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Sexual Precocity in a 16-Month-Old) ~9 a: M( W9 H! i2 g! M" ?8 y% Y
Boy Induced by Indirect Topical
- z+ j% o8 Z- ^0 z N* [Exposure to Testosterone- j- v' K/ L# S1 a1 l6 `3 P
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2. L/ L9 M# q7 p8 U0 E
and Kenneth R. Rettig, MD1: M+ @1 A! [* X0 H& B3 f% _5 I
Clinical Pediatrics' q! w+ Y Q: G# E! z
Volume 46 Number 6
% j! E* [ |- N3 I# j& W5 tJuly 2007 540-543
3 T0 U6 U* k+ }1 b$ W( V9 ]0 s( L8 z© 2007 Sage Publications& p b( C: p1 f
10.1177/0009922806296651, p( I. C0 I4 ?
http://clp.sagepub.com
% e* i) U) t6 y. rhosted at
( M0 W8 n$ z- T+ e4 ahttp://online.sagepub.com2 y4 G( b- p! U$ p! f7 N
Precocious puberty in boys, central or peripheral,9 R1 C$ ^' X4 }7 ~
is a significant concern for physicians. Central
K" N" e3 m) h" }9 e& \precocious puberty (CPP), which is mediated+ q- K5 n& l+ R0 l) U/ @, H6 a- ]& q
through the hypothalamic pituitary gonadal axis, has `) ?# T% l3 u/ d5 c* q7 k
a higher incidence of organic central nervous system( N9 t) A' Y' P* W" _4 l0 y
lesions in boys.1,2 Virilization in boys, as manifested" W6 ?2 E; z2 {, i8 f7 [% o
by enlargement of the penis, development of pubic
! w3 R8 D' y/ q& Qhair, and facial acne without enlargement of testi-
7 B2 Z" {: h, s |cles, suggests peripheral or pseudopuberty.1-3 We0 ?6 a' b, q- r; b( k& g2 e& v
report a 16-month-old boy who presented with the* R/ u8 D- _* K) e; A! q7 X5 q
enlargement of the phallus and pubic hair develop-5 \$ h' p4 Y# J- `8 U v
ment without testicular enlargement, which was due) r7 D# V5 C+ j$ ~
to the unintentional exposure to androgen gel used by) E& c2 j0 v5 W1 h# e
the father. The family initially concealed this infor-
9 c; u2 q( q& \! o9 Hmation, resulting in an extensive work-up for this1 d+ L J4 _$ N9 p
child. Given the widespread and easy availability of
& |4 e! r! m% O8 p: C% h1 |testosterone gel and cream, we believe this is proba-
. h3 O0 y$ i6 ?! Z) `bly more common than the rare case report in the
0 g5 Q1 g* N9 I% r9 ^literature.4( F9 `2 A) y2 ~4 K
Patient Report
@* ~) E, J9 |. `# CA 16-month-old white child was referred to the9 m8 e: R5 y) [$ ?. a
endocrine clinic by his pediatrician with the concern7 a J8 f' {2 Y/ X5 K% `
of early sexual development. His mother noticed" F7 Y5 X; o2 u
light colored pubic hair development when he was
) J! ]& o* j2 D6 m( y* nFrom the 1Division of Pediatric Endocrinology, 2University of
/ T( x# d$ n7 E: ESouth Alabama Medical Center, Mobile, Alabama.
6 P! f- z: }7 A: R/ ~Address correspondence to: Samar K. Bhowmick, MD, FACE,
8 q' E+ y6 ?+ h1 w3 L1 kProfessor of Pediatrics, University of South Alabama, College of. L- p! k% q! ~7 `* W9 E
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;3 J3 |# a& e! q' Z, a' b
e-mail: [email protected].
4 x8 z9 `, M8 i4 fabout 6 to 7 months old, which progressively became
# O# [8 w2 h! c& @ @& Fdarker. She was also concerned about the enlarge-6 e1 i# M! N# V/ k+ H# E/ {
ment of his penis and frequent erections. The child
: J5 Y# O% H3 r3 u, Ywas the product of a full-term normal delivery, with
+ }5 H: C \/ {" m. x% _) }a birth weight of 7 lb 14 oz, and birth length of5 q( K1 V. c; v% z+ n
20 inches. He was breast-fed throughout the first year5 V) E0 d1 l7 E8 x/ z
of life and was still receiving breast milk along with
, x& d8 C& b; q# H ~& G! }6 _solid food. He had no hospitalizations or surgery,; ~! j, r3 u, k3 o3 \
and his psychosocial and psychomotor development& B( Z1 K8 n3 l! |9 Z3 v
was age appropriate.
