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Sexual Precocity in a 16-Month-Old
8 U6 I" o- F; A* qBoy Induced by Indirect Topical; M- }, V/ B B, r, e
Exposure to Testosterone
. N C; n2 \- KSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2' t' i2 S; u$ O/ N$ T
and Kenneth R. Rettig, MD1) |7 i% G: c0 ~! S2 O2 R. M
Clinical Pediatrics. L6 Y, j/ z: W! }2 V
Volume 46 Number 6
8 V3 E/ t' B$ }. z% ~, _1 H6 fJuly 2007 540-543
" U' s' q: l5 z0 C A! B© 2007 Sage Publications
5 P$ H3 ~) C6 t8 u$ o1 L7 L- ?2 @10.1177/0009922806296651) Q+ S# |( v# p. J: [
http://clp.sagepub.com
% u' B5 \' U5 H6 w0 J) l' \. u* |" Mhosted at' } ~+ }8 Z. p: N: _* g
http://online.sagepub.com
4 X$ m4 {2 j. j3 D( p9 uPrecocious puberty in boys, central or peripheral,8 k; C! ]5 y) o
is a significant concern for physicians. Central
( C" y; q9 D4 B( ~1 {# u5 ^, Uprecocious puberty (CPP), which is mediated
) L6 Q& Q' h3 t5 mthrough the hypothalamic pituitary gonadal axis, has
+ n1 \5 p8 L( v9 O3 ^; [a higher incidence of organic central nervous system
# y. r9 d; ?7 o. I/ N2 Y6 k' Slesions in boys.1,2 Virilization in boys, as manifested
7 N F2 E" S& |+ v* L+ g3 aby enlargement of the penis, development of pubic. P+ j9 r4 }" b/ G# W" @
hair, and facial acne without enlargement of testi-) c8 N* L! r' I& S+ v) v/ B
cles, suggests peripheral or pseudopuberty.1-3 We
( ?9 e1 h6 T- K% J i Jreport a 16-month-old boy who presented with the
- ^9 g! z. O/ C) p2 Henlargement of the phallus and pubic hair develop-
% d3 a! l8 u4 E0 `$ v: tment without testicular enlargement, which was due
3 a, A1 U7 U3 y& h2 p6 d; \7 t1 I7 Bto the unintentional exposure to androgen gel used by
7 K1 ]6 {* h' kthe father. The family initially concealed this infor-
" ?9 I0 x( S z Fmation, resulting in an extensive work-up for this! [- j, C" x. u; ~- T* X& H+ p0 `
child. Given the widespread and easy availability of
3 k, _9 U- K: Stestosterone gel and cream, we believe this is proba-
- B9 K3 ~! K0 m3 H' k8 Rbly more common than the rare case report in the1 F, @2 } o5 j+ \% a8 p
literature.4
, \+ F, k+ p6 Y5 \% [Patient Report4 V6 y2 w: P# `1 ^
A 16-month-old white child was referred to the
" H: P! j, Y3 Cendocrine clinic by his pediatrician with the concern0 q- H# z. |1 Z2 M
of early sexual development. His mother noticed
6 \0 N$ J# ~+ O* o6 elight colored pubic hair development when he was
# v8 J, q/ F& h/ f6 D" f% A, c9 DFrom the 1Division of Pediatric Endocrinology, 2University of4 e6 k+ g/ \5 ]/ ]
South Alabama Medical Center, Mobile, Alabama.3 k% v' l; G' y, G; A
Address correspondence to: Samar K. Bhowmick, MD, FACE,4 [" ]: {$ q" I9 `; W) c e7 `- c) D4 |
Professor of Pediatrics, University of South Alabama, College of& u( h. Q" `6 e/ R! t& N
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
6 ~8 A7 ^/ H% M+ u. @1 O) z; p' qe-mail: [email protected].
% ~/ b/ u* ^1 babout 6 to 7 months old, which progressively became9 t- }' Q5 N* b6 H7 i3 e ?$ F
darker. She was also concerned about the enlarge-; U' N$ Y! X4 w$ X0 c% P
ment of his penis and frequent erections. The child
: J) v3 k& s$ Dwas the product of a full-term normal delivery, with. O1 _. W8 ^, t/ M+ Q/ z
a birth weight of 7 lb 14 oz, and birth length of. y1 @, G! y- E/ T, b
20 inches. He was breast-fed throughout the first year
! ]8 V4 U- z. E; g8 I& tof life and was still receiving breast milk along with
( w0 k/ T0 J h( r4 d5 Zsolid food. He had no hospitalizations or surgery,# s! M' L5 v8 E* p1 Z
and his psychosocial and psychomotor development' a; w6 \% g/ e6 ?, U
was age appropriate.
