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Sexual Precocity in a 16-Month-Old6 U- L% q/ E3 H* q2 o1 }# r
Boy Induced by Indirect Topical3 t$ S$ K/ W% Y0 `
Exposure to Testosterone
2 d9 m# S6 f! zSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
2 u2 O% C: q$ ]! jand Kenneth R. Rettig, MD1
) W9 n: |( |" }% a4 t1 vClinical Pediatrics8 Y; u/ L6 _3 P! v# `
Volume 46 Number 6- j( ~* D2 M. d' y+ e: y2 Q5 v
July 2007 540-543) A. i4 h) P2 {
© 2007 Sage Publications1 `! K, b1 o4 I+ a8 x. A
10.1177/0009922806296651
" F9 O1 f# a: @. |, Lhttp://clp.sagepub.com, p& V. Q0 C/ v4 j7 B
hosted at+ K0 I# }- t" } n5 e
http://online.sagepub.com5 W8 @: m& Y# J5 E, _+ r' I: \
Precocious puberty in boys, central or peripheral,
/ W, k" z7 ~9 v: n- C. X# Xis a significant concern for physicians. Central/ F v, G* A. p- Y
precocious puberty (CPP), which is mediated
1 @3 O: v8 Y( j1 k3 |through the hypothalamic pituitary gonadal axis, has1 E6 ?4 @+ V- V5 S7 I, A6 }* o
a higher incidence of organic central nervous system; H! x! w) ?% `" v
lesions in boys.1,2 Virilization in boys, as manifested
$ v" ~% h! ]6 bby enlargement of the penis, development of pubic0 k# d- H0 V: s8 R
hair, and facial acne without enlargement of testi-- ?1 d1 Z! D* M4 n
cles, suggests peripheral or pseudopuberty.1-3 We
/ O8 r K* \) w* `' ?7 a7 Q& ereport a 16-month-old boy who presented with the
6 @0 f. J& f6 V' A8 d: Cenlargement of the phallus and pubic hair develop-
, p0 v& q* L- J# H7 Mment without testicular enlargement, which was due
7 K2 }! H. Z3 W: H6 J2 p( _" u7 m* Xto the unintentional exposure to androgen gel used by6 s0 a, A3 w; U6 b& Y" t. \( W
the father. The family initially concealed this infor-, ]" [+ [- {+ x+ k
mation, resulting in an extensive work-up for this9 i+ E- j2 l' |( n' T1 z
child. Given the widespread and easy availability of
9 A) W/ a0 Y- m' Ttestosterone gel and cream, we believe this is proba-, p. y+ \8 k) i: }7 A- s4 H
bly more common than the rare case report in the
' C P9 y% a5 B, g" Gliterature.4
. m* B3 p6 A& g' e; YPatient Report
. F+ u: v" b) F7 @- f' @- BA 16-month-old white child was referred to the+ U7 q& I5 n( F/ d( P! Y* D
endocrine clinic by his pediatrician with the concern& M- [; c4 R9 b1 K5 f6 r
of early sexual development. His mother noticed1 | o' F- k$ p6 g
light colored pubic hair development when he was
/ `6 B0 j- A) E3 e" ]) Z' }From the 1Division of Pediatric Endocrinology, 2University of
$ v- E" D/ z& u' {/ wSouth Alabama Medical Center, Mobile, Alabama.3 J. o! P+ g( E# O1 p* T o9 U
Address correspondence to: Samar K. Bhowmick, MD, FACE,& p& D* W, [& |7 _1 a. {( L
Professor of Pediatrics, University of South Alabama, College of% q; v |0 h# @0 r7 n$ G9 b
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
' w3 }; u. B+ W; |: {+ [e-mail: [email protected].- H' g Z/ ~4 h1 F+ F
about 6 to 7 months old, which progressively became
" q7 ?, X; r1 w, p7 o/ p" r9 Z7 K, Ddarker. She was also concerned about the enlarge-' G' `& X( G& l! V; W& f0 I6 F
ment of his penis and frequent erections. The child' {9 ?; E6 B" W4 ]1 h: u
was the product of a full-term normal delivery, with3 D. s, a! T# g0 r2 ]2 Y
a birth weight of 7 lb 14 oz, and birth length of
1 j* L2 l* P" j/ e. T" I( N) s) Y% ^20 inches. He was breast-fed throughout the first year# O/ s% k. A4 ~# D5 o, V
of life and was still receiving breast milk along with9 z$ X( g }: z+ r
solid food. He had no hospitalizations or surgery,% ?+ Z! E* b5 o/ z- _( a& _
and his psychosocial and psychomotor development% P. a) c& K- `/ U: Y4 w% |2 |6 @
was age appropriate.& N( r# M. V% P, {# B
The family history was remarkable for the father,
* {8 Y! C, \& [+ \who was diagnosed with hypothyroidism at age 16,
# o/ v9 V {; S4 s" twhich was treated with thyroxine. The father’s
3 S a) ?1 `; g, p' [4 }height was 6 feet, and he went through a somewhat* ?5 b; a2 u+ |8 s* h
early puberty and had stopped growing by age 14.
