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Sexual Precocity in a 16-Month-Old+ d7 N% _: w: u! `' O h0 z& Y
Boy Induced by Indirect Topical
+ {0 \; e$ B) z: X! P# x8 SExposure to Testosterone2 S3 E d& q! f5 i9 S1 {3 D# l
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2 |# s% t- f+ Z ^# L" R
and Kenneth R. Rettig, MD1
# C$ t; r& K1 V. o. XClinical Pediatrics' r, _- d& D/ ` O' v& b+ y5 `, u2 s
Volume 46 Number 6
/ ^9 |2 d" s* J! @8 ?July 2007 540-543
0 f2 k6 A$ H- d© 2007 Sage Publications
7 W/ }7 _5 C* O B10.1177/0009922806296651
% ?7 e& [; T d* P% C5 U# m: Dhttp://clp.sagepub.com; j T9 ]. b) H% e# L0 _8 Z
hosted at
, o; c" c7 u/ } o9 ?! ihttp://online.sagepub.com
# M% W5 w' `4 a6 rPrecocious puberty in boys, central or peripheral,
- ^5 T( s# U' \' j2 O. fis a significant concern for physicians. Central! O$ W# T# z, V* Y* [; m+ Q
precocious puberty (CPP), which is mediated* g9 t( j6 \( `) w6 _5 M2 @
through the hypothalamic pituitary gonadal axis, has
- Y# F* j0 G4 u* q/ i, R% Ca higher incidence of organic central nervous system
7 K0 D, \" l* L, \" b8 Z5 ]5 \0 `& {lesions in boys.1,2 Virilization in boys, as manifested
& P7 F% x6 l* ]3 k6 Z5 S* ?by enlargement of the penis, development of pubic
7 \7 o% ]) k9 L+ t+ P( dhair, and facial acne without enlargement of testi-
2 W+ D! \; X" J# xcles, suggests peripheral or pseudopuberty.1-3 We
* N' V1 F8 v) P1 Z! `- t" s2 vreport a 16-month-old boy who presented with the
. v$ ?* @( J" g; m# Menlargement of the phallus and pubic hair develop-
5 Z" ~6 R6 `% z1 a2 Rment without testicular enlargement, which was due
) n) {: }0 L4 V$ l* ^( x- Lto the unintentional exposure to androgen gel used by1 W: M4 I( y) ^- g5 i
the father. The family initially concealed this infor-
5 G% L2 `, x5 ?. m; e1 amation, resulting in an extensive work-up for this* H3 G: E/ P5 j) |4 p* t
child. Given the widespread and easy availability of
, g! o# V3 ~% @4 W L) etestosterone gel and cream, we believe this is proba-
9 m0 y( M) d% ?% w/ Ebly more common than the rare case report in the, N3 P0 Y, h/ t1 N3 p# c! V
literature.4
& \( b8 I! [. o5 e' {6 I" VPatient Report
2 P/ Y1 y* l/ D, tA 16-month-old white child was referred to the, i8 y6 [4 W5 P4 c. F
endocrine clinic by his pediatrician with the concern5 j, D" D4 I. _1 W
of early sexual development. His mother noticed, O5 J, z- G3 k* K$ }9 W; N
light colored pubic hair development when he was6 j! M9 j% B) h% I9 X0 w
From the 1Division of Pediatric Endocrinology, 2University of
4 X& ?5 b: g: VSouth Alabama Medical Center, Mobile, Alabama.
& b/ R; X0 k: pAddress correspondence to: Samar K. Bhowmick, MD, FACE,
, g! x7 _1 W. t; V2 g) s" I7 HProfessor of Pediatrics, University of South Alabama, College of3 x1 I) g S) P, k" ]
