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Sexual Precocity in a 16-Month-Old
. m0 ?6 j, r( |: vBoy Induced by Indirect Topical) l6 [" l( D+ F V& Z
Exposure to Testosterone
) c$ z) U% F) b* _7 G5 E0 V1 fSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
" a# j; O) ^/ z5 R6 T( i- u5 }8 ^and Kenneth R. Rettig, MD1; I8 g4 p) L, t1 P+ L- X+ e
Clinical Pediatrics
0 M/ N4 X/ j3 _3 h7 LVolume 46 Number 6; d6 T# c& |! D6 S4 a, c/ o! i" l
July 2007 540-543
0 p- b( t. D& g! \( q, V© 2007 Sage Publications
9 p" q( i8 v7 \" x3 C7 x10.1177/0009922806296651
9 N" v- e: J. Y% }# Y8 Dhttp://clp.sagepub.com
) h7 `9 k# B' j1 P; rhosted at9 S. [! [! @5 j' |
http://online.sagepub.com6 L$ x/ ]; x4 q
Precocious puberty in boys, central or peripheral,
7 u( S+ Q$ ~3 e3 Y3 t" I# Cis a significant concern for physicians. Central
; _; n. I# B9 Nprecocious puberty (CPP), which is mediated
2 L" S8 c$ u6 n% K6 F. rthrough the hypothalamic pituitary gonadal axis, has
) A: i. c9 G. s1 ~1 qa higher incidence of organic central nervous system
, O" W: q, n+ @! g# {$ J0 N/ ?7 @lesions in boys.1,2 Virilization in boys, as manifested1 o1 j) x& T6 o' ~0 p8 i
by enlargement of the penis, development of pubic
: Y1 i ^& A' ~! T: [hair, and facial acne without enlargement of testi-
+ E0 \ x5 k3 S; F7 q0 }; Wcles, suggests peripheral or pseudopuberty.1-3 We
( M5 _ Y6 V @2 k& Z+ K# J" zreport a 16-month-old boy who presented with the
+ k3 G% r# P# T. q) V( genlargement of the phallus and pubic hair develop-
j% S$ H& R- u: x8 W, R6 gment without testicular enlargement, which was due
+ `! V2 S! Z5 H& \8 b" D# e7 n- G% ?to the unintentional exposure to androgen gel used by
2 Z3 I: Z: R+ Pthe father. The family initially concealed this infor-2 {5 i) B6 R$ c: ~9 [' w0 B. c
mation, resulting in an extensive work-up for this3 S7 x9 F ~: \+ I7 Y
child. Given the widespread and easy availability of
+ b( D0 O6 p% q M6 Etestosterone gel and cream, we believe this is proba-
2 e* C& I- B4 M8 n tbly more common than the rare case report in the
+ D/ e3 e+ c- o+ O; x# Y% ~literature.4
B/ }, v0 \- D# g& ^2 H6 qPatient Report: [1 u9 w; @7 @ w' ]1 s+ T9 [1 @
A 16-month-old white child was referred to the1 L# B, h, v* T: d
endocrine clinic by his pediatrician with the concern" ]+ \- ]+ L0 g# I) r/ m4 [
of early sexual development. His mother noticed
Y) E O& G/ C! {" @2 X; Tlight colored pubic hair development when he was
) z" |5 ]9 A* e4 g. {" X5 [" GFrom the 1Division of Pediatric Endocrinology, 2University of7 Z n/ N3 r2 }7 y( V/ y W
South Alabama Medical Center, Mobile, Alabama.
