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Sexual Precocity in a 16-Month-Old( [/ }: s$ \+ d4 O4 F
Boy Induced by Indirect Topical9 m, R+ ], k5 H- S; n; p
Exposure to Testosterone! j3 X. ]: j6 ]1 M, y. l
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
! P' Z8 n, `; nand Kenneth R. Rettig, MD1
9 |" ], v- m& s( h; @Clinical Pediatrics
+ S1 j5 n" ]5 k& R/ A) e- ~Volume 46 Number 6
. u0 J+ ?7 J# E% u! j& E: J/ H, ZJuly 2007 540-543
$ E( c( h* \6 w© 2007 Sage Publications6 T( T5 i& K! ]7 H3 v0 b
10.1177/0009922806296651
8 H: d$ h% m! a4 E, x* shttp://clp.sagepub.com- r/ X" e/ R) c4 ^6 R( ^
hosted at# g1 A& W0 V2 z8 |0 G5 x
http://online.sagepub.com$ I( {% J6 p: q0 E- Z- l/ X
Precocious puberty in boys, central or peripheral,
4 z7 n# K5 W6 Iis a significant concern for physicians. Central
" Z" j' Y4 W5 N) U4 ]' Oprecocious puberty (CPP), which is mediated; |# T- _* ~1 l9 x
through the hypothalamic pituitary gonadal axis, has
4 U# ]" |7 U5 Sa higher incidence of organic central nervous system
1 i, j5 ?% \, h4 ]+ }1 s* S7 glesions in boys.1,2 Virilization in boys, as manifested
% J% e5 r) {. v hby enlargement of the penis, development of pubic
2 [; u2 o% u: }- s: a9 Bhair, and facial acne without enlargement of testi-
" `; ]: O3 ]' [2 mcles, suggests peripheral or pseudopuberty.1-3 We7 p. x5 L& U4 u/ h, N
report a 16-month-old boy who presented with the
8 @8 s5 d. z& Q+ v+ c0 Y1 f, H( J( xenlargement of the phallus and pubic hair develop-) r# S% I6 a, h- L* j
ment without testicular enlargement, which was due
8 [( \" m7 `" ]to the unintentional exposure to androgen gel used by! S) ?# ]5 A8 k
the father. The family initially concealed this infor-% T0 i- d: z. U$ m! u8 m" _
mation, resulting in an extensive work-up for this0 l7 Y# |" ^ f7 J2 I
child. Given the widespread and easy availability of' h7 g; ^1 F% f7 ^/ [
testosterone gel and cream, we believe this is proba-
, _/ Y& K! P4 e1 V! T9 \bly more common than the rare case report in the3 u% |: ?- q3 _4 P
literature.4
+ v8 k- C5 @ H& C/ gPatient Report
: U$ A8 G: }, E/ D; ~$ oA 16-month-old white child was referred to the
, }1 m4 y! N1 ~# s" d1 yendocrine clinic by his pediatrician with the concern
% z- n, p' H+ X7 y$ xof early sexual development. His mother noticed4 Z. [) B7 u0 x3 H; T+ e! W0 R
light colored pubic hair development when he was8 x' H( D0 ]; R1 O( i
From the 1Division of Pediatric Endocrinology, 2University of1 n9 F* Q& u8 x& S% M4 ~
South Alabama Medical Center, Mobile, Alabama.
7 n2 X t' `+ {) q* i# u, PAddress correspondence to: Samar K. Bhowmick, MD, FACE,
2 b. O9 }5 O n ?9 @) i' @Professor of Pediatrics, University of South Alabama, College of& d# i* `4 I( @; o4 L5 A
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;) E+ |0 y# n, P6 q
e-mail: [email protected].
# k- y* t- X" H: T8 e- A8 i% l( Oabout 6 to 7 months old, which progressively became
0 K, m4 M) r4 }. g7 p5 Bdarker. She was also concerned about the enlarge-* O8 C$ z t, h
ment of his penis and frequent erections. The child C# G0 O+ }- A2 |. W P! B
was the product of a full-term normal delivery, with3 J$ o+ l' @7 K
a birth weight of 7 lb 14 oz, and birth length of/ M; H7 n4 @0 r0 A5 m
20 inches. He was breast-fed throughout the first year
" N5 b4 }' |* S V: }of life and was still receiving breast milk along with+ r) V$ j" `% g: b
solid food. He had no hospitalizations or surgery,0 W4 Y" J9 p- n& d
and his psychosocial and psychomotor development7 m: T7 b. a5 v4 N. _% E) s5 ]4 F* u# n9 X
was age appropriate.
