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Sexual Precocity in a 16-Month-Old
2 }! q- q6 `' v: h- r3 o nBoy Induced by Indirect Topical
$ X9 l: o8 _8 V/ m6 iExposure to Testosterone
5 P6 K& t y9 Q3 qSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2+ r; I6 o. M% Z) D" S* d) {
and Kenneth R. Rettig, MD1
- Y* p) k- [: c' h, o: `1 A; W4 C8 sClinical Pediatrics8 E' H$ p7 q& g
Volume 46 Number 6
+ M! O; s9 ^8 A$ l* [' H% i. w5 R2 _July 2007 540-543
|5 {3 D8 a9 y6 \& x' J© 2007 Sage Publications9 V/ K6 F1 o7 a
10.1177/00099228062966510 N9 g6 y' w2 y2 p& ~6 F# T4 ?
http://clp.sagepub.com7 D8 V1 A3 q% [ t4 w
hosted at. p% j, D! {) K* v: M! T) S7 |
http://online.sagepub.com6 w/ m7 Y* K' G U
Precocious puberty in boys, central or peripheral,) [1 \2 Y& a: P$ b, n6 ?) m
is a significant concern for physicians. Central: E) w; k4 X" u& e: q3 B l
precocious puberty (CPP), which is mediated
: B8 L& P$ U- }+ t9 bthrough the hypothalamic pituitary gonadal axis, has
% o+ z! }) \8 _5 i' |8 S6 r$ Ua higher incidence of organic central nervous system
- [. d/ C+ v3 U) hlesions in boys.1,2 Virilization in boys, as manifested* o0 T! {/ S4 d1 Y
by enlargement of the penis, development of pubic
5 d y3 I$ c5 Y9 q( Nhair, and facial acne without enlargement of testi-( ?5 Z5 Y* j, P4 u
cles, suggests peripheral or pseudopuberty.1-3 We; Y% C7 j# X( o5 {: \
report a 16-month-old boy who presented with the
& ~; r; I& p" @enlargement of the phallus and pubic hair develop-
1 o) k! f+ I6 }* Ument without testicular enlargement, which was due
0 I7 K: E4 t" Mto the unintentional exposure to androgen gel used by
6 ?- N, M- _1 R1 E8 R5 d9 t* Tthe father. The family initially concealed this infor-
7 a% M6 F0 D1 a* A7 y2 xmation, resulting in an extensive work-up for this# L) J4 i2 v$ D7 V" T
child. Given the widespread and easy availability of* W s0 n, K! b8 V" {
testosterone gel and cream, we believe this is proba-
( v' d. @3 b8 f1 _0 f0 M8 mbly more common than the rare case report in the
2 i& h1 Y/ N6 j; ~4 Oliterature.4% e0 _& y& B( q3 G! j! v
Patient Report9 {. d3 r' _" z+ F& m
A 16-month-old white child was referred to the
& B |) j4 N' V& s4 b( aendocrine clinic by his pediatrician with the concern1 H5 C, r6 E: `# ]& l
of early sexual development. His mother noticed
; W, X# C0 u7 B5 C; k- x! plight colored pubic hair development when he was+ B+ R2 _' C# i! \7 q: K
From the 1Division of Pediatric Endocrinology, 2University of
, V/ H" o1 r1 ~+ \- Y8 RSouth Alabama Medical Center, Mobile, Alabama.. G) E# _) n4 c! J
Address correspondence to: Samar K. Bhowmick, MD, FACE,
: A7 P0 g H/ J/ Z* I* PProfessor of Pediatrics, University of South Alabama, College of& p) t# z" N x5 e1 A! Y
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
9 V) }* |( D5 Y# ?0 i% h ue-mail: [email protected].2 _1 Y; f* J# B
about 6 to 7 months old, which progressively became
& V) T9 c8 }- m5 t+ C" t+ R6 xdarker. She was also concerned about the enlarge-
5 s0 ~6 h- f, R7 u I8 jment of his penis and frequent erections. The child
. B: e' `$ s" i. D! U( Z0 [was the product of a full-term normal delivery, with& o, Q) y/ n: K/ O3 D$ W. r
a birth weight of 7 lb 14 oz, and birth length of
/ i: H) a3 L1 x20 inches. He was breast-fed throughout the first year2 x) v6 r9 v& f V( ?3 h
of life and was still receiving breast milk along with
' }, G5 c, @# lsolid food. He had no hospitalizations or surgery,
2 `. r! V6 B5 k. G2 Q2 Aand his psychosocial and psychomotor development- v1 W6 X- f- Z) ^$ p- `
was age appropriate.+ \* G" M- `$ c; a5 p
The family history was remarkable for the father," K) K e. J# X
who was diagnosed with hypothyroidism at age 16,
& n' x; N4 R0 Y3 t1 G" Cwhich was treated with thyroxine. The father’s6 ~& _& p- Y5 f2 m) W
height was 6 feet, and he went through a somewhat, M8 Y$ Y& r5 k9 y0 s7 V
early puberty and had stopped growing by age 14.
