- 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
$ ]) U% r+ j! ^( FBoy Induced by Indirect Topical* A# W5 \( Z0 g9 K3 {% R0 r
Exposure to Testosterone, W4 x" `, J Q+ I
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2! b4 C& s! u. ?6 d5 \/ X7 ?, Y7 n; p
and Kenneth R. Rettig, MD1
; Y( W: k. r C+ QClinical Pediatrics
. c3 v& j3 i- D% cVolume 46 Number 6
$ J( g0 w/ Y( [8 f6 q- kJuly 2007 540-543$ M7 Z3 i( n* R7 q
© 2007 Sage Publications
1 |# W% ^, L& ^; y r, l10.1177/0009922806296651$ q" L* u/ ?9 i( [
http://clp.sagepub.com
) j2 Q9 @" C$ w5 h Fhosted at
+ t9 `" p7 `3 `6 L+ Mhttp://online.sagepub.com) s. z) Q, d) |# `5 ]
Precocious puberty in boys, central or peripheral,
- o/ \. I, B, W$ W: o# i" cis a significant concern for physicians. Central& V8 B- Q% ^0 F' {# V5 D
precocious puberty (CPP), which is mediated
' c f; Z( p% X2 |through the hypothalamic pituitary gonadal axis, has! a9 w. G' f, p3 O& v+ _
a higher incidence of organic central nervous system X7 Q4 O7 {1 w) ^: l5 r8 P
lesions in boys.1,2 Virilization in boys, as manifested
( N T9 j* w$ n3 N# S, z1 I' ~by enlargement of the penis, development of pubic
/ _# n' r( a2 i1 F1 [ M, Fhair, and facial acne without enlargement of testi-
6 ], q( w0 ?6 G; T* dcles, suggests peripheral or pseudopuberty.1-3 We
# z) S- |( G5 C8 F; Freport a 16-month-old boy who presented with the8 L# g& m) I, d
enlargement of the phallus and pubic hair develop- K+ R1 K, Y q/ n
ment without testicular enlargement, which was due* a% b) r& _, p
to the unintentional exposure to androgen gel used by; t1 [ t! o z0 P
the father. The family initially concealed this infor-
2 P" n6 ^& X5 j: ?0 Gmation, resulting in an extensive work-up for this* ~* [. p$ x2 X0 [+ m4 ?
child. Given the widespread and easy availability of
! e6 C5 p" [/ d' U2 y# v8 ?3 `& Q) p9 mtestosterone gel and cream, we believe this is proba- S. W7 X7 X8 W4 F/ ~' ^
bly more common than the rare case report in the
" f8 A7 v' _: k6 g9 `: ^+ \. `/ B! C" lliterature.4: \2 M( J& J% D) u! V- T: l( Q
Patient Report) t0 {+ u( C3 F+ @
A 16-month-old white child was referred to the N# y+ Y! x: ~
endocrine clinic by his pediatrician with the concern6 ~( \( f6 i7 n- x
of early sexual development. His mother noticed- L, L$ l/ w% I7 Z6 t" ~
light colored pubic hair development when he was
5 w( Q' ^) T7 R$ WFrom the 1Division of Pediatric Endocrinology, 2University of
$ @# Q. Z& k Y+ E( Q& R1 A( kSouth Alabama Medical Center, Mobile, Alabama.- p; |3 T. ~/ Q$ R" D8 x% g0 v. U
Address correspondence to: Samar K. Bhowmick, MD, FACE,# ]- w% @9 Q* d0 z! V
Professor of Pediatrics, University of South Alabama, College of& g& Z5 U. R$ o0 q! ?$ T
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
+ |/ [& {, q+ G Pe-mail: [email protected].
