- 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 03:27:02
|
顯示全部樓層
Sexual Precocity in a 16-Month-Old* W" V" S) {8 W
Boy Induced by Indirect Topical& l" R$ s# x0 A& a
Exposure to Testosterone7 @; Y0 V- `8 d+ H+ m8 w" G3 {
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2- u7 `( J2 ^' a. Q
and Kenneth R. Rettig, MD1
+ _8 Z2 _1 Y$ f1 I- L# vClinical Pediatrics
+ e4 H2 _$ {$ U, Z/ D9 LVolume 46 Number 6. J) _8 a9 q6 j/ x" F
July 2007 540-543
; D6 W* r+ d q- L b- v& n© 2007 Sage Publications
9 _5 F- | O+ z0 s10.1177/0009922806296651
1 ^6 E# v$ q" o6 a1 ]3 B1 lhttp://clp.sagepub.com, S3 p# z4 j6 A0 n5 ^
hosted at
/ f4 N+ P e1 c, r# i' B Uhttp://online.sagepub.com% F! \/ R+ O" h) X7 z
Precocious puberty in boys, central or peripheral,
# ~6 ]; f) ]5 v. V3 Yis a significant concern for physicians. Central
8 H$ E) a& f* Xprecocious puberty (CPP), which is mediated2 f4 s$ r, r. H* @4 R4 Q
through the hypothalamic pituitary gonadal axis, has
- S1 S1 ?- z$ da higher incidence of organic central nervous system1 Q# K7 P1 h: ?+ h* y
lesions in boys.1,2 Virilization in boys, as manifested7 K' E P1 V. D* K+ J& K
by enlargement of the penis, development of pubic: @9 S$ U' I6 B% E& ]
hair, and facial acne without enlargement of testi-9 p( l. j- { w3 h" q6 u& J
cles, suggests peripheral or pseudopuberty.1-3 We
4 c6 C5 B0 x) l" a) X$ Z6 Ureport a 16-month-old boy who presented with the
, ]2 m; C5 X, ], Eenlargement of the phallus and pubic hair develop-
, p5 v8 Q4 \9 @' n" [ment without testicular enlargement, which was due h6 Y% @/ S. q9 q/ A' i5 O1 w
to the unintentional exposure to androgen gel used by+ _% z* X/ b5 t! Q! B4 t8 ]* w
the father. The family initially concealed this infor-7 S- t3 ?% h/ m' p. I; n
mation, resulting in an extensive work-up for this
. n3 L, s' f' \; E( `child. Given the widespread and easy availability of* M. q# Q* Y5 q
testosterone gel and cream, we believe this is proba-
3 \4 Y! A5 B8 \bly more common than the rare case report in the7 A( {: j& B! q( `% D
literature.4
0 ~ c7 K! o+ ~5 _3 \4 {2 wPatient Report
/ q# r: M- ]' a0 e+ PA 16-month-old white child was referred to the
$ H; I9 M+ z( dendocrine clinic by his pediatrician with the concern2 f; L I! U, Q5 Y
of early sexual development. His mother noticed
% ?" ^" n/ B' ~. i+ t2 vlight colored pubic hair development when he was$ m: d3 i3 O/ |. Y$ {8 z/ ]
From the 1Division of Pediatric Endocrinology, 2University of8 V2 D% a4 {7 O
South Alabama Medical Center, Mobile, Alabama.
/ s3 b* ~- O8 T' K0 pAddress correspondence to: Samar K. Bhowmick, MD, FACE,
0 ]- K1 i1 s& Q; e% A$ g: P# x* aProfessor of Pediatrics, University of South Alabama, College of
+ W$ ]1 ?2 W3 d Z L# W7 k/ tMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;8 d; {0 D& [$ c
e-mail: [email protected].% j5 T& Y" H5 Y/ I- d& g
about 6 to 7 months old, which progressively became
9 j q( h) c- f6 k( Udarker. She was also concerned about the enlarge-6 E$ j2 q, K2 J/ z% i5 M: K
ment of his penis and frequent erections. The child7 C. Y: D$ T9 C5 L! ?: X2 E1 ?
