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Sexual Precocity in a 16-Month-Old
. i# Y; P' o0 a! BBoy Induced by Indirect Topical
1 R5 t( h9 O- l, pExposure to Testosterone9 W( F% n5 U) V" u
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2! `; Q# r* ^0 p n3 m/ m
and Kenneth R. Rettig, MD1
# c6 a4 g) `: S3 @6 ]* XClinical Pediatrics* R0 u5 I6 p2 W1 _! C, o
Volume 46 Number 6 ~( c- s7 L+ s# M# x# {& }. f
July 2007 540-543, u! I. W1 q4 `8 |2 w; o
© 2007 Sage Publications6 V: h: B* w, _+ J7 f0 T7 k
10.1177/0009922806296651, j4 u8 T* G6 c: }- U
http://clp.sagepub.com- a$ y, L6 F. l9 _
hosted at1 f; U" {* d% L/ n; k
http://online.sagepub.com
0 R1 B) v7 X. V7 h7 p: yPrecocious puberty in boys, central or peripheral,& ^* {6 }1 D5 M5 W
is a significant concern for physicians. Central
7 l- Z2 @. [! D( m8 Y2 x5 I' Mprecocious puberty (CPP), which is mediated
' c Q! V2 \9 k' L$ ]7 qthrough the hypothalamic pituitary gonadal axis, has$ C& |4 ~2 L, m" |. \, Z
a higher incidence of organic central nervous system2 g7 R% |0 r9 q5 U( i
lesions in boys.1,2 Virilization in boys, as manifested! a7 ?0 A, s5 R% Y: C g+ }% e
by enlargement of the penis, development of pubic, Q' A" j- A0 I5 y: J$ M' R( M9 X
hair, and facial acne without enlargement of testi-
$ {/ v3 t& T$ w$ ~9 P6 dcles, suggests peripheral or pseudopuberty.1-3 We: p0 {; H0 m( Z% \
report a 16-month-old boy who presented with the7 P# |! u; p+ K, V0 Q
enlargement of the phallus and pubic hair develop-
% T# L0 S7 i9 r7 q* x0 Yment without testicular enlargement, which was due
% |0 o& f* p, z+ Vto the unintentional exposure to androgen gel used by
2 O: {6 S7 _ T. Wthe father. The family initially concealed this infor-
" J& f/ u% t# v$ E0 O: omation, resulting in an extensive work-up for this
! t+ y. R: X8 M- bchild. Given the widespread and easy availability of" i/ X* U5 N5 v7 Y& E8 y
testosterone gel and cream, we believe this is proba-5 V( i/ n& o, N) F' v: E, h6 v
bly more common than the rare case report in the/ A' J- s& {3 r! e/ a' X
literature.4/ b: @' @' Q* i
Patient Report
; Y* L5 X- v$ M0 i5 ZA 16-month-old white child was referred to the
W' u/ G" g, Z/ P/ V! l) C& hendocrine clinic by his pediatrician with the concern; Q( @0 F3 O! t4 Y z) w+ }
of early sexual development. His mother noticed
1 L: \6 C, p" u$ v# m( [light colored pubic hair development when he was7 u0 D& A1 O( `& h9 Q
From the 1Division of Pediatric Endocrinology, 2University of
) f2 l2 d! ]) ~ {6 B, n. W& lSouth Alabama Medical Center, Mobile, Alabama.4 \9 y" \+ }: D0 Q+ p, v- z0 L
Address correspondence to: Samar K. Bhowmick, MD, FACE,: F: _; p! d8 d+ f9 Z
Professor of Pediatrics, University of South Alabama, College of
1 u! l* I a2 f- }+ Z; ] FMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
) c9 @; x, v6 V- N' E' X0 De-mail: [email protected].& }2 p$ O' N5 E7 u/ [5 a
about 6 to 7 months old, which progressively became
" M2 ?: ^5 P( a- x6 E: ]darker. She was also concerned about the enlarge-0 ]; s# b K+ Q# H- _
ment of his penis and frequent erections. The child( I- E* i1 ~ F" {7 n7 [1 }# c
was the product of a full-term normal delivery, with7 o; i- x. T4 r# j3 Z4 k
