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Sexual Precocity in a 16-Month-Old/ z! T$ T3 j/ d
Boy Induced by Indirect Topical( H8 G% t% C1 _! J9 ?5 _5 l
Exposure to Testosterone: V2 \9 z. m2 t8 P6 Q9 h
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
8 z% _+ e. N( v, [ q4 jand Kenneth R. Rettig, MD1& R9 |9 Z# J' ]. v% X) U1 U& T
Clinical Pediatrics
$ Y2 T( Z3 X' y+ k' I+ T* GVolume 46 Number 6! t# p T& D1 e/ |( ?8 G
July 2007 540-543
9 q* ]7 u& P" ]5 S0 A© 2007 Sage Publications; b: w) _8 A7 \1 Z3 r6 b
10.1177/0009922806296651
9 R+ F; ]" H* J; O+ Whttp://clp.sagepub.com" H1 L/ }( |% D8 ~1 p( y3 e
hosted at
/ T' F, _# g1 b5 Q r$ M$ F. Y2 h0 bhttp://online.sagepub.com( G3 K; u x' X- u; W
Precocious puberty in boys, central or peripheral,
1 _* J5 t) d! K9 f& I. Xis a significant concern for physicians. Central
- g- }6 n$ a! T8 cprecocious puberty (CPP), which is mediated
( d/ U k0 n2 z$ J) Zthrough the hypothalamic pituitary gonadal axis, has
7 c$ _( h+ v3 S$ C# ?5 [ @a higher incidence of organic central nervous system
, e; \4 ^% W& n% Xlesions in boys.1,2 Virilization in boys, as manifested. X% g" R8 X! B' p
by enlargement of the penis, development of pubic
' L) y3 q3 {, i# Y' xhair, and facial acne without enlargement of testi-1 u: u; v# q% u L' Q. K
cles, suggests peripheral or pseudopuberty.1-3 We0 v6 v0 _5 m' `& x
report a 16-month-old boy who presented with the
7 ~/ y3 E5 P2 | `- wenlargement of the phallus and pubic hair develop-. U) v' o9 F. L; V B
ment without testicular enlargement, which was due! ?3 N4 f/ u5 P; l: z6 r. \3 Y% z! |
to the unintentional exposure to androgen gel used by
4 k+ ?- Z9 s2 x0 [5 Ythe father. The family initially concealed this infor-1 `% c# t; |8 l+ r5 `( d
mation, resulting in an extensive work-up for this
9 |# b$ Z; c! ?/ q2 L$ C6 \child. Given the widespread and easy availability of) _7 L7 w. ~6 J! o& o
testosterone gel and cream, we believe this is proba-0 v$ u/ o- ?( _9 l, B
bly more common than the rare case report in the
! [" `, |( _% }) Vliterature.4
# H& W& Q" M# V" JPatient Report
6 T5 v' N9 ?- I! M, d6 V+ ~A 16-month-old white child was referred to the/ Y6 n9 _+ ^( u0 H
endocrine clinic by his pediatrician with the concern5 U+ W/ U6 b- T+ m
of early sexual development. His mother noticed" n# A: Y; R# R, A# }* Q7 Y( K
light colored pubic hair development when he was
4 J3 e) n5 g5 U, s# BFrom the 1Division of Pediatric Endocrinology, 2University of, p9 ^% k0 n% \
South Alabama Medical Center, Mobile, Alabama.8 X S: a9 {( ^7 f" @4 F
Address correspondence to: Samar K. Bhowmick, MD, FACE,
. K. W9 }* [8 _( ]# P7 `Professor of Pediatrics, University of South Alabama, College of0 D3 H* a2 _3 V2 w: H" v( ]( w6 H
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;: c: d9 R$ s; d$ t* q0 p5 p% B0 t7 A+ d
e-mail: [email protected].