; M$ G# C) r0 ]" v5 babout 6 to 7 months old, which progressively became
1 R# P/ o" W i$ Z! L, N9 Z; r1 P2 Tdarker. She was also concerned about the enlarge-
1 Z3 e- F( X: _* s- gment of his penis and frequent erections. The child
+ q7 y5 O4 K+ I' kwas the product of a full-term normal delivery, with' z4 a9 F4 N! V3 x U
a birth weight of 7 lb 14 oz, and birth length of- D; c. y$ s. z
20 inches. He was breast-fed throughout the first year }! Z5 ~8 L, \9 g$ g/ ~
of life and was still receiving breast milk along with
! a& W" X! U+ J+ z; Gsolid food. He had no hospitalizations or surgery,2 B+ Q- b2 R8 W2 W2 C) a$ C, a
and his psychosocial and psychomotor development! f6 ?0 F1 Y! l& z+ E4 c: f
was age appropriate.' Z P3 @) A: C' T/ S4 E
The family history was remarkable for the father,
4 R7 u4 S- N" L o0 k4 Cwho was diagnosed with hypothyroidism at age 16,! I% x3 H9 Z0 G: D
which was treated with thyroxine. The father’s
" ?" J9 g6 Z# M& K5 e, ?. hheight was 6 feet, and he went through a somewhat! ]9 v; n: ^ Z# a- x$ O, O$ F `; Z5 @ X
early puberty and had stopped growing by age 14." y! R4 R( W6 [ W3 {, ?; H
The father denied taking any other medication. The G4 @0 ]8 h7 J& U
child’s mother was in good health. Her menarche: z# B2 x3 e* q& p
was at 11 years of age, and her height was at 5 feet% W% X) L' z8 Z6 z4 L
5 inches. There was no other family history of pre-
. R6 f$ U }, @2 }cocious sexual development in the first-degree rela-
0 t [3 ]( D0 f/ O, }8 utives. There were no siblings.. R0 ?- s% |$ o9 w7 U4 o" @, N7 r
Physical Examination& V3 j! f$ N3 W" w
The physical examination revealed a very active,
% I) [- }/ }9 K0 U4 P8 eplayful, and healthy boy. The vital signs documented
. O& ~% ^; e8 G4 Z* ]7 J F( A9 }a blood pressure of 85/50 mm Hg, his length was
8 U% T$ i# `! ~3 ^' h$ |9 S% S- `: Z1 Q90 cm (>97th percentile), and his weight was 14.4 kg
( g2 l6 Z* u6 X6 k$ b3 l(also >97th percentile). The observed yearly growth- ]+ T# u& G, p- I# x3 M
velocity was 30 cm (12 inches). The examination of
6 ^7 S0 ]8 n; b J# ?# r+ o: \the neck revealed no thyroid enlargement.0 i8 P! ^' F$ q, s: W
The genitourinary examination was remarkable for1 Q& h% P0 |! Q/ A; t4 O3 ^: r
enlargement of the penis, with a stretched length of1 s+ ~1 M5 y; \4 Z; G- j9 K
8 cm and a width of 2 cm. The glans penis was very well. f6 E& I. j% i. o
developed. The pubic hair was Tanner II, mostly around
, j4 f0 B0 @$ w T A! B540
% K0 e1 b q2 |+ X( c$ u, G) {! hat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from9 n8 S3 l) o3 L2 L0 Y% M" s
the base of the phallus and was dark and curled. The
+ g4 w7 ~) C3 _# e# v+ htesticular volume was prepubertal at 2 mL each.1 x: {; P6 H9 J( D2 v
The skin was moist and smooth and somewhat
: I8 e% L9 x! w' k2 z0 A4 ooily. No axillary hair was noted. There were no
$ y, N6 n# q% p% _" Fabnormal skin pigmentations or café-au-lait spots.2 R7 p5 N" _' C: T8 N
Neurologic evaluation showed deep tendon reflex 2+
3 L2 x: N8 {0 _bilateral and symmetrical. There was no suggestion
# Y- L% |# [5 t E7 r: r) o, t8 Gof papilledema.. B$ b1 D& c7 n+ A. M7 B
Laboratory Evaluation- T8 H& l% B- y4 s. s- \- v
The bone age was consistent with 28 months by
n7 @4 {: M4 ^: B. zusing the standard of Greulich and Pyle at a chrono-+ W1 z0 l; S4 E
logic age of 16 months (advanced).5 Chromosomal
3 b4 n& U; Y" zkaryotype was 46XY. The thyroid function test9 N3 F3 o8 s5 ?8 ^" |, {6 c) ]
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
) p- R* M. D( w" w |lating hormone level was 1.3 µIU/mL (both normal)., s: W/ O3 {$ W* w
The concentrations of serum electrolytes, blood
6 I: F4 T: V% w8 H; Surea nitrogen, creatinine, and calcium all were
. s) Y# w2 l# n8 Q1 _& Q9 ?within normal range for his age. The concentration, _7 K) k$ t( [: G
of serum 17-hydroxyprogesterone was 16 ng/dL# T; N8 W- D" q" u/ u
(normal, 3 to 90 ng/dL), androstenedione was 206 O0 O/ k6 t+ i1 v8 f5 o
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
& t2 O" @( Y' @0 X9 Cterone was 38 ng/dL (normal, 50 to 760 ng/dL),2 D: a6 p+ C0 |! ?
