- 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
+ j! k4 }) d: m0 C9 \4 u+ l9 \Boy Induced by Indirect Topical+ x3 `- t' Z! w
Exposure to Testosterone
' N, l6 x- ^" t; {! z" h' T% B7 q* WSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
4 k3 w5 @# |' s$ P( iand Kenneth R. Rettig, MD1. b: N# S" J5 A& K
Clinical Pediatrics" ^. b7 r3 ?' c: Y5 R+ H. Y1 O! X
Volume 46 Number 6* q: P0 q9 C+ F$ V& ^, {
July 2007 540-543
z# B# w- F3 f( V© 2007 Sage Publications8 E& ~, ~. S; m8 B
10.1177/0009922806296651
, g& S# y+ o' Q+ Chttp://clp.sagepub.com& Y9 f; B4 Q. ?+ ]! `, x# E1 `+ N+ t; z
hosted at4 `9 v& ~. @! u( x+ m9 d4 A* ?% ?/ N. a
http://online.sagepub.com/ a+ Z9 x7 J- F& O K& |# Z
Precocious puberty in boys, central or peripheral,
: z, [+ w P& w" _is a significant concern for physicians. Central# G9 k% k f, V8 g0 }
precocious puberty (CPP), which is mediated
6 i( {6 e/ k. j$ [5 i6 a+ w' Rthrough the hypothalamic pituitary gonadal axis, has
1 k/ v% q8 t( x# f* Sa higher incidence of organic central nervous system+ n- \. d, h/ S4 U+ a* U
lesions in boys.1,2 Virilization in boys, as manifested
. ~$ s5 a% A4 s; ?$ Yby enlargement of the penis, development of pubic. Y J- `6 z# S7 `/ D: o4 b
hair, and facial acne without enlargement of testi-, t# M T7 i& _8 r
cles, suggests peripheral or pseudopuberty.1-3 We
( U. b5 G8 }% C$ i: |report a 16-month-old boy who presented with the
/ ^9 s9 n8 z' l2 ]enlargement of the phallus and pubic hair develop-/ W8 g! R: e, n% K1 E
ment without testicular enlargement, which was due! F3 _& b4 `, a$ F' p; D# G
to the unintentional exposure to androgen gel used by
. r0 Z) O+ A4 v; E; r0 mthe father. The family initially concealed this infor-2 ?# ]# m$ U' }
mation, resulting in an extensive work-up for this* c9 z' a, Y! g# U7 m' ~& r$ M
child. Given the widespread and easy availability of8 \$ a) ~% \, A9 _% |9 V2 S5 k
testosterone gel and cream, we believe this is proba-
8 C* E* r8 a# M' L5 Mbly more common than the rare case report in the
( b5 I+ x0 F6 _7 O0 ^4 uliterature.4
! ]* I6 N# x% h$ F! ?6 x6 Z" H9 iPatient Report2 |4 N" J" Q8 z$ }7 v" ~* [
A 16-month-old white child was referred to the
2 \$ M. K# y, n1 Z! s5 iendocrine clinic by his pediatrician with the concern+ j+ H) A& C, r. K( z7 V# k
of early sexual development. His mother noticed5 c: F" t8 ~/ j5 X* O d5 B
light colored pubic hair development when he was% y* V; {4 ^+ X
From the 1Division of Pediatric Endocrinology, 2University of6 P. |, R9 O/ h, @
South Alabama Medical Center, Mobile, Alabama.* W' s F2 }" E) y
Address correspondence to: Samar K. Bhowmick, MD, FACE,
% q4 u7 i( d1 D, p5 H6 @, SProfessor of Pediatrics, University of South Alabama, College of. n- W2 r, V7 ?: `3 w- U+ F