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
7 A+ g' [- \0 X: `e-mail: [email protected].
5 t f) W) _ E0 I/ n" F/ u5 N, zabout 6 to 7 months old, which progressively became" r: q4 c; r. L
darker. She was also concerned about the enlarge-
3 h/ ]. D, ^/ j8 N3 Q' Lment of his penis and frequent erections. The child
( n$ f+ g% ]2 f- E5 hwas the product of a full-term normal delivery, with1 M7 m! H* R8 {5 N+ H
a birth weight of 7 lb 14 oz, and birth length of/ Y+ G, g1 D! }# u7 ]
20 inches. He was breast-fed throughout the first year
8 P, P) K. |) X% x. O4 Jof life and was still receiving breast milk along with/ ~' y* s% ^6 ^& S
solid food. He had no hospitalizations or surgery,, k3 O, x' ]: B7 [4 A- I
and his psychosocial and psychomotor development4 S1 Z2 z- G* U0 K
was age appropriate.; M" _- ]! I6 U' P5 n! i
The family history was remarkable for the father,* j1 ]9 Q* l s8 z, q& _; O
who was diagnosed with hypothyroidism at age 16,
% R1 c- _& P" j5 A v5 i( Zwhich was treated with thyroxine. The father’s. r- M# q% b# t6 K( W* ~0 i
height was 6 feet, and he went through a somewhat
! y( e5 M' l) M8 mearly puberty and had stopped growing by age 14.
. h, L7 s |% r( { t9 b1 Y- ^The father denied taking any other medication. The- a6 U# e7 P' j0 O
child’s mother was in good health. Her menarche+ ^9 x+ X0 t+ O ^- x: m8 I
was at 11 years of age, and her height was at 5 feet
) j# J1 `! ^( |2 }5 t% t5 inches. There was no other family history of pre-
; }3 X+ d# J- m% ?, \$ Acocious sexual development in the first-degree rela-
3 F8 O5 E ]0 L0 k0 o2 l1 P o7 Xtives. There were no siblings.# u3 P8 X! Q; i }
Physical Examination
# w* T. ^) X' h; lThe physical examination revealed a very active,
5 k8 K3 v6 B- f+ Bplayful, and healthy boy. The vital signs documented
5 v- d7 g7 ?# N" }6 F0 Da blood pressure of 85/50 mm Hg, his length was z2 `8 i7 x9 O) k7 [
90 cm (>97th percentile), and his weight was 14.4 kg3 e' e. `1 e8 m% t1 j
(also >97th percentile). The observed yearly growth
1 A8 P$ s V7 g, Tvelocity was 30 cm (12 inches). The examination of- K5 O! N, J- s3 y2 ~* V7 u7 K8 X
the neck revealed no thyroid enlargement.7 o; ]9 c* K- k& K" A. ?: b
The genitourinary examination was remarkable for! a# b& r. ~ d3 q
enlargement of the penis, with a stretched length of. k, P! \! M% x$ a( v4 A
8 cm and a width of 2 cm. The glans penis was very well
% t9 {$ S. t3 o9 j9 edeveloped. The pubic hair was Tanner II, mostly around
a5 }! ]& | b, n- |. c540
) S+ `. B/ a( @' s/ L, i# S% dat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
4 s2 D" g& j5 V- r- a6 vthe base of the phallus and was dark and curled. The
5 h+ [& k( h# y9 O6 I! g. Ztesticular volume was prepubertal at 2 mL each. `! C- }8 Y' X8 [% c7 H
The skin was moist and smooth and somewhat
, o, F9 |7 [) ], b9 w! L6 Z& @# soily. No axillary hair was noted. There were no9 J( g5 j# h, }( g6 j- c# S
abnormal skin pigmentations or café-au-lait spots.* T/ M1 E2 d4 b# s# r; N' y
Neurologic evaluation showed deep tendon reflex 2+9 ~3 C. g6 r5 H0 t! N0 I
bilateral and symmetrical. There was no suggestion
" f2 c8 x, q) V7 e( G: lof papilledema.' t+ T' n" H3 e- n; ]
Laboratory Evaluation
, G2 \$ Q# N7 {# ]3 f2 nThe bone age was consistent with 28 months by
2 h1 O2 \- {. h4 \: P/ s1 h, T! A5 Uusing the standard of Greulich and Pyle at a chrono-
+ G5 c$ \$ i7 x2 w8 Vlogic age of 16 months (advanced).5 Chromosomal
, M9 W/ s, A8 R& b0 |karyotype was 46XY. The thyroid function test" j1 s3 B$ Y/ S! ^. ]1 V% F
