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Sexual Precocity in a 16-Month-Old
0 @- A( V) T, @: Y J; Y* I( {3 gBoy Induced by Indirect Topical/ [& R0 r) `* i$ p# j
Exposure to Testosterone
( K4 T/ v( N4 q/ q! e1 \4 x# U* xSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
& h5 m; ` }/ L( ^4 iand Kenneth R. Rettig, MD1+ k1 p; G |3 x* E9 T3 U" k$ ^' `
Clinical Pediatrics) b' A5 S8 h9 Q! x
Volume 46 Number 6' e8 ~5 ^8 R1 j3 Y g/ j
July 2007 540-543- n* R* k) p0 |. i
© 2007 Sage Publications5 I/ y, H3 Z3 v+ v9 @1 p l+ L6 j! p
10.1177/0009922806296651
% F% D1 [; O; y# J1 P% Rhttp://clp.sagepub.com
/ s/ K7 F+ W* Q8 E' r; [6 J# ihosted at5 f3 O( h r! T/ D. o
http://online.sagepub.com: d; E& P4 o9 n8 h
Precocious puberty in boys, central or peripheral,& h X! y( j0 ^& b# q" C' a1 J) o
is a significant concern for physicians. Central
' b& h; F) B9 O+ e( Jprecocious puberty (CPP), which is mediated
% h+ m: Y8 J8 v+ v5 Nthrough the hypothalamic pituitary gonadal axis, has
0 {9 k! g. f4 X; S' ]# ja higher incidence of organic central nervous system. Y5 I" S% x |
lesions in boys.1,2 Virilization in boys, as manifested- }% E! Q, v9 S7 a' F
by enlargement of the penis, development of pubic
$ K/ C. m+ E" N- @hair, and facial acne without enlargement of testi-1 E% X9 q0 b) d; b$ y0 B
cles, suggests peripheral or pseudopuberty.1-3 We$ r" z1 c4 k; f; a4 H( O
report a 16-month-old boy who presented with the; W3 }3 ?( N) P9 p
enlargement of the phallus and pubic hair develop-
' J) g3 z8 I" M( E) [+ ^ment without testicular enlargement, which was due
8 v4 @: b" V1 M+ U( ?to the unintentional exposure to androgen gel used by( o! f3 I- i/ t# M$ ]7 {; W
the father. The family initially concealed this infor-7 d U/ v0 F$ W+ M
mation, resulting in an extensive work-up for this: @. @* Z- W- t$ j, c
child. Given the widespread and easy availability of5 w6 ]0 S @% K8 N8 X0 B7 ^# T4 U
testosterone gel and cream, we believe this is proba-
7 V1 }3 y0 `( v# S* o. |) dbly more common than the rare case report in the
9 N ]! a' z& |" C" l, X, Hliterature.4
. r! {: o8 l6 Y5 r1 Z1 ePatient Report8 Z/ J. e x/ |
A 16-month-old white child was referred to the
& N7 \8 U& f# Cendocrine clinic by his pediatrician with the concern
0 M+ B9 t+ U4 ?+ d f+ n4 ~/ |+ M% {of early sexual development. His mother noticed
; e2 ?4 b# n1 K0 U8 n+ olight colored pubic hair development when he was8 |4 w8 Z" c7 A7 ~! C0 C
From the 1Division of Pediatric Endocrinology, 2University of
+ N3 v, h+ f/ ~& w1 o% FSouth Alabama Medical Center, Mobile, Alabama.
