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Sexual Precocity in a 16-Month-Old
3 |( \9 C) i2 LBoy Induced by Indirect Topical
5 e6 u. o! T6 R0 Z- X& r/ H! T# {Exposure to Testosterone
3 V }4 ?' B6 U! SSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
' R0 W5 ^, W: \! q( d* U p* Q. Tand Kenneth R. Rettig, MD1
2 M/ j% t' \" |$ \7 O. l; eClinical Pediatrics. c3 Q) L8 g$ b2 x
Volume 46 Number 6
9 T7 U6 P1 s" A) o% d3 J+ FJuly 2007 540-543
. U( m5 }; ]# I+ P0 h8 U© 2007 Sage Publications# `8 W. t! Q6 E9 @' G& S
10.1177/0009922806296651+ W" c$ a0 R9 Z
http://clp.sagepub.com
2 I4 c+ M/ r1 @1 |( dhosted at
# u4 N2 z. T9 T. r( Fhttp://online.sagepub.com
. G; s2 e* U- ^/ S) {( DPrecocious puberty in boys, central or peripheral,
; `1 Q x% I- _& lis a significant concern for physicians. Central+ {5 Y# N' B9 O! f
precocious puberty (CPP), which is mediated* N& a- O7 a2 P6 T2 c
through the hypothalamic pituitary gonadal axis, has" m& B0 k, |+ T& a
a higher incidence of organic central nervous system0 J' e$ I2 Q7 `0 r; q
lesions in boys.1,2 Virilization in boys, as manifested4 I, u/ P( U! ~7 [( b1 i
by enlargement of the penis, development of pubic3 ?: b: k7 } w+ k& s) W8 W9 }4 R* v
hair, and facial acne without enlargement of testi-$ z! ?# [- D: h5 Y0 `+ l7 J
cles, suggests peripheral or pseudopuberty.1-3 We
) X8 r3 k) o f: U0 Z$ ]% r, rreport a 16-month-old boy who presented with the
7 K6 x" H2 m' ]! _, I% T# Aenlargement of the phallus and pubic hair develop-
" L, l) G( v0 D. o+ g! h% Vment without testicular enlargement, which was due
+ N6 t: T. l7 {) R8 {+ {. Bto the unintentional exposure to androgen gel used by6 Q5 L6 A0 B o" {4 z. p- n2 U
the father. The family initially concealed this infor-
2 N( T+ _" k8 w6 Mmation, resulting in an extensive work-up for this, f! @% _* l" R$ j" B
child. Given the widespread and easy availability of
$ U, D, m8 r d: c; `! u, n- o( ~* ~5 ^" rtestosterone gel and cream, we believe this is proba-
/ p& p) h7 D! _0 Gbly more common than the rare case report in the
$ k: `5 P# G m# |* Kliterature.4" V1 `! v, L! I# J" @
Patient Report
& q8 n! z. u3 K6 JA 16-month-old white child was referred to the
* p5 z- K) M: Q9 P/ L3 t/ Zendocrine clinic by his pediatrician with the concern
/ d3 a' H f7 [8 Y& g9 uof early sexual development. His mother noticed
' V+ j6 `) ?2 M3 Olight colored pubic hair development when he was
/ d! ~. i1 R8 XFrom the 1Division of Pediatric Endocrinology, 2University of5 n* U, O* M* t1 I8 [
South Alabama Medical Center, Mobile, Alabama. _! C. F6 Q/ W" J" H
Address correspondence to: Samar K. Bhowmick, MD, FACE,$ w8 T4 w i) J! D
Professor of Pediatrics, University of South Alabama, College of
9 o, _& o8 T4 t3 f8 yMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;, C4 A4 ?% e3 P
e-mail: [email protected].
- [7 g0 d- W! Y7 X( kabout 6 to 7 months old, which progressively became q0 J, g/ v0 m* n
darker. She was also concerned about the enlarge-
) M" z! {! }6 W% g" Kment of his penis and frequent erections. The child
9 x( B+ B& ^; K) ?! L2 ~+ {) M1 Z$ qwas the product of a full-term normal delivery, with' a4 b$ i1 p& K% h9 o9 a8 m# F
a birth weight of 7 lb 14 oz, and birth length of
8 w% i7 U; \0 e" T7 D( E. I20 inches. He was breast-fed throughout the first year; A. C' r5 f7 F9 c
of life and was still receiving breast milk along with
- ]" H0 \, o2 ? V" m; r' {solid food. He had no hospitalizations or surgery,
7 o! |6 z% r1 aand his psychosocial and psychomotor development
; B- X8 n; \9 |& O5 ^was age appropriate.