showed a free T4 of 1.69 ng/dL, and thyroid stimu-6 L. k" C* `' ^. V
lating hormone level was 1.3 µIU/mL (both normal).5 ?8 L* T7 c8 R: {6 T; |
The concentrations of serum electrolytes, blood
+ u, }% M2 N* u; b5 H. o" Q: |urea nitrogen, creatinine, and calcium all were
; S+ w+ @; Q5 m4 ]within normal range for his age. The concentration( a+ S- A& [3 q0 W$ x; j. k/ ~$ H
of serum 17-hydroxyprogesterone was 16 ng/dL
. k4 A; }( Q! m9 V4 {7 T' L1 {8 U(normal, 3 to 90 ng/dL), androstenedione was 20- F6 c7 \' c: {4 I
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
: A9 j+ a2 Z. k" m0 H4 Q( uterone was 38 ng/dL (normal, 50 to 760 ng/dL),
* v4 I* g! i$ n$ j' j: ddesoxycorticosterone was 4.3 ng/dL (normal, 7 to
- k e' ]* h4 Y8 d3 s0 m/ v1 {8 E' u49ng/dL), 11-desoxycortisol (specific compound S)
- u/ M) o- u5 f; v6 V3 j1 `was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
- X: p+ e) V; Ktisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total+ V2 m. M- ?4 Q% ?4 o
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
( @1 I5 S1 f2 X' { yand β-human chorionic gonadotropin was less than/ r6 g d/ M; z0 J2 e) f. ^
5 mIU/mL (normal <5 mIU/mL). Serum follicular
& X8 ~+ P) E- E' Y3 nstimulating hormone and leuteinizing hormone5 c. a5 e8 |) p
concentrations were less than 0.05 mIU/mL* |6 J, n& w Q. Y7 {" S U
(prepubertal).2 ^0 ?4 D% I, ^/ ]! Y
The parents were notified about the laboratory
# k2 l8 v D3 |+ Cresults and were informed that all of the tests were% M, |9 |8 D5 ]
normal except the testosterone level was high. The
" O2 {. d% k& m. O- J u4 ufollow-up visit was arranged within a few weeks to
3 D" S& T* ?! Y; ~+ k" f0 oobtain testicular and abdominal sonograms; how-
$ s3 k9 u; o0 P! ^6 K/ a! W2 gever, the family did not return for 4 months.0 A5 E D- Y/ L3 p+ o
Physical examination at this time revealed that the
# B% ?2 V8 g0 w, d' P8 k+ _child had grown 2.5 cm in 4 months and had gained
- K1 U" r" A6 y" W2 kg of weight. Physical examination remained
% U& B% W" |) y$ Iunchanged. Surprisingly, the pubic hair almost com-. {' w& V& R) H4 G: u% J# S) N
pletely disappeared except for a few vellous hairs at
2 M) }; J; ~( h% qthe base of the phallus. Testicular volume was still 2& _! w9 W# W6 s# m
mL, and the size of the penis remained unchanged. I) E5 c, I; j3 p) [$ J* o5 l
The mother also said that the boy was no longer hav-/ Y) m1 \6 u' R9 w2 B, P7 i
ing frequent erections.# k" b: U6 ^) Z8 D
Both parents were again questioned about use of
% u+ B9 N+ W. W, b5 p+ a qany ointment/creams that they may have applied to4 N" \# F; G. N s4 y
the child’s skin. This time the father admitted the3 Z6 U- g7 h4 Y: B; X7 f
Topical Testosterone Exposure / Bhowmick et al 541! q O8 r+ I: A- m6 h
use of testosterone gel twice daily that he was apply-) e) C4 X+ \7 [7 w, O
ing over his own shoulders, chest, and back area for! w4 B& k2 Z- H9 V" Y4 J
a year. The father also revealed he was embarrassed
2 u* p3 d3 \; r& A8 E, B$ Fto disclose that he was using a testosterone gel pre-+ e% F1 q: A+ [+ _4 o; n/ Q9 b% h
scribed by his family physician for decreased libido
3 o+ L5 V2 i" d+ R2 Tsecondary to depression.( D e- H) s# R5 T; }; ?; _
The child slept in the same bed with parents.* ?! v" R, S/ B
The father would hug the baby and hold him on his
; U3 O% T6 ^6 h' \6 D2 M4 Vchest for a considerable period of time, causing sig-
e' K+ O8 X$ P. e; z' ^, {nificant bare skin contact between baby and father.
