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Sexual Precocity in a 16-Month-Old
) U5 O3 b' E1 c9 z- @Boy Induced by Indirect Topical
) A- f9 {% ~9 |Exposure to Testosterone- q! F. B) C9 a/ D# d" E
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2" { J, M$ W6 b' V
and Kenneth R. Rettig, MD1
' `) d: ^+ e' V$ P2 ^: l6 UClinical Pediatrics
8 S1 y5 v; Z& ^Volume 46 Number 6
/ a' O R8 O( H5 @3 ?* cJuly 2007 540-543
& x$ i( O; u7 X7 l" h- G$ J9 q. M© 2007 Sage Publications
- }: n# K/ B' f0 w4 R6 D) M! z10.1177/0009922806296651
: J# X( R/ O1 @http://clp.sagepub.com
, ?9 x, l7 u, G! m4 H1 _3 ]% Phosted at
8 k; {7 s! R/ ^2 A- J" shttp://online.sagepub.com$ \" g# B* m3 A1 B0 H! E ^
Precocious puberty in boys, central or peripheral,& ^- E q! r( w4 [
is a significant concern for physicians. Central
, R/ w" d& {5 d0 Z& \precocious puberty (CPP), which is mediated8 X) w& X) {4 t; e
through the hypothalamic pituitary gonadal axis, has- k" F! Y- `5 A! B" P* y
a higher incidence of organic central nervous system- I u+ P( D. _
lesions in boys.1,2 Virilization in boys, as manifested+ y4 s' u: |, P$ o
by enlargement of the penis, development of pubic
9 T2 H8 k9 X/ \5 ]7 [ Fhair, and facial acne without enlargement of testi-
6 |& A8 e' _4 ccles, suggests peripheral or pseudopuberty.1-3 We
1 H+ h0 |% n% y+ D: ]8 W/ A# {report a 16-month-old boy who presented with the
1 W h4 b7 `. t% u1 d# ^% Zenlargement of the phallus and pubic hair develop-9 H+ M- X7 i, K7 W6 \$ H
ment without testicular enlargement, which was due
2 L0 b7 M5 J$ q( j2 ^( {to the unintentional exposure to androgen gel used by& T/ h) N# y0 O6 i
the father. The family initially concealed this infor-: p$ o9 w& E3 B& `8 N
mation, resulting in an extensive work-up for this( I8 S* O, e& h# a& B( g. N
child. Given the widespread and easy availability of
; [! X) O3 i) z9 D! Ltestosterone gel and cream, we believe this is proba-6 R9 Y8 ~7 Q3 G E
bly more common than the rare case report in the
2 e ]" c! d2 R/ q1 [; gliterature.4
' Y8 N" |2 V4 H! I+ uPatient Report
) ]+ {% F: ?8 PA 16-month-old white child was referred to the( f6 P* S B% X9 O6 E( ~9 E! {9 @
endocrine clinic by his pediatrician with the concern( @0 w- D3 j0 w' q1 z8 h- M
of early sexual development. His mother noticed2 N$ s4 J& \! C w, G- N- P
light colored pubic hair development when he was
* A6 ]- n- ]8 H) x8 U- Z B# CFrom the 1Division of Pediatric Endocrinology, 2University of3 j3 b6 W! X6 s! [% p: h
South Alabama Medical Center, Mobile, Alabama.5 u* c+ V7 @; U
Address correspondence to: Samar K. Bhowmick, MD, FACE,1 N; I- b: i7 R* r0 `) o
Professor of Pediatrics, University of South Alabama, College of8 @$ z7 S1 v: |, W) P' t" M
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;. {& m7 H2 m: O! I! X0 ]: g6 R
e-mail: [email protected].
