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Sexual Precocity in a 16-Month-Old, n' o, T, W1 T1 s
Boy Induced by Indirect Topical
1 P, l5 h: {# B# t" M. t; ?% OExposure to Testosterone, ] U9 \+ m3 z7 ?$ s
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,23 H6 G! ]) U& _/ P' X
and Kenneth R. Rettig, MD1
% I, \+ V$ X/ f8 I7 aClinical Pediatrics' x; E# z* i1 e) S9 S* h" I/ i
Volume 46 Number 6
4 Y; d {# v/ m% u; o/ oJuly 2007 540-543: u3 Q# c1 n8 X H# \
© 2007 Sage Publications
. L) J* ?. ?& a( w- n10.1177/00099228062966515 [8 V" l/ V4 F& n( e3 V9 m2 K
http://clp.sagepub.com
7 C+ }$ _" c/ }& Z" }/ ehosted at& D7 [- z# g9 ~9 Y1 s7 o2 A
http://online.sagepub.com5 Q. Z7 U$ T/ u$ C. Y; e8 @
Precocious puberty in boys, central or peripheral,6 w b( N1 o$ a( Q: T$ }9 G* d
is a significant concern for physicians. Central
# J: Q% g% R3 z% o/ w2 \precocious puberty (CPP), which is mediated
$ A9 |8 M* p B; H6 [, B; ? Vthrough the hypothalamic pituitary gonadal axis, has# ?5 T! X5 L) u' Y8 g8 h
a higher incidence of organic central nervous system
3 z) V/ W" s1 p. ~0 T7 G' S; glesions in boys.1,2 Virilization in boys, as manifested
! @& s$ t. t, V6 N9 Q3 Pby enlargement of the penis, development of pubic
$ D! ~8 ~4 [3 Vhair, and facial acne without enlargement of testi-; @0 [. M% K1 s# C
cles, suggests peripheral or pseudopuberty.1-3 We
* D$ U7 j c; y* z4 ~" K' x1 }2 Lreport a 16-month-old boy who presented with the
9 U$ [" V5 \9 Eenlargement of the phallus and pubic hair develop-& }7 ]6 X7 N+ E' D6 R
ment without testicular enlargement, which was due
8 X7 K) K6 _) Y# }to the unintentional exposure to androgen gel used by
0 ?0 p: z4 q$ n6 }$ e) fthe father. The family initially concealed this infor-% |& q; E/ s* L* Z8 v
mation, resulting in an extensive work-up for this
, q. C! q, S1 b! y* Kchild. Given the widespread and easy availability of6 I9 D% O. v: u( e( B" }2 d
testosterone gel and cream, we believe this is proba-
3 O! N+ ~6 R1 f& g- lbly more common than the rare case report in the8 ]& K- T5 E$ c
literature.4
$ B3 G7 u- G' s7 \/ s- D. O4 EPatient Report! j8 u4 @# k- @7 u* w" R# k- o1 X
A 16-month-old white child was referred to the
, p! p# w0 `1 @) e$ A2 Nendocrine clinic by his pediatrician with the concern. z8 |1 A/ B# n( \1 X% P0 r
of early sexual development. His mother noticed; T- ^& Z& {) u2 {+ R, R$ U
light colored pubic hair development when he was
$ t! |9 x# y/ e' OFrom the 1Division of Pediatric Endocrinology, 2University of# U4 a* ]" @4 J' {& q# ?6 x+ q! `
South Alabama Medical Center, Mobile, Alabama.9 \8 \- |" e# g# K
Address correspondence to: Samar K. Bhowmick, MD, FACE,$ v3 z! Z% ?: f9 h
Professor of Pediatrics, University of South Alabama, College of
6 }# D3 p5 r- F& d+ @Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;+ s2 e- E4 B- @: p1 G
e-mail: [email protected].8 O- K1 W8 w L$ Q# L3 z
about 6 to 7 months old, which progressively became
& r* `5 p5 D6 w1 i, R$ S0 jdarker. She was also concerned about the enlarge-
9 p& p+ t: `& m- T3 E! `$ N& wment of his penis and frequent erections. The child- I4 d2 p; t' m) R7 v# }
was the product of a full-term normal delivery, with
