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Sexual Precocity in a 16-Month-Old7 J) D; V$ P* J6 m7 \- U
Boy Induced by Indirect Topical
# q* n: o, Q% W* h* H5 y9 M( b) ]Exposure to Testosterone: W8 p/ K6 F5 p1 ?
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
) l2 i! j4 p* }2 J( t. j L% zand Kenneth R. Rettig, MD1
; h3 I! O# `6 @Clinical Pediatrics; A; E5 B. o7 z! z ?1 ]3 z
Volume 46 Number 6+ d& T: T- V) u9 Y/ I
July 2007 540-5435 g3 X* ~3 L8 _0 p' m
© 2007 Sage Publications
& M% A& `3 C4 K" C& X+ r10.1177/0009922806296651
3 d% I1 P! @* z4 chttp://clp.sagepub.com1 x5 W' ` _( a& I: I
hosted at [3 G4 T; B0 i, `; t u& v2 C
http://online.sagepub.com
# P) E9 K2 C( v2 g. mPrecocious puberty in boys, central or peripheral,
" e" t& m+ J; ^: c3 pis a significant concern for physicians. Central
: p( M2 R$ r; G- b! R+ _/ ]precocious puberty (CPP), which is mediated
* v2 o1 A5 r7 m# {through the hypothalamic pituitary gonadal axis, has
4 J" _. r. ?, }! ya higher incidence of organic central nervous system; X- l) E( M0 I; @' U
lesions in boys.1,2 Virilization in boys, as manifested+ D5 t) y8 ~5 M. p' |
by enlargement of the penis, development of pubic7 e) f* f2 _- C$ L4 _
hair, and facial acne without enlargement of testi-4 L5 l; s8 V6 P' M) t3 j, C/ q' n
cles, suggests peripheral or pseudopuberty.1-3 We
6 S1 O- c5 [* r7 K$ nreport a 16-month-old boy who presented with the) p: E/ W7 u( C, h- B" x9 x- _
enlargement of the phallus and pubic hair develop-/ x4 \' o! Z/ d1 l$ K& K# g
ment without testicular enlargement, which was due/ [2 ~9 B" r n5 [: C) [9 o ]8 g
to the unintentional exposure to androgen gel used by; ^4 ^( r: k9 B) Q+ A# p6 v
the father. The family initially concealed this infor-
4 `- h* S% r: \$ \+ Kmation, resulting in an extensive work-up for this
$ h7 F- J# h7 p0 S/ ^( ~: [child. Given the widespread and easy availability of9 Q; }! X4 N. U, m1 w
testosterone gel and cream, we believe this is proba-
$ r, [* J# x2 e5 m9 Zbly more common than the rare case report in the) |! F4 {+ e8 E* S0 P. o6 K
literature.4
I6 h" M- Z# }4 s- C1 EPatient Report
; f" J( R' @ _1 h9 @* QA 16-month-old white child was referred to the
# u2 |5 _# W- o7 S9 X% hendocrine clinic by his pediatrician with the concern
( L, b1 ]0 M) z$ D% K. Hof early sexual development. His mother noticed
2 o/ H+ `& B) }5 U0 o4 klight colored pubic hair development when he was- u4 q5 y. a' u: B4 m O
From the 1Division of Pediatric Endocrinology, 2University of; T+ j, s7 l/ Y- [/ K. ?0 y) x
South Alabama Medical Center, Mobile, Alabama.
/ V) X: a$ T9 D2 r/ l/ JAddress correspondence to: Samar K. Bhowmick, MD, FACE,
" l' N4 j1 X) D! t XProfessor of Pediatrics, University of South Alabama, College of6 r( h- i) N# e- L' l8 |
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;4 t/ p5 Y8 ]& J; Y. H2 P
e-mail: [email protected].
