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Sexual Precocity in a 16-Month-Old9 I( Y& c0 J5 [/ Z- d
Boy Induced by Indirect Topical+ [2 x( K5 B7 T( ~) h( T
Exposure to Testosterone, |1 ?9 d5 m' @: L4 H0 I5 ~
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2! m3 l, X8 b" S; s' _0 O" o) n/ a* w
and Kenneth R. Rettig, MD1
+ r. U# }: r; V, B2 g2 z BClinical Pediatrics# k3 U+ f8 n/ ^* I3 |% ~* k
Volume 46 Number 65 @" E% t) h& R* K) P2 r
July 2007 540-543
" Y. K. p8 ?! s# `" j© 2007 Sage Publications/ i7 u/ g4 s, m4 Z/ @' Y
10.1177/00099228062966513 h* a0 u9 T( E% q
http://clp.sagepub.com
$ ]) A; U4 C4 d# l+ y" e/ n Chosted at
0 D% I! }5 l0 a, ? D" k/ k% Ohttp://online.sagepub.com
" Q( @) w: q# s9 u) w: h5 GPrecocious puberty in boys, central or peripheral,2 d7 i$ Y: ~0 a- t" m/ A# {8 y
is a significant concern for physicians. Central8 G! t& h+ T8 w" Y: |) w F
precocious puberty (CPP), which is mediated7 w: _' p' \! o
through the hypothalamic pituitary gonadal axis, has y2 z2 R1 S' ^5 b+ Q& M5 P! h
a higher incidence of organic central nervous system5 R! |' ]2 _" P% U1 ?
lesions in boys.1,2 Virilization in boys, as manifested* d. N4 K# o) Q+ j- d3 Z; ~
by enlargement of the penis, development of pubic7 A0 z9 e; p! f' Q$ {$ \9 w$ b( Z) v. i
hair, and facial acne without enlargement of testi-* I. J! n: w$ b- b
cles, suggests peripheral or pseudopuberty.1-3 We
/ d/ j, ]: W3 I- I+ y |report a 16-month-old boy who presented with the1 U2 ]/ m$ l5 A/ \3 ?# _
enlargement of the phallus and pubic hair develop-4 A0 _% S6 G6 |; R+ \& v
ment without testicular enlargement, which was due
( {( q* }; z+ i3 D0 Sto the unintentional exposure to androgen gel used by: @6 O B6 }: v5 i% W: J8 D% O
the father. The family initially concealed this infor-0 P C( ~9 G! D5 q" D3 w* y2 a& y8 J
mation, resulting in an extensive work-up for this+ B0 ?7 l8 s3 C' p
child. Given the widespread and easy availability of( s$ [3 f" t' e3 t2 m% K e N
testosterone gel and cream, we believe this is proba-2 ]' U/ j4 S# m1 V( l3 ^
bly more common than the rare case report in the
' X+ `7 D: w! H# J, oliterature.4/ E$ Z" \2 n5 g# W9 y, S! g& R
Patient Report4 E- }) m7 ?+ }6 C: y# e( R3 H
A 16-month-old white child was referred to the8 d: B( N" D6 d; S, R( z: L
endocrine clinic by his pediatrician with the concern* C) j5 y; r e- R
of early sexual development. His mother noticed7 A- R% O) A- d
light colored pubic hair development when he was+ G2 j2 D% b3 i3 v" d
From the 1Division of Pediatric Endocrinology, 2University of4 }* u* P& F } [0 A l+ y0 D
South Alabama Medical Center, Mobile, Alabama.- S* i# U2 ?4 @% b8 c5 G4 J( q- u
Address correspondence to: Samar K. Bhowmick, MD, FACE,- w% c! q6 y U u0 p. b V
Professor of Pediatrics, University of South Alabama, College of) U0 T1 R/ Q: H) F4 @
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;# G; K$ Z- B- o) Y8 M& P
e-mail: [email protected].