: M" g T# g. l2 `0 \* NThe family history was remarkable for the father,
7 T3 y2 q# C! P3 M5 Nwho was diagnosed with hypothyroidism at age 16,
# a9 G. X5 g0 H" t) h1 t: I; Owhich was treated with thyroxine. The father’s q9 @9 d/ ` y6 {
height was 6 feet, and he went through a somewhat% d! c/ G1 K9 }& o. t: N1 L
early puberty and had stopped growing by age 14.
. R7 S1 H% I# Y; H7 ]# j. v0 |The father denied taking any other medication. The% m0 f& i1 _1 _
child’s mother was in good health. Her menarche
' w% A$ Q0 j( }2 pwas at 11 years of age, and her height was at 5 feet, b, C n. k ?" _5 v9 d4 ?1 _. y
5 inches. There was no other family history of pre-
, H7 K' A: ?* V; C( p2 J3 m9 [cocious sexual development in the first-degree rela-
4 z* S( A) i3 f6 z+ Y- e) @: S$ ^tives. There were no siblings./ Z0 ?8 M4 g/ p# f* A7 g+ P
Physical Examination
. Z, K7 r, b1 u( r0 m8 h# c# B' xThe physical examination revealed a very active,
, S3 t. c- e, W; D4 Y& t1 Aplayful, and healthy boy. The vital signs documented# N. l1 a! d: X0 u% p7 }
a blood pressure of 85/50 mm Hg, his length was
% G/ h" s% g% k90 cm (>97th percentile), and his weight was 14.4 kg
. o. I% z% W" v* @% ^& P(also >97th percentile). The observed yearly growth
7 V8 g* P3 v, t& e4 Wvelocity was 30 cm (12 inches). The examination of0 [7 {, `$ v4 f" e r+ {
the neck revealed no thyroid enlargement.1 i4 `( F8 B, o, x
The genitourinary examination was remarkable for; c9 r$ Z- K9 [# w( r
enlargement of the penis, with a stretched length of
$ _2 m# c" r4 u; o! U8 cm and a width of 2 cm. The glans penis was very well7 p- e4 M, n* \$ e! d, s# w" v
developed. The pubic hair was Tanner II, mostly around
: ~: D6 A* y4 B2 B5 D$ j! o, y F9 Y0 P540
2 l7 V( p8 z# W- S S- f( \* ?; yat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from' O: Q+ L* d) X4 C" T. E/ v
the base of the phallus and was dark and curled. The0 F+ N3 K( [- K0 R# d u Z
testicular volume was prepubertal at 2 mL each.
* h# G7 o7 L a* _The skin was moist and smooth and somewhat
' _- @) d/ y- g9 Q6 E/ `oily. No axillary hair was noted. There were no- X8 k2 S8 w" t/ z
abnormal skin pigmentations or café-au-lait spots.
% m4 \! B* q! K2 ]1 c8 @7 VNeurologic evaluation showed deep tendon reflex 2+% T/ q7 g7 G* c' K$ w6 i$ l2 C
bilateral and symmetrical. There was no suggestion
2 e. r+ Q$ i8 }9 I5 e3 \of papilledema.2 v$ _5 W, `6 m/ p* N' |1 b" Y! z
Laboratory Evaluation7 p5 g3 F7 @' J4 t# T, ?) T( n& E. ?
The bone age was consistent with 28 months by/ v0 g! W" ~& H$ }5 x' K! S0 L. \
using the standard of Greulich and Pyle at a chrono-
+ _# w7 B" ^: B' b$ H& P3 `logic age of 16 months (advanced).5 Chromosomal
5 y! k- T% A3 b4 h% Y/ n! Akaryotype was 46XY. The thyroid function test- ~4 u: w2 i- w* L% M0 P+ L
showed a free T4 of 1.69 ng/dL, and thyroid stimu-1 y* F" f( B0 l( m
lating hormone level was 1.3 µIU/mL (both normal).