a birth weight of 7 lb 14 oz, and birth length of; f4 _( W/ H0 r# f& ^+ j3 t
20 inches. He was breast-fed throughout the first year4 f5 J" o3 N2 P2 j, n6 Z$ b) k- ~* t
of life and was still receiving breast milk along with7 |5 r/ _ c$ M; q9 u8 k! u/ N8 u
solid food. He had no hospitalizations or surgery,. G6 D( B, e$ Q9 q- `. X
and his psychosocial and psychomotor development
1 B5 Z6 P5 m% nwas age appropriate.4 a; d5 K, O& }$ A( S
The family history was remarkable for the father,' S3 Z5 l! C4 W/ E
who was diagnosed with hypothyroidism at age 16,4 \$ I) p/ j5 I8 P. W8 M
which was treated with thyroxine. The father’s/ }( K" i/ p9 G5 @$ _
height was 6 feet, and he went through a somewhat
1 J' G/ G1 A: L+ l. K# mearly puberty and had stopped growing by age 14.0 _% h, v$ M# d5 O( y- q
The father denied taking any other medication. The8 S. m9 I. X8 b
child’s mother was in good health. Her menarche
5 S+ S* \' ^5 O+ o+ T- fwas at 11 years of age, and her height was at 5 feet
9 p7 A5 m3 `* D5 inches. There was no other family history of pre-/ ^6 p4 w0 R9 u$ o! t
cocious sexual development in the first-degree rela-# s' k# R4 q1 @) f
tives. There were no siblings.
Z% z4 X3 I( s2 }" p' b ZPhysical Examination
. x0 R3 U1 c" ]! P% q7 Z' N$ _# W# nThe physical examination revealed a very active,
$ K3 S( D- b/ o. {8 w3 J3 nplayful, and healthy boy. The vital signs documented
+ ~, N4 d) u. g: m, D2 X Ja blood pressure of 85/50 mm Hg, his length was
, G; d, e' |. e: |# K90 cm (>97th percentile), and his weight was 14.4 kg
" U4 e" `1 }" M8 O) h(also >97th percentile). The observed yearly growth3 h. T1 \3 a! O& ]" ~1 Z* w$ m
velocity was 30 cm (12 inches). The examination of! P8 w" {& E/ D% g6 B& h
the neck revealed no thyroid enlargement.6 q5 w8 O: j* h: T
The genitourinary examination was remarkable for
" y( {# ]6 X2 Z1 F9 oenlargement of the penis, with a stretched length of4 `9 {: N+ {! V1 A$ u @- i, C
8 cm and a width of 2 cm. The glans penis was very well
; R2 ]6 w O7 @- W% \5 qdeveloped. The pubic hair was Tanner II, mostly around/ D0 ]0 X% O9 B+ _! ~' t5 E
540
+ p- w& Z7 N1 B; bat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from3 q9 M! e( Z/ H. k
the base of the phallus and was dark and curled. The* ~. U9 W. r$ q
testicular volume was prepubertal at 2 mL each.
9 h7 w! i) w* \* ~The skin was moist and smooth and somewhat
) S" }/ G0 p7 P/ B: \. ]* poily. No axillary hair was noted. There were no
9 m- Y$ J) B. aabnormal skin pigmentations or café-au-lait spots.
& @ X+ V) v$ ^ C7 e7 |4 ~Neurologic evaluation showed deep tendon reflex 2+
6 ~/ }- U2 R$ u4 H2 M& Ibilateral and symmetrical. There was no suggestion& |' ^4 J; f# k* n! {
of papilledema.) q4 a! g, n2 K& b3 ?" N1 i
Laboratory Evaluation
$ y0 V) t) s5 ?/ m" ^/ AThe bone age was consistent with 28 months by1 ?# u' Z0 d6 A% @- x( w8 Y
using the standard of Greulich and Pyle at a chrono-
; M; i+ E) }2 x1 B% o4 s" r4 e, llogic age of 16 months (advanced).5 Chromosomal
" t" N \1 @4 n. {6 N" Bkaryotype was 46XY. The thyroid function test
8 u4 M; f' t: p/ ]4 ^/ }! t( Yshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
; v* A" T) ?8 Y5 }% s# Llating hormone level was 1.3 µIU/mL (both normal).
