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Sexual Precocity in a 16-Month-Old
* j7 w- l( o' B5 a+ Y$ [7 E. {Boy Induced by Indirect Topical
. g9 `& ~6 X/ g# YExposure to Testosterone! `( U0 L$ E! N7 i i, w
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
( G. Z0 n4 d- ^! p- Z# z' oand Kenneth R. Rettig, MD1
1 ~/ p7 F1 y1 {' f# a3 [Clinical Pediatrics
; x7 |, `' U6 d6 c3 F4 IVolume 46 Number 6
, \ [# n+ D' X6 RJuly 2007 540-543
+ Z# Q6 V; ]0 V" S* q* V h, _© 2007 Sage Publications
* I& s' ]+ j1 i! o, B4 z" C10.1177/00099228062966517 S7 S8 L: }( i p" {7 [
http://clp.sagepub.com0 M* h/ \( w! `, ? j9 Y& }
hosted at
9 H1 |( R% u. c! Yhttp://online.sagepub.com0 P& m6 {# X7 B/ H, s) N7 O7 k
Precocious puberty in boys, central or peripheral,
$ @4 d1 i/ P: cis a significant concern for physicians. Central
: q }9 c1 [) V# I, y4 S V0 [precocious puberty (CPP), which is mediated
/ @: V/ f. x# j8 \2 [through the hypothalamic pituitary gonadal axis, has
. k$ \5 A; S" |) M% _' b8 Ea higher incidence of organic central nervous system, A- ~0 `4 ?* Y& P& K' I* W, k4 a
lesions in boys.1,2 Virilization in boys, as manifested# b* }( t/ \, x) _
by enlargement of the penis, development of pubic
4 j& B4 e2 s* t& {( Nhair, and facial acne without enlargement of testi-
5 E+ U' C# c5 J; b6 |) U; rcles, suggests peripheral or pseudopuberty.1-3 We
0 z$ I4 Y* h; T7 I' Ireport a 16-month-old boy who presented with the
& a! p) E+ ~$ j& a0 q" penlargement of the phallus and pubic hair develop-
6 p o0 S9 m! E& [, m" B+ }5 vment without testicular enlargement, which was due
0 U2 {4 o+ f! W* _+ @6 |to the unintentional exposure to androgen gel used by
7 z# k a3 N4 zthe father. The family initially concealed this infor-
1 L/ _2 k. S$ Vmation, resulting in an extensive work-up for this7 b& G( I0 t. R, E* E4 [
child. Given the widespread and easy availability of
' [. T, @4 R8 d6 qtestosterone gel and cream, we believe this is proba-
" }% y# F0 P1 A. U7 Nbly more common than the rare case report in the2 U. X' W9 c' k
literature.4
1 u, j$ [! b2 c- Q) KPatient Report I! \$ v" Q) E4 c7 [& R. H7 V
A 16-month-old white child was referred to the
4 S* z0 Z- J' ^3 h* ^endocrine clinic by his pediatrician with the concern% v8 x; x9 W+ s& b- L! ~
of early sexual development. His mother noticed x7 z! n+ _5 w" O6 D
light colored pubic hair development when he was
2 M- x7 v2 M5 e- ~# s( s/ |( @From the 1Division of Pediatric Endocrinology, 2University of
& q; m. T8 e G0 }/ g3 X5 FSouth Alabama Medical Center, Mobile, Alabama.* f7 h, I/ b5 [, G. E# P' j
Address correspondence to: Samar K. Bhowmick, MD, FACE,8 L1 O: i2 d9 Y8 A0 Q
Professor of Pediatrics, University of South Alabama, College of
6 J0 ]4 L+ y- |) ~3 Y# K! ]3 S' uMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
: i% {4 z! m4 x6 J# t5 i' c4 be-mail: [email protected].