& ?- b' d7 h' _+ D( Wabout 6 to 7 months old, which progressively became! ]1 q) Q" d8 U2 F7 o, L
darker. She was also concerned about the enlarge-
) O x0 n6 U& h6 k( x$ _ment of his penis and frequent erections. The child- R* @# e2 i# u% a% _
was the product of a full-term normal delivery, with
. ?( p9 s% t% M h- R) Z' Oa birth weight of 7 lb 14 oz, and birth length of6 r, U6 x1 S* [! j/ O) L5 L( S$ L
20 inches. He was breast-fed throughout the first year) A S: m. s- p$ M7 @8 S/ [7 z
of life and was still receiving breast milk along with
/ t/ L% k3 _, ~9 v4 x# T* h; N' {solid food. He had no hospitalizations or surgery,
5 i4 z! L) Y9 Q9 _2 Iand his psychosocial and psychomotor development
/ |8 a6 a- G: I8 s5 {1 v9 ?was age appropriate.
, I; j3 Z' I: g) o% F$ ~The family history was remarkable for the father,
7 M7 ?* K! {# G& Kwho was diagnosed with hypothyroidism at age 16,& `" L- z6 t5 p9 P) d1 z
which was treated with thyroxine. The father’s3 l8 X( y! L6 h
height was 6 feet, and he went through a somewhat9 \& |% M7 a5 X6 N% m0 k$ y
early puberty and had stopped growing by age 14.6 [1 I h. f& E; a3 T9 \- u8 ?
The father denied taking any other medication. The" x- m' t9 \' z
child’s mother was in good health. Her menarche
4 \7 b2 i) R/ z2 rwas at 11 years of age, and her height was at 5 feet+ F, a, \( ~, D1 P
5 inches. There was no other family history of pre-7 E% j/ _2 n: J L0 N
cocious sexual development in the first-degree rela-8 ?& i& Y0 k6 P$ G
tives. There were no siblings.
* W8 B# c7 y2 w/ Y& K4 \7 g3 aPhysical Examination7 n$ G; w n/ M, D, `* `7 \6 \9 |- J3 ]
The physical examination revealed a very active,
( R) S- ^# F, _; [6 n# y# ~playful, and healthy boy. The vital signs documented
% f- A) P0 V E* Ba blood pressure of 85/50 mm Hg, his length was( w2 r* \& s* r3 X
90 cm (>97th percentile), and his weight was 14.4 kg
4 x3 z# n3 I) I# s+ d# ^(also >97th percentile). The observed yearly growth3 f' ^) h2 M: y! S
velocity was 30 cm (12 inches). The examination of
4 x; [0 S: {3 ^1 P9 Mthe neck revealed no thyroid enlargement.
( k5 F/ ]& |+ S; e$ G# ZThe genitourinary examination was remarkable for
$ I, ?3 g: j4 o* j! A1 d+ Uenlargement of the penis, with a stretched length of
+ K( S: o! V& v8 cm and a width of 2 cm. The glans penis was very well
9 o/ w1 n/ C' ideveloped. The pubic hair was Tanner II, mostly around
4 I3 p5 L1 Y7 ?! W. X9 @: Q540
6 q* L# S& Q* F% {3 }- cat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
* ~1 a3 Y T4 B. E i9 jthe base of the phallus and was dark and curled. The
; @* H3 L$ k! I5 s8 W2 Ctesticular volume was prepubertal at 2 mL each.
& x5 x) U4 O' t6 [# t1 OThe skin was moist and smooth and somewhat
. m" H0 e- t+ J8 }2 woily. No axillary hair was noted. There were no2 @4 Y4 N3 O$ n( H+ I3 h( t
abnormal skin pigmentations or café-au-lait spots.
# K/ N6 b7 X# j" @Neurologic evaluation showed deep tendon reflex 2+. Y% p8 F, u9 o- M% [
bilateral and symmetrical. There was no suggestion
8 n1 C. M4 e; G* oof papilledema.: n3 B- G% @% F: o5 p
Laboratory Evaluation
) ]0 V# K6 n5 \The bone age was consistent with 28 months by" Z; Y/ c% Q& ~- i5 w8 V& g( q6 F
using the standard of Greulich and Pyle at a chrono-1 T: B5 G- |9 g u; v* e2 m
logic age of 16 months (advanced).5 Chromosomal
2 D* g2 B* Z' Z( @( Mkaryotype was 46XY. The thyroid function test
3 s' R8 W, @2 A: i/ @showed a free T4 of 1.69 ng/dL, and thyroid stimu-8 S0 v; U8 W7 c( P8 W A! V
lating hormone level was 1.3 µIU/mL (both normal). P% L" ` q- L# m+ A! t
The concentrations of serum electrolytes, blood: @' r. k. B4 l$ T' E/ P+ ]
urea nitrogen, creatinine, and calcium all were2 U! O+ |) G1 x' K
within normal range for his age. The concentration
* ~6 l# K3 z# G, Gof serum 17-hydroxyprogesterone was 16 ng/dL) u7 T; Y7 c* m/ C& h+ l9 k
(normal, 3 to 90 ng/dL), androstenedione was 20
! k& q n1 y# P- p: s$ Y6 [( Mng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-, R/ I6 n* P$ e) v
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
/ q3 H, s- {2 ^# [desoxycorticosterone was 4.3 ng/dL (normal, 7 to$ K" w! X0 s! P; W, m4 K
49ng/dL), 11-desoxycortisol (specific compound S), ~2 N3 c$ c% v+ `5 f" [& ?