; E# a! `5 l2 `1 r4 NThe concentrations of serum electrolytes, blood# y* T( Q+ G9 c7 W. K" F
urea nitrogen, creatinine, and calcium all were! d0 Z: H/ n9 A: [7 D
within normal range for his age. The concentration6 ^1 {$ _% y* C' o5 X: r. @
of serum 17-hydroxyprogesterone was 16 ng/dL' u' P& b' r, B. m
(normal, 3 to 90 ng/dL), androstenedione was 20 }: r" X, U7 t/ o( e
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-0 H& ^ t1 k7 N; F" n5 b
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
8 _$ i Z" q7 sdesoxycorticosterone was 4.3 ng/dL (normal, 7 to$ k) C% V3 B) ?8 J2 @+ G
49ng/dL), 11-desoxycortisol (specific compound S)0 f. W* h% p9 u; j3 _. S4 A3 o
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-" X5 S$ N( t8 P: h- x
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
: R9 ~- ~" v6 o: M# t. m& Xtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
# e2 l- M, `- B! dand β-human chorionic gonadotropin was less than& C; D- {/ T( q' ~) Z
5 mIU/mL (normal <5 mIU/mL). Serum follicular
0 Q# _$ X$ e& o" I5 istimulating hormone and leuteinizing hormone, Z( n3 U+ S2 M- ^4 l5 ~3 g. J
concentrations were less than 0.05 mIU/mL
6 f) X: W2 W z/ E' W% X* ]4 ](prepubertal).
' W9 K' p7 ~# Z" d( CThe parents were notified about the laboratory
+ [2 B7 A5 Q5 h0 ~8 [4 bresults and were informed that all of the tests were
9 x+ ~1 f5 E6 {5 v- N5 s$ m) lnormal except the testosterone level was high. The
H: J5 \4 V) yfollow-up visit was arranged within a few weeks to
/ Q: Q8 }) g6 K' \& h( M" J0 l% Jobtain testicular and abdominal sonograms; how-/ u: c* B& R: B, ~( ~
ever, the family did not return for 4 months.) D0 F R& i5 T2 ?
Physical examination at this time revealed that the
) t4 y1 q) s5 V& X+ Tchild had grown 2.5 cm in 4 months and had gained8 Q* H1 y0 O# @& } F; [/ u
2 kg of weight. Physical examination remained7 V6 {! x! J, ~2 K8 t7 a2 U& X
unchanged. Surprisingly, the pubic hair almost com-4 U- O. P3 a+ L$ k5 k2 F
pletely disappeared except for a few vellous hairs at
" S- U$ s8 L2 X" @% ythe base of the phallus. Testicular volume was still 21 @" E$ u& D0 @# g3 t
mL, and the size of the penis remained unchanged." v$ k( h3 h( }$ z3 K b4 g
The mother also said that the boy was no longer hav-
7 J" e/ Z, v, C, ying frequent erections.# n0 l. C, Z5 g
Both parents were again questioned about use of
2 s' y F9 R9 J& M7 `: l" Fany ointment/creams that they may have applied to+ }5 w/ _; e/ n' H8 |" h( Y
the child’s skin. This time the father admitted the
: ?( G% c# ~1 G0 C: rTopical Testosterone Exposure / Bhowmick et al 541
; G5 L, `1 X7 m7 ^/ Y L$ o$ W1 vuse of testosterone gel twice daily that he was apply-
- z) ^$ m% L5 j0 Ping over his own shoulders, chest, and back area for2 k9 h: R& d+ h, Q# w3 h
a year. The father also revealed he was embarrassed9 B) P% n; f, `! T$ C3 Z
to disclose that he was using a testosterone gel pre-
; I# g, A N; p- X1 y1 Q% B0 U: Oscribed by his family physician for decreased libido
6 ^/ S: o2 c6 H Ssecondary to depression.9 R/ }. O& _, H0 f. T' v5 N" j
The child slept in the same bed with parents.2 H% J* ~( a, T1 s$ T- r' ]4 J
The father would hug the baby and hold him on his
0 ?& n0 c% I( C" t3 o% jchest for a considerable period of time, causing sig-! f6 q8 i' U. u* N' Q( \
nificant bare skin contact between baby and father.2 I) Q& W" X, A1 c% o6 \
The father also admitted that after the phone call,3 H1 L) Z0 K0 x
when he learned the testosterone level in the baby
1 k$ w/ B: {& u/ \) ~4 M5 mwas high, he then read the product information
8 t# e9 e6 R4 L kpacket and concluded that it was most likely the rea-* d% x9 [4 s6 Y
son for the child’s virilization. At that time, they