/ M* }* C; l0 i2 d o0 B" uThe family history was remarkable for the father,
/ X1 w$ R7 o/ rwho was diagnosed with hypothyroidism at age 16,
Y- V; z, _2 z' @* [which was treated with thyroxine. The father’s5 j3 C. r% ^) f$ e
height was 6 feet, and he went through a somewhat
6 v7 d/ v, a5 d( e5 Y+ Q5 u, rearly puberty and had stopped growing by age 14.
* O$ ^& y* J$ X6 s+ E$ sThe father denied taking any other medication. The9 E( b$ ^* X% Y$ v7 c
child’s mother was in good health. Her menarche$ f3 \! p* M2 s; B% v, s4 e3 f
was at 11 years of age, and her height was at 5 feet6 z9 s2 T3 ^8 c8 ]9 |* I
5 inches. There was no other family history of pre-
! \: e2 z) l% X$ b# ^cocious sexual development in the first-degree rela-4 q2 I& E% B# t& C" _" a7 D9 B
tives. There were no siblings.3 l; T/ k7 K) m- y7 a1 U9 Q
Physical Examination: N' f6 K! S# N8 \' z; ^
The physical examination revealed a very active,- x+ s7 q2 U1 T4 i: U9 u& C
playful, and healthy boy. The vital signs documented
8 z8 e" r" l/ r4 Oa blood pressure of 85/50 mm Hg, his length was
4 L, f5 }) f* C4 L! B90 cm (>97th percentile), and his weight was 14.4 kg
8 O2 {. p, J0 c3 M% c/ A0 G(also >97th percentile). The observed yearly growth ~6 i: Y6 Q7 H7 h
velocity was 30 cm (12 inches). The examination of
3 O1 r/ S' G& G) s& o. w2 H ~+ Dthe neck revealed no thyroid enlargement.
4 s3 q6 h; n/ @' iThe genitourinary examination was remarkable for8 Z" A" Y6 i/ c; H# S
enlargement of the penis, with a stretched length of
/ K+ e5 |7 c: G" Y6 h9 }8 L8 cm and a width of 2 cm. The glans penis was very well8 B" A( a4 o- i; N& h
developed. The pubic hair was Tanner II, mostly around
/ G+ a9 v# n b$ I& m x540
5 s: U" R7 U3 O5 Gat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from( d% A: Y; t* w( J3 Z& M
the base of the phallus and was dark and curled. The+ [0 ]/ z) `# P& Z; m
testicular volume was prepubertal at 2 mL each.
% j1 K% F9 o' J0 h" LThe skin was moist and smooth and somewhat/ F5 B: F z6 V U/ y9 K4 @
oily. No axillary hair was noted. There were no* J' }1 I& L. x- g$ P! |, E" r
abnormal skin pigmentations or café-au-lait spots.- x: E( x6 }5 M3 `9 G% {
Neurologic evaluation showed deep tendon reflex 2+
6 r B" F# P( r+ j/ `. lbilateral and symmetrical. There was no suggestion6 s3 ?" p Z$ @1 Y6 O
of papilledema.
/ a3 X. E7 N, T3 }5 m1 B7 qLaboratory Evaluation5 ~" v' [% p+ C( f
The bone age was consistent with 28 months by
9 g k9 k' F3 }: X5 ]8 C t/ xusing the standard of Greulich and Pyle at a chrono-
% w: M' K. H6 I P% S' T0 ^6 Hlogic age of 16 months (advanced).5 Chromosomal
' Z" F* R2 K2 e( \) C8 M* R e/ Skaryotype was 46XY. The thyroid function test; ?8 g/ t: Y$ u' {8 h7 J
showed a free T4 of 1.69 ng/dL, and thyroid stimu-6 ]9 J$ c/ E1 o
lating hormone level was 1.3 µIU/mL (both normal).