0 C4 i G* l7 l5 }- F: }The family history was remarkable for the father,- w, L6 i5 N: s% O/ E H% p
who was diagnosed with hypothyroidism at age 16,
1 S h+ y1 C) m, bwhich was treated with thyroxine. The father’s4 S" b- t- W1 A* f2 [4 R
height was 6 feet, and he went through a somewhat
8 w* z0 w" N: z* w0 h; I+ h6 vearly puberty and had stopped growing by age 14.
" I9 V+ X+ J3 S' }1 P" fThe father denied taking any other medication. The" ?( h/ `& e8 D' @, D6 q. b7 |
child’s mother was in good health. Her menarche, g) S- ?4 z3 w" t7 Y( z
was at 11 years of age, and her height was at 5 feet# w/ H. |+ D- w6 A2 m+ d
5 inches. There was no other family history of pre-
0 h+ J9 j; P; R) T ] r' l, ccocious sexual development in the first-degree rela-
/ l' Q8 M& U5 y- y0 F5 Ntives. There were no siblings.
` R. m1 U IPhysical Examination9 r% @0 M& V# f. L$ T
The physical examination revealed a very active,
) H% L7 B5 v+ |7 ]) Rplayful, and healthy boy. The vital signs documented; ~+ B, N* P3 c
a blood pressure of 85/50 mm Hg, his length was
8 C" Q1 s( K6 T( ?+ ?90 cm (>97th percentile), and his weight was 14.4 kg
/ D, i3 v0 J" x* z* l(also >97th percentile). The observed yearly growth6 {- f& [2 u1 \
velocity was 30 cm (12 inches). The examination of( j$ X3 C) T( {- j1 ^1 C8 q
the neck revealed no thyroid enlargement.) k: c, v" l: X, X
The genitourinary examination was remarkable for
6 ? ?! |2 ~. B4 \9 ienlargement of the penis, with a stretched length of
6 d x9 j) y( W* p1 ^: Z4 B8 cm and a width of 2 cm. The glans penis was very well4 ], W+ ]0 P* A/ ^
developed. The pubic hair was Tanner II, mostly around0 M! Y8 p" N7 y; k: P0 Z
5402 t* m3 S$ `, u: U4 f+ B
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
1 J3 a2 k2 u$ b" _5 mthe base of the phallus and was dark and curled. The
* [* a1 G) R, @6 C ktesticular volume was prepubertal at 2 mL each.# h0 D* k$ t) G; R
The skin was moist and smooth and somewhat
$ _% |0 ~! z5 z5 D0 n7 joily. No axillary hair was noted. There were no
O0 G3 u6 Y8 \, G, b. @8 P- Y' gabnormal skin pigmentations or café-au-lait spots.
1 R) v! z b3 E( UNeurologic evaluation showed deep tendon reflex 2+( S2 ^9 o Q2 k# R% [7 p/ n2 p
bilateral and symmetrical. There was no suggestion
+ g8 X& h9 s, r5 eof papilledema." N0 E9 L: z& @2 E" g
Laboratory Evaluation
0 i* o; B R# d4 \+ ~# SThe bone age was consistent with 28 months by8 A0 W; @8 \* H" h( G: e
using the standard of Greulich and Pyle at a chrono-* v5 e) O& m. |6 a
logic age of 16 months (advanced).5 Chromosomal; R+ a, P6 y$ ~% H6 V
karyotype was 46XY. The thyroid function test- i7 g8 z- f) s- ~7 g3 \/ o
showed a free T4 of 1.69 ng/dL, and thyroid stimu-# a- M3 p9 i, e0 o7 s; Z) R* H
lating hormone level was 1.3 µIU/mL (both normal).6 ~9 D; m! u( }$ i7 z0 f# {
The concentrations of serum electrolytes, blood0 R% ^% m4 S. I, C. ~7 q
urea nitrogen, creatinine, and calcium all were
! N- Z8 }$ o" Y. M! `' Ewithin normal range for his age. The concentration
+ S% I- e/ r; ]9 qof serum 17-hydroxyprogesterone was 16 ng/dL4 F2 t% _- O& M
(normal, 3 to 90 ng/dL), androstenedione was 209 d5 C( g9 M3 Z N. K1 x1 h* Y I% u
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
( B; s0 o( t% S# nterone was 38 ng/dL (normal, 50 to 760 ng/dL),( ]$ N. F/ a( ~ ~
desoxycorticosterone was 4.3 ng/dL (normal, 7 to# j: x& Q0 S7 o) N6 D: S* ~
49ng/dL), 11-desoxycortisol (specific compound S)) U6 |# P. V9 M9 }# f) P' T- z
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
# m1 f+ p% e7 y. S" Ztisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
: `9 r! }) R3 w, J7 o3 Z$ jtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
- e9 ?' e% u6 U( g2 iand β-human chorionic gonadotropin was less than
. w" i* O2 ]0 v1 A5 mIU/mL (normal <5 mIU/mL). Serum follicular4 s' C( b( b( v
stimulating hormone and leuteinizing hormone
( e# l6 ]8 w$ s, V. mconcentrations were less than 0.05 mIU/mL1 a, Y' Y; w* p s. G
(prepubertal).