9 ~$ M- u& M/ s4 X! hAddress correspondence to: Samar K. Bhowmick, MD, FACE,
: \4 k/ e- ], m2 K: DProfessor of Pediatrics, University of South Alabama, College of
( ?% v- K; [. I3 Q0 B4 eMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
; q7 @, i* X s0 L' Q5 ]e-mail: [email protected].& B* p! l- _! l$ X- v" O
about 6 to 7 months old, which progressively became
! {9 Z: O0 k# A% W% odarker. She was also concerned about the enlarge-
2 ~9 K X4 D. }. Q* Xment of his penis and frequent erections. The child
% o, V2 D. B3 {2 p% q" ewas the product of a full-term normal delivery, with
9 Z% {0 z1 ?" G/ W5 a# Q! ta birth weight of 7 lb 14 oz, and birth length of0 { J" t6 X2 r* X/ E
20 inches. He was breast-fed throughout the first year
7 x8 I* G c% [" h$ zof life and was still receiving breast milk along with
9 ?* x% g4 c) Dsolid food. He had no hospitalizations or surgery,
# W( U1 m c' t) \and his psychosocial and psychomotor development
2 _4 S4 ^2 K* U. _9 f6 ~was age appropriate.9 m% o, k$ ]: H ]& ~: }
The family history was remarkable for the father,: j0 f% Y7 [8 f/ l a
who was diagnosed with hypothyroidism at age 16,% J$ ]9 V, s+ B7 a
which was treated with thyroxine. The father’s
7 I1 z1 A# r b2 s% |6 J! Lheight was 6 feet, and he went through a somewhat
S- k+ P: M) _" [early puberty and had stopped growing by age 14.
3 K5 u, O$ _( W) A) F4 F% t% q @The father denied taking any other medication. The0 S: Q4 D& o2 ]
child’s mother was in good health. Her menarche
3 n! ~; R9 u9 T9 N p) w9 D6 y ]( Awas at 11 years of age, and her height was at 5 feet
' Q6 |& {! R8 c+ ]% }7 h5 inches. There was no other family history of pre-
, C$ w7 f' G5 A& q3 p$ ~cocious sexual development in the first-degree rela-
% F& v# B/ s$ n& \tives. There were no siblings.% @& E- k' J% t2 V+ I: a+ _
Physical Examination
) y" A/ m. a- t9 U7 vThe physical examination revealed a very active,
) a% C& ~( i; V% }1 K, ~2 pplayful, and healthy boy. The vital signs documented' s: s% w4 t- Z* ^0 z/ K* j
a blood pressure of 85/50 mm Hg, his length was
. Y, N {9 a9 Z+ @+ I( @) B S9 N90 cm (>97th percentile), and his weight was 14.4 kg
. D0 ^+ J1 j: @/ a- P& m(also >97th percentile). The observed yearly growth
- [0 ?# f# q B3 A( Fvelocity was 30 cm (12 inches). The examination of6 G* f! @$ l+ e. b8 f: D
the neck revealed no thyroid enlargement.
! \7 n O: B: ?! NThe genitourinary examination was remarkable for
9 X4 N9 ?7 n6 ^. b' b3 U) Eenlargement of the penis, with a stretched length of
( }+ c3 m I' ^) ?8 n5 A. H: c( o8 cm and a width of 2 cm. The glans penis was very well( Y* A. I. C" n& B! {6 S5 _; [
developed. The pubic hair was Tanner II, mostly around C3 ]. r# @. e7 T
540
|8 T4 Z: a- c& u' xat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from4 V$ U3 x* F* W# ]" h+ B3 S" i
the base of the phallus and was dark and curled. The; \5 i$ v' h$ a5 T$ x" Q" ~
testicular volume was prepubertal at 2 mL each.
# a/ n" a; x3 J, L6 m6 S4 Q- c9 uThe skin was moist and smooth and somewhat
; R0 x% A2 i7 y8 g ]/ Coily. No axillary hair was noted. There were no; j" N" R' T3 G. u
abnormal skin pigmentations or café-au-lait spots.
% h" H2 V6 l0 L- _) cNeurologic evaluation showed deep tendon reflex 2+
1 {2 F! P$ v v9 {7 c; |( n5 Dbilateral and symmetrical. There was no suggestion2 m, m7 y3 z d' s. U8 ^# |, x
of papilledema.
" A5 w% R$ q: Z" W6 C! z+ `Laboratory Evaluation" h2 u5 m& h, \3 |
The bone age was consistent with 28 months by
4 y, q& C8 a- d. b5 s- ]using the standard of Greulich and Pyle at a chrono-
5 I: X6 J! S3 @: }6 o. hlogic age of 16 months (advanced).5 Chromosomal7 u H6 @ Y9 z6 r: Y# m; ^
karyotype was 46XY. The thyroid function test
2 M& L; p( x# x5 U1 Oshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
8 r; B: u7 m! ?' \lating hormone level was 1.3 µIU/mL (both normal). M1 z* n2 ~# f2 c6 ?