+ ?2 l$ _2 G$ v# _! z& BThe father denied taking any other medication. The$ V; y) D$ [: W) D1 J; r' I8 L8 D
child’s mother was in good health. Her menarche
. T* e5 P1 J. q |- Iwas at 11 years of age, and her height was at 5 feet: B- R% Y9 T. K f% f* v1 @1 s
5 inches. There was no other family history of pre-7 z @. @; \+ y9 B1 r% S: A# B
cocious sexual development in the first-degree rela-5 l4 x/ f2 t; {( g
tives. There were no siblings.
' n& o2 f2 h, J* o. I8 TPhysical Examination
- l& \& D$ q$ @6 |The physical examination revealed a very active,
- C6 Z% [/ k8 H! P. v3 H& w* nplayful, and healthy boy. The vital signs documented
3 L% E5 U) u& h# V2 u6 S# ya blood pressure of 85/50 mm Hg, his length was
2 n( |/ ]+ z& I& L* z z) `90 cm (>97th percentile), and his weight was 14.4 kg
3 a" D6 _0 S3 h }) S# _7 Z: ^(also >97th percentile). The observed yearly growth% G& }$ |5 S/ E' J! W
velocity was 30 cm (12 inches). The examination of. H6 W/ g7 @! ~( V, m
the neck revealed no thyroid enlargement.
. w& T3 n+ ?4 H* N b6 C& JThe genitourinary examination was remarkable for+ ^- H8 I$ `/ x' Q
enlargement of the penis, with a stretched length of( h# v( M% I) o% Z
8 cm and a width of 2 cm. The glans penis was very well& q: J4 x+ Z( O! V4 K! V$ h
developed. The pubic hair was Tanner II, mostly around
@+ b* y. M2 R S: n/ i540+ B( m$ {( l# k
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from" x7 Z8 L- `3 \0 V
the base of the phallus and was dark and curled. The
* c0 p& ]$ L( E+ |testicular volume was prepubertal at 2 mL each.# d4 o1 A7 g& X4 e" o/ b
The skin was moist and smooth and somewhat- y% O# e& N. m5 D- G- j
oily. No axillary hair was noted. There were no
7 j0 N5 ?2 o" x5 N# Q* r! [abnormal skin pigmentations or café-au-lait spots.0 t( c0 r! \+ G3 Q8 h8 k! x
Neurologic evaluation showed deep tendon reflex 2+. {* o0 ?) p+ R9 p: c+ l, L
bilateral and symmetrical. There was no suggestion
: C' n. M6 t- \- K3 Fof papilledema.3 k7 n8 a6 z& G x& Q: w' n
Laboratory Evaluation
. P2 v2 |5 b7 v- U/ U; OThe bone age was consistent with 28 months by9 B! w) ]8 O1 J8 V5 E
using the standard of Greulich and Pyle at a chrono-1 v6 u: Z# q- _3 K: Q
logic age of 16 months (advanced).5 Chromosomal
+ j3 J/ r) Q& S7 B* h. i9 s) wkaryotype was 46XY. The thyroid function test+ U+ U, B# Y& a8 V* @0 n
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
4 I( O6 M. n. H1 P/ hlating hormone level was 1.3 µIU/mL (both normal).2 L" F5 c# w6 M$ _6 I1 \
The concentrations of serum electrolytes, blood/ E' w1 O$ b, L5 h' l* N3 D: l
urea nitrogen, creatinine, and calcium all were
( P$ r2 o& _2 |: {within normal range for his age. The concentration
' l; b! `( G& E9 F7 k$ Z0 iof serum 17-hydroxyprogesterone was 16 ng/dL* |; k& V2 d# G$ l# h9 \" x; x
(normal, 3 to 90 ng/dL), androstenedione was 20- e8 n; ]0 n8 V' U
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