7 w4 R' A1 F9 P+ w. a! yabout 6 to 7 months old, which progressively became4 D2 _& i' ?3 |6 `# A$ ~2 G
darker. She was also concerned about the enlarge-
) h' M6 n# ?& L& p z& j$ O# rment of his penis and frequent erections. The child
5 K: s; m: J, W* P3 v2 s, w n: swas the product of a full-term normal delivery, with: y; y1 E& i% }% }0 S2 o3 V
a birth weight of 7 lb 14 oz, and birth length of
4 n1 l3 q6 m0 U N: k$ }5 `20 inches. He was breast-fed throughout the first year
) }1 V. ~; M4 @' Bof life and was still receiving breast milk along with
' S& {$ t. Y8 q$ w, b psolid food. He had no hospitalizations or surgery,
" S3 r* R P8 b! zand his psychosocial and psychomotor development
$ V2 D2 _0 d0 j* Rwas age appropriate.! ^4 S+ t$ T+ X" r4 w
The family history was remarkable for the father,- C7 S1 w" C$ V4 m
who was diagnosed with hypothyroidism at age 16,
( t2 ~& j6 [# A+ a$ F; `' l5 }# C* U' Cwhich was treated with thyroxine. The father’s
0 j, b. B) R" t }height was 6 feet, and he went through a somewhat4 ?/ ]% {. T& {
early puberty and had stopped growing by age 14.3 m2 t7 Y, K( M" g' g
The father denied taking any other medication. The
' Y/ h( w- Q6 q1 S+ E. wchild’s mother was in good health. Her menarche# `: x2 P: v! U
was at 11 years of age, and her height was at 5 feet
9 p( ?# e, m3 x$ _) {5 inches. There was no other family history of pre-
7 H7 }8 \' n" }( ^9 B" xcocious sexual development in the first-degree rela-9 [6 Q' Z- D' s. l
tives. There were no siblings.
4 C" G9 v0 s) X xPhysical Examination
- ~' J; b9 U- f# J* b# w; L( eThe physical examination revealed a very active,
% w- S6 H( H+ s8 h2 k- xplayful, and healthy boy. The vital signs documented3 H% W& G2 P# M" h
a blood pressure of 85/50 mm Hg, his length was
5 x5 R; L: ?0 B2 M: P1 A& b- |! |90 cm (>97th percentile), and his weight was 14.4 kg
9 t7 B4 n$ ]; h9 S(also >97th percentile). The observed yearly growth
1 R+ W+ w4 |8 g) Mvelocity was 30 cm (12 inches). The examination of6 Z0 E! X' t$ t" Q) c+ l4 [
the neck revealed no thyroid enlargement.; D- z) o* T2 _. Q4 s
The genitourinary examination was remarkable for/ F" ?& f4 B' F5 F
enlargement of the penis, with a stretched length of" v% F9 Z. S" X: D" D- D
8 cm and a width of 2 cm. The glans penis was very well
6 u0 {9 e2 d8 z% a& mdeveloped. The pubic hair was Tanner II, mostly around% F1 V! E p* _, W" f( p3 t
540
: m' X$ ?* G2 [at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
8 D/ G4 [ Y& J1 y" m3 B! Rthe base of the phallus and was dark and curled. The0 p8 S7 Q3 I' I. Z' D
testicular volume was prepubertal at 2 mL each.+ s3 R9 w# z, ~% t
The skin was moist and smooth and somewhat/ a6 ?. P) R: {% M; U+ \( a4 y
oily. No axillary hair was noted. There were no
& V% d, T) W" D- O$ habnormal skin pigmentations or café-au-lait spots.
' g0 k* k% ?4 @9 c0 iNeurologic evaluation showed deep tendon reflex 2+% [% Y1 q0 u! {+ y2 {$ J
bilateral and symmetrical. There was no suggestion, Z0 i5 p( l4 t
of papilledema.
. z4 A9 x* I: F/ z# H5 Q6 yLaboratory Evaluation0 S6 l2 T6 E* Y: q" h+ c9 n$ h
The bone age was consistent with 28 months by
, c6 F2 i- E6 {8 {# Musing the standard of Greulich and Pyle at a chrono-9 W) D1 @7 W, Q5 ~7 d& \
logic age of 16 months (advanced).5 Chromosomal
. O- K4 L* _3 M, z n [karyotype was 46XY. The thyroid function test
) p6 `3 U' N5 vshowed a free T4 of 1.69 ng/dL, and thyroid stimu-: |: I$ `: D( b/ I S2 [
lating hormone level was 1.3 µIU/mL (both normal).