7 S0 f7 x% c. ~: aabout 6 to 7 months old, which progressively became
- K6 \. Z* |) ^darker. She was also concerned about the enlarge-! h/ r. ]. O1 D( I
ment of his penis and frequent erections. The child4 x/ g+ T: A, t& t/ `' V9 Z: e1 w) o
was the product of a full-term normal delivery, with+ M6 v5 V) w) V; s; M
a birth weight of 7 lb 14 oz, and birth length of8 X% Z8 z, a, X7 u$ I
20 inches. He was breast-fed throughout the first year
5 I# n l \! d6 sof life and was still receiving breast milk along with/ I3 A8 c" @6 `! s& b( Q2 y
solid food. He had no hospitalizations or surgery,
7 `" r- p' |- B( [: nand his psychosocial and psychomotor development
9 H" R0 S% }( W- jwas age appropriate. r7 }5 S1 P v6 Z$ P2 s
The family history was remarkable for the father,
d& r+ W5 m! G7 V7 O$ owho was diagnosed with hypothyroidism at age 16, |) q, K+ L' Z( a- V- y
which was treated with thyroxine. The father’s
; d8 ^! H# r, c( K2 Z. lheight was 6 feet, and he went through a somewhat. @1 \. u. y. ^% B8 ^. Z
early puberty and had stopped growing by age 14.* J3 i. j3 x7 N0 _
The father denied taking any other medication. The
" m8 m* H, B! h! {: ~child’s mother was in good health. Her menarche
! R/ c% P4 U. i/ X. uwas at 11 years of age, and her height was at 5 feet
* r' h, z5 W/ e+ G5 inches. There was no other family history of pre-# s; ~$ u$ X. d
cocious sexual development in the first-degree rela-- U( M" \4 Q* V2 E, ?
tives. There were no siblings./ |& R O5 b3 ~0 V. ^9 F. N
Physical Examination b" Z8 ~( T2 ^" \( K
The physical examination revealed a very active,
2 F: h6 q( g" @8 p/ b* bplayful, and healthy boy. The vital signs documented
! s6 w0 g1 v. s* ?8 l; w0 sa blood pressure of 85/50 mm Hg, his length was3 r7 @( l/ Z- y$ o
90 cm (>97th percentile), and his weight was 14.4 kg4 q# Q' X1 I; p: O, }* P
(also >97th percentile). The observed yearly growth* {' X# R- e. U! G% z! W
velocity was 30 cm (12 inches). The examination of5 b b$ P2 ?2 ]& G# Z& R
the neck revealed no thyroid enlargement.0 B; d' y5 v- K$ `& |
The genitourinary examination was remarkable for
3 K' p. O% j* o7 ^, uenlargement of the penis, with a stretched length of% p; H/ v7 U; l1 c3 w P. P+ M
8 cm and a width of 2 cm. The glans penis was very well
& T/ o9 {' P) f) U, X; Z5 ideveloped. The pubic hair was Tanner II, mostly around
- g5 m& J- T6 x* A540% [% U. N' V0 \. V- S' _; D
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from, x' b" I6 l% v/ h! J4 W3 W
the base of the phallus and was dark and curled. The
. T3 d3 k0 }) S' h( F5 S$ xtesticular volume was prepubertal at 2 mL each. V+ i: }5 z9 Y: {
The skin was moist and smooth and somewhat
! |- [9 Y4 T$ e5 h6 hoily. No axillary hair was noted. There were no
& [6 D0 \! `9 m5 habnormal skin pigmentations or café-au-lait spots.
; }; |3 N0 p: dNeurologic evaluation showed deep tendon reflex 2+; y; S3 b, F* Q& _% ?1 p
bilateral and symmetrical. There was no suggestion7 Z9 ? X( K0 \! l; U; E3 z P
of papilledema.
/ C X& m" @. p9 n* g7 w) E" A; H5 rLaboratory Evaluation
( f% H, |7 ]: L! B5 y. p; ?' gThe bone age was consistent with 28 months by, B4 |7 l: m& I: X& b: c- K
using the standard of Greulich and Pyle at a chrono-
3 a; G6 C3 N9 L- D* f' vlogic age of 16 months (advanced).5 Chromosomal
' e; _* k: i( [3 a0 i. Xkaryotype was 46XY. The thyroid function test0 x0 A# M6 O- O! v! ~% f' G3 ^
showed a free T4 of 1.69 ng/dL, and thyroid stimu-2 `9 a9 c% h, q# F$ \2 K$ W
lating hormone level was 1.3 µIU/mL (both normal).