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
& L- \1 f7 u1 I; R t3 stisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total# J* m% `( ^* R- B- e8 Y3 g# ^
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),3 J" B) p2 o6 F, Z. D
and β-human chorionic gonadotropin was less than, y% H7 R7 F8 U6 U5 h
5 mIU/mL (normal <5 mIU/mL). Serum follicular
; w- N; o9 f) } Z& M; Tstimulating hormone and leuteinizing hormone/ B7 }; H7 H. d( Z1 B
concentrations were less than 0.05 mIU/mL' _) b- C9 ]' \* `, t5 ~* n: o* i
(prepubertal).
0 [9 y2 D3 G) U7 t0 `4 }! rThe parents were notified about the laboratory" t+ B$ n3 ]& G( T' t( J
results and were informed that all of the tests were
- c) k5 V8 |2 o& v" ^normal except the testosterone level was high. The: i/ |- h7 z& k* x' `
follow-up visit was arranged within a few weeks to ~/ D) I2 c! e2 e' v2 I" w/ ?' d
obtain testicular and abdominal sonograms; how-' t# k7 _9 b+ r9 H* ~) H" U' e
ever, the family did not return for 4 months.
6 I- |% W* Y9 _1 X1 tPhysical examination at this time revealed that the: M( x5 a+ _2 r) {" \
child had grown 2.5 cm in 4 months and had gained8 m% T) l! `' M- e: G3 u8 c
2 kg of weight. Physical examination remained5 j( u5 z: t# k$ l j
unchanged. Surprisingly, the pubic hair almost com-
7 _+ b" Z/ ]4 a8 [5 F6 a# i' ]2 {9 Cpletely disappeared except for a few vellous hairs at
9 L1 z: u2 V/ x. G% R5 J, Ethe base of the phallus. Testicular volume was still 2' f2 v) j& C g, v! Q1 u
mL, and the size of the penis remained unchanged.; `( `: j2 e% o% G) l3 q
The mother also said that the boy was no longer hav-' P* B+ C% ~% E# ?* T( c
ing frequent erections.
' ^$ d% H$ O- J. g$ ^Both parents were again questioned about use of O6 f& P$ c! ]( h# k
any ointment/creams that they may have applied to6 c* j: M$ T8 T$ G, `
the child’s skin. This time the father admitted the9 L# Q- m' r" b( H0 w5 I
Topical Testosterone Exposure / Bhowmick et al 541! S- h1 c3 z) `' U q- u
use of testosterone gel twice daily that he was apply-
! H# i! r9 F3 u0 ]7 W( ling over his own shoulders, chest, and back area for2 c o% Y, m3 X
a year. The father also revealed he was embarrassed
% e7 [8 S4 H. f- w/ Vto disclose that he was using a testosterone gel pre-
. y1 Y1 B+ W% {5 y" C: a* Q7 t! L/ nscribed by his family physician for decreased libido
V" R; ]! Q6 b( ysecondary to depression.
2 G7 R: \) p. G; f8 EThe child slept in the same bed with parents.3 a% p3 L+ @9 p! \: Q" _5 D7 a
The father would hug the baby and hold him on his
/ Z" v+ \$ ?. Vchest for a considerable period of time, causing sig-
. B8 J$ y. A$ m( Onificant bare skin contact between baby and father.