: _( v4 ~" c# b: g9 I: o4 w2 Lterone was 38 ng/dL (normal, 50 to 760 ng/dL),
( M7 y& q1 Z; P4 Y+ y! q1 kdesoxycorticosterone was 4.3 ng/dL (normal, 7 to
+ C5 B0 K2 @7 L9 V- l# P8 S49ng/dL), 11-desoxycortisol (specific compound S): z6 h" k5 T# C! h. D/ \8 P
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-( \( a% S" V' [& z4 `% @
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
/ L3 ]1 u. ]& c2 q+ {1 ?testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
" R# H6 b# B/ |8 u+ h: d: @and β-human chorionic gonadotropin was less than
3 V0 U5 m7 Z! L6 t* V5 mIU/mL (normal <5 mIU/mL). Serum follicular! V- z5 ~( N9 N% x" r
stimulating hormone and leuteinizing hormone
( f6 ^& p( u2 @6 Tconcentrations were less than 0.05 mIU/mL) J+ D$ c1 R. \8 O- l
(prepubertal).
6 F+ r; S w: Y6 qThe parents were notified about the laboratory
, S; Z6 r, s3 kresults and were informed that all of the tests were
* z' N, R8 y; |1 Mnormal except the testosterone level was high. The
' V3 o& Y! s- C: p9 Y% ~$ qfollow-up visit was arranged within a few weeks to1 o8 K( ]1 F" {+ `! q
obtain testicular and abdominal sonograms; how-. B, W) b, L C4 s) i
ever, the family did not return for 4 months.
! `3 t- p8 F- A' n" E- dPhysical examination at this time revealed that the
# [# V: D( D6 @; y( Zchild had grown 2.5 cm in 4 months and had gained
, A& r& I. I6 ]" h0 c* `2 kg of weight. Physical examination remained$ H) v h& J- h
unchanged. Surprisingly, the pubic hair almost com-3 C, a" l& u2 Z7 r' \' \, _4 V
pletely disappeared except for a few vellous hairs at
. V$ Q! F q4 T) b: F5 uthe base of the phallus. Testicular volume was still 2
2 _. _( r. x; g4 `) MmL, and the size of the penis remained unchanged.
2 {9 B9 _9 B( L1 Y! NThe mother also said that the boy was no longer hav-# U/ `: G' ^5 s0 T& x
ing frequent erections.4 _1 [# s' C8 O+ H0 M
Both parents were again questioned about use of
+ d* H2 f0 _. V9 Dany ointment/creams that they may have applied to0 ^& Y+ j5 g: m4 i0 U
the child’s skin. This time the father admitted the& B5 w! v; e) @+ j
Topical Testosterone Exposure / Bhowmick et al 541
, x& p; S }$ H/ f; muse of testosterone gel twice daily that he was apply-
" ?: F z' O$ Ving over his own shoulders, chest, and back area for
# D3 `1 k" U' o5 F+ Q" la year. The father also revealed he was embarrassed
0 a8 f. ]( B, d0 }8 n5 Z* S" zto disclose that he was using a testosterone gel pre-2 b8 x8 h; L e( C9 u
scribed by his family physician for decreased libido6 p* D. I. u' _7 [# {' w F" X
secondary to depression.0 l' t1 Y$ {) v* n: W5 {: ~
The child slept in the same bed with parents.
+ w) p8 W; Q$ Z1 ]$ t# r, |The father would hug the baby and hold him on his
( U, K; s$ o0 c& l$ _/ ^) _chest for a considerable period of time, causing sig-
: g; V0 ~# s) H! C" Cnificant bare skin contact between baby and father.