! c5 f- k* ~0 P7 z3 f, e* Cabout 6 to 7 months old, which progressively became
5 x4 T& M/ }! t A. S3 odarker. She was also concerned about the enlarge-
8 {- y2 j. o! e; ~ment of his penis and frequent erections. The child
8 Q! X- i( c! b* W) uwas the product of a full-term normal delivery, with
9 m" A8 W: f6 S* V5 R) e2 X$ Fa birth weight of 7 lb 14 oz, and birth length of/ z" f' m$ L& Z3 U- s
20 inches. He was breast-fed throughout the first year( O: E. r% E/ F( H0 N
of life and was still receiving breast milk along with
% q4 {" R, g4 K7 Usolid food. He had no hospitalizations or surgery,% o1 D- v5 U; V X6 _- |, ^2 d
and his psychosocial and psychomotor development
; X2 p9 t* W/ W# ]6 Q' F+ S6 Bwas age appropriate.
f: Q5 q. T0 M! I% Q- nThe family history was remarkable for the father, N9 W4 `5 ?# G$ {
who was diagnosed with hypothyroidism at age 16,3 B1 A- q. B5 T- b
which was treated with thyroxine. The father’s. ?3 X( H0 p, `& C
height was 6 feet, and he went through a somewhat
5 d4 G, U* J. f+ kearly puberty and had stopped growing by age 14.
. A) @) W# I rThe father denied taking any other medication. The
. A2 v2 P) ]3 E. t( Vchild’s mother was in good health. Her menarche0 _* B0 n' r* Q6 D# V6 ~/ a
was at 11 years of age, and her height was at 5 feet
1 Q7 N, \4 U% ^; I/ P, A5 inches. There was no other family history of pre-
0 h8 Q& P8 o6 e/ r+ Y1 ncocious sexual development in the first-degree rela-( c3 s) {9 n. W+ B; r; z
tives. There were no siblings.
; P1 ~% q: Y! E1 v: `- dPhysical Examination! Z/ F" [4 j9 u$ A1 e( L' _% {
The physical examination revealed a very active,1 Z5 w$ c5 j" ^) _" S7 n7 V+ u( V
playful, and healthy boy. The vital signs documented
; O! Z, ~, R3 I0 h5 h7 Da blood pressure of 85/50 mm Hg, his length was" x" M$ d+ C9 [, S
90 cm (>97th percentile), and his weight was 14.4 kg- W2 [( x; _2 F! k% }' U i& J
(also >97th percentile). The observed yearly growth5 ?5 ~! `( @9 o6 M6 M6 B0 M
velocity was 30 cm (12 inches). The examination of8 U7 h. B8 l0 E3 [+ P% ]! K1 `" W5 z
the neck revealed no thyroid enlargement./ I) `8 g" v# F) Q, k7 c+ E
The genitourinary examination was remarkable for8 M G# ?# U/ g, S
enlargement of the penis, with a stretched length of
+ e, C4 x# v$ j& m8 cm and a width of 2 cm. The glans penis was very well) J% Q; ] g+ @3 |) S
developed. The pubic hair was Tanner II, mostly around0 _8 k) D- b% H5 T$ r
540( W( C! l9 A$ h) d$ F
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
i1 g) V. `% G2 ^5 |the base of the phallus and was dark and curled. The
& r+ P! K1 B& z# t( p) Rtesticular volume was prepubertal at 2 mL each.5 F) Z4 W' P' ~0 a3 n3 J
The skin was moist and smooth and somewhat
5 ` S2 S1 T% H9 E' r, Coily. No axillary hair was noted. There were no1 a7 a) E" ~! r4 \8 Y, T- l
abnormal skin pigmentations or café-au-lait spots.
" u* H. H( r" A2 Z$ CNeurologic evaluation showed deep tendon reflex 2+
8 h$ S5 k9 t4 @, i' U% ?. Lbilateral and symmetrical. There was no suggestion
7 Y D, K/ x# E0 D s' N9 Sof papilledema.' R; g2 S; i4 b g
Laboratory Evaluation
5 O' G- |1 G) M! P9 G' yThe bone age was consistent with 28 months by
4 J% F% f( b* t% ^# e* P$ X6 Ausing the standard of Greulich and Pyle at a chrono-
3 Y2 v, T, V+ U, O( e& \logic age of 16 months (advanced).5 Chromosomal
& V2 { N% X( ~5 j+ B$ skaryotype was 46XY. The thyroid function test) y, L0 V3 m: F& q$ \. q
showed a free T4 of 1.69 ng/dL, and thyroid stimu-& M* {. {/ i0 N$ ]# y- v' n; o3 o
lating hormone level was 1.3 µIU/mL (both normal).
