- 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) f- h& S. M/ i& D2 B
Boy Induced by Indirect Topical% j5 T+ Q$ [) M
Exposure to Testosterone
, P6 r$ L3 X4 _) x& }3 CSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
4 }0 c' O, ~" p; u6 [; A- a8 E1 zand Kenneth R. Rettig, MD1/ O P& \0 P$ g3 Y( i9 U
Clinical Pediatrics
* G# v4 V k8 ?6 Q7 I3 M5 P9 {1 wVolume 46 Number 6/ ^" d! Q$ _, l( I
July 2007 540-543& Z; S8 @1 e; H0 C
© 2007 Sage Publications5 t" E+ F" \0 y" W" Y
10.1177/00099228062966512 s( V; y2 \& c4 l! `
http://clp.sagepub.com
# x/ z4 Z. D7 N% ^hosted at; @5 I; T& g3 w' q- s/ |
http://online.sagepub.com
1 d. l" s: Q% z" SPrecocious puberty in boys, central or peripheral,! d1 {& J' }/ \5 U( V# L
is a significant concern for physicians. Central7 T5 M6 z, s7 g4 n" u: m- D
precocious puberty (CPP), which is mediated4 K2 Y% p. y( p& X7 c. a" v
through the hypothalamic pituitary gonadal axis, has
9 _1 m8 G [7 q5 E! @a higher incidence of organic central nervous system# h9 n: n+ `* ^+ l0 B m
lesions in boys.1,2 Virilization in boys, as manifested! p$ c4 m5 g' x0 o
by enlargement of the penis, development of pubic2 H" \$ ?4 W* O9 U. Q8 w1 U/ _5 t0 T
hair, and facial acne without enlargement of testi-5 P7 H2 T* Y8 B+ H9 ?
cles, suggests peripheral or pseudopuberty.1-3 We
& c3 T/ W* z a, c2 W- V8 U" Vreport a 16-month-old boy who presented with the
) b N& k; Q8 D% k1 F4 \: T4 m: wenlargement of the phallus and pubic hair develop-
i8 j! n% _! @+ D- n- i& l1 }; N2 zment without testicular enlargement, which was due
) {; ^# x2 @; j9 X5 |0 B9 lto the unintentional exposure to androgen gel used by! r: }9 w. g+ \
the father. The family initially concealed this infor-
) _7 Q9 F! K% h9 o: q% K( wmation, resulting in an extensive work-up for this8 o9 t1 c9 ~4 M
child. Given the widespread and easy availability of
5 @' s" @* \' w3 o$ a9 rtestosterone gel and cream, we believe this is proba-5 a( F% g; S/ J
bly more common than the rare case report in the
+ w) H f# d( M: B% Yliterature.4* }4 S5 A6 k9 N* F9 m! w
Patient Report
' f& k8 u- Y. p* E% [A 16-month-old white child was referred to the( B1 D* f5 u5 m% \# V2 g) _
endocrine clinic by his pediatrician with the concern! m2 \; i. Q! X: [- j
of early sexual development. His mother noticed" c" J/ \! ]! W5 s# ^% G
light colored pubic hair development when he was$ K2 f' J4 t) z) Y: C. `
From the 1Division of Pediatric Endocrinology, 2University of" Z$ W# Y/ W9 ?/ {
South Alabama Medical Center, Mobile, Alabama.5 C! e8 A* o: S3 K. R3 C4 l; E
Address correspondence to: Samar K. Bhowmick, MD, FACE,) P- f I: p3 P% S8 P2 h0 L
Professor of Pediatrics, University of South Alabama, College of" r8 a0 {2 u( l; \$ d0 J
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;1 w6 A/ [/ \. x9 y4 Q, L% p
e-mail: [email protected].) w! z+ a2 Z7 p" Q# F
about 6 to 7 months old, which progressively became
2 P6 G- U1 ^- _, X7 v# ]5 bdarker. She was also concerned about the enlarge-
* k. S. e* |& }3 ^; @ ]ment of his penis and frequent erections. The child1 A3 t- H. E: h4 m; C
was the product of a full-term normal delivery, with& {8 _6 m( \: Q( {) h
a birth weight of 7 lb 14 oz, and birth length of' W' H1 y; o# J8 C5 D
20 inches. He was breast-fed throughout the first year5 J, h$ {0 `% T/ S: }, S" {; A
of life and was still receiving breast milk along with
7 ^0 \ ~1 f7 [4 ~# m8 Msolid food. He had no hospitalizations or surgery,
8 m" y/ q+ t7 L, o* k- Kand his psychosocial and psychomotor development
; O H+ t- _, R5 e) A/ u# lwas age appropriate.