P- E6 U- ]# K8 U$ A, g; {3 [' nThe concentrations of serum electrolytes, blood
) _0 c. u# T. f5 P; Z3 j" Murea nitrogen, creatinine, and calcium all were
6 J" Z$ i& @0 f2 p# ~2 gwithin normal range for his age. The concentration
0 I. j! e% G Q% Gof serum 17-hydroxyprogesterone was 16 ng/dL
1 r9 d% q& s1 T. k7 W" R& a% @! r(normal, 3 to 90 ng/dL), androstenedione was 20
" n/ j" t4 ?( ong/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
$ U6 e: Y" S$ `# s2 v" P3 U8 Oterone was 38 ng/dL (normal, 50 to 760 ng/dL),
- a4 c$ f t2 |& x' J# y w C' Edesoxycorticosterone was 4.3 ng/dL (normal, 7 to' u% S) q, T! A* V1 p" o
49ng/dL), 11-desoxycortisol (specific compound S)3 H$ p: F$ G$ i, I( k
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
- C6 Z- o/ P; u; \- E/ e" Utisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total5 v2 n0 ?3 f* J& Y+ r+ z* w) m" ?
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),1 a0 h+ C( o9 Z* d
and β-human chorionic gonadotropin was less than* \* F A9 u+ K
5 mIU/mL (normal <5 mIU/mL). Serum follicular
5 G3 {' B( z3 V3 M# W6 |stimulating hormone and leuteinizing hormone
9 s4 \, x/ P, H% b% o" Mconcentrations were less than 0.05 mIU/mL* z" [! T( v% x: y+ j" F% X
(prepubertal).8 n5 r0 l# M7 G& U5 h: Y
The parents were notified about the laboratory
- V E* `5 ~ [* n7 i8 `+ presults and were informed that all of the tests were! E1 Y% _& N+ B3 f1 [9 A& B
normal except the testosterone level was high. The
, x) _: w$ E" `1 Gfollow-up visit was arranged within a few weeks to" a* P% g' V# q6 }
obtain testicular and abdominal sonograms; how-
$ y2 t9 j4 G+ D Z( B0 }6 v& L; |. `ever, the family did not return for 4 months.
) B- \0 n" g3 Y/ S, c9 i3 w& EPhysical examination at this time revealed that the
; ?, ~0 E% Q0 ]) ^5 gchild had grown 2.5 cm in 4 months and had gained
2 o! K4 u0 G5 b* ~8 z& V# N7 O) E2 kg of weight. Physical examination remained% q+ S# A* _$ g$ l X% Z; D
unchanged. Surprisingly, the pubic hair almost com-
: K) z: s c* I0 O8 m8 v; l9 Upletely disappeared except for a few vellous hairs at
' U* l+ |% ]% l+ _the base of the phallus. Testicular volume was still 2# G6 P' q1 Y' m# y6 z, G
mL, and the size of the penis remained unchanged.
! B- `+ x1 F, h( h! h I- yThe mother also said that the boy was no longer hav-
5 g3 C q$ G, E1 }4 W o/ Xing frequent erections.% o* K9 a0 J' G
Both parents were again questioned about use of3 U' K" O! _- s" e Q- ^
any ointment/creams that they may have applied to+ T& B# `: A- F8 V
the child’s skin. This time the father admitted the7 n+ `4 t1 Z& v5 b0 n
Topical Testosterone Exposure / Bhowmick et al 5411 ^3 K& v r2 I _' |/ Z i
use of testosterone gel twice daily that he was apply-$ O0 Y: g& o( h
ing over his own shoulders, chest, and back area for
3 M7 U2 c: _$ z( Qa year. The father also revealed he was embarrassed& w" A( }: F( }: _
to disclose that he was using a testosterone gel pre-
4 ~! \% G# r, Z# Uscribed by his family physician for decreased libido
1 S3 k% m: D. g; o( qsecondary to depression." z6 J/ Y% g# U8 I
The child slept in the same bed with parents.* F4 X1 a, s8 T6 K# [4 K: a! o
The father would hug the baby and hold him on his5 n; l4 i0 `5 f; f
chest for a considerable period of time, causing sig-
5 E& Z$ J7 T) pnificant bare skin contact between baby and father.% K1 ?! q; L, i4 S; _) g, r
