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Sexual Precocity in a 16-Month-Old# ~8 u- g4 [- H; y
Boy Induced by Indirect Topical( V2 } U( Q: Q' o/ C
Exposure to Testosterone
4 i3 E, t" V1 ]" ~3 D' d# q! |Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,28 @5 F. I6 T b9 n" Z. B
and Kenneth R. Rettig, MD1
( J0 O1 T( L, B( j) @+ }3 UClinical Pediatrics
7 h- ^" X1 c5 z$ E5 ?$ Q& jVolume 46 Number 6( X' Z3 Z: a8 i4 j" Z
July 2007 540-543& J4 }- o! y# s9 a, i5 Y0 W) s
© 2007 Sage Publications4 g _/ W3 j g; C
10.1177/0009922806296651
0 J9 Y9 C& z0 G) Ghttp://clp.sagepub.com
' q. T$ D6 W* rhosted at* y& e; H N+ a/ V- E& m
http://online.sagepub.com
+ g+ j/ ^3 s7 t3 d0 S# M" w2 WPrecocious puberty in boys, central or peripheral,
0 \4 e1 B' j) z2 W( ]! _7 K2 g7 L& Z3 uis a significant concern for physicians. Central
) Y. s- \3 t9 b3 ]0 R( f j: y7 X) Fprecocious puberty (CPP), which is mediated4 H8 e* M. \* v4 l, V; K. e
through the hypothalamic pituitary gonadal axis, has* @ W4 J+ F, t, B' Z5 b: b- {2 D
a higher incidence of organic central nervous system, E' w( f: B/ ^, M5 Y
lesions in boys.1,2 Virilization in boys, as manifested
" ~& @5 i, ]6 k, N7 Q, P. rby enlargement of the penis, development of pubic
1 X* Z* Q2 L# s9 B, ^4 k" Shair, and facial acne without enlargement of testi-6 s( J" ~+ Q+ d! A/ t$ p7 H
cles, suggests peripheral or pseudopuberty.1-3 We
% z8 {1 U6 O1 [: g2 z, kreport a 16-month-old boy who presented with the3 Z3 @; h; t3 H" r
enlargement of the phallus and pubic hair develop-
5 q+ s' Q2 `9 ]ment without testicular enlargement, which was due
? X3 x" c7 k$ z6 @+ Qto the unintentional exposure to androgen gel used by
' Z! _' [4 S% [the father. The family initially concealed this infor-
, Q3 b8 u# y3 m1 O0 Z& lmation, resulting in an extensive work-up for this% R( e8 x M" V" b/ M2 b* U. i
child. Given the widespread and easy availability of. z2 S& P3 p6 g$ {9 J) f
testosterone gel and cream, we believe this is proba-2 {6 p B* `8 x* v. K9 I" k
bly more common than the rare case report in the- K0 V/ n5 M1 g( m3 E) t; W, R
literature.4
" @/ B0 ?% H8 a' x6 d vPatient Report' a& h7 o+ e1 s3 e
A 16-month-old white child was referred to the% j: v! T# d, h
endocrine clinic by his pediatrician with the concern
; V/ k0 [4 R! V' Gof early sexual development. His mother noticed
2 {( d* W' d8 B1 _) Q/ m+ m6 h' jlight colored pubic hair development when he was
1 v/ R2 O. v( {& x6 d& @/ m2 G5 pFrom the 1Division of Pediatric Endocrinology, 2University of
, L0 ^# r( z; i3 t0 D0 S' rSouth Alabama Medical Center, Mobile, Alabama.
: E# d6 z4 l# L9 ^( eAddress correspondence to: Samar K. Bhowmick, MD, FACE,4 y- q6 |9 {- q
Professor of Pediatrics, University of South Alabama, College of
% b/ P, I. Y$ C) I/ p3 X8 \7 A+ c2 T2 tMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
0 o2 u! d; V8 a) a I6 _1 _e-mail: [email protected].
