- 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* @1 a- ]9 o2 nBoy Induced by Indirect Topical
8 u1 b$ j: {7 F7 }! \Exposure to Testosterone2 L9 K& A+ c6 K) Z1 a
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
& j( {" b; P# d& ~. Y [and Kenneth R. Rettig, MD1# u I- h9 D* Y) B |
Clinical Pediatrics& T, N/ C% a( ^+ e8 o0 o
Volume 46 Number 6
5 g$ `3 B7 S7 p/ B5 ?% P P- d& r! @July 2007 540-5438 h+ H; @5 u; E- L) i+ T5 _6 Y! S
© 2007 Sage Publications( _ K7 x1 ]9 k, _3 H2 {( D
10.1177/00099228062966518 |+ K9 f5 S$ p. @1 X. H$ q5 D
http://clp.sagepub.com
, f- l6 K4 u/ w0 N: z$ hhosted at/ i1 x v' {* O c: @" L+ c
http://online.sagepub.com
- ?! r! S2 b, W* k, XPrecocious puberty in boys, central or peripheral,
# X4 f; [! j: T6 U& yis a significant concern for physicians. Central
. N/ c( ^) q6 fprecocious puberty (CPP), which is mediated1 k/ y- L5 e2 p' [& S4 `
through the hypothalamic pituitary gonadal axis, has
( k/ u+ t1 s2 p# P4 Ua higher incidence of organic central nervous system
h1 F4 v& [4 z3 ]5 L& Mlesions in boys.1,2 Virilization in boys, as manifested( z) m- c* l3 O& w) `) e9 a
by enlargement of the penis, development of pubic
1 _! I9 ~: j# W2 K+ H. khair, and facial acne without enlargement of testi-
( @5 N. b- b+ }% U2 V: Q& acles, suggests peripheral or pseudopuberty.1-3 We2 J& P; v; ?+ w2 h* F% G6 l" r
report a 16-month-old boy who presented with the' [4 y* V0 }) |- h8 u5 M1 b
enlargement of the phallus and pubic hair develop-
, i8 l6 A' x- e1 y) Nment without testicular enlargement, which was due
7 _/ ?- F$ `, D) k6 Pto the unintentional exposure to androgen gel used by1 ^3 r' l: y1 L7 ~' g
the father. The family initially concealed this infor-
$ W0 p- h( Y8 smation, resulting in an extensive work-up for this
' P2 F+ k# o7 o0 d) Z6 gchild. Given the widespread and easy availability of
Z- L. [0 m% p( o& }testosterone gel and cream, we believe this is proba-
3 }' p7 i# `4 W& B: X* Jbly more common than the rare case report in the
: w9 P' E3 ?/ n$ Y, c, R8 [literature.4) C7 [' Z ]+ H, p" n/ F, m
Patient Report/ U. Z7 R8 d: B @% u
A 16-month-old white child was referred to the
8 D( j h: m& y! V9 Nendocrine clinic by his pediatrician with the concern
$ I% O0 k, u! y ^! C- t1 [( cof early sexual development. His mother noticed
+ d0 s, b: r0 p. w& N' S! S6 p8 v; Rlight colored pubic hair development when he was( I* z! p6 ]# k3 ~
From the 1Division of Pediatric Endocrinology, 2University of
1 G: z5 M) B8 W! Y N! hSouth Alabama Medical Center, Mobile, Alabama.* C& p; s# y3 {+ {: W8 W
Address correspondence to: Samar K. Bhowmick, MD, FACE,
2 S u8 r0 \$ a- s8 T! y( gProfessor of Pediatrics, University of South Alabama, College of
7 @1 V0 m, y; |( ]Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;# B5 Q* m: O! B7 r; g y( _
e-mail: [email protected].