& J6 ]3 z( M. _# g7 YThe family history was remarkable for the father,
4 ?, I7 R% P7 o0 F+ m4 ?who was diagnosed with hypothyroidism at age 16,
' c0 l( H" f z9 y- xwhich was treated with thyroxine. The father’s
& l( |7 F) O4 rheight was 6 feet, and he went through a somewhat
2 n! S( }* c; @& ?0 e9 dearly puberty and had stopped growing by age 14.( z5 h& ?& S# p7 y+ u7 X1 I8 ]
The father denied taking any other medication. The
C$ K& v$ n: Y8 mchild’s mother was in good health. Her menarche% m) n5 w [. Y# k$ Z/ K& ^; t3 n
was at 11 years of age, and her height was at 5 feet
. O. {# I8 `- ] d: }1 Y6 F5 inches. There was no other family history of pre-" t6 _; O7 i; e/ A" R
cocious sexual development in the first-degree rela-# G* A. f( G) K' r p: ], X
tives. There were no siblings.# P e* U- m' r, y I( `; p7 Y1 z
Physical Examination2 ?9 `3 V1 o- Z6 J
The physical examination revealed a very active,$ b# \5 P6 T) R3 B
playful, and healthy boy. The vital signs documented
; W% z1 ~- z, w% q) la blood pressure of 85/50 mm Hg, his length was; {) L& h5 ^! d7 P* ^8 z
90 cm (>97th percentile), and his weight was 14.4 kg! D2 S4 J y6 D1 O; F* l
(also >97th percentile). The observed yearly growth- B! I- ~# A2 e! E! Q3 Q( ^
velocity was 30 cm (12 inches). The examination of) F9 L; s" W6 c
the neck revealed no thyroid enlargement.
( f/ [7 |6 S w$ J7 q( ~, S# BThe genitourinary examination was remarkable for/ _. M+ P# F) a8 a, \! T
enlargement of the penis, with a stretched length of' n0 B' U2 a0 B: m
8 cm and a width of 2 cm. The glans penis was very well
$ @7 \3 w; d/ e9 e3 {, I! v- bdeveloped. The pubic hair was Tanner II, mostly around; t3 F7 O$ p2 ^4 |; k, b
540
" G- O% R2 w4 K" {6 t" zat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
, N0 _; }7 {+ D7 \5 l9 u1 u+ kthe base of the phallus and was dark and curled. The
+ O0 k2 |4 }! f6 Ytesticular volume was prepubertal at 2 mL each.
4 A. X5 U$ o; yThe skin was moist and smooth and somewhat& W0 X$ T& C$ Q- A9 `/ A9 Q% Y
oily. No axillary hair was noted. There were no" L( w$ H1 u i6 f. f: f
abnormal skin pigmentations or café-au-lait spots.* K( ` }0 J/ A8 g- \- B6 b% a. Y% I4 h( E
Neurologic evaluation showed deep tendon reflex 2+
" D$ A% ?7 ^; k5 N) }( |bilateral and symmetrical. There was no suggestion
. r% K0 N0 k; i6 p7 Fof papilledema.
