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Sexual Precocity in a 16-Month-Old) B5 `2 P$ L l- r2 V: G( q, Y
Boy Induced by Indirect Topical
4 @" V* F; x3 \5 g4 dExposure to Testosterone+ A6 z& M3 r' J1 R3 b
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
+ N' e8 \; a7 |& land Kenneth R. Rettig, MD1
3 @$ V% L$ w9 ]) U, y- @, WClinical Pediatrics
3 ?/ e$ z( N! B# Z# O! F- g, V; sVolume 46 Number 66 B B4 D: S" R) d& _
July 2007 540-543; ^- J, q: Y# t$ ^/ q( p8 k, t" f
© 2007 Sage Publications
1 T9 C0 t/ G+ n' l; {, o4 v10.1177/0009922806296651
, V) @9 q+ s d- ~( ], G# s9 Chttp://clp.sagepub.com
* i+ Q+ M8 \; {" Dhosted at
; Z. Y% f& M( _0 o, m# B7 Y6 _http://online.sagepub.com
# U4 T- k8 E1 w4 r) |( VPrecocious puberty in boys, central or peripheral,# H4 _9 N% S8 @; Y' u. \
is a significant concern for physicians. Central
0 O. U- i2 g1 _% `$ j0 _precocious puberty (CPP), which is mediated
5 s { E* m* P0 T# c4 x, Cthrough the hypothalamic pituitary gonadal axis, has
4 l* y- ^6 H: E5 Q: Ta higher incidence of organic central nervous system& N) w# \2 Y8 U: a2 L' C
lesions in boys.1,2 Virilization in boys, as manifested
. ^. a$ O5 `3 y8 l3 K& Bby enlargement of the penis, development of pubic
/ Q1 L5 o0 P8 u& k* Q9 [7 }, Bhair, and facial acne without enlargement of testi-
0 ]7 h$ {% |6 u ? m1 rcles, suggests peripheral or pseudopuberty.1-3 We
. b% k( R( J* ~report a 16-month-old boy who presented with the
4 F! `8 _! D2 |7 _2 j0 Nenlargement of the phallus and pubic hair develop-- W: p8 f0 d6 z/ a; R5 k
ment without testicular enlargement, which was due- C9 |7 D7 k; N2 f! u- b @8 `1 T
to the unintentional exposure to androgen gel used by% u; D3 }# D- B1 z6 X
the father. The family initially concealed this infor-* k/ y7 P8 m0 w' h, ~3 H# K
mation, resulting in an extensive work-up for this
3 w- l& _% i8 `child. Given the widespread and easy availability of- x3 R& s) f- J, C% O
testosterone gel and cream, we believe this is proba-
5 M# O2 Z3 m' S" d$ c# H: Dbly more common than the rare case report in the: {+ ]5 `- j$ L7 _+ u. H4 M( G
literature.4
/ z" x- z* `5 [- X. z* }; W3 cPatient Report
! {: `" g( |# m; p* B7 j% y; `A 16-month-old white child was referred to the4 T8 p$ D q% i& _6 N) V" O
endocrine clinic by his pediatrician with the concern
' F P1 H! f2 @$ _+ ]4 M aof early sexual development. His mother noticed$ M% L' b! o8 v! M6 E: G
light colored pubic hair development when he was
6 D1 q% Z1 K0 D2 QFrom the 1Division of Pediatric Endocrinology, 2University of
8 }6 l: E/ j, _South Alabama Medical Center, Mobile, Alabama.: r* j- k' L' R5 L
Address correspondence to: Samar K. Bhowmick, MD, FACE,
( m2 I, b$ f0 F2 bProfessor of Pediatrics, University of South Alabama, College of
_3 C: A+ L' p) c: m6 p+ K# dMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
& j, I. Z( B3 T# u. A4 me-mail: [email protected].! I7 o. j+ T# U3 a% C7 c
about 6 to 7 months old, which progressively became
! A5 m! E r5 D7 L# G4 J( kdarker. She was also concerned about the enlarge-0 y9 e& a. Y! i1 s) z+ c' X7 S7 d
ment of his penis and frequent erections. The child
6 i- U4 |8 ?6 x+ ~, A5 E& i. kwas the product of a full-term normal delivery, with
5 ^; `" c& P* D5 h1 w1 ?% qa birth weight of 7 lb 14 oz, and birth length of
/ q2 c+ Y, c1 R20 inches. He was breast-fed throughout the first year3 E' k8 g2 Z- v& f; t
of life and was still receiving breast milk along with) a; }/ z# P! a8 J& r# F9 R
solid food. He had no hospitalizations or surgery,( d7 J0 i' [& Q; k) I- P0 x
and his psychosocial and psychomotor development
% K, l+ i% v, |was age appropriate.& H8 q+ ]9 ]8 c
The family history was remarkable for the father,
) U( w& g* J6 E$ n! N) l6 ewho was diagnosed with hypothyroidism at age 16,) j$ X6 x: G7 p8 @; [9 A1 I0 H- c: Z
which was treated with thyroxine. The father’s- H+ S% R1 J$ E( J
height was 6 feet, and he went through a somewhat
/ R( x) ]' x3 m4 pearly puberty and had stopped growing by age 14.