was the product of a full-term normal delivery, with7 d g5 {; b% j6 f: l! N
a birth weight of 7 lb 14 oz, and birth length of' c; r5 } ^2 K& J: V' ?7 H% L7 l) I
20 inches. He was breast-fed throughout the first year( X5 A5 c2 Y; x# V: U* B5 R6 d
of life and was still receiving breast milk along with
U1 F" w9 T3 }; R; l! g. ssolid food. He had no hospitalizations or surgery,
4 h' @- ?3 x9 o' B6 band his psychosocial and psychomotor development
8 C8 `/ S3 \) R1 }( C& m. `6 b; Cwas age appropriate.
# \9 U3 u/ w6 ?+ k4 ?The family history was remarkable for the father,. J1 [) R) ~- L% P
who was diagnosed with hypothyroidism at age 16,# P4 l$ B* k1 X% U7 e8 [4 [
which was treated with thyroxine. The father’s
+ \$ ~1 G9 g/ S) L" d5 iheight was 6 feet, and he went through a somewhat
1 ~7 E2 t! s8 n& @* A& U/ Pearly puberty and had stopped growing by age 14.
8 P. i+ B8 k3 M* A: e. {The father denied taking any other medication. The8 w5 v7 D; m" m: K+ _/ M
child’s mother was in good health. Her menarche" g$ r+ {# p) q) c) c
was at 11 years of age, and her height was at 5 feet8 j; ^& w- m x( Z+ O9 D( _. F. M
5 inches. There was no other family history of pre-* g/ p$ m2 G1 E6 s- `* A
cocious sexual development in the first-degree rela-
7 _! K/ Y! ~, n* z0 {tives. There were no siblings.
. x5 ^' }+ H* I0 vPhysical Examination
8 Z& x4 d3 ?2 Z! O3 O) LThe physical examination revealed a very active,, m5 V' c7 v8 g2 h- l( R
playful, and healthy boy. The vital signs documented
9 _/ \) n. f/ Y/ Ia blood pressure of 85/50 mm Hg, his length was
5 I2 @# I' e' y90 cm (>97th percentile), and his weight was 14.4 kg- f, N6 b, P( g; m* u3 D
(also >97th percentile). The observed yearly growth$ S L# S9 l1 C8 }6 m/ T
velocity was 30 cm (12 inches). The examination of
5 ?" T3 Y1 x. m' s/ ythe neck revealed no thyroid enlargement.
. S: ~7 }1 m7 \* y+ g. DThe genitourinary examination was remarkable for" y+ L: z& t5 H: o3 J4 d! L4 W
enlargement of the penis, with a stretched length of# ?2 u) M$ ~' m* _9 v- y
8 cm and a width of 2 cm. The glans penis was very well
: B1 s2 `* ]" E& u+ Vdeveloped. The pubic hair was Tanner II, mostly around- n0 @- k4 [1 J" m$ J' K& Y6 P1 |: J
5409 l; R9 l/ Z- m( b5 d8 d% m" e
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
0 d- o5 g3 z: Y( i$ r3 d, @the base of the phallus and was dark and curled. The; V; Q3 ]6 q% R% g& @4 y+ l
testicular volume was prepubertal at 2 mL each.
; ]- r; s1 x* m0 s2 x" C* u7 O( O& g+ M0 QThe skin was moist and smooth and somewhat
5 R: W- p" u# `4 k1 Moily. No axillary hair was noted. There were no+ l( q3 ~& g) G6 g
abnormal skin pigmentations or café-au-lait spots.
' v8 G# f2 Q6 g: a3 L2 p7 kNeurologic evaluation showed deep tendon reflex 2+
% E9 |5 N0 F3 M" g4 ]8 o1 I4 F5 Gbilateral and symmetrical. There was no suggestion+ U$ q3 l# y$ w4 x
of papilledema.( Z4 }7 I' C X
Laboratory Evaluation0 S N! f9 C: x- {
The bone age was consistent with 28 months by" w3 h# d3 m. a2 Y% f1 x
using the standard of Greulich and Pyle at a chrono-7 ^% G+ X& }+ R; D+ c/ }
logic age of 16 months (advanced).5 Chromosomal4 j f3 R. G; E6 W4 N' a/ y& t' g& B
karyotype was 46XY. The thyroid function test; f: J" E. v; z2 K- E* L u
showed a free T4 of 1.69 ng/dL, and thyroid stimu-' O0 O' k( N6 X+ o9 f
lating hormone level was 1.3 µIU/mL (both normal).