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
# Q! F& ]* W y) y1 Y9 N; x1 Ue-mail: [email protected].
5 V2 z5 _2 {. c" U6 B7 s/ ^4 T4 i& dabout 6 to 7 months old, which progressively became" ^; J! W0 Z) K' V4 Y% W5 B
darker. She was also concerned about the enlarge-* b2 U5 T% Y; Y: l/ K( }
ment of his penis and frequent erections. The child
2 ]1 u/ ~: Q/ W9 Y3 p% N1 w$ hwas the product of a full-term normal delivery, with5 z' Z0 n# T1 Y* w
a birth weight of 7 lb 14 oz, and birth length of0 V( v+ k5 f: d7 d& S w- L, i
20 inches. He was breast-fed throughout the first year. C' q7 j4 k; z, Y
of life and was still receiving breast milk along with
1 W. X1 L. Y3 osolid food. He had no hospitalizations or surgery,4 W7 Y7 A5 K% @ u' }
and his psychosocial and psychomotor development# L& [- v. m9 R z. r
was age appropriate.0 H4 m* I5 F; x, Q. \. J6 E
The family history was remarkable for the father,) S( F: v4 |; l3 W0 M
who was diagnosed with hypothyroidism at age 16,2 y# f; z# D" d' v! f3 e( \: C
which was treated with thyroxine. The father’s! d5 D1 I+ v2 L- a" l/ ^
height was 6 feet, and he went through a somewhat. [ n. F0 e+ t% ? l. g* K
early puberty and had stopped growing by age 14.; x* n9 c8 m: ~# {
The father denied taking any other medication. The
1 T" ~+ H" w$ i* y: I6 fchild’s mother was in good health. Her menarche( E1 m+ M* u# P4 Q
was at 11 years of age, and her height was at 5 feet; X. X+ A9 Z2 ^/ _% ^, W& o$ c
5 inches. There was no other family history of pre-/ |" s* l" {& o- r u
cocious sexual development in the first-degree rela-$ S) }6 ?. ]" A2 p% _6 A3 K
tives. There were no siblings.
7 y$ b& Q* j. s9 ]5 C* q% H! RPhysical Examination" M1 X8 C* m, P% q# q
The physical examination revealed a very active,
T: o2 x! C4 w+ pplayful, and healthy boy. The vital signs documented
$ P7 E) R! a2 Ka blood pressure of 85/50 mm Hg, his length was, y- j+ y; c; |. B
90 cm (>97th percentile), and his weight was 14.4 kg1 g: d' z, H, V+ L8 R6 R: |
(also >97th percentile). The observed yearly growth
$ h; [/ G. L; j8 @! tvelocity was 30 cm (12 inches). The examination of' Y- h) K# R# T/ Q9 y$ w8 Q) O8 U
the neck revealed no thyroid enlargement. ~) d$ a! E' d: w' F2 y
The genitourinary examination was remarkable for
7 o" A. }6 }, Renlargement of the penis, with a stretched length of$ W0 o; d/ V0 y2 X' ^
8 cm and a width of 2 cm. The glans penis was very well0 F. `' r! k* p) j; P
developed. The pubic hair was Tanner II, mostly around4 |% U3 L3 ?$ L/ _1 L9 A0 @
540+ L; T9 D# ]8 M! K
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
/ t5 ?# }; J# `5 o- h$ W1 Pthe base of the phallus and was dark and curled. The+ q$ Z: I3 W! l
testicular volume was prepubertal at 2 mL each.
$ u' [' o8 L+ KThe skin was moist and smooth and somewhat. t. `, t3 e, d4 [/ ]
oily. No axillary hair was noted. There were no
1 l" }7 ^- W6 cabnormal skin pigmentations or café-au-lait spots.5 s, }) q. r6 W2 }# k
Neurologic evaluation showed deep tendon reflex 2+' E" {; x' f3 a, ^( V2 q
bilateral and symmetrical. There was no suggestion/ A1 A8 a' S# Y9 l
of papilledema.
4 @& f! z$ p: \2 j' J9 T3 mLaboratory Evaluation- O+ Y9 G* M% s" \, o! d' `. n
The bone age was consistent with 28 months by5 j2 X; }: p' c1 T
using the standard of Greulich and Pyle at a chrono-0 \6 {1 @1 C+ ]; w
logic age of 16 months (advanced).5 Chromosomal3 G) l5 V. V. ^# g' X9 T+ m
karyotype was 46XY. The thyroid function test# P3 j/ k# G: `! M
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
$ A. G. e' L+ k! ^8 U; `: i2 nlating hormone level was 1.3 µIU/mL (both normal).