' [: @% F* B$ z/ @' dThe father denied taking any other medication. The
8 _* r( G) S; rchild’s mother was in good health. Her menarche
( W; Q* e$ P4 l1 n7 l* }( Owas at 11 years of age, and her height was at 5 feet6 X1 X4 x& H0 e
5 inches. There was no other family history of pre-
! J9 g, V6 ]( H+ c0 u" A/ e( Lcocious sexual development in the first-degree rela-9 G! f' |) c1 v! Y4 C
tives. There were no siblings.
0 h$ {4 D. v1 EPhysical Examination
+ n% _7 \; d2 m, h1 K3 j, f- qThe physical examination revealed a very active,3 T0 b4 M3 p4 h6 J# N9 w9 N
playful, and healthy boy. The vital signs documented
: x* H$ ^- a! q5 @a blood pressure of 85/50 mm Hg, his length was
u: u2 \* [, z5 ?90 cm (>97th percentile), and his weight was 14.4 kg9 ]6 M& z) |2 C
(also >97th percentile). The observed yearly growth
, C! l3 Q7 M. ^velocity was 30 cm (12 inches). The examination of) F- W; n/ _! Y+ Z$ q2 C3 W
the neck revealed no thyroid enlargement.
( U3 B$ D7 @9 d# i$ uThe genitourinary examination was remarkable for9 o+ H9 ^3 _3 A
enlargement of the penis, with a stretched length of
5 h% w1 i$ |/ T6 ^" E8 cm and a width of 2 cm. The glans penis was very well
$ i! m8 A, b/ B, ndeveloped. The pubic hair was Tanner II, mostly around
' L0 Y; H+ p0 x; [/ K& B. {540
1 j7 W2 I& }8 w; d' r1 Yat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from0 f( A0 ?3 p8 e1 U- ^
the base of the phallus and was dark and curled. The
3 Q6 v/ x8 T% ^4 H4 H/ ptesticular volume was prepubertal at 2 mL each.
+ \3 n. y/ \9 B- }% \The skin was moist and smooth and somewhat& A$ Q/ G& @. c% R7 u6 e6 K
oily. No axillary hair was noted. There were no
( q$ h6 D' T. S4 Rabnormal skin pigmentations or café-au-lait spots.- C6 C/ t6 p% @ b$ B; ?
Neurologic evaluation showed deep tendon reflex 2+3 U( {5 E+ X2 I7 L
bilateral and symmetrical. There was no suggestion
, b! D! B$ S6 I: Uof papilledema.
