% _8 I/ Z1 \The genitourinary examination was remarkable for* s1 V: V4 U+ r5 ^
enlargement of the penis, with a stretched length of" Y/ f- A) I% j% M9 d$ q! `
8 cm and a width of 2 cm. The glans penis was very well
7 G5 m, T$ T, Bdeveloped. The pubic hair was Tanner II, mostly around5 Q& E- r9 X8 F8 W9 o
540! ?% ^. v6 B$ _% d; L9 n
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
1 o; n$ g0 d: ?8 K9 V1 j; E$ S' rthe base of the phallus and was dark and curled. The: b9 K: d- M- u4 y. i. ~% R
testicular volume was prepubertal at 2 mL each.6 O/ Z G }9 I! R8 z$ M S, C
The skin was moist and smooth and somewhat
, t) E! A$ k+ ?* }0 L0 a+ j, H) }oily. No axillary hair was noted. There were no, B( i; g0 \, M9 c+ L
abnormal skin pigmentations or café-au-lait spots.2 {; P+ U9 n3 x2 E3 c- o
Neurologic evaluation showed deep tendon reflex 2+
. o: f5 H% x$ mbilateral and symmetrical. There was no suggestion* |6 z0 Q" N9 W; q, o. b- h7 k2 Y
of papilledema.* {7 w O9 }# |
Laboratory Evaluation% _0 M/ j7 x+ P
The bone age was consistent with 28 months by5 f% X' P- x) O6 [0 U% s
using the standard of Greulich and Pyle at a chrono-
& M/ n @: L4 P) w% C' Dlogic age of 16 months (advanced).5 Chromosomal) v. Q" N, j, W; q
karyotype was 46XY. The thyroid function test' u! Y9 e0 \; x$ r
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
" d) I D7 q8 O2 y# l1 Slating hormone level was 1.3 µIU/mL (both normal).
! W0 h U' f8 h# z! ~0 n% g% AThe concentrations of serum electrolytes, blood
* f# l6 p" \5 vurea nitrogen, creatinine, and calcium all were+ ?* m- i- p+ ]! y0 ^; a
within normal range for his age. The concentration. ^: [) F! a! c! A0 @& D9 ~7 |
of serum 17-hydroxyprogesterone was 16 ng/dL9 B* P; T9 \2 B3 \' }
(normal, 3 to 90 ng/dL), androstenedione was 20! k! y* R# L4 l% T) Q( y9 v, q6 L9 w% T. S
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-9 Y, {# s& f* S8 P8 Z' M1 A& t+ R
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
% B1 r% P3 `( u1 }* B xdesoxycorticosterone was 4.3 ng/dL (normal, 7 to* w( X3 o/ x, g! n
49ng/dL), 11-desoxycortisol (specific compound S)
7 @5 D3 q+ Y3 F, I' g8 @was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-6 u) D, Z' _& B; E
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total7 z, J8 p. r* E& P* g* E9 c: p7 K) P
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
# a3 S5 w. v9 n8 h, i2 C6 J6 Oand β-human chorionic gonadotropin was less than2 U# c- V5 r4 f4 B0 b8 j5 z
5 mIU/mL (normal <5 mIU/mL). Serum follicular
/ T N# L7 S: ]) R: M) ystimulating hormone and leuteinizing hormone
- h, ?; u& k- C$ T" h+ d3 k$ jconcentrations were less than 0.05 mIU/mL
& ^( U5 h0 L2 ?' x) D" q& C+ K t(prepubertal).
8 Y0 a' ?) T. Z+ \, W/ jThe parents were notified about the laboratory
2 x7 ~+ I: M8 J: }0 U. V% _results and were informed that all of the tests were$ B# f& t [ ]1 T6 h, D
normal except the testosterone level was high. The
0 B# ~" e& A: ?- Jfollow-up visit was arranged within a few weeks to
: o8 q" [" v/ D+ s8 eobtain testicular and abdominal sonograms; how-* `4 ?$ H# ]- d- U/ E( M. Z
ever, the family did not return for 4 months.