4 J* [0 t$ G( C) _' CThe father also admitted that after the phone call,9 u2 f- A4 f3 H; B# J
when he learned the testosterone level in the baby
0 J( o: A' V3 }" Mwas high, he then read the product information0 @& e2 j2 p0 e8 F3 K
packet and concluded that it was most likely the rea-2 q! Z0 J2 p* ?" q
son for the child’s virilization. At that time, they
I& w3 d* t* I q# ^decided to put the baby in a separate bed, and the
, M) @- W' J$ g8 }+ gfather was not hugging him with bare skin and had
9 i0 W, T: j% M5 c- S. @: C) Xbeen using protective clothing. A repeat testosterone
: G% @- O/ s( C Wtest was ordered, but the family did not go to the# H: L8 A2 h3 ?9 g' v$ L ]
laboratory to obtain the test.1 c4 m' M% U6 L* r
Discussion) e) m- Y2 N+ ~ z( i9 r
Precocious puberty in boys is defined as secondary
" o6 O' B3 K* s! Usexual development before 9 years of age.1,4
0 w3 X! z8 u x1 t, i/ D: Z8 APrecocious puberty is termed as central (true) when& H& Q c+ I9 K. J9 ]2 g
it is caused by the premature activation of hypo-) W( `) F2 |+ ~% H& n6 D+ J
thalamic pituitary gonadal axis. CPP is more com-
& S9 C, r/ B( z7 U9 T0 T5 f8 D! ?& Tmon in girls than in boys.1,3 Most boys with CPP
; ]$ |; j, ?; U+ I: ]7 V/ `may have a central nervous system lesion that is9 v6 o* j* U- p. ]$ W
responsible for the early activation of the hypothal-3 H$ L% l6 B, Z8 Q4 K
amic pituitary gonadal axis.1-3 Thus, greater empha-
/ Q# K# P+ K5 @$ Ysis has been given to neuroradiologic imaging in
7 e+ x- Z( ]2 g) e8 tboys with precocious puberty. In addition to viril-0 s( {+ a& P! S
ization, the clinical hallmark of CPP is the symmet-5 b/ f: }3 B5 Y5 d( M* h5 u) z
rical testicular growth secondary to stimulation by) F9 |: N! v; O+ @
gonadotropins.1,3( o# ]2 q x6 Y6 K7 @5 k5 [
Gonadotropin-independent peripheral preco-
, n) Z4 r5 W# [5 ~3 I, Zcious puberty in boys also results from inappropriate
+ S3 k; L9 I1 U+ ~androgenic stimulation from either endogenous or* Z$ E2 Y ]( b- a9 g
exogenous sources, nonpituitary gonadotropin stim-$ f$ \4 O8 R0 H4 b# Q# g
ulation, and rare activating mutations.3 Virilizing
5 q7 R/ O, ~9 dcongenital adrenal hyperplasia producing excessive
$ W! O' V& X8 Ladrenal androgens is a common cause of precocious. S% G% z# h( l
puberty in boys.3,4
8 z( G$ W" k! F x# LThe most common form of congenital adrenal) i5 M) g- z. Z" I! t
hyperplasia is the 21-hydroxylase enzyme deficiency.4 \4 p" \! z. c R. i4 i+ q
The 11-β hydroxylase deficiency may also result in
2 S u& t3 y' p( W$ K! T! qexcessive adrenal androgen production, and rarely,
) |* U2 z! C+ ]; E$ Q7 gan adrenal tumor may also cause adrenal androgen
# X: Z9 ?' h: L' Y }* t f( u" s% ?, Rexcess.1,3. f; p+ U: x+ E1 k k/ i' l
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
- E% y: f* R' i* X. d& Y, L542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
2 ~; w# H* s' A. d9 D( SA unique entity of male-limited gonadotropin-' H4 [: X: L9 R% X
independent precocious puberty, which is also known
. l& v% O: d& T* x+ ^as testotoxicosis, may cause precocious puberty at a
; _$ Y3 E P3 t F" z* q& ?very young age. The physical findings in these boys
# d @' |: h" K5 B; Ywith this disorder are full pubertal development,
& ]! f M6 m1 n# b! ~: t; T w8 [6 t' dincluding bilateral testicular growth, similar to boys