The father also admitted that after the phone call,
- U+ m5 @1 v; p; N6 w% Kwhen he learned the testosterone level in the baby
) G# @" ^2 h/ ywas high, he then read the product information
+ r; k& y3 k( B1 opacket and concluded that it was most likely the rea-
( U4 s2 B6 e6 [- S# v+ w9 F. |son for the child’s virilization. At that time, they
! B0 y1 O7 F8 i/ ^decided to put the baby in a separate bed, and the! C4 Z' U/ E, r9 ]: {
father was not hugging him with bare skin and had
* M- c0 ?. I) ubeen using protective clothing. A repeat testosterone: B, Y" M6 L# L+ A" d. Q6 T8 D0 @
test was ordered, but the family did not go to the
7 G- }2 C2 A. s8 Q9 K" ylaboratory to obtain the test.6 P: B! C" ^ p6 _
Discussion }; U+ x4 Z; c
Precocious puberty in boys is defined as secondary$ q* c$ @8 u7 U
sexual development before 9 years of age.1,4* T, |5 A3 @# q% C; O
Precocious puberty is termed as central (true) when" M; [+ ^- {" D/ n* W
it is caused by the premature activation of hypo-
' O; w1 L H/ S! x3 e9 D& j/ [thalamic pituitary gonadal axis. CPP is more com-
; `# r9 f7 K- Z, s2 c, P% G+ u4 o$ Emon in girls than in boys.1,3 Most boys with CPP% }1 E" P" k3 }
may have a central nervous system lesion that is4 t$ z9 i% N* i. y# _* o" O1 H u
responsible for the early activation of the hypothal-7 V" Y4 h- q$ C5 {; L
amic pituitary gonadal axis.1-3 Thus, greater empha-
2 l l. r, \, T( w9 a- Asis has been given to neuroradiologic imaging in
1 u+ R: r. Q1 k# k+ }, s9 X7 ]boys with precocious puberty. In addition to viril-
, u/ x: Q7 M' w7 @5 @ization, the clinical hallmark of CPP is the symmet-; ^! k# F, m% [
rical testicular growth secondary to stimulation by
; p8 [8 s4 z2 ?" B' j$ b0 X. Cgonadotropins.1,3; g* Q: Y) d9 P$ L" k2 b7 Y
Gonadotropin-independent peripheral preco-
+ Q/ I. Y3 _" o2 L% d0 C; V; vcious puberty in boys also results from inappropriate2 l; M+ P5 g" k3 p) p( _5 W
androgenic stimulation from either endogenous or
$ t$ p1 E; K& H [5 e1 J1 |exogenous sources, nonpituitary gonadotropin stim-- c9 f2 Y; w, L n) F: i8 T8 M1 S/ A& U
ulation, and rare activating mutations.3 Virilizing
! ^/ M+ h1 ^" E# s" m. A0 F# I2 Bcongenital adrenal hyperplasia producing excessive* [2 J) }( W! h* ~
adrenal androgens is a common cause of precocious' N' D; G1 _; T6 f( M
puberty in boys.3,4+ C5 U. [1 f2 f) O' P3 d) _. F
The most common form of congenital adrenal4 n8 T2 L7 E4 v: Q, ?- m. Z
hyperplasia is the 21-hydroxylase enzyme deficiency.: F5 H V$ E( S: c/ T& i
The 11-β hydroxylase deficiency may also result in
5 G1 \2 U, O# Q9 j) m4 c2 dexcessive adrenal androgen production, and rarely,
- h# E& ]3 u/ ~! d# ]an adrenal tumor may also cause adrenal androgen
5 l0 ^' ]8 D9 l8 X- ^excess.1,3& z: P0 r+ c+ J$ c, G* u# A0 W- g
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
7 B) @+ v. K2 e; j5 `! Q542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
6 Z, p' r3 z% hA unique entity of male-limited gonadotropin-
0 F( _2 ?6 ~4 p6 tindependent precocious puberty, which is also known0 T. R% \; d: d/ a- ]
as testotoxicosis, may cause precocious puberty at a3 Y; ~" Y" z; K ^: @
very young age. The physical findings in these boys
4 ^. E t, \) a: v( B1 I+ F) wwith this disorder are full pubertal development,& B6 S0 k6 B& b: O" s0 ^