5 P/ ?4 F! A" z& a6 M* h3 Iabout 6 to 7 months old, which progressively became
! v$ v7 O. m8 Q I4 G$ W1 r# hdarker. She was also concerned about the enlarge-3 {2 q" `3 T2 l8 V L
ment of his penis and frequent erections. The child
1 ]5 l5 A( Q7 d: V8 O5 Mwas the product of a full-term normal delivery, with s$ F0 x$ K: c* x* r, D1 w* e
a birth weight of 7 lb 14 oz, and birth length of3 V- {. \6 q0 T p/ Z& i/ G3 ]
20 inches. He was breast-fed throughout the first year- j! y0 @/ u! K9 O
of life and was still receiving breast milk along with, q; K1 t7 p# @" [: s
solid food. He had no hospitalizations or surgery,( A0 {# n1 }7 [& d- O' c
and his psychosocial and psychomotor development0 O1 U8 q, p2 d" R$ p; d9 T" `
was age appropriate.
9 j' _9 Z! y+ Y/ T8 bThe family history was remarkable for the father,
K* E, Q; h" d+ e7 dwho was diagnosed with hypothyroidism at age 16,
{$ I# y& D; K) I2 Owhich was treated with thyroxine. The father’s/ p+ s3 c5 y% |! K
height was 6 feet, and he went through a somewhat
- k& N: i) V+ D5 Nearly puberty and had stopped growing by age 14.. H2 ]; S1 w; K( ` p4 N6 N
The father denied taking any other medication. The
9 C2 a k" f* M$ O' ^2 M8 ichild’s mother was in good health. Her menarche, V- p8 V/ `; q0 P ?8 P/ O
was at 11 years of age, and her height was at 5 feet: h' k1 _5 c7 j0 d# Y: n
5 inches. There was no other family history of pre-' V1 X) X1 G4 N+ X
cocious sexual development in the first-degree rela-( h' W; w! y1 P, a& f# v. H$ }- m
tives. There were no siblings.
2 c, V; |! _ ]4 UPhysical Examination% d% e4 M* C0 Y& b/ v, E8 a& ^
The physical examination revealed a very active,3 k6 p2 v& i- E
playful, and healthy boy. The vital signs documented' A1 X' \2 f! p9 B x& k9 f
a blood pressure of 85/50 mm Hg, his length was
1 D2 m5 t- U1 l$ }/ H90 cm (>97th percentile), and his weight was 14.4 kg
8 {4 G8 X: b, q6 K0 S6 S(also >97th percentile). The observed yearly growth7 \! o! j( A/ S% [ e
velocity was 30 cm (12 inches). The examination of
* a( ]9 S/ b, x# R/ U Bthe neck revealed no thyroid enlargement.
9 O8 r+ Y5 I' P' i6 [The genitourinary examination was remarkable for
+ m4 y1 {0 E+ B, I( E; m4 uenlargement of the penis, with a stretched length of
: @8 n( t( k8 m' ]* ]+ l- W. {8 cm and a width of 2 cm. The glans penis was very well1 l2 l3 S; e' v% h
developed. The pubic hair was Tanner II, mostly around$ k1 k3 t( ?) {! R4 {( v- E1 P) y
540
4 i1 \+ O0 g4 pat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from' D. p- _( t& R8 f3 m
the base of the phallus and was dark and curled. The
9 g1 h$ N) J1 _; _testicular volume was prepubertal at 2 mL each.
3 h d+ A9 U/ j" DThe skin was moist and smooth and somewhat
4 M. W$ ?+ n6 L- U0 }- i: R; aoily. No axillary hair was noted. There were no
; B- B4 J; H+ o3 D8 }abnormal skin pigmentations or café-au-lait spots.. y; M; a! _, [+ q0 E) n& p: M
Neurologic evaluation showed deep tendon reflex 2+
* K* ?' z# V) W1 ]( s u0 Dbilateral and symmetrical. There was no suggestion
T' K* d7 a; q" o$ n- Rof papilledema.