- }; r% p9 h" L7 ]! ^with CPP. The gonadotropin levels in this disorder
" N! a3 {" J- m( Y. tare suppressed to prepubertal levels and do not show% f" U, G) \4 m/ L) \5 D, _1 M) Q
pubertal response of gonadotropin after gonadotropin-
* `4 l& d/ G0 Q$ f6 w Rreleasing hormone stimulation. This is a sex-linked% F/ [8 L2 \. V# {
autosomal dominant disorder that affects only
9 X( y6 V- o! ]( X% p- m7 _males; therefore, other male members of the family* { w5 a: Z! R8 j- R7 p
may have similar precocious puberty.3( v- P* u" y" L) u5 q. ?( `
In our patient, physical examination was incon-) g% `& n* S- ~ b
sistent with true precocious puberty since his testi-
) y; _) ^, R" \cles were prepubertal in size. However, testotoxicosis
4 `+ \ Y+ x- i/ c- O0 t4 }was in the differential diagnosis because his father
1 w ] n# a2 t. K: xstarted puberty somewhat early, and occasionally,8 I" ^# |1 _& ?5 t
testicular enlargement is not that evident in the3 q# y6 X# q5 Y( e; [9 d. g( p8 ]' U
beginning of this process.1 In the absence of a neg-" q8 V) z+ h3 V" A
ative initial history of androgen exposure, our4 v* Q* L" Y' i+ S4 D8 _. I
biggest concern was virilizing adrenal hyperplasia,. B3 b* w" G3 p( r! @- w; |
either 21-hydroxylase deficiency or 11-β hydroxylase6 g/ @" G2 a6 A1 _ C' u. X
deficiency. Those diagnoses were excluded by find-4 i5 c; A2 S; d u) Q3 h" w2 v
ing the normal level of adrenal steroids./ K0 L+ C* {5 V4 H
The diagnosis of exogenous androgens was strongly$ q3 d" @0 |, ] k5 c8 O. `7 |" l
suspected in a follow-up visit after 4 months because
; Y( c& Z6 M9 o. v2 ^3 d: rthe physical examination revealed the complete disap-" j% I8 U& ^: w0 A0 P& ~
pearance of pubic hair, normal growth velocity, and
8 ?3 U7 ^. m' g/ G9 ~ |decreased erections. The father admitted using a testos-
) {, v2 I, w1 Wterone gel, which he concealed at first visit. He was
3 H# e8 f E; wusing it rather frequently, twice a day. The Physicians’. P) i, |6 y7 i
Desk Reference, or package insert of this product, gel or
9 a9 B% c$ Y3 L+ c# D& }cream, cautions about dermal testosterone transfer to. D8 ~# D+ z Y% k% }
unprotected females through direct skin exposure.% w. F4 V6 b! H. D7 k
Serum testosterone level was found to be 2 times the6 |- v% G9 U6 D8 b& v/ q( u
baseline value in those females who were exposed to" x0 b7 m$ L8 S, P
even 15 minutes of direct skin contact with their male
4 L& f& A! W. s! P3 hpartners.6 However, when a shirt covered the applica-* j6 o0 e: _, s0 Q1 Z
tion site, this testosterone transfer was prevented.+ B2 q# S. u+ i7 y8 F. |5 A
Our patient’s testosterone level was 60 ng/mL,6 K. }6 s0 A2 @8 R
which was clearly high. Some studies suggest that
4 f, c6 U0 ?6 i* G$ J8 fdermal conversion of testosterone to dihydrotestos-
. b! a4 |8 c9 `9 p& A! Z4 bterone, which is a more potent metabolite, is more" M7 h4 C3 Z% a1 x! y/ \
active in young children exposed to testosterone, W/ o4 \. Q! u4 ?7 o! L/ E+ N! X, I
exogenously7; however, we did not measure a dihy-
: s1 Y; P% o& ^ J1 v% t+ t. Cdrotestosterone level in our patient. In addition to
/ k; m! I7 ^) U% X& {virilization, exposure to exogenous testosterone in
% p/ ? x/ \$ C1 M! k" Y7 ichildren results in an increase in growth velocity and# c; Y0 J, f$ w# R( C% u. L# u
advanced bone age, as seen in our patient.