2 s6 F* M, }0 yLaboratory Evaluation0 ?" A) V5 ?( Y: t5 R* W6 y# ?& T
The bone age was consistent with 28 months by+ l/ _ l7 C" a; u1 k1 ?; b) t
using the standard of Greulich and Pyle at a chrono-: Z. W: C# T6 l7 V2 q7 O9 y
logic age of 16 months (advanced).5 Chromosomal
T% D) o% H- n3 m# U5 |; ~karyotype was 46XY. The thyroid function test6 D- _3 A8 V& H4 ^4 W! J
showed a free T4 of 1.69 ng/dL, and thyroid stimu-! G/ b5 }5 f) _9 u; d/ f+ Q
lating hormone level was 1.3 µIU/mL (both normal)." W+ C0 q2 V4 ?' e9 w4 E9 F
The concentrations of serum electrolytes, blood
) y0 x1 Y$ ?! [* u7 purea nitrogen, creatinine, and calcium all were8 t5 M) ~2 o/ G- O n3 C# M
within normal range for his age. The concentration
( ^/ P4 L: y6 R6 F" qof serum 17-hydroxyprogesterone was 16 ng/dL
. f* d" H1 r' ^* i) p(normal, 3 to 90 ng/dL), androstenedione was 20% X7 [" y; a+ `; y* ~; |
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-0 x1 y Z# V* u5 I
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
+ s/ d2 @& l/ b6 `9 s8 o& q% kdesoxycorticosterone was 4.3 ng/dL (normal, 7 to8 i9 U! q: D9 N" J0 D! a( E
49ng/dL), 11-desoxycortisol (specific compound S)+ ~" f0 P7 T; `6 e# s5 @
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-7 c: P. ?. a7 W; L; a+ M
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total% y% A% Y9 Q0 \ G x2 a6 |, }
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),& E- w& [ g' P, S8 Y
and β-human chorionic gonadotropin was less than
1 {8 ^2 P* S ~0 ~1 m! ~5 mIU/mL (normal <5 mIU/mL). Serum follicular. s9 E7 r2 y% x$ h% f
stimulating hormone and leuteinizing hormone6 s$ E0 \2 w+ S! o1 f. X7 a
concentrations were less than 0.05 mIU/mL
3 ]6 I6 x( P- ^8 W2 [/ Y(prepubertal)./ G" V Z& w8 @$ y q! c
The parents were notified about the laboratory
' `$ W5 l- ]; P% Wresults and were informed that all of the tests were$ T$ t$ g5 b: Z
normal except the testosterone level was high. The$ e S7 \ D' s% z6 p+ R& M( p$ }
follow-up visit was arranged within a few weeks to8 \* B8 z! k8 K
obtain testicular and abdominal sonograms; how-! }* G7 V' b* N/ u0 M7 l
ever, the family did not return for 4 months.
6 I( h+ s- j. @5 |Physical examination at this time revealed that the
# k! j3 O4 S% R, c, _child had grown 2.5 cm in 4 months and had gained
1 s& }) H% |$ \* S. Y, v' H, x1 u2 kg of weight. Physical examination remained" ?6 v @9 C( U& F* x
unchanged. Surprisingly, the pubic hair almost com-
2 r/ j- H P/ _& F; ?# Kpletely disappeared except for a few vellous hairs at
, ?" ]: R2 M2 J% L' v q' t h0 g* Pthe base of the phallus. Testicular volume was still 2' Q9 l/ G2 ^) K. z1 n) R
mL, and the size of the penis remained unchanged.
% ^* o- }, {$ VThe mother also said that the boy was no longer hav-
$ O+ C5 S9 m" h% N. }7 x3 t+ xing frequent erections.
. o# [& H6 O: R( oBoth parents were again questioned about use of5 t# z9 U2 t9 W# U8 J
any ointment/creams that they may have applied to
" H" e* E, N {' [. U) r$ gthe child’s skin. This time the father admitted the
4 ?' Q' I8 z3 w% Q9 L+ qTopical Testosterone Exposure / Bhowmick et al 541/ X8 ~2 \ y! N& Y
use of testosterone gel twice daily that he was apply-
. `1 B6 J3 G: oing over his own shoulders, chest, and back area for0 s: s; ~3 `, ]2 ^3 N& C
a year. The father also revealed he was embarrassed4 S5 H' }: p4 ^) R1 @$ s; s- o
to disclose that he was using a testosterone gel pre-% i' r8 m q" y" U2 }! f
scribed by his family physician for decreased libido
' U) ~- K) h2 ^1 K0 }; ]5 [secondary to depression.3 I) H7 p3 q+ F* Z, _% m E
The child slept in the same bed with parents.
