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Sexual Precocity in a 16-Month-Old4 | v8 n1 a R
Boy Induced by Indirect Topical
! ?! j* `. p; D0 |- QExposure to Testosterone1 ]: u6 A* m u# ?4 F8 {
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2+ C3 w2 Y7 m$ @2 p$ ]$ a, D3 ]& R
and Kenneth R. Rettig, MD1) E ^# _7 K0 b V' u% c9 l
Clinical Pediatrics
7 U& h V5 t( Q. P* [/ y, J- ?" TVolume 46 Number 6. O+ }. V7 {% O2 i
July 2007 540-5438 U# O- R) {) x+ z; u) K: s0 y/ S
© 2007 Sage Publications3 t' D- Q: \3 @4 z
10.1177/0009922806296651
/ a: v) E3 z7 C$ Ohttp://clp.sagepub.com- D# a8 ~1 L7 j% f# t, ~* ^$ g. l
hosted at
' b0 [8 ^1 f/ A4 K$ H& y" Xhttp://online.sagepub.com ]5 r [- D; c
Precocious puberty in boys, central or peripheral,& m5 @0 ^9 u$ W4 M* ` V& A
is a significant concern for physicians. Central
( |! z3 s( d1 L; l5 i/ Tprecocious puberty (CPP), which is mediated
* q: \+ a% o; L! G3 m9 y) Othrough the hypothalamic pituitary gonadal axis, has
+ }, G, i4 q$ r* A, d: L0 W2 e$ x6 l4 _a higher incidence of organic central nervous system
5 b0 b& I& b; e g0 ylesions in boys.1,2 Virilization in boys, as manifested. Y c9 q1 D" s0 m* P$ `
by enlargement of the penis, development of pubic
- {( q# Q8 J; J3 thair, and facial acne without enlargement of testi-
+ U! q% B- E0 C* I' Scles, suggests peripheral or pseudopuberty.1-3 We
% V' G7 @" h4 Jreport a 16-month-old boy who presented with the- ^! L" r6 O5 l/ G# A) @& R
enlargement of the phallus and pubic hair develop-5 z& q# L1 w+ h; N
ment without testicular enlargement, which was due
+ @1 {: U. J3 Z: Wto the unintentional exposure to androgen gel used by5 I/ w( n0 p$ M% y
the father. The family initially concealed this infor-
j" h& Z4 O9 x; F9 t7 }mation, resulting in an extensive work-up for this
! X; g6 D- Z1 d: q" Echild. Given the widespread and easy availability of' |7 B; o: |' B7 a: _
testosterone gel and cream, we believe this is proba-
* l4 u" B# ?$ R) P4 X5 Nbly more common than the rare case report in the
. e" h6 j2 L1 {% {" P8 H/ [, U/ zliterature.4. d8 E. q+ m" W: _; f7 s
Patient Report$ O* y- {; f) T
A 16-month-old white child was referred to the- O+ u3 z2 p& I( _) _4 H0 w% V
endocrine clinic by his pediatrician with the concern
2 \4 Q8 u" m* Bof early sexual development. His mother noticed
b; l% I% N" Qlight colored pubic hair development when he was/ u% o2 s5 }5 K/ Z
From the 1Division of Pediatric Endocrinology, 2University of
2 V. h, V) c. NSouth Alabama Medical Center, Mobile, Alabama. ?1 g" B$ W" y! v7 r, Q9 d
Address correspondence to: Samar K. Bhowmick, MD, FACE, P6 @( a1 W+ D5 D! @, m5 w: x# j8 n( W
Professor of Pediatrics, University of South Alabama, College of
1 \; u1 T# E$ d) a8 Q: K: G. kMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
2 J" y: K0 [8 k+ |3 ?1 Ce-mail: [email protected].
' B* j' X$ a5 jabout 6 to 7 months old, which progressively became
, K$ L, j* o: V- Edarker. She was also concerned about the enlarge-
! D. ]: \) A8 @1 p; Tment of his penis and frequent erections. The child' w% N7 t) A0 @8 X3 r! Z% c