/ p2 b7 X1 _$ s8 S0 U2 _' _The concentrations of serum electrolytes, blood1 d2 W6 }* J6 p8 Q" t
urea nitrogen, creatinine, and calcium all were# ~' M# b- u7 C: |, i3 O9 u
within normal range for his age. The concentration
! B6 D+ q9 A0 V8 y! P6 d7 [. @+ p8 Sof serum 17-hydroxyprogesterone was 16 ng/dL# H3 s8 H! J' W" v8 I1 m
(normal, 3 to 90 ng/dL), androstenedione was 200 p7 L5 Q {2 x# F% U: _
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-" y6 _) I) R6 q2 y* |
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
: W$ v' d3 @/ w( A6 |4 o+ G& I, cdesoxycorticosterone was 4.3 ng/dL (normal, 7 to& c2 f8 T( Z+ L* f" X
49ng/dL), 11-desoxycortisol (specific compound S)" b" K9 y( e- d( @, W, K/ a
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
- d) B" {% S0 t4 [% [9 ztisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
; i F9 v, @' i ytestosterone was 60 ng/dL (normal <3 to 10 ng/dL),3 N2 Z) a% |' Q
and β-human chorionic gonadotropin was less than2 S3 J, g, z- \4 u6 S; l
5 mIU/mL (normal <5 mIU/mL). Serum follicular& Y1 T6 t4 h. M4 i6 G' `9 L
stimulating hormone and leuteinizing hormone
/ v6 [- v8 M) b! z3 p/ G' Z) L( Zconcentrations were less than 0.05 mIU/mL5 T! z; Y0 W% Q8 {4 Q
(prepubertal).
$ P1 W0 z& `- K/ A: OThe parents were notified about the laboratory6 i/ L5 z0 _2 ]+ o
results and were informed that all of the tests were
! O" d( U( K+ E& \+ Y, knormal except the testosterone level was high. The8 z* }- @, A: e1 i+ j7 k# p
follow-up visit was arranged within a few weeks to |/ o* l+ O6 d4 U5 D( B
obtain testicular and abdominal sonograms; how-* u( F7 |/ x) X. |
ever, the family did not return for 4 months.
. [& M7 `( x! X5 Y9 B( tPhysical examination at this time revealed that the
5 i/ E0 Y/ G" d: t4 C5 b8 Q$ Hchild had grown 2.5 cm in 4 months and had gained* g9 `0 f: p, F: z& i H* j
2 kg of weight. Physical examination remained1 c( O; X: e. F5 @2 v
unchanged. Surprisingly, the pubic hair almost com-# x9 |/ B. L- o( `( P2 F
pletely disappeared except for a few vellous hairs at$ [; e- Z; y! m; Q8 Y
the base of the phallus. Testicular volume was still 25 { p K* I% X5 C: h. G
mL, and the size of the penis remained unchanged. c3 A' ?* a! E9 M8 t1 J
The mother also said that the boy was no longer hav-9 t4 }, @+ ?% [3 {+ _: [8 s/ D
ing frequent erections.
/ E6 G3 S9 K' z2 s! UBoth parents were again questioned about use of' F* x. a0 D7 v8 B" P+ a; c
any ointment/creams that they may have applied to O, r9 Y! c7 q( d( |! l7 H
the child’s skin. This time the father admitted the' M5 k8 Y& _/ S/ K& A: w% G
Topical Testosterone Exposure / Bhowmick et al 541
5 _3 x2 P' d, Q B0 m+ ]% y5 S2 T* ` ouse of testosterone gel twice daily that he was apply-3 _2 [* ]) m* i' G9 ~$ [# t
ing over his own shoulders, chest, and back area for
- c7 q3 u4 D: w8 \# ea year. The father also revealed he was embarrassed
! K( l& i- a W, ?2 Hto disclose that he was using a testosterone gel pre-" T/ B t6 M2 x1 j5 N- f+ a t
scribed by his family physician for decreased libido, f( x T% d# M
secondary to depression.) @% I \% R ]8 |
The child slept in the same bed with parents.