; R/ G$ T3 O: c4 d3 Y. Vabout 6 to 7 months old, which progressively became
( {* o# \" `8 \darker. She was also concerned about the enlarge-
2 U7 a* [: L7 \" ^* u4 J3 G# T; Nment of his penis and frequent erections. The child
1 |0 ~% H' m3 d' u1 zwas the product of a full-term normal delivery, with
; F: [9 _5 n) ]" x, }8 P9 T! `a birth weight of 7 lb 14 oz, and birth length of
6 J- Z( p+ T7 ~* y20 inches. He was breast-fed throughout the first year
( j' x* n' m8 | Iof life and was still receiving breast milk along with) L! ^' W! T; X3 ^3 `6 _4 E
solid food. He had no hospitalizations or surgery,
( t# n6 c% h9 a1 K2 U: S6 o8 _and his psychosocial and psychomotor development
% P) L X2 K0 J6 e8 o3 Lwas age appropriate.6 ]; W$ q w$ h
The family history was remarkable for the father,7 o6 n* _* v( ?$ f; G- N, R
who was diagnosed with hypothyroidism at age 16,% h8 |! V% g I4 `2 z* c# I; J
which was treated with thyroxine. The father’s
9 w$ o" A; g( M9 ~" Pheight was 6 feet, and he went through a somewhat7 Y3 k$ c/ C6 [7 p5 o) v1 x8 \/ i' g
early puberty and had stopped growing by age 14." t$ u1 `+ Y+ `2 x$ E# D
The father denied taking any other medication. The
5 [5 E/ Y/ F J' E% t7 ochild’s mother was in good health. Her menarche
1 j# _) w( ? hwas at 11 years of age, and her height was at 5 feet
. c) Y+ [) b0 x+ C0 _* H' S6 q. O5 inches. There was no other family history of pre-8 p% E2 O7 {! l0 G4 [
cocious sexual development in the first-degree rela-
# {9 ]" U8 a* |+ htives. There were no siblings.
j7 G- ~7 p D1 ]( bPhysical Examination8 Z5 Y% _* l# M- m7 }* ^* l
The physical examination revealed a very active,5 m+ Z( M# f( h. [) s. M) u5 N
playful, and healthy boy. The vital signs documented
/ t% Q& F. S2 v" ~% j; Ua blood pressure of 85/50 mm Hg, his length was$ a8 F ~" C/ }& ?/ M3 ` o
90 cm (>97th percentile), and his weight was 14.4 kg- s7 b$ }3 m& U# F/ E, d- m" W
(also >97th percentile). The observed yearly growth! E/ c9 { L# Y) j
velocity was 30 cm (12 inches). The examination of' L& w4 j$ B* w3 ?6 V; [
the neck revealed no thyroid enlargement.
8 W- Q7 y" Y, lThe genitourinary examination was remarkable for/ S* Y3 |9 S2 \ R( @5 Z2 |) b6 i1 s
enlargement of the penis, with a stretched length of& V# Z; M& _. Y2 T
8 cm and a width of 2 cm. The glans penis was very well
. z5 R+ c# S$ C8 I* T4 q ?! ]developed. The pubic hair was Tanner II, mostly around
" N4 }' i! W+ ~* ^540
3 K$ l7 |6 Y& {/ `4 f" Uat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
2 }. r- ^# ~$ p! w1 K1 Cthe base of the phallus and was dark and curled. The
, |' Y9 Q0 v8 J$ btesticular volume was prepubertal at 2 mL each.. g( C# r- o: M+ @. D% n6 \/ j6 w
The skin was moist and smooth and somewhat0 ?* |3 C5 F: }4 Y" _
oily. No axillary hair was noted. There were no3 y9 |7 m6 f0 Z" V6 d, t( r8 ]) j
abnormal skin pigmentations or café-au-lait spots.
3 n+ ^ N! i/ |5 Y, d$ O* W# u" B% oNeurologic evaluation showed deep tendon reflex 2+
/ w0 `! r8 l3 b2 sbilateral and symmetrical. There was no suggestion
( z5 \8 c# S& S# m) Z ?1 p1 Xof papilledema.