5 T6 i" O# q( b0 I' @. v. r: Ca birth weight of 7 lb 14 oz, and birth length of
/ z( V( J- w6 e$ Z20 inches. He was breast-fed throughout the first year ]% A j7 k- [3 l6 h- \! J
of life and was still receiving breast milk along with) {0 l; s0 C2 C7 C! C' F. ~8 f
solid food. He had no hospitalizations or surgery,# |$ f# t; n4 L
and his psychosocial and psychomotor development
9 W1 k3 ]$ _8 F2 v# a, ewas age appropriate.. L9 F- @1 b# Y6 |$ H* q
The family history was remarkable for the father,4 ]3 ~/ `3 g. H" ~
who was diagnosed with hypothyroidism at age 16,
' x; h1 b3 ?9 B: gwhich was treated with thyroxine. The father’s8 X- o1 M+ |% m5 i p1 m! F
height was 6 feet, and he went through a somewhat, W9 @* h" [2 m6 T% h
early puberty and had stopped growing by age 14./ j5 T* B. X0 M! ~7 h1 M4 O# i# u
The father denied taking any other medication. The
W5 { R0 C) T8 k! i" }0 cchild’s mother was in good health. Her menarche& h9 C4 o. ?0 V& P
was at 11 years of age, and her height was at 5 feet
: i# j; W8 x+ m5 inches. There was no other family history of pre-
( \4 G5 h* i( t( ` V- Jcocious sexual development in the first-degree rela-2 D& Q* Z+ r& M1 x1 j
tives. There were no siblings.
( ^2 c" L3 }3 y" O' APhysical Examination' D$ U. X2 E& H# e T F1 d% r
The physical examination revealed a very active,5 E* s% H4 X. K" D ~3 a
playful, and healthy boy. The vital signs documented) j+ h5 C0 @. ~; j9 Q
a blood pressure of 85/50 mm Hg, his length was
( q/ L+ A1 z5 X! L; _& S8 @0 t1 O: X90 cm (>97th percentile), and his weight was 14.4 kg
$ q! @/ S# u4 Q(also >97th percentile). The observed yearly growth% I. ~1 a* C; R" e: G
velocity was 30 cm (12 inches). The examination of
2 R+ Z% |- x' |% E# r" ~$ _( w3 A+ Nthe neck revealed no thyroid enlargement.
6 u, X) a8 c5 pThe genitourinary examination was remarkable for: o- C b( W) {
enlargement of the penis, with a stretched length of
2 v" m1 a0 M$ b6 d8 cm and a width of 2 cm. The glans penis was very well4 O* Z' k! H0 Y5 t/ H8 E7 i
developed. The pubic hair was Tanner II, mostly around- C/ S& N" w0 p9 b1 f
540
3 D5 ]( X6 ?6 [0 O9 Oat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
" H. h! B$ C/ ]5 ?) U# C; ythe base of the phallus and was dark and curled. The
7 R! ^( k0 ^, q; h& dtesticular volume was prepubertal at 2 mL each.9 o; ]& T% M; O& e2 l1 Y
The skin was moist and smooth and somewhat- W6 [; y5 c4 ^6 K
oily. No axillary hair was noted. There were no
* _5 m& J+ t% Jabnormal skin pigmentations or café-au-lait spots.
0 j; l) o4 L5 `/ W+ c* p2 dNeurologic evaluation showed deep tendon reflex 2+2 M1 V$ y6 v6 `7 H! l
bilateral and symmetrical. There was no suggestion- f1 R) n0 P n; W1 ~- a4 q$ T
of papilledema.6 L4 ?) J \# V3 L3 F
Laboratory Evaluation5 f) J8 D8 m& |/ U& L" n
The bone age was consistent with 28 months by- _$ s* B' ^* O& ~' }& ]
using the standard of Greulich and Pyle at a chrono-+ l8 I8 \& _, U0 J5 \; @, o- I: B" w
logic age of 16 months (advanced).5 Chromosomal2 Q0 t7 T3 Z H b7 U' K2 v7 Q
karyotype was 46XY. The thyroid function test3 R5 s& o! r; b) ^8 u
showed a free T4 of 1.69 ng/dL, and thyroid stimu-9 N$ W" ^- w' z* c" h9 h. \, {
lating hormone level was 1.3 µIU/mL (both normal).