9 R2 L" v& c4 f' J8 S% WThe father would hug the baby and hold him on his- ~: i& X; E8 _7 _) o
chest for a considerable period of time, causing sig-
$ L& {( u* ^: a! G/ b( Anificant bare skin contact between baby and father.8 \+ Y0 w- H2 Z4 C
The father also admitted that after the phone call,
( U3 c4 ^ h" R8 _4 h9 d& Dwhen he learned the testosterone level in the baby$ W0 b: [: q- V% U
was high, he then read the product information+ q5 H p f) r+ Z4 S
packet and concluded that it was most likely the rea-3 D+ f# _* _: o2 n; W D" S/ t$ g; Q
son for the child’s virilization. At that time, they; |% x: i0 g5 b! t& a
decided to put the baby in a separate bed, and the5 D3 ?8 C" ~! x3 x
father was not hugging him with bare skin and had/ m/ j+ y& ?+ a! I0 s7 r; Z* S
been using protective clothing. A repeat testosterone" `+ _. Q8 W# W* ?7 P% }6 P
test was ordered, but the family did not go to the
' C! i. o' i( K! W: o) j3 xlaboratory to obtain the test.( U: d3 u) g' m: e7 _$ k
Discussion
1 U$ E5 D, f4 e% nPrecocious puberty in boys is defined as secondary
2 A( s+ J) ]# n. lsexual development before 9 years of age.1,4# c! b6 c0 I' X" I+ Q6 g5 Q
Precocious puberty is termed as central (true) when
$ g* E5 \0 h; c( o: v4 O$ g o, k7 [: Fit is caused by the premature activation of hypo-
1 ^2 x2 N8 y) Y+ {4 p9 Bthalamic pituitary gonadal axis. CPP is more com-- [& _( y h9 |9 G# L
mon in girls than in boys.1,3 Most boys with CPP. B: V' q2 H9 a- t/ D+ [& l. Q
may have a central nervous system lesion that is" v8 z: ~! R+ n. O
responsible for the early activation of the hypothal-
Z Z! _; H2 ~amic pituitary gonadal axis.1-3 Thus, greater empha-
' Z/ g7 ?% L: e2 M1 esis has been given to neuroradiologic imaging in" Y: U! h& V- I9 H0 s1 M5 B
boys with precocious puberty. In addition to viril-
3 `! N7 B9 ?0 w* Q/ m1 b. w4 Rization, the clinical hallmark of CPP is the symmet-