2 K- b q6 \9 D& i [6 v3 TLaboratory Evaluation1 m; K' e# f& X# M6 p6 v# d
The bone age was consistent with 28 months by
3 O h6 v @6 Z, Q7 _using the standard of Greulich and Pyle at a chrono-* d( b: Z+ H* T2 H' f7 o
logic age of 16 months (advanced).5 Chromosomal% E7 h0 A2 }+ _& i( j n" m
karyotype was 46XY. The thyroid function test6 a& j/ h) _& m2 k! H9 @
showed a free T4 of 1.69 ng/dL, and thyroid stimu-$ x3 O9 f4 U4 d! K; E; M' a
lating hormone level was 1.3 µIU/mL (both normal).) u3 _+ V* ]6 u8 }
The concentrations of serum electrolytes, blood
! g# O1 U5 |& K+ R1 U- S' d$ \' gurea nitrogen, creatinine, and calcium all were
7 h8 n( M$ R" \2 K5 ~6 Awithin normal range for his age. The concentration
0 I6 O& s( y: ~, Oof serum 17-hydroxyprogesterone was 16 ng/dL
- |' e2 Z* i" H. M5 U+ R z% ^5 J(normal, 3 to 90 ng/dL), androstenedione was 20- f2 c+ e9 J$ m+ J0 ?; m
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
; ]" @5 ?9 {+ ^5 I- Z( w/ x+ `, Y9 `terone was 38 ng/dL (normal, 50 to 760 ng/dL),
/ d% @) `- K% g; y( W* s. ydesoxycorticosterone was 4.3 ng/dL (normal, 7 to
" n, g8 O' {- s1 b$ a5 F' q49ng/dL), 11-desoxycortisol (specific compound S)& ^; A' [! t6 t8 N. p- M. p" r- ]
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-3 @) N8 \5 A+ i
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
) v/ Y4 S, Q5 u% P( Ntestosterone was 60 ng/dL (normal <3 to 10 ng/dL),% T9 s4 `. ]6 _
and β-human chorionic gonadotropin was less than$ r2 J" o6 p1 `8 x% Z! C, H' c
5 mIU/mL (normal <5 mIU/mL). Serum follicular. A u' Q) Q" _* J! c8 F
stimulating hormone and leuteinizing hormone* a: X9 K% X9 e9 P, ?2 A: m/ h
concentrations were less than 0.05 mIU/mL! V6 Q9 |. R: R: H% A
(prepubertal).
' Z9 C( z& U, I; Y* h" rThe parents were notified about the laboratory
, {2 E4 L3 _6 {5 K9 C6 Jresults and were informed that all of the tests were; @6 c- b5 F% ]) ?$ [/ S
normal except the testosterone level was high. The% T+ t; C6 |3 D' n3 v* j
follow-up visit was arranged within a few weeks to3 j) J9 ~6 d& \! F
obtain testicular and abdominal sonograms; how-8 _2 G' d! v7 e- p9 a) T
ever, the family did not return for 4 months. f3 K. P, e! ?
Physical examination at this time revealed that the
0 x- h4 u$ \6 M1 z; i% l5 G# C1 Nchild had grown 2.5 cm in 4 months and had gained0 q5 u) k0 K- T7 t3 t
2 kg of weight. Physical examination remained* e. _, k: ], U" z
unchanged. Surprisingly, the pubic hair almost com-& u# _$ F7 z6 H; Q$ T! T
pletely disappeared except for a few vellous hairs at
: n3 M, A8 G: |6 Y# q$ x, l* V2 j H5 [the base of the phallus. Testicular volume was still 2% m2 o( ^( K; W- r
mL, and the size of the penis remained unchanged.
5 Y8 G; p( M0 u" o$ G1 pThe mother also said that the boy was no longer hav-
' }8 `9 o) V4 x) qing frequent erections.+ ^) H- y# c7 z' L* E7 }. P
Both parents were again questioned about use of) B. b, M" @* g' m* K
any ointment/creams that they may have applied to8 u# O% k5 z! A( n
the child’s skin. This time the father admitted the
1 A! _$ V* X4 K# R TTopical Testosterone Exposure / Bhowmick et al 541
7 `; L: {2 P* v* q5 Y2 a/ x8 Kuse of testosterone gel twice daily that he was apply-- P1 d3 Y* m) Z& `
ing over his own shoulders, chest, and back area for* |/ ` [" J* P& t( a% Y- A5 i
a year. The father also revealed he was embarrassed
( d: e9 f5 |- |; v& y+ Oto disclose that he was using a testosterone gel pre-1 A$ E$ k/ S! i3 \# l
scribed by his family physician for decreased libido2 X: {, ^, s0 n1 S
secondary to depression.0 G& Q7 v; w. _, @; i* G9 E1 n
The child slept in the same bed with parents.
7 j, h2 |4 ~+ v7 CThe father would hug the baby and hold him on his# ]7 C8 M5 a" o) y+ H2 Y" I
chest for a considerable period of time, causing sig-
y' V, I" A( d! e' C# i! Knificant bare skin contact between baby and father.
