- 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" _) D+ i2 |' f7 N+ W, F
Boy Induced by Indirect Topical! j: E( ^8 ]9 ~
Exposure to Testosterone
# u1 Z9 H( D6 {$ u# FSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2- l9 r5 g. C# }$ s2 A
and Kenneth R. Rettig, MD1
0 }6 W* a f" H5 T+ j+ d$ p2 UClinical Pediatrics* _/ r$ I/ f. @) @* ^
Volume 46 Number 62 r- J4 N0 h! R5 i: v
July 2007 540-5430 h/ I4 T3 I% U: j$ T6 f
© 2007 Sage Publications
' [4 f- C3 _( I" ^; Z2 @10.1177/00099228062966516 w y L7 q4 F7 W, C3 T
http://clp.sagepub.com$ N' z: k: _0 {/ i! |* \: j
hosted at
8 V, t) c, m/ Zhttp://online.sagepub.com! ^( d: u0 ~, ?8 l& T
Precocious puberty in boys, central or peripheral,% ]5 h& [; J d0 t0 x4 M. z
is a significant concern for physicians. Central* I/ r9 X3 w1 H) Q5 _
precocious puberty (CPP), which is mediated. ]" m7 |5 H. J
through the hypothalamic pituitary gonadal axis, has9 f# C& D8 c7 i" Q
a higher incidence of organic central nervous system
- [2 W2 X H' Z8 m( _ Glesions in boys.1,2 Virilization in boys, as manifested
- m0 X. z6 @- K' s- L; f8 b4 Eby enlargement of the penis, development of pubic& g( c* \: \4 a8 D
hair, and facial acne without enlargement of testi-3 S$ l$ @. B' r7 Z: q
cles, suggests peripheral or pseudopuberty.1-3 We
/ n$ G. e3 Y) N- D( \report a 16-month-old boy who presented with the3 s; t4 h+ W5 V& b6 E I) L0 v
enlargement of the phallus and pubic hair develop-
4 z9 w' e. O0 B! o: K7 e8 hment without testicular enlargement, which was due
+ ~4 U/ s$ d3 \! _4 sto the unintentional exposure to androgen gel used by
6 O" L" w: ]) R3 C( Dthe father. The family initially concealed this infor-; d0 f/ M& Q d% e/ T' ~
mation, resulting in an extensive work-up for this4 W8 I3 f. C! ?4 a' z, i; M
child. Given the widespread and easy availability of! a2 p1 V! ^* H0 W* L+ ]
testosterone gel and cream, we believe this is proba-
1 b4 x+ q* J4 B! Q9 G# r8 f6 Ibly more common than the rare case report in the
( ?* Q, M' b& G' a0 r' Dliterature.4
6 v' \3 A- L5 BPatient Report
6 b: q1 b2 V) l% {7 m1 j8 G: D$ fA 16-month-old white child was referred to the
2 L, m$ j; h4 K" Xendocrine clinic by his pediatrician with the concern6 U2 h# V y' q$ M; n. d
of early sexual development. His mother noticed
6 C7 H# _" w1 T: T( \* ?" P" }light colored pubic hair development when he was9 s: _4 x5 Z X3 L' z5 E& F
From the 1Division of Pediatric Endocrinology, 2University of
# l; O* ~ Y2 S- J1 h3 jSouth Alabama Medical Center, Mobile, Alabama.
; t2 |. `6 I5 k9 u8 [0 Y' EAddress correspondence to: Samar K. Bhowmick, MD, FACE,% j" K) w6 l1 ?3 f3 D3 C8 ^
Professor of Pediatrics, University of South Alabama, College of
u& l6 T: K8 {' n5 | gMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;/ W" W4 y" y& {* e3 B
e-mail: [email protected].6 e+ P- W5 a. v c) X w# F7 e% Y5 f* \
about 6 to 7 months old, which progressively became4 e9 l4 I' Z, j f
darker. She was also concerned about the enlarge-3 ^+ L. r3 N) _5 F0 D
ment of his penis and frequent erections. The child
$ v8 @! h$ j' ~ ?* q1 t3 d8 uwas the product of a full-term normal delivery, with& c5 K* b: c5 a$ i* v% }
a birth weight of 7 lb 14 oz, and birth length of
- _. {; k; m; [- O20 inches. He was breast-fed throughout the first year
% O+ Z9 S' L4 L$ o- zof life and was still receiving breast milk along with
/ U. W; b Y% ` g- a# \; \% Jsolid food. He had no hospitalizations or surgery,6 P- n, W. J+ d
and his psychosocial and psychomotor development
: A) N) J% J7 R! v8 B" }was age appropriate.