was the product of a full-term normal delivery, with! ]6 w; Y8 ?/ P; a* a: ~
a birth weight of 7 lb 14 oz, and birth length of( `; G8 y V6 d. c/ t5 Z
20 inches. He was breast-fed throughout the first year
; f. ]4 { D; ?0 m5 L/ K$ fof life and was still receiving breast milk along with
* V9 K" h/ l. z [+ w) dsolid food. He had no hospitalizations or surgery,
8 E* v/ j6 y( l. eand his psychosocial and psychomotor development
# i' c! v9 B/ S- K, T3 Y/ [was age appropriate.
# d4 K: m- w6 k6 B" `The family history was remarkable for the father,
/ p+ B2 L9 r1 _! Z, j% h$ Twho was diagnosed with hypothyroidism at age 16,' [% B) x* y0 U/ |2 V
which was treated with thyroxine. The father’s1 ]. Z& y$ R1 ^ J9 D+ [
height was 6 feet, and he went through a somewhat
' v4 s: m. e6 u8 W, i& I6 Rearly puberty and had stopped growing by age 14.
& {1 S9 s1 {) V6 D8 G& O4 }The father denied taking any other medication. The
: ]6 H+ B8 b: ^- Lchild’s mother was in good health. Her menarche+ M+ z0 k1 @( l" s
was at 11 years of age, and her height was at 5 feet& t* N& G' S! e1 W1 R" X
5 inches. There was no other family history of pre-# y. {( r1 Y3 \+ _) K0 H' {- J# ^
cocious sexual development in the first-degree rela-
# b" p! e T/ j0 P$ U! W. ]tives. There were no siblings., T' |4 Z# u, s J$ s, P
Physical Examination+ o* o! v& x$ P$ ^! p* J4 c
The physical examination revealed a very active,
% i7 [, }- I9 _% @1 y4 iplayful, and healthy boy. The vital signs documented
i- S! a0 o" e2 E5 s; }a blood pressure of 85/50 mm Hg, his length was
0 }2 g# J) ?+ T6 r; C" c90 cm (>97th percentile), and his weight was 14.4 kg# h! \4 S& ^; O7 [ z- f( j: _) ^
(also >97th percentile). The observed yearly growth
$ I! P$ g8 L" Bvelocity was 30 cm (12 inches). The examination of9 W) U; D% ]( }) m m3 o6 T3 J$ n
the neck revealed no thyroid enlargement.: [, u; C6 ]* x4 G+ v
The genitourinary examination was remarkable for
, q# M, |- j5 f" O3 S8 \enlargement of the penis, with a stretched length of
0 |1 H& u7 {2 J. @8 cm and a width of 2 cm. The glans penis was very well
}, r; l" W D8 M) G% j V$ xdeveloped. The pubic hair was Tanner II, mostly around; }4 ?8 e" Z9 `: b- G0 \
540: O/ V# G9 \; W* Y
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
1 a: h/ @$ _8 S4 M& Jthe base of the phallus and was dark and curled. The
* n1 P3 ?$ E4 ~3 @: C- ]testicular volume was prepubertal at 2 mL each.
( C, d5 i# d) f/ |( u9 E7 uThe skin was moist and smooth and somewhat, c& U- g1 A! v' U& w7 [
oily. No axillary hair was noted. There were no
, S6 P; r, Y# j* q# gabnormal skin pigmentations or café-au-lait spots.
+ l% C0 J8 W2 ~( E# ^6 m8 ]Neurologic evaluation showed deep tendon reflex 2++ k6 j; h, ~# O6 T% X$ f# l
bilateral and symmetrical. There was no suggestion2 H9 L) v f7 ~" p
of papilledema.
! T9 P6 ]+ P" iLaboratory Evaluation3 @. ]0 B6 P$ D( x; J7 k( _9 x2 i
The bone age was consistent with 28 months by) w& ~5 g+ B2 ^) |# h/ J& C
using the standard of Greulich and Pyle at a chrono-
$ ?% o( Y+ X' k) x5 {$ klogic age of 16 months (advanced).5 Chromosomal" l3 R6 h( k6 w8 H- K B! m; B
karyotype was 46XY. The thyroid function test
8 v8 v! c- ~3 I1 q3 h4 C! Lshowed a free T4 of 1.69 ng/dL, and thyroid stimu-) ]1 a0 U, M2 ~7 }& b' s/ Z' H
lating hormone level was 1.3 µIU/mL (both normal).