* U/ q. G1 ?/ s$ M- PThe concentrations of serum electrolytes, blood& P9 c2 S" A- O- R) t7 M, O$ `& T- M
urea nitrogen, creatinine, and calcium all were
7 k3 f' S" A/ U, mwithin normal range for his age. The concentration& O5 [1 J3 E$ f+ D
of serum 17-hydroxyprogesterone was 16 ng/dL
- w2 t+ U0 s! l r5 x6 F(normal, 3 to 90 ng/dL), androstenedione was 20! u+ o# e" F' T5 n3 a% H! K8 \9 I8 j
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
$ T* H j$ E* h3 Xterone was 38 ng/dL (normal, 50 to 760 ng/dL),
2 [: K& {( p4 o7 u: X$ [desoxycorticosterone was 4.3 ng/dL (normal, 7 to' o$ H+ q% G/ c1 F8 f: v7 i- X. k* q
49ng/dL), 11-desoxycortisol (specific compound S)
/ D$ A% i1 o8 D dwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-: e" T7 e# t% g$ A6 t% d- I; L3 J W
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
1 R& G1 ?4 ?( U+ @3 j& E2 H3 Vtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),5 D6 \! y' g* ~7 C- d( x! r6 g
and β-human chorionic gonadotropin was less than! t4 s. J5 a- S. h% f1 G* a
5 mIU/mL (normal <5 mIU/mL). Serum follicular
) I) x: L% g, M" sstimulating hormone and leuteinizing hormone" b/ E( N+ r, {( {' H: Y% |
concentrations were less than 0.05 mIU/mL
3 e) \& k5 }4 r! D) w+ c" Z' c; o% L(prepubertal).6 n4 ~+ ?& {+ I
The parents were notified about the laboratory; w- c* {7 u1 t4 s0 G
results and were informed that all of the tests were% h8 X4 s6 K6 G+ E$ A J- a
normal except the testosterone level was high. The) O/ y% u2 a9 L6 F
follow-up visit was arranged within a few weeks to6 A* R; h, Y( M7 ]- k6 @
obtain testicular and abdominal sonograms; how-
, L& d- s1 `9 _( dever, the family did not return for 4 months., T, `4 N. C1 S% j- p
Physical examination at this time revealed that the o. \! C" ~2 [ x
child had grown 2.5 cm in 4 months and had gained2 Q0 {; K* E' ^) m& m
2 kg of weight. Physical examination remained
# f' N* V' U" x- a' }. w! Nunchanged. Surprisingly, the pubic hair almost com-
6 ]5 A% h# |6 T1 u) M! opletely disappeared except for a few vellous hairs at
[6 L3 l+ B$ e7 z: k/ \the base of the phallus. Testicular volume was still 2
{* d: {. Z6 k! B2 n8 c' {mL, and the size of the penis remained unchanged.( E1 ]; G8 D" @9 I' t
The mother also said that the boy was no longer hav-
9 F% y# w4 ~* D z8 Aing frequent erections.* D; c: H* n, L0 c: F: K" [
Both parents were again questioned about use of! E F. v. d# }; {9 C2 ?
any ointment/creams that they may have applied to# n' O1 @& }. l$ s, m
the child’s skin. This time the father admitted the
" ?- C" j5 \8 o' \9 |Topical Testosterone Exposure / Bhowmick et al 541
; x2 W6 G1 B# r2 k) \use of testosterone gel twice daily that he was apply-
4 J. \" V) V" z1 m/ ding over his own shoulders, chest, and back area for* a6 u; y8 } s& k0 a" M- m
a year. The father also revealed he was embarrassed
^. R+ z1 [# Y# q" fto disclose that he was using a testosterone gel pre-
* T% `* Q! c+ C j4 T: ]scribed by his family physician for decreased libido
! X5 q2 s( t* ?8 P- \secondary to depression.
- S$ m( H( S, v0 u0 p5 P- W5 {; _: O6 nThe child slept in the same bed with parents. b1 Q, D; L% R' O& C0 h- d
The father would hug the baby and hold him on his
. n+ V9 z4 b j+ a" pchest for a considerable period of time, causing sig-4 V. H% b1 _) w' x, L K4 Q
nificant bare skin contact between baby and father.