. ]9 G/ q# T+ dPhysical examination at this time revealed that the& @0 B8 N6 r* v5 {
child had grown 2.5 cm in 4 months and had gained0 b# R# O9 [" \7 g2 p6 D
2 kg of weight. Physical examination remained
! j+ a" n0 D$ h9 V" e w( [unchanged. Surprisingly, the pubic hair almost com-2 R" ~4 c9 V/ k+ y6 j' Y! ^
pletely disappeared except for a few vellous hairs at
5 B2 }$ G: b4 x1 Z) Pthe base of the phallus. Testicular volume was still 2$ v1 P# o- ^4 I7 T8 }3 y+ U/ g& J! Y& f
mL, and the size of the penis remained unchanged., g, `2 d$ T( o' p8 G
The mother also said that the boy was no longer hav-; l$ X8 z; o- W; P z8 [
ing frequent erections.3 ?: `3 Y( }. B& t2 J+ o
Both parents were again questioned about use of
; ?3 Q4 \* ~$ p5 Vany ointment/creams that they may have applied to
" T2 T+ g) Q. y! Kthe child’s skin. This time the father admitted the
5 ^* n$ Z& r, j3 d0 KTopical Testosterone Exposure / Bhowmick et al 5411 a# B& T( m6 X" E% x
use of testosterone gel twice daily that he was apply-2 ]8 S; `9 Q4 q& }% s
ing over his own shoulders, chest, and back area for
- G2 D: Z& B* Y( }: ^a year. The father also revealed he was embarrassed
% S; g" f! |) e6 D( i/ e. Wto disclose that he was using a testosterone gel pre-
7 q1 h+ {- K+ E4 ?$ n- f8 wscribed by his family physician for decreased libido1 K+ V' r4 {& u
secondary to depression.9 k. P7 U; i6 p# k& v9 L
The child slept in the same bed with parents.0 ]4 X m1 O% Q, W2 n- O. |
The father would hug the baby and hold him on his( w# r9 O w* @0 s" Q
chest for a considerable period of time, causing sig-
O; \4 E3 `0 g- @/ \9 o6 wnificant bare skin contact between baby and father.; i0 F! V. B1 Q" V$ X( d
The father also admitted that after the phone call,
2 w' I2 n) H' Zwhen he learned the testosterone level in the baby( c( b( o% Y1 ~* v
was high, he then read the product information! v5 C" Q. E$ H3 e5 c7 |! U
packet and concluded that it was most likely the rea-
( j( B( Y6 a6 t' gson for the child’s virilization. At that time, they
$ j! |) _/ v! C/ E+ B5 wdecided to put the baby in a separate bed, and the; X- |3 s+ u t' x4 E
father was not hugging him with bare skin and had
3 ?% n* K' E B: f7 u/ Obeen using protective clothing. A repeat testosterone0 {. j0 M5 Y2 b2 J/ i3 F. T2 a: {9 J