* A6 u8 ~2 x# W; VThe concentrations of serum electrolytes, blood
4 V) ~ o! V% H, y3 B. R3 Wurea nitrogen, creatinine, and calcium all were
. ?' r0 _% H1 Q( ^within normal range for his age. The concentration* W& q) z: m/ E8 L1 L
of serum 17-hydroxyprogesterone was 16 ng/dL+ _6 w/ X9 E, E/ w7 K
(normal, 3 to 90 ng/dL), androstenedione was 20
% I# B8 ?: u% R9 ]+ x; Yng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
4 B2 @8 h* ^6 w* iterone was 38 ng/dL (normal, 50 to 760 ng/dL),
6 N- V. F; l: H9 b, T2 V. \, Xdesoxycorticosterone was 4.3 ng/dL (normal, 7 to, ] r" O; R* O+ a4 j
49ng/dL), 11-desoxycortisol (specific compound S)& x) e6 M6 B8 }; G7 c6 J
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-" s+ N5 ?$ U! ?. G# J" p! B
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total7 k" m, _8 K, w3 u9 x2 q, o
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),4 h2 T- e# y7 V; J) G
and β-human chorionic gonadotropin was less than
) r5 n) B" \5 [ X. g5 mIU/mL (normal <5 mIU/mL). Serum follicular
+ Q, O, K1 X. T8 p6 [stimulating hormone and leuteinizing hormone ?) a% B( B4 a7 v4 {# F
concentrations were less than 0.05 mIU/mL
$ Q4 A" d; X% @# W3 |+ R* c8 Q(prepubertal).( o) j; G6 `. d6 w& t8 X; f: w* }
The parents were notified about the laboratory
7 u% F { U/ R3 B% gresults and were informed that all of the tests were
% b) A0 j3 Q8 R' Tnormal except the testosterone level was high. The
( C/ L7 a; @* mfollow-up visit was arranged within a few weeks to& |0 Y& x6 J- \# \+ O/ Q
obtain testicular and abdominal sonograms; how-
0 c* K! I* |& X5 o* n( s9 _* i' jever, the family did not return for 4 months.4 R0 p1 v9 r& Z9 H) j1 X" Q
Physical examination at this time revealed that the& d I3 [% ?$ N/ k9 p
child had grown 2.5 cm in 4 months and had gained/ O4 o- J8 d( K, [; F2 f
2 kg of weight. Physical examination remained# M, M2 H8 ]& b. v: G/ O" T% t
unchanged. Surprisingly, the pubic hair almost com-
2 h& M5 {0 \" v# Z' T- p d1 t% qpletely disappeared except for a few vellous hairs at
, k$ |* g7 a, othe base of the phallus. Testicular volume was still 2
9 @7 f2 {! v1 g4 m, KmL, and the size of the penis remained unchanged.3 ?" O- `6 H) G' B( {) c
The mother also said that the boy was no longer hav-) M: }2 X7 v4 z9 E) g
ing frequent erections.
) q0 ]! C& [5 Q9 J9 FBoth parents were again questioned about use of! w! n3 n- _- |9 V! R4 _4 p; t7 H* d
any ointment/creams that they may have applied to
, k' j! J, C0 g" I7 hthe child’s skin. This time the father admitted the: Y" ^6 k) x' M0 V4 o# S* K
Topical Testosterone Exposure / Bhowmick et al 5412 K, T6 `( ?, G- [9 K
use of testosterone gel twice daily that he was apply-
. {! S, t( K. U2 M% Xing over his own shoulders, chest, and back area for7 H4 w& }' p6 ^7 q. i
a year. The father also revealed he was embarrassed
" I4 K! n; `7 @4 W9 p+ {) Fto disclose that he was using a testosterone gel pre-
7 L3 }8 }+ ^, r6 H2 m8 S: Wscribed by his family physician for decreased libido
) m$ [% S8 T! ]0 ]9 Z: B" w, r& Csecondary to depression.
+ W* ?- R) D$ J% |0 v. ^$ mThe child slept in the same bed with parents.