! B0 Y3 c& g4 J' H0 p% @/ hThe concentrations of serum electrolytes, blood
" a x7 f# e& f f. ^urea nitrogen, creatinine, and calcium all were
- `2 w/ O: z Y( T7 R( u. Ewithin normal range for his age. The concentration% k& i8 Z0 w7 S2 Y
of serum 17-hydroxyprogesterone was 16 ng/dL
6 N' S- N3 O8 o0 {% X4 K4 x(normal, 3 to 90 ng/dL), androstenedione was 20: F' x0 R; A( b8 ?* @( r4 l; Q
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
; K8 i2 d: V5 H) Q7 i5 wterone was 38 ng/dL (normal, 50 to 760 ng/dL),
" D7 g v0 ^0 V! A7 b2 ^. B5 adesoxycorticosterone was 4.3 ng/dL (normal, 7 to* l3 \9 [* h/ }7 x3 N2 n' b( v
49ng/dL), 11-desoxycortisol (specific compound S)
( p/ F2 r& H4 h" a1 B/ v8 T Dwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
( f2 L2 y- [, I8 Q% Q h5 j- ]# `tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
! F$ O' ` w# f3 T& h# b$ ltestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
8 L9 {$ Y6 S9 S# m( K$ eand β-human chorionic gonadotropin was less than
0 u+ e/ a2 F- n+ _* ^6 Z5 mIU/mL (normal <5 mIU/mL). Serum follicular
! A2 j/ B8 Z7 D+ F+ H/ k8 y4 V6 rstimulating hormone and leuteinizing hormone
. ` l5 `9 v3 I6 \3 n7 pconcentrations were less than 0.05 mIU/mL' T; _/ c8 ^" g; Z
(prepubertal).
1 k: A" }% r" k9 O- tThe parents were notified about the laboratory
1 G0 r( r; _; H7 Cresults and were informed that all of the tests were# d9 N6 s# l- J: s }8 b9 [
normal except the testosterone level was high. The; t' `- T3 q' s: L* ~
follow-up visit was arranged within a few weeks to
2 p- d4 c* _' D. C; c3 g; T& Qobtain testicular and abdominal sonograms; how-* k8 M7 u% [- y0 P" w& k
ever, the family did not return for 4 months.
9 l0 g4 X! ]. ?$ Y0 k: Y( GPhysical examination at this time revealed that the
: ~4 Y5 x# h$ ~9 M7 Kchild had grown 2.5 cm in 4 months and had gained$ z# ?: ?9 B# T: g
2 kg of weight. Physical examination remained
' Y; E- ~* U/ K/ n" ?unchanged. Surprisingly, the pubic hair almost com-
) k8 x4 a! z' f5 Q2 ?' `pletely disappeared except for a few vellous hairs at
( {$ E X4 _ _the base of the phallus. Testicular volume was still 2
6 P- j4 k/ w0 N) UmL, and the size of the penis remained unchanged.# E& \& ], S# R: |5 o4 ?; l
The mother also said that the boy was no longer hav-% S2 ~9 Z2 X: P1 W# D8 O( H
ing frequent erections.2 i) V8 |" `9 R7 w& L4 Q- ?8 }
Both parents were again questioned about use of
s1 e8 p" s- N! [any ointment/creams that they may have applied to
( @8 j( k$ b% l2 M7 [; r7 \the child’s skin. This time the father admitted the
4 x) h6 }4 x2 W4 WTopical Testosterone Exposure / Bhowmick et al 541
) G( ~% c( y9 p$ n G/ kuse of testosterone gel twice daily that he was apply-, z' f* \: ^0 e) H! p4 }
ing over his own shoulders, chest, and back area for
' E: ^- |* Z1 G: Ka year. The father also revealed he was embarrassed
/ u8 `: b- i6 ]+ uto disclose that he was using a testosterone gel pre-
& Q* [; v: [1 R2 Y( s$ qscribed by his family physician for decreased libido
7 X8 ^. B* K" V; O L0 }secondary to depression.% I! i3 K+ Q, }- J
The child slept in the same bed with parents.' L' O& E" k8 }0 u3 i; `. d
The father would hug the baby and hold him on his
- {& K; H4 n# J9 schest for a considerable period of time, causing sig-. O. W& C/ c% w. p6 G
nificant bare skin contact between baby and father.; x! R* A; U3 l/ |' i- d3 S1 M
The father also admitted that after the phone call,
7 o, O5 i2 Q6 v2 `: Twhen he learned the testosterone level in the baby
% H2 V0 J" c, j0 z* ?9 ?2 Kwas high, he then read the product information
! j9 ?) u0 m! L, [8 w1 Mpacket and concluded that it was most likely the rea-7 C& c% y' e# ^* X. I" J
son for the child’s virilization. At that time, they
" z; G/ I- @! }+ c4 M# Cdecided to put the baby in a separate bed, and the
2 G. z: B7 M2 H. ^& }# E) pfather was not hugging him with bare skin and had
* v& k; u5 l& |: {9 bbeen using protective clothing. A repeat testosterone( b4 o" m: r% ]5 [
test was ordered, but the family did not go to the6 t' K( c9 h7 s9 v1 K' M8 I) A
laboratory to obtain the test.