test was ordered, but the family did not go to the
3 J$ H8 u( h6 K2 a5 rlaboratory to obtain the test.
$ Y4 m- h2 l$ d$ E. }, qDiscussion+ l: X& v2 f% h8 [/ _8 s) S- M
Precocious puberty in boys is defined as secondary
8 j8 j! ~" s% \& Q% P' Tsexual development before 9 years of age.1,4
3 L8 d1 [, a3 P- VPrecocious puberty is termed as central (true) when3 z5 H7 R& h0 b$ k; o
it is caused by the premature activation of hypo-( P3 V: x8 A' L& l, {( p
thalamic pituitary gonadal axis. CPP is more com-% Q8 o5 F2 n; s+ k% v
mon in girls than in boys.1,3 Most boys with CPP/ m( b0 r$ k7 _) ^6 g% z5 Z
may have a central nervous system lesion that is
7 m) e8 M# S8 X+ O6 @responsible for the early activation of the hypothal-, D% C2 k; o( J. x V
amic pituitary gonadal axis.1-3 Thus, greater empha-
! [* k. F) H7 H$ l3 {sis has been given to neuroradiologic imaging in* z$ H2 U! K2 V- [- O
boys with precocious puberty. In addition to viril-
7 @+ v7 j4 n/ \* x: {ization, the clinical hallmark of CPP is the symmet- B! [# {! h- T! X" r
rical testicular growth secondary to stimulation by, o9 T& M. \1 s; h7 r3 E4 [! Q
gonadotropins.1,3
; H. Q+ f. k2 x. JGonadotropin-independent peripheral preco-/ e( d0 {6 y m
cious puberty in boys also results from inappropriate
- T; z3 h7 m& n |: M6 j+ Jandrogenic stimulation from either endogenous or6 p7 R T2 Q' ?9 `1 b/ N8 p( \
exogenous sources, nonpituitary gonadotropin stim-9 n, r& O6 v! y4 M, P6 R) n
ulation, and rare activating mutations.3 Virilizing- W" v4 E2 H2 `7 ], o
congenital adrenal hyperplasia producing excessive
/ `. H2 o+ I# Y+ ^$ n* Nadrenal androgens is a common cause of precocious
. w- m4 S/ N2 }1 y* v. K$ f" Dpuberty in boys.3,48 h7 H" T. q1 C% h5 G! T `; v& e+ h
The most common form of congenital adrenal4 s: B+ O. U1 y. ^5 g( [6 q, p( D
hyperplasia is the 21-hydroxylase enzyme deficiency.
. N7 \& S u/ s8 I+ xThe 11-β hydroxylase deficiency may also result in2 v9 R# e; N* p/ B2 {. |8 Q- B
excessive adrenal androgen production, and rarely,
/ J( R! g/ Q2 A9 V( e$ Z z3 F4 ^an adrenal tumor may also cause adrenal androgen
/ q4 E; O: J3 f0 Sexcess.1,3
7 h5 B0 A# K1 k$ Y* [( Oat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from9 ]$ g# _& ?8 Q. V7 V
542 Clinical Pediatrics / Vol. 46, No. 6, July 20072 `3 R1 L0 u; r$ D
A unique entity of male-limited gonadotropin-
8 \8 E6 J$ L4 I0 N3 oindependent precocious puberty, which is also known% Z- X9 k X( ]. j+ B4 e
as testotoxicosis, may cause precocious puberty at a% J9 Y, a( D" b. q! j
very young age. The physical findings in these boys
; |3 w9 J0 V- R: k! }with this disorder are full pubertal development,
# W$ {. Y' S9 f/ l7 {" g" {including bilateral testicular growth, similar to boys5 h0 i, }+ N8 n& C* U7 Z
with CPP. The gonadotropin levels in this disorder
`1 f# ~( x+ U$ l- S" Dare suppressed to prepubertal levels and do not show1 _8 F$ n0 }4 e c0 x$ F/ U9 M
pubertal response of gonadotropin after gonadotropin-& o; [, M/ N; {2 r k/ o2 Q) C) U" u
releasing hormone stimulation. This is a sex-linked" k/ {2 v" {' ? {0 J$ e
autosomal dominant disorder that affects only
, n. t* s/ ~+ G+ w/ ]9 {* ymales; therefore, other male members of the family
1 w( G2 J0 V8 x; k' hmay have similar precocious puberty.3' s7 \( G2 P! z' \$ t" y) D& `- g* J
In our patient, physical examination was incon-
9 r: O; [( D4 {0 d0 N, K9 r O0 Esistent with true precocious puberty since his testi-9 W9 Q3 A! ] g0 d5 T" g
cles were prepubertal in size. However, testotoxicosis* d- f7 {$ E8 P6 l$ a
was in the differential diagnosis because his father
0 k0 C, Q/ h& S% ]started puberty somewhat early, and occasionally,
+ @# o" z( S$ r, ytesticular enlargement is not that evident in the: p t8 z2 k4 o. _8 B
beginning of this process.1 In the absence of a neg-
# s2 I" v) c& @7 m* @ative initial history of androgen exposure, our
& f/ F- @; j' A) [& `biggest concern was virilizing adrenal hyperplasia,
+ s* n, d3 h1 Geither 21-hydroxylase deficiency or 11-β hydroxylase# a3 c+ w+ I6 }$ ?+ h