$ ^# d4 a) H6 L( }4 XThe concentrations of serum electrolytes, blood
3 g1 R3 g. {+ i$ @2 \urea nitrogen, creatinine, and calcium all were6 f- u, p+ H' P3 X- |
within normal range for his age. The concentration
: S. @$ B4 Z7 `of serum 17-hydroxyprogesterone was 16 ng/dL( H6 O9 Q7 U8 [9 d1 c
(normal, 3 to 90 ng/dL), androstenedione was 204 |2 ~. M) q& n0 D
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
' G; {8 y' e3 m. I' V+ {terone was 38 ng/dL (normal, 50 to 760 ng/dL),
/ ^" H2 Q4 F- X# [" Tdesoxycorticosterone was 4.3 ng/dL (normal, 7 to9 }' C3 k3 L9 ?
49ng/dL), 11-desoxycortisol (specific compound S)+ @+ z& U j0 s/ U' I
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-& W6 r' ^$ f( P) X7 f
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
0 x! e" N4 W! e [4 X: Otestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
' @6 | K# t( {* O% Tand β-human chorionic gonadotropin was less than
, \2 }5 i, {5 v4 h& `/ g z5 mIU/mL (normal <5 mIU/mL). Serum follicular
0 }7 d0 K3 W: Y8 ^( I, t: `, Kstimulating hormone and leuteinizing hormone+ M0 L8 l. C, s B7 N, Y
concentrations were less than 0.05 mIU/mL3 J: y- g8 e2 i; l
(prepubertal).
2 x6 ~4 l/ g$ y f' r7 OThe parents were notified about the laboratory
- u/ ^2 I: S) Tresults and were informed that all of the tests were
$ V$ i, G: [# ]* r0 i1 hnormal except the testosterone level was high. The
: Q/ ?" F! V- J! q$ sfollow-up visit was arranged within a few weeks to7 H- C! T" F! U. B
obtain testicular and abdominal sonograms; how-
; M2 r1 C6 O6 G9 W7 F. c+ f5 bever, the family did not return for 4 months.
; f8 w, s: V% L7 h' \Physical examination at this time revealed that the6 h; |4 D4 d& y0 w5 x+ R+ X2 T
child had grown 2.5 cm in 4 months and had gained; i) f2 F6 q0 q' W0 y( K
2 kg of weight. Physical examination remained2 W5 x! s7 p1 `
unchanged. Surprisingly, the pubic hair almost com-& q$ b- `/ A9 Z5 z- G) [
pletely disappeared except for a few vellous hairs at5 B/ k# V$ L& K7 U& P0 O( q
the base of the phallus. Testicular volume was still 23 i/ Y1 A* |, C% e3 c( a& ^
mL, and the size of the penis remained unchanged.
/ _2 c5 n) b- P, `( @3 u3 I9 F# xThe mother also said that the boy was no longer hav-
4 H" \- s$ L( l, a# ]1 zing frequent erections.
8 o7 S, A* N2 h! }0 ]4 E7 [) YBoth parents were again questioned about use of
2 b+ ~: F j; x& b1 ?) d) `& Iany ointment/creams that they may have applied to4 v: V1 o2 ^$ b; s
the child’s skin. This time the father admitted the
) x" `5 a r; eTopical Testosterone Exposure / Bhowmick et al 541' Z$ T* m) w% t0 k8 ^
use of testosterone gel twice daily that he was apply-
( ~3 m3 {/ U4 D& K4 e- Ping over his own shoulders, chest, and back area for7 t9 A/ l7 _/ E& Y) `+ _7 u1 z7 S
a year. The father also revealed he was embarrassed7 ^* u3 n! q, @& A8 U
to disclose that he was using a testosterone gel pre-7 w' G- ]: G J! O6 f- v3 o
scribed by his family physician for decreased libido) n* T! m6 X& U; ~ Q- F$ n& P9 ~
secondary to depression.
0 @, z1 j; m) U8 g+ kThe child slept in the same bed with parents.
! u, _2 `/ K0 {' _8 t. AThe father would hug the baby and hold him on his
5 a; B! }: E S( I. Mchest for a considerable period of time, causing sig-5 x$ L$ v) [, @/ n# w
nificant bare skin contact between baby and father.