9 v- |. O9 B WThe parents were notified about the laboratory1 T |4 [* I* {8 m( _" t; |: m
results and were informed that all of the tests were3 o+ m% G2 o+ Z0 Q% I- X
normal except the testosterone level was high. The0 _% q) r; A; d- x7 `% H
follow-up visit was arranged within a few weeks to
7 l0 p4 O- i& R1 E6 Sobtain testicular and abdominal sonograms; how-
- c6 f; o& X6 q9 o1 U9 \; ?+ i! iever, the family did not return for 4 months.
8 h7 j$ g+ W8 M" wPhysical examination at this time revealed that the! ?8 }7 V2 c8 y. @. h" t
child had grown 2.5 cm in 4 months and had gained2 x% R" ?! S2 `; m
2 kg of weight. Physical examination remained, }0 L( f o* @' g' r, f
unchanged. Surprisingly, the pubic hair almost com-
0 p0 h, _. p1 ~5 i, Dpletely disappeared except for a few vellous hairs at9 ~1 n, z- M* Q6 W, H4 J$ b7 E
the base of the phallus. Testicular volume was still 2
9 _* s- i' n, A0 U7 XmL, and the size of the penis remained unchanged.* l! d5 e/ h' r9 p
The mother also said that the boy was no longer hav-0 l. B: F! l4 q/ Y0 R# V1 ~+ k
ing frequent erections.
3 z' {" U9 ]* Y; lBoth parents were again questioned about use of
7 H5 B! P, ?& }: a2 P0 rany ointment/creams that they may have applied to
- q' Q/ u% E; W9 x. Cthe child’s skin. This time the father admitted the
4 }& ~( e6 X( E/ ?. ITopical Testosterone Exposure / Bhowmick et al 541& r0 ^" j9 l7 v* `$ Q# k
use of testosterone gel twice daily that he was apply-
' N' f" X6 X9 `7 Q# V; g: cing over his own shoulders, chest, and back area for2 q6 c7 g# A/ t+ ]4 j7 V2 w! S! y' O
a year. The father also revealed he was embarrassed0 Y! n4 l; N8 X2 a m
to disclose that he was using a testosterone gel pre-
; p2 u. n9 o5 u, E3 e$ K5 R: _% f) q$ tscribed by his family physician for decreased libido
5 T- `( v4 M) L' Osecondary to depression.6 R$ w# N* C: R: I4 C. `& v
The child slept in the same bed with parents.1 D2 P+ f. R$ z1 h$ }" [: u4 ~6 Y8 W
The father would hug the baby and hold him on his
& p0 v, B r; u" u) Wchest for a considerable period of time, causing sig-8 L! n, v8 y/ T
nificant bare skin contact between baby and father.