7 @$ R1 @3 J; q" a4 VThe father also admitted that after the phone call,. Z: n. n6 U' c/ p& y- \" c" O6 \ |& N
when he learned the testosterone level in the baby
3 h; `4 z$ o- x6 W4 p5 G h6 U+ nwas high, he then read the product information0 }# U3 t( G8 ?& _# ?+ j
packet and concluded that it was most likely the rea-* d/ |% @8 n8 E/ `. N% s
son for the child’s virilization. At that time, they
' @6 F: j5 E, wdecided to put the baby in a separate bed, and the! J% p4 d/ ]5 e% r2 F3 J
father was not hugging him with bare skin and had, }0 ]" w Z" |( J6 O! X
been using protective clothing. A repeat testosterone
' B$ J' j, z6 ?4 J/ R* @: Rtest was ordered, but the family did not go to the) i5 q7 d5 h% Z8 l( K2 k
laboratory to obtain the test.
+ [) d& l D7 ]* ~7 Z% bDiscussion
- |4 a# l: v4 ~- A c0 h+ F; P! xPrecocious puberty in boys is defined as secondary
& o) k. K* h& R3 Vsexual development before 9 years of age.1,4" ?0 B9 `; w( `0 p' E
Precocious puberty is termed as central (true) when
" T1 J/ b* ] ?% ~" Kit is caused by the premature activation of hypo-
; R6 X2 {; ~2 d) V3 Athalamic pituitary gonadal axis. CPP is more com-5 e9 b/ K9 o. Q. C# ]+ b- B
mon in girls than in boys.1,3 Most boys with CPP. J8 T& {# U, H& ~2 Z+ G1 f
may have a central nervous system lesion that is
/ \/ l0 H* b" Y8 qresponsible for the early activation of the hypothal-
. b! h/ `# c6 C" t0 R C1 i4 j; pamic pituitary gonadal axis.1-3 Thus, greater empha-
1 F# L- X# r* q; M3 m6 v3 `sis has been given to neuroradiologic imaging in
5 c' |" d% m8 x; R1 T. C1 Lboys with precocious puberty. In addition to viril-
5 h4 f) b/ h0 m! h* X W3 Cization, the clinical hallmark of CPP is the symmet-
( X6 F. A( l4 Y& jrical testicular growth secondary to stimulation by
: X( M4 `' G( sgonadotropins.1,3 W, B" W. A1 c
Gonadotropin-independent peripheral preco-+ p: p0 ^, [; Z6 J7 z
cious puberty in boys also results from inappropriate. W6 K; N; v% B+ s+ Y
androgenic stimulation from either endogenous or# A. f, \6 w) k y- [
exogenous sources, nonpituitary gonadotropin stim-
" [& h" F) W9 ^5 Lulation, and rare activating mutations.3 Virilizing
! ~# p+ [' M$ M: D. T: F* Xcongenital adrenal hyperplasia producing excessive
8 |, N1 ?$ q" nadrenal androgens is a common cause of precocious
0 M" n' V2 e' w9 Q, Spuberty in boys.3,4: C& U( T6 X- c7 m$ F7 P
The most common form of congenital adrenal
) H s5 N4 {! w$ G5 lhyperplasia is the 21-hydroxylase enzyme deficiency.
' D: j4 E1 @0 z% k: Z) y m+ Y+ ]/ |& B3 ]The 11-β hydroxylase deficiency may also result in
9 }" y$ F* c5 |1 {* s9 Fexcessive adrenal androgen production, and rarely,/ f. R \ a D1 K8 u, t$ B$ C, T
an adrenal tumor may also cause adrenal androgen
: s( K, _1 `5 q' ^, f6 @: L; Vexcess.1,31 y3 v3 ~+ n' H
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from# a# q- T7 m/ W2 P
542 Clinical Pediatrics / Vol. 46, No. 6, July 20072 _6 L9 w1 Z) J
A unique entity of male-limited gonadotropin-* n$ ^3 p( V$ [6 [7 q! ^
independent precocious puberty, which is also known
! ?' j e c/ I' d6 Pas testotoxicosis, may cause precocious puberty at a8 A; L' K7 s1 b
very young age. The physical findings in these boys
6 _- g& J& O% c2 c' a* |9 r* q% _6 Cwith this disorder are full pubertal development,
+ c8 A2 P9 a. h0 h: e7 P) Zincluding bilateral testicular growth, similar to boys y& `$ m7 c0 S. Q" Q+ W; ~
with CPP. The gonadotropin levels in this disorder+ N! ^- g% U0 M: B) a
are suppressed to prepubertal levels and do not show
+ D+ b1 L8 J7 `$ K( s, T0 ?pubertal response of gonadotropin after gonadotropin-
4 r* f+ m) e Z- c3 K9 oreleasing hormone stimulation. This is a sex-linked D& b, _* h5 U1 q" e% F' C
autosomal dominant disorder that affects only. t! f; c* F$ o
males; therefore, other male members of the family
S7 [% S3 Y; o% O2 T* h2 ]may have similar precocious puberty.3, M5 {) K, c: K2 u7 L
In our patient, physical examination was incon-8 B6 \" V6 b; y' K# |8 w