( n( m' u2 T$ `" s- {- {The father also admitted that after the phone call,
# B% }, P0 a' Xwhen he learned the testosterone level in the baby
# {1 ?6 e' a! ^; i" e& \; K' {was high, he then read the product information
/ h; R% M! f1 Q% t+ p' J4 b; r; fpacket and concluded that it was most likely the rea-: t8 q/ b( {. ^& O& i
son for the child’s virilization. At that time, they
% ~" T* f1 u# r( t9 S( m8 Gdecided to put the baby in a separate bed, and the# X. R, ]; M" T6 y9 |5 \6 H# f- N1 p$ E
father was not hugging him with bare skin and had3 }* g: x6 z8 D* A/ a" b# E4 C$ I
been using protective clothing. A repeat testosterone6 G* z3 ~ g$ W
test was ordered, but the family did not go to the9 h& M7 a! P6 f H5 r) c, D
laboratory to obtain the test.# S& j7 H% V% W$ u
Discussion0 F& C2 x: a% L+ w
Precocious puberty in boys is defined as secondary
6 J" c; @& @1 E2 Hsexual development before 9 years of age.1,4
' ?! Q; U+ R, X6 f' WPrecocious puberty is termed as central (true) when# ~; z) }/ w* \/ J- P" P! K+ l
it is caused by the premature activation of hypo- l% i+ y9 ]# e& _: C% a" R
thalamic pituitary gonadal axis. CPP is more com-& i: }( V" x- ^8 h) ^
mon in girls than in boys.1,3 Most boys with CPP
5 t& P2 c, a! @! ^) [9 m4 S1 m& K7 emay have a central nervous system lesion that is
- k3 F2 [+ A: k- |3 }) ?responsible for the early activation of the hypothal-
6 C- j. } s; `6 h; m- |amic pituitary gonadal axis.1-3 Thus, greater empha-
" Z' X6 Z8 k; D8 esis has been given to neuroradiologic imaging in% ]% U' Q$ y' k# H
boys with precocious puberty. In addition to viril-
, d N7 Z/ t# _; K. l3 A/ m. qization, the clinical hallmark of CPP is the symmet-
* `( Z6 t4 ^! R8 E: b) d. i1 L2 }rical testicular growth secondary to stimulation by# J. y( G" n3 }4 E& Q+ d5 `3 f
gonadotropins.1,3: u6 D" s6 X+ U, F( ?; B
Gonadotropin-independent peripheral preco-7 s- ?5 P* w1 \2 R6 L$ q
cious puberty in boys also results from inappropriate' V* P Y& w' N0 R( G
androgenic stimulation from either endogenous or7 F; |* z+ V8 ?6 y
exogenous sources, nonpituitary gonadotropin stim-
1 V7 s- x J. Y# J7 Nulation, and rare activating mutations.3 Virilizing& M/ m& Q; ~8 L. K. `
congenital adrenal hyperplasia producing excessive
) V5 J0 B5 f1 t$ Iadrenal androgens is a common cause of precocious
. B* t. r; R5 n. D5 V1 D8 a" Y# gpuberty in boys.3,4: @7 X, j! t% O# O1 V8 [
The most common form of congenital adrenal. N: c9 Q0 ?4 [. Y
hyperplasia is the 21-hydroxylase enzyme deficiency.