- D, m1 d5 i' s7 \4 K% ?* oabout 6 to 7 months old, which progressively became
7 }; b9 r8 M: Ldarker. She was also concerned about the enlarge-* ^# ?+ i, Y# l# A5 p0 j2 P
ment of his penis and frequent erections. The child5 ^6 M8 i( K; q: G
was the product of a full-term normal delivery, with
) g0 Q+ |: r) d8 F9 Q8 za birth weight of 7 lb 14 oz, and birth length of
' K, x* p+ M0 U- ^20 inches. He was breast-fed throughout the first year( J& q2 ?7 d+ W, x. m
of life and was still receiving breast milk along with
0 g- y$ `2 ^% F+ v4 d4 l, {0 @4 v0 csolid food. He had no hospitalizations or surgery,) x8 l; C- `; e: M1 U' @# h# D
and his psychosocial and psychomotor development
: f9 \2 g) X8 L& a9 X+ m4 dwas age appropriate." D4 T3 R7 D, |1 K
The family history was remarkable for the father,
* `; }, l1 {# S$ ]1 p0 ]/ ~who was diagnosed with hypothyroidism at age 16,; \1 J6 m3 j4 I8 W& Q
which was treated with thyroxine. The father’s
, C9 E2 L- [ z7 F9 B4 \height was 6 feet, and he went through a somewhat
D6 m- R' Z0 G* K$ Yearly puberty and had stopped growing by age 14.
$ j) G }- G1 I7 q- J8 r: fThe father denied taking any other medication. The
2 n* _7 |2 E. @6 g! R9 g# ]child’s mother was in good health. Her menarche# [( }6 X t) y9 S
was at 11 years of age, and her height was at 5 feet8 G- `9 ?. c0 L7 U
5 inches. There was no other family history of pre-
9 F1 {0 F6 _6 Q$ @! a# F8 {cocious sexual development in the first-degree rela-
( c8 k- r. S" [% r. m- d4 d, t1 Utives. There were no siblings.
7 L0 `1 W0 _4 I% wPhysical Examination3 d0 R% H9 N& n; @7 o9 r) T2 p8 ~
The physical examination revealed a very active,
+ R0 z9 e; X- A8 g& \: p Splayful, and healthy boy. The vital signs documented
# t6 E$ {0 Q5 q: A) i, Ja blood pressure of 85/50 mm Hg, his length was, R. D. d. b4 r3 A6 }4 _9 d) O
90 cm (>97th percentile), and his weight was 14.4 kg1 Y* W3 v" z/ h+ u+ }. h+ Z
(also >97th percentile). The observed yearly growth1 R9 O e% e$ f- {3 B. H) H. t& a
velocity was 30 cm (12 inches). The examination of
+ B, ~* C6 t- N) c% k0 q' tthe neck revealed no thyroid enlargement.
: g: y' ]+ z' G& M, }9 Y8 E9 IThe genitourinary examination was remarkable for$ A; j c7 j- M/ ~, |
enlargement of the penis, with a stretched length of
& b8 q. m: t; w! D! N$ x8 cm and a width of 2 cm. The glans penis was very well
& A4 H9 y5 c" ~+ K2 z% P- S- H3 }7 adeveloped. The pubic hair was Tanner II, mostly around8 _/ w* [! ]& G; o$ @8 ?
540$ h, e" n8 D/ V% _
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
. M0 |9 A& E9 Q- i) Y/ ]the base of the phallus and was dark and curled. The' C N5 X) |9 V% k: y3 F( A% V7 ^
testicular volume was prepubertal at 2 mL each./ ]3 F, M- I3 T' t1 C
The skin was moist and smooth and somewhat
) f5 w5 e% |1 ^. H2 ^oily. No axillary hair was noted. There were no" y! Y6 ?( B/ P7 z# t
abnormal skin pigmentations or café-au-lait spots./ W5 S: E0 {( a! A/ f
Neurologic evaluation showed deep tendon reflex 2+6 T. u, M' u2 d
bilateral and symmetrical. There was no suggestion
& p" D, B6 j- @) a8 m6 {of papilledema.. C7 e$ W$ @* ?( ?$ M- c# p* `' [
Laboratory Evaluation6 ^- B/ s2 G+ a
The bone age was consistent with 28 months by/ s7 W) X2 d3 E& `* F% F
using the standard of Greulich and Pyle at a chrono-5 q0 L+ N4 O+ k% K. V7 t6 J
logic age of 16 months (advanced).5 Chromosomal. Q6 T- v) E s b
karyotype was 46XY. The thyroid function test
# j- h6 @- N& Q' Bshowed a free T4 of 1.69 ng/dL, and thyroid stimu-1 I, l# e$ T# R" v$ B$ P
lating hormone level was 1.3 µIU/mL (both normal).