+ c: y* Z& p5 W8 s5 a2 O7 SAddress correspondence to: Samar K. Bhowmick, MD, FACE,
" P. z" Y c& d# r$ [" a+ H, E5 aProfessor of Pediatrics, University of South Alabama, College of; T8 k' F$ p% k8 y* P
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;: }' M' M( ]; a
e-mail: [email protected].7 [2 @ |1 ^$ [7 U( w+ V- B# h% }" h
about 6 to 7 months old, which progressively became/ \1 X; ~: f% T4 g
darker. She was also concerned about the enlarge-
; L# E7 I+ M6 kment of his penis and frequent erections. The child) Z; z: e6 j1 k8 ~0 |* W2 Y
was the product of a full-term normal delivery, with& C% L( ~) @5 b. D7 Q
a birth weight of 7 lb 14 oz, and birth length of) U" {% @9 K' j6 N, d8 w8 Q
20 inches. He was breast-fed throughout the first year
6 ]8 Q! ^: u- X9 @- L7 r+ |9 k2 @/ t( rof life and was still receiving breast milk along with" C/ V6 y4 {+ B+ c% a
solid food. He had no hospitalizations or surgery,) }! U: ]/ r# U- D4 g: ~
and his psychosocial and psychomotor development
* H9 T) S1 b R' ]6 Zwas age appropriate.( S: V: D8 U1 V% _% }
The family history was remarkable for the father,
- J6 h7 u) z6 [. D8 W3 N8 ^ Nwho was diagnosed with hypothyroidism at age 16,
0 h' S' m9 L+ ^! \" ~* h, O/ H) ~0 M' @! Rwhich was treated with thyroxine. The father’s( R/ [+ ?3 R$ u9 d' K* }5 N8 k
height was 6 feet, and he went through a somewhat+ a; M& d7 K0 A
early puberty and had stopped growing by age 14.
0 s# Y I" f7 `, s9 b8 H# eThe father denied taking any other medication. The% h- u! t3 Z# W$ [8 Z
child’s mother was in good health. Her menarche
& |5 q0 F/ H0 S. A" ~0 u4 s, Owas at 11 years of age, and her height was at 5 feet$ i9 J6 m8 J$ I& e/ S* F
5 inches. There was no other family history of pre-
. M* H! b8 y' f o3 V* {4 ococious sexual development in the first-degree rela-
; M0 f: p K; h! |tives. There were no siblings.
7 g' L8 m0 e& n# T5 B# xPhysical Examination
3 D* F# k% b" m& M3 r, O. iThe physical examination revealed a very active,( u$ r8 s7 ^( c9 \$ t9 I9 Y
playful, and healthy boy. The vital signs documented
$ o* p4 G4 k1 F5 ba blood pressure of 85/50 mm Hg, his length was* ?$ c3 V5 f" {6 q
90 cm (>97th percentile), and his weight was 14.4 kg
! Y5 w/ j+ W# A: B2 K; O4 S+ r9 B+ c(also >97th percentile). The observed yearly growth
; [ R- S' q. J, u \; A& O' W' dvelocity was 30 cm (12 inches). The examination of- e: E! R" z# t0 ^9 }& D: R0 a) o$ f
the neck revealed no thyroid enlargement.3 f; a. U, {8 H$ g, ]5 M
The genitourinary examination was remarkable for% F. X7 V8 c& F3 j
enlargement of the penis, with a stretched length of
; F* D5 n' u5 T* }) }8 cm and a width of 2 cm. The glans penis was very well
% s1 q2 F% e8 x* q- t# Ddeveloped. The pubic hair was Tanner II, mostly around$ U: k* l& Z- ^
5406 |6 P# r) D4 `* ?
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from) r/ I' I& I- M9 p9 [# r/ ^4 e
the base of the phallus and was dark and curled. The- S& |" G( I* Q, R: Z3 R
testicular volume was prepubertal at 2 mL each.8 O3 t5 _0 c; I* M) B
The skin was moist and smooth and somewhat" E# P6 ~' P: E& d" O
oily. No axillary hair was noted. There were no5 ]* g: [. }0 p' N4 [: S
abnormal skin pigmentations or café-au-lait spots.
3 G# X) B9 n7 y9 ^% A) _+ sNeurologic evaluation showed deep tendon reflex 2+8 L0 z$ b, T0 P# p" K' t8 K$ z6 d; c
bilateral and symmetrical. There was no suggestion
. B. K6 Y) m1 Z* s- }. n; W% Jof papilledema." a5 V* s9 J7 Z% N) ?
Laboratory Evaluation! z( H a; ] f2 i- g1 [
The bone age was consistent with 28 months by+ s5 J! i' G. m3 a
using the standard of Greulich and Pyle at a chrono-8 I$ ^ |; @2 p1 z' g& D: E+ {
logic age of 16 months (advanced).5 Chromosomal. ]5 @4 D: \$ F+ ^1 I9 {9 n0 F
karyotype was 46XY. The thyroid function test
# U- f9 P) ^; [4 M- P \% u. D5 Lshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
; T% W& B' d6 Y6 P/ clating hormone level was 1.3 µIU/mL (both normal).