" r- C" x6 p3 RThe concentrations of serum electrolytes, blood
: J4 V3 R& H; u2 p Lurea nitrogen, creatinine, and calcium all were
. L( v% W# I3 ]: awithin normal range for his age. The concentration
, Q- i' M* `9 a7 o% B3 Fof serum 17-hydroxyprogesterone was 16 ng/dL
- ~: x& g/ x; D) j% C1 \& m(normal, 3 to 90 ng/dL), androstenedione was 20
0 h' \& N+ c8 } H, f* Z! x: O: xng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-0 R1 j" L3 V+ d( s3 K5 p* D( w
terone was 38 ng/dL (normal, 50 to 760 ng/dL),3 ]9 D3 N4 o8 h7 m/ S Y9 |
desoxycorticosterone was 4.3 ng/dL (normal, 7 to$ x; w8 {& F( Y$ F+ L
49ng/dL), 11-desoxycortisol (specific compound S)
; A- j ^! p( {, k8 E- A$ pwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
! ^, C9 T7 ?0 r) ^' ftisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
8 o9 ~4 H1 _ u: `4 i& U: h$ F; r4 f& x5 gtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
! I$ d% e0 v+ Y6 R; Cand β-human chorionic gonadotropin was less than; [9 p, D S- \% h% A% t: ]0 n
5 mIU/mL (normal <5 mIU/mL). Serum follicular
7 ^2 ^4 Q& N7 Y! F6 `. ^8 [# k5 v2 ostimulating hormone and leuteinizing hormone P0 ] l. N. ]( z, o. ]1 y1 U
concentrations were less than 0.05 mIU/mL
' i) ]( a! l) J8 _% Z(prepubertal).
# g8 J2 V9 X7 a/ \- r2 wThe parents were notified about the laboratory% I$ c2 K4 `6 ~2 \% M* L5 T; O
results and were informed that all of the tests were2 K2 n1 o6 S3 I; \6 ^
normal except the testosterone level was high. The
$ ?) \% |5 V2 R/ P; jfollow-up visit was arranged within a few weeks to* I3 [8 F4 v& `8 B
obtain testicular and abdominal sonograms; how-
# w: A/ s, D/ P! `* `2 gever, the family did not return for 4 months.
* X0 q# D, G& U" z5 C( l$ D; VPhysical examination at this time revealed that the
8 Z) I$ k4 S+ B5 y8 K1 }( B- Hchild had grown 2.5 cm in 4 months and had gained
, F( }5 b8 I. S0 F8 s2 kg of weight. Physical examination remained* G5 ?4 {3 k L
unchanged. Surprisingly, the pubic hair almost com-
' \8 a6 _5 X, {5 T3 O" Mpletely disappeared except for a few vellous hairs at
# t f5 e9 C9 B& h1 U1 @' tthe base of the phallus. Testicular volume was still 21 ]8 }, p# V8 j# n3 U
mL, and the size of the penis remained unchanged.
- a- ?7 o7 n2 ?1 s! v& qThe mother also said that the boy was no longer hav-( |- E. f; Y. h. l
ing frequent erections.
( G, w. M, d: z# K% \" q, sBoth parents were again questioned about use of5 O4 C" `2 ]6 i
any ointment/creams that they may have applied to" P+ E. g% k& N) z, g8 P8 D
the child’s skin. This time the father admitted the
* i1 E; Y9 E' Y( R! z* b# C9 VTopical Testosterone Exposure / Bhowmick et al 541. ]; t! P2 [- R
use of testosterone gel twice daily that he was apply-
( M5 y( e* Y9 Ling over his own shoulders, chest, and back area for
5 k! g5 ~2 C6 e. W' U: Ia year. The father also revealed he was embarrassed, o' z$ e! h2 i4 y8 I
to disclose that he was using a testosterone gel pre-
" T( ?6 A' J( r, R5 c. g" ]5 _: vscribed by his family physician for decreased libido
. T4 t# z C; H) ^2 W" tsecondary to depression. B2 t% w+ {( i; E( [% l
The child slept in the same bed with parents.9 g: a7 s, ]( l& Q/ |
The father would hug the baby and hold him on his( W/ G# ~/ f+ ]- K b4 | `
chest for a considerable period of time, causing sig-5 F' e8 x2 I' ]; E3 o
nificant bare skin contact between baby and father.