& T; R9 z3 R$ T! x5 J& }5 x EThe concentrations of serum electrolytes, blood# f' Q- |( K2 ]) d; |! v
urea nitrogen, creatinine, and calcium all were$ i3 G5 T* c) w2 b) }2 J
within normal range for his age. The concentration( b7 w4 W# B! C" v- p% ^: d3 v
of serum 17-hydroxyprogesterone was 16 ng/dL
0 R: }& E4 W$ v9 T(normal, 3 to 90 ng/dL), androstenedione was 20* g% P. g% `$ _* m
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros- p% d2 r! d- q! C5 d
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
, {3 p4 `* j! d4 Xdesoxycorticosterone was 4.3 ng/dL (normal, 7 to& u6 J$ V! D7 S, h
49ng/dL), 11-desoxycortisol (specific compound S)
& Q2 ^) N# l% U1 O, G% Qwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-# K. X% m) N/ M2 w1 O+ ?6 P
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total. J( Q& L; G( K
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
; s0 F. p D$ g- U( K7 Cand β-human chorionic gonadotropin was less than2 n: ?2 n" C5 C7 `: w
5 mIU/mL (normal <5 mIU/mL). Serum follicular+ i& L/ O/ r' A$ C
stimulating hormone and leuteinizing hormone
$ W9 M6 d& j. \' ^0 Y$ }concentrations were less than 0.05 mIU/mL | \7 u" n& m( M! d: I8 b
(prepubertal).0 F$ z- I4 U8 H6 s' L! z' V
The parents were notified about the laboratory
+ S2 {1 \6 V7 v! iresults and were informed that all of the tests were
) S8 v+ T( ^+ j: e& v0 O' rnormal except the testosterone level was high. The
& P" ]# ?/ F4 ^5 z" E$ ?follow-up visit was arranged within a few weeks to& |5 F" ^( C/ S5 O. H' o6 }( a$ K
obtain testicular and abdominal sonograms; how-+ c: d+ L D) b! ?, V. b
ever, the family did not return for 4 months.
" F8 |+ V3 i& @Physical examination at this time revealed that the
' \- O! E. O2 D: a7 R& l( _8 ^child had grown 2.5 cm in 4 months and had gained9 r/ v4 g+ u- d; S
2 kg of weight. Physical examination remained+ h* c) r4 S5 H7 A6 {* A
unchanged. Surprisingly, the pubic hair almost com-
+ _4 U5 f! _/ i6 ^0 `. F9 ]pletely disappeared except for a few vellous hairs at4 N6 A1 z1 r* `) q/ y
the base of the phallus. Testicular volume was still 2
% b$ j1 t4 e# }# R/ N; i q9 rmL, and the size of the penis remained unchanged.5 |* A. U9 y1 \! n0 A* |
The mother also said that the boy was no longer hav-
( d8 T' T. s: [6 X# Iing frequent erections.
* x7 v. D/ U$ `! U- r: j6 Q1 |Both parents were again questioned about use of
1 \! n( |. |- L: Rany ointment/creams that they may have applied to/ P6 Z+ Y* u, N" D' V# G
the child’s skin. This time the father admitted the
" J& W4 J: w: ^* kTopical Testosterone Exposure / Bhowmick et al 5414 v) Y; \! L8 _0 t
use of testosterone gel twice daily that he was apply-
1 \; q% ] H% S+ z; l+ _7 D$ aing over his own shoulders, chest, and back area for
0 ?- m0 k$ U$ j! P4 K5 ma year. The father also revealed he was embarrassed
3 T |. N! I3 v1 A# F" e& Zto disclose that he was using a testosterone gel pre-
3 @& u, h% \ l" r, V( Cscribed by his family physician for decreased libido) [1 P/ q" r( a* H) \, D! t$ Q
secondary to depression.7 Y3 v z m2 c" e. t k2 ]
The child slept in the same bed with parents.