5 Q9 o4 x. p6 c$ P0 G) g# C" LThe father also admitted that after the phone call,# d$ B' M5 e! i: x4 ]7 i; }
when he learned the testosterone level in the baby) C" h' j5 b) t2 o; m0 D4 Y" c
was high, he then read the product information
7 N; z( E( X! U7 d: j5 Z) P+ l1 R# @packet and concluded that it was most likely the rea-; E; w* x# G! r0 b! V
son for the child’s virilization. At that time, they! w$ d& X- b' ^1 D% L) k3 V5 {1 P4 |
decided to put the baby in a separate bed, and the6 w! b# m9 h4 S1 ?8 M7 |
father was not hugging him with bare skin and had
0 g8 B5 l: E# l. cbeen using protective clothing. A repeat testosterone& [! x A3 @3 Z, g0 ^
test was ordered, but the family did not go to the/ R3 ?0 W- G) D8 C- Z
laboratory to obtain the test.
) g3 S D$ K; C8 u, v. O5 K; K8 mDiscussion
+ ]6 S# j3 O8 N' |; E* RPrecocious puberty in boys is defined as secondary5 h$ C' W7 G/ B; K
sexual development before 9 years of age.1,4
/ }+ w2 _7 w! D5 Y( rPrecocious puberty is termed as central (true) when
: m+ I( |0 ^' V% _5 {it is caused by the premature activation of hypo-- t5 b4 G) x( N+ G2 }2 C, n
thalamic pituitary gonadal axis. CPP is more com-! t, ~: h% E1 i+ |1 N
mon in girls than in boys.1,3 Most boys with CPP
! E& \/ y& M \8 L8 p& }may have a central nervous system lesion that is
& R9 v# b/ ?0 s+ E. vresponsible for the early activation of the hypothal-5 P7 _8 t1 ~0 I5 F* w" T1 k
amic pituitary gonadal axis.1-3 Thus, greater empha-
2 D( f- g1 D; a' u) p3 m* ?sis has been given to neuroradiologic imaging in
9 {( h8 d+ c4 qboys with precocious puberty. In addition to viril-
. V# U6 {; s( h1 s2 g' pization, the clinical hallmark of CPP is the symmet-
8 g* W. n7 F) w V2 _/ Arical testicular growth secondary to stimulation by+ S Y' E) t. y/ n+ Q
gonadotropins.1,3! z: u& {* J9 Y. l; E( i9 _6 ]
Gonadotropin-independent peripheral preco-
* @& C" W6 `* I0 k" |cious puberty in boys also results from inappropriate
* o! N& C h. Y4 R3 e1 ?androgenic stimulation from either endogenous or. ^9 y& R5 j$ r c( K( O$ V8 p
exogenous sources, nonpituitary gonadotropin stim-
! F% H& H1 S# |* O zulation, and rare activating mutations.3 Virilizing9 N: o' C& h4 z7 W9 {+ o E* K
congenital adrenal hyperplasia producing excessive, p. v$ N( T) I( _4 p8 G2 R9 g2 p
adrenal androgens is a common cause of precocious
0 ]- X& @( q+ L6 rpuberty in boys.3,4
( z# |$ k% @% f; X! j; Q. TThe most common form of congenital adrenal
! V" A% {- f% s2 E; I- i3 M$ n- }hyperplasia is the 21-hydroxylase enzyme deficiency.8 R+ D0 ^7 _9 `& Z$ w6 K
The 11-β hydroxylase deficiency may also result in
8 h% T6 w4 m: c9 B. |3 s. k8 Lexcessive adrenal androgen production, and rarely,: L9 J, ^6 e3 }0 e3 x5 T! B
an adrenal tumor may also cause adrenal androgen: _& y- q1 C) M/ g- f, N1 y* @* X
excess.1,3; r- b' r' L7 z" j/ J f& p
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
* H$ R" _2 j/ W' M# g542 Clinical Pediatrics / Vol. 46, No. 6, July 2007. U2 [2 v$ H) Y7 @* ~8 v
A unique entity of male-limited gonadotropin-, k# J3 W9 d M: q+ z! R6 K4 t6 K- i: \
independent precocious puberty, which is also known" \' Z6 P2 o4 W7 S; e# B+ c1 R
as testotoxicosis, may cause precocious puberty at a* z6 E; M, r+ Z( R+ s$ j
very young age. The physical findings in these boys
$ U9 [5 X" j! V& P2 U: Mwith this disorder are full pubertal development,3 G. T0 t3 ]8 a0 r
including bilateral testicular growth, similar to boys0 @! Z5 V) k- J% y/ P