8 D/ G7 K3 s: N8 P! C( aThe father also admitted that after the phone call,1 p1 X$ J8 G) l% l' J: z
when he learned the testosterone level in the baby- W2 M9 c: O; u' b8 G$ j/ U K
was high, he then read the product information
: ~* ~; i. C+ O8 a- Y7 \packet and concluded that it was most likely the rea-
( w& n( q% V! p+ s1 w$ Oson for the child’s virilization. At that time, they- U q" ^; d' _1 z
decided to put the baby in a separate bed, and the" z! z' O/ _+ v6 `. s0 w
father was not hugging him with bare skin and had( N1 f: K) w( U* T
been using protective clothing. A repeat testosterone
1 u% B; T4 r; w. Dtest was ordered, but the family did not go to the' s8 |; N1 V: O! }1 m2 U( ~& |* l; k
laboratory to obtain the test. X5 V v( t6 O, {& P" \3 \+ r
Discussion+ I7 l$ ?: [( X( d; X0 u1 @
Precocious puberty in boys is defined as secondary
9 _0 q6 l6 w3 `+ ?1 b1 ksexual development before 9 years of age.1,4
3 A, W) i2 C' ^$ `, kPrecocious puberty is termed as central (true) when
6 m% M# O* G F) n" G* k: j; Sit is caused by the premature activation of hypo-
7 d5 E- A/ z8 F" J* I# S U- Ithalamic pituitary gonadal axis. CPP is more com-0 \5 o ^* O7 n1 b4 t- ?$ T% |5 B
mon in girls than in boys.1,3 Most boys with CPP
: Z. m) h3 V% i. R! nmay have a central nervous system lesion that is
0 Y& |& }. W# iresponsible for the early activation of the hypothal-
- D" c: @+ O9 Bamic pituitary gonadal axis.1-3 Thus, greater empha-. U: a/ O9 U+ ]+ U4 c
sis has been given to neuroradiologic imaging in4 s/ p7 d0 }+ h5 f
boys with precocious puberty. In addition to viril-
* {4 |4 d" @# \) Bization, the clinical hallmark of CPP is the symmet-# b- y& ]2 y: E$ f( m2 q7 }
rical testicular growth secondary to stimulation by, L1 H0 |6 A( z7 ~6 g
gonadotropins.1,3, M$ p* ]+ M7 E: r( O
Gonadotropin-independent peripheral preco-
, k y2 U) Q5 b* k! K& E# @4 {cious puberty in boys also results from inappropriate
3 I0 U! h! |. j7 Fandrogenic stimulation from either endogenous or
/ `* o. _( i5 G) yexogenous sources, nonpituitary gonadotropin stim-# S# f3 {% y/ k* C. H
ulation, and rare activating mutations.3 Virilizing
# C( u7 K" M& c) j6 Y8 E) K* Tcongenital adrenal hyperplasia producing excessive
; } n% w) ]6 P" X/ y; n5 uadrenal androgens is a common cause of precocious, ~) X Z$ T2 f* c
puberty in boys.3,4$ H `5 s- T- l8 S. K% y8 I7 u" h
The most common form of congenital adrenal
3 y, ?: k6 W4 H, n/ phyperplasia is the 21-hydroxylase enzyme deficiency.