" [: h# s+ h0 J3 G2 C" ~2 MThe father would hug the baby and hold him on his/ \' r- n6 o( [4 e. f
chest for a considerable period of time, causing sig-6 d+ z" C: @9 i; [& l5 Y; W- L
nificant bare skin contact between baby and father., u3 {6 u/ C: X* o( h
The father also admitted that after the phone call,
' ^9 m! S/ U* D3 `2 Dwhen he learned the testosterone level in the baby: h9 o( p$ ]/ x
was high, he then read the product information$ t f, K1 v; Y3 ?
packet and concluded that it was most likely the rea-
0 o1 ^+ M& O" Fson for the child’s virilization. At that time, they
' \# [- i& b: udecided to put the baby in a separate bed, and the2 D8 i: h# p" A, K4 v& [& d; ^
father was not hugging him with bare skin and had# S* ]( c, i; m5 ], B9 I' D2 n" s
been using protective clothing. A repeat testosterone4 `; a; J: q5 B) N$ g6 g3 m2 B( n- z
test was ordered, but the family did not go to the
& S. e! Y' O& e. X1 Mlaboratory to obtain the test.3 o; \; E5 A6 b1 U5 q* p
Discussion! f6 n) J) Q! `
Precocious puberty in boys is defined as secondary
+ U! i* F6 t( x) z! Fsexual development before 9 years of age.1,49 K! C H% m& r/ u- g$ P
Precocious puberty is termed as central (true) when
8 D# X R7 D. n {0 x5 X" X7 jit is caused by the premature activation of hypo- c; z8 ]5 ]) D# E/ P
thalamic pituitary gonadal axis. CPP is more com-: [$ M. c5 l0 s: D
mon in girls than in boys.1,3 Most boys with CPP7 v* u' H! a/ N" H9 |
may have a central nervous system lesion that is
* J' F8 G! N2 |/ O+ a0 Aresponsible for the early activation of the hypothal-
0 U# Y2 G. w6 z) Z2 k! _amic pituitary gonadal axis.1-3 Thus, greater empha-
- G% X% p" B- K$ g- Z: H9 Dsis has been given to neuroradiologic imaging in
4 `8 u5 H& b+ j8 v7 U8 P2 Vboys with precocious puberty. In addition to viril-4 I; c. F# Z2 l. @% z0 V
ization, the clinical hallmark of CPP is the symmet-' \5 {6 F7 V0 N7 i& p8 B5 \2 y
rical testicular growth secondary to stimulation by
p# c1 ?- ^6 bgonadotropins.1,3
: }' K# A: }( k: ]" M0 rGonadotropin-independent peripheral preco-- w% h5 o f4 k- G
cious puberty in boys also results from inappropriate
" D# M$ k- Z, |# h; u Dandrogenic stimulation from either endogenous or
/ f2 I6 D, b$ s9 Uexogenous sources, nonpituitary gonadotropin stim-7 j; L7 A& O& {" Q
ulation, and rare activating mutations.3 Virilizing9 a* x. f2 M7 I
congenital adrenal hyperplasia producing excessive
, a, `* v7 q2 c& V8 Z4 t: m" Iadrenal androgens is a common cause of precocious
& W+ c4 T) ?# k1 `, fpuberty in boys.3,45 ^* k' l2 c4 Y+ u8 r; o9 n* A( c
The most common form of congenital adrenal. I) |; b2 P8 j+ L' u
hyperplasia is the 21-hydroxylase enzyme deficiency.