0 y4 [5 \$ z( E; i& ^The family history was remarkable for the father,6 N* A; i% S3 `0 g( s: a: {: h6 [3 ~0 |
who was diagnosed with hypothyroidism at age 16,0 ^6 I; O! D, p; Y
which was treated with thyroxine. The father’s
6 k. G5 z8 `5 n1 ^! w& s0 H5 [height was 6 feet, and he went through a somewhat* q; Y0 k- \: V% X2 R. V2 L# ?+ w5 J
early puberty and had stopped growing by age 14.
" I7 [% ]; B8 t/ ]4 ^The father denied taking any other medication. The
; P9 [$ d0 p, {child’s mother was in good health. Her menarche
4 T: U3 U7 Y/ X% twas at 11 years of age, and her height was at 5 feet" s9 P3 e9 l, m: [$ Z K1 w
5 inches. There was no other family history of pre-* ~5 ^& O3 ?- D& t
cocious sexual development in the first-degree rela-3 M* c6 h' s. |( t7 i! S
tives. There were no siblings.
! a" H) E8 Z9 g% u8 N6 d- \$ U" t0 rPhysical Examination
. v( V. O) O. IThe physical examination revealed a very active,
9 i3 p' }+ w+ A3 ~playful, and healthy boy. The vital signs documented
$ W. k/ S9 _3 [2 u8 V5 B4 ]( F9 Ha blood pressure of 85/50 mm Hg, his length was' i3 Z+ B# [8 D! }% m: Y0 |
90 cm (>97th percentile), and his weight was 14.4 kg
: J( ?8 U# E0 s, \(also >97th percentile). The observed yearly growth. T. M7 h. f2 e) \
velocity was 30 cm (12 inches). The examination of8 F1 c+ `* i% V9 o
the neck revealed no thyroid enlargement.: w& ?0 q7 g. ?, A8 O- i: I
The genitourinary examination was remarkable for+ N1 i# y6 |" s/ t# A
enlargement of the penis, with a stretched length of
2 E* B3 i8 }- F0 y7 C9 F8 cm and a width of 2 cm. The glans penis was very well2 h8 j7 W. j$ {& \9 C" W
developed. The pubic hair was Tanner II, mostly around8 v* A: W4 j7 f/ D4 x
540! t/ Y5 _2 x; }! }
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from. I# N2 ]7 o9 C# f+ X
the base of the phallus and was dark and curled. The
+ t5 D( O! @2 ~testicular volume was prepubertal at 2 mL each.
$ @% B7 s. i. I9 F$ UThe skin was moist and smooth and somewhat0 b- ^% L4 O4 ?9 H9 M
oily. No axillary hair was noted. There were no
X @' }2 ^$ Fabnormal skin pigmentations or café-au-lait spots.
$ F/ i9 A9 Z# r) q* ZNeurologic evaluation showed deep tendon reflex 2+
5 ]% n; Y9 r" c/ ubilateral and symmetrical. There was no suggestion% P! G* r$ Q/ [3 T- Q! T
of papilledema.
! t: i4 o3 n; C. r% H- FLaboratory Evaluation
; E* K+ z" Y; i1 `. u1 bThe bone age was consistent with 28 months by. f, `6 U. M" p9 X2 a Z* q. ~
using the standard of Greulich and Pyle at a chrono-
9 e3 x' [8 J4 Y3 J* K$ w* Q' B+ D' ulogic age of 16 months (advanced).5 Chromosomal0 v+ X9 T8 e+ a1 K8 N
karyotype was 46XY. The thyroid function test0 B8 o8 `. C5 h/ t- F
showed a free T4 of 1.69 ng/dL, and thyroid stimu-7 g" y9 u, x' B5 y
lating hormone level was 1.3 µIU/mL (both normal).