7 h" D) c% S8 K; E6 C) l' X. XThe 11-β hydroxylase deficiency may also result in/ D: \1 S- Y U
excessive adrenal androgen production, and rarely,* L( c$ r9 B6 S7 H9 I
an adrenal tumor may also cause adrenal androgen8 Y; E' o P; a
excess.1,3+ r1 M2 ]0 N) c- k i- Z1 W' A
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from/ Y/ E4 d K( A5 X; P' p% A
542 Clinical Pediatrics / Vol. 46, No. 6, July 20072 U- p$ `8 X- F5 p8 s
A unique entity of male-limited gonadotropin-
/ [& }, q( ?5 T+ a& D4 ^( X4 X2 Vindependent precocious puberty, which is also known5 k# Z9 `0 T! J
as testotoxicosis, may cause precocious puberty at a s8 k# }/ {$ R( M& o
very young age. The physical findings in these boys& V4 I6 F# V- @8 U' r4 C( C2 d' l
with this disorder are full pubertal development,
& o+ K. j* W$ C+ Xincluding bilateral testicular growth, similar to boys% z1 B5 {2 m( }8 B# M5 _% E
with CPP. The gonadotropin levels in this disorder
/ B! b Q7 R3 j/ D( G4 B$ M) mare suppressed to prepubertal levels and do not show
( j' e9 X2 _$ l* Kpubertal response of gonadotropin after gonadotropin-9 P$ |; ?# q4 e+ s
releasing hormone stimulation. This is a sex-linked; b& j" W: S! C& U; |
autosomal dominant disorder that affects only0 U6 ~) \9 p8 }; T' y# m
males; therefore, other male members of the family
3 l4 W/ L& M% D" Rmay have similar precocious puberty.3
. ~; s7 Z( Z- p' O3 K: AIn our patient, physical examination was incon-+ d$ O2 }2 E5 Z0 ~+ i
sistent with true precocious puberty since his testi-
# g* `" e6 [0 ~+ {2 F' Xcles were prepubertal in size. However, testotoxicosis" w( S9 b3 t8 o8 V6 Z- t
was in the differential diagnosis because his father) P' M7 C0 x; z5 f+ p& B) g" q3 A2 C
started puberty somewhat early, and occasionally,
7 J- t+ w/ j6 C% J/ |0 Ktesticular enlargement is not that evident in the* I: T) }8 l# Z @' n
beginning of this process.1 In the absence of a neg-
8 M6 J( @9 Z& Hative initial history of androgen exposure, our
; L' k1 c6 y e4 @0 Lbiggest concern was virilizing adrenal hyperplasia,
$ k2 l! v4 ^- A6 c/ g5 f! X) r; @either 21-hydroxylase deficiency or 11-β hydroxylase% e, ~" o+ K' g
deficiency. Those diagnoses were excluded by find-$ B# b" Z* C9 a" I6 I( a& Z* C/ Y2 j9 K
ing the normal level of adrenal steroids.! C' Z8 b2 [, l8 Z( q' H8 O
The diagnosis of exogenous androgens was strongly. F3 O: _; U/ w2 ?; X' @, M
suspected in a follow-up visit after 4 months because
5 J# \# x/ P& D3 A" Fthe physical examination revealed the complete disap-
, J" J$ e9 O! Q* O& v8 {! e! Fpearance of pubic hair, normal growth velocity, and
2 L5 `: M6 L2 R7 B/ c8 P) z% `decreased erections. The father admitted using a testos-
* I5 L/ D5 S S1 o6 D9 cterone gel, which he concealed at first visit. He was+ n+ I0 A* h" }2 y3 n
using it rather frequently, twice a day. The Physicians’' v: K4 |1 M4 l4 \& y* u3 L/ v7 e
Desk Reference, or package insert of this product, gel or
1 ~8 M! L2 O0 ^ Scream, cautions about dermal testosterone transfer to7 O; m0 Q7 f0 F# O2 m$ M7 n+ l
unprotected females through direct skin exposure.5 |/ d; x7 a8 m; b7 n) ?
Serum testosterone level was found to be 2 times the9 r2 g) i: ^# o; o( m: N2 r
baseline value in those females who were exposed to# Q8 K4 N$ `# Y! d7 N
even 15 minutes of direct skin contact with their male3 R' I2 ~% f1 Q5 u$ F
partners.6 However, when a shirt covered the applica-& T8 d1 O0 B, q' T
tion site, this testosterone transfer was prevented.8 |# |( l C j0 Z
Our patient’s testosterone level was 60 ng/mL,
) n" H8 ?1 c- ?which was clearly high. Some studies suggest that4 _% } P( \: |& \$ g
dermal conversion of testosterone to dihydrotestos-
! t( l2 L: M3 ~0 ]4 X( gterone, which is a more potent metabolite, is more
0 M4 G% w% V7 A# R: Z, d6 R; uactive in young children exposed to testosterone
/ M: C% w3 G. @4 z& Q( }exogenously7; however, we did not measure a dihy-, s) G( D& M5 X, d! O9 h; E# a
drotestosterone level in our patient. In addition to
8 i* L5 l- p/ _9 U$ Wvirilization, exposure to exogenous testosterone in
: Z2 S6 Y' ?3 `' ichildren results in an increase in growth velocity and
4 h8 x2 D0 c* \5 Ladvanced bone age, as seen in our patient.