sistent with true precocious puberty since his testi-; T, A n% f* d* Y9 F# [8 s' C
cles were prepubertal in size. However, testotoxicosis; w4 T0 D- O9 |3 i3 P
was in the differential diagnosis because his father
0 q* E4 y. P6 S6 R. o- j7 Gstarted puberty somewhat early, and occasionally,) m! X, k# U. w$ N4 _
testicular enlargement is not that evident in the
0 L: D3 g) i6 g1 D+ P ebeginning of this process.1 In the absence of a neg-' A1 u, ?4 _% k
ative initial history of androgen exposure, our
4 N M c7 Q1 kbiggest concern was virilizing adrenal hyperplasia,
1 @2 Z2 P3 [' g# Ceither 21-hydroxylase deficiency or 11-β hydroxylase
, o- e7 T( m& r3 {5 cdeficiency. Those diagnoses were excluded by find-
1 B% h7 T; V, n: [& p- ting the normal level of adrenal steroids.
" E. ^+ W/ o4 J: ^6 r5 K5 r& oThe diagnosis of exogenous androgens was strongly
& {+ J3 v1 ^- ]suspected in a follow-up visit after 4 months because" a4 v! h/ j: b: j) c& O
the physical examination revealed the complete disap-
# t5 i, l2 b, F' D; a+ Ppearance of pubic hair, normal growth velocity, and
8 e( d; g; K: D( Y9 udecreased erections. The father admitted using a testos-7 W3 [ {# I- E. j! O% u/ g
terone gel, which he concealed at first visit. He was- Z6 @& w- w/ B! x7 [- l& j& y
using it rather frequently, twice a day. The Physicians’
8 q+ z x! k! vDesk Reference, or package insert of this product, gel or
1 _( d" J! h# ]' d0 a& Tcream, cautions about dermal testosterone transfer to, x3 J* P* j; j% O9 x
unprotected females through direct skin exposure.
! Z. T$ s* G' u5 k4 e" oSerum testosterone level was found to be 2 times the& U* y. [" U1 ?; @
baseline value in those females who were exposed to. x4 }2 F/ s) A. k! N' [! E
even 15 minutes of direct skin contact with their male* w- i6 ^* u W$ D' {& P
partners.6 However, when a shirt covered the applica-
! O9 [$ m8 P( I' ?4 i4 t9 m# Ttion site, this testosterone transfer was prevented.
3 V, f' v5 @3 A9 K6 ]Our patient’s testosterone level was 60 ng/mL,( A. S8 U2 m0 R- A/ m
which was clearly high. Some studies suggest that: v- \3 X* C9 P2 y: f0 K% @
dermal conversion of testosterone to dihydrotestos-1 D. c' r7 A9 u U8 v
terone, which is a more potent metabolite, is more
6 j& T0 y- q# ?' \" o5 d1 qactive in young children exposed to testosterone
" L, N* H U( F- G" ~, R3 C% yexogenously7; however, we did not measure a dihy-1 \7 ]( r- R1 b8 p$ n
drotestosterone level in our patient. In addition to F$ | o! e; }5 q( v
virilization, exposure to exogenous testosterone in
$ I2 K( z" U+ Z1 j; N4 `6 G6 R6 mchildren results in an increase in growth velocity and2 [# K# ]. q$ j$ Q, Y2 V2 ^0 B0 C
advanced bone age, as seen in our patient.$ u4 N0 Z" Y5 g) k* E4 t
The long-term effect of androgen exposure during( X5 W: s! a4 p4 m( R# E
early childhood on pubertal development and final
9 H$ q8 t2 ]% y' N+ W; b; G9 d O; \adult height are not fully known and always remain8 ?! ^7 T; \4 ]0 `( b2 m. k' b
a concern. Children treated with short-term testos-
; g- M4 y8 f- d$ X- {+ }terone injection or topical androgen may exhibit some
2 z" A( U. X* S5 z: tacceleration of the skeletal maturation; however, after
. t7 X* U8 B1 ]- X2 d2 F: Ycessation of treatment, the rate of bone maturation
1 k# X& w. Z* q9 Udecelerates and gradually returns to normal.8,9
% s- B1 c0 O- v3 MThere are conflicting reports and controversy0 y% E7 b4 q4 P" Q. e$ |5 t$ l
over the effect of early androgen exposure on adult' Z0 Z* e* O6 X' @& `
penile length.10,11 Some reports suggest subnormal
x$ t" M9 G% W7 G1 m0 Zadult penile length, apparently because of downreg-
- _+ v- X: D. H; z$ Fulation of androgen receptor number.10,12 However,
- @+ B9 D9 i) d6 LSutherland et al13 did not find a correlation between5 j( X6 m0 d t6 \ ^$ }/ f
childhood testosterone exposure and reduced adult3 g4 T/ K1 r5 r0 z8 d
penile length in clinical studies.