' o; m& a" d( ~4 J1 QThe concentrations of serum electrolytes, blood
" j2 ~9 R! {) V- b& m% f, q2 wurea nitrogen, creatinine, and calcium all were
a' p0 ]7 a3 e1 y' N$ b3 D# xwithin normal range for his age. The concentration7 ?$ M. m$ I* t$ ^5 h7 i. E
of serum 17-hydroxyprogesterone was 16 ng/dL0 P, K9 M5 X2 R1 B7 L7 n
(normal, 3 to 90 ng/dL), androstenedione was 20& E% D a" {3 N0 c9 A3 J
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
! T; g9 X p0 Y6 nterone was 38 ng/dL (normal, 50 to 760 ng/dL),
/ p7 y# g. }9 \! b2 i& s( ~. \desoxycorticosterone was 4.3 ng/dL (normal, 7 to
& K- R; @/ R) o) I( Z' t49ng/dL), 11-desoxycortisol (specific compound S)
) y( }- n! g5 A9 lwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
8 h: F! v" I' U, r+ h( z/ etisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total- p% A9 I9 A9 u, j' U" Q
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
5 o/ } E' |9 m- v% D; nand β-human chorionic gonadotropin was less than
2 S( ?* a% W( W6 a" r5 mIU/mL (normal <5 mIU/mL). Serum follicular& ~# o5 s+ ^' P
stimulating hormone and leuteinizing hormone& k# D" V: ~0 ^( x3 m# A( M$ `, N
concentrations were less than 0.05 mIU/mL
* o. `5 {0 q3 C/ a4 H+ A) r(prepubertal)., L$ i$ V% `3 f- U
The parents were notified about the laboratory; X4 M. H7 C( H" |5 c5 W7 W) D
results and were informed that all of the tests were% I8 @, K+ M# F- g% _) r
normal except the testosterone level was high. The; A& b' p" j1 ^
follow-up visit was arranged within a few weeks to% v. |4 \4 ?, s( a- P; q
obtain testicular and abdominal sonograms; how-" f5 K" z4 |" l: T6 G; T
ever, the family did not return for 4 months.
/ L0 Z0 ~6 `; _; dPhysical examination at this time revealed that the0 H( x5 e% e2 w5 _+ }* w( ]
child had grown 2.5 cm in 4 months and had gained
v L* P+ j% q4 b1 U& d# Z2 kg of weight. Physical examination remained1 V, a& t1 w+ `+ V8 ^ Q
unchanged. Surprisingly, the pubic hair almost com-+ w- B3 W. s. `; o) l
pletely disappeared except for a few vellous hairs at- t3 p5 {9 b% P
the base of the phallus. Testicular volume was still 2
3 p% w+ \* x; N# h5 tmL, and the size of the penis remained unchanged./ G( [& R: Q$ o' ^
The mother also said that the boy was no longer hav-
+ a' N+ P" c# R- q$ s8 Ping frequent erections.
% }& A& e3 [2 L2 I& ~Both parents were again questioned about use of
: B) G* r" S7 h7 B$ w6 V( gany ointment/creams that they may have applied to
( j0 g" `# d. j: e. Othe child’s skin. This time the father admitted the- v8 ?& p% N$ N& w2 s
Topical Testosterone Exposure / Bhowmick et al 541) c8 ]7 N' h, ?# @& a: P8 W; [( W
use of testosterone gel twice daily that he was apply-: P" o: V$ Y; D( q
ing over his own shoulders, chest, and back area for5 ~( E2 |4 r+ A E1 [1 r7 c, l" R
a year. The father also revealed he was embarrassed
8 e( `: [- H( H8 o8 `7 e( O% o: Vto disclose that he was using a testosterone gel pre-
% C3 Q8 z) b3 O- Kscribed by his family physician for decreased libido3 Q' y1 e7 s( P
secondary to depression.