% d( g, t! P, b, [* h% c8 ?The concentrations of serum electrolytes, blood& Z7 f5 ]& H% H6 ?# c
urea nitrogen, creatinine, and calcium all were& e/ M) [/ k9 Y$ o
within normal range for his age. The concentration
. o/ P- W: m, J) H. yof serum 17-hydroxyprogesterone was 16 ng/dL' c' ?# x5 l# K3 R6 b- q( v
(normal, 3 to 90 ng/dL), androstenedione was 20
5 O- h2 ]) M! p5 t& ]ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
7 m% L8 J0 j# {( L$ s) u8 yterone was 38 ng/dL (normal, 50 to 760 ng/dL),
6 L: T8 C7 l* j. hdesoxycorticosterone was 4.3 ng/dL (normal, 7 to
: y+ I% o5 l5 z. d6 H( ]3 i' v: q49ng/dL), 11-desoxycortisol (specific compound S)
1 O6 I; v* q% Q0 Z- k; kwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-( P% \7 o1 I( t" b) r
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total, |4 B$ t9 z4 g2 r% W6 v- [7 t ~
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),% `1 e4 C. E1 Y
and β-human chorionic gonadotropin was less than6 ]: t4 Q& Z: ~' k( C
5 mIU/mL (normal <5 mIU/mL). Serum follicular
& D9 Z* z- \" m4 e( K; |stimulating hormone and leuteinizing hormone. M# r% r" k0 [& {2 w
concentrations were less than 0.05 mIU/mL# k+ K, J3 t# R# n
(prepubertal).6 ^- _9 v* c; [$ q
The parents were notified about the laboratory
$ H+ q0 p9 t: S) V+ I6 Wresults and were informed that all of the tests were- z7 ]- O9 F9 t& ^" N3 `& F
normal except the testosterone level was high. The
. H8 l$ @$ p) U+ v! b% n6 nfollow-up visit was arranged within a few weeks to: B/ C0 t4 C/ t+ I
obtain testicular and abdominal sonograms; how-
* ^2 k1 ~) x* I' O' G: Qever, the family did not return for 4 months.: g: B ]" x! N+ C
Physical examination at this time revealed that the
1 N! ]9 [; r+ z! C: B z3 Nchild had grown 2.5 cm in 4 months and had gained% D* b* Z& x5 Z* W! _
2 kg of weight. Physical examination remained. D% u6 r1 O$ P/ y
unchanged. Surprisingly, the pubic hair almost com-/ x$ b7 A! n. ?6 K
pletely disappeared except for a few vellous hairs at
& l U% v1 {' L# C$ Kthe base of the phallus. Testicular volume was still 2
+ S- I1 m6 z4 P0 m4 L& PmL, and the size of the penis remained unchanged.
# D9 G; t& v4 F$ AThe mother also said that the boy was no longer hav-) v# H$ W2 y6 v9 o
ing frequent erections.
d: U+ X2 B" x' B8 J! w. }Both parents were again questioned about use of; N3 b9 |, ^; U
any ointment/creams that they may have applied to
/ x* z) H# V; Sthe child’s skin. This time the father admitted the
2 x5 s5 Y! a& _7 W. t; f/ UTopical Testosterone Exposure / Bhowmick et al 541
) r1 D$ t: J7 [5 _$ Y$ P' ruse of testosterone gel twice daily that he was apply- M3 E: N/ K$ a) i
ing over his own shoulders, chest, and back area for# i+ b. L9 h9 Q0 l) X, r, F4 l
a year. The father also revealed he was embarrassed
& R1 ]% a) h" K) rto disclose that he was using a testosterone gel pre-/ k% L) s! Y2 F0 @. n" h
scribed by his family physician for decreased libido
* ?. ^2 ?; T6 A7 D+ n# lsecondary to depression.
* V! s% v9 H5 b0 z6 L) UThe child slept in the same bed with parents.