0 z/ y4 O/ X4 I. _- V8 ELaboratory Evaluation' T, R4 `0 ]# j+ j7 |
The bone age was consistent with 28 months by/ k1 v0 K' |- k2 m+ R' D8 E# o
using the standard of Greulich and Pyle at a chrono-0 L- X3 @2 X" `+ a) A3 I6 @
logic age of 16 months (advanced).5 Chromosomal& r: J+ G; {& P1 w
karyotype was 46XY. The thyroid function test) r9 M( Q3 R4 ] }6 i# ~$ W; X
showed a free T4 of 1.69 ng/dL, and thyroid stimu-) ?1 m- w; F! D/ y3 M
lating hormone level was 1.3 µIU/mL (both normal).+ X/ b: h# p. X0 P
The concentrations of serum electrolytes, blood1 y& C8 G5 e3 l" e
urea nitrogen, creatinine, and calcium all were+ T* x3 F2 F# u. G! _5 k6 \: T
within normal range for his age. The concentration
. U: S7 P f; z( M3 g% Sof serum 17-hydroxyprogesterone was 16 ng/dL) r- k" x% {: x) T+ W9 @4 Y' S1 ~
(normal, 3 to 90 ng/dL), androstenedione was 20
+ p# ?- b, e5 a# F6 m, mng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-+ H5 ~( k/ m) o" S) [9 p, i
terone was 38 ng/dL (normal, 50 to 760 ng/dL),9 S' _2 u! j- J$ @
desoxycorticosterone was 4.3 ng/dL (normal, 7 to+ g4 ^! Y: j7 }! v5 R# c! v
49ng/dL), 11-desoxycortisol (specific compound S)/ D: h. F7 C/ s
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-+ T6 |) X) z9 x- p
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
* t" M! V% k1 v5 G1 H* Wtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
/ Y: |8 o9 q o! K9 j3 L8 ?and β-human chorionic gonadotropin was less than
1 z* H# ^+ R4 Y% L* |4 Y; E8 ? |5 mIU/mL (normal <5 mIU/mL). Serum follicular+ B% ~: D* _6 O
stimulating hormone and leuteinizing hormone+ o' G4 _) ~! O. k7 S' s7 u# R. g
concentrations were less than 0.05 mIU/mL2 T! c/ I1 A' k' G; }8 B9 a/ ^' Q E3 y) |
(prepubertal).
, y j* R7 h6 k1 {2 y( NThe parents were notified about the laboratory
( H; k. G' t4 F+ vresults and were informed that all of the tests were
9 z+ q& w) f, z5 H! C( c' E7 gnormal except the testosterone level was high. The4 G0 [3 B5 E7 _% A2 m
follow-up visit was arranged within a few weeks to
5 V4 n1 t2 P3 u4 Yobtain testicular and abdominal sonograms; how-
, m) `2 R g- [* M% Kever, the family did not return for 4 months.
7 Q/ h* c8 w& c% P& i* D/ iPhysical examination at this time revealed that the- R0 S& s9 {7 X7 H! E9 m
child had grown 2.5 cm in 4 months and had gained' ]9 [7 v, n* `+ o6 p1 z
2 kg of weight. Physical examination remained; ~& l% G; f$ u( ~- v. j
unchanged. Surprisingly, the pubic hair almost com-
7 A& _ t6 d9 E% D2 ipletely disappeared except for a few vellous hairs at1 D4 s2 a& H2 P
the base of the phallus. Testicular volume was still 2
; x# U6 U. S2 H0 B- @mL, and the size of the penis remained unchanged.' N+ r* s! `9 [9 U8 Z; l8 _1 p- A
The mother also said that the boy was no longer hav-
$ l3 A4 M# y) ying frequent erections.6 G' M4 I5 ^7 R
Both parents were again questioned about use of. M$ ?0 Q+ t7 `9 Y
any ointment/creams that they may have applied to% }$ t8 w" W8 f) F2 o) ^
the child’s skin. This time the father admitted the
5 W7 x% x9 g1 G a7 f+ _Topical Testosterone Exposure / Bhowmick et al 541
; p6 G6 X# V" Y8 Euse of testosterone gel twice daily that he was apply-5 v0 _/ R2 k4 w4 n% B
ing over his own shoulders, chest, and back area for
, D+ B, g: O2 ya year. The father also revealed he was embarrassed
; X0 E1 c) C9 b O/ ato disclose that he was using a testosterone gel pre-) F _6 X) i' }% {! M# I9 r
scribed by his family physician for decreased libido/ S' G" `1 Q+ \; ?. Q
secondary to depression.