6 N, s: r V7 z( J5 ]The father also admitted that after the phone call,/ J8 ~5 p% l5 T9 U4 m' s9 e
when he learned the testosterone level in the baby$ y5 i! n% Z; S) `. B6 A
was high, he then read the product information
5 I. J( W9 }3 a U& G* b# X+ y3 Cpacket and concluded that it was most likely the rea-7 b& L5 Q6 c( h f: c% @
son for the child’s virilization. At that time, they
' }" n; z$ J% [' F3 Wdecided to put the baby in a separate bed, and the: f1 h0 ] p5 Q8 Q' C7 d
father was not hugging him with bare skin and had
1 I5 g3 s, \" t- L |" f% d9 Obeen using protective clothing. A repeat testosterone) }$ W4 J% }: w& M) N
test was ordered, but the family did not go to the
' ~ J" F7 ?4 jlaboratory to obtain the test.
$ } n% [/ J% E$ n/ ~Discussion
N% ~) B. F; C$ M1 YPrecocious puberty in boys is defined as secondary5 K( K+ h n& \3 v m+ D9 ~
sexual development before 9 years of age.1,4
; Z/ }3 O: V9 ^3 Y: Y; n2 qPrecocious puberty is termed as central (true) when
' h, r9 Y1 L" Yit is caused by the premature activation of hypo-
' J# g& w" U9 Y, s" c% R2 o8 ]thalamic pituitary gonadal axis. CPP is more com-
$ p) R1 w" Z$ z: u; t/ c" ~) f% rmon in girls than in boys.1,3 Most boys with CPP, p) ~5 N9 o4 H; J3 l% d# |
may have a central nervous system lesion that is
- `1 K4 {) N7 K6 A; {% uresponsible for the early activation of the hypothal-
. ^, `% t- W: a9 Famic pituitary gonadal axis.1-3 Thus, greater empha-* x4 y5 r& h& J: s1 X" y
sis has been given to neuroradiologic imaging in9 f3 G1 @: w/ E2 v
boys with precocious puberty. In addition to viril-
S# U7 R: B1 N( Q2 ^/ y& aization, the clinical hallmark of CPP is the symmet-
1 p0 |% h- Q7 x: U9 Frical testicular growth secondary to stimulation by
3 n+ t* U% {$ a5 F/ }) K9 ?gonadotropins.1,3
. |. m# R; w3 w: rGonadotropin-independent peripheral preco-
4 {* n, `: j! c5 ~4 ccious puberty in boys also results from inappropriate% Q2 X, v' \3 P- c, M