$ h4 C; j( g7 RThe 11-β hydroxylase deficiency may also result in3 G8 I' s( P: N. Q
excessive adrenal androgen production, and rarely,2 j7 \# N; B5 h+ ~1 _$ b, I
an adrenal tumor may also cause adrenal androgen+ V% C, X7 K" e
excess.1,3
( r3 h/ ~6 f* H, F+ i+ X/ |& `9 S$ wat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
* V' Z$ _8 b @8 y1 r- X542 Clinical Pediatrics / Vol. 46, No. 6, July 2007, G- O' N, _' Z6 B3 F# b! n
A unique entity of male-limited gonadotropin-
2 [. v5 }7 Z. qindependent precocious puberty, which is also known
: k9 C2 p+ t5 ^5 s4 L( D# @ c6 `4 Aas testotoxicosis, may cause precocious puberty at a
2 o: C/ L q- w. Hvery young age. The physical findings in these boys! T# v& O( M; Z' @& l
with this disorder are full pubertal development,
& c0 g. a: v/ ?including bilateral testicular growth, similar to boys
M, `8 L, U9 {- I# H9 c( p: Bwith CPP. The gonadotropin levels in this disorder/ ?7 b! ?3 d* N
are suppressed to prepubertal levels and do not show. Z1 [9 _1 r% o4 h. l
pubertal response of gonadotropin after gonadotropin-
- I. Y$ O t0 Y6 d _ yreleasing hormone stimulation. This is a sex-linked
; s5 \6 p9 v* Q/ z- Fautosomal dominant disorder that affects only; s. R m5 o* m0 v, ~( K; ]" p
males; therefore, other male members of the family
) c" [3 m M/ }% y. tmay have similar precocious puberty.3" a4 l) |% a, r4 P! T( i
In our patient, physical examination was incon-
( Z: L$ X$ i: ^" A3 I0 \( lsistent with true precocious puberty since his testi-- W5 U; }/ u$ J; ^+ B3 h3 ^
cles were prepubertal in size. However, testotoxicosis# P. `5 c" O/ M2 J- C2 W
was in the differential diagnosis because his father6 G1 ^' ?3 Y% T3 X5 s
started puberty somewhat early, and occasionally,
1 | {- `3 v1 ftesticular enlargement is not that evident in the
0 w+ {( q0 k# Q4 b$ M: Wbeginning of this process.1 In the absence of a neg-7 B) o& C/ X" k. q( L
ative initial history of androgen exposure, our
2 I. z( T1 I" R8 K$ Rbiggest concern was virilizing adrenal hyperplasia,
+ v" W0 T( L) B8 e& ]: Beither 21-hydroxylase deficiency or 11-β hydroxylase, u. s, j. e' e U, r9 u9 X
deficiency. Those diagnoses were excluded by find-: \8 b( i) y: H$ F+ C& h
ing the normal level of adrenal steroids.
' y! [4 C. N( P! R8 X1 v5 O1 DThe diagnosis of exogenous androgens was strongly% G6 ?5 m, U! l* }* {7 d. T
suspected in a follow-up visit after 4 months because
$ M- q$ C, Z8 W) F& \% lthe physical examination revealed the complete disap-
9 i- D; m* y! L$ t3 }6 ]8 tpearance of pubic hair, normal growth velocity, and% t+ ^) C+ f& r5 N) F' J$ g
decreased erections. The father admitted using a testos-
" K$ M: b6 X, S" Nterone gel, which he concealed at first visit. He was! P! T# z- ?4 Z0 [: i" b( v
using it rather frequently, twice a day. The Physicians’! ~& H* D1 R9 p- F
Desk Reference, or package insert of this product, gel or
F* T. g8 ~6 E% w) I' scream, cautions about dermal testosterone transfer to
; z' j, I4 P& l. vunprotected females through direct skin exposure. G! Y0 Z$ V* w1 c5 w
Serum testosterone level was found to be 2 times the" g0 n) K( n2 H3 o: j
baseline value in those females who were exposed to
7 i( l& y5 G4 M9 ?) Q ? yeven 15 minutes of direct skin contact with their male
0 U8 h0 U$ I6 ]! Y) v* Opartners.6 However, when a shirt covered the applica-
3 O- C! d/ Z0 a3 W4 d9 Dtion site, this testosterone transfer was prevented.
/ t) W3 D, Q# u# `- B- o' ]Our patient’s testosterone level was 60 ng/mL,, E2 }7 [& g5 U7 G$ E0 x) ?