% i1 O5 F3 W- j; I9 aThe 11-β hydroxylase deficiency may also result in, \9 N9 L* a7 t$ f0 V
excessive adrenal androgen production, and rarely,
8 N* a: z8 n6 x# F+ ` {an adrenal tumor may also cause adrenal androgen) K/ X- E0 r# b# g+ P% a" j
excess.1,33 i3 I, l4 K% \$ O7 Q
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542 Clinical Pediatrics / Vol. 46, No. 6, July 2007" I d" D3 H* i( G, J( ^
A unique entity of male-limited gonadotropin-
6 R3 q5 |! p4 O: ?& j& H! uindependent precocious puberty, which is also known
& ]) Z9 z8 T2 b6 a# k6 ^& tas testotoxicosis, may cause precocious puberty at a
) L9 r7 J# r" | X* z1 ^5 ^% Gvery young age. The physical findings in these boys
; N! E% c4 J ~, y. Awith this disorder are full pubertal development,( ~# C& f- u7 e1 f5 ^& i. p! Q
including bilateral testicular growth, similar to boys8 k. O& ?; I) B
with CPP. The gonadotropin levels in this disorder
$ ]! `- X, ~' ], yare suppressed to prepubertal levels and do not show
1 s! P: \3 f1 t: g) f; vpubertal response of gonadotropin after gonadotropin-. |. {4 ?, V' f5 J8 }$ f; N: O$ j
releasing hormone stimulation. This is a sex-linked$ S+ T J# _3 F( ] w3 w
autosomal dominant disorder that affects only
$ X+ k; s* a7 e% d* Vmales; therefore, other male members of the family
% V9 b2 p- C1 lmay have similar precocious puberty.3
5 ^" w6 C& r$ @" s: S4 iIn our patient, physical examination was incon-
1 A! q: o/ Y* q: R5 xsistent with true precocious puberty since his testi-
* j& j1 ^& x% J7 ~2 ncles were prepubertal in size. However, testotoxicosis3 q% t' R# {! G- A6 C
was in the differential diagnosis because his father
6 ]& t4 e8 V% M4 s+ [started puberty somewhat early, and occasionally,0 a3 y4 }/ {- W0 T$ V
testicular enlargement is not that evident in the+ D7 Z9 j2 q1 @# A+ h9 Q) @ \
beginning of this process.1 In the absence of a neg-! f$ `* o' a% [
ative initial history of androgen exposure, our& _/ x, n& X; ^ z7 O" E$ g" l& p
biggest concern was virilizing adrenal hyperplasia,
/ S! U K l0 T. heither 21-hydroxylase deficiency or 11-β hydroxylase( P" n4 z+ z d9 _
deficiency. Those diagnoses were excluded by find-. m) Q' s; L6 M% @) `, ?7 R1 J; f. s
ing the normal level of adrenal steroids.
' l1 e1 [9 r, f! ~1 eThe diagnosis of exogenous androgens was strongly$ M8 b. x4 l7 O$ N: ?
suspected in a follow-up visit after 4 months because
. ^8 q! L2 B# V! E Nthe physical examination revealed the complete disap-
5 x+ u2 z6 t7 y$ ~4 n4 h/ rpearance of pubic hair, normal growth velocity, and
. I5 q+ H, `# { sdecreased erections. The father admitted using a testos-
3 N; p9 i/ Y2 k, wterone gel, which he concealed at first visit. He was/ t$ _2 n6 V! ~4 c- h
using it rather frequently, twice a day. The Physicians’8 @* ^7 m. @% Z
Desk Reference, or package insert of this product, gel or
1 ]+ q7 h& D& rcream, cautions about dermal testosterone transfer to; a t2 p4 g* U5 v5 Z8 g: ?
unprotected females through direct skin exposure.
|6 m1 i# _6 L* pSerum testosterone level was found to be 2 times the
9 K/ _+ E% \6 Y; A' Dbaseline value in those females who were exposed to
" h7 G! M" \5 e; o* [even 15 minutes of direct skin contact with their male
5 z5 K5 e4 D6 Q. S5 k/ l6 Kpartners.6 However, when a shirt covered the applica-
" {( s; ^% a( k; P9 Q6 f0 c8 Btion site, this testosterone transfer was prevented.