& e( {5 u+ W$ e: u7 ?5 W' l: c+ NThe father also admitted that after the phone call,
4 ~" c8 g' e" C* l: Y b, hwhen he learned the testosterone level in the baby
, g6 G( j( J% l0 P0 \was high, he then read the product information
+ B8 B, B2 S# \6 w! Y0 ypacket and concluded that it was most likely the rea-1 m; G+ e$ W$ }1 f2 Z2 n7 t
son for the child’s virilization. At that time, they
$ F: ]( S7 `3 a4 P; }$ H( p; ]decided to put the baby in a separate bed, and the; L1 a" G7 _" m, j' h5 n) y
father was not hugging him with bare skin and had$ ~8 g9 W/ q$ O3 |4 t5 S3 b1 @3 |
been using protective clothing. A repeat testosterone
+ |) h; |: i- l- Y* _9 Btest was ordered, but the family did not go to the
# V8 M( R. n' k7 T% ?+ Q) P" alaboratory to obtain the test.
' C& `8 ]! q! m# T* |Discussion) T( C) J2 z) H W
Precocious puberty in boys is defined as secondary2 @$ w6 T' M9 f' m6 P4 w ~
sexual development before 9 years of age.1,4
% e) E) A% D& ^Precocious puberty is termed as central (true) when
! s/ Q! M) I7 Tit is caused by the premature activation of hypo-
! D6 Z9 o, M4 `0 ^3 Y" Zthalamic pituitary gonadal axis. CPP is more com- ?, r% t. }- ]# N! x
mon in girls than in boys.1,3 Most boys with CPP" [$ z$ ?' D4 r# R4 D% `
may have a central nervous system lesion that is
7 y, V2 x' d% W" R! _. ]responsible for the early activation of the hypothal- d- S! z- o! B8 e4 T1 p: p9 i
amic pituitary gonadal axis.1-3 Thus, greater empha-
' S" j) P( P, Ysis has been given to neuroradiologic imaging in/ \/ g7 `7 W* Y9 r2 ]0 @* l4 O
boys with precocious puberty. In addition to viril-
6 g/ w+ m% B) t+ x; t9 J' p5 gization, the clinical hallmark of CPP is the symmet-% B: M S6 E" c1 F; A
rical testicular growth secondary to stimulation by- W7 O, Z6 b( D! I4 J6 }* H
gonadotropins.1,3: ^4 W0 {, z$ {) F
Gonadotropin-independent peripheral preco-( s6 E- z! p1 K/ o1 o$ h
cious puberty in boys also results from inappropriate
; P, ?6 P- _' r5 dandrogenic stimulation from either endogenous or7 V+ I/ Q% p8 {
exogenous sources, nonpituitary gonadotropin stim-; p. ]& x- h7 S+ c3 _4 V
ulation, and rare activating mutations.3 Virilizing
& T. P) p' i) F5 W* econgenital adrenal hyperplasia producing excessive; |' P [2 M; Z) [8 A
adrenal androgens is a common cause of precocious7 p- ~% K# M- X8 g6 e& R/ v1 T
puberty in boys.3,4
& F3 K0 ~* r9 q& H+ LThe most common form of congenital adrenal
2 I' R/ T7 L2 a" lhyperplasia is the 21-hydroxylase enzyme deficiency.
; b* Q4 U0 P0 _4 i uThe 11-β hydroxylase deficiency may also result in
) Q( W; Y3 M! S0 L7 E/ q$ oexcessive adrenal androgen production, and rarely,0 s( C. M- \$ v4 d% l$ N: M; U
an adrenal tumor may also cause adrenal androgen7 d* \+ R i4 c. R' u. q" n$ v5 A
excess.1,3
9 T/ s3 _! _; ~. L) U) ?at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from9 i( c1 x! u7 _
542 Clinical Pediatrics / Vol. 46, No. 6, July 20073 o& M" @5 z/ F( f9 {! X/ Q2 w! D
A unique entity of male-limited gonadotropin-. Y$ g/ l. r( [2 |( w0 ^9 G5 j" E
independent precocious puberty, which is also known" J' D- {, p: y/ f( c
as testotoxicosis, may cause precocious puberty at a+ m. P u5 l T& n5 J e9 n# l; W
very young age. The physical findings in these boys
0 e7 ?5 G7 P, H% } W' U8 Fwith this disorder are full pubertal development,$ v8 z: [0 Q) F/ E3 e- Z$ d
including bilateral testicular growth, similar to boys
5 K! h/ Z8 f" }with CPP. The gonadotropin levels in this disorder- \/ p$ x- p9 Y0 d: B7 v" u
are suppressed to prepubertal levels and do not show" ^) R; S7 U2 ?, B S% V1 r% J
pubertal response of gonadotropin after gonadotropin-+ ]6 u9 ~+ Y- {2 U+ N
releasing hormone stimulation. This is a sex-linked
# r( y& `# T; L/ g, a4 \' B% Nautosomal dominant disorder that affects only3 Z3 o: O1 }$ p" f! w: d7 n
males; therefore, other male members of the family4 l6 {/ {+ a# q2 L7 @! v! k! z
may have similar precocious puberty.3. {& r$ K( Q4 e- j9 d9 J