desoxycorticosterone was 4.3 ng/dL (normal, 7 to* {3 g) Q E, I! Z$ g) N7 S' R0 h
49ng/dL), 11-desoxycortisol (specific compound S)2 u4 I b3 M- s" H1 v1 Z* `* }5 D
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
# R/ O- ?7 B4 P. _- }tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
4 g* {4 ?$ h4 itestosterone was 60 ng/dL (normal <3 to 10 ng/dL),' F/ `) I+ _( Q9 W7 J* ?3 ?
and β-human chorionic gonadotropin was less than
0 ?, y" Z4 V1 ?5 mIU/mL (normal <5 mIU/mL). Serum follicular3 h; m; E ~4 D
stimulating hormone and leuteinizing hormone
5 h7 N$ B$ g6 u6 ]. uconcentrations were less than 0.05 mIU/mL) c3 M8 y! O: v) z; I% y6 z7 Z
(prepubertal).
9 U3 g' v# Z$ Z pThe parents were notified about the laboratory5 d( m# @" [. v$ T c1 H! ~
results and were informed that all of the tests were$ E# S2 \5 K) `9 Q( [; M
normal except the testosterone level was high. The
! ]* m1 O/ a, A( pfollow-up visit was arranged within a few weeks to
0 E+ S- V8 ?2 _ I2 q8 Pobtain testicular and abdominal sonograms; how-
Q/ i' b4 K% o ?& R; y7 T4 Wever, the family did not return for 4 months.9 [, I7 h2 I2 p3 t& m$ D; a
Physical examination at this time revealed that the
! ]# q3 Y) W6 I* C- Vchild had grown 2.5 cm in 4 months and had gained
+ a- I" {6 J/ F* o K2 kg of weight. Physical examination remained
& m: b4 \9 u# n/ b0 r0 Ounchanged. Surprisingly, the pubic hair almost com-
- L5 @. P2 Z+ S1 s, E& fpletely disappeared except for a few vellous hairs at
5 @. [% J* I- Y3 }% d7 Uthe base of the phallus. Testicular volume was still 2) t: e, g! s# e/ m5 a5 a5 A% ?
mL, and the size of the penis remained unchanged.4 o- h1 C w1 q$ z' {: j# c- u
The mother also said that the boy was no longer hav-3 h1 i9 x' _4 z! }0 E# Q
ing frequent erections.* x* N# r; L2 ^' ]; z
Both parents were again questioned about use of
# Z" _# U5 A3 ^9 j, n( l0 @any ointment/creams that they may have applied to, D7 G) t# j5 Q2 L, s
the child’s skin. This time the father admitted the
* O$ W. {. Z( ?8 J: y7 M$ g2 X# a: W; ~Topical Testosterone Exposure / Bhowmick et al 541
% e8 P- w5 X' r7 W* p( b; E9 u, ~use of testosterone gel twice daily that he was apply-) t; p2 |: ~: L5 F2 o1 C
ing over his own shoulders, chest, and back area for4 F# O4 {' z+ \- @
a year. The father also revealed he was embarrassed2 U8 M6 N( p5 C" p7 N6 K
to disclose that he was using a testosterone gel pre-
$ ], r& x* a' @7 Y4 M8 xscribed by his family physician for decreased libido
$ H+ X5 o& h/ O% p( S! l! Isecondary to depression.
% N& z+ I& U7 V3 RThe child slept in the same bed with parents.
# } H/ }" O& g% N' d9 PThe father would hug the baby and hold him on his
' W( J* h7 z ~3 Kchest for a considerable period of time, causing sig-8 U* K5 d% y. y1 O
nificant bare skin contact between baby and father.