0 U8 u& Q, s. \# X( V) Y: ^The child slept in the same bed with parents.; Y+ w% K" i: {! @) [
The father would hug the baby and hold him on his
7 W% X( m1 t% Xchest for a considerable period of time, causing sig-
- m8 s2 F; [0 F5 t2 ]8 d8 fnificant bare skin contact between baby and father.; J6 v1 t. H1 S' ]' v$ v9 l7 h
The father also admitted that after the phone call,
: I* m' }" U( b5 M* ]when he learned the testosterone level in the baby2 |& o x5 }8 R" m
was high, he then read the product information
8 O: R, k$ }! l. l8 [' t* T$ n; Y$ ?packet and concluded that it was most likely the rea-
2 u8 ~1 H3 a- E! mson for the child’s virilization. At that time, they
9 H) ?! I5 v' D. `( n0 [7 r+ Tdecided to put the baby in a separate bed, and the7 \5 ^! \; Y0 w
father was not hugging him with bare skin and had: E$ Q5 z7 W4 w& d8 y; O
been using protective clothing. A repeat testosterone$ H( `- X& v+ Z! l; {3 c2 g
test was ordered, but the family did not go to the
# M1 p! y1 `" h* d+ H+ L; Dlaboratory to obtain the test.
1 w1 q0 f! s2 {0 i* }/ k" y& E8 TDiscussion
5 N( d" @8 v& w: y9 _3 S7 d& H6 bPrecocious puberty in boys is defined as secondary
, g s% z2 D* Z- z+ J; Ksexual development before 9 years of age.1,4( q$ e! p( B% H+ f1 R, l/ C
Precocious puberty is termed as central (true) when7 o" e# d; ]0 ]; t
it is caused by the premature activation of hypo-2 h: y! j) n Z0 r
thalamic pituitary gonadal axis. CPP is more com-
' S. R8 m6 P! I* Z! }mon in girls than in boys.1,3 Most boys with CPP: Z2 }0 O. m1 E* h, w" ~% G
may have a central nervous system lesion that is% [. t7 D e2 Z. \
responsible for the early activation of the hypothal-- X- t1 K$ M k4 g$ f2 b9 ~# v
amic pituitary gonadal axis.1-3 Thus, greater empha-
, D0 {, I% {$ `" P' Nsis has been given to neuroradiologic imaging in
3 F; N5 B: S& pboys with precocious puberty. In addition to viril-3 ^$ U5 W9 U- q; M7 S# L
ization, the clinical hallmark of CPP is the symmet-# K, I, k9 h: `# a% c
rical testicular growth secondary to stimulation by
, Y; F! b( t4 A9 X/ X8 Z7 F: X& zgonadotropins.1,3& ^. o) H! M$ X% d* U, F& K% S
Gonadotropin-independent peripheral preco-
; d# ~4 _. r8 j" ncious puberty in boys also results from inappropriate
9 d' @5 o' g$ t# xandrogenic stimulation from either endogenous or1 b" c S6 h( z5 }( [1 g
exogenous sources, nonpituitary gonadotropin stim-
9 ^: n* j3 B' pulation, and rare activating mutations.3 Virilizing7 f( t5 J0 a# Q; N8 h5 N
congenital adrenal hyperplasia producing excessive
6 a$ X1 p( i/ l# sadrenal androgens is a common cause of precocious
/ I1 y C6 [' [; c1 ^ Xpuberty in boys.3,44 T, z' j3 @* b$ R" i; b
The most common form of congenital adrenal6 `8 K. O* u# ?' n! p
hyperplasia is the 21-hydroxylase enzyme deficiency.