' @9 [8 V7 ?2 k! o! eThe father denied taking any other medication. The
9 K6 h, P* |1 M y3 ^child’s mother was in good health. Her menarche
- r( m4 Q. ]( \8 @# u0 E% w) }was at 11 years of age, and her height was at 5 feet2 z5 U4 N' M% _; Y7 N
5 inches. There was no other family history of pre-
: D' S8 n* C4 j: `% ~+ U$ Rcocious sexual development in the first-degree rela-
4 D+ Q6 R7 R; ~- i5 c$ p1 H1 qtives. There were no siblings.
) ^% d+ F' O" lPhysical Examination
% X2 J4 d- T. tThe physical examination revealed a very active,
; A5 G/ ]% c- ~1 H/ }8 Mplayful, and healthy boy. The vital signs documented
( Q( \" C7 ?, D, R# ^, S, b( u2 \a blood pressure of 85/50 mm Hg, his length was
% a8 a$ `. x! L' h$ a, e; K" s90 cm (>97th percentile), and his weight was 14.4 kg- A$ n5 m( L. w" E$ `' E+ Y: \5 E- z
(also >97th percentile). The observed yearly growth
7 F0 J; i. P3 n# \velocity was 30 cm (12 inches). The examination of& V. n9 s5 s. j
the neck revealed no thyroid enlargement.1 M$ V8 P. C$ ?5 x0 V* J
The genitourinary examination was remarkable for0 \+ m" ]; J4 e! f! p9 Z& C- E
enlargement of the penis, with a stretched length of8 B: X2 U7 m. [8 l, ]/ W* }" Y
8 cm and a width of 2 cm. The glans penis was very well5 c6 P% ^# ~+ g0 N
developed. The pubic hair was Tanner II, mostly around
. J; _& [- ^( v5400 s7 [7 m( C: y. i4 g+ D E
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from( S. @8 A; t0 o
the base of the phallus and was dark and curled. The
% r; G( t- `* N# a. ttesticular volume was prepubertal at 2 mL each.
9 f, Y, G1 `6 r1 U: RThe skin was moist and smooth and somewhat
3 R% x! ]* ~& W+ j; ^ C& A) ~& {oily. No axillary hair was noted. There were no* Z8 p( k. Z- b# y; j) z2 @) ]
abnormal skin pigmentations or café-au-lait spots.