$ G3 h: V2 `: q) }+ ZThe concentrations of serum electrolytes, blood
' Q5 a2 M5 p5 ^+ d; V& D! v, ~% Ourea nitrogen, creatinine, and calcium all were( C G3 s% ]6 m) ?* U: P% c
within normal range for his age. The concentration6 U. S* `! v1 l! k* x
of serum 17-hydroxyprogesterone was 16 ng/dL" @/ f, f- t2 Y$ P+ u2 m
(normal, 3 to 90 ng/dL), androstenedione was 20
( A* u5 B! P7 m. Yng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-+ p8 G) Y# ?2 U: Q: S* ?( u
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
- T, x: K) X$ \- ~9 H6 I h8 h/ Mdesoxycorticosterone was 4.3 ng/dL (normal, 7 to! U" O3 W" r' b3 x. m
49ng/dL), 11-desoxycortisol (specific compound S)! C! _6 z) i& R, m0 B0 x, x7 I" T0 A
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-$ ?! f8 Y8 N N' C
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total: E: e# n& B$ n) Y% W7 s
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),& f: b4 t7 H! x/ n
and β-human chorionic gonadotropin was less than j& y' D( f) l+ ^! c2 T+ Y
5 mIU/mL (normal <5 mIU/mL). Serum follicular) |% i( ]5 Z1 P
stimulating hormone and leuteinizing hormone
" M( c7 a1 n5 `6 uconcentrations were less than 0.05 mIU/mL5 N' t4 G# X, d+ e- p; L0 |2 b
(prepubertal).
. x ^# N$ ^# u% t$ Z- K7 ~The parents were notified about the laboratory
4 R2 X. h9 p3 j `5 R1 ?0 x( s' I. zresults and were informed that all of the tests were2 o. T; O. _% p& Z4 N, `- Y
normal except the testosterone level was high. The: {+ {) X% H l
follow-up visit was arranged within a few weeks to! |* N1 F1 D' E. }6 ~
obtain testicular and abdominal sonograms; how-
, T8 |1 ?8 ^! I0 _) Gever, the family did not return for 4 months.4 v: p G0 A! J+ L0 @7 A" g8 [
Physical examination at this time revealed that the) @" \% v( G y U( o/ t/ j
child had grown 2.5 cm in 4 months and had gained6 y0 N1 P5 q* I J1 B$ N! \
2 kg of weight. Physical examination remained2 z2 ]7 ]& o# x3 {
unchanged. Surprisingly, the pubic hair almost com-
( X3 a. x" Q' a( Jpletely disappeared except for a few vellous hairs at
; N# k: J% P& s$ G5 ithe base of the phallus. Testicular volume was still 2
+ _* g! o2 j2 {9 @& c5 m- tmL, and the size of the penis remained unchanged.3 ]$ {( N" r1 u5 w% n: R, |
The mother also said that the boy was no longer hav-
, q; k+ o* H! ging frequent erections.
e3 i# s* U) N6 X) u' A9 r) CBoth parents were again questioned about use of5 Y f: A( r) W6 n$ d( d
any ointment/creams that they may have applied to8 D" f7 w$ U" o& w8 ^
the child’s skin. This time the father admitted the. r$ k- m0 |. h! ?& B
Topical Testosterone Exposure / Bhowmick et al 541$ e' ?3 _5 r2 F, ? t9 y, I
use of testosterone gel twice daily that he was apply-9 I# G7 K( q2 r0 b) W) @0 ?
ing over his own shoulders, chest, and back area for
H# D. m e& W. ma year. The father also revealed he was embarrassed# S! Z. s# O# Y V. S. @8 g
to disclose that he was using a testosterone gel pre-8 [& }: g9 @- D/ l. y8 g/ \4 l" d2 C. d
scribed by his family physician for decreased libido0 k* o. m$ w+ x$ \6 p- k. S0 o
secondary to depression.
) t# t5 R4 U; t; j5 Y2 V6 h3 tThe child slept in the same bed with parents.