androgenic stimulation from either endogenous or
2 P) N0 S: a1 ^6 m4 C* X- c! S1 dexogenous sources, nonpituitary gonadotropin stim-
. j! O+ H9 D$ |! ?ulation, and rare activating mutations.3 Virilizing
, B8 N, _ Q3 X3 R, ycongenital adrenal hyperplasia producing excessive
' y; Y, L- w. ?0 Z9 _! p, [adrenal androgens is a common cause of precocious
# O4 v' O3 P1 d$ u3 A# F+ @puberty in boys.3,4
4 O) i$ p2 j3 g- T% S: ^9 L9 ]The most common form of congenital adrenal
8 Q) ~" B7 b& fhyperplasia is the 21-hydroxylase enzyme deficiency.
* F, |6 t s+ J) HThe 11-β hydroxylase deficiency may also result in
6 L5 m7 x# N: W) @% }excessive adrenal androgen production, and rarely,+ y. B! K: u, i# x
an adrenal tumor may also cause adrenal androgen
& C9 y+ p4 Z6 i3 sexcess.1,3' }) W3 z) q# w" e
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from& B8 Z1 H8 \5 L
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007. z; e+ Z$ g, p$ b8 V; R
A unique entity of male-limited gonadotropin-( C9 ?9 [5 Q. G5 l% O
independent precocious puberty, which is also known8 L! u' v. O8 K9 @ V0 A# c6 r6 h
as testotoxicosis, may cause precocious puberty at a
4 f' v" c* }( ~ u8 Every young age. The physical findings in these boys5 { X- u" o% s
with this disorder are full pubertal development,, K. o, I: r" `' V5 i9 Y
including bilateral testicular growth, similar to boys
( d7 ~0 J: m3 [- x5 L% ]with CPP. The gonadotropin levels in this disorder
7 R/ n1 N7 n! B0 ]3 Rare suppressed to prepubertal levels and do not show
: c* \8 n2 N% }; _! y$ f0 w2 H( Cpubertal response of gonadotropin after gonadotropin-
+ D* Y2 m4 q; _& Creleasing hormone stimulation. This is a sex-linked
2 T* ] D6 f3 X0 v4 l* Bautosomal dominant disorder that affects only. E, I1 [. Q! y: T2 C" X
males; therefore, other male members of the family
. S+ ~5 V6 K" \& G- K6 o nmay have similar precocious puberty.34 @9 _8 p# R0 \' l& M
In our patient, physical examination was incon-( z. ?* P7 g" ~/ {! N$ r
sistent with true precocious puberty since his testi-" q2 m: ?' E1 Z4 a1 Y# ~
cles were prepubertal in size. However, testotoxicosis& i4 g7 G: ~) k9 _2 d6 U4 s! X2 B
was in the differential diagnosis because his father. w0 B. b8 |# V6 V, d7 U
started puberty somewhat early, and occasionally,% i, L1 V6 e- p- d6 Q) A! M! ?
testicular enlargement is not that evident in the/ n+ M! x% E! d+ B( i
beginning of this process.1 In the absence of a neg-$ O2 f( |6 P. ?8 Q/ l; m( [
ative initial history of androgen exposure, our
+ T" W x5 |! O0 g" ?# W" {/ tbiggest concern was virilizing adrenal hyperplasia,
4 B' @4 B2 D( n- }) reither 21-hydroxylase deficiency or 11-β hydroxylase
: P& _, @8 H9 m+ P* y3 u9 ~* _! ~! Ydeficiency. Those diagnoses were excluded by find-
7 N, J3 l+ e6 }) v8 H" r: u% p( _- Ling the normal level of adrenal steroids.& E3 E, V, N- K6 D. z
The diagnosis of exogenous androgens was strongly
, G5 S/ P5 C2 q' ?suspected in a follow-up visit after 4 months because
0 T. v. _* \/ r" _ K+ W* [the physical examination revealed the complete disap-8 j9 J1 F9 n, C7 m
pearance of pubic hair, normal growth velocity, and
1 A* W5 S1 ^0 ~3 g5 s G4 Cdecreased erections. The father admitted using a testos-% ~, w& W% \! r/ r
terone gel, which he concealed at first visit. He was. T4 U( n3 r3 \
using it rather frequently, twice a day. The Physicians’. J: @3 X' P! m( _0 U h! ^9 j
Desk Reference, or package insert of this product, gel or3 _4 a6 c6 x1 j% F
cream, cautions about dermal testosterone transfer to
4 j: N. R; {5 [2 B7 _8 `8 bunprotected females through direct skin exposure.2 v8 i g# {# ^
Serum testosterone level was found to be 2 times the% J' \6 s# T8 b
baseline value in those females who were exposed to- A9 W& L3 @2 b
even 15 minutes of direct skin contact with their male7 w1 ^' S; r6 j; |: J7 u9 s