a6 I) m$ H/ r" NDiscussion
d/ C _6 m' P) NPrecocious puberty in boys is defined as secondary& Z: g i/ a. E8 K1 S. C x
sexual development before 9 years of age.1,46 g1 P2 X6 A( W
Precocious puberty is termed as central (true) when4 w/ n3 Z) F6 y. F) n/ k3 E3 D
it is caused by the premature activation of hypo-: ^% d, r, J* A
thalamic pituitary gonadal axis. CPP is more com-
/ |) f* f0 A' C2 A. O0 Pmon in girls than in boys.1,3 Most boys with CPP
, C) |, I5 H. Y0 K w8 Zmay have a central nervous system lesion that is
! N0 f6 H, h( {responsible for the early activation of the hypothal-* o- U. F1 ^& I3 }; M, X
amic pituitary gonadal axis.1-3 Thus, greater empha-
3 ]* \- {. j/ s5 E6 Rsis has been given to neuroradiologic imaging in
) D$ a' w# E% a6 s) [2 h( Dboys with precocious puberty. In addition to viril-
5 \/ M: ]0 {) v8 fization, the clinical hallmark of CPP is the symmet-
" c% Y9 F4 R: T0 @ V9 Y2 ^0 frical testicular growth secondary to stimulation by* p2 N; | a9 S$ X
gonadotropins.1,3- d) Y5 j/ m4 S
Gonadotropin-independent peripheral preco-
' [: O1 x$ }& J: b1 ?5 `- F3 q8 ~4 rcious puberty in boys also results from inappropriate0 G) A8 [+ _; `& ^7 b% V
androgenic stimulation from either endogenous or3 X$ R T6 q3 f- m3 K$ ^* ^
exogenous sources, nonpituitary gonadotropin stim-5 G6 K! Q; p) x h7 r$ m
ulation, and rare activating mutations.3 Virilizing
$ E8 y4 X) G# T v" W! F- e0 n% Zcongenital adrenal hyperplasia producing excessive' l- o* `, d, J/ t4 w% t u7 v0 S
adrenal androgens is a common cause of precocious/ v+ w4 w- [) t; G7 {9 l& b2 w
puberty in boys.3,4
; K/ Z. @! ~: O* ?The most common form of congenital adrenal
" l, q1 E8 M5 s7 {hyperplasia is the 21-hydroxylase enzyme deficiency.* c" a- q) y0 D* O) x! p! t
The 11-β hydroxylase deficiency may also result in& ?6 M( s/ S- D; }2 H
excessive adrenal androgen production, and rarely,& w) P1 z \ w5 j
an adrenal tumor may also cause adrenal androgen9 }% K$ Z7 {. t, [+ G' A$ Y ?