7 M7 `; K$ B5 ~- }; ?Neurologic evaluation showed deep tendon reflex 2+
1 b: T, t6 F1 ~bilateral and symmetrical. There was no suggestion
, Z4 m, F: M$ k3 Y% J$ Lof papilledema.5 y3 w7 F8 w% w$ t8 q
Laboratory Evaluation
* ?, P5 V' q, J- Z, cThe bone age was consistent with 28 months by
3 r7 Z8 w* R, E3 C Lusing the standard of Greulich and Pyle at a chrono-" l3 s1 t4 X' E* A) ^! k
logic age of 16 months (advanced).5 Chromosomal. V3 @. D! g, x6 x* a a
karyotype was 46XY. The thyroid function test* [! x. r0 u+ I8 t) y0 u: u
showed a free T4 of 1.69 ng/dL, and thyroid stimu-! G- W9 w' L5 a& e k" W" W
lating hormone level was 1.3 µIU/mL (both normal).( _( i( m& ?6 ]( C$ |" r q- v
The concentrations of serum electrolytes, blood
( B/ a$ y8 o; surea nitrogen, creatinine, and calcium all were
+ i2 ?2 ?( R# F& q$ Q, Z3 g( zwithin normal range for his age. The concentration
4 k# u3 @( _( Qof serum 17-hydroxyprogesterone was 16 ng/dL
6 l) E; Z8 h9 |1 r7 l# J+ F(normal, 3 to 90 ng/dL), androstenedione was 20- G2 \% M8 ]# L) f7 [6 `$ G
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-# b" `9 l) {. o% w4 R
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
. M$ S/ ~9 b1 y' d8 P. _9 |; wdesoxycorticosterone was 4.3 ng/dL (normal, 7 to6 \% @$ D7 Y# m
49ng/dL), 11-desoxycortisol (specific compound S). G6 h1 t8 ^3 \. h% U" Z: u4 q
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-+ l) K( v! m, g! p0 _$ f
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
! d1 u! f! O" Y; ~, ]0 ^& X* r+ Rtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),: @# X( n4 d7 v" G
and β-human chorionic gonadotropin was less than
1 w/ z# ]% c0 K0 D' @1 l$ Y5 mIU/mL (normal <5 mIU/mL). Serum follicular0 f; |2 n, o: q% u
stimulating hormone and leuteinizing hormone
9 K- O g t3 u" p! D6 N. q8 z+ wconcentrations were less than 0.05 mIU/mL
o- \% \; S9 z9 R4 `: y(prepubertal).
+ J( P& Q. ?3 R. _4 b; s9 SThe parents were notified about the laboratory6 e) Z/ [8 {" R+ n+ u7 ~
results and were informed that all of the tests were* N# c. B2 N. w2 `1 u: E) I) f) b
normal except the testosterone level was high. The
0 ~% A6 ^8 ^' J* m# u& }; Kfollow-up visit was arranged within a few weeks to+ {6 I; |8 V. e5 ?+ [! Y) l: @9 }
obtain testicular and abdominal sonograms; how-: J, M: L0 S8 c0 l( ?& }6 O+ q
ever, the family did not return for 4 months.
8 n2 I6 S/ O8 N2 \, d5 ?$ q9 DPhysical examination at this time revealed that the: H: p# G; I- K" N# o$ H
child had grown 2.5 cm in 4 months and had gained' m; x. u3 ~& `2 g$ }
2 kg of weight. Physical examination remained
. s& `$ g: r8 Z. Z$ {unchanged. Surprisingly, the pubic hair almost com-! m5 X0 ?( x* c8 Q* X
pletely disappeared except for a few vellous hairs at
& r9 R" c/ N- V; S" d8 fthe base of the phallus. Testicular volume was still 2
9 [0 e5 |5 O4 U0 r+ p" s$ cmL, and the size of the penis remained unchanged." Z5 D/ ^ ^8 \4 N9 f0 `( C
The mother also said that the boy was no longer hav-0 ]) L9 \2 k0 \) s$ r j: D
ing frequent erections.
) i% W0 L! v% g2 Q( P& C7 sBoth parents were again questioned about use of- {2 S$ S: E {( ~" V C0 n% K9 k
any ointment/creams that they may have applied to& j# w" U# N5 |/ I% k
the child’s skin. This time the father admitted the- C- y$ H9 I( w; l# B