7 x( ~! G* r4 eThe long-term effect of androgen exposure during
: g/ g8 u' k) y, Gearly childhood on pubertal development and final
, L1 |3 H: ]+ q* Kadult height are not fully known and always remain
& O7 [5 w d8 b0 Ia concern. Children treated with short-term testos-
- Z$ L% |+ Z$ I2 Kterone injection or topical androgen may exhibit some, w$ `7 V% A* R0 o
acceleration of the skeletal maturation; however, after
1 u0 H$ X4 o, E7 Mcessation of treatment, the rate of bone maturation
% C2 n6 q: N% `* w3 v! G0 Zdecelerates and gradually returns to normal.8,97 }* i, @8 D! X( Q9 {' E2 S
There are conflicting reports and controversy
9 G, F1 T H) G6 t6 X2 a" F, ^, Zover the effect of early androgen exposure on adult
% @ z6 W* n$ D/ ~ g2 X% Wpenile length.10,11 Some reports suggest subnormal5 \$ y- O. o6 D( h5 {! A
adult penile length, apparently because of downreg-" l0 J' \, g! s! I$ ~) @$ ~9 ~
ulation of androgen receptor number.10,12 However,
! a) U d) { r' u% O* zSutherland et al13 did not find a correlation between
8 @# p$ S& A( r$ e/ t5 F- tchildhood testosterone exposure and reduced adult* a- R6 {+ x. h0 m; z
penile length in clinical studies.
7 L7 G, k- X# w! TNonetheless, we do not believe our patient is
- P) b' g! U5 M- s' ggoing to experience any of the untoward effects from) N+ c+ Y, p& m! y5 o" A0 P
testosterone exposure as mentioned earlier because% ~3 g: U2 v7 S4 O
the exposure was not for a prolonged period of time.7 L4 l. e! p; ^8 s9 {& K2 O
Although the bone age was advanced at the time of |- f+ T7 i7 z# }
diagnosis, the child had a normal growth velocity at
# R; z X( C8 L- g7 K5 c: vthe follow-up visit. It is hoped that his final adult0 ]$ A, |% M% w A9 f$ }2 I* ?
height will not be affected.. a) l% K5 d. [3 \8 p. U3 Q" L
Although rarely reported, the widespread avail-) u0 j. ]% w7 F
ability of androgen products in our society may; d7 J# j8 u% @- N/ V# D2 u% K' U
indeed cause more virilization in male or female
" R+ y. f3 d- n; `2 w2 ~+ w) Rchildren than one would realize. Exposure to andro-! K( \: V$ J6 F9 G; {( _& l
gen products must be considered and specific ques-2 G& U# `$ ]9 O, J+ F: x/ g
tioning about the use of a testosterone product or( y. m9 p' r* Q; E
gel should be asked of the family members during
! L# x) v) E0 ~) bthe evaluation of any children who present with vir-) f7 U5 b2 S- n3 p' q6 R
ilization or peripheral precocious puberty. The diag-; z1 f9 Y" u) F$ ?- J
nosis can be established by just a few tests and by* V0 q+ v- p5 B% c
appropriate history. The inability to obtain such a! u3 e# A$ A+ `+ F, P
history, or failure to ask the specific questions, may4 u& b- z. b: B1 @, e
result in extensive, unnecessary, and expensive& g' w7 @; H! S+ O2 P- l0 H" `
investigation. The primary care physician should be3 n' ^% z# f/ P' H, ~. ^5 @8 p) q
aware of this fact, because most of these children! S$ Y P" E1 D+ O2 @; a1 K. g
may initially present in their practice. The Physicians’
& u: F3 G8 x$ o+ X& H# ?0 V# S# }Desk Reference and package insert should also put a9 G: K6 w7 F8 q& q# p4 c( S
warning about the virilizing effect on a male or
! E% Z+ K( W! ufemale child who might come in contact with some-+ Y. W! E9 U+ Z( q8 h6 g
one using any of these products.
3 ], v8 ?( c, Q9 s, `9 _References
6 o2 G! J. K; t! F9 v1. Styne DM. The testes: disorder of sexual differentiation, g ~7 A, B/ G, `! f
and puberty in the male. In: Sperling MA, ed. Pediatric
" e! ^" V& J7 K7 B/ R' pEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;% a+ i$ E& s6 B( \: a
2002: 565-628.! I4 j# {* Y5 D/ U% X) s* A. [
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
& n$ V6 T# g+ N5 npuberty in children with tumours of the suprasellar pineal |
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