. p1 k% }' s3 v' q( M! G: G$ _The father also admitted that after the phone call,' `" q ?8 p7 }
when he learned the testosterone level in the baby
& q% ^0 ]8 s5 P* m( bwas high, he then read the product information- J5 j/ A. t7 m/ k$ P
packet and concluded that it was most likely the rea-' v" v9 a9 |3 T( R( E
son for the child’s virilization. At that time, they! x" w, g$ \: h7 _( ]
decided to put the baby in a separate bed, and the) K4 D0 a( t3 l
father was not hugging him with bare skin and had' m# h4 e, z$ Q J/ i5 y8 g
been using protective clothing. A repeat testosterone" A- `* Y7 D: M0 U& D- k# ^
test was ordered, but the family did not go to the
0 n* L5 F7 l5 ]$ H) xlaboratory to obtain the test.
# `3 k% O& f+ X* vDiscussion- A! x1 V' L0 t
Precocious puberty in boys is defined as secondary
9 p$ L- G$ d* N+ z% P+ A& t- P! wsexual development before 9 years of age.1,4: _5 m) S: r- R. d' K, ^" k
Precocious puberty is termed as central (true) when' I C3 S( q0 W& U6 k
it is caused by the premature activation of hypo-1 h6 a" u0 P* L) P, i# N2 |- L; Q
thalamic pituitary gonadal axis. CPP is more com-8 L5 c( T8 u) T4 p
mon in girls than in boys.1,3 Most boys with CPP
5 w- _ c, b0 Y* Bmay have a central nervous system lesion that is
6 X: s$ F5 V3 s( T4 z2 r: o) Xresponsible for the early activation of the hypothal-" B4 Y. `4 F/ |7 ` d0 l( |
amic pituitary gonadal axis.1-3 Thus, greater empha-+ m) T, B7 H0 M6 H0 N1 Y: ~
sis has been given to neuroradiologic imaging in
, G6 q* S. q, b2 a) x+ Dboys with precocious puberty. In addition to viril-/ G) V" N6 V" I9 I% a" Y$ q
ization, the clinical hallmark of CPP is the symmet-
* Y4 H0 X0 _' n! i6 M; \' @+ Trical testicular growth secondary to stimulation by
; _1 |3 g) M; {9 U8 fgonadotropins.1,3
7 [' e0 `" w( j$ ?( hGonadotropin-independent peripheral preco-
- ]+ b9 }% B/ r4 F* l ccious puberty in boys also results from inappropriate& x) L, Z$ G) l' z7 P1 t
androgenic stimulation from either endogenous or, J3 B# J% e. |7 t$ j
exogenous sources, nonpituitary gonadotropin stim-0 m" c5 o! T8 L, V1 I/ X
ulation, and rare activating mutations.3 Virilizing
: J) a( w/ m+ A: [- ncongenital adrenal hyperplasia producing excessive
4 _5 K! e# Y% p4 g U. d* Aadrenal androgens is a common cause of precocious
1 H- E O) p) x( A- [' X" tpuberty in boys.3,4' _! B& R! L! N1 b
The most common form of congenital adrenal
0 ~+ B' h6 }( D, P0 ~hyperplasia is the 21-hydroxylase enzyme deficiency.