1 W: F7 U9 p- U6 lrical testicular growth secondary to stimulation by
# ~( w# U, K' p ], B ^! ggonadotropins.1,3
* ~( t; {* a3 |* d- k! kGonadotropin-independent peripheral preco-
9 T1 d! k3 \3 E& Kcious puberty in boys also results from inappropriate
8 W9 q4 P; x+ p5 sandrogenic stimulation from either endogenous or& Z+ S# Z6 h4 m' t" j
exogenous sources, nonpituitary gonadotropin stim-
4 D) E3 R3 w% X" Julation, and rare activating mutations.3 Virilizing0 J: L4 h x$ B$ I8 X4 q# i% q9 u, O/ l
congenital adrenal hyperplasia producing excessive
: N; B- K; N: |2 w9 X e0 e. Tadrenal androgens is a common cause of precocious
' P6 s- U O& i' Gpuberty in boys.3,4
7 S5 |8 G/ H$ xThe most common form of congenital adrenal
4 T/ O! X, _9 v' ]; W: ]hyperplasia is the 21-hydroxylase enzyme deficiency.
4 q$ P) I1 z" P: K HThe 11-β hydroxylase deficiency may also result in- ^9 q, r( I7 h% s5 r
excessive adrenal androgen production, and rarely,
3 h1 f1 l [5 ]* M i9 d& van adrenal tumor may also cause adrenal androgen" R2 ~1 `* d* U% q
excess.1,3
# p# O5 E, E0 [at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from4 R2 n; w" \6 ~2 @* _+ ]
542 Clinical Pediatrics / Vol. 46, No. 6, July 20077 r9 V5 H2 ^6 o. t: }! j4 s. `
A unique entity of male-limited gonadotropin-% |. @' ^( T* F) a8 r
independent precocious puberty, which is also known a8 @$ Q* [+ t4 a
as testotoxicosis, may cause precocious puberty at a
p1 j- M. f$ D: }very young age. The physical findings in these boys
1 l; ^: Q2 T6 t# q$ L3 `with this disorder are full pubertal development,
) h# q. Y# x c/ r8 O1 cincluding bilateral testicular growth, similar to boys1 W4 K8 K; W9 } C: `
with CPP. The gonadotropin levels in this disorder
" D! B! a0 k& e+ Xare suppressed to prepubertal levels and do not show7 o* v* ]/ r, S: d5 h w
pubertal response of gonadotropin after gonadotropin-
4 V" Z* s6 z$ i/ t( q" E- Rreleasing hormone stimulation. This is a sex-linked
0 i% f$ e$ O/ |" @" U qautosomal dominant disorder that affects only
3 }* l# I. Q# X! _; qmales; therefore, other male members of the family: Z7 F+ ]0 v+ U3 O7 Q8 I
may have similar precocious puberty.3
. A |" `8 t9 Q+ B* fIn our patient, physical examination was incon-" ~+ B& g# s! ?/ G* b/ t# w
sistent with true precocious puberty since his testi-# f$ k* z3 E6 Z( X% Y8 A5 M* Y9 N
cles were prepubertal in size. However, testotoxicosis
6 G3 C0 [+ T$ m# a% E( `1 rwas in the differential diagnosis because his father
. m8 j% m' E* e+ d6 @) sstarted puberty somewhat early, and occasionally,
* i, W9 D& W& O2 Htesticular enlargement is not that evident in the
0 P) [2 ~0 N5 _( {( k5 t, Y6 ]- Jbeginning of this process.1 In the absence of a neg-( v9 V. T' u) m7 B
ative initial history of androgen exposure, our! x- T) _" L: T6 I+ \5 m
biggest concern was virilizing adrenal hyperplasia,
' U3 S$ w$ a( Leither 21-hydroxylase deficiency or 11-β hydroxylase
- @1 \" x {* d8 N: Kdeficiency. Those diagnoses were excluded by find-
2 a/ d1 H/ v) Jing the normal level of adrenal steroids.& \7 U7 p( e- c$ b% K1 y* f8 J
The diagnosis of exogenous androgens was strongly0 q: @6 U5 e$ b% l3 @
suspected in a follow-up visit after 4 months because% G: @& r8 T# W$ Y
the physical examination revealed the complete disap-
+ m6 ^ S9 T, q1 Y% O8 Y9 [8 Hpearance of pubic hair, normal growth velocity, and
/ i, `* _, P8 g2 ndecreased erections. The father admitted using a testos-
7 O+ ]/ i' V% `* e+ d+ q$ |terone gel, which he concealed at first visit. He was% v) ~+ J @6 @9 i& G/ _5 y
using it rather frequently, twice a day. The Physicians’
2 Q* j, ]5 X! W( HDesk Reference, or package insert of this product, gel or. n+ B/ g. C+ W6 s _6 Q& Q
cream, cautions about dermal testosterone transfer to9 w* B- X2 z6 \. o4 g" _. V- {/ S
unprotected females through direct skin exposure.- U7 [0 q7 x& r! }6 T' u& p5 |4 H
Serum testosterone level was found to be 2 times the
$ H0 R" b; P7 \7 Qbaseline value in those females who were exposed to# n9 h* f1 _+ u4 R v
even 15 minutes of direct skin contact with their male
5 j+ ]( |. M$ K' [5 X; _/ Rpartners.6 However, when a shirt covered the applica-. V9 x3 m# w4 K/ f4 F3 c
tion site, this testosterone transfer was prevented.% p2 s1 z$ [! \
Our patient’s testosterone level was 60 ng/mL,
5 j8 F$ L# i$ X( Twhich was clearly high. Some studies suggest that