( Y) _- ~6 F" m# E LThe concentrations of serum electrolytes, blood
7 K- Q0 D! P4 L( d1 W. `urea nitrogen, creatinine, and calcium all were
2 Y1 h/ e9 Z# w+ Gwithin normal range for his age. The concentration) \; l: v6 o' i" `
of serum 17-hydroxyprogesterone was 16 ng/dL; o4 n( }3 C( S# T3 k
(normal, 3 to 90 ng/dL), androstenedione was 20
0 g1 D$ v1 s5 n; _9 j, x% @9 @- T2 |ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
/ I- ]: d7 W1 U8 F8 d6 vterone was 38 ng/dL (normal, 50 to 760 ng/dL),
1 K6 b+ d% c) O: \3 g! X! _. Xdesoxycorticosterone was 4.3 ng/dL (normal, 7 to
9 e0 e5 d5 O; B& G5 u; x( ]( ?49ng/dL), 11-desoxycortisol (specific compound S)
" |/ ?$ v- s) x1 k2 Q' D. L" e1 y+ ywas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
+ W2 J: i7 [" a( |# q# etisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
8 X; I6 E, Q, d' m. A7 Xtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
8 v' |8 A$ t! Land β-human chorionic gonadotropin was less than+ \ | t4 O8 B0 A# j
5 mIU/mL (normal <5 mIU/mL). Serum follicular
* A8 s" y: p7 t* e; o. dstimulating hormone and leuteinizing hormone
! @) @2 d; O6 s' ~2 gconcentrations were less than 0.05 mIU/mL1 q- K6 F8 Z( |5 f4 C8 t6 I& d* f
(prepubertal).& ]( D r: T, e2 D# L* e' U) Y. M
The parents were notified about the laboratory
& M* u1 z" e7 ?+ Yresults and were informed that all of the tests were6 B9 V1 x* U( b- M2 c
normal except the testosterone level was high. The
/ a( j( [+ Z0 k" l; efollow-up visit was arranged within a few weeks to
3 l+ h4 }' O' [* Uobtain testicular and abdominal sonograms; how-% n& y* z4 J; g6 \+ G. u0 R
ever, the family did not return for 4 months.
2 W3 J. z( s0 u! {( j, `( X& ePhysical examination at this time revealed that the
, ~3 q0 |4 Q* X' ^1 M0 Zchild had grown 2.5 cm in 4 months and had gained9 k. t$ L/ `) C( I
2 kg of weight. Physical examination remained
- X5 A- e4 o* S& H% i F% }unchanged. Surprisingly, the pubic hair almost com-
8 i0 H; M4 V' ?* h# G. \pletely disappeared except for a few vellous hairs at
/ U- y" R b! K' ythe base of the phallus. Testicular volume was still 25 J# D. B. z2 A% B* X
mL, and the size of the penis remained unchanged.) r- W# ]; C( N9 ]4 N2 |
The mother also said that the boy was no longer hav-$ |$ N. g9 }; z! H; f0 p
ing frequent erections.
9 c& g7 p: ~) B0 g7 O! G2 UBoth parents were again questioned about use of
, N# Y$ M/ |- I3 Oany ointment/creams that they may have applied to
' s, T3 n# o( S% \the child’s skin. This time the father admitted the' _8 w* X8 _+ Q3 ~2 F8 D/ m
Topical Testosterone Exposure / Bhowmick et al 541
- u/ G& d& c& Buse of testosterone gel twice daily that he was apply- e+ h0 o, n. w0 A5 A
ing over his own shoulders, chest, and back area for
( J* l+ c A A# C( n4 p/ h7 _0 aa year. The father also revealed he was embarrassed
9 \, q# ?+ F# N; dto disclose that he was using a testosterone gel pre-
# |! E! K: o) ~9 j. |, Zscribed by his family physician for decreased libido
. ]5 f0 c7 P- ysecondary to depression. A Y% L8 p. F+ e0 n
The child slept in the same bed with parents.