( l8 m8 R( l4 b- X# ?$ q `! yThe father would hug the baby and hold him on his, d' E8 r9 w1 L* g, x, n6 }
chest for a considerable period of time, causing sig-
2 G* ^4 n0 m3 @5 N* |( \nificant bare skin contact between baby and father." l9 J) p% e i+ i+ r
The father also admitted that after the phone call,
9 h* g J' S. ~9 V( i! Nwhen he learned the testosterone level in the baby/ | g5 p) J- x5 O
was high, he then read the product information( K. v2 y$ C' p! s6 u4 w5 k! F
packet and concluded that it was most likely the rea-, r! v" K6 L7 {1 P
son for the child’s virilization. At that time, they, v# K8 \, k( f( z$ v2 ^
decided to put the baby in a separate bed, and the
4 g, D! b9 y: {% D& nfather was not hugging him with bare skin and had. y# S5 S' n2 n% v. `/ }% _
been using protective clothing. A repeat testosterone. k: G% _" [& X' D8 b' \
test was ordered, but the family did not go to the2 A3 J; z9 `( p6 u5 T
laboratory to obtain the test.
2 ~6 k+ ?0 j' N0 g* h/ sDiscussion
, ~( y1 `0 \) JPrecocious puberty in boys is defined as secondary
4 E" f6 |# L4 Tsexual development before 9 years of age.1,4" u0 @% l: M3 X1 S. g' y/ }, t
Precocious puberty is termed as central (true) when
0 S" t3 J% O& p- y. ?% {* Qit is caused by the premature activation of hypo-
* v7 R0 B% S u: e3 x( x' Lthalamic pituitary gonadal axis. CPP is more com-
% O& M, b F& g6 I8 _7 ~mon in girls than in boys.1,3 Most boys with CPP
6 {0 N1 ~# p" {" {$ B( t; G: gmay have a central nervous system lesion that is( l; B: A0 F9 Q6 f7 z" W5 j$ P+ i
responsible for the early activation of the hypothal-) c n; }4 X2 B- I% B
amic pituitary gonadal axis.1-3 Thus, greater empha-
- ^5 p0 J9 d( U8 gsis has been given to neuroradiologic imaging in5 x6 M* E" R+ K! |& \
boys with precocious puberty. In addition to viril-) d8 u% l9 Q8 D5 |6 P$ J; T
ization, the clinical hallmark of CPP is the symmet-! O7 Q2 Z# O" l& }/ v( H* @" I
rical testicular growth secondary to stimulation by; H) ~6 g6 G( H
gonadotropins.1,3 u) W$ x6 N! i( }# F+ u
Gonadotropin-independent peripheral preco-
5 J2 J. I: I3 G! Zcious puberty in boys also results from inappropriate8 ^) V' _! [% V3 w w
androgenic stimulation from either endogenous or
9 B/ E% j& ?* k" ~exogenous sources, nonpituitary gonadotropin stim-( G" w7 S- M! C6 E) O0 ?
ulation, and rare activating mutations.3 Virilizing; i, {; X' x2 {; w2 v
congenital adrenal hyperplasia producing excessive+ m" }# s6 m3 x0 j
adrenal androgens is a common cause of precocious$ E- K; y0 S. U4 `9 \: p1 @
puberty in boys.3,4' r/ A% l* k( W* ^: B9 L" t
The most common form of congenital adrenal
3 Q8 Z, O; Z' C) Fhyperplasia is the 21-hydroxylase enzyme deficiency.: U: a: q- _: t( h
The 11-β hydroxylase deficiency may also result in
: h; ~5 C r, M H# @, Y- s& Sexcessive adrenal androgen production, and rarely,
& ?2 i8 `, Z) t; j! Fan adrenal tumor may also cause adrenal androgen
* z, M# V0 ]. Jexcess.1,3 X7 ?! W; k& u& ]" j/ d) b- G" N' o
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
3 O( B: K) t' @, u# L3 W; D+ `542 Clinical Pediatrics / Vol. 46, No. 6, July 2007( p: d6 S+ \! j4 C: ?9 G1 r& ?+ ]
A unique entity of male-limited gonadotropin-
7 u: O+ W0 p& v, ^; L4 Iindependent precocious puberty, which is also known0 o; P' u9 t p# M- c
as testotoxicosis, may cause precocious puberty at a( u6 T8 H3 ]1 d k2 X5 n6 R( g
very young age. The physical findings in these boys; w9 Z0 K$ A9 k# ~( M' A- x/ w; Q