In our patient, physical examination was incon-
2 y# ~5 G- u9 r R% [$ ksistent with true precocious puberty since his testi-3 Y4 {+ }, K- M5 k7 Y2 X7 M5 r3 j
cles were prepubertal in size. However, testotoxicosis- Q' ?: g3 U& Z& l8 Z* v1 b
was in the differential diagnosis because his father
( ^7 ]( L/ g& D' ystarted puberty somewhat early, and occasionally,
# _+ A) E7 p7 M& M7 ]* Utesticular enlargement is not that evident in the# C/ p; A: ?* J- J# |
beginning of this process.1 In the absence of a neg-
% F- i, Q; K. K: N8 K& C ] W+ cative initial history of androgen exposure, our
" {/ m0 q& [& Y8 z1 @3 E$ Abiggest concern was virilizing adrenal hyperplasia,
. U0 \: B! }: Heither 21-hydroxylase deficiency or 11-β hydroxylase
B; h1 t# Y2 Q( B! v+ Jdeficiency. Those diagnoses were excluded by find-/ l$ [3 Z* t$ m: s7 k* y3 N* m
ing the normal level of adrenal steroids.5 T) L# b; p5 }9 M7 ?+ L
The diagnosis of exogenous androgens was strongly2 S& S% c( c' U4 g
suspected in a follow-up visit after 4 months because
$ D ~0 G" F- U. G7 rthe physical examination revealed the complete disap-
( Y; }6 }, q2 spearance of pubic hair, normal growth velocity, and
" u# ^* _4 T, u9 h9 B# @3 ddecreased erections. The father admitted using a testos-+ U) P" l. ]* c' @2 ^1 _
terone gel, which he concealed at first visit. He was
S" X" C2 g1 q! m- d: G! Wusing it rather frequently, twice a day. The Physicians’
- A4 T- I3 _) GDesk Reference, or package insert of this product, gel or
7 }5 e7 z: j5 \( _9 g+ ~cream, cautions about dermal testosterone transfer to
3 ~/ Y& Y8 O$ Q; U, U0 d7 `7 n2 ^unprotected females through direct skin exposure.
7 I" q! Y# f! ZSerum testosterone level was found to be 2 times the
& L, ^8 y" z& O* G& c5 jbaseline value in those females who were exposed to
9 ~4 C% A. h( beven 15 minutes of direct skin contact with their male0 N5 F$ [# V+ T( e9 G' B* \
partners.6 However, when a shirt covered the applica-
5 C9 Q# g, D: d5 k" ]tion site, this testosterone transfer was prevented.
+ {5 m' U- D+ {9 [Our patient’s testosterone level was 60 ng/mL,
# d; R3 d5 t* Swhich was clearly high. Some studies suggest that( G8 V% E: H, e
dermal conversion of testosterone to dihydrotestos-
5 E3 q- u5 `. K5 p4 Uterone, which is a more potent metabolite, is more6 ]8 }* z) Z0 q
active in young children exposed to testosterone) E( H# k$ D; _0 }* E0 `! n- @
exogenously7; however, we did not measure a dihy-9 B5 J9 c9 J* b1 l6 H. z6 | c
drotestosterone level in our patient. In addition to
4 p; C8 g' L+ z# y0 M0 hvirilization, exposure to exogenous testosterone in
5 ?" ?& C$ D( dchildren results in an increase in growth velocity and
( V% o, z/ \% Eadvanced bone age, as seen in our patient.1 y) `( ~: t4 b6 e, u, ?8 K
The long-term effect of androgen exposure during
* a: x7 C5 V8 w* {early childhood on pubertal development and final
( g* E: F+ _+ s6 a0 E) ]3 `adult height are not fully known and always remain3 i% h8 {/ H! m1 o- ]0 Y
a concern. Children treated with short-term testos-) h2 F& X3 |4 L" F" L3 O' N+ f
terone injection or topical androgen may exhibit some
' I! G2 }1 M& r, U' Facceleration of the skeletal maturation; however, after
9 ?+ Y, K: F+ Y! Tcessation of treatment, the rate of bone maturation
6 P- Q! Y5 M" L6 o* B/ mdecelerates and gradually returns to normal.8,9/ N" D- ^3 R2 P V: ~/ |
There are conflicting reports and controversy
+ g! }4 V0 i# t2 {3 a# v# [5 L% yover the effect of early androgen exposure on adult, l2 t/ H7 @5 ~" D; p$ j
penile length.10,11 Some reports suggest subnormal
" E5 I* ?4 a. l2 y/ o/ Kadult penile length, apparently because of downreg-* c# |+ \& z1 D8 ?' H% X
ulation of androgen receptor number.10,12 However,' C- H' P7 i% D: H
Sutherland et al13 did not find a correlation between+ t6 @ k3 z9 A3 X3 k5 w7 U
childhood testosterone exposure and reduced adult4 A' Z3 @4 r" e
penile length in clinical studies.