which was clearly high. Some studies suggest that# o4 ~, V2 p2 W& K* [
dermal conversion of testosterone to dihydrotestos-
' Q# Z3 T' R) y2 t* rterone, which is a more potent metabolite, is more
x0 i; n4 h7 J' w3 S4 V. z; Vactive in young children exposed to testosterone
$ f0 ?3 T' K2 |" s( I: Mexogenously7; however, we did not measure a dihy-
0 {0 _5 W3 t. ^' g5 @/ |: X9 s, h0 O V( ldrotestosterone level in our patient. In addition to
/ j9 c6 @7 o; G* O$ o' xvirilization, exposure to exogenous testosterone in
& Q8 i. G' C7 \& ~: l$ c% y9 mchildren results in an increase in growth velocity and
- w2 k8 {$ A* sadvanced bone age, as seen in our patient.; k( C! R9 W# ^. k' m# V
The long-term effect of androgen exposure during6 z- c2 X+ P5 Y6 c* d
early childhood on pubertal development and final
C/ [- ~2 Z3 n% l- g( ]adult height are not fully known and always remain
( V* {+ \3 @1 D: La concern. Children treated with short-term testos-; j& u9 H8 F* x9 d
terone injection or topical androgen may exhibit some
1 {, e. ?. h _" x( zacceleration of the skeletal maturation; however, after
. X V: h$ n1 R" B$ t2 [4 [, l1 ccessation of treatment, the rate of bone maturation
( Q! ^ X7 F4 _% Bdecelerates and gradually returns to normal.8,99 y' f$ `' Y; S. B2 f
There are conflicting reports and controversy- @' T1 J$ I7 r
over the effect of early androgen exposure on adult4 s: w5 y6 r/ ?8 U: p
penile length.10,11 Some reports suggest subnormal3 n* ]2 u7 E9 b1 D( U3 l) q
adult penile length, apparently because of downreg-: f9 n2 O( |% i0 K
ulation of androgen receptor number.10,12 However,
5 p, s) C% ]9 A# Z5 W& U# q, zSutherland et al13 did not find a correlation between! w# B' T& k9 x8 _- i
childhood testosterone exposure and reduced adult q/ _2 J6 j2 I; N' U+ v3 F0 l
penile length in clinical studies.
) q. V5 F! \# w% F3 @; S/ {, pNonetheless, we do not believe our patient is
- ^: r* t# t) |; g$ u+ u! n2 D0 L- hgoing to experience any of the untoward effects from" d5 C8 o- g' G! H+ |# w
testosterone exposure as mentioned earlier because
& W0 Q. G* R' o0 C$ B2 wthe exposure was not for a prolonged period of time.
$ Q+ A% j9 a: n( o, c+ U& }Although the bone age was advanced at the time of5 J& h6 c7 {- B* r" f- }
diagnosis, the child had a normal growth velocity at
* U" o. v* H. l9 H2 z5 jthe follow-up visit. It is hoped that his final adult2 B+ a1 u- }5 p: g
height will not be affected.: }9 r1 C8 w. e- \5 a3 E1 q
Although rarely reported, the widespread avail-* b' k- y: C4 O4 P- t
ability of androgen products in our society may4 O8 V# r- E) R- N3 n2 S, B) T( D
indeed cause more virilization in male or female' I# S5 S, v9 f0 r6 ]* p" }( [
children than one would realize. Exposure to andro-
9 M; u2 I+ S# x* X6 A4 v! _gen products must be considered and specific ques-
8 s( F; J Z5 A1 y1 }# {tioning about the use of a testosterone product or
0 f7 d' v7 i o" y4 B! ygel should be asked of the family members during
: ^: ~) L+ f) a1 {2 g8 j V* Ithe evaluation of any children who present with vir-
7 j" P& g& k' i; b2 `( p: o# _ilization or peripheral precocious puberty. The diag-
& f' y4 c7 G- D# A/ d; k1 Mnosis can be established by just a few tests and by
' U; ~4 \# x; f, I* H* aappropriate history. The inability to obtain such a) g: N' P6 Y" A
history, or failure to ask the specific questions, may
: F. H5 \( @& u; h. u u' cresult in extensive, unnecessary, and expensive
6 K1 A) {/ g0 w: H% Iinvestigation. The primary care physician should be. f5 X3 ]) N" w
aware of this fact, because most of these children9 t" C, q- k% l" N9 Q7 {
may initially present in their practice. The Physicians’( ~+ Y: P" J7 Z3 N H
Desk Reference and package insert should also put a
! b; h3 C4 n% f8 w5 `1 Ewarning about the virilizing effect on a male or
! E4 ?/ ?: B) J6 a3 A* U. a; Sfemale child who might come in contact with some-% ?7 |- }! C B8 z& g5 c
one using any of these products.+ c* U# }+ R& a4 H3 @# t
References
) R0 P: c8 }5 t9 A: F1. Styne DM. The testes: disorder of sexual differentiation* p! o: } i; V
and puberty in the male. In: Sperling MA, ed. Pediatric2 [. x3 X6 U/ Q }* A: F
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;+ `4 {! }5 S0 ?, ^
2002: 565-628.
( O) Y n. ^! z3 G0 D2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
" Z2 t. N( M$ N7 A4 L! spuberty in children with tumours of the suprasellar pineal |
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