' b& A1 p2 D- H! r$ uThe family history was remarkable for the father,
! D! H% h6 O/ ~1 M3 o+ @, mwho was diagnosed with hypothyroidism at age 16,
' |: |2 ?8 I: [* `which was treated with thyroxine. The father’s8 n; r" I4 G1 p$ h
height was 6 feet, and he went through a somewhat2 r s$ ]" O! K- O. u: O1 e, k
early puberty and had stopped growing by age 14.7 w0 g9 L q- W3 u3 @0 d
The father denied taking any other medication. The
2 V* Z4 d/ T0 T( [6 \child’s mother was in good health. Her menarche
+ B- i' F" L: x0 F( Vwas at 11 years of age, and her height was at 5 feet7 J6 e6 D6 r* y
5 inches. There was no other family history of pre-
- c8 P' G+ y2 ccocious sexual development in the first-degree rela-
4 B1 n3 e( c2 W! l5 L/ gtives. There were no siblings.3 d4 E' u/ d% y' n# y
Physical Examination
9 |9 }' A" D) G6 i" E# k, jThe physical examination revealed a very active,
+ s- K& x' n8 _5 }( i+ K6 g2 `playful, and healthy boy. The vital signs documented
, Y% w. a# e9 z1 ja blood pressure of 85/50 mm Hg, his length was1 m& `3 V8 b$ `, s. o* [! s- s; l
90 cm (>97th percentile), and his weight was 14.4 kg" K; C/ ?1 P/ u* Q' {3 T Z; c
(also >97th percentile). The observed yearly growth
0 R1 }3 K7 i( ?( W5 u6 f/ L; Mvelocity was 30 cm (12 inches). The examination of3 P/ W& J! k: `
the neck revealed no thyroid enlargement.
$ p% O! i; q7 k, R. DThe genitourinary examination was remarkable for
7 A0 f, @( `% l- M1 X5 Penlargement of the penis, with a stretched length of4 h2 [5 `/ m* B8 z
8 cm and a width of 2 cm. The glans penis was very well
& o {% c0 c: Y6 Z5 X& Ideveloped. The pubic hair was Tanner II, mostly around
, [) U1 H( Y. ~' A$ \' Y4 ~. }540
$ ~; C* G4 c6 x$ t1 p) Wat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from/ A6 u5 d# U- \1 j9 ?4 x7 W( X' ]
the base of the phallus and was dark and curled. The; b) l& H" L; b2 T
testicular volume was prepubertal at 2 mL each.
! \2 H; f9 G# g& ?The skin was moist and smooth and somewhat8 ?8 u; X) L/ H$ C0 v( f3 j
oily. No axillary hair was noted. There were no6 G+ C+ ?* L, D4 Q
abnormal skin pigmentations or café-au-lait spots.
! S! R4 [% x. G) ZNeurologic evaluation showed deep tendon reflex 2+
, o/ D" l7 W: L$ w7 b( ?+ `2 p7 H% ?bilateral and symmetrical. There was no suggestion
0 F- ?+ _0 l* v7 aof papilledema.
% Z8 O# v2 u" G" r( [Laboratory Evaluation( [0 ^+ f6 h; A( W; a
The bone age was consistent with 28 months by
3 Y3 V1 c' `9 s7 ~' X6 G$ t1 zusing the standard of Greulich and Pyle at a chrono-5 E9 i: l" f; i4 l8 y6 u. o$ O# R) z
logic age of 16 months (advanced).5 Chromosomal0 j: J/ g; p v9 O+ A4 A: h
karyotype was 46XY. The thyroid function test
2 Y7 N" D8 m! l0 W9 d. z) m2 ^- W* }showed a free T4 of 1.69 ng/dL, and thyroid stimu-! T0 q; C9 _) G. v
lating hormone level was 1.3 µIU/mL (both normal).