6 }+ R5 Y$ H/ G7 K! n3 Z( dThe father would hug the baby and hold him on his
6 [8 Z, ]1 r# r! L" xchest for a considerable period of time, causing sig-$ D7 B0 t r3 \3 S/ J
nificant bare skin contact between baby and father. ?9 o0 m! {! n/ q
The father also admitted that after the phone call,% X. j$ q) Y4 ~7 l
when he learned the testosterone level in the baby6 y1 A2 F# ?1 D& V8 y
was high, he then read the product information
) B$ k; H& }' E: F2 W' o1 u- [packet and concluded that it was most likely the rea-& v! W6 C' T: y3 B' T
son for the child’s virilization. At that time, they
p& J7 U" d! Udecided to put the baby in a separate bed, and the' D t5 M. [$ n" D% m
father was not hugging him with bare skin and had
3 n/ T9 Y5 m% u( Z {( X: Kbeen using protective clothing. A repeat testosterone6 E: ?+ G B: m! L8 `7 e* _1 b/ }
test was ordered, but the family did not go to the
' t3 ?+ `, o% j4 \, e+ wlaboratory to obtain the test.
* D, L' d3 y+ DDiscussion
* l4 G' y5 B+ f, f7 q8 m. J8 l# YPrecocious puberty in boys is defined as secondary
z: U5 z3 X" v! J4 G4 o' W$ F- [( T9 xsexual development before 9 years of age.1,4
" [( Q" d, s. @. C0 g! }' f- F6 TPrecocious puberty is termed as central (true) when7 s) k! o( [1 U; _" X( Z
it is caused by the premature activation of hypo-
3 D& x% Q& c3 D& s3 X7 E$ nthalamic pituitary gonadal axis. CPP is more com-) E$ G2 I. G3 J; f$ g2 i
mon in girls than in boys.1,3 Most boys with CPP
- c7 w+ G5 J2 imay have a central nervous system lesion that is+ k% @ h: h, d: O9 X4 [2 w4 s6 Y
responsible for the early activation of the hypothal-
, ] w3 J7 k1 M, L) X/ o0 ?! `2 xamic pituitary gonadal axis.1-3 Thus, greater empha-! @1 x0 R3 J1 ]# Q9 S" r; |
sis has been given to neuroradiologic imaging in
$ Y! F r# s" ~- G+ Eboys with precocious puberty. In addition to viril-" s, l3 E! _# q4 ^" [+ E
ization, the clinical hallmark of CPP is the symmet-5 T6 S8 o1 `0 z/ ~! Q
rical testicular growth secondary to stimulation by
' q$ G2 M5 E' {; h/ V0 ggonadotropins.1,3
' G3 x8 _6 D, f1 P/ U; iGonadotropin-independent peripheral preco-
* w3 a1 o# M/ J' Acious puberty in boys also results from inappropriate4 P- \+ H- l: m+ \9 }
androgenic stimulation from either endogenous or7 k! Q% ~* ]0 k' E. Y }& `9 U
exogenous sources, nonpituitary gonadotropin stim-
4 t6 z+ n0 d* \ulation, and rare activating mutations.3 Virilizing0 j5 [- B+ T& m; N# d
congenital adrenal hyperplasia producing excessive
# K$ g$ |+ o- Q, [# f# v% j4 Iadrenal androgens is a common cause of precocious
' v2 Z6 ^2 k8 c1 xpuberty in boys.3,4# H# C% q. t; x0 \4 T, @; ?
The most common form of congenital adrenal9 p( e8 t/ F$ q" T( d9 [" G
hyperplasia is the 21-hydroxylase enzyme deficiency.