5 {+ G7 R9 Z1 {4 LThe father would hug the baby and hold him on his. ]* G5 [) r3 o* S
chest for a considerable period of time, causing sig-
' T3 O* p) p* x# Y) x# c3 Unificant bare skin contact between baby and father.+ B- ]' e+ q$ O& I1 H6 x
The father also admitted that after the phone call,
) p1 \ b' r: y& {% |) K* a: J9 ~! zwhen he learned the testosterone level in the baby
9 w" m- w8 r/ y$ Wwas high, he then read the product information
# X6 r# Z$ p( `2 @, qpacket and concluded that it was most likely the rea-
; z4 d" L/ o# zson for the child’s virilization. At that time, they
F( L0 v$ p1 \; Xdecided to put the baby in a separate bed, and the
. J- K9 @' H( d0 V$ t2 _) t5 rfather was not hugging him with bare skin and had: v. I' o2 m5 D
been using protective clothing. A repeat testosterone
6 v/ [# h- Z7 g" btest was ordered, but the family did not go to the
+ ?5 a1 M4 D/ C9 y- F1 Slaboratory to obtain the test.
5 X4 [6 r% U2 A( \8 zDiscussion9 G" W, ~3 ^" n, r3 U
Precocious puberty in boys is defined as secondary5 p3 y0 _7 ]+ [$ I& q1 u' j/ d1 E1 k' d
sexual development before 9 years of age.1,4+ H) J, \# h1 U# K
Precocious puberty is termed as central (true) when8 R* J4 D# S" ^% n& M W, j+ r
it is caused by the premature activation of hypo-! e, f9 Z$ c& @4 {/ U1 L
thalamic pituitary gonadal axis. CPP is more com-
( Z% ^6 Y/ D9 g# M6 Q3 c9 t& Tmon in girls than in boys.1,3 Most boys with CPP
6 \' i" {! F; V0 Y9 {may have a central nervous system lesion that is5 C% X0 N" T7 n( [
responsible for the early activation of the hypothal-' K: q' u: C: W' S$ O
amic pituitary gonadal axis.1-3 Thus, greater empha-- W2 ]& A3 B9 O; ^
sis has been given to neuroradiologic imaging in
2 b1 `! l8 u7 a- U/ Cboys with precocious puberty. In addition to viril-
" Y$ q7 R' p3 _6 c+ o9 k6 fization, the clinical hallmark of CPP is the symmet-. T5 ]. ~/ [5 u: d l, [
rical testicular growth secondary to stimulation by
9 n( ~1 g% G6 N) n2 q8 kgonadotropins.1,35 h, _4 P& V. q/ M2 k: ]
Gonadotropin-independent peripheral preco-8 h! f. \0 t7 x9 r
cious puberty in boys also results from inappropriate- p2 g( \2 ?( u4 G. P1 }
androgenic stimulation from either endogenous or
5 u% K- j- C& d) r2 h7 z; I2 [: nexogenous sources, nonpituitary gonadotropin stim-) a* w2 E" ` E0 L) H" f2 Y( v
ulation, and rare activating mutations.3 Virilizing& B7 p h- h6 Z! |8 {# X
congenital adrenal hyperplasia producing excessive
7 a; ~, F. |( q; A# U1 Xadrenal androgens is a common cause of precocious
3 ^: ~) @# D5 z* t: G5 L0 z% l2 Wpuberty in boys.3,4
, ^) u& U/ `7 g# M1 v5 o1 dThe most common form of congenital adrenal1 k* T3 n( a% ?2 i$ `1 d
hyperplasia is the 21-hydroxylase enzyme deficiency.