6 @. w. ~. V+ \4 @4 r( i" y- SThe father also admitted that after the phone call,/ }0 k' F6 [$ _" |1 d
when he learned the testosterone level in the baby
& P# k/ z( G. Jwas high, he then read the product information
" {+ W! Z7 N$ w0 G5 W& O( ?packet and concluded that it was most likely the rea-. o) ^5 Y; @/ a7 q. T. K
son for the child’s virilization. At that time, they5 B& I% T* ?- N2 G
decided to put the baby in a separate bed, and the2 @+ o/ c8 `2 p" Q Z/ a8 O
father was not hugging him with bare skin and had
; t8 \7 h0 a$ c) g- r6 Xbeen using protective clothing. A repeat testosterone
! B& ~% ]# l& A D9 D/ D/ y0 Htest was ordered, but the family did not go to the
" i- Y& Y8 {( v& y) e( a4 ylaboratory to obtain the test.
3 s$ q' Y" l; D4 v+ n( IDiscussion3 t, ^2 _0 |, I" v) I. ?
Precocious puberty in boys is defined as secondary& O; ^/ ?& T" @
sexual development before 9 years of age.1,4
- [$ p' G7 o$ S/ T. `; SPrecocious puberty is termed as central (true) when
. H; J. j9 i; q6 W9 b3 q+ N0 p" e( oit is caused by the premature activation of hypo-
; k! A/ `8 t4 ^! F" }thalamic pituitary gonadal axis. CPP is more com-
4 {- k& F7 E8 nmon in girls than in boys.1,3 Most boys with CPP
! d2 G3 Y6 r1 \: p$ |. n0 {may have a central nervous system lesion that is- }8 e, X) i7 ^, ]" u
responsible for the early activation of the hypothal-
2 h7 N9 P5 ^" K& R+ v. }( Gamic pituitary gonadal axis.1-3 Thus, greater empha-
9 Q4 i, Z' O$ r, c: L; gsis has been given to neuroradiologic imaging in! Q& ]& o$ H& T+ U4 T8 j8 H
boys with precocious puberty. In addition to viril-' f6 b0 P8 l8 K4 @7 f& S
ization, the clinical hallmark of CPP is the symmet-
1 F7 ]; z) W, ^) vrical testicular growth secondary to stimulation by7 l- N6 D3 j9 z/ f! u1 s
gonadotropins.1,3
3 t& y2 B- E8 \" w6 f7 |! l% A' W8 {Gonadotropin-independent peripheral preco-/ h6 z* Z: q4 F8 V9 ^7 E1 ^ f
cious puberty in boys also results from inappropriate
% q t- Y% {$ Y8 ^) G5 H. A8 candrogenic stimulation from either endogenous or3 |3 k! R, d8 g2 Q. R
exogenous sources, nonpituitary gonadotropin stim-
, U# {0 t5 h8 {& u* K; v: j$ b2 Mulation, and rare activating mutations.3 Virilizing