1 \1 {; u) W" @2 q' H1 R. JThe 11-β hydroxylase deficiency may also result in3 D3 V) G0 j$ d
excessive adrenal androgen production, and rarely,
! `$ U7 a9 o. j3 C( Man adrenal tumor may also cause adrenal androgen" O8 b4 m4 i& Q; _# n9 ^
excess.1,3" P% y4 E0 X( ~* m
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from& Y+ U; _$ l2 t% L k5 n# Y5 H
542 Clinical Pediatrics / Vol. 46, No. 6, July 20073 _0 x; Y6 u# n5 I; Z1 p
A unique entity of male-limited gonadotropin-
8 R% \$ T4 e' zindependent precocious puberty, which is also known
& e4 y6 c/ v: J1 ~% x6 ~as testotoxicosis, may cause precocious puberty at a
( j' d' D6 a L F: L8 |) Bvery young age. The physical findings in these boys/ J b- `6 v7 a
with this disorder are full pubertal development,
3 K8 v5 K# w/ R: n2 bincluding bilateral testicular growth, similar to boys
& b5 y6 g/ A a5 }1 O8 Nwith CPP. The gonadotropin levels in this disorder! _+ B+ L. A8 I. M( Z
are suppressed to prepubertal levels and do not show
; Q, v( S. Z* v7 \$ apubertal response of gonadotropin after gonadotropin-
q& i% h6 \5 p" O6 Treleasing hormone stimulation. This is a sex-linked
+ a" U" w, c! {3 J. d( U8 Aautosomal dominant disorder that affects only
: ^3 e$ h; W& x, Bmales; therefore, other male members of the family- X j0 B: @5 L
may have similar precocious puberty.3
9 S% f: Y4 w: J& b+ A- bIn our patient, physical examination was incon-1 _1 I0 D2 M9 z0 L; g
sistent with true precocious puberty since his testi-7 U X8 T7 g9 {, v! m% n
cles were prepubertal in size. However, testotoxicosis
1 \) y9 W$ ]3 n4 C; ~! r6 t# xwas in the differential diagnosis because his father+ g# v2 S4 }% ^" U/ ~
started puberty somewhat early, and occasionally,
/ C F) d& [/ ~& d. N ?testicular enlargement is not that evident in the- I# J( q0 M" c& [0 R- B+ Q0 i; c
beginning of this process.1 In the absence of a neg-
8 n7 x$ U- [' x4 }$ Iative initial history of androgen exposure, our# M" K6 I# ]8 u( _+ u& x
biggest concern was virilizing adrenal hyperplasia,. @# U6 v2 D' @9 D* a. @
either 21-hydroxylase deficiency or 11-β hydroxylase$ p: h# |) |4 M! a3 U
deficiency. Those diagnoses were excluded by find-) j" l. ?1 ?3 @3 {) n
ing the normal level of adrenal steroids.' Y5 u8 l' ^9 ?" x7 q
The diagnosis of exogenous androgens was strongly& r4 c! _8 M# _) A
suspected in a follow-up visit after 4 months because* G/ W# ^& P5 u: Y; B
the physical examination revealed the complete disap-
/ p$ _& j- m0 Q8 m$ a- X. Cpearance of pubic hair, normal growth velocity, and' T |, X7 m/ t0 C
decreased erections. The father admitted using a testos-
8 j1 Y# v6 j4 t- Z: Zterone gel, which he concealed at first visit. He was
5 B( x8 B; C6 _using it rather frequently, twice a day. The Physicians’0 e1 Y) _ o! C" w* F
Desk Reference, or package insert of this product, gel or' F" T) ]/ \+ K' C: ^: S" H
cream, cautions about dermal testosterone transfer to- g. L+ T6 w$ N( C' e, @- E0 y3 K0 x
unprotected females through direct skin exposure.
* U, _: F4 g! |2 wSerum testosterone level was found to be 2 times the; v# a) p. E/ q. t1 l2 Z
baseline value in those females who were exposed to
% G/ ?: R' p: i5 ?# [6 oeven 15 minutes of direct skin contact with their male
; D2 a0 n- ?1 V% Kpartners.6 However, when a shirt covered the applica-' X1 Z$ B! I9 C* Y! V$ M. d2 t
tion site, this testosterone transfer was prevented.4 S4 S9 O- Y; K0 J- i
Our patient’s testosterone level was 60 ng/mL,# P. @6 J/ y% A+ G) m
which was clearly high. Some studies suggest that5 {- h* e2 R& X7 h
dermal conversion of testosterone to dihydrotestos-
; r/ _/ _4 u3 Rterone, which is a more potent metabolite, is more9 S* b# R6 J6 y+ n- S/ _
active in young children exposed to testosterone
/ k1 E+ t, K# N7 }0 A; xexogenously7; however, we did not measure a dihy-. N/ ^0 b1 @) B. A
drotestosterone level in our patient. In addition to9 w9 Z& Q5 F7 Z, h' o4 l
virilization, exposure to exogenous testosterone in
. [8 n2 C2 s! @9 cchildren results in an increase in growth velocity and
* j# @4 Z1 c5 i* z" b( C7 H+ ?advanced bone age, as seen in our patient.- ?* ] i$ J; S- E5 D
The long-term effect of androgen exposure during+ l' @) |7 D/ M) g% X2 j9 i4 Y( N3 D
early childhood on pubertal development and final
& ?& R/ d+ ], y1 X: R4 w' m) Tadult height are not fully known and always remain+ ]3 B9 L( v4 g
a concern. Children treated with short-term testos-
y$ _$ w" m5 N' c! \terone injection or topical androgen may exhibit some
5 Y& E8 ~- K6 Z8 y& aacceleration of the skeletal maturation; however, after0 F5 ?& r( {$ {8 X5 ]- W
cessation of treatment, the rate of bone maturation( q/ j' b0 q' @5 ]; ?) [( m# c
decelerates and gradually returns to normal.8,9. E3 S" q, D3 U& r+ z
There are conflicting reports and controversy
& u8 v \# I- n* `over the effect of early androgen exposure on adult
' F3 c/ a" Z0 b' z4 I) l! w3 tpenile length.10,11 Some reports suggest subnormal; I6 X/ z( o3 r: n* m
adult penile length, apparently because of downreg-) p M& B( Y0 |6 O
ulation of androgen receptor number.10,12 However,- f3 N8 e! [( j! b4 w$ K
Sutherland et al13 did not find a correlation between, T+ c8 g& C3 Z* _2 [' E
childhood testosterone exposure and reduced adult* {2 ]$ {# P9 r e, g
penile length in clinical studies.