5 m# i; w5 G8 P' JNonetheless, we do not believe our patient is& H" y, a) b7 O* N1 E
going to experience any of the untoward effects from
, s; [2 e1 m2 F# qtestosterone exposure as mentioned earlier because0 V6 x% R0 M% \
the exposure was not for a prolonged period of time.
% W1 b( m1 M* o9 ]8 _. r1 ]2 GAlthough the bone age was advanced at the time of! B" b. _% g7 |5 ]6 w, l
diagnosis, the child had a normal growth velocity at8 K& ~% s1 |* a! h2 q/ [+ O
the follow-up visit. It is hoped that his final adult5 t" v! [9 O8 m# }4 @# g( {) g2 {
height will not be affected.
9 y8 J$ J4 Y4 H' A( BAlthough rarely reported, the widespread avail-
' S9 Z5 c8 `7 @ iability of androgen products in our society may
7 C$ q/ t8 ?% L# B) D% t/ }8 A findeed cause more virilization in male or female! w1 x1 ~2 F! r9 `2 O0 C4 f, ~
children than one would realize. Exposure to andro-
3 Q6 U1 E# c! a! e) |; d; n/ Hgen products must be considered and specific ques-6 T4 W# _2 ?- R( N6 ?" c% k
tioning about the use of a testosterone product or
8 t v4 ]; [0 e/ v) }gel should be asked of the family members during" R( t0 d* a- g! @) _* p0 i6 q" ^
the evaluation of any children who present with vir-- ?0 G2 v/ N* |# p) P4 V1 }
ilization or peripheral precocious puberty. The diag-; n; d; R. R* ]) ~1 G
nosis can be established by just a few tests and by
) k! a& ~8 u" Qappropriate history. The inability to obtain such a
[/ S/ x9 q6 m% O# }history, or failure to ask the specific questions, may9 J7 N- H6 T2 Q3 L/ \* Y/ \8 l+ `$ n6 K
result in extensive, unnecessary, and expensive- O0 P2 A2 _, X! F
investigation. The primary care physician should be2 v2 Z, d+ |3 Q0 |: ~: A
aware of this fact, because most of these children" q% V6 K( z+ V7 f
may initially present in their practice. The Physicians’
/ g6 t# G# V" n) ?4 v6 ^Desk Reference and package insert should also put a% Q. _6 O8 A4 b! b+ Z7 f: t0 v7 `
warning about the virilizing effect on a male or
& V. F) |0 O' u7 R; i2 E ofemale child who might come in contact with some-
; x+ ^* m; Y7 U$ L8 a8 J. c" p% H5 none using any of these products.7 R2 \1 o! W ]' V6 f1 ?" O
References
0 v" O( ^% C, ^2 H9 B1. Styne DM. The testes: disorder of sexual differentiation
2 s8 G! ^0 f) y; \0 g6 Rand puberty in the male. In: Sperling MA, ed. Pediatric L! m& h3 m% E( q$ h* j9 B
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;! n4 [" q! a3 c; X; {! S4 @
2002: 565-628.: Y7 n+ ?; S4 x, U8 e4 \
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious. v0 q1 W7 V" B K) s) A' |
puberty in children with tumours of the suprasellar pineal |
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