3 V4 v1 y1 P+ a" [Our patient’s testosterone level was 60 ng/mL,
9 ?7 Y+ b+ K0 c: a& J9 Pwhich was clearly high. Some studies suggest that6 p4 d: l* T- D+ h7 e
dermal conversion of testosterone to dihydrotestos-
$ e0 I1 a' @8 {3 b: @terone, which is a more potent metabolite, is more! M, A7 t) }. V$ M1 h* X7 i
active in young children exposed to testosterone
- N- w9 t9 e- ]exogenously7; however, we did not measure a dihy-
5 @7 `9 j! N+ b* i. z& A( V& `0 D1 Zdrotestosterone level in our patient. In addition to) j( d1 h, S3 p
virilization, exposure to exogenous testosterone in- J* ^; H1 _1 i) @( _% C* c, M H
children results in an increase in growth velocity and, E g3 i- d+ j) k; k" a4 D$ ^
advanced bone age, as seen in our patient.9 v% B7 m+ D# d
The long-term effect of androgen exposure during# o* q S+ ]3 f: `7 c1 e% \
early childhood on pubertal development and final6 ]9 n3 Y3 v+ Q4 Q
adult height are not fully known and always remain
: d. o' S. i+ t$ p+ N9 r7 L$ s+ pa concern. Children treated with short-term testos-$ x6 x( H4 g3 z% Q
terone injection or topical androgen may exhibit some, ^+ {+ @' A0 [# o5 C! g0 X6 `
acceleration of the skeletal maturation; however, after! i7 C1 g$ c( H
cessation of treatment, the rate of bone maturation
7 S+ I6 n1 ^! J z( x, B- udecelerates and gradually returns to normal.8,9
: u K& O0 w! `8 {. h. n* F5 [+ cThere are conflicting reports and controversy/ Y/ V" b4 \1 k* E a [
over the effect of early androgen exposure on adult
7 \4 ^6 S+ `- A" A% B) r3 Upenile length.10,11 Some reports suggest subnormal
. L; L+ \7 H f$ padult penile length, apparently because of downreg-
) i! Y" J" x9 k+ D+ x2 m4 mulation of androgen receptor number.10,12 However,/ D9 b2 x5 y% P$ u
Sutherland et al13 did not find a correlation between: S9 t4 \* @& K; a( T9 I
childhood testosterone exposure and reduced adult
9 s- a3 q) B* R( G3 g0 qpenile length in clinical studies.
- B4 o) E+ M5 F' g( H1 R2 r8 YNonetheless, we do not believe our patient is
' U3 \! P" r2 m' C) dgoing to experience any of the untoward effects from0 t$ r' C+ v3 D5 G) a* r
testosterone exposure as mentioned earlier because
3 m0 u c3 n2 l- ^7 tthe exposure was not for a prolonged period of time.+ V( A0 c2 p- D$ X7 K$ m
Although the bone age was advanced at the time of/ e, g7 [, Z( E4 F- [4 I
diagnosis, the child had a normal growth velocity at
* C9 F% _: `( G1 M( rthe follow-up visit. It is hoped that his final adult \* @+ p, B5 ?9 z6 V
height will not be affected.
$ r3 U8 ^1 y, I$ NAlthough rarely reported, the widespread avail-3 l" s6 m/ a# n3 G( G& J
ability of androgen products in our society may9 J& L8 a' U* n2 q
indeed cause more virilization in male or female2 b, j& S C9 ?8 L) x
children than one would realize. Exposure to andro-
+ X0 y. U, f. z5 }' K rgen products must be considered and specific ques-
Z- U$ w( m( Xtioning about the use of a testosterone product or6 N2 w, s$ S; c6 {2 J# q
gel should be asked of the family members during# L$ Q8 p. f; `; E4 v
the evaluation of any children who present with vir-% R$ Y' j/ N3 u( c/ T/ ~0 @
ilization or peripheral precocious puberty. The diag-
' B8 j9 D- v5 S4 H2 D4 vnosis can be established by just a few tests and by0 y" c7 i7 k$ |' b" E3 R3 U! ?# f4 ~& H
appropriate history. The inability to obtain such a7 Y( H' c1 b% v/ Y% i8 G
history, or failure to ask the specific questions, may1 A& i$ m5 Q/ z$ U
result in extensive, unnecessary, and expensive
4 n# n+ w9 X/ e! c" ^/ J+ X" T% e2 hinvestigation. The primary care physician should be
8 [) L8 f4 P- y8 taware of this fact, because most of these children5 N5 L1 h2 R7 H9 T
may initially present in their practice. The Physicians’% }& q6 Y; t! w3 b5 L: z! q) D
Desk Reference and package insert should also put a" |9 {5 n2 a7 D$ ?* g
warning about the virilizing effect on a male or' p- P: K$ \! g0 a8 c
female child who might come in contact with some-
, y0 K2 g- l1 n# G% v1 _one using any of these products.7 L3 g# [9 }2 {; w; C: I& \
References
8 r1 i& G% B8 `" J' ^1. Styne DM. The testes: disorder of sexual differentiation
9 F4 A) U x0 o8 cand puberty in the male. In: Sperling MA, ed. Pediatric, v- t5 q. {1 Y- q
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
4 X4 m5 z. [1 Q2 H2002: 565-628.$ f- e9 M/ O# M: E, t! O% E7 B/ `
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious: s# Q4 n7 _( X' Z% c! |
puberty in children with tumours of the suprasellar pineal |
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