with CPP. The gonadotropin levels in this disorder+ B& d' F, _( Q' L$ ~
are suppressed to prepubertal levels and do not show
, A7 S) i2 U0 v9 i/ T6 b7 K+ xpubertal response of gonadotropin after gonadotropin-; u, B! {. D1 h7 d
releasing hormone stimulation. This is a sex-linked
3 K% ]; m+ D8 O) f+ q* ?autosomal dominant disorder that affects only
0 S) }1 h" }) a# Jmales; therefore, other male members of the family: G# H0 l7 ?5 o7 `6 m/ c( S
may have similar precocious puberty.30 m0 H$ m& Z, L% u$ H
In our patient, physical examination was incon-1 y2 v7 e; c1 ?% w& H \5 }: S
sistent with true precocious puberty since his testi-% ~) u3 y- V0 o
cles were prepubertal in size. However, testotoxicosis
: R* |& N5 b$ b7 {9 dwas in the differential diagnosis because his father
; X: k# Y6 K' |0 t* qstarted puberty somewhat early, and occasionally,
4 h$ h3 M' H! O2 D5 h$ r3 Xtesticular enlargement is not that evident in the- @$ i0 l0 V: y( _ {: L6 k
beginning of this process.1 In the absence of a neg-8 A$ A# S! B+ j5 N6 I( N7 p |
ative initial history of androgen exposure, our
+ D3 r: u" e3 E T' w0 `biggest concern was virilizing adrenal hyperplasia,
; Z* }( m/ k3 p9 ]5 F# jeither 21-hydroxylase deficiency or 11-β hydroxylase9 u5 y4 L$ _* {0 y
deficiency. Those diagnoses were excluded by find-/ A$ R0 L- m1 J. x. o$ @
ing the normal level of adrenal steroids.9 J( }# I9 T: _- @% i
The diagnosis of exogenous androgens was strongly
4 W# f+ j1 a* ?/ E$ i6 Ssuspected in a follow-up visit after 4 months because
( S% b& }' B* m: V/ dthe physical examination revealed the complete disap-0 _; K/ M- z3 j# y9 K
pearance of pubic hair, normal growth velocity, and: B6 l9 G4 U1 i0 a
decreased erections. The father admitted using a testos-: g p0 r. @' u5 ^2 C2 b
terone gel, which he concealed at first visit. He was1 H; x/ ]2 N9 {* D; ^; l! b
using it rather frequently, twice a day. The Physicians’! K- v0 C2 P2 W
Desk Reference, or package insert of this product, gel or( s. [. X3 u( _% u* ^' b4 Y
cream, cautions about dermal testosterone transfer to
' r5 N) C( W Q' ~unprotected females through direct skin exposure.
) L7 d( a: N+ ?2 _Serum testosterone level was found to be 2 times the
/ W9 C: o& c8 x* _6 Rbaseline value in those females who were exposed to& E% o! F$ q* i, S% x
even 15 minutes of direct skin contact with their male2 P# |' B5 c% Q! l" j( Y: U
partners.6 However, when a shirt covered the applica-
+ f6 ^% T4 z* N# S' B+ @7 ktion site, this testosterone transfer was prevented.( \# S' Z) m; W+ s9 b$ O
Our patient’s testosterone level was 60 ng/mL,
/ S) I: e6 u1 N* Bwhich was clearly high. Some studies suggest that
5 k3 x9 ?9 I6 ^: s( ^- Ldermal conversion of testosterone to dihydrotestos-
* z0 P# W: h7 w; R, u0 q) [terone, which is a more potent metabolite, is more
8 n# `- {. S a4 p0 X9 m% Mactive in young children exposed to testosterone
# c0 a1 q) @/ r* xexogenously7; however, we did not measure a dihy-6 P1 e5 F$ J8 D0 ]8 A
drotestosterone level in our patient. In addition to
' |4 N b8 N6 ?% k- Nvirilization, exposure to exogenous testosterone in @/ v8 X+ D/ x$ i9 h
children results in an increase in growth velocity and
& F9 k: J" v8 J5 l: j$ Uadvanced bone age, as seen in our patient.# ` p$ S! I1 v. _, B: ?# ~
The long-term effect of androgen exposure during
# H' x- C+ I: V6 j. Dearly childhood on pubertal development and final
4 G. G( D, h5 o" b6 @: d5 K, ladult height are not fully known and always remain% I4 E8 |4 U7 j" _8 E
a concern. Children treated with short-term testos-