The concentrations of serum electrolytes, blood
5 E; ], x) T! @6 burea nitrogen, creatinine, and calcium all were
+ X2 Q& a4 j2 o9 J( @' ?$ Dwithin normal range for his age. The concentration$ F4 F3 i6 D* [# o/ J7 I6 P
of serum 17-hydroxyprogesterone was 16 ng/dL
- \" D/ c- \3 _0 K* W* y: a(normal, 3 to 90 ng/dL), androstenedione was 20
8 O$ `0 C, R. J+ m4 w1 u/ Jng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
( B( |" `" K4 W. v6 k1 V7 T' Iterone was 38 ng/dL (normal, 50 to 760 ng/dL)," N- C& N }8 {! J! G8 X
desoxycorticosterone was 4.3 ng/dL (normal, 7 to" T3 H; ?( [4 F7 z. P+ P2 z
49ng/dL), 11-desoxycortisol (specific compound S)
- K" G3 E) u" S% u6 N$ J. @was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-9 V( o* X! m6 j6 u+ b/ X7 N% j
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
: x; N& D A2 J( m! n3 x1 Y& ntestosterone was 60 ng/dL (normal <3 to 10 ng/dL),; V/ N" b. E1 b6 }9 F
and β-human chorionic gonadotropin was less than H, Z. H$ k! G
5 mIU/mL (normal <5 mIU/mL). Serum follicular
0 V+ O$ R& C4 q& @! @$ Dstimulating hormone and leuteinizing hormone6 V% ]1 ~6 X/ l7 R' Y
concentrations were less than 0.05 mIU/mL7 X4 u0 S9 p% m& }. \5 R/ Q1 U
(prepubertal).% b5 F! ] c+ k" t5 I1 Y3 Q7 M
The parents were notified about the laboratory" i; Z6 b! T3 Y; T
results and were informed that all of the tests were
6 q/ Z7 D, A& g) u8 v( c- xnormal except the testosterone level was high. The
7 @% J9 \/ A0 pfollow-up visit was arranged within a few weeks to0 D! `" h& ?% t9 O. I
obtain testicular and abdominal sonograms; how-3 O9 @0 S/ p, y# R
ever, the family did not return for 4 months.
+ [5 p* o1 S2 @Physical examination at this time revealed that the6 o1 H9 e2 q* a6 c# v% `4 [: L
child had grown 2.5 cm in 4 months and had gained6 R, q) D% Y8 ^5 |) P+ W0 A9 k
2 kg of weight. Physical examination remained' @2 @) |3 X1 ]- w0 |) ?0 O; ]' X& e
unchanged. Surprisingly, the pubic hair almost com-
& p7 `' q% D5 t2 N+ e/ w x3 f/ dpletely disappeared except for a few vellous hairs at! T3 i J) B( {2 ]3 b0 s& |% i& {7 q
the base of the phallus. Testicular volume was still 2: \% s" _- R9 f4 w' F: E! ]
mL, and the size of the penis remained unchanged.1 Z: ?" E$ }# d, ~2 \+ s% B
The mother also said that the boy was no longer hav-, }3 q3 I$ ~5 B3 t6 w
ing frequent erections.# a* E; V3 W" r$ b1 b
Both parents were again questioned about use of& F% M3 g. `( g( Q4 K! ]
any ointment/creams that they may have applied to" v6 k! s! n6 P" T
the child’s skin. This time the father admitted the
# @5 ]: Z/ A3 O0 D5 zTopical Testosterone Exposure / Bhowmick et al 541
$ [ c8 @" U) |* huse of testosterone gel twice daily that he was apply-6 M% N3 ?+ x+ x% W9 e- e
ing over his own shoulders, chest, and back area for
% t8 H1 _ Z" b0 ha year. The father also revealed he was embarrassed
- j) l) s. k( G6 bto disclose that he was using a testosterone gel pre-# g" J( p! _' E. ]/ o! s/ C
scribed by his family physician for decreased libido
1 @. [0 x% g+ |8 usecondary to depression.8 o' Z0 q4 O3 K/ m2 d3 d2 C
The child slept in the same bed with parents.
8 |* H# e8 z1 V. d. M, J' e/ E% NThe father would hug the baby and hold him on his" l% g# ?7 c: E8 v, ^
chest for a considerable period of time, causing sig-, A6 B+ F W/ c0 H0 Q- @
nificant bare skin contact between baby and father.8 }+ q& o/ F7 K; C, r1 ?