+ q! |" @( r7 Z2 CThe child slept in the same bed with parents.( t; p* J4 H7 K: o
The father would hug the baby and hold him on his7 R$ M% n& g6 v. L
chest for a considerable period of time, causing sig-0 v+ R8 L( { a, a$ F
nificant bare skin contact between baby and father.7 q) Q; d3 b% C( o, t
The father also admitted that after the phone call,
$ l1 ?1 ?; v( T( M+ Pwhen he learned the testosterone level in the baby
7 ]; r4 G6 `% a; E8 Q/ H/ ]was high, he then read the product information, M5 K% ]8 | L T* v
packet and concluded that it was most likely the rea-
; S* ~" v" R1 a& T+ y$ n) \son for the child’s virilization. At that time, they5 b: y. Z+ Q* b( r
decided to put the baby in a separate bed, and the
8 A& ]5 w5 ^2 p- P( s: Kfather was not hugging him with bare skin and had
; X9 a; L( F# }been using protective clothing. A repeat testosterone
0 H/ d6 T, h! ~$ Ytest was ordered, but the family did not go to the
. q* e9 r, f: e( M, S+ @: Jlaboratory to obtain the test.3 c7 a( }) n; J5 R4 s- u% g
Discussion
0 {2 a* M, N- R% M( m0 yPrecocious puberty in boys is defined as secondary6 `: q8 A; b- I# r5 C" O
sexual development before 9 years of age.1,4( J* ?0 Z8 p! x" v; z5 @, E
Precocious puberty is termed as central (true) when
$ \ V: W2 o7 r sit is caused by the premature activation of hypo-
; f8 B9 \2 t$ m% Pthalamic pituitary gonadal axis. CPP is more com-
A, A7 {: @7 R# pmon in girls than in boys.1,3 Most boys with CPP
( X+ `6 Z9 u" h6 P8 V# g" hmay have a central nervous system lesion that is" M. p: n! W0 ?" @: Y! J
responsible for the early activation of the hypothal-1 i9 M0 ]2 y5 H
amic pituitary gonadal axis.1-3 Thus, greater empha-
! Y) p9 F6 z) Rsis has been given to neuroradiologic imaging in
, r* _' a0 Z) mboys with precocious puberty. In addition to viril-
. i& x4 o: O \ization, the clinical hallmark of CPP is the symmet-; A2 L: Z. w j( ]* T6 g8 l; w! o
rical testicular growth secondary to stimulation by
4 K6 ~% l7 T+ g" W# Vgonadotropins.1,34 j+ t. V, Q9 R+ _6 q7 r
Gonadotropin-independent peripheral preco-7 j) e7 }1 {( s8 s* D& E
cious puberty in boys also results from inappropriate
: C6 U3 t0 n3 Z, Y! q$ Nandrogenic stimulation from either endogenous or
3 U: {6 L% L+ ]+ k6 @exogenous sources, nonpituitary gonadotropin stim-2 `, w [! g5 {! O# w" k
ulation, and rare activating mutations.3 Virilizing: G$ B% i- Y9 F# j
congenital adrenal hyperplasia producing excessive& k1 V A4 y+ f' V
adrenal androgens is a common cause of precocious
' M8 E2 L# d ]4 f; zpuberty in boys.3,4
3 {5 \7 Z! |2 V y% G- \The most common form of congenital adrenal6 c: l5 F2 |% O: E+ }. h n" \
hyperplasia is the 21-hydroxylase enzyme deficiency.