8 X& C+ J! w5 \4 N. ^- c3 B: uThe concentrations of serum electrolytes, blood$ z* s; D5 k' K7 d) {4 j, B
urea nitrogen, creatinine, and calcium all were) _) @2 c+ b* |# i' [, `) @5 u
within normal range for his age. The concentration) {; A8 _5 k* ?7 b5 ?
of serum 17-hydroxyprogesterone was 16 ng/dL( V" G! F0 |5 }+ V
(normal, 3 to 90 ng/dL), androstenedione was 208 U7 G9 R5 `; H. L5 O1 J' n( {
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
: e% Y( X4 a4 k" v! K) t) K: ?terone was 38 ng/dL (normal, 50 to 760 ng/dL),
! Q2 \) c7 [$ r5 Y- Ddesoxycorticosterone was 4.3 ng/dL (normal, 7 to
) i; R! T! `+ z: h8 ]1 o/ Q49ng/dL), 11-desoxycortisol (specific compound S)
* W" g0 E! I; b ywas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
" _) V0 ~- m4 S; v& rtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total! P) ^7 q) B! H% J. @8 J
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),& d- Z" Q0 m4 X& k$ g/ s
and β-human chorionic gonadotropin was less than, ^1 s/ f4 N8 W
5 mIU/mL (normal <5 mIU/mL). Serum follicular
+ A6 j' U. `7 b5 n% Xstimulating hormone and leuteinizing hormone* E% q/ F5 O9 i' _
concentrations were less than 0.05 mIU/mL# N& O1 A6 B/ g: K0 ` g. h5 k* G
(prepubertal).
- [, R1 D; ~# t# G4 Y" M, e# kThe parents were notified about the laboratory: a. W1 o, C4 [0 Z! U) n, |# K
results and were informed that all of the tests were+ Q4 D% W7 _, x$ T* x) g5 a
normal except the testosterone level was high. The" S: Q, j8 x1 g6 A2 @; w% J8 z
follow-up visit was arranged within a few weeks to
8 D4 o: h' m& H6 @" b3 s* V, vobtain testicular and abdominal sonograms; how-
" i W0 g6 U' u6 L+ u& g' {ever, the family did not return for 4 months.
/ P x/ X% c$ x/ m: y! jPhysical examination at this time revealed that the
) ]' ?9 G" e$ @0 C* t. achild had grown 2.5 cm in 4 months and had gained2 k0 ~, ~" z. [
2 kg of weight. Physical examination remained
3 i& ^, w" ~- `4 E" ^2 Vunchanged. Surprisingly, the pubic hair almost com-
$ H8 f- O& j' V" U0 tpletely disappeared except for a few vellous hairs at
% \- U8 a/ w! }( G8 W9 b, othe base of the phallus. Testicular volume was still 2
% U4 }* O1 h$ }' E2 }, bmL, and the size of the penis remained unchanged.
2 H X. q) d+ c6 NThe mother also said that the boy was no longer hav-% |' z5 r& Z, N4 D; S
ing frequent erections.0 {6 H( ?" t$ M! ?
Both parents were again questioned about use of' k* E- V4 j9 N% E: h
any ointment/creams that they may have applied to. B5 _% [% g2 ^7 h7 ~
the child’s skin. This time the father admitted the8 b4 i+ ]+ q' p0 F) {' v6 F; _
Topical Testosterone Exposure / Bhowmick et al 541' G3 G" u2 L1 ~0 E# N4 w
use of testosterone gel twice daily that he was apply-
+ H0 w5 i: \9 j9 u: o1 ]' Wing over his own shoulders, chest, and back area for( u8 {3 R1 V: Z! N5 Y0 c; ^# B: p! e
a year. The father also revealed he was embarrassed
- [1 T) G( t. dto disclose that he was using a testosterone gel pre-
2 U/ o- k- z+ W; K/ a1 L3 Escribed by his family physician for decreased libido- K; h% s/ Z( q5 j v
secondary to depression.