3 u( E1 k8 u8 @( {6 D3 nThe 11-β hydroxylase deficiency may also result in
: @) K( ` J5 d6 D3 ^- `excessive adrenal androgen production, and rarely,# ?, }$ _) m( g: n$ ^. z
an adrenal tumor may also cause adrenal androgen' s- \" K' k( k7 m6 b6 O5 t
excess.1,31 u% O+ G" Q* o- G
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
l3 c- f+ i k4 X# a542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
( M* @: J$ S4 p% P. EA unique entity of male-limited gonadotropin-& Z U, H ~, z1 K2 M2 x
independent precocious puberty, which is also known
' ] [* |! h; c J/ Zas testotoxicosis, may cause precocious puberty at a
7 \( {% `4 R7 s. L- x* d0 fvery young age. The physical findings in these boys
3 r6 v: v* S. D+ v! c6 L, ^2 R7 swith this disorder are full pubertal development,; H! z: ^. U7 Z1 y! f0 L
including bilateral testicular growth, similar to boys
2 S7 a! }; B& @9 Ywith CPP. The gonadotropin levels in this disorder3 Q9 D9 h0 _; p- g* D1 b
are suppressed to prepubertal levels and do not show6 ?0 z4 V d* C% ?1 C+ m: r
pubertal response of gonadotropin after gonadotropin-) `$ V; n! T1 [$ E
releasing hormone stimulation. This is a sex-linked
+ ]# V5 t8 c' w5 Zautosomal dominant disorder that affects only6 n. Q( f4 C) x% P
males; therefore, other male members of the family) f4 w3 V. b7 ^2 O1 z( L% w
may have similar precocious puberty.3
) s# e9 M( [ _: F. rIn our patient, physical examination was incon-
0 V% n. G: i' L# d3 e9 ^. ysistent with true precocious puberty since his testi-
3 t, a1 b0 D* c8 ]cles were prepubertal in size. However, testotoxicosis n2 O, L l) y0 B" F
was in the differential diagnosis because his father- @: {$ t" q( [* C
started puberty somewhat early, and occasionally,
8 M7 L0 K, O- s" Z0 |+ stesticular enlargement is not that evident in the
" C' w. l7 f1 z9 R; G) B; f! t- [' Lbeginning of this process.1 In the absence of a neg-2 w: J7 M+ h. j2 ~' H. F' V
ative initial history of androgen exposure, our
) G% d8 H: l$ [5 Z9 A: abiggest concern was virilizing adrenal hyperplasia,2 m' E7 y4 e) a1 t y
either 21-hydroxylase deficiency or 11-β hydroxylase
7 ?( V+ v3 U# S. Vdeficiency. Those diagnoses were excluded by find-
2 L% o0 \7 Y5 U2 ]2 m6 D" Ning the normal level of adrenal steroids.3 B" M7 o+ W( K& b# q. @
The diagnosis of exogenous androgens was strongly
6 A- B' E) [- Osuspected in a follow-up visit after 4 months because
S$ j7 \& R6 Ithe physical examination revealed the complete disap-
# K2 f. w1 T& Wpearance of pubic hair, normal growth velocity, and$ @% n2 ~" |1 ~2 g2 _
decreased erections. The father admitted using a testos-
& s. y# _, Q$ nterone gel, which he concealed at first visit. He was
( b. A& s3 T" H3 {; i. Y- y# Gusing it rather frequently, twice a day. The Physicians’, S1 n1 J* C! ~$ \' k/ R1 v" O, Y
Desk Reference, or package insert of this product, gel or
\2 G4 z! Q2 Y/ X, m+ ccream, cautions about dermal testosterone transfer to
9 r) B, v2 z7 G: Q4 |1 B6 X" |% Wunprotected females through direct skin exposure.
: \, @( f, Z8 X: cSerum testosterone level was found to be 2 times the2 N6 a* _& d' J* C: R
baseline value in those females who were exposed to) U4 P8 k( r+ r l7 _- U, l
even 15 minutes of direct skin contact with their male; Q5 G9 m3 g: U3 @+ @
partners.6 However, when a shirt covered the applica-
/ ^: ?( {& d3 h* ^tion site, this testosterone transfer was prevented.
8 ?- ^2 v4 R1 `% E% iOur patient’s testosterone level was 60 ng/mL,- k3 r9 ?/ }- Y* v( p, `
which was clearly high. Some studies suggest that' ~; D4 `6 n5 t
dermal conversion of testosterone to dihydrotestos-
0 G( {4 j* p) s& V5 @; Yterone, which is a more potent metabolite, is more# _2 {0 a! d- p" S
active in young children exposed to testosterone7 x/ ~- Q& E/ d+ C$ h0 b
exogenously7; however, we did not measure a dihy-
$ {+ O7 k3 ]5 Cdrotestosterone level in our patient. In addition to' r- ~* Q1 {0 w7 o# D: H. |* I0 W% ?
virilization, exposure to exogenous testosterone in
) h! \: a. ~$ K) P' Bchildren results in an increase in growth velocity and
. ^4 K# `2 E% Y$ j5 K+ ]1 @4 A$ xadvanced bone age, as seen in our patient.& c" e& R. N9 a% g* ?