partners.6 However, when a shirt covered the applica-
3 A, w, Q5 v q: P, |7 ktion site, this testosterone transfer was prevented.
% z2 l4 w" u- P K$ h0 WOur patient’s testosterone level was 60 ng/mL,
5 V6 Q: r; \, z" v8 c( ?which was clearly high. Some studies suggest that
# ~! W/ J- N5 E1 W# h/ Ndermal conversion of testosterone to dihydrotestos-
& m8 |; U% H/ c2 H5 W7 a3 u5 jterone, which is a more potent metabolite, is more- K: w$ _- Z! ~2 V
active in young children exposed to testosterone
, D. J3 Z# S& p1 \3 |! Cexogenously7; however, we did not measure a dihy-" x6 x1 n7 Q2 l: r! a2 p
drotestosterone level in our patient. In addition to
% Z9 ]; S8 r q9 j( E1 mvirilization, exposure to exogenous testosterone in l5 T0 m0 y# Y% s) ]- O
children results in an increase in growth velocity and
% `- Y0 Z* l0 e8 i3 _, n; oadvanced bone age, as seen in our patient. t' I& m+ {0 j+ ^, O5 a
The long-term effect of androgen exposure during1 I0 M3 z, Q. u5 g( U8 t( d
early childhood on pubertal development and final
! Y6 n+ o/ u6 M6 \adult height are not fully known and always remain
- f# M }0 w* m7 Q8 q8 B5 Ya concern. Children treated with short-term testos-/ O! o( K% a/ L1 v. l
terone injection or topical androgen may exhibit some
) `" d J* {# L6 Zacceleration of the skeletal maturation; however, after
9 Q) a! W6 f2 ~! C, b; s2 |. ` D7 Bcessation of treatment, the rate of bone maturation2 X# w1 u4 `5 X, L
decelerates and gradually returns to normal.8,9 u+ y% N- l1 g
There are conflicting reports and controversy% Z) B3 {; P& W( H b
over the effect of early androgen exposure on adult! ]9 s# j: W$ E8 n% [3 z
penile length.10,11 Some reports suggest subnormal
0 j6 c9 y# E" N3 k- D9 n, M, Xadult penile length, apparently because of downreg-# C k9 [: z9 U
ulation of androgen receptor number.10,12 However,
7 f0 J' C! F: }( c7 eSutherland et al13 did not find a correlation between, A* y W) @) a9 Z6 O1 [1 [
childhood testosterone exposure and reduced adult. d$ @% u: v0 k: u+ U# l
penile length in clinical studies.
( V+ h' R* _$ R, fNonetheless, we do not believe our patient is* x. M/ o4 ]3 z1 M& `" `4 x
going to experience any of the untoward effects from* d- [/ v/ _' {+ x4 m5 M
testosterone exposure as mentioned earlier because
* y4 u2 |9 k% X2 ~) S! F- o$ R+ othe exposure was not for a prolonged period of time.& n8 d7 V2 ^; d$ P I4 t
Although the bone age was advanced at the time of) H) x6 [2 R( d: v& b6 a
diagnosis, the child had a normal growth velocity at
: }, ?% s8 G% Y; Ythe follow-up visit. It is hoped that his final adult2 R$ D; O0 z! @. D6 F
height will not be affected.
) w& W9 i/ U8 y+ TAlthough rarely reported, the widespread avail-
, Z6 r' r0 w2 G) d' Uability of androgen products in our society may
8 R% l& s4 Q( G/ |+ m1 V/ Z! hindeed cause more virilization in male or female$ V7 y: B" E- S. Q9 T2 p1 L; S: W
children than one would realize. Exposure to andro-0 L3 Y. j( Y7 x1 c3 }
gen products must be considered and specific ques-& L% I- X1 S! q
tioning about the use of a testosterone product or
" B, R1 M/ v; m! jgel should be asked of the family members during
9 g: T9 S3 @) H, dthe evaluation of any children who present with vir-
1 l, }2 H% r2 h+ c8 k8 z) Iilization or peripheral precocious puberty. The diag-5 \6 y+ W% M: P0 g" r
nosis can be established by just a few tests and by8 V, R' }0 L0 S
appropriate history. The inability to obtain such a1 a9 P' t+ z7 s
history, or failure to ask the specific questions, may
. N# N- i2 V0 f% L1 {result in extensive, unnecessary, and expensive. w0 `4 \; }3 |1 q5 H2 q8 T
investigation. The primary care physician should be
! X6 k& y' ?* Oaware of this fact, because most of these children Y0 V6 O" s |- r# ]
may initially present in their practice. The Physicians’$ t {7 L8 `9 J& ]+ P+ p
Desk Reference and package insert should also put a
& Q' e% S8 c3 t2 P ?+ E/ C8 dwarning about the virilizing effect on a male or4 W6 f/ |: ?* v$ @
female child who might come in contact with some-8 @. S* _: P8 }0 A, e
one using any of these products.
) y& X" F' o- B3 Y9 MReferences& {8 s0 y5 e. V3 S* r( W1 b7 S- \ V
1. Styne DM. The testes: disorder of sexual differentiation
, o& w4 z9 s c: S a5 D! Eand puberty in the male. In: Sperling MA, ed. Pediatric9 U4 }! k0 m7 v
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;3 t5 P2 k$ u4 p1 Q
2002: 565-628.
- m; v. a1 J6 v4 |& |- N" t6 T2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious" ^, E' I9 e( _6 z: L' I8 M
puberty in children with tumours of the suprasellar pineal |
|