9 O! F1 M5 ~% D0 YThe child slept in the same bed with parents.
7 W6 Y7 U! R8 H6 XThe father would hug the baby and hold him on his" U0 C% X9 R7 n+ o1 v
chest for a considerable period of time, causing sig-' a6 J' r& O" | D1 d6 X
nificant bare skin contact between baby and father.$ C6 X; k" ~# L7 n& N |1 O
The father also admitted that after the phone call,
9 R% ?8 o$ j- R0 M; P8 y# cwhen he learned the testosterone level in the baby
/ c/ Z2 K N, x" a% o$ }! Xwas high, he then read the product information" x) ?: H& r9 V; m
packet and concluded that it was most likely the rea-
0 [5 F' R& Z! k% j+ p! P$ }son for the child’s virilization. At that time, they9 ?) p A: V. k! r
decided to put the baby in a separate bed, and the! V D2 v1 s% n) g7 }! S+ L
father was not hugging him with bare skin and had
7 S/ i+ |3 T/ L+ C, `& }+ e7 k& |! nbeen using protective clothing. A repeat testosterone
6 ?; q7 r! l/ W3 V6 s# \test was ordered, but the family did not go to the! ~' g+ S; ]4 P$ ^! ^- m
laboratory to obtain the test.: b. f0 D' K9 Q3 ~$ e
Discussion- c c* f3 B3 S( A; T
Precocious puberty in boys is defined as secondary
& s' b+ e& Y9 [4 ~sexual development before 9 years of age.1,4
: m0 p+ i/ {& q' KPrecocious puberty is termed as central (true) when6 d1 ]4 P9 _8 o- d" ?6 L
it is caused by the premature activation of hypo-
( V8 D. f' Z. \6 tthalamic pituitary gonadal axis. CPP is more com-- ^: Q9 K$ F2 J+ {
mon in girls than in boys.1,3 Most boys with CPP
) W$ h$ Q6 q7 P0 r& i9 tmay have a central nervous system lesion that is0 Z# S+ ]; x3 @2 A2 c2 ~
responsible for the early activation of the hypothal-
. f2 [+ x4 ]# T$ ~' v/ D3 n7 Hamic pituitary gonadal axis.1-3 Thus, greater empha-
1 Q: D' o. E4 {+ X5 _0 \sis has been given to neuroradiologic imaging in
& L, B" @& @/ ^9 |9 {' `& ?boys with precocious puberty. In addition to viril-1 r3 N U, w8 l# G- v+ ~; r
ization, the clinical hallmark of CPP is the symmet-# F0 N3 k6 O# e% B. Q
rical testicular growth secondary to stimulation by
8 m% c5 a# V7 Ygonadotropins.1,3. d: H5 S& b: p \$ y
Gonadotropin-independent peripheral preco-: V9 u8 z; h! K, t9 s. X% v, l
cious puberty in boys also results from inappropriate; }4 G% l; R8 B. w' I6 z4 [9 v- D
androgenic stimulation from either endogenous or0 t: m5 b9 n/ K! t* h' e; k
exogenous sources, nonpituitary gonadotropin stim-
0 Y( ]$ _- p% ?ulation, and rare activating mutations.3 Virilizing
+ Y) M, P5 v$ Y5 J4 K+ tcongenital adrenal hyperplasia producing excessive# ^1 L. W0 j y
adrenal androgens is a common cause of precocious
5 ]& k! c) D# {9 kpuberty in boys.3,4* C2 F B: s$ L3 O
The most common form of congenital adrenal8 Y) M" N0 T7 u2 Z
hyperplasia is the 21-hydroxylase enzyme deficiency.6 v: J% M3 S1 A
The 11-β hydroxylase deficiency may also result in
' g. R# ] m/ M( C Jexcessive adrenal androgen production, and rarely,3 q+ z0 q' X0 ~. v7 N. I# s9 ^- [ f
an adrenal tumor may also cause adrenal androgen4 n3 i3 a1 B( e, g/ _* ~% r
excess.1,3
5 U1 s1 N) S3 J2 a9 J- ]7 |" |at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
: `/ y& @7 j# I: s+ {! @542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
( O7 m9 \3 J- ?9 b1 W7 ]3 XA unique entity of male-limited gonadotropin-
0 c" a l0 {% h( L$ A$ iindependent precocious puberty, which is also known
1 r2 v8 r, [; T: Ras testotoxicosis, may cause precocious puberty at a
: T) N" E5 F& r& M8 ^. o7 X! a1 Overy young age. The physical findings in these boys! H. L: U3 E0 L! ]0 U
with this disorder are full pubertal development,
: G0 ? v# V/ e7 P7 K/ ]) V- xincluding bilateral testicular growth, similar to boys
: W' V9 J5 L5 ]* M/ ]with CPP. The gonadotropin levels in this disorder
0 F" m! A/ g2 ^5 b. [0 l0 L2 Yare suppressed to prepubertal levels and do not show* [, `( b2 r+ }# _" R; k
pubertal response of gonadotropin after gonadotropin-: x, F. p- n8 d
releasing hormone stimulation. This is a sex-linked& Q- r) O, @. [, E
autosomal dominant disorder that affects only! q; z. P! a1 }$ i
males; therefore, other male members of the family