1 ]0 M" s$ a! e* K! ZThe 11-β hydroxylase deficiency may also result in
9 s w& b+ p. [excessive adrenal androgen production, and rarely,
# E& s7 R' E, e, ]% Yan adrenal tumor may also cause adrenal androgen
8 R( U7 U8 R0 R& x) k' cexcess.1,3& D& j J" V) K& a8 f# Q
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
& x& S% h& d% w! ^$ R542 Clinical Pediatrics / Vol. 46, No. 6, July 2007- Y$ d! W, k @& `/ d
A unique entity of male-limited gonadotropin-: D5 ~3 ]0 \: N6 u- ~ X2 }
independent precocious puberty, which is also known0 u# ]8 t+ ~7 f9 r7 r7 I
as testotoxicosis, may cause precocious puberty at a; J# V& X& v( D- \! ~+ W
very young age. The physical findings in these boys7 E2 X F( n, c, ~: l2 _( `, _* d
with this disorder are full pubertal development,! N/ u) M( @% V# H
including bilateral testicular growth, similar to boys9 @4 _4 x" b1 v6 u
with CPP. The gonadotropin levels in this disorder
# R% R- t& D" h0 care suppressed to prepubertal levels and do not show2 o2 B* ~/ s' e# f3 |$ P( F+ P
pubertal response of gonadotropin after gonadotropin-
) W3 f5 d* W J) @/ `releasing hormone stimulation. This is a sex-linked' s3 B, b% F& k' O7 J8 n f
autosomal dominant disorder that affects only6 R0 \7 v- f; l e6 H' k) r
males; therefore, other male members of the family( a3 \& P2 p' ?. P9 X$ B4 O- w$ N
may have similar precocious puberty.3
% o. `5 ^5 h' z5 M9 kIn our patient, physical examination was incon-
4 y% y4 g% y8 ?4 W3 y& E& P: t1 G. ksistent with true precocious puberty since his testi-
# e* j; A: c% U/ C8 L1 zcles were prepubertal in size. However, testotoxicosis
$ K3 z) f3 L) S$ Twas in the differential diagnosis because his father8 A, k3 A, J2 Q& m- `7 k @
started puberty somewhat early, and occasionally,, X% I+ B3 q8 k ^; ^& I! K
testicular enlargement is not that evident in the9 A, W8 @; c: L" x" v8 @
beginning of this process.1 In the absence of a neg-
6 I2 I4 s7 F d8 [4 mative initial history of androgen exposure, our; P* d0 ^6 [6 }( k1 n# V% @, }0 z6 T
biggest concern was virilizing adrenal hyperplasia,
0 \. o- y4 e# ~/ M1 p1 L( x; ceither 21-hydroxylase deficiency or 11-β hydroxylase' i, O! C5 d+ F- { ?1 S1 ]
deficiency. Those diagnoses were excluded by find-! p# @0 Q1 b* P: y% }
ing the normal level of adrenal steroids.
8 h; W/ ]: W* z. Y2 H/ xThe diagnosis of exogenous androgens was strongly+ @/ U* e9 I3 s( t5 f5 e0 [' Z
suspected in a follow-up visit after 4 months because
# E" r' r3 W$ m& w8 J: ~- N6 Bthe physical examination revealed the complete disap-
3 t, N/ ~" V" k" ^+ N+ ^$ S+ c- Xpearance of pubic hair, normal growth velocity, and
- t' Z3 i* H, Z2 D8 N6 Ldecreased erections. The father admitted using a testos-
/ n2 H2 j0 v& F2 Kterone gel, which he concealed at first visit. He was
$ \8 \0 M9 m5 s- d; D! Rusing it rather frequently, twice a day. The Physicians’
1 H. }$ C3 l+ O' F& ]6 uDesk Reference, or package insert of this product, gel or9 i' I$ K) ^) T7 G7 o( V% ?; |# _
cream, cautions about dermal testosterone transfer to# A4 q0 U" a" ]% o" n& g3 b8 h
unprotected females through direct skin exposure.4 f9 H2 Z2 O$ t8 {8 Q% k- m1 _
Serum testosterone level was found to be 2 times the$ S$ v# |5 ` T: J: `. I( |: h
baseline value in those females who were exposed to
/ p) H, u& t" Seven 15 minutes of direct skin contact with their male
( c) L$ T& o& _5 D& N* v. I" Y8 G- Upartners.6 However, when a shirt covered the applica-' u: i" D! ?, `
tion site, this testosterone transfer was prevented./ ^4 Z. A) {* B, G
Our patient’s testosterone level was 60 ng/mL,1 Q, p( \1 a v5 g7 M) x3 s. k
which was clearly high. Some studies suggest that# C5 f2 G# o7 ~9 O5 Q: G5 ]
dermal conversion of testosterone to dihydrotestos-
; Z* v+ y" X- j2 `terone, which is a more potent metabolite, is more4 S6 Q/ Y. m6 q/ R
active in young children exposed to testosterone$ G# J1 f4 x) W0 z( Q' W$ ?" e+ k/ F
exogenously7; however, we did not measure a dihy-& Y( s- t1 R( X3 I
drotestosterone level in our patient. In addition to
+ v* {/ T9 A. n( n+ ^0 Lvirilization, exposure to exogenous testosterone in& G6 K; A' b3 u; ]- S