! p7 E1 P {! s, S# N9 |decided to put the baby in a separate bed, and the3 O: J# w0 {8 w; W6 u/ q
father was not hugging him with bare skin and had3 q8 O/ z9 C1 r) L6 o2 @
been using protective clothing. A repeat testosterone* ^" [6 G7 e2 r0 d1 P K( `( W
test was ordered, but the family did not go to the O! k( f$ f0 e6 Q0 e ?& H7 O# t
laboratory to obtain the test./ W8 }% q% |' j
Discussion8 A+ I7 A2 h- @4 ~9 g9 H) ]9 D
Precocious puberty in boys is defined as secondary* U( ~. A+ b. m. h( o
sexual development before 9 years of age.1,4 A; v7 m; C" l; |3 x; {* M
Precocious puberty is termed as central (true) when
1 h& o7 ~) c! M3 j. r5 l# Rit is caused by the premature activation of hypo-
% [! L; z# b+ c8 Z. \thalamic pituitary gonadal axis. CPP is more com-
! Q6 |/ `6 e4 _) d5 qmon in girls than in boys.1,3 Most boys with CPP
4 e) Z6 k3 x* [may have a central nervous system lesion that is
. V1 w3 J R6 a$ _4 mresponsible for the early activation of the hypothal-. c. x8 b& m6 G O& }) S. E
amic pituitary gonadal axis.1-3 Thus, greater empha-* S- S! T% r; K! c2 h# I
sis has been given to neuroradiologic imaging in: ]! ^( W' V1 }" B
boys with precocious puberty. In addition to viril-9 w- @5 _! } G! r# l! M
ization, the clinical hallmark of CPP is the symmet-. G& `7 G7 _' ]+ R, i
rical testicular growth secondary to stimulation by
( b2 G' v7 t# c2 ^. U4 Y) N4 ]5 igonadotropins.1,3
# c" x6 s) X: bGonadotropin-independent peripheral preco-& \8 T) u. U& H% e1 ^
cious puberty in boys also results from inappropriate* H9 q7 Q6 V4 ~( @. G+ J
androgenic stimulation from either endogenous or
7 ^. B0 W! G( y5 X+ ~exogenous sources, nonpituitary gonadotropin stim-. a0 h/ ?. B" S. c& I3 r2 S
ulation, and rare activating mutations.3 Virilizing% V8 ~$ F: q' h
congenital adrenal hyperplasia producing excessive2 ?' M, j" G7 J) S7 l B* O) o
adrenal androgens is a common cause of precocious: W# K3 x6 N9 Y
puberty in boys.3,4
0 ?# u1 a" G' ]The most common form of congenital adrenal+ n# v: e; O3 s" C6 m+ k g6 E
hyperplasia is the 21-hydroxylase enzyme deficiency.( e+ e" d6 a3 p" n% o* n; J
The 11-β hydroxylase deficiency may also result in. a" B7 Y' _* |. M$ Y- T3 _; o4 Y
excessive adrenal androgen production, and rarely,
a0 j! s- D6 A. y) q) aan adrenal tumor may also cause adrenal androgen
5 |5 X- z3 {' e4 ` B+ N# b0 I2 |excess.1,3
) Y5 w3 l# S' ?; Zat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
4 ]& D5 e! b2 j& y, g0 J4 I ?542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
9 n3 Y' ` a' n& i% j6 sA unique entity of male-limited gonadotropin-8 T' g4 ]. I/ d2 I2 u. ]3 g
independent precocious puberty, which is also known3 m" \7 z+ u% ^6 X4 j% F
as testotoxicosis, may cause precocious puberty at a# _ F( S# k2 e* ]
very young age. The physical findings in these boys% D& a: v, S+ e; w' n6 y6 K2 Y# A
with this disorder are full pubertal development,+ ]+ N9 H6 x$ U T* G
including bilateral testicular growth, similar to boys
0 v) b9 o0 l* u0 ?6 {, }& dwith CPP. The gonadotropin levels in this disorder
5 t5 H: H/ [& G. a# Q% Fare suppressed to prepubertal levels and do not show5 r( K/ `' l+ g) N# e6 b/ B0 D8 w' X7 K4 [
pubertal response of gonadotropin after gonadotropin-" V2 ]" ]& d" M3 M* p% e" z
releasing hormone stimulation. This is a sex-linked
) o! q# _: l h7 z3 Z& fautosomal dominant disorder that affects only4 v3 p ^* @, g; k' O& k+ _; c
males; therefore, other male members of the family7 w- _7 {1 Q1 Y2 ?" j" F6 S
may have similar precocious puberty.3
5 }9 z' A4 l/ X- ^3 X, D7 hIn our patient, physical examination was incon-% U* A" h$ \5 Z* l8 L. e% Y
sistent with true precocious puberty since his testi-! s% ~; C. v7 q
cles were prepubertal in size. However, testotoxicosis