The long-term effect of androgen exposure during
+ _, v$ Q# `4 D* b5 Xearly childhood on pubertal development and final
+ Q& Y5 z4 g0 q0 A: @( O% A& Dadult height are not fully known and always remain
- T4 Q0 W9 L3 ~* b) {3 |a concern. Children treated with short-term testos-9 ]( V( M% O4 B
terone injection or topical androgen may exhibit some
& N. H8 l5 R( t3 R9 @. Xacceleration of the skeletal maturation; however, after" R3 n$ j2 R9 g. o- {" V, T
cessation of treatment, the rate of bone maturation
$ A0 ^$ B( ]7 fdecelerates and gradually returns to normal.8,91 b: J& [5 r, u6 Z: K" a
There are conflicting reports and controversy
# I7 Y% Q$ x) G# pover the effect of early androgen exposure on adult: `4 u2 ^ i# ^6 s9 h
penile length.10,11 Some reports suggest subnormal
6 M, Z2 C; \! sadult penile length, apparently because of downreg-
9 h. O5 F1 V5 k% P! c! mulation of androgen receptor number.10,12 However,
' \# V o/ ?) K& |Sutherland et al13 did not find a correlation between1 u& o; q1 {$ K$ |
childhood testosterone exposure and reduced adult
) I7 Y+ I; C7 v; C) q) m1 m* \ ipenile length in clinical studies.5 k% {, t' Q& M4 H4 i
Nonetheless, we do not believe our patient is7 ]! x" c; b' }$ p, `5 ^/ u
going to experience any of the untoward effects from0 A9 u! w% \* l9 j
testosterone exposure as mentioned earlier because* n) X9 s, ~, W$ M6 p0 {4 j7 V
the exposure was not for a prolonged period of time.; W' D" @) e8 q3 U6 C( H7 S0 `: r# {
Although the bone age was advanced at the time of
- D- M; T8 r- J; ^2 Mdiagnosis, the child had a normal growth velocity at
& A+ T- c- i3 ]) lthe follow-up visit. It is hoped that his final adult6 l( B+ h7 f7 D' h# W4 j& l
height will not be affected.
7 q! ^* ]3 d) G) {1 @/ @8 p, kAlthough rarely reported, the widespread avail-
4 [% o3 y3 {% S+ E9 V: y- Xability of androgen products in our society may! ^ U$ l6 u3 f( S
indeed cause more virilization in male or female5 b: K5 ^$ t6 v
children than one would realize. Exposure to andro-
8 _) H) F9 K% i4 o7 W1 q4 x' H4 ogen products must be considered and specific ques-$ s" y" R5 O! D& o9 g5 w
tioning about the use of a testosterone product or
' i2 e' z6 t: C5 ?- Vgel should be asked of the family members during
0 C% o5 Q0 v8 J, O- }9 Sthe evaluation of any children who present with vir-9 Q; R% n/ J8 ^+ S: _0 N
ilization or peripheral precocious puberty. The diag-/ s* f K/ x7 Q% W3 Q
nosis can be established by just a few tests and by- @( `3 ]2 [: Z# o2 A+ R
appropriate history. The inability to obtain such a+ j& e* I- r/ r1 f9 k) _- o- k
history, or failure to ask the specific questions, may
7 p) l4 D/ E, S3 R1 ], g) vresult in extensive, unnecessary, and expensive
& ~8 p* a2 s& Z% a9 finvestigation. The primary care physician should be5 O+ |( X! @) U; G' B& h- y$ t4 N9 k
aware of this fact, because most of these children
3 o! s) r3 \0 e9 C }4 @$ jmay initially present in their practice. The Physicians’
) }7 u- x Q5 p' J! uDesk Reference and package insert should also put a
+ W/ ]( ~1 l2 _8 Hwarning about the virilizing effect on a male or
7 l! j1 l2 ^* j+ X. a* n: r Ffemale child who might come in contact with some-
; \% ~6 a! @' s$ ione using any of these products.
% O5 b* [7 o0 m' e' @- z! gReferences3 y6 o8 S: V: }- N, a
1. Styne DM. The testes: disorder of sexual differentiation
3 v1 v/ L8 V) z- ^* Z6 U; xand puberty in the male. In: Sperling MA, ed. Pediatric2 d3 d. X. |( F ~" @2 J
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
6 W1 T+ I, ]( _' E2002: 565-628.
$ L: q- i. }6 X A2 _' N! t ?! R2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious& s; A/ v+ l0 ?6 |* b" q( b2 h
puberty in children with tumours of the suprasellar pineal |
|