excess.1,35 B% Q9 k1 G/ g2 `
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from! A9 ]: y; U1 C- q0 Z
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
- A! o2 w. V1 I4 C E+ Z2 D6 dA unique entity of male-limited gonadotropin-
+ I" m, u3 m2 L5 _independent precocious puberty, which is also known
" Q6 e0 H. d2 H' R4 x9 K9 S9 }as testotoxicosis, may cause precocious puberty at a
; j) W' k6 C. Y# j; X+ n( s- Y+ J5 {very young age. The physical findings in these boys
8 s4 x2 A* I1 j& [3 Uwith this disorder are full pubertal development,+ C+ y1 B" W3 ~! x( E$ P
including bilateral testicular growth, similar to boys' G, i* j5 e7 T% v$ x
with CPP. The gonadotropin levels in this disorder
4 y' [8 }6 c! b8 ~0 mare suppressed to prepubertal levels and do not show
$ y- t3 Q+ i! x- p& r/ Fpubertal response of gonadotropin after gonadotropin-% ~& `: `5 R5 c3 G! x* r& \: p* T
releasing hormone stimulation. This is a sex-linked% a5 _7 W! g6 Q8 W8 m; l
autosomal dominant disorder that affects only
* |7 g' N, b* ~' ^( ~3 z1 w7 }males; therefore, other male members of the family
( R5 P4 _" C$ ^7 G9 \* \, O- ~0 l# ymay have similar precocious puberty.3
0 J7 T+ M( {8 C$ B: nIn our patient, physical examination was incon-
( B) Z( A6 t, D" E0 ]8 y9 O$ ssistent with true precocious puberty since his testi-
. l/ X# Q' V4 T& [, zcles were prepubertal in size. However, testotoxicosis
! B: H' c% D# _) c3 ^was in the differential diagnosis because his father
. Z- D+ Z& V' T$ {! kstarted puberty somewhat early, and occasionally,
2 L2 D% L! w l4 Y, Otesticular enlargement is not that evident in the5 ]7 I) q6 C3 r- }7 [' b, Q- s0 R1 R2 j
beginning of this process.1 In the absence of a neg-1 X. }3 Y% ?! |7 ~! v
ative initial history of androgen exposure, our; {1 |- v/ W/ i9 x( [8 g+ l
biggest concern was virilizing adrenal hyperplasia,
- K3 h: O4 R: u% k" i+ heither 21-hydroxylase deficiency or 11-β hydroxylase! }0 i4 s* Q; y+ |- L7 J6 j
deficiency. Those diagnoses were excluded by find-
0 Z/ U3 `& i- K% `& Fing the normal level of adrenal steroids.
: h' r9 T$ K9 x7 [* dThe diagnosis of exogenous androgens was strongly
0 t4 g/ D" u* N3 d; |+ fsuspected in a follow-up visit after 4 months because
1 Y2 E4 S2 D+ Z# kthe physical examination revealed the complete disap-
1 ?6 S w$ D2 e/ ~pearance of pubic hair, normal growth velocity, and/ A8 Z' w/ f% g+ I0 V6 X
decreased erections. The father admitted using a testos-- F5 [2 {1 E' `8 p: r
terone gel, which he concealed at first visit. He was9 d3 X0 q, ` O; M" V8 B
using it rather frequently, twice a day. The Physicians’9 z; c: ?; W, G6 _8 ]$ F
Desk Reference, or package insert of this product, gel or' {$ @6 H# `( E' `1 T. R: u
cream, cautions about dermal testosterone transfer to
: r/ q3 @* _$ `unprotected females through direct skin exposure.
7 {) Q$ z8 R k+ lSerum testosterone level was found to be 2 times the
; P p$ N+ y! m7 zbaseline value in those females who were exposed to
* F* J! r9 g$ o6 T9 }even 15 minutes of direct skin contact with their male7 M( v, e; e5 b: ^
partners.6 However, when a shirt covered the applica-
* n' k4 L/ n6 n& [9 L. vtion site, this testosterone transfer was prevented.