% s0 G; z1 x, N; swas in the differential diagnosis because his father
, ^" \' B" d3 Cstarted puberty somewhat early, and occasionally,
; y& D% Q7 `- Atesticular enlargement is not that evident in the
' X' i; m$ V; _4 E6 mbeginning of this process.1 In the absence of a neg-6 B* H& Q& B1 x d3 i
ative initial history of androgen exposure, our# { Q- B8 U1 j2 p8 t9 I* I! K
biggest concern was virilizing adrenal hyperplasia,9 T' f2 s) C2 ]; p& W, q
either 21-hydroxylase deficiency or 11-β hydroxylase
. {, p; M) L: \deficiency. Those diagnoses were excluded by find-
; S. N: Z7 H2 g, R/ [7 G: p1 _ing the normal level of adrenal steroids.
s! u& h- p# R! fThe diagnosis of exogenous androgens was strongly1 ~+ t/ z0 X9 ~; \/ s, ~! t
suspected in a follow-up visit after 4 months because
7 s# Z# O5 L& h2 L+ b. cthe physical examination revealed the complete disap-
5 [' M: S" Q3 ?/ Ypearance of pubic hair, normal growth velocity, and# v @$ b8 u# [0 l; q2 P5 V* C5 O
decreased erections. The father admitted using a testos-
6 R/ k1 e! P! ~4 i# B6 nterone gel, which he concealed at first visit. He was
& O5 A! U0 a5 i* Jusing it rather frequently, twice a day. The Physicians’- l( y3 {- I+ ~# p/ F8 J% ^+ x9 V
Desk Reference, or package insert of this product, gel or
7 O: d% ~) R( rcream, cautions about dermal testosterone transfer to
3 Y9 g& \& o' b5 W% f+ e5 U; Uunprotected females through direct skin exposure.
" E8 G/ r6 N+ N" t; ~Serum testosterone level was found to be 2 times the
# E8 C V) G: ^$ Rbaseline value in those females who were exposed to/ u+ l+ N( H+ F; B; U2 w
even 15 minutes of direct skin contact with their male& G% k: B$ b1 u( G% v2 U
partners.6 However, when a shirt covered the applica-
/ s3 V# @, P+ E" _tion site, this testosterone transfer was prevented.
$ R3 @! k' P" J. \% K4 g b8 OOur patient’s testosterone level was 60 ng/mL,' d5 w" y* c% r h7 ]/ Z" }
which was clearly high. Some studies suggest that
5 n0 `% R0 U. Gdermal conversion of testosterone to dihydrotestos-
& j8 F) W4 X/ {, Y0 k: l$ b6 _terone, which is a more potent metabolite, is more# b4 [9 P1 t. y! R. R; ?" M
active in young children exposed to testosterone
, p; W/ d* i. j4 Q; fexogenously7; however, we did not measure a dihy-! N' t+ T. |9 w* @( s. l2 S
drotestosterone level in our patient. In addition to/ s& O) c# l/ i$ q& K$ ?( ~2 K( x
virilization, exposure to exogenous testosterone in
0 k$ S, j! D4 }children results in an increase in growth velocity and
: i* z7 ?1 i3 {: s6 H8 Padvanced bone age, as seen in our patient., V& {7 a% }4 f1 n: O+ } t3 e
The long-term effect of androgen exposure during) U7 d+ e- w" r1 |$ l" P2 I
early childhood on pubertal development and final% f, J2 r9 k$ l. A' K0 n
adult height are not fully known and always remain# e% [& _% c8 H. R9 ]* w H O
a concern. Children treated with short-term testos-
+ n+ M5 p1 A( a$ C1 o# C& @, Zterone injection or topical androgen may exhibit some
. @5 p1 y/ N* e0 E vacceleration of the skeletal maturation; however, after; M4 p5 ^2 @" ?- N
cessation of treatment, the rate of bone maturation
\3 n& g3 n0 g+ m4 Zdecelerates and gradually returns to normal.8,9
, h `- W, @6 K0 E5 r1 c5 mThere are conflicting reports and controversy
$ l5 F9 ?3 Q, ?over the effect of early androgen exposure on adult
: [5 ?- ?1 g- l2 w/ Ipenile length.10,11 Some reports suggest subnormal+ D7 ^, o# G% V
adult penile length, apparently because of downreg-! x& W' n* c3 [8 p
ulation of androgen receptor number.10,12 However,8 ^4 d% e- p& k+ u# S
Sutherland et al13 did not find a correlation between# n/ ~, ~/ O r1 r% y3 M. V
childhood testosterone exposure and reduced adult
- h# y( j1 u' I% k- R' {penile length in clinical studies.