The father also admitted that after the phone call,
0 T, J4 |; E) O2 o! Dwhen he learned the testosterone level in the baby
' J& s; K/ w8 o4 ?' nwas high, he then read the product information; v1 Q2 _' r) [: E9 ^) I
packet and concluded that it was most likely the rea-2 e4 R" {6 g6 C! F0 G; _
son for the child’s virilization. At that time, they/ J0 x r" i1 D& I
decided to put the baby in a separate bed, and the
8 }' k" c& o1 O S! Kfather was not hugging him with bare skin and had
5 H/ c' V' h( D" M J# s5 n0 j: vbeen using protective clothing. A repeat testosterone
: r9 L9 F2 U& }test was ordered, but the family did not go to the# O2 c" |; i' _, B7 j5 v
laboratory to obtain the test.
! B2 [! n7 D+ T$ |Discussion
0 ^: m a& z9 ^9 {. `7 YPrecocious puberty in boys is defined as secondary9 d1 \5 J( z0 c- H% d8 h
sexual development before 9 years of age.1,4
* j# h3 z% |# a* m) f5 YPrecocious puberty is termed as central (true) when/ H7 `. D9 J) \9 Y1 D
it is caused by the premature activation of hypo-# c, s' g/ u1 K N3 H/ J
thalamic pituitary gonadal axis. CPP is more com-6 r" u! i/ G) G3 `
mon in girls than in boys.1,3 Most boys with CPP
5 B5 L+ ]: G, Kmay have a central nervous system lesion that is+ B4 \- }3 R; {# {$ j5 x q6 O | \
responsible for the early activation of the hypothal-
: \# U* S V" Q( Lamic pituitary gonadal axis.1-3 Thus, greater empha-- H8 c: [/ h/ \/ y) L
sis has been given to neuroradiologic imaging in
9 e1 I5 X2 r/ e0 G* Xboys with precocious puberty. In addition to viril-
# U7 q5 A7 Y" _+ cization, the clinical hallmark of CPP is the symmet-: T; n( H& o& w! C
rical testicular growth secondary to stimulation by* }% F2 s9 F7 H) F# C
gonadotropins.1,3
G2 [: [0 O' M3 mGonadotropin-independent peripheral preco-
7 S$ N: h9 D" F, u6 Q: q& [cious puberty in boys also results from inappropriate% [6 q3 L2 f" J0 g0 {
androgenic stimulation from either endogenous or4 g7 \; ~$ P- {. Q) U
exogenous sources, nonpituitary gonadotropin stim-# j9 q7 z7 w, f
ulation, and rare activating mutations.3 Virilizing
! X' e4 i6 P4 O' D) A, Xcongenital adrenal hyperplasia producing excessive! ^4 d, ]# |/ \9 e/ y3 h
adrenal androgens is a common cause of precocious+ k* x# |8 [5 _) O: h5 ?; k
puberty in boys.3,4& F( l& `# `3 u: Z# R
The most common form of congenital adrenal7 ^- Q/ L5 v, p* |" n
hyperplasia is the 21-hydroxylase enzyme deficiency.