7 a0 ~* h2 Q g9 G0 bThe father would hug the baby and hold him on his. v1 j. ^% ?( }/ q2 s6 o
chest for a considerable period of time, causing sig-( y8 M: P$ C7 D' g+ h* x& ~
nificant bare skin contact between baby and father.1 Q! V# _% z; b, @
The father also admitted that after the phone call,% H; |/ ^1 A9 Z1 e! D/ M# D
when he learned the testosterone level in the baby
4 A3 M" @: O( F, h1 k+ pwas high, he then read the product information1 w1 o. I7 T7 }, W" Z3 x
packet and concluded that it was most likely the rea-5 d/ |! o3 {" n2 K# K
son for the child’s virilization. At that time, they& G3 K% _4 |: b- b
decided to put the baby in a separate bed, and the
# t- C- o0 K- E& I C3 x1 U, xfather was not hugging him with bare skin and had
& G( q3 Z) u5 M g8 i, U$ hbeen using protective clothing. A repeat testosterone
: r& s! C7 n# p" S/ _0 |test was ordered, but the family did not go to the
$ [" _7 A5 T4 j7 Ylaboratory to obtain the test.; Q9 ? ^) j t, Y" B
Discussion/ p, i1 c2 }- A) t
Precocious puberty in boys is defined as secondary
9 A1 p2 J/ u+ g4 W. bsexual development before 9 years of age.1,4) G$ n9 ^ l3 S% e/ f
Precocious puberty is termed as central (true) when# j5 E* J& k: S9 Y {# H4 j& j0 ~
it is caused by the premature activation of hypo-
: [/ \3 t- @# O4 |4 vthalamic pituitary gonadal axis. CPP is more com-' F3 |0 n c' B( G$ C7 y
mon in girls than in boys.1,3 Most boys with CPP
' X+ g+ V. Y% O* g0 N6 Cmay have a central nervous system lesion that is
3 ?& t& U, _4 p6 l8 Mresponsible for the early activation of the hypothal-
3 I7 p7 N. z" K, Camic pituitary gonadal axis.1-3 Thus, greater empha-
: ~9 m$ B$ S% O0 b/ k" M, I F8 usis has been given to neuroradiologic imaging in* ?# |. W0 D9 U- G) J
boys with precocious puberty. In addition to viril-
, x0 q" v5 ?/ G# |ization, the clinical hallmark of CPP is the symmet-7 a5 ]) E) t7 h3 S9 Q
rical testicular growth secondary to stimulation by J% `' p3 f$ v( g
gonadotropins.1,3
: ?: R6 G" a4 h K, `' m% S8 ~" EGonadotropin-independent peripheral preco-3 O7 G5 s5 O" O1 u
cious puberty in boys also results from inappropriate
8 l l% K3 v5 i9 g/ J! Mandrogenic stimulation from either endogenous or0 M9 _( N2 K1 Y3 J- R( K+ F
exogenous sources, nonpituitary gonadotropin stim-
8 [3 N/ g5 c5 t5 H5 a* Nulation, and rare activating mutations.3 Virilizing o% u, `; h9 Y( z
congenital adrenal hyperplasia producing excessive
; C- f5 t' b; Jadrenal androgens is a common cause of precocious
9 u* z) e# \9 _, F, T$ k9 G, f: F/ ~puberty in boys.3,4- v- L: o% G* Y& r& A
The most common form of congenital adrenal+ X( |1 b0 i8 a1 R$ D; y6 }
hyperplasia is the 21-hydroxylase enzyme deficiency.