# R2 x1 {4 m% F N6 q, |dermal conversion of testosterone to dihydrotestos-! n2 v, ^7 u* T7 [2 p0 T9 R6 E
terone, which is a more potent metabolite, is more N: v0 f) k& e) X
active in young children exposed to testosterone2 \5 L1 h8 u# E! D1 M7 B
exogenously7; however, we did not measure a dihy-- F# n$ w: N8 n$ W/ ^
drotestosterone level in our patient. In addition to ?8 n+ H, M7 d
virilization, exposure to exogenous testosterone in
* J" g4 ^# q- Lchildren results in an increase in growth velocity and* J- Y- ?$ S( v
advanced bone age, as seen in our patient., c( ]6 o- J# A1 j
The long-term effect of androgen exposure during
/ m7 E2 o4 p9 F, jearly childhood on pubertal development and final
9 E2 V4 } \% A( v0 C8 v3 _2 Gadult height are not fully known and always remain% o! W% z6 E# \" l; Q; P
a concern. Children treated with short-term testos-) E0 N& {: G5 T2 V" j% l+ ^
terone injection or topical androgen may exhibit some
& h+ e# U' H0 T1 s* C' ^acceleration of the skeletal maturation; however, after* V. Q. |0 t5 C& i9 |; r9 T+ o
cessation of treatment, the rate of bone maturation
5 k! c" ^& n/ X/ B2 z$ ddecelerates and gradually returns to normal.8,9. m: M- ]2 G$ V1 I- b0 m# |' v' X
There are conflicting reports and controversy* R8 H# \9 K& f7 k
over the effect of early androgen exposure on adult) S) P6 v2 r& w& v. Z* k& K0 d* _
penile length.10,11 Some reports suggest subnormal
! L( l% t2 G( k. U8 Gadult penile length, apparently because of downreg-
4 z' n, _6 c% B1 ], Q. fulation of androgen receptor number.10,12 However,
9 ^$ K( N) ~% JSutherland et al13 did not find a correlation between
) i# D0 f2 f) A: w! D3 [childhood testosterone exposure and reduced adult
" l2 ?' \2 ?3 y% ~, C- t% b, Ppenile length in clinical studies.& R7 u3 H, l' ~3 d) t6 \' s
Nonetheless, we do not believe our patient is; |0 o: v0 Q& |6 f: o; B G
going to experience any of the untoward effects from
, X" Z9 X& ]+ k. d* ctestosterone exposure as mentioned earlier because/ |: n8 }% _) |8 S ~( w3 w% ^
the exposure was not for a prolonged period of time.
5 t- D8 }5 ?" C9 |Although the bone age was advanced at the time of* e) s- w u, j( R, ^
diagnosis, the child had a normal growth velocity at" q7 W5 }; M; j9 Z
the follow-up visit. It is hoped that his final adult
( M! [1 p3 d& z% l6 e3 Aheight will not be affected.& T8 q3 ~ E$ Z* M( q
Although rarely reported, the widespread avail-
2 j5 y ^# ~1 c8 Xability of androgen products in our society may
( U/ b I* t# w( {; Iindeed cause more virilization in male or female" U4 h9 p8 h5 P. m1 t4 j
children than one would realize. Exposure to andro- |& G" k4 Z( Z
gen products must be considered and specific ques-1 ]7 W9 F; T' f: e
tioning about the use of a testosterone product or" c$ B E4 h7 c; w% s# h
gel should be asked of the family members during# d4 r8 k1 r* B% T) U
the evaluation of any children who present with vir-& i, y# J# E) l& p9 i' h
ilization or peripheral precocious puberty. The diag-
2 K, \! R$ i% Fnosis can be established by just a few tests and by2 N! h7 x1 T3 M- W0 Q0 X: h/ X
appropriate history. The inability to obtain such a% e/ d* ?$ x3 o; k2 q3 p0 G4 h( P. M
history, or failure to ask the specific questions, may
( B( F' Z. }2 M, hresult in extensive, unnecessary, and expensive
8 R$ @3 \. g+ u: m( }5 D/ c cinvestigation. The primary care physician should be# a7 ]% q$ k" H6 ^! l
aware of this fact, because most of these children
( m6 G+ G3 q3 Q7 k7 u/ J- hmay initially present in their practice. The Physicians’, n& r% `; A+ }
Desk Reference and package insert should also put a" O, [5 R' [* c: i/ ]
warning about the virilizing effect on a male or$ N% V2 X& p0 M8 d
female child who might come in contact with some-
! Q s5 E2 t# c# a8 z M: Oone using any of these products.+ p. Y% s6 u% D7 _4 K
References
& [3 `: N, ]6 H. R; @ Q/ t1. Styne DM. The testes: disorder of sexual differentiation4 {4 `& w# R2 {9 e5 \7 o$ D7 Z
and puberty in the male. In: Sperling MA, ed. Pediatric
9 q4 Z, v" F; Z$ t9 OEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
- \7 E: t" k: \, P2002: 565-628.
: e# {0 }+ J2 [1 v4 i, q+ [& `, _! @2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious: b! N, p& X+ x
puberty in children with tumours of the suprasellar pineal |
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