7 c7 h/ S2 m( r+ fThe 11-β hydroxylase deficiency may also result in: |( V2 O+ m+ s3 y
excessive adrenal androgen production, and rarely,7 ^% ]# Q6 _* Q
an adrenal tumor may also cause adrenal androgen) ]+ z. ~7 l- q) U. ^
excess.1,36 b3 p9 ?1 D4 R; g" y
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from$ x( X, w# L6 E' D# ]" u0 a
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007, x: C \. `, J, e
A unique entity of male-limited gonadotropin-, r9 j: E. {; Q" v/ }1 h
independent precocious puberty, which is also known$ [0 e4 a7 S9 E9 m! L6 ^) y
as testotoxicosis, may cause precocious puberty at a6 ~8 O3 F/ x3 ? Y' v
very young age. The physical findings in these boys/ j0 a: y) X0 I& w, d9 k
with this disorder are full pubertal development,
' B, I' ] W5 Sincluding bilateral testicular growth, similar to boys
$ p' P. v1 ~$ q0 P5 H& r; gwith CPP. The gonadotropin levels in this disorder
$ v- d; x' H8 oare suppressed to prepubertal levels and do not show' K* @" f( `( X9 o% z$ L
pubertal response of gonadotropin after gonadotropin-% @ n; o. q3 A$ z- X* r
releasing hormone stimulation. This is a sex-linked" g) f. |, B0 z1 T* s- r
autosomal dominant disorder that affects only3 P* B$ `* ?1 q) Q; Z
males; therefore, other male members of the family$ }: m4 i: F; }8 p
may have similar precocious puberty.3; \/ Y4 l$ p+ ?: ]3 N
In our patient, physical examination was incon-$ W% J" S" m3 P/ b' e3 s
sistent with true precocious puberty since his testi-
( K. J, I. z6 s( A ` Dcles were prepubertal in size. However, testotoxicosis
3 f% R/ |: d% g" wwas in the differential diagnosis because his father/ a( m/ B- Q0 t/ g! S2 R+ c
started puberty somewhat early, and occasionally,
- u, J6 |/ _2 a. G5 B0 A/ i0 r. rtesticular enlargement is not that evident in the5 O% w3 V. N1 D. n! d
beginning of this process.1 In the absence of a neg-
% B( s" r6 B4 m4 ]) N, s3 k2 s- ]$ Sative initial history of androgen exposure, our0 @( y/ L" ?# c9 s/ X7 B, V
biggest concern was virilizing adrenal hyperplasia,, _+ a% Y$ V8 V& O5 R7 D
either 21-hydroxylase deficiency or 11-β hydroxylase+ m4 p2 A) ?7 F+ e: B$ N, n" z7 G& ?
deficiency. Those diagnoses were excluded by find-
) u$ p' T3 k4 l. B% I" Z2 ying the normal level of adrenal steroids.
# H2 j' c8 ]4 hThe diagnosis of exogenous androgens was strongly9 G0 i0 k+ M! w% k# H# P
suspected in a follow-up visit after 4 months because. _* C& T' ]2 I
the physical examination revealed the complete disap-
/ c1 u5 o; g$ L" s) Jpearance of pubic hair, normal growth velocity, and2 U! [5 M5 E, E# Z* c, w
decreased erections. The father admitted using a testos-
+ ?" N9 y0 u4 B; E! _terone gel, which he concealed at first visit. He was
+ x, C3 I1 ^" {, A; q! s6 T( fusing it rather frequently, twice a day. The Physicians’
+ U9 ?7 H; n6 X3 @5 }; o/ l4 s3 x9 q' bDesk Reference, or package insert of this product, gel or4 G4 N$ y$ A. y% U/ h% e3 U e
cream, cautions about dermal testosterone transfer to
2 K" L: Y5 R7 L$ Y% w# y0 K: uunprotected females through direct skin exposure.
8 z) B" o/ z4 n1 E) CSerum testosterone level was found to be 2 times the
" O) w) s1 l- rbaseline value in those females who were exposed to
) A& Y/ y5 O! ^8 n) i: feven 15 minutes of direct skin contact with their male( A& a- H% Z* P- \' [" j8 A) _
partners.6 However, when a shirt covered the applica-/ i) i5 ?1 ?+ z5 @& v* i" V
tion site, this testosterone transfer was prevented.+ b" h- a( y* q2 Z6 f( D
Our patient’s testosterone level was 60 ng/mL,6 p4 s" e1 b" E5 N( k% ^- q$ X
which was clearly high. Some studies suggest that( f) B, k! x' q0 N6 C7 \8 H) W5 D2 m
dermal conversion of testosterone to dihydrotestos-2 \) R, k& J, Q
terone, which is a more potent metabolite, is more
- P l5 e" M/ s% xactive in young children exposed to testosterone/ B9 X6 h! J7 p* ?6 o" z
exogenously7; however, we did not measure a dihy-! g' G1 v3 I& }+ H! o" \5 _9 X
drotestosterone level in our patient. In addition to
8 j0 ?, x7 C4 M, avirilization, exposure to exogenous testosterone in
& y2 Y/ V0 k% C; k" f6 S( _0 t! rchildren results in an increase in growth velocity and
2 b* ^" m, Q# Z/ I7 aadvanced bone age, as seen in our patient.( [0 _( @3 h5 |7 P
The long-term effect of androgen exposure during$ [3 h9 x, u) o+ i* ^- h
early childhood on pubertal development and final2 f [. O( o6 o) L
adult height are not fully known and always remain8 U8 }+ \8 V0 j5 ^3 d0 \
a concern. Children treated with short-term testos-) @! T% f8 M0 y t" r$ ` m
terone injection or topical androgen may exhibit some
4 h! H- ~. Q6 m0 Z$ N) dacceleration of the skeletal maturation; however, after
- k7 N9 Y/ f4 W6 t* K4 _cessation of treatment, the rate of bone maturation
& o" w9 k& W* h$ r$ u* y; ^decelerates and gradually returns to normal.8,9
7 i0 J- A9 B2 {- J' nThere are conflicting reports and controversy; _9 ^& P' H% X0 l9 P
over the effect of early androgen exposure on adult1 c T( y/ b: U1 t, E( F- [, e
penile length.10,11 Some reports suggest subnormal# t$ Z+ V4 d1 _$ w/ x6 s- f9 u3 K
adult penile length, apparently because of downreg-. L0 J% b! r* x. m* H: v
ulation of androgen receptor number.10,12 However,
' |1 i/ o& @" z& R1 u4 W$ Z9 t+ CSutherland et al13 did not find a correlation between
1 f% ^) z% F9 u) U5 m( bchildhood testosterone exposure and reduced adult
5 z V: F$ r5 I0 l3 Lpenile length in clinical studies.