% K6 A; L2 i8 D& {The father would hug the baby and hold him on his P* h9 s9 w* X' A9 W
chest for a considerable period of time, causing sig-
0 O* @8 v/ |0 J0 Unificant bare skin contact between baby and father.' D) A" c1 K* l O# b4 x
The father also admitted that after the phone call,
7 C7 i) s: J( |- e+ r, N( A6 Jwhen he learned the testosterone level in the baby
* k; |! p6 s6 c3 f/ ]' Z# v3 ~6 ?8 Swas high, he then read the product information
! y: x4 f0 g4 H+ `6 r8 V! |0 i& ppacket and concluded that it was most likely the rea-
1 v" o8 Z9 H3 w- }* Zson for the child’s virilization. At that time, they
/ I# l! w9 E/ H5 f, \5 t8 fdecided to put the baby in a separate bed, and the0 v( o5 f; _& i& h$ _; J4 u
father was not hugging him with bare skin and had& \2 r4 |% N) A0 g1 X2 p/ a( O
been using protective clothing. A repeat testosterone1 q d/ U* s9 [* k) L
test was ordered, but the family did not go to the
/ N# M* g+ d0 ^6 F4 Flaboratory to obtain the test." Y! e8 p% [4 ]9 a2 C3 ?
Discussion' J$ n0 y3 \" {3 [+ \. _. A
Precocious puberty in boys is defined as secondary0 v3 U! ]0 F8 y/ ~: _* |
sexual development before 9 years of age.1,4
, ^- j; Q/ h3 a bPrecocious puberty is termed as central (true) when
& @' ]$ f5 ~. ^# ait is caused by the premature activation of hypo-
6 N. I, _, I, @. P4 s4 a" g1 j- n0 Rthalamic pituitary gonadal axis. CPP is more com-5 H6 U1 S4 \1 m' m1 N
mon in girls than in boys.1,3 Most boys with CPP
' Y. [9 `" y4 }5 }! Pmay have a central nervous system lesion that is
+ s. k" H( I+ Z* G L7 w& qresponsible for the early activation of the hypothal-
1 a% H4 Z# ~, t( ~amic pituitary gonadal axis.1-3 Thus, greater empha-' `5 W$ U+ ]) u# X0 @: c' p% I
sis has been given to neuroradiologic imaging in
1 ]& T9 V3 d( P8 g- z+ n% hboys with precocious puberty. In addition to viril-9 Z& O" ~% m6 i
ization, the clinical hallmark of CPP is the symmet-
, {+ B! ?2 H7 E9 o. B5 Vrical testicular growth secondary to stimulation by
0 U% B9 W! l: I0 b* q5 agonadotropins.1,3
; d- {' X6 v1 r# Z6 H, g+ zGonadotropin-independent peripheral preco-
+ j/ g* _3 P0 Z7 O1 Q. @cious puberty in boys also results from inappropriate2 q7 x: \8 t2 |# H. o
androgenic stimulation from either endogenous or
4 j6 }# f5 s* o7 k6 uexogenous sources, nonpituitary gonadotropin stim-
) u6 L: d0 P+ [; Wulation, and rare activating mutations.3 Virilizing: ]8 M+ m6 Y6 x9 f3 w. W
congenital adrenal hyperplasia producing excessive& t6 ~! M) {$ M0 I
adrenal androgens is a common cause of precocious1 U/ ?9 F$ U4 w- A
puberty in boys.3,4
2 L% y, M% N) S2 C: gThe most common form of congenital adrenal
1 J y6 L* Q4 X3 T* D5 i$ Thyperplasia is the 21-hydroxylase enzyme deficiency.: e5 z; X3 G: h
The 11-β hydroxylase deficiency may also result in
$ I/ y! m9 q; T. p# Pexcessive adrenal androgen production, and rarely,9 p t' o' J0 S. y6 V* M
an adrenal tumor may also cause adrenal androgen, H! F2 p2 F& I$ B
excess.1,3
& z0 k4 v+ m, N4 ^at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
; [* c5 Y, C7 w5 s* C7 K542 Clinical Pediatrics / Vol. 46, No. 6, July 20074 B8 N" @" C# O$ M0 V) O8 K
A unique entity of male-limited gonadotropin-" c+ _+ O7 S U5 K3 h* K& @
independent precocious puberty, which is also known' u0 u8 ^2 S, }& t
as testotoxicosis, may cause precocious puberty at a/ Y3 p7 T5 o% ~2 D% |
very young age. The physical findings in these boys
; r; A+ _" B7 q* mwith this disorder are full pubertal development,
6 h, [. m# k' `+ p4 H4 Sincluding bilateral testicular growth, similar to boys" v+ q5 ]! ]2 V. v5 j) C" G
with CPP. The gonadotropin levels in this disorder