Topical Testosterone Exposure / Bhowmick et al 541
- c% ?. [$ ]- E/ i3 `8 puse of testosterone gel twice daily that he was apply-; v$ M( N' E4 G( m
ing over his own shoulders, chest, and back area for
0 _9 v8 ~: x: }5 p: Va year. The father also revealed he was embarrassed
2 z. U9 z' p' D+ ito disclose that he was using a testosterone gel pre-
' E1 c* [" L, y+ |/ ]scribed by his family physician for decreased libido/ [0 K1 v8 |9 @1 T
secondary to depression.3 O0 I( B3 J* D& x4 p; D- j
The child slept in the same bed with parents. `; w8 q8 g4 E+ n' b! {4 W
The father would hug the baby and hold him on his/ l: p% D0 H* a# {$ b3 `
chest for a considerable period of time, causing sig-
- i, y: U, V3 [5 d @! O; Cnificant bare skin contact between baby and father.4 K) F0 p4 ?* @* p6 f1 ^$ }
The father also admitted that after the phone call,
4 Z( X8 D0 b7 O/ a" d3 D2 Twhen he learned the testosterone level in the baby! ^/ I, X( i. h% n) ^, U
was high, he then read the product information
( \& g7 R% ]- Q' s/ z! b& j; xpacket and concluded that it was most likely the rea-' G5 `) s# u8 Q
son for the child’s virilization. At that time, they
- O1 ]- l0 D* U+ q2 f. Z3 u, ndecided to put the baby in a separate bed, and the
2 Y* R: a7 G- A. K6 P' D, v/ mfather was not hugging him with bare skin and had; H. |" Z X5 _0 R q/ }, F
been using protective clothing. A repeat testosterone9 L' c# |6 V) A0 o
test was ordered, but the family did not go to the: d8 W; L9 J2 G. @' s6 P* | _
laboratory to obtain the test.) s4 `. f% }; l% v2 ?% T
Discussion
# H1 o2 Y5 L* p' _' L) J, rPrecocious puberty in boys is defined as secondary
1 t3 f3 g# L7 R, lsexual development before 9 years of age.1,4- N q! v+ d0 S+ k) E
Precocious puberty is termed as central (true) when- T5 k; B5 q: X- ^3 w& H: A
it is caused by the premature activation of hypo-
/ [" i" g9 |8 J" k# fthalamic pituitary gonadal axis. CPP is more com-' r) V; l# r* @0 w u8 W) M: v
mon in girls than in boys.1,3 Most boys with CPP
. ^1 J8 ?# ~. m4 ~( Emay have a central nervous system lesion that is% z! [4 S- G w- {
responsible for the early activation of the hypothal-
- w' b2 q# `! F6 m K8 _6 W( Famic pituitary gonadal axis.1-3 Thus, greater empha-
1 H4 z0 C4 ^- f5 h+ T# usis has been given to neuroradiologic imaging in
L8 p' F+ S. Q6 A" p2 H4 @) P3 {boys with precocious puberty. In addition to viril-% R4 B9 \7 y7 Q! y
ization, the clinical hallmark of CPP is the symmet-8 I9 _5 [0 R/ H. ?4 @( ~
rical testicular growth secondary to stimulation by
/ ]# }& Y# J- P3 B6 vgonadotropins.1,3
t6 @. I/ j9 C4 ^& N% Z9 |Gonadotropin-independent peripheral preco-# Y9 Z! [& @4 {/ j
cious puberty in boys also results from inappropriate. |7 n" m$ _# I* _- J/ M* }
androgenic stimulation from either endogenous or
$ w* D6 p3 h3 G, \6 @exogenous sources, nonpituitary gonadotropin stim-
( q- J& A( U* j. Y3 Aulation, and rare activating mutations.3 Virilizing
/ `3 _6 y& M. x) V4 p+ xcongenital adrenal hyperplasia producing excessive+ h% z5 g) Z3 F J% H0 G
adrenal androgens is a common cause of precocious
( h( x- g& P( T. J. E! mpuberty in boys.3,4
- N/ D0 z* X. z7 ]The most common form of congenital adrenal
! a$ W$ _4 K6 j! _* Qhyperplasia is the 21-hydroxylase enzyme deficiency.