deficiency. Those diagnoses were excluded by find-
8 Q; p! h c8 c' f+ w8 s! hing the normal level of adrenal steroids.
8 c' K! |: x# C3 R3 dThe diagnosis of exogenous androgens was strongly2 U% M+ T0 f' g
suspected in a follow-up visit after 4 months because
! P ?. E! Z, t* z4 b9 Pthe physical examination revealed the complete disap-
, h3 `3 j( j3 Z, m, J) qpearance of pubic hair, normal growth velocity, and) W+ W& P& [/ @
decreased erections. The father admitted using a testos- Z6 C0 Q8 g5 G c* L
terone gel, which he concealed at first visit. He was
; x& [9 f4 A! ~6 {: qusing it rather frequently, twice a day. The Physicians’/ z# B9 Y+ b1 Z
Desk Reference, or package insert of this product, gel or: E, g/ N3 m7 G3 k% d- i8 p
cream, cautions about dermal testosterone transfer to
7 F! p- u0 g) z7 F" Hunprotected females through direct skin exposure.0 f+ K" Q, s7 L; p
Serum testosterone level was found to be 2 times the
' h+ u' i2 n" G( _! Mbaseline value in those females who were exposed to6 S% Q8 O1 t4 F
even 15 minutes of direct skin contact with their male
8 p7 v; k! X6 D, s# ]: G( k0 wpartners.6 However, when a shirt covered the applica-- m# N5 Q) k( d6 M8 k& L+ ?7 p
tion site, this testosterone transfer was prevented.8 m/ T. J! D/ l: L
Our patient’s testosterone level was 60 ng/mL,
4 i1 A, h7 _) N& u5 Dwhich was clearly high. Some studies suggest that7 _" ~' _- ]4 `& o- @
dermal conversion of testosterone to dihydrotestos-! T. m# R1 y* p9 r& z8 d$ L/ L
terone, which is a more potent metabolite, is more
% A2 ?: L( Y; s, H( s) [9 O. ?; ~' W, oactive in young children exposed to testosterone
$ |6 ?& ^6 D" e+ p% x, O8 ]4 }exogenously7; however, we did not measure a dihy-
d* X! ^+ L- K- W0 Z: p1 D* Q. p$ Bdrotestosterone level in our patient. In addition to# X" m( g) ]! r4 ^6 C2 M3 m9 H
virilization, exposure to exogenous testosterone in. X# M0 F! |" B: z) v. y6 N5 P
children results in an increase in growth velocity and
( D7 d5 o O5 ?% N n; ~. Nadvanced bone age, as seen in our patient./ l# Y" w- f3 D0 p$ ?# c5 p
The long-term effect of androgen exposure during8 H4 W+ B$ p6 w+ f. U* f3 T
early childhood on pubertal development and final
; F w5 q$ z4 \! c) N* J7 madult height are not fully known and always remain
1 j" }& C2 `* ~6 n7 ~3 W! t; Ia concern. Children treated with short-term testos-
4 u9 L: K% l5 E1 m8 \ ?terone injection or topical androgen may exhibit some$ f7 y0 y- l1 ^% G- I ]
acceleration of the skeletal maturation; however, after; {5 b* F ?5 F2 r: r' f0 M0 O
cessation of treatment, the rate of bone maturation2 Q! y) }1 q6 `3 S4 J
decelerates and gradually returns to normal.8,9( O! R9 T+ E$ D8 o" u
There are conflicting reports and controversy
. n# s$ e* f% E/ y# @, [1 Lover the effect of early androgen exposure on adult3 x" @# J( S) R9 [; \; @
penile length.10,11 Some reports suggest subnormal
( f' ^7 u: v. Madult penile length, apparently because of downreg-
6 D3 W- e+ z1 G- Rulation of androgen receptor number.10,12 However,
) }6 Q9 k. j5 J0 D) DSutherland et al13 did not find a correlation between
$ l3 @$ H* ]' ]2 _ U! zchildhood testosterone exposure and reduced adult
5 W( m2 u3 ]6 e) ^6 I2 |$ Bpenile length in clinical studies.2 y2 B# L/ i! ^* j2 Q) S
Nonetheless, we do not believe our patient is
8 e" ^. i3 U2 A) W& fgoing to experience any of the untoward effects from5 D0 N! s* S8 Q& d+ J7 m" v8 F4 v. ]
testosterone exposure as mentioned earlier because) K+ V$ W3 M: E
the exposure was not for a prolonged period of time.