" t% b& [) r1 hNonetheless, we do not believe our patient is
% ^" o8 F: q$ Ogoing to experience any of the untoward effects from* {, c8 a6 B* p: s
testosterone exposure as mentioned earlier because5 R7 i% w2 o2 [! U8 l1 i! I
the exposure was not for a prolonged period of time.5 _/ d7 k# O o- m! T- s1 i1 _
Although the bone age was advanced at the time of
G6 u& H3 \/ D! i+ U* Udiagnosis, the child had a normal growth velocity at. m$ q2 a$ c: i; Z0 Z0 i! B
the follow-up visit. It is hoped that his final adult6 z2 H) z+ Z& a$ t
height will not be affected.
- h9 m" b: s2 \+ z& G \- `& L h2 e( KAlthough rarely reported, the widespread avail-4 z" s7 U+ m3 u1 }6 \, q8 A
ability of androgen products in our society may
, y2 `2 V! r, M) o* z! y% {6 `indeed cause more virilization in male or female, }1 P% k; q( c. {
children than one would realize. Exposure to andro-& t1 H _8 k8 G1 u/ Q7 g
gen products must be considered and specific ques-
9 W6 F& q. A' ~8 ftioning about the use of a testosterone product or+ K2 `2 n; B: ]! D% t& J
gel should be asked of the family members during
' f$ q) Q( l! ?; l, zthe evaluation of any children who present with vir-
" G5 [) Y1 b7 { g" C) o% g) oilization or peripheral precocious puberty. The diag-; l" ?. G( \4 F, U3 W) w
nosis can be established by just a few tests and by
5 `* M" O5 G* D7 bappropriate history. The inability to obtain such a
, s7 K0 e' p: W$ j& {9 x* Ghistory, or failure to ask the specific questions, may# [5 W+ x% |. T1 e8 c
result in extensive, unnecessary, and expensive
3 f1 v" M0 q& ^: [- B' ]5 Dinvestigation. The primary care physician should be
: z8 v; _' I5 |' u. T3 caware of this fact, because most of these children* H9 U' j5 w/ z- S0 }
may initially present in their practice. The Physicians’2 A& U3 V# \& t) o3 F
Desk Reference and package insert should also put a
# R1 T3 R% H" C" A' D( J0 H8 vwarning about the virilizing effect on a male or
1 x' w) c O5 ]5 w& ?7 Ufemale child who might come in contact with some-3 c5 \5 r) D, S- \
one using any of these products.' K: e. \! U9 i4 k M
References$ ~" t5 ~+ G) Y% Z0 z7 f |3 o
1. Styne DM. The testes: disorder of sexual differentiation
3 O8 u: T7 L- F+ X& V; Z8 Wand puberty in the male. In: Sperling MA, ed. Pediatric
/ ?" ~2 ]! k, m9 s, yEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
- n. u, i; E4 q- O3 n$ k- b2002: 565-628.
5 L; p8 X% v3 @' X% F- x2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious9 n+ k. t& D; P$ h" {! B+ M
puberty in children with tumours of the suprasellar pineal |
|