1 t6 A7 v& G6 C+ r' jThe 11-β hydroxylase deficiency may also result in
7 t2 u6 K& i/ j1 W6 ^* J) iexcessive adrenal androgen production, and rarely," o' Q+ _, Z* D' `3 o
an adrenal tumor may also cause adrenal androgen
8 D; u ~; v% B" Jexcess.1,3
7 W$ @/ P% Z' W# W- Mat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from* n, `, B& Z/ i! k3 F; e
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
- o- o& D2 o! E' }A unique entity of male-limited gonadotropin-+ g3 e" v( Z1 S0 R/ V5 _2 e
independent precocious puberty, which is also known) Q8 t5 I4 y7 F6 Z( L
as testotoxicosis, may cause precocious puberty at a) U9 p7 ^, P# D1 u) n
very young age. The physical findings in these boys
+ S' ?0 H8 `2 jwith this disorder are full pubertal development,
0 J; x D# D, Y" U6 Z5 X. X/ Tincluding bilateral testicular growth, similar to boys& r3 b- t; U- d& ~1 h
with CPP. The gonadotropin levels in this disorder
* ?. ?* q& G7 C/ n* v# E; H3 Sare suppressed to prepubertal levels and do not show$ I, }# \$ v2 l! E( L1 r7 n) B& O# z
pubertal response of gonadotropin after gonadotropin-; ], M6 [' \. J! F$ V" Q7 {% o- v
releasing hormone stimulation. This is a sex-linked
' [. \5 E& t; l1 s& M- U0 B" Jautosomal dominant disorder that affects only
* L% { S2 t1 z8 w5 _males; therefore, other male members of the family: G$ a1 Y$ D5 e- Q7 ^
may have similar precocious puberty.3
1 K$ W3 X0 R9 s2 VIn our patient, physical examination was incon-
: W, _) r. t, G0 s `3 H9 @% s3 psistent with true precocious puberty since his testi-3 d& z3 Y8 T+ e" y; t* ^* e/ [
cles were prepubertal in size. However, testotoxicosis: K: X4 @8 Y+ T* ?) X% `+ S
was in the differential diagnosis because his father
3 ], }& i1 O8 c+ K) d2 Hstarted puberty somewhat early, and occasionally,5 j+ s3 k) V k% [7 F. C9 H
testicular enlargement is not that evident in the
' I; ?& A r" l, D Y6 {beginning of this process.1 In the absence of a neg-
1 r# ?2 d, ?4 }( L; u9 Y; E% z/ aative initial history of androgen exposure, our0 K) [' r5 g6 }8 f; }+ z: H
biggest concern was virilizing adrenal hyperplasia,( W0 E, Q3 K. |7 f/ E/ F
either 21-hydroxylase deficiency or 11-β hydroxylase
& M. R( [6 a. m- ^deficiency. Those diagnoses were excluded by find-
9 |5 h- k: L# l9 d! jing the normal level of adrenal steroids.7 q7 `+ u/ g& G1 l( r$ A. h! n. [+ w
The diagnosis of exogenous androgens was strongly0 j! S: R7 U4 m" I
suspected in a follow-up visit after 4 months because
1 }* J+ q! w9 n, kthe physical examination revealed the complete disap-
3 r* o8 _2 Z' Zpearance of pubic hair, normal growth velocity, and
' I, }& P3 u1 D& }, C" R: F- w& Kdecreased erections. The father admitted using a testos-! V8 N# K6 i/ p$ M
terone gel, which he concealed at first visit. He was
+ l6 n& H7 u5 M& [- l/ f; }using it rather frequently, twice a day. The Physicians’% y; o$ O, D- s! o
Desk Reference, or package insert of this product, gel or
/ a+ [, r$ ^; i7 L5 [cream, cautions about dermal testosterone transfer to
6 z. S4 y/ D; }: K7 Kunprotected females through direct skin exposure.
. U/ M7 j7 D ?2 ` zSerum testosterone level was found to be 2 times the
, d3 ?- Z$ e1 O! Pbaseline value in those females who were exposed to% u% h7 G [$ x" T. v3 o
even 15 minutes of direct skin contact with their male
! I: N/ ~; E0 Q2 B; g3 Epartners.6 However, when a shirt covered the applica-/ {* ~1 O. p( Z) J+ A
tion site, this testosterone transfer was prevented.5 y0 H8 C4 m g/ @
Our patient’s testosterone level was 60 ng/mL,
+ f8 [4 S0 D% q2 b4 H) E8 xwhich was clearly high. Some studies suggest that4 U9 m: H( B1 R. `4 u |
dermal conversion of testosterone to dihydrotestos-" K8 _# `3 y0 f. G" [$ N' }
terone, which is a more potent metabolite, is more
! u- X7 ^) Y# U6 x! @+ [active in young children exposed to testosterone) }8 b3 Z6 R# b1 B0 N0 E
exogenously7; however, we did not measure a dihy-5 X" W: A! P4 Z' _% j. Q) l
drotestosterone level in our patient. In addition to