5 A: e" v# T% r. mThe 11-β hydroxylase deficiency may also result in
2 \ J/ i2 b5 z6 c# C8 G5 X5 B. {excessive adrenal androgen production, and rarely,; r( l; v% G, z0 V) s. g5 v
an adrenal tumor may also cause adrenal androgen% ?5 j R, f2 G4 m4 X2 x" m
excess.1,3
7 f7 t% l) W! x- p* eat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from4 \3 {: b! v* Y; B8 s' p
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
$ m, d; i4 K n6 E1 \. XA unique entity of male-limited gonadotropin-
* E0 E9 q; H% Z' U# Zindependent precocious puberty, which is also known
0 z: R( {1 H F$ |- v: r+ H3 bas testotoxicosis, may cause precocious puberty at a
4 j9 {5 ~4 h0 Y8 `* Pvery young age. The physical findings in these boys# K6 `! ]' g* g+ J# \7 T1 @3 R& ]
with this disorder are full pubertal development,
+ G, Z( @. G5 Yincluding bilateral testicular growth, similar to boys8 d' w$ O- g2 i2 F
with CPP. The gonadotropin levels in this disorder1 \1 I9 J" @- x' W2 j
are suppressed to prepubertal levels and do not show y& j+ W$ H! C5 m! D" p7 Y; o+ K
pubertal response of gonadotropin after gonadotropin-
$ Z+ A' [' v/ B6 t1 H% Breleasing hormone stimulation. This is a sex-linked" _6 Q6 A. Q( a, c) L: j1 G
autosomal dominant disorder that affects only
$ Y9 \1 |0 A* ^8 ~ \- ?males; therefore, other male members of the family
1 m% u1 a+ B6 B% w' ?0 Gmay have similar precocious puberty.3
6 b& x- `8 T% F$ zIn our patient, physical examination was incon-5 M! |" g9 v" \. I4 A; z$ W
sistent with true precocious puberty since his testi-4 H' f5 ^* z/ D# ?: S
cles were prepubertal in size. However, testotoxicosis, k& W1 w8 q5 e- k: v& s
was in the differential diagnosis because his father5 o: W! O3 T/ q8 `/ z
started puberty somewhat early, and occasionally,
- p- E1 x% ]4 b. o4 ^2 Qtesticular enlargement is not that evident in the
2 ?0 H% [) e/ W" o& \beginning of this process.1 In the absence of a neg-
0 x: X! y: m: P7 \" m2 Y# ^7 Wative initial history of androgen exposure, our+ ]+ M. }0 L3 E( ^! R
biggest concern was virilizing adrenal hyperplasia,
- F6 o j& B1 A. meither 21-hydroxylase deficiency or 11-β hydroxylase% m' F& l3 D! D0 L0 Q! _9 D
deficiency. Those diagnoses were excluded by find-/ e" f! k7 k/ K, H( L3 G- |
ing the normal level of adrenal steroids., c3 ^; {- D3 ?1 Q, v+ |* I" `3 R& k
The diagnosis of exogenous androgens was strongly& t4 b! O) u. i/ J
suspected in a follow-up visit after 4 months because
% K6 @2 X' A4 I1 r, {the physical examination revealed the complete disap-0 N# K% ^2 d) | t+ i1 c; r
pearance of pubic hair, normal growth velocity, and! |# \4 j0 b, W9 M5 H9 P
decreased erections. The father admitted using a testos-
" S, D( h/ x Q- m. \terone gel, which he concealed at first visit. He was
9 g Z7 j4 I7 ^) m; |/ Iusing it rather frequently, twice a day. The Physicians’ C5 x2 E I3 Y- j' n
Desk Reference, or package insert of this product, gel or
' R# g' ~) z* Q+ @cream, cautions about dermal testosterone transfer to
$ {6 y% `$ B& x% o0 r4 r4 I. `" runprotected females through direct skin exposure.: g# w0 w) M5 t* O
Serum testosterone level was found to be 2 times the
. P6 Z( J- x0 vbaseline value in those females who were exposed to
5 q4 u, b0 ]' X, P/ ~' `4 S- keven 15 minutes of direct skin contact with their male; ? ]- A' e* [# ]" G: N( ^. M
partners.6 However, when a shirt covered the applica-# o/ {$ B# K, t) V% {( M3 u3 D
tion site, this testosterone transfer was prevented.