with this disorder are full pubertal development,
. n" p/ t* z9 X! D( s5 o5 zincluding bilateral testicular growth, similar to boys" ?/ G! `9 _- h( @4 M5 N% U" ]
with CPP. The gonadotropin levels in this disorder
, m. u& x# p/ Rare suppressed to prepubertal levels and do not show
( C, | |% |5 M( ^: f+ F$ @pubertal response of gonadotropin after gonadotropin-
1 T& b$ n2 k$ Q2 J/ x, F( ], zreleasing hormone stimulation. This is a sex-linked: V1 q$ j3 S' j0 ]8 _
autosomal dominant disorder that affects only
. G' j2 P9 I) N4 z% Umales; therefore, other male members of the family
5 l% _) s5 d4 ?/ d7 Kmay have similar precocious puberty.3& u( S( }: P; g4 Y5 J# G% p
In our patient, physical examination was incon-" b8 j" S4 P/ `9 ^' s7 r; f
sistent with true precocious puberty since his testi-) \. \9 {1 _4 m& V
cles were prepubertal in size. However, testotoxicosis
4 v' v. x# M/ ewas in the differential diagnosis because his father4 f! H. z: o2 m2 r
started puberty somewhat early, and occasionally,
& k2 ?/ F ? u% u$ q3 ~testicular enlargement is not that evident in the9 D" f( k% g4 _# e0 { l
beginning of this process.1 In the absence of a neg-$ G7 \/ d- B' _ Z9 q. O2 ]& `/ _
ative initial history of androgen exposure, our# \: R9 u' d1 U( \
biggest concern was virilizing adrenal hyperplasia,
6 @8 Y7 h3 B- W4 ]/ aeither 21-hydroxylase deficiency or 11-β hydroxylase, I9 l) \9 o+ Q4 `3 A9 T4 ] K
deficiency. Those diagnoses were excluded by find-
) z5 k# ~- M5 B% K9 _' A+ E- `ing the normal level of adrenal steroids.
* t, n! v& v+ Q& Q `3 i7 ^The diagnosis of exogenous androgens was strongly d: h6 q& O; j
suspected in a follow-up visit after 4 months because! M ]4 a1 G4 s8 r
the physical examination revealed the complete disap-
/ k% W$ U- C' b, M: ppearance of pubic hair, normal growth velocity, and: u, Z, b: Z& f: H0 ] X' N, Q5 k
decreased erections. The father admitted using a testos-
% k B, Q C5 S5 a! b- w1 bterone gel, which he concealed at first visit. He was
2 V: A5 o6 A r+ _( w# p1 Qusing it rather frequently, twice a day. The Physicians’. T1 S' L* {: S/ p) a; b9 h3 C
Desk Reference, or package insert of this product, gel or+ X6 \+ i/ P+ [; ^ L' H( z- j
cream, cautions about dermal testosterone transfer to1 H' C1 @% h: P7 |
unprotected females through direct skin exposure.
! g# ~9 x! G+ {; q# SSerum testosterone level was found to be 2 times the# C; P% i! y* N! d1 `( q% b7 L8 a
baseline value in those females who were exposed to& l: Y; f. N* D1 \2 z
even 15 minutes of direct skin contact with their male
" }, \8 X& w( F1 d9 Z% m5 zpartners.6 However, when a shirt covered the applica-, |# U( @, y- a D* Q: M" ]% ~/ k
tion site, this testosterone transfer was prevented.; i' X& R X* S& @- L" m
Our patient’s testosterone level was 60 ng/mL,
1 Q) G% k$ C0 [" a# s Qwhich was clearly high. Some studies suggest that
+ c- ~. S2 D' P% \, @0 l. n( u7 qdermal conversion of testosterone to dihydrotestos-$ i( D) y1 y3 |
terone, which is a more potent metabolite, is more
$ L8 ~! ^) t: }% Kactive in young children exposed to testosterone
* Y! d4 z8 v% f& |+ m+ `exogenously7; however, we did not measure a dihy-6 h5 b& m6 t1 q' E% z# v0 V1 d
drotestosterone level in our patient. In addition to
8 C- ~4 u& O% \! c* vvirilization, exposure to exogenous testosterone in
" t& a" V5 u* G/ g5 V, G- cchildren results in an increase in growth velocity and/ m l( p a s* }2 D9 E( N; V# x
advanced bone age, as seen in our patient.