8 F) r5 m/ O0 C/ R! h8 pLaboratory Evaluation
+ v: i0 M1 a: j$ H7 X3 dThe bone age was consistent with 28 months by
& u" U4 c/ x1 w8 L1 o9 Z. t: e: Wusing the standard of Greulich and Pyle at a chrono-. ~# ?5 s& X5 w0 n/ F9 Q3 R/ E$ o: C
logic age of 16 months (advanced).5 Chromosomal+ Q. y4 R6 _5 e9 d
karyotype was 46XY. The thyroid function test$ A" z) |- J( T
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
" R6 ]7 m& B" B( p4 q6 [lating hormone level was 1.3 µIU/mL (both normal).. l4 G/ b$ m5 e
The concentrations of serum electrolytes, blood
6 o. `/ e4 @- [ _7 eurea nitrogen, creatinine, and calcium all were
* B2 G- O* A4 [5 E8 B L# pwithin normal range for his age. The concentration
- B( j0 e9 g/ ]of serum 17-hydroxyprogesterone was 16 ng/dL N5 M, U) f" `3 k% L+ a
(normal, 3 to 90 ng/dL), androstenedione was 20# Q. V/ c4 I& ?1 I5 M- v+ M4 b3 x
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
( X, O/ {, i) F+ u$ yterone was 38 ng/dL (normal, 50 to 760 ng/dL),
$ o. C. f1 \& w5 [4 C2 I& q: {desoxycorticosterone was 4.3 ng/dL (normal, 7 to4 r% h- y a2 c3 e1 A. w
49ng/dL), 11-desoxycortisol (specific compound S)7 F" \1 L! u( T$ Z
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
, H k4 z6 c* t- B! h- G" f5 _! ]( ktisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
5 W7 w- f" M/ R! Ntestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
' k w! @) S kand β-human chorionic gonadotropin was less than
5 _" w& {8 W6 d% s1 X5 mIU/mL (normal <5 mIU/mL). Serum follicular+ J/ t% [9 Q, @: Y2 i1 Z j
stimulating hormone and leuteinizing hormone
7 F, B8 j$ a% g( M4 p! ^concentrations were less than 0.05 mIU/mL/ L* o: i3 \6 o4 L D2 t
(prepubertal)., }* ^4 y2 q2 i! T4 m
The parents were notified about the laboratory
' M( W) G5 O, a, Z2 tresults and were informed that all of the tests were
0 d$ b+ j- g0 |# A( W5 Y8 j& Vnormal except the testosterone level was high. The
3 n) E( @9 a2 o* g% s+ v6 Kfollow-up visit was arranged within a few weeks to
7 ?! L9 i2 i& y" ]obtain testicular and abdominal sonograms; how-3 t$ {# r+ ^: S( L" D+ O$ s( Y
ever, the family did not return for 4 months.
" S+ i! X1 n8 M* D ~6 XPhysical examination at this time revealed that the/ d4 ^( W. I7 b
child had grown 2.5 cm in 4 months and had gained' k V3 ]7 H( m3 m( z& e
2 kg of weight. Physical examination remained- h; Q0 P) q( U \" K
unchanged. Surprisingly, the pubic hair almost com-. P# K% S D$ C0 ?9 k; k( |, ?
pletely disappeared except for a few vellous hairs at
d* S# H* u/ {9 z! v7 h/ Tthe base of the phallus. Testicular volume was still 25 i( h/ ^5 N+ b
mL, and the size of the penis remained unchanged.
" |# i1 {+ u2 v) g/ Y/ h) L. {- qThe mother also said that the boy was no longer hav-# d3 ?: b2 @- @6 |9 U
ing frequent erections.
+ ]/ w* G; W/ O8 cBoth parents were again questioned about use of3 i. ^* `" q" o+ p) _
any ointment/creams that they may have applied to* N9 @! B2 _8 K' Q
the child’s skin. This time the father admitted the, y4 B! u; H* {0 V l9 x
Topical Testosterone Exposure / Bhowmick et al 5410 X. m( P( e$ M5 ?) Z# B
use of testosterone gel twice daily that he was apply-2 {6 U' b. w) ]3 A* D# S
ing over his own shoulders, chest, and back area for0 _. g2 n( \) X1 |: I0 [
a year. The father also revealed he was embarrassed. q4 G/ D5 y; o% r$ d! s0 H0 g
to disclose that he was using a testosterone gel pre-3 P# K) p" U5 o8 U' y
scribed by his family physician for decreased libido0 m8 U/ L6 V0 x; u+ T6 S& E) Q) B
secondary to depression.! A2 v& _% \6 ]0 E2 F" @
The child slept in the same bed with parents.