$ x5 \+ R- L4 z% ^6 f6 g6 n- Kmay have similar precocious puberty.3
& x0 l1 @# g4 d9 _4 ?/ T( V" YIn our patient, physical examination was incon-9 r# L# [% J M1 X7 I- j8 e
sistent with true precocious puberty since his testi-2 V& ~: B, b& M) D1 ~
cles were prepubertal in size. However, testotoxicosis0 Q0 @& f0 h9 X
was in the differential diagnosis because his father8 e q q6 C8 I+ u0 A
started puberty somewhat early, and occasionally,& g' ]. F( ]7 V, T
testicular enlargement is not that evident in the3 S, F- I% v! _
beginning of this process.1 In the absence of a neg-5 a* \ |) c( u+ J, B* v! w; l
ative initial history of androgen exposure, our
% E }% {- W, o, \, b. _! Nbiggest concern was virilizing adrenal hyperplasia,
$ U+ _, E2 }6 _% Deither 21-hydroxylase deficiency or 11-β hydroxylase0 P4 X: z! D: W6 }+ N3 Z
deficiency. Those diagnoses were excluded by find-5 c; A& r: y- f4 t( d3 u6 l
ing the normal level of adrenal steroids.! ^: X) w% S% P& w3 X/ T5 k% R
The diagnosis of exogenous androgens was strongly
& U1 K c l( {. |: xsuspected in a follow-up visit after 4 months because
: o3 }' X6 Z0 v1 s/ U; l; v3 `the physical examination revealed the complete disap-5 ?2 d7 W1 w. C/ k, T: t" o7 t
pearance of pubic hair, normal growth velocity, and
k, s8 @$ o0 ldecreased erections. The father admitted using a testos-) b5 x& J1 N- n( r( o/ I4 N% b
terone gel, which he concealed at first visit. He was
; W% j: R7 A1 d4 M6 r' k" j. lusing it rather frequently, twice a day. The Physicians’
! x) N5 j6 o* ~2 Z; G3 xDesk Reference, or package insert of this product, gel or
, m. J' T- }6 o0 X3 `0 j. Rcream, cautions about dermal testosterone transfer to u8 ?6 ]! ~7 x. y
unprotected females through direct skin exposure.- A9 J& {0 t g, ^
Serum testosterone level was found to be 2 times the
) D: ~" H5 g. H; T3 | q/ W- nbaseline value in those females who were exposed to, E1 U N; W q: z, `
even 15 minutes of direct skin contact with their male
/ F# N* R0 c: s1 lpartners.6 However, when a shirt covered the applica-. @* \3 o/ @2 {! T
tion site, this testosterone transfer was prevented.3 G) l9 k& f$ w8 c
Our patient’s testosterone level was 60 ng/mL,
/ {1 B% e" K& l3 }which was clearly high. Some studies suggest that( y+ [/ i1 H |' R5 {/ f; M
dermal conversion of testosterone to dihydrotestos-
' y9 U c8 B( r) d/ ^" Dterone, which is a more potent metabolite, is more+ L2 g# t% M, y; \. X
active in young children exposed to testosterone
/ f3 {* }# C. B) Y# ~$ Nexogenously7; however, we did not measure a dihy-
0 X& `4 }# P: r$ I: G" }2 [drotestosterone level in our patient. In addition to
, a* W4 \" Y7 S: l1 T0 x: Uvirilization, exposure to exogenous testosterone in
0 |/ t! ]2 r4 Wchildren results in an increase in growth velocity and
/ B |1 h& T3 l9 K- O; Gadvanced bone age, as seen in our patient.3 ], r1 N9 b6 `/ n8 W. c/ t- ^- p
The long-term effect of androgen exposure during
- l) e' e( [ wearly childhood on pubertal development and final
9 C: W' J" @' s5 c7 F" A4 {adult height are not fully known and always remain1 Y- l% y8 g" y$ J, @! ~7 T6 C
a concern. Children treated with short-term testos-
: J6 Q; Z3 a3 z1 \+ H( q; tterone injection or topical androgen may exhibit some
( k& p9 s5 R" tacceleration of the skeletal maturation; however, after
- \& T+ x7 c: i& Pcessation of treatment, the rate of bone maturation
( c8 K1 B& d2 Y& D% C6 y9 |: ^decelerates and gradually returns to normal.8,96 d& p4 c, I( q- ]* e* h( z( _
There are conflicting reports and controversy
! T% Y' j3 V0 J; e4 Q8 z$ a7 Wover the effect of early androgen exposure on adult* v f, L- g s" C, p6 m
penile length.10,11 Some reports suggest subnormal# R7 V/ T& G5 C# U; l
adult penile length, apparently because of downreg-
4 y& C1 D2 I7 O0 M! |ulation of androgen receptor number.10,12 However,
* d4 ?0 c4 _; W, aSutherland et al13 did not find a correlation between0 v5 ?0 |& e" u1 J
childhood testosterone exposure and reduced adult" {' n' J9 Y9 j0 C/ i2 N$ |
penile length in clinical studies.