( Y& C! Y4 x1 b4 Y3 L6 PThe long-term effect of androgen exposure during3 d! C; C5 S* B
early childhood on pubertal development and final
/ q! i1 a: h+ i1 K3 N4 r- \adult height are not fully known and always remain
$ { ~! c9 z) L9 T" a- q8 M- m. Da concern. Children treated with short-term testos-
c9 _) ^2 p$ I" P$ k" f+ Xterone injection or topical androgen may exhibit some1 l9 h: i. Y4 C* C
acceleration of the skeletal maturation; however, after7 \) P: Q( g( n2 D
cessation of treatment, the rate of bone maturation
) z7 u* z' F, j+ xdecelerates and gradually returns to normal.8,9$ G8 A0 J5 ?! I5 X% l* e/ ^
There are conflicting reports and controversy
! B9 G8 M8 F- g4 Sover the effect of early androgen exposure on adult
2 b* u1 } r/ ^( V! e, \0 j+ tpenile length.10,11 Some reports suggest subnormal
9 f4 Q7 x- P4 Z7 ^8 }: Sadult penile length, apparently because of downreg-" b2 h' B/ M, K8 K/ Q
ulation of androgen receptor number.10,12 However,
" F1 k! O1 T; u/ U4 ]9 lSutherland et al13 did not find a correlation between
' y; s. P4 ]5 X. F. k. Echildhood testosterone exposure and reduced adult) z1 j6 A. y3 ^% y
penile length in clinical studies.
1 m3 N* {, ~* l2 z1 o/ d4 D+ ONonetheless, we do not believe our patient is
, K8 y, _, a) l' u& b Fgoing to experience any of the untoward effects from
6 f) J: N M* q2 M# \4 p( o) s4 otestosterone exposure as mentioned earlier because
8 o7 n/ U9 A& @the exposure was not for a prolonged period of time.: @: ?. I/ h- Q( h
Although the bone age was advanced at the time of# G m; ]3 F! g* M
diagnosis, the child had a normal growth velocity at
3 ]! W" X% s$ T5 |% ^the follow-up visit. It is hoped that his final adult
F, L8 o# M( L- o0 B( o4 Jheight will not be affected.+ H2 k F/ V( d$ _& [. a1 f
Although rarely reported, the widespread avail-
, T0 z) q/ N) Q( k0 oability of androgen products in our society may
+ o: w8 q* Y$ S8 p$ v. s' ~+ E! {indeed cause more virilization in male or female
M: V# ~- }) achildren than one would realize. Exposure to andro-6 i/ {& p0 ?4 y+ e8 x N+ j- e
gen products must be considered and specific ques-
2 F+ `1 \* R* }7 m0 T# x- I( Ctioning about the use of a testosterone product or, k; t7 a3 E2 m& \5 e
gel should be asked of the family members during" \9 e2 I( V) ~4 ?$ \) s$ l8 T8 l
the evaluation of any children who present with vir-
: J- T w- R; Y- f( [ilization or peripheral precocious puberty. The diag-
- S1 H1 c/ I" q% [nosis can be established by just a few tests and by
' T! ^, F1 z6 N4 L4 q; a1 Uappropriate history. The inability to obtain such a: D" Q$ Z' W+ x( p
history, or failure to ask the specific questions, may; x c# P, u) d
result in extensive, unnecessary, and expensive$ O0 R, U# p, V4 l
investigation. The primary care physician should be
" j2 I, H2 }& E7 V. waware of this fact, because most of these children
. b" A3 L. p* T$ wmay initially present in their practice. The Physicians’
0 L" L8 L7 G: ?: V1 a: t9 YDesk Reference and package insert should also put a! v* S4 C! N. q/ ]
warning about the virilizing effect on a male or
2 Y* l( y9 u: {7 u1 _female child who might come in contact with some-5 Y% @- N" u# \* p* [# d
one using any of these products.6 r( b" N* d& h4 T. e, I& G9 P
References
( |/ R! @/ n! ?9 A- q7 q1. Styne DM. The testes: disorder of sexual differentiation& ]5 }& N2 b) {# q, X; j
and puberty in the male. In: Sperling MA, ed. Pediatric
$ Z* _% L6 w$ z% `Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;0 e: X3 h5 i0 D6 m! j7 o) l
2002: 565-628.
, V# G3 c [2 z- v1 J2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
5 N. O: a5 b/ F: G; Qpuberty in children with tumours of the suprasellar pineal |
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