. [% z. a, N3 S: S' j- wThe father would hug the baby and hold him on his1 J8 C7 n& |! i6 H) x
chest for a considerable period of time, causing sig-
1 J6 T( k6 }3 H% n2 f0 e/ Knificant bare skin contact between baby and father.. A5 F4 J% h; e' E; D% U
The father also admitted that after the phone call,! g( V8 [: \8 s9 b, k' V p
when he learned the testosterone level in the baby
8 A8 Z( t, ?( n2 w( U# S1 H$ B5 V6 bwas high, he then read the product information
, }3 P! f* h' l* r4 o7 hpacket and concluded that it was most likely the rea-4 a4 M, a3 t0 K' O
son for the child’s virilization. At that time, they
/ }6 P4 K9 {$ s" \ p- Gdecided to put the baby in a separate bed, and the5 ~; Q: e! B9 a7 A' a8 }! K2 _
father was not hugging him with bare skin and had
, Q- z, H8 b% Z# k& [; B3 Bbeen using protective clothing. A repeat testosterone
/ K+ n+ D0 m0 a+ q1 ?test was ordered, but the family did not go to the
6 y$ k) v" h7 g9 {: l% llaboratory to obtain the test.& i6 V; A5 L6 q$ G# w2 W+ {
Discussion
) J1 z5 \: e. ?4 r- }Precocious puberty in boys is defined as secondary0 W' K6 B' N4 [
sexual development before 9 years of age.1,4
/ }- v' @0 e* v3 S) N( m7 k4 UPrecocious puberty is termed as central (true) when
5 ]7 F4 M: q6 w* P% |: [it is caused by the premature activation of hypo-& h2 C9 D/ F; J: o K/ A
thalamic pituitary gonadal axis. CPP is more com-3 M t d) @4 u! [
mon in girls than in boys.1,3 Most boys with CPP
6 K5 d4 O& ~: Tmay have a central nervous system lesion that is
8 a0 N( R& W$ m' hresponsible for the early activation of the hypothal-4 [) F& u. Q& q* l
amic pituitary gonadal axis.1-3 Thus, greater empha-
& `) z' h$ b5 ~sis has been given to neuroradiologic imaging in
8 j2 X* s1 Q1 a* R) b4 u( {boys with precocious puberty. In addition to viril-
" \% d, P' N$ H! d, Kization, the clinical hallmark of CPP is the symmet-3 X+ t0 B9 J5 C: c9 V" s
rical testicular growth secondary to stimulation by
( I1 ~9 C8 z3 Q6 G6 Y' {0 rgonadotropins.1,3
J0 ^/ l/ e( W9 }* c+ lGonadotropin-independent peripheral preco-9 {/ E7 @% M( F% K7 b
cious puberty in boys also results from inappropriate( p/ S. r3 f; g5 S$ f5 c7 _- W$ e
androgenic stimulation from either endogenous or
1 @2 W0 Y) t8 }exogenous sources, nonpituitary gonadotropin stim-
& b0 m7 c# L; b2 @# G: {: g$ vulation, and rare activating mutations.3 Virilizing
! d m4 i3 g) P1 U- a: t* Mcongenital adrenal hyperplasia producing excessive
: [+ c$ l, g2 t/ Gadrenal androgens is a common cause of precocious7 y9 v$ O' x- P9 L
puberty in boys.3,49 Y8 q( H1 t% i& r
The most common form of congenital adrenal, E" s/ r: L6 {3 \
hyperplasia is the 21-hydroxylase enzyme deficiency.