: c3 G) }& A5 B0 VAlthough the bone age was advanced at the time of' l0 i9 i: N a: J! F& d
diagnosis, the child had a normal growth velocity at" C9 C: ^9 r" a: e
the follow-up visit. It is hoped that his final adult9 v4 f: ]! y: L& @
height will not be affected.# m$ b$ q# P$ z: `1 t
Although rarely reported, the widespread avail-" E, {$ E: i1 M# o: T
ability of androgen products in our society may1 `1 B" b a; a9 {
indeed cause more virilization in male or female& g; l* P, H( v6 g7 F0 Q
children than one would realize. Exposure to andro-' h! h. W* t' |, j7 X+ ]( C
gen products must be considered and specific ques-+ W7 c0 w/ c0 a1 c" x, Y3 {" |1 S3 b
tioning about the use of a testosterone product or
- s P8 t9 e% u' j9 J+ c3 r, t( Pgel should be asked of the family members during
/ B5 G; `% I; O* K; L+ X/ Q$ ^the evaluation of any children who present with vir-
# g) z7 U3 H4 P' s# R/ dilization or peripheral precocious puberty. The diag-
! ?/ f" G# w+ A* W3 q$ k4 `& Gnosis can be established by just a few tests and by
4 a! u; a) @3 A5 p' I; Dappropriate history. The inability to obtain such a. W* u1 T- t1 N( ]& N, l) ^) r
history, or failure to ask the specific questions, may, `% J" ?* [6 R [) k: [9 n+ ]# F9 ?
result in extensive, unnecessary, and expensive
$ z3 o; ]; F- k5 F4 `0 B+ w- }investigation. The primary care physician should be# O/ Y& \0 L. s! z
aware of this fact, because most of these children
5 j9 S( I1 ]$ c: @: d4 O7 Omay initially present in their practice. The Physicians’
X3 M: C3 \ d* i' ~Desk Reference and package insert should also put a: {8 v7 h7 G* P, s6 d
warning about the virilizing effect on a male or
8 d" g: o) |/ X) p% K Qfemale child who might come in contact with some-
5 K" {3 _7 a+ t) hone using any of these products.
5 R3 x2 I1 k4 o4 C* O) ~+ I% `- UReferences: x$ ^5 j' I' L7 d( E2 Z' W
1. Styne DM. The testes: disorder of sexual differentiation
/ _5 ]) X. v% E4 s9 ^: {: Oand puberty in the male. In: Sperling MA, ed. Pediatric
" P; I* V, P) s# qEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;1 t5 S* H5 P: h- i' h4 F+ ?- [
2002: 565-628.
- Y/ V; q E& P# F2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
; _3 j2 i4 C! b/ z |" V0 zpuberty in children with tumours of the suprasellar pineal |
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