9 Y; f) P9 [ Y) c0 h& YNonetheless, we do not believe our patient is% `' p, i5 s4 X
going to experience any of the untoward effects from- k9 n4 q' `4 B7 i4 l% r) j
testosterone exposure as mentioned earlier because9 _9 O/ @ { w
the exposure was not for a prolonged period of time.
q3 V( c) R4 r8 c; kAlthough the bone age was advanced at the time of
" Q8 q/ E3 W1 I- z: y% p5 ~0 e1 x8 Zdiagnosis, the child had a normal growth velocity at f0 r* |! C. X3 l9 X
the follow-up visit. It is hoped that his final adult
8 T$ f6 c9 e. ]0 jheight will not be affected.
9 Z" Y0 o' x6 S4 E, L" L- z, gAlthough rarely reported, the widespread avail-+ M6 \* T7 R0 T0 C
ability of androgen products in our society may \# ^& Y) p9 W" Q# a0 N
indeed cause more virilization in male or female
8 t( ^1 T$ g/ {# t( [# ichildren than one would realize. Exposure to andro-* V, Y; ]9 c+ }, V
gen products must be considered and specific ques-
9 ~( I8 {1 j/ G- O' htioning about the use of a testosterone product or
$ H( ^! v1 }. B0 O9 agel should be asked of the family members during5 @1 G+ W4 p/ |
the evaluation of any children who present with vir-
K$ c/ f9 N* X# vilization or peripheral precocious puberty. The diag-9 P, J2 m7 d( l1 V& `1 v0 H
nosis can be established by just a few tests and by
6 K: z% V+ F. X4 K8 ~/ o4 _appropriate history. The inability to obtain such a
. ^" L( {5 U3 Z3 whistory, or failure to ask the specific questions, may
/ @! ?1 N4 V8 _0 z$ {3 X3 wresult in extensive, unnecessary, and expensive
1 y# l$ o' Q' D; R* M! @investigation. The primary care physician should be
: [' }$ F# m& N( Z7 }) D3 ]aware of this fact, because most of these children* Y2 k+ D* b5 w
may initially present in their practice. The Physicians’8 X% w4 r9 _! I/ s& l3 z
Desk Reference and package insert should also put a2 t+ e9 d2 s1 f, ^
warning about the virilizing effect on a male or
4 I& S; L8 ?# _' ^3 B0 M- Nfemale child who might come in contact with some-
0 Y7 {9 O5 Z9 m9 ^; U$ a- k- J2 Done using any of these products.
% ]* @0 ?! P3 j, H* l- A- gReferences1 D, {* |- x1 t* O
1. Styne DM. The testes: disorder of sexual differentiation
: ~5 I( o5 E: Z- ]# Iand puberty in the male. In: Sperling MA, ed. Pediatric
/ G8 ]/ o3 r: P* G; MEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
2 L+ O) g6 a! u& h$ k2002: 565-628.
" q( E$ N. ?" U7 J0 ]2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
' [- n$ R9 n8 E+ rpuberty in children with tumours of the suprasellar pineal |
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