children results in an increase in growth velocity and
6 A5 I" X7 D% d( D( r4 L: ~% i% Eadvanced bone age, as seen in our patient.
% C0 D+ [) O, T DThe long-term effect of androgen exposure during
! o+ I/ o1 K3 M* w7 B& bearly childhood on pubertal development and final$ h8 e f6 |: H$ s
adult height are not fully known and always remain
* v+ `$ D- c# m& D7 A- j+ L& t6 Ma concern. Children treated with short-term testos-0 M5 ]% t. J ]6 w x y
terone injection or topical androgen may exhibit some+ ^/ \! K9 _3 |" w
acceleration of the skeletal maturation; however, after
3 o/ [- [2 ?: V% L4 Lcessation of treatment, the rate of bone maturation
; n. C2 t" L. o8 S! X- Z4 ^decelerates and gradually returns to normal.8,9: T" b+ L- q9 F' j1 \: u* z& \. J
There are conflicting reports and controversy1 x* c/ z C! C1 F
over the effect of early androgen exposure on adult
7 x$ \- v' Y! q0 [penile length.10,11 Some reports suggest subnormal
: ~% V1 x% W5 B3 {( a! q) ]adult penile length, apparently because of downreg-+ Q) c3 A( _% n; z! r
ulation of androgen receptor number.10,12 However,! W6 I# K0 V3 u4 _9 r# S
Sutherland et al13 did not find a correlation between
0 v/ ]" c) I+ e3 Bchildhood testosterone exposure and reduced adult" t" v0 e$ l, ]. M- }+ n# V4 |
penile length in clinical studies.
4 w/ S b. K8 H8 P5 r& gNonetheless, we do not believe our patient is, g- c; M3 C6 E. \7 Y* n6 h4 V$ i5 G
going to experience any of the untoward effects from. m5 c. ?! g! N6 |
testosterone exposure as mentioned earlier because
, A1 `/ M g' @. R! H$ \the exposure was not for a prolonged period of time. P' [% E/ B3 |7 w9 _
Although the bone age was advanced at the time of- o; Y2 M- f9 s8 x1 y h
diagnosis, the child had a normal growth velocity at0 P" m. L& j1 M9 V7 c
the follow-up visit. It is hoped that his final adult. k, R# N5 s& f Q/ I% r2 o
height will not be affected.
- C. ~ P8 v; _, x" d* MAlthough rarely reported, the widespread avail-
; O0 R5 t4 F* v/ n( fability of androgen products in our society may3 @+ K" z8 A9 h7 A
indeed cause more virilization in male or female
3 t. D! p0 W( B* Jchildren than one would realize. Exposure to andro-
@8 f5 Z# C( I0 j& T; p- T! tgen products must be considered and specific ques-
3 F$ s( F5 q( R3 F, S: I3 J5 wtioning about the use of a testosterone product or X; W2 y% ^: s
gel should be asked of the family members during
' y( w" W) B9 Wthe evaluation of any children who present with vir-
$ V) g# O& S+ pilization or peripheral precocious puberty. The diag-) c/ U2 t8 P: j! ~- B* X
nosis can be established by just a few tests and by
* z; @3 P: B; Y- Q! W8 rappropriate history. The inability to obtain such a r, D, G9 P& z: Q& |
history, or failure to ask the specific questions, may
6 B; } J' q! w [* n/ @2 Dresult in extensive, unnecessary, and expensive
9 B/ I6 M/ s+ ainvestigation. The primary care physician should be- Z4 W; o+ w, P" u" p
aware of this fact, because most of these children
( i2 n7 ?% x* R* A4 B+ ~may initially present in their practice. The Physicians’/ n, j& J( ]7 X6 r
Desk Reference and package insert should also put a; T1 R) F1 A# |! ~
warning about the virilizing effect on a male or( y; J8 X; `' e9 n
female child who might come in contact with some-* C0 _& S: t |7 _; ?
one using any of these products.
( O& m6 e: u, p8 x4 ~5 LReferences
$ q4 x1 Y M; m s1. Styne DM. The testes: disorder of sexual differentiation
| I% p; ^* I0 R$ S0 eand puberty in the male. In: Sperling MA, ed. Pediatric
2 d( j' E' k! ^( Z l1 vEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
* C6 B! |. ?0 @) E' @& ?4 h1 X2002: 565-628.
9 l4 B4 \ Q, M* C2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious# s7 k3 n) l8 D( S; r6 W
puberty in children with tumours of the suprasellar pineal |
|