* M+ G# b* t: V: v& T5 C. V, cOur patient’s testosterone level was 60 ng/mL,8 N: p5 M8 K, B6 p3 j& z
which was clearly high. Some studies suggest that% F9 g {: J, h D# S( t8 \! U; n
dermal conversion of testosterone to dihydrotestos-
4 [% K* q2 ~, s! _* d# Lterone, which is a more potent metabolite, is more' J1 j1 k! b! R) o0 n' n
active in young children exposed to testosterone
& r2 K [- D) ?: E5 `1 _exogenously7; however, we did not measure a dihy-
1 `) s8 o; f1 ~, edrotestosterone level in our patient. In addition to: Y/ @( m, Z3 w; z
virilization, exposure to exogenous testosterone in2 ^7 \! e! |" A2 J6 T
children results in an increase in growth velocity and6 E2 ?! @4 E. |' a
advanced bone age, as seen in our patient.4 O4 r5 o% h: N
The long-term effect of androgen exposure during
5 B( R# [6 W% o* ^early childhood on pubertal development and final, V) c8 ?2 X& o: `2 M
adult height are not fully known and always remain
3 I% _( f+ r- s/ K+ n+ @ H$ Ja concern. Children treated with short-term testos-
4 C5 w( x9 N0 B" h5 L8 P0 C/ s" fterone injection or topical androgen may exhibit some
7 [, r! h* B6 G1 E4 {acceleration of the skeletal maturation; however, after
/ h( t [/ `. `2 a. Qcessation of treatment, the rate of bone maturation" q5 L z9 R$ Y/ D; H: s- q& [5 ~
decelerates and gradually returns to normal.8,9
6 S1 W- z) `4 L9 j3 eThere are conflicting reports and controversy
: G/ ]( C; t. J0 {9 v' \" [over the effect of early androgen exposure on adult; j& D1 d: s3 ]+ {
penile length.10,11 Some reports suggest subnormal/ }( k( d2 v2 ^) q/ k& b1 ?6 `
adult penile length, apparently because of downreg- L: T. J% K4 b4 K* S
ulation of androgen receptor number.10,12 However,# B6 @! D/ d, y7 _, \
Sutherland et al13 did not find a correlation between# v2 }& m6 K0 ~2 c
childhood testosterone exposure and reduced adult
- I/ y1 _" v/ u: i9 i, hpenile length in clinical studies.
; U; H) z+ Q* ^+ r8 g2 dNonetheless, we do not believe our patient is
7 u6 u, U& I* y- d5 g0 Jgoing to experience any of the untoward effects from2 I; n( J8 | o1 [- y1 g8 {
testosterone exposure as mentioned earlier because
1 t4 D' U2 U4 C, t( Vthe exposure was not for a prolonged period of time.
4 E5 J$ h+ Y1 V: E6 g7 y5 f! `6 H- w; pAlthough the bone age was advanced at the time of
. R) f, j4 [0 t+ o; E' W# Kdiagnosis, the child had a normal growth velocity at
% l- @' Y1 C& x3 sthe follow-up visit. It is hoped that his final adult
8 p+ L; }+ }4 o9 Pheight will not be affected.. h8 N w, h( F5 Q
Although rarely reported, the widespread avail-
- V8 T4 d8 V1 P$ C3 [ability of androgen products in our society may
2 h4 L7 y8 N0 m2 l, E+ q% Mindeed cause more virilization in male or female
0 z+ N" D4 [# J |children than one would realize. Exposure to andro-
3 N, a# y: ]7 a) I- _. mgen products must be considered and specific ques-
$ }0 |8 l# I) G( Ftioning about the use of a testosterone product or
2 q, K5 w* C; q9 |gel should be asked of the family members during
( c/ J" O# m$ r v5 @& `; Ythe evaluation of any children who present with vir-
( r; \# G/ E6 _) ~. ^3 L Filization or peripheral precocious puberty. The diag-& Q0 @, n5 x% c1 H/ j5 Z" [& B
nosis can be established by just a few tests and by& u3 J; f" \5 K
appropriate history. The inability to obtain such a+ k& p% S4 ?; m2 |, u
history, or failure to ask the specific questions, may: q2 s; U, K6 o- K$ X/ N. ?( ~ ^, m
result in extensive, unnecessary, and expensive
+ B: A3 c1 L' ]) Vinvestigation. The primary care physician should be
& q' j3 K" z6 a7 N7 Vaware of this fact, because most of these children
3 t C) P2 b3 d# ~( u9 k7 w$ {may initially present in their practice. The Physicians’/ E$ v0 o) _( Y4 Y5 A4 V# l& R
Desk Reference and package insert should also put a
9 J; h; Y L$ |# u6 J% w9 Jwarning about the virilizing effect on a male or1 n- x- h& A' h. Y \: o
female child who might come in contact with some-
2 Y# U4 N) `9 e0 j' [one using any of these products.- P( d- g7 s1 F+ e
References
7 O$ w& q! B9 Y4 o$ l9 X7 `1. Styne DM. The testes: disorder of sexual differentiation
9 h, k( b! p: B; x# {/ l" @and puberty in the male. In: Sperling MA, ed. Pediatric% [" h9 W X( v J
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
- U% S; l& O/ S. q5 ]2002: 565-628.
4 L& P4 @5 f: | F! I$ o! o1 `2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious+ c1 w2 _& _) Q1 D
puberty in children with tumours of the suprasellar pineal |
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