1 @' T, f5 E1 ]* I; w# j' kThe 11-β hydroxylase deficiency may also result in4 J' H+ e1 E" `$ d' s6 }
excessive adrenal androgen production, and rarely,
Y7 L, b! {) m" O/ M' n% `8 oan adrenal tumor may also cause adrenal androgen
# @# g# T% v7 V) I6 o; Bexcess.1,30 g2 Y, r# ^' e% r: x2 M3 [9 C$ u
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
+ Z! i5 K# B- ` x5 f542 Clinical Pediatrics / Vol. 46, No. 6, July 20070 g6 `& n, N# M5 c. O
A unique entity of male-limited gonadotropin-
& k4 N3 g+ I* ^; ~& p# a4 }independent precocious puberty, which is also known* a# h3 w/ V9 h7 ~+ _# C1 F. P5 i4 r
as testotoxicosis, may cause precocious puberty at a
5 {, A+ d. B, k5 pvery young age. The physical findings in these boys
5 m* F$ U9 a" @9 Cwith this disorder are full pubertal development,
; o% l! T3 m$ ^3 s F+ O1 [0 Bincluding bilateral testicular growth, similar to boys
7 c8 u9 w9 f8 a) W7 lwith CPP. The gonadotropin levels in this disorder8 q/ ^/ G4 L" l6 _3 V+ V
are suppressed to prepubertal levels and do not show
( \* o/ U6 p; U4 Wpubertal response of gonadotropin after gonadotropin-
* k: P7 P; g7 e+ o/ o" h( sreleasing hormone stimulation. This is a sex-linked
6 S) ?/ }1 g# k Y$ W; A8 Sautosomal dominant disorder that affects only/ I5 L5 N6 C6 q/ P; V
males; therefore, other male members of the family
5 `" [) m) R5 l/ a6 Umay have similar precocious puberty.3, A. @5 Z5 F$ k0 c
In our patient, physical examination was incon-: m2 f. |# _, R- ]0 E; L4 F
sistent with true precocious puberty since his testi-/ y. O: {- j; n4 v
cles were prepubertal in size. However, testotoxicosis3 J+ |, H* W; K$ s1 b. b m' v
was in the differential diagnosis because his father; L; @/ n+ t1 k( N9 O
started puberty somewhat early, and occasionally,* x5 C+ F4 q7 d/ l
testicular enlargement is not that evident in the& @) c% r9 r6 }% I: C; m$ S# _
beginning of this process.1 In the absence of a neg-& S' w7 ~% O/ }8 }5 X% e
ative initial history of androgen exposure, our n( c4 p. ]5 H+ p8 a0 Y3 E, g5 Y
biggest concern was virilizing adrenal hyperplasia,) T- E* g7 J, p* D# [# |+ g: f" ^3 ]7 _
either 21-hydroxylase deficiency or 11-β hydroxylase, V& O$ M& ^ K1 h2 m0 }
deficiency. Those diagnoses were excluded by find-
' n% ~ I2 ^& T6 E" P. _ n9 Ring the normal level of adrenal steroids.) w3 [( D9 X: r$ J
The diagnosis of exogenous androgens was strongly+ e3 i3 B+ a( Z
suspected in a follow-up visit after 4 months because. x2 E1 B6 I" [! i
the physical examination revealed the complete disap-4 ~( m$ N2 ~, Z6 \! i# o
pearance of pubic hair, normal growth velocity, and
1 L( i# t3 F+ E0 ~6 V$ Pdecreased erections. The father admitted using a testos-9 W: F; Q" O, n- @0 o( x
terone gel, which he concealed at first visit. He was
& C3 l a& l& E8 T& ~& t) Vusing it rather frequently, twice a day. The Physicians’
9 {1 R8 Q: w& U& cDesk Reference, or package insert of this product, gel or2 f# J% |+ D# c3 w
cream, cautions about dermal testosterone transfer to0 T7 L1 a( I8 O# ^7 j
unprotected females through direct skin exposure.' U: L4 ^4 i i- j3 h
Serum testosterone level was found to be 2 times the
6 |; }; ]3 O) a1 U' W: [& r3 Rbaseline value in those females who were exposed to
+ H6 K" n. a2 U* u) t1 y7 a$ M9 qeven 15 minutes of direct skin contact with their male
; w* m" l" x6 G0 R$ n1 Wpartners.6 However, when a shirt covered the applica-* d2 r* W2 H$ \8 S
tion site, this testosterone transfer was prevented.