( Z+ c4 V( s+ t- z+ Y6 \Nonetheless, we do not believe our patient is
0 a) | n, D* o0 k; ngoing to experience any of the untoward effects from
4 N2 i0 S5 t2 d* Otestosterone exposure as mentioned earlier because
( B M8 L0 _1 j! E5 x6 I5 Uthe exposure was not for a prolonged period of time.
; h+ d m) F! _/ b" [3 c. L& eAlthough the bone age was advanced at the time of/ J/ |0 e# K- f
diagnosis, the child had a normal growth velocity at9 K5 h1 p2 U6 P2 ~
the follow-up visit. It is hoped that his final adult. A) T/ P& l d7 }, _, d. w
height will not be affected.
4 b {* R8 _( J+ K' R8 r6 IAlthough rarely reported, the widespread avail-2 k0 T7 c- E2 [1 E( y0 P
ability of androgen products in our society may" w& w, X/ B9 `4 Q, J
indeed cause more virilization in male or female; g1 r; _/ l% c0 }5 c( }
children than one would realize. Exposure to andro-
5 C* T3 H" w ]# H' kgen products must be considered and specific ques-4 P3 i/ m( T8 W6 ^; ^
tioning about the use of a testosterone product or
" K3 G" s5 d# J$ @4 m/ F1 agel should be asked of the family members during
) {- Q) f- Y* ~, ~6 Q' C1 H- Gthe evaluation of any children who present with vir-
& @; L) A* K1 |8 V1 rilization or peripheral precocious puberty. The diag-4 W, U( |4 `6 K: I& }% O8 D
nosis can be established by just a few tests and by& V& w! }; _" v9 C" R! Q( v z& z$ N
appropriate history. The inability to obtain such a4 b" G% r) `) |' r: D; _; H6 i, r
history, or failure to ask the specific questions, may+ ]0 K% @. c2 F4 q9 w
result in extensive, unnecessary, and expensive
+ x4 m2 M$ z/ u! sinvestigation. The primary care physician should be9 T0 ?, ~+ ^; H3 y9 T( L3 k9 X. Q" ?
aware of this fact, because most of these children
# A# f) N, O( c o8 b, ~) @6 ?may initially present in their practice. The Physicians’5 W' k; y$ M0 g& M* I! ]( Y' {
Desk Reference and package insert should also put a
9 S8 f5 w7 C! s! Z' Dwarning about the virilizing effect on a male or+ |( `8 M2 X, O( f& w' J9 [
female child who might come in contact with some- e/ s& a; Q- Y/ l' O+ C @5 Z: l$ T
one using any of these products.* C2 U1 l' J! u3 ~. h4 s
References
! G. |/ p/ X# F& A- i! S8 Q1. Styne DM. The testes: disorder of sexual differentiation
! c) s3 ~ Y. ]6 i& Xand puberty in the male. In: Sperling MA, ed. Pediatric
6 } \ Z- L' \$ c# t5 {% @Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;, c1 `2 j, W, @$ m
2002: 565-628.
4 _3 [3 g6 r! @2 @2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious: u" N7 `% S! Q9 L0 a( c* O( v
puberty in children with tumours of the suprasellar pineal |
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