5 C7 }+ O7 B& B1 @9 |Nonetheless, we do not believe our patient is
F! V$ ?' {6 ~) Ggoing to experience any of the untoward effects from
( _3 M/ @4 e5 j: m0 Ztestosterone exposure as mentioned earlier because
) H Q7 h& |' qthe exposure was not for a prolonged period of time.
. K* m, `0 s2 H+ i& y' HAlthough the bone age was advanced at the time of% E5 V. h2 E- e4 o1 H
diagnosis, the child had a normal growth velocity at
% w2 y/ o# C H5 Y) k( H0 ethe follow-up visit. It is hoped that his final adult
# p# n, B+ V, s' \: ]height will not be affected.
, P- A% ]) t! H* o) Q8 mAlthough rarely reported, the widespread avail-
8 _) d; K& `+ U' c, g3 Gability of androgen products in our society may
' v- y. D% b& w( y5 Qindeed cause more virilization in male or female
4 N5 q1 w3 J4 L& ^9 A. `children than one would realize. Exposure to andro-0 ? G Q- r0 f
gen products must be considered and specific ques-
2 m' h* v8 f9 J* _' z' o8 ationing about the use of a testosterone product or
- h% C! s4 m7 R7 _2 K/ x" jgel should be asked of the family members during
% x0 v4 `2 ~2 ?! U! J# X9 i# ] hthe evaluation of any children who present with vir-
" @& S+ i0 _. j4 p3 `ilization or peripheral precocious puberty. The diag-
) G9 `7 ^. F M7 k9 n* p6 I8 {nosis can be established by just a few tests and by
7 y% t7 J& }% [/ Z7 Cappropriate history. The inability to obtain such a
: ?$ D! \, S" f5 _9 Phistory, or failure to ask the specific questions, may: M ? Z; @4 v: I: w
result in extensive, unnecessary, and expensive$ K/ R+ k7 _$ n, e U3 K1 ~6 @# C) ^
investigation. The primary care physician should be9 ^7 U& N/ A, t0 Q
aware of this fact, because most of these children
* ?2 g( j) Q3 G8 A, |+ j3 {may initially present in their practice. The Physicians’: w: Z6 F0 [0 a: o
Desk Reference and package insert should also put a
& V. U. ~3 D9 Y6 ~- awarning about the virilizing effect on a male or" ^& ]4 b; ~ Y+ ^7 u: u
female child who might come in contact with some-# y7 v! j, T+ J4 t4 g
one using any of these products.6 \# v" o5 _) K% b
References, Q1 \+ y r9 d8 I* q
1. Styne DM. The testes: disorder of sexual differentiation3 a! `) J/ |4 D7 Z+ v' h1 q
and puberty in the male. In: Sperling MA, ed. Pediatric
* b5 r8 X2 {" o% G9 F5 C4 X+ IEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
( h1 M. d* N6 g, _6 P2002: 565-628.
9 m* B. g# N7 o2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
( }- s5 ^& f8 l& G4 M) _puberty in children with tumours of the suprasellar pineal |
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