/ H$ a- ?6 f6 f; VThe 11-β hydroxylase deficiency may also result in
+ i# P! b" M L6 O9 Z! @ ^2 ?excessive adrenal androgen production, and rarely,& {+ Y3 c: P9 r" Z- o) s! c
an adrenal tumor may also cause adrenal androgen( q8 h3 A2 }- w
excess.1,3
6 L: s9 j" k% L4 H5 zat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
) k, r1 ~$ R2 H- v! X542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
2 {; ^: |+ u3 v5 A5 E# M+ O! \A unique entity of male-limited gonadotropin-9 y/ r- a$ y; w6 C9 e* G. R
independent precocious puberty, which is also known l* F5 }; E9 I9 v; F
as testotoxicosis, may cause precocious puberty at a' T( V: N% O2 z
very young age. The physical findings in these boys* Q( X; j! {. i" l0 ~
with this disorder are full pubertal development,
7 v+ T% C% m8 sincluding bilateral testicular growth, similar to boys5 U7 a; x$ M, P
with CPP. The gonadotropin levels in this disorder
# o; k: U# v R/ Q4 Q5 h1 g3 G- b8 Care suppressed to prepubertal levels and do not show n9 }/ d1 B) }& B! v ^
pubertal response of gonadotropin after gonadotropin-# J1 K+ u% l, W
releasing hormone stimulation. This is a sex-linked" w0 E! w0 Z. a1 i4 z( ?4 \
autosomal dominant disorder that affects only7 T* z8 y( m% I ?" i
males; therefore, other male members of the family
9 X: c0 {+ ^* wmay have similar precocious puberty.35 p# x- ^. c, h; T
In our patient, physical examination was incon-- f @# G9 k3 g. K- K% `; l
sistent with true precocious puberty since his testi-
! S3 {& p1 Z) x, s- Xcles were prepubertal in size. However, testotoxicosis; E" n3 z/ s/ Z, X% a' I7 u9 W; Q1 S
was in the differential diagnosis because his father8 s; m2 k( D$ w8 G( ^
started puberty somewhat early, and occasionally,
I5 Z, R5 s( B+ k f1 Xtesticular enlargement is not that evident in the6 B; [* K4 m5 f+ b! B0 o; J# X2 m
beginning of this process.1 In the absence of a neg-
* }) [/ E2 U7 Z! b& z7 r. K1 @7 native initial history of androgen exposure, our9 F" w! L& h4 I
biggest concern was virilizing adrenal hyperplasia,
5 v) u; T, @, D+ k Beither 21-hydroxylase deficiency or 11-β hydroxylase( M6 j1 g8 S+ J/ C2 n9 X
deficiency. Those diagnoses were excluded by find-7 Q ?5 t/ t0 o5 R* {% O
ing the normal level of adrenal steroids.
' q% T. v0 n) [/ BThe diagnosis of exogenous androgens was strongly A( X0 b6 X% ]% s f
suspected in a follow-up visit after 4 months because
* q+ K+ h( ?4 P) g% M1 l1 V( ^& Y, Xthe physical examination revealed the complete disap-# S& V/ X: V2 x' b# C
pearance of pubic hair, normal growth velocity, and! p- H; J4 h+ R o/ }
decreased erections. The father admitted using a testos-
* b8 k$ c( V/ w. N |terone gel, which he concealed at first visit. He was
7 B. w0 \ y, z! d- P" t, eusing it rather frequently, twice a day. The Physicians’
& O* Z, ]+ {, i5 FDesk Reference, or package insert of this product, gel or
3 X9 M2 H- ]5 n( S) G' {, o; j- ocream, cautions about dermal testosterone transfer to
! L/ o$ ], m& dunprotected females through direct skin exposure., \% X8 ~7 F9 n
Serum testosterone level was found to be 2 times the
4 ?$ M0 W7 |, ^- E! ^4 I) z' Obaseline value in those females who were exposed to
5 }+ I$ @5 ~) M7 |% |2 Teven 15 minutes of direct skin contact with their male) j! h s8 W8 b: x' {! B; h& m
partners.6 However, when a shirt covered the applica-8 C6 a9 ]5 Y, [) \5 }3 A% o' D
tion site, this testosterone transfer was prevented.