) X( d7 o/ O" n5 i hThe long-term effect of androgen exposure during
9 y5 [/ w; @3 Learly childhood on pubertal development and final# }4 f' T& b0 F# i: K4 e# {: G
adult height are not fully known and always remain' _# @6 L6 H- c' h
a concern. Children treated with short-term testos-6 B O& J0 e L7 ^! j0 N" a
terone injection or topical androgen may exhibit some, U) w0 Y/ M: L
acceleration of the skeletal maturation; however, after0 c7 ]: [ u( E* }; L3 Q# h
cessation of treatment, the rate of bone maturation; [ u( C; r' ?: y
decelerates and gradually returns to normal.8,9
0 e: N: D+ E3 s% }There are conflicting reports and controversy. {9 L8 C( k$ H% i( b" y0 c
over the effect of early androgen exposure on adult% d$ ~0 I0 T1 J4 B
penile length.10,11 Some reports suggest subnormal1 [4 Y& y( x8 R
adult penile length, apparently because of downreg-
* S( }0 y! x1 C5 F# o1 R mulation of androgen receptor number.10,12 However,+ O1 y# I9 C9 o! B2 @: e
Sutherland et al13 did not find a correlation between H2 x: R$ g0 G( \, R4 T3 h
childhood testosterone exposure and reduced adult
9 L& x% k3 o. Y$ Q9 ^" W, ~penile length in clinical studies.( U" ]' ^7 h- h
Nonetheless, we do not believe our patient is
* W) h; [5 R1 m( }- _going to experience any of the untoward effects from
8 C; Y$ K: p: |8 [0 U8 v, ^testosterone exposure as mentioned earlier because6 S: h1 N: R. W2 H" E; s
the exposure was not for a prolonged period of time.6 g( B2 q0 e# {" m, C
Although the bone age was advanced at the time of6 X4 S/ x% `% A! W' v$ c, N! R- i6 d
diagnosis, the child had a normal growth velocity at- P4 `5 m) Z/ x7 B9 r
the follow-up visit. It is hoped that his final adult
8 B& d7 y7 a- I' i7 \height will not be affected.
4 u7 e1 `2 @' a' b5 Y4 W. [5 MAlthough rarely reported, the widespread avail-
) f, Q: t1 A$ F+ b, bability of androgen products in our society may: u5 |* ^/ F: L9 P, B
indeed cause more virilization in male or female
: [; O) P$ P4 o; l# D+ ~% p4 i# A5 [children than one would realize. Exposure to andro-
* E! t4 L: I, m8 z5 dgen products must be considered and specific ques-
' R* O1 J+ n: x; y% q4 f" l; c2 {tioning about the use of a testosterone product or8 ^* ]7 R0 C2 y3 }
gel should be asked of the family members during
8 i4 o! j. I7 K3 i8 W( Kthe evaluation of any children who present with vir-7 l( x! n/ i# |
ilization or peripheral precocious puberty. The diag-/ g. W0 V( J! h
nosis can be established by just a few tests and by
; @! R, c3 f; R+ t) Happropriate history. The inability to obtain such a" e6 V& r* h0 e. e
history, or failure to ask the specific questions, may
0 `; {# C0 o% l; `: D1 }result in extensive, unnecessary, and expensive
3 M8 V0 `4 O# N7 N- a" Linvestigation. The primary care physician should be0 C1 d1 \9 h4 c
aware of this fact, because most of these children$ p( y; a# X2 B: o+ ^. `' ]
may initially present in their practice. The Physicians’1 r: U2 j. @+ W0 K# Z
Desk Reference and package insert should also put a3 H- D2 N, \6 ^: M0 b0 t& G
warning about the virilizing effect on a male or
9 w. R# j; g! ^female child who might come in contact with some-
: k/ K' x3 S0 X. f. a0 Zone using any of these products.
5 @, ^# O; F. ?References. v% ~4 f1 ~( F4 O5 }( e
1. Styne DM. The testes: disorder of sexual differentiation
) e! J( L4 q) ~$ l/ B. r/ Rand puberty in the male. In: Sperling MA, ed. Pediatric- }: c8 x' t0 k% h* C2 i
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
5 P. L) M$ o" D- g* R, `+ K q2002: 565-628.1 }4 ?$ [, [9 C- R* f$ n$ k- U
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
6 k4 J0 S1 U6 d5 s3 R: \puberty in children with tumours of the suprasellar pineal |
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