$ O8 _5 J3 g! Y1 @+ ~, G/ C: Dcongenital adrenal hyperplasia producing excessive
0 n& R! u/ n7 i; yadrenal androgens is a common cause of precocious
2 S2 \3 d( Z& Y0 m" Xpuberty in boys.3,4% X7 X9 E' n) y$ h; z* V
The most common form of congenital adrenal
7 B1 _# k ?9 A, e O5 {hyperplasia is the 21-hydroxylase enzyme deficiency.
5 K" Z; V( E3 h) z/ f# oThe 11-β hydroxylase deficiency may also result in
" U d/ t- v7 r5 uexcessive adrenal androgen production, and rarely,2 i& P% m) z8 V+ j
an adrenal tumor may also cause adrenal androgen2 h Z2 w1 J5 H' g
excess.1,3
! O& P+ B" c& ]- F' u+ U9 [at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from7 n0 p& I& Z; C6 |
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
$ Q5 G3 \ M# [* ?A unique entity of male-limited gonadotropin-
+ |/ K [/ [* ~4 T6 ~. n' Nindependent precocious puberty, which is also known
$ \4 d3 G9 T: Z8 ]9 fas testotoxicosis, may cause precocious puberty at a
- w* a* \ ], q0 K( R6 g7 jvery young age. The physical findings in these boys- b8 ~4 X7 b6 S( a
with this disorder are full pubertal development,/ N8 Z# I! J' O% G& K1 o' G
including bilateral testicular growth, similar to boys3 {! w s. D: B; J. p& ]" A5 U8 v% @
with CPP. The gonadotropin levels in this disorder
$ \9 [2 e: W/ a! P# l! Hare suppressed to prepubertal levels and do not show
4 l8 t1 p6 @9 O$ ]pubertal response of gonadotropin after gonadotropin-
' j1 E+ r a% _/ u* j" b& Greleasing hormone stimulation. This is a sex-linked( |: I" o: C7 ?7 I
autosomal dominant disorder that affects only
. L4 J% V3 W/ ~) n& H4 H. smales; therefore, other male members of the family E9 ?9 n% r/ |
may have similar precocious puberty.3# k6 g7 t4 L% v
In our patient, physical examination was incon-# H% G- ^% N3 }( `5 V5 R4 N' B
sistent with true precocious puberty since his testi-. y7 r L- p8 u9 S
cles were prepubertal in size. However, testotoxicosis0 X8 ~1 i4 t6 j2 T& s5 p
was in the differential diagnosis because his father$ G$ f+ i" H. K1 r; W. E
started puberty somewhat early, and occasionally,9 l$ `# C. Y% d& {
testicular enlargement is not that evident in the
, P) W! u9 f0 t2 nbeginning of this process.1 In the absence of a neg-
9 Q4 Q! o ^- F' K, J, `+ F! zative initial history of androgen exposure, our" f3 a T9 K* b; w9 W y6 G
biggest concern was virilizing adrenal hyperplasia,
, E9 Q5 k; Y6 h3 T( Seither 21-hydroxylase deficiency or 11-β hydroxylase$ e+ s% Q6 V2 z3 X0 }% h
deficiency. Those diagnoses were excluded by find-
% ^3 p1 {: U/ J! b/ Aing the normal level of adrenal steroids.. l' K5 O" u- v& F+ n* B- M( O
The diagnosis of exogenous androgens was strongly( F: a4 C/ p8 f5 \- z1 n; h5 K
suspected in a follow-up visit after 4 months because. P% j+ Y" C! A: Y2 i
the physical examination revealed the complete disap-+ u f! E+ z4 N; h: j/ H2 {9 J
pearance of pubic hair, normal growth velocity, and
) s0 B+ ~% ^, zdecreased erections. The father admitted using a testos-4 e O$ _0 P# y0 c5 M
terone gel, which he concealed at first visit. He was
7 g' j( `# {7 @ \7 b4 Kusing it rather frequently, twice a day. The Physicians’
( }4 s2 t: B( r/ iDesk Reference, or package insert of this product, gel or
7 t$ b s A5 Y+ M4 y8 L! Ocream, cautions about dermal testosterone transfer to: T5 W( _" O+ n; c: _5 P
unprotected females through direct skin exposure.- S* v' J! y. x( v3 F' x
Serum testosterone level was found to be 2 times the
9 M% T2 f# V+ H& ^baseline value in those females who were exposed to
. |7 @; l& o' K1 q% \even 15 minutes of direct skin contact with their male
) A) r' x* w/ [8 a: npartners.6 However, when a shirt covered the applica-
! D {5 f" R# @7 ^ otion site, this testosterone transfer was prevented.! [, C" K" F$ `% E( _
Our patient’s testosterone level was 60 ng/mL,/ G2 Z8 U( z. ~" J# U2 b3 c) c
which was clearly high. Some studies suggest that' W4 O6 K- {! W4 r( L" H
dermal conversion of testosterone to dihydrotestos- e& {3 j8 |+ T& y4 e B$ D
terone, which is a more potent metabolite, is more
m( O0 m) ^" `active in young children exposed to testosterone
5 i, u5 l+ ?) _( \3 Lexogenously7; however, we did not measure a dihy-+ L! O6 z2 c1 z8 d# Y! a, w
drotestosterone level in our patient. In addition to
/ Z: N, K" }* V: r( Uvirilization, exposure to exogenous testosterone in
& _( [7 L- r+ @7 @. I G+ Z P8 r) P4 tchildren results in an increase in growth velocity and