8 l5 P) X5 S1 L, q# kThe 11-β hydroxylase deficiency may also result in
. G: [# Z3 q5 \4 b: Uexcessive adrenal androgen production, and rarely,
4 B$ R: X9 u0 D+ f* b/ Ean adrenal tumor may also cause adrenal androgen
7 p5 d' q4 f- J* Z% @- e9 iexcess.1,3* V6 c& V: W& i2 s
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
6 ?9 V) T: Q" p! [3 b. }542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
, X+ e1 Q2 E: |( BA unique entity of male-limited gonadotropin-$ F. H9 h4 z9 v- u
independent precocious puberty, which is also known( b' M3 ^+ q6 A+ Z2 z: U8 l
as testotoxicosis, may cause precocious puberty at a
! K5 Q+ t+ j3 Q$ ~& Q# _8 cvery young age. The physical findings in these boys
6 G( w* T8 [& Qwith this disorder are full pubertal development,5 ]& L0 M' ~( C9 g, p
including bilateral testicular growth, similar to boys
: J0 A3 E* F& w+ jwith CPP. The gonadotropin levels in this disorder! s7 K+ v/ A' m0 b! J( J2 d4 F
are suppressed to prepubertal levels and do not show& P# |* T% k' Y4 k$ O* e7 r6 G1 s
pubertal response of gonadotropin after gonadotropin-6 T z; B4 {8 r$ t
releasing hormone stimulation. This is a sex-linked R3 X& v8 s( e+ J5 a/ W: F, b# N. I
autosomal dominant disorder that affects only
8 T' s6 d2 D( Y+ Nmales; therefore, other male members of the family) u: e5 j$ ?, o- [" V6 P
may have similar precocious puberty.3
8 g, \8 r3 j! n% i+ P7 _- jIn our patient, physical examination was incon-0 u5 n, _& B: b* I
sistent with true precocious puberty since his testi-( {/ P% Y. j5 }5 K! p
cles were prepubertal in size. However, testotoxicosis
4 B$ s# m/ N" R, v4 Ywas in the differential diagnosis because his father
/ G3 ?' j# l0 L9 E4 J i9 astarted puberty somewhat early, and occasionally,% e/ W# c& z& l" Q3 B% r: W
testicular enlargement is not that evident in the* c! \; V8 ^+ n7 }# h& F- j5 l% H
beginning of this process.1 In the absence of a neg-
# Y; p4 L7 P3 m9 dative initial history of androgen exposure, our% j2 |: }8 c& J7 |" S
biggest concern was virilizing adrenal hyperplasia,
% o, M1 |% F8 C7 `: E4 u- Geither 21-hydroxylase deficiency or 11-β hydroxylase
' N- V! G! C7 E+ ~0 ^! ^deficiency. Those diagnoses were excluded by find-
; M$ I! j6 j) A5 D4 e! w4 l' e7 p7 ding the normal level of adrenal steroids.
8 z1 l/ h5 W" a5 L- l U9 `The diagnosis of exogenous androgens was strongly
2 M" {2 \2 E' i" }1 g: L; ?suspected in a follow-up visit after 4 months because) H& \8 v( D8 ?
the physical examination revealed the complete disap-
5 [; V) |8 C( p x. x3 ypearance of pubic hair, normal growth velocity, and$ v. }! x# o+ Z
decreased erections. The father admitted using a testos-& w- x& \# w3 Z
terone gel, which he concealed at first visit. He was- m( W5 ]9 }$ Z+ H
using it rather frequently, twice a day. The Physicians’
, n V1 W; a- E# g1 dDesk Reference, or package insert of this product, gel or" h8 k" i# f3 L F. \+ w' v
cream, cautions about dermal testosterone transfer to
* F6 p. E K, w* U3 Sunprotected females through direct skin exposure.5 z6 m. \" [, K. N$ q/ y; Z) K: S/ `
Serum testosterone level was found to be 2 times the
) [. n$ Z4 |2 \: ^2 V/ l* h- x4 zbaseline value in those females who were exposed to
/ E0 D+ W$ C- p3 [3 M5 C' g3 Z' F* reven 15 minutes of direct skin contact with their male8 T8 T1 M+ ^" h' N6 v9 h0 ^
partners.6 However, when a shirt covered the applica-( R9 Y. I6 Q Y, d$ \
tion site, this testosterone transfer was prevented.0 n; B X5 W1 d+ k
Our patient’s testosterone level was 60 ng/mL,- J6 m- V; G1 ]5 A
which was clearly high. Some studies suggest that' |6 Q6 B h8 q- A! T, }
dermal conversion of testosterone to dihydrotestos-* d4 X* e$ V6 I/ v
terone, which is a more potent metabolite, is more
5 y& X. t/ ?& [+ X% h; y7 ~active in young children exposed to testosterone
3 B2 b) q* i. a' C- m" P) B( }exogenously7; however, we did not measure a dihy-
0 ~3 G7 R( Q1 h' Idrotestosterone level in our patient. In addition to7 m$ w% H" M' V2 l- Y. V
virilization, exposure to exogenous testosterone in; S2 ?" L- g# k1 V ]) U) ?0 r
children results in an increase in growth velocity and
+ U% P4 x: X \) V' @4 jadvanced bone age, as seen in our patient.