including bilateral testicular growth, similar to boys
/ Y$ U2 m5 Z- t _6 Bwith CPP. The gonadotropin levels in this disorder! L) q; T b' c
are suppressed to prepubertal levels and do not show
1 X3 ]) \) ]# S$ O- f, P% lpubertal response of gonadotropin after gonadotropin-
) @3 Q) d) A' s# o+ l: k" areleasing hormone stimulation. This is a sex-linked
& k9 b% F; o3 K3 y+ E- Qautosomal dominant disorder that affects only" r: _9 n% @8 N
males; therefore, other male members of the family
3 |9 K& l- ^% }+ O6 K2 f emay have similar precocious puberty.32 R$ v5 r: `5 D3 x% |! j
In our patient, physical examination was incon-
! B1 a7 W2 d% X" x; [sistent with true precocious puberty since his testi-
0 ^- Z* }3 Z% c- `7 s, Vcles were prepubertal in size. However, testotoxicosis' `; {7 T$ S1 F
was in the differential diagnosis because his father
8 S( o5 r ^. `) y+ estarted puberty somewhat early, and occasionally,4 w5 l2 T* n% [: X
testicular enlargement is not that evident in the
; @9 Y- i; Q8 e" G) |beginning of this process.1 In the absence of a neg-
$ S4 T3 _+ p4 N3 n, V: o, zative initial history of androgen exposure, our5 K- V% _% `2 `7 J8 B
biggest concern was virilizing adrenal hyperplasia,
0 L+ w% c2 P! Y$ Q" Yeither 21-hydroxylase deficiency or 11-β hydroxylase
! u: C3 x) a t, \9 [2 j& Hdeficiency. Those diagnoses were excluded by find-- G5 f' w4 x' u R4 R' ?
ing the normal level of adrenal steroids.
. ~7 y3 |; J p6 b0 _The diagnosis of exogenous androgens was strongly+ A' Q/ u% E, V' A' \
suspected in a follow-up visit after 4 months because% s# W4 V6 |/ Q% a" y' ?
the physical examination revealed the complete disap-# G& P" W$ ?8 f; j' L& C
pearance of pubic hair, normal growth velocity, and
0 @+ {4 G7 G# {1 c8 [+ l( ddecreased erections. The father admitted using a testos-: p, H. U$ u9 _5 }2 j6 X/ @1 \
terone gel, which he concealed at first visit. He was
: Q% [) K- [: A1 d4 r9 Ausing it rather frequently, twice a day. The Physicians’
/ e5 n- m: B* \6 [# VDesk Reference, or package insert of this product, gel or
5 Z: ~- p$ `: M2 A% b l# scream, cautions about dermal testosterone transfer to
: z$ a! O, @, Iunprotected females through direct skin exposure. F% c" D. k& b8 D
Serum testosterone level was found to be 2 times the3 n' ]% f0 @- f/ [1 I3 W. L0 ~9 J
baseline value in those females who were exposed to8 v$ g3 Y/ j* x6 n' [; K
even 15 minutes of direct skin contact with their male
2 t1 ^9 ~! r) B5 R Q2 epartners.6 However, when a shirt covered the applica-
' s, l6 x7 U( \/ Ftion site, this testosterone transfer was prevented.( Y. V+ U' ^8 X
Our patient’s testosterone level was 60 ng/mL,
) {6 ^4 r+ Z7 rwhich was clearly high. Some studies suggest that8 X% I8 X" l Q, N; b2 d
dermal conversion of testosterone to dihydrotestos-
7 G- X! w/ g% p4 g3 Mterone, which is a more potent metabolite, is more
2 d( r* g, b9 s- lactive in young children exposed to testosterone
' U, N6 D5 f" ~5 u, fexogenously7; however, we did not measure a dihy-, q# J& Q" x |- @9 r' g/ j
drotestosterone level in our patient. In addition to
0 \6 T; F1 Y' V6 f3 `virilization, exposure to exogenous testosterone in5 T/ R7 Z# B8 }+ r
children results in an increase in growth velocity and
/ W, H3 v3 G' H) \! O8 vadvanced bone age, as seen in our patient.