. s. V9 v, Z( ^) l2 O+ tOur patient’s testosterone level was 60 ng/mL,; k4 C% k! t: k- P2 C* \
which was clearly high. Some studies suggest that6 f5 C" P2 ]: Z& g/ }
dermal conversion of testosterone to dihydrotestos- w" w! ^2 y5 o0 p. L
terone, which is a more potent metabolite, is more, d3 x5 [5 k) i$ y7 L$ w
active in young children exposed to testosterone
8 S+ d+ X# L8 e: P8 H( u. L4 dexogenously7; however, we did not measure a dihy-
2 k+ M9 U6 F' g$ f- Ydrotestosterone level in our patient. In addition to
+ d E0 ?; {) ?% Avirilization, exposure to exogenous testosterone in& W* R p/ M9 C$ J
children results in an increase in growth velocity and
* Q" r" N! \) r ]. U9 }advanced bone age, as seen in our patient." D9 q! ^# j, l. a0 q( a: K* Y
The long-term effect of androgen exposure during: V+ p) C* t- C* m
early childhood on pubertal development and final
0 a2 E3 n, y# k! B5 D0 Jadult height are not fully known and always remain% U' x. _) m+ Z# R0 A* Y5 k5 r
a concern. Children treated with short-term testos-
J) Z* f$ e: W, ]terone injection or topical androgen may exhibit some
6 [2 {& p3 ?; e! Z- z iacceleration of the skeletal maturation; however, after
/ |1 w1 c; F: _2 b: ocessation of treatment, the rate of bone maturation; ^, ^" P5 W c# d8 x. A
decelerates and gradually returns to normal.8,9
: R! x/ f) J( Q8 B, QThere are conflicting reports and controversy/ z4 w! n4 {! y/ J! Y& J
over the effect of early androgen exposure on adult
5 i/ D7 e# z( Z4 Bpenile length.10,11 Some reports suggest subnormal
& _& Q3 X. q ]& oadult penile length, apparently because of downreg-
8 ]7 @! M* n5 r: b1 c* L4 hulation of androgen receptor number.10,12 However,
: Z3 x5 S# M, W6 Y+ {Sutherland et al13 did not find a correlation between
+ h8 w- o$ Z" z5 ychildhood testosterone exposure and reduced adult+ ?! ~ b- a `. P9 ]0 b. `
penile length in clinical studies.
+ S8 ^% s4 j1 M% pNonetheless, we do not believe our patient is
0 Y3 V7 }5 U! G: W! p# Egoing to experience any of the untoward effects from8 s# o+ x U) @% Y# o
testosterone exposure as mentioned earlier because/ |1 E5 t1 K! g* [9 [5 \8 Y4 v) k
the exposure was not for a prolonged period of time.3 _/ j$ n/ o$ h1 z2 k7 T& ^
Although the bone age was advanced at the time of5 o8 Q/ A/ P/ L% ~
diagnosis, the child had a normal growth velocity at
; u, {" _, Z6 v! p. F* r- ?& [the follow-up visit. It is hoped that his final adult
7 V9 Z& _* n, C7 _height will not be affected.. I) a& [7 J# s8 y6 D
Although rarely reported, the widespread avail-
( n! {6 X; {- P6 iability of androgen products in our society may
6 e& I q; ` C' U3 v- u1 sindeed cause more virilization in male or female
2 I9 ~+ t$ c. i, K# Z; b- Wchildren than one would realize. Exposure to andro-
L, y( }' ?% m' X0 Y" Ugen products must be considered and specific ques-
( e* G8 H7 c8 ` e( v% {) ftioning about the use of a testosterone product or
0 H' m) D7 J8 |7 P- @* B+ T; ^; rgel should be asked of the family members during& m9 P! A) c' o% b! k
the evaluation of any children who present with vir-, m6 ^0 v& i- K$ g* e
ilization or peripheral precocious puberty. The diag-1 `* U: k" |- X
nosis can be established by just a few tests and by
$ \2 g. T; \. L4 w( Y u; w3 o( t) oappropriate history. The inability to obtain such a
# d. I! K, \; {% H# Ehistory, or failure to ask the specific questions, may
2 [$ l! a$ I7 x/ y% Y6 kresult in extensive, unnecessary, and expensive
?9 F, h( x9 Oinvestigation. The primary care physician should be* h! u3 E4 @2 B2 L* W1 G
aware of this fact, because most of these children' k& n) r3 X& G2 f! x9 Q8 u
may initially present in their practice. The Physicians’
0 n+ @* A# _! wDesk Reference and package insert should also put a- H- T! V ^4 P$ N/ k
warning about the virilizing effect on a male or
6 T- \' z7 Y; `8 kfemale child who might come in contact with some-2 |( c& z! P P: j; @
one using any of these products.
& {9 w ^. `2 J$ N3 o0 S; t5 eReferences, z* n* ^5 J' t7 a: n* k- R
1. Styne DM. The testes: disorder of sexual differentiation) i F c' M( v% n; }1 Z9 i
and puberty in the male. In: Sperling MA, ed. Pediatric" [' K# ` p r/ ]- e$ Z' F6 q
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;2 h* q4 ]0 a0 m3 [& O
2002: 565-628.- v: H% _. Y2 v9 L2 V2 \
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious7 e) W, d6 ~- r2 u" r, R
puberty in children with tumours of the suprasellar pineal |
|