+ H2 I1 v3 I; xvirilization, exposure to exogenous testosterone in
: @6 M2 z R2 i# _% Vchildren results in an increase in growth velocity and
& A& E+ O% T+ g! c& ?0 X& Padvanced bone age, as seen in our patient.3 I3 t& W0 E: u0 e* i
The long-term effect of androgen exposure during( F# ], g' ~" ~2 r" W8 W
early childhood on pubertal development and final
: W; ]7 c9 r- ]* b' @% Vadult height are not fully known and always remain' e0 K1 O( \/ ^4 Z
a concern. Children treated with short-term testos-! y4 }, q1 |, y: S, h' O
terone injection or topical androgen may exhibit some
2 H2 L4 v7 F( m) n/ s, c7 @acceleration of the skeletal maturation; however, after
8 Q4 s$ J3 Q1 b1 x5 U, m$ @$ dcessation of treatment, the rate of bone maturation3 W$ D& n6 p" I f' K6 k
decelerates and gradually returns to normal.8,9
k& w% B( k- R* ?4 Q/ A+ RThere are conflicting reports and controversy+ F3 T |" D4 x: }0 \2 ^, Y
over the effect of early androgen exposure on adult- u: p# u- l0 N |* u
penile length.10,11 Some reports suggest subnormal5 M# a$ y) g) A# S# `/ y
adult penile length, apparently because of downreg-4 h$ x& z ?: o' a
ulation of androgen receptor number.10,12 However,4 w+ ?! Z* }3 c! p: {0 e
Sutherland et al13 did not find a correlation between
( A2 g- u' v4 n2 i" B7 hchildhood testosterone exposure and reduced adult' f2 g5 X! K& L1 R5 D
penile length in clinical studies., t& S. h0 K& ^
Nonetheless, we do not believe our patient is
( y; O" F( j7 ygoing to experience any of the untoward effects from4 `4 A. v1 U. D
testosterone exposure as mentioned earlier because* M' P i* n6 L, W
the exposure was not for a prolonged period of time.
) v7 M" G& \2 v# A3 ~- X8 B0 CAlthough the bone age was advanced at the time of
1 j2 F" r |8 f4 e, jdiagnosis, the child had a normal growth velocity at' L6 Z0 Y' d7 {9 d
the follow-up visit. It is hoped that his final adult# G" n# M4 _, {4 z& `8 h8 g& C( o
height will not be affected.
: h" e/ A% d5 SAlthough rarely reported, the widespread avail-9 Y9 D$ D& ~% J3 z& `1 B1 a
ability of androgen products in our society may
+ W, [4 W9 p/ Z8 w4 rindeed cause more virilization in male or female
# [- U- S. T5 v9 Lchildren than one would realize. Exposure to andro-- l; m- j% W3 t9 _
gen products must be considered and specific ques-! f4 ?; J* K& n4 h/ s( v) o
tioning about the use of a testosterone product or
4 g3 u/ u7 w- N$ ?' {( W) q2 @) hgel should be asked of the family members during
! i3 f. O3 W& s1 |/ [- z6 f# B6 c' @& j2 Uthe evaluation of any children who present with vir-
. B" |1 g. S; ?& w4 silization or peripheral precocious puberty. The diag-7 d& Y2 G) F0 } R3 q [
nosis can be established by just a few tests and by# w: e" ?- F) q9 t% H7 {* G
appropriate history. The inability to obtain such a: q0 Q" K/ v& j
history, or failure to ask the specific questions, may! b; a- h, d) l% o
result in extensive, unnecessary, and expensive
6 Y: I: \$ ~8 ?8 k0 h$ Z% W! Xinvestigation. The primary care physician should be
- z, O4 W1 G% }- n P' Yaware of this fact, because most of these children: |( q8 D) K; d' }; a7 ?
may initially present in their practice. The Physicians’
. C5 j' e$ k, g, b( g9 f& ZDesk Reference and package insert should also put a& Y' m3 q7 Z% S0 Y+ @1 E( K
warning about the virilizing effect on a male or' X$ R2 A' ]2 k& b, V# p# @: \
female child who might come in contact with some-
" n1 g" P @+ y. w1 zone using any of these products.2 i; F4 B% U, x# h
References
% R: X% ] U- \8 @- }$ ^1. Styne DM. The testes: disorder of sexual differentiation
2 B. n1 I+ k/ {5 L! |/ qand puberty in the male. In: Sperling MA, ed. Pediatric8 i/ n. H6 M5 t$ |, J6 V
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
! b7 `7 U1 E, g) ]& m9 J2002: 565-628.
9 b* d! t9 d F0 Y e" |! L2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious" K# I1 N# U$ f: w m c
puberty in children with tumours of the suprasellar pineal |
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