3 R2 u3 F5 f+ r' y- p/ J$ qThe long-term effect of androgen exposure during: P# ?& E/ t* |2 a2 [" _2 h5 U
early childhood on pubertal development and final4 \2 v/ g5 e$ o; N' \; l
adult height are not fully known and always remain
7 W, M/ N( L v. Y; d; A1 f- la concern. Children treated with short-term testos-
2 X+ J( k3 p, W/ l Q8 B1 nterone injection or topical androgen may exhibit some
1 ^* t# g# C; q; ~8 Y% Bacceleration of the skeletal maturation; however, after0 s; b0 m: b% {8 W
cessation of treatment, the rate of bone maturation
2 R. d+ R# x( Z# E Y+ i. idecelerates and gradually returns to normal.8,95 m; @' X7 D9 h( p" n/ i' F0 U* o
There are conflicting reports and controversy6 X, Y% B, q5 n4 x# M: U ~
over the effect of early androgen exposure on adult
+ c) ~9 {7 H8 M; Ypenile length.10,11 Some reports suggest subnormal
3 i; s. h) Z0 ^6 l0 Tadult penile length, apparently because of downreg-8 C2 p# D) v1 ]' x: O
ulation of androgen receptor number.10,12 However,/ d+ r* [0 R! Q" o" S7 Z
Sutherland et al13 did not find a correlation between4 S) } _& e5 z, E ^
childhood testosterone exposure and reduced adult
( e( Z) k( M) [/ S% h, x! L# s2 Openile length in clinical studies.
6 h2 F, {# X, ?4 m$ [1 u9 X& VNonetheless, we do not believe our patient is
/ M' j7 C/ N5 r9 \/ m6 F# Tgoing to experience any of the untoward effects from
3 p* r* I. T! u1 ktestosterone exposure as mentioned earlier because
7 O- d: w V% h* P$ Z; w8 fthe exposure was not for a prolonged period of time.2 k" X/ Z% _ c% W8 T+ P
Although the bone age was advanced at the time of
; \% X% v. K) \+ ldiagnosis, the child had a normal growth velocity at
3 {+ I: f! C7 Z4 f* @the follow-up visit. It is hoped that his final adult
3 i, o. o& T. r; fheight will not be affected.- W3 t2 k4 z1 w0 Q' j
Although rarely reported, the widespread avail-/ F* z Z# p+ v1 j
ability of androgen products in our society may
]6 V p9 W1 t( Hindeed cause more virilization in male or female
+ a% f. y6 _# ]& O# Jchildren than one would realize. Exposure to andro-- |" U# U I& D9 k
gen products must be considered and specific ques-
3 K6 R8 Y; O: L, H- T( c: C" ptioning about the use of a testosterone product or
! L" I+ F, `5 B7 a# B5 |gel should be asked of the family members during
9 ^( h3 L _: f0 |7 R! Uthe evaluation of any children who present with vir-, F# H! p; t% d
ilization or peripheral precocious puberty. The diag-$ D% l% y+ L: t t
nosis can be established by just a few tests and by2 l9 k% q; L7 Z/ {: e( l
appropriate history. The inability to obtain such a
6 P1 r4 h2 u# {" m. K2 Z9 T, Khistory, or failure to ask the specific questions, may5 D1 Q! ~, D: ]; B4 N/ M
result in extensive, unnecessary, and expensive
2 d: w) j- @2 T F( {: _' e Xinvestigation. The primary care physician should be
+ h( i* `+ d* i$ Oaware of this fact, because most of these children4 [2 a. H* t& W4 y% ?! t
may initially present in their practice. The Physicians’7 q$ M. u& A& Z8 `8 G# ]* a9 F
Desk Reference and package insert should also put a7 v) h" y7 @; X- G) W% Y
warning about the virilizing effect on a male or
* K3 [# T7 V/ r9 P7 z F9 o% efemale child who might come in contact with some-
6 a; i9 H, c7 z" {; oone using any of these products.* g" p& `9 d0 r/ I6 r
References
2 i+ m, y- V/ G m1 G0 s1. Styne DM. The testes: disorder of sexual differentiation% W) `/ ]) V& L! [
and puberty in the male. In: Sperling MA, ed. Pediatric4 C. @3 @, z) y# m8 i
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
( ?4 Y# }% D( c O8 Q( |2002: 565-628.
( G1 r/ C; v5 E2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious2 r$ q. ]* u( ?! V6 j
puberty in children with tumours of the suprasellar pineal |
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