! c' P. Y2 {# Z% g1 B. e$ l# NOur patient’s testosterone level was 60 ng/mL,0 C5 \8 b3 q/ e5 _3 G1 A/ I
which was clearly high. Some studies suggest that( y" ? S5 S+ Y) k
dermal conversion of testosterone to dihydrotestos-" J" A5 [0 f! B: a6 u+ \
terone, which is a more potent metabolite, is more: D7 N! v' p& U- f! {
active in young children exposed to testosterone* |6 W* [0 \ h/ `7 o/ Y
exogenously7; however, we did not measure a dihy-% W- u7 t6 \- d" L. \
drotestosterone level in our patient. In addition to9 S" }% _- t/ H
virilization, exposure to exogenous testosterone in
, ?8 T2 |% Z7 p5 R' R7 B% t4 xchildren results in an increase in growth velocity and
( Z# x$ ?$ n- f/ ?- L- j' Wadvanced bone age, as seen in our patient.+ e( ^3 y) f, c; E5 K, W
The long-term effect of androgen exposure during
4 g2 i" A1 E3 u" w Eearly childhood on pubertal development and final
& W" E5 U' B) U( f/ m- u" fadult height are not fully known and always remain5 X, I; y/ K( @
a concern. Children treated with short-term testos-1 g' y# h# o- a8 W) ]
terone injection or topical androgen may exhibit some
* l7 Y4 e) Q# W1 h* g3 H1 J! [ pacceleration of the skeletal maturation; however, after: n, P# j6 \7 v* h! c7 R
cessation of treatment, the rate of bone maturation$ A/ i# j% B+ }# R/ \0 S
decelerates and gradually returns to normal.8,9$ K# S; {& S8 ?+ e8 ]: t, G
There are conflicting reports and controversy! [5 J7 N/ y1 ` W- H
over the effect of early androgen exposure on adult7 Q. H. L6 ^) H
penile length.10,11 Some reports suggest subnormal
! V; p; A6 \# u6 eadult penile length, apparently because of downreg-
( t0 z9 g& G& b6 Vulation of androgen receptor number.10,12 However,
5 f0 X7 e, A; N" d$ USutherland et al13 did not find a correlation between8 H N! v8 E- V; C2 U$ X
childhood testosterone exposure and reduced adult
$ F- k9 Z& o/ E0 \penile length in clinical studies.2 s% U9 }9 o. p! C5 |
Nonetheless, we do not believe our patient is. h9 J4 X" L% N( e1 Q2 O
going to experience any of the untoward effects from1 M* L- e* D3 y# Z" @3 E( Q: W* S
testosterone exposure as mentioned earlier because
+ u/ @9 u+ Y. v# cthe exposure was not for a prolonged period of time.& S+ G% M2 O3 _% w
Although the bone age was advanced at the time of
; n& u4 ~6 Z; g5 i% cdiagnosis, the child had a normal growth velocity at
& T+ T x3 z- }# b% Xthe follow-up visit. It is hoped that his final adult$ ^0 }( G1 T* u6 n3 G# n3 e2 M, ^
height will not be affected.( \/ Q- {3 K7 m1 l% U0 j
Although rarely reported, the widespread avail-% _& ~; w9 j8 \' L! l8 X3 O) Q
ability of androgen products in our society may
, |( M2 _# K$ g7 M8 p9 pindeed cause more virilization in male or female
) P r4 L$ m9 K! D: J( Nchildren than one would realize. Exposure to andro-! f5 m& R+ u$ q- ?
gen products must be considered and specific ques-4 n7 [' b5 m' }: P1 w3 u
tioning about the use of a testosterone product or; ~ d* d6 }5 N) T9 x! r
gel should be asked of the family members during* u8 k5 G0 p: W7 k6 }$ s7 k
the evaluation of any children who present with vir-9 x. M; ]" j b p
ilization or peripheral precocious puberty. The diag-8 m# n1 [) ]2 f
nosis can be established by just a few tests and by
* d: p+ b& K$ l' `$ C$ mappropriate history. The inability to obtain such a
& B8 {1 b8 G) K0 O* @, ^history, or failure to ask the specific questions, may& U# @+ Z+ C- O/ v7 G1 e
result in extensive, unnecessary, and expensive
! e% g8 \. M) X3 v- g7 z# j( n/ kinvestigation. The primary care physician should be! L, d5 Z# d, T) `1 d( o) W0 e
aware of this fact, because most of these children3 o+ r2 _7 |' p& E) @& K
may initially present in their practice. The Physicians’
# k) t0 U& w; Q7 IDesk Reference and package insert should also put a+ T2 A5 R2 i1 ]( Z" J& @* E, c7 K
warning about the virilizing effect on a male or
# \! K4 ~4 @' e) B# C$ Vfemale child who might come in contact with some-2 _: Q8 P, S. X
one using any of these products.
+ T0 W, e ], X( I+ {, ^References
: N& Q f+ i% L }" x; d1. Styne DM. The testes: disorder of sexual differentiation' J6 G/ @7 }7 v6 |9 O; J: ]& ^
and puberty in the male. In: Sperling MA, ed. Pediatric) z4 K. o% @2 T* R$ k. t1 o
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;0 o" ~9 R$ b" \* z" k' c
2002: 565-628.4 m% R5 G" s+ v0 `+ v0 {
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious, C# p7 v7 T4 q+ v2 k$ h/ G
puberty in children with tumours of the suprasellar pineal |
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