9 O/ q- {4 n" Hadvanced bone age, as seen in our patient.
5 T7 d8 b. J2 D: a: L! r* FThe long-term effect of androgen exposure during- d% @! q. ]8 S! L3 e" s
early childhood on pubertal development and final
% }4 Z2 v& F; J; @adult height are not fully known and always remain
+ Q: r% M7 F! s# ea concern. Children treated with short-term testos-: O' {- b1 t! n6 T( K# D/ ` O
terone injection or topical androgen may exhibit some
6 i+ D7 Q7 {$ w4 E! Bacceleration of the skeletal maturation; however, after5 o+ ~5 b6 Y- I* `
cessation of treatment, the rate of bone maturation
0 x0 }& M" a% v+ u* Q6 vdecelerates and gradually returns to normal.8,9, ]# \. \0 { N9 Y
There are conflicting reports and controversy
3 r# \" K- C0 |' h. W7 pover the effect of early androgen exposure on adult9 W) ]6 q2 q. k+ K& @+ a
penile length.10,11 Some reports suggest subnormal. X# T0 a5 S3 ~! D% D: u
adult penile length, apparently because of downreg-
& r* s p$ Z+ ]- Nulation of androgen receptor number.10,12 However,
% Z* c) G9 b3 f+ G- eSutherland et al13 did not find a correlation between( W8 t. J9 Q. p
childhood testosterone exposure and reduced adult8 x6 ?( Z. D7 h1 x! U0 Y% N
penile length in clinical studies.) a z- a) L; f+ x; V: o- j
Nonetheless, we do not believe our patient is
( m) s/ |" c: E; ]8 G9 Q- C; qgoing to experience any of the untoward effects from% ^. w6 m9 H& X! o$ P5 B' J" ]; q
testosterone exposure as mentioned earlier because
# z& A3 ]3 ?; ]. |2 {the exposure was not for a prolonged period of time.5 b+ R* z, }2 d. `
Although the bone age was advanced at the time of
' [/ h U* ], w: T/ J. K$ U. }diagnosis, the child had a normal growth velocity at) E- Q/ y' Q+ i# \
the follow-up visit. It is hoped that his final adult
7 M( s! |; v0 S& ?" \$ {! b# vheight will not be affected.) y1 J2 x, a, M @4 ]4 M
Although rarely reported, the widespread avail-
5 s% ~4 [; P* q- b- aability of androgen products in our society may
' C. W' _) S5 @4 x2 U9 ^indeed cause more virilization in male or female
/ d( I. x+ a# |' L4 B( }children than one would realize. Exposure to andro-! i9 ^- f7 @6 A& C5 |' [" d1 p! t1 H
gen products must be considered and specific ques-
9 R5 {3 o# u7 Ytioning about the use of a testosterone product or
- M& E1 u- R5 x+ |gel should be asked of the family members during3 U. Y. ~ `9 S7 ?! G& w+ }, b6 Q
the evaluation of any children who present with vir-
' ~& C7 X$ l0 D0 K: U; _& b6 ?ilization or peripheral precocious puberty. The diag-. H) D) G+ s. i% Z, w" O
nosis can be established by just a few tests and by4 c3 a5 I, O& }: D
appropriate history. The inability to obtain such a8 u& F3 H$ m6 u4 A& K/ r* k
history, or failure to ask the specific questions, may" b8 H/ R7 N: b
result in extensive, unnecessary, and expensive1 K) l( _! N: c0 ^. j& ]
investigation. The primary care physician should be% K5 A& |( q! H- k9 a3 U, G; Y/ b
aware of this fact, because most of these children8 O$ H0 I# K5 [# n0 d
may initially present in their practice. The Physicians’! ?! U# v6 e. Y" s* U! A& O
Desk Reference and package insert should also put a
9 Y. m( u% p: g, |1 p/ n* [warning about the virilizing effect on a male or
* M+ e3 y$ e. r; X: O% V+ ]9 rfemale child who might come in contact with some-' y- `! M2 Q4 e' k
one using any of these products.
N! A1 d- Y; x9 H L( Y0 H( _References2 ^* D; Z8 F2 C4 `
1. Styne DM. The testes: disorder of sexual differentiation
% z5 F5 c: h+ K% J1 ?: v& S9 Dand puberty in the male. In: Sperling MA, ed. Pediatric- x3 A* g+ q D u! ?" W
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
$ W$ N- f1 z- l: E0 L2002: 565-628.
+ }% J/ V/ f1 f _* } I/ s1 z2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
# \ K7 D6 R/ ?$ b5 o7 ipuberty in children with tumours of the suprasellar pineal |
|