8 x7 o2 z8 K5 Q+ d! XThe long-term effect of androgen exposure during7 \9 u' R/ ^7 K: g8 c$ E
early childhood on pubertal development and final+ {0 e5 e8 q7 \2 O
adult height are not fully known and always remain
( B! U- Q1 S3 R2 La concern. Children treated with short-term testos-8 q7 Z0 a& K+ }
terone injection or topical androgen may exhibit some. v* O" {4 f8 [" o' F
acceleration of the skeletal maturation; however, after
& o) ?8 s) c7 |cessation of treatment, the rate of bone maturation
' I* S6 }+ k" ?7 Q6 X; Pdecelerates and gradually returns to normal.8,9" }$ y0 |% d7 j8 x O( K) Y6 k
There are conflicting reports and controversy4 t& v& S4 B5 `- H: B" P4 a
over the effect of early androgen exposure on adult7 ~9 h; T# [2 e* \% K9 r1 q
penile length.10,11 Some reports suggest subnormal
_2 G9 e# p1 ?6 u: Z7 qadult penile length, apparently because of downreg-0 F4 H4 V9 r% }4 p/ c
ulation of androgen receptor number.10,12 However,
( p( S% E) b% L/ H/ o' [" HSutherland et al13 did not find a correlation between
. s% t4 [5 o5 N3 L- T/ f+ d- ?childhood testosterone exposure and reduced adult
, ?- _' U8 b4 ?# {7 r) M+ A. Mpenile length in clinical studies. n F+ r( b5 R! e3 q# x+ {# J
Nonetheless, we do not believe our patient is
]( K3 h, U) T# D: Sgoing to experience any of the untoward effects from: l8 d) G6 E# z* F( r7 o! d* C
testosterone exposure as mentioned earlier because
( a( ~ {& T. w! M. }# ?5 |' ]the exposure was not for a prolonged period of time.
9 R# k9 c& _2 B1 |1 D# _Although the bone age was advanced at the time of$ `! j/ w1 M: S: K& x
diagnosis, the child had a normal growth velocity at) t0 n6 _. l# b1 ?% \
the follow-up visit. It is hoped that his final adult+ }2 s7 k8 U+ n. I3 L
height will not be affected.
8 F: K& A7 p9 @1 v. fAlthough rarely reported, the widespread avail-. F7 p! C+ Y" `: Z, T
ability of androgen products in our society may- ]( D, q: y& n, N5 N
indeed cause more virilization in male or female1 N. e* n g% q, L
children than one would realize. Exposure to andro-9 G) D1 p% m5 l
gen products must be considered and specific ques-9 B6 y( S5 u ?( W# `" |! O
tioning about the use of a testosterone product or. M7 e& G' `- Z# D: e, N% ~4 G q
gel should be asked of the family members during J3 C H: m4 s' h
the evaluation of any children who present with vir-
- Q8 ~# D5 i; R2 Z& H9 m+ zilization or peripheral precocious puberty. The diag-9 Y* e8 M2 Q8 q
nosis can be established by just a few tests and by! g6 B: @ j; _6 L
appropriate history. The inability to obtain such a
0 W& X, S' i9 |0 Shistory, or failure to ask the specific questions, may; \; _, r' Y& w7 [7 o
result in extensive, unnecessary, and expensive8 j) L8 H5 d X5 Q( D( n
investigation. The primary care physician should be8 e0 s% [& P. V
aware of this fact, because most of these children
9 ~) _+ @. d# ]may initially present in their practice. The Physicians’
7 l0 [- ~! ?0 y6 c( CDesk Reference and package insert should also put a: V* Y! i& V9 u; L
warning about the virilizing effect on a male or9 M6 x$ ~. h" D* f
female child who might come in contact with some-4 z8 g. r u9 P4 A
one using any of these products.
& G7 O1 [1 Z: b; J L6 ^2 N# R. o1 qReferences- Z$ M% F/ {, [6 o
1. Styne DM. The testes: disorder of sexual differentiation5 E+ A9 I# U9 e2 z
and puberty in the male. In: Sperling MA, ed. Pediatric5 ?2 w" |- y4 a6 w: O7 U
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;! \; p% I. R: h; r" m! J4 N, ~
2002: 565-628.* J! m2 X$ P2 { b- I8 k* G
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious# | w1 h+ N" i) R" r
puberty in children with tumours of the suprasellar pineal |
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