+ T6 C4 z+ O, C. P& {+ gterone injection or topical androgen may exhibit some
1 a6 U: G. O }: [. Facceleration of the skeletal maturation; however, after
0 Y/ M# w# g! a' w2 q- T4 rcessation of treatment, the rate of bone maturation
4 ~1 a( p. I/ T+ f4 Ddecelerates and gradually returns to normal.8,9% p2 y5 W, F& v/ \1 j" U* m/ F6 C
There are conflicting reports and controversy Z0 p+ R Z, [4 _
over the effect of early androgen exposure on adult1 I! D$ ?) N$ V$ Q' V
penile length.10,11 Some reports suggest subnormal9 Z4 b, W( j# E4 l3 b+ N7 {
adult penile length, apparently because of downreg-
9 X/ F" U* u1 p1 Y2 p$ n2 i" rulation of androgen receptor number.10,12 However,& M- L4 J; k( G6 U, t" d0 t7 l% ^
Sutherland et al13 did not find a correlation between
% w8 l h. ^) p& L3 _; Rchildhood testosterone exposure and reduced adult
( o+ n' r- G: D, h# b- ~" K% upenile length in clinical studies.
6 \# e- E$ z3 l, w8 D: _2 dNonetheless, we do not believe our patient is: c' s) W! S2 _6 K3 ]. V8 E
going to experience any of the untoward effects from* \, C6 j. W, ]8 V1 Z" z
testosterone exposure as mentioned earlier because: e! Z/ i3 Q' c
the exposure was not for a prolonged period of time.# x7 J; w/ p M5 J2 v- d
Although the bone age was advanced at the time of
* b9 g+ ^5 f$ D+ ~" C2 o; z* {diagnosis, the child had a normal growth velocity at3 j0 L/ P& v$ S" y% y
the follow-up visit. It is hoped that his final adult
x7 q' q) H }" Gheight will not be affected.
. K! b$ {: p' O1 h- uAlthough rarely reported, the widespread avail-
- @* j2 b5 G4 h- q$ @5 M8 Q. v. Wability of androgen products in our society may+ I+ f7 w' W( |1 g
indeed cause more virilization in male or female: [4 N% z$ q- X
children than one would realize. Exposure to andro-: ?2 Q, z2 T! w* }7 ~6 T% ^ E
gen products must be considered and specific ques-
( i% p2 g8 |1 Rtioning about the use of a testosterone product or
! L# k+ c' D* `: K0 pgel should be asked of the family members during
& Q7 Q' [! @4 ?+ Kthe evaluation of any children who present with vir-$ Z3 { \( \9 g* Y7 b
ilization or peripheral precocious puberty. The diag-; n- I1 x6 F- e! k* J8 E
nosis can be established by just a few tests and by
% R+ R4 n8 r8 uappropriate history. The inability to obtain such a
& v. p. |6 o4 E' ?8 F" thistory, or failure to ask the specific questions, may
1 p% }) q" B" I) L+ A3 gresult in extensive, unnecessary, and expensive3 n5 h/ K' z# ~5 f
investigation. The primary care physician should be% Z2 t# s" e0 T) q& T/ V/ Y5 ~
aware of this fact, because most of these children
! J* D( L! G7 Q0 ^! A9 r* cmay initially present in their practice. The Physicians’" v6 v4 U/ _+ G! x
Desk Reference and package insert should also put a
7 I Z1 E4 w- pwarning about the virilizing effect on a male or+ \! Q$ y2 q! W3 O4 f
female child who might come in contact with some-
9 \# a. U5 o4 o {one using any of these products.
$ Y% L) z3 e' A; f) ?! vReferences$ Y# Z( O" Z- c; E. L7 N$ @) L
1. Styne DM. The testes: disorder of sexual differentiation
+ ~) p A+ Y- `6 M) {: O( v* Band puberty in the male. In: Sperling MA, ed. Pediatric% U* w7 q& l* \; C( k9 c7 ]
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
) n$ B) y6 p8 H6 w2002: 565-628.
' f1 N3 p0 t- Z" I2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
4 r7 ^+ a0 V4 O2 D% X) Q. Q }puberty in children with tumours of the suprasellar pineal |
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