; C p) p2 `( f" P, U7 G9 H# sOur patient’s testosterone level was 60 ng/mL,
: Z& A6 C4 c! j3 S1 nwhich was clearly high. Some studies suggest that
1 C! M. X0 O' b: ~" }8 [0 c, z) Odermal conversion of testosterone to dihydrotestos-
+ B' {3 J; { ?/ D/ q7 Eterone, which is a more potent metabolite, is more# |7 d$ n( h$ \ H3 u0 ~, L
active in young children exposed to testosterone; \- ^, p. p3 a n& j3 F' E
exogenously7; however, we did not measure a dihy-
" v% F/ R* A- ~: Pdrotestosterone level in our patient. In addition to
0 q+ ` D6 U; q% y8 d$ U% Gvirilization, exposure to exogenous testosterone in/ O9 c. V& a3 a% f" q2 b% x% l
children results in an increase in growth velocity and: P9 Y, e9 T, E, r
advanced bone age, as seen in our patient.% B& T$ D [/ K
The long-term effect of androgen exposure during
$ x1 y( b! `# B# u( q8 @# Z8 fearly childhood on pubertal development and final5 e3 J4 m' U$ M5 O& O5 B) y/ T) T0 w
adult height are not fully known and always remain
& ~$ M1 \5 V2 J! @/ y2 |a concern. Children treated with short-term testos-
6 g- M R$ Z6 } Z, Z/ G$ Qterone injection or topical androgen may exhibit some
9 U5 k) B- J4 m; _& m0 V. kacceleration of the skeletal maturation; however, after
5 C4 R8 X* t' m/ q# t& a8 xcessation of treatment, the rate of bone maturation$ z B9 B$ a: ~8 }9 o% [
decelerates and gradually returns to normal.8,98 o1 h' w0 O' U& z
There are conflicting reports and controversy
! p9 t% D8 o' C r* S( c# _: xover the effect of early androgen exposure on adult/ G7 P/ a( a5 C A* ?* h( e7 @
penile length.10,11 Some reports suggest subnormal
- z& f4 c& N, h& g- Z! \adult penile length, apparently because of downreg-
! i3 B: Q% q$ a$ C \/ T5 P1 Culation of androgen receptor number.10,12 However,
' {1 v# Y$ t$ Y1 k" ~Sutherland et al13 did not find a correlation between
( ]9 S6 H) B r& n4 B) Y- z bchildhood testosterone exposure and reduced adult
, o8 d( M3 Z7 z" Ypenile length in clinical studies.
- W, F' M; i7 W9 YNonetheless, we do not believe our patient is& j( k+ a. u/ y, U( [' n2 H5 U
going to experience any of the untoward effects from
5 g0 {+ L& q6 v9 _testosterone exposure as mentioned earlier because) W/ o4 b7 `/ D7 k' ~7 V
the exposure was not for a prolonged period of time.$ z5 L% t7 e/ k& [
Although the bone age was advanced at the time of
+ A3 i" p; Y, `% Sdiagnosis, the child had a normal growth velocity at
) m1 a7 v" w$ Jthe follow-up visit. It is hoped that his final adult
$ Z% k+ s, J) e7 a1 kheight will not be affected.
. f" n; d, l) w9 gAlthough rarely reported, the widespread avail-
9 N. l1 v) g: _4 K1 s3 o! Fability of androgen products in our society may
8 {# [( F- e# oindeed cause more virilization in male or female5 V: V; `2 w7 r9 E5 t
children than one would realize. Exposure to andro-
! s( c7 f# t6 A6 \gen products must be considered and specific ques-1 t* X5 I/ d# u0 P9 ?9 O
tioning about the use of a testosterone product or" Y3 j: h i4 A$ w( D5 r4 K1 s7 g
gel should be asked of the family members during# X* C3 m" v, A; x: V A F
the evaluation of any children who present with vir-0 H1 r* S+ _) C) l
ilization or peripheral precocious puberty. The diag-. r5 g6 s6 b4 H- ?, _
nosis can be established by just a few tests and by
7 B. D) M1 ~( }9 u: t& jappropriate history. The inability to obtain such a
9 S! f: D. q! K ~( Hhistory, or failure to ask the specific questions, may, M/ ?1 m% f; ]$ _( E! m# g
result in extensive, unnecessary, and expensive
( L$ e0 {+ @2 s2 j7 einvestigation. The primary care physician should be! v" n1 D: A8 p3 P; W
aware of this fact, because most of these children( D9 U: d* Q6 v2 b
may initially present in their practice. The Physicians’$ A* ^- d I+ N( {$ ~% M
Desk Reference and package insert should also put a
" J+ u# k; n- w' ^( q- wwarning about the virilizing effect on a male or, `4 Q* @, y" X9 i
female child who might come in contact with some-% O6 Z6 P/ ~4 _) y: S! F; G
one using any of these products.
* O5 |3 k3 ?$ d0 lReferences3 R: s0 X( ]: P5 g( |
1. Styne DM. The testes: disorder of sexual differentiation
) }+ \" a: j$ s# Eand puberty in the male. In: Sperling MA, ed. Pediatric
/ b, I" B) L$ p: a0 KEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
* q& F# o, h) u' W5 t4 r2002: 565-628.( p# h2 x6 |, Z4 S7 Q! c4 [/ U
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
2 k+ s t3 \$ H" Z: g8 F2 Kpuberty in children with tumours of the suprasellar pineal |
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