6 F% `2 w0 r# f& V& W8 Z" fNonetheless, we do not believe our patient is
- y# b4 A! t$ _ Hgoing to experience any of the untoward effects from
! d) l- O7 \3 [6 z/ U: J9 P" R3 Etestosterone exposure as mentioned earlier because
& M$ b9 \: I8 l% N8 O0 Othe exposure was not for a prolonged period of time.( c- H# ^5 T) u/ X
Although the bone age was advanced at the time of% l1 g9 J2 ~ O7 E
diagnosis, the child had a normal growth velocity at
4 a" q' |7 b2 o$ V: ythe follow-up visit. It is hoped that his final adult
. o- H" Y+ s4 L+ b' W. Yheight will not be affected.
( h, N: k5 w+ |8 |/ a& aAlthough rarely reported, the widespread avail-
: a1 ?9 p9 n" x- C* u" x5 o9 [# c4 yability of androgen products in our society may: D5 v+ n. r( j8 Z/ Y, {
indeed cause more virilization in male or female& W; z4 l) _: R7 j+ r3 n6 R
children than one would realize. Exposure to andro-5 Z3 L% Y; j: z8 \$ l4 T: l
gen products must be considered and specific ques-5 P' L7 w7 S9 H2 v
tioning about the use of a testosterone product or' O: q" h$ K2 _! M ~1 |' h
gel should be asked of the family members during
* {) u7 F9 a1 B9 ithe evaluation of any children who present with vir-* l# K3 ^% k$ n/ \$ W. D
ilization or peripheral precocious puberty. The diag-: W4 Y5 S7 c# k
nosis can be established by just a few tests and by
0 Y' U1 s: a m" |. u( Bappropriate history. The inability to obtain such a+ l* V" X+ q% s5 k2 t$ u) f# ?
history, or failure to ask the specific questions, may4 `: V: o) d6 r1 E! L! I5 _1 q7 J+ P
result in extensive, unnecessary, and expensive6 I1 w- W3 e, s6 `2 h
investigation. The primary care physician should be
: j* I, w, l4 E3 _6 b, {2 Iaware of this fact, because most of these children
, D" W7 r G- g+ @9 }& R# O9 p9 pmay initially present in their practice. The Physicians’. X9 u: c1 L6 F# p, J9 @
Desk Reference and package insert should also put a) y/ Y6 v, M; e, |: k
warning about the virilizing effect on a male or8 o: d. ]5 X& c" P5 U
female child who might come in contact with some-" n) o# ^4 P5 Q# f Y3 v
one using any of these products.
5 u# ~/ c' n' Y2 W, P! ?2 F0 D. j: DReferences
2 A$ |9 ^ x- m8 a1. Styne DM. The testes: disorder of sexual differentiation0 t) Z {8 _4 g K$ @: U. F- `
and puberty in the male. In: Sperling MA, ed. Pediatric
. {5 V/ S2 K Z, } UEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;# `" |# ]- y) u! W3 a
2002: 565-628.. L2 I! |& i0 M# N
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
8 a3 `6 m9 b# [% Rpuberty in children with tumours of the suprasellar pineal |
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