* {' d* E( ?, [! u: I1 Nare suppressed to prepubertal levels and do not show3 m7 C( m# k) L: l
pubertal response of gonadotropin after gonadotropin-: B0 [4 c1 l9 p9 f' ^4 T5 D$ t
releasing hormone stimulation. This is a sex-linked. B2 |/ ]1 T# y9 N9 \2 ~
autosomal dominant disorder that affects only
$ g, u' A! H5 N$ ?8 X) k9 Umales; therefore, other male members of the family$ E7 L4 K4 E& z
may have similar precocious puberty.32 r" D3 ]$ G+ ]% o
In our patient, physical examination was incon-1 h1 Q$ m; x1 u$ A$ r+ L
sistent with true precocious puberty since his testi- H' J3 r$ T# y
cles were prepubertal in size. However, testotoxicosis9 P4 ^2 P6 H3 ?$ n" p
was in the differential diagnosis because his father5 [9 ]5 x3 H. `; s2 S; Z S
started puberty somewhat early, and occasionally,' I. d* t1 Y9 D7 z4 J" _
testicular enlargement is not that evident in the
) z# x8 s" p5 H. vbeginning of this process.1 In the absence of a neg-
, t5 i/ B+ u! r0 v1 Z2 dative initial history of androgen exposure, our
. |3 y1 {) m( B& U, {; D2 c8 abiggest concern was virilizing adrenal hyperplasia,
`+ {) W; a5 {1 w1 _8 Feither 21-hydroxylase deficiency or 11-β hydroxylase
5 w4 C; n7 b6 f* Pdeficiency. Those diagnoses were excluded by find-
) o- u& y3 c. n6 C% W" n' }) Fing the normal level of adrenal steroids.: f! r$ W* }0 G' z# K4 C* d" _1 W% {
The diagnosis of exogenous androgens was strongly7 y5 L& [3 D; ]9 l
suspected in a follow-up visit after 4 months because( F0 m' i9 o- L. V( _8 E7 Q+ G
the physical examination revealed the complete disap-) W& O7 Y" k. T# w. _) x' ?
pearance of pubic hair, normal growth velocity, and& _/ f0 `' Z3 x0 E. r
decreased erections. The father admitted using a testos-4 P, O+ R" |9 D2 O: H* C7 E( r
terone gel, which he concealed at first visit. He was# H+ ]- f9 Q3 O9 v; f% B' x
using it rather frequently, twice a day. The Physicians’/ g- D# S" @, U, `1 r* h) P
Desk Reference, or package insert of this product, gel or
e8 j( N4 }' c3 H! }cream, cautions about dermal testosterone transfer to. J3 p/ x6 O9 n% a$ `7 i
unprotected females through direct skin exposure.
: H- Z' U- O# B* S7 |3 D+ \( T2 q3 m" NSerum testosterone level was found to be 2 times the& C& |: O Z" Z
baseline value in those females who were exposed to
4 G0 N+ p6 E8 t3 \, |even 15 minutes of direct skin contact with their male6 ~& k3 c9 u1 p9 Q6 }0 o, q1 W
partners.6 However, when a shirt covered the applica-
; i/ W6 F! V' E* a7 }tion site, this testosterone transfer was prevented.
. z0 _: b7 O- i. YOur patient’s testosterone level was 60 ng/mL,6 F* U( C i# X6 \' N) ]
which was clearly high. Some studies suggest that+ {: x0 A2 b! u' I. ~
dermal conversion of testosterone to dihydrotestos-
- N, j6 m7 t& aterone, which is a more potent metabolite, is more& I6 R% c1 a% j' f
active in young children exposed to testosterone. o U; }1 {" t* Q4 e9 x
exogenously7; however, we did not measure a dihy-5 F2 n# X7 n% j/ c
drotestosterone level in our patient. In addition to
- v% b2 p- Z5 l8 L7 v. Jvirilization, exposure to exogenous testosterone in
& A; ]% L& Y4 h, m7 s! R! i% J) y0 _children results in an increase in growth velocity and
6 O; i0 k8 S# ]advanced bone age, as seen in our patient. D/ A5 H$ a! y4 W2 E5 B' w
The long-term effect of androgen exposure during
* O3 Y9 V7 w7 eearly childhood on pubertal development and final
, W7 t5 X. D: |9 l9 \" f2 `2 radult height are not fully known and always remain
- W6 h. B* s# v# o, ia concern. Children treated with short-term testos-
$ {. [7 U% g8 d( `% q* v4 W& Sterone injection or topical androgen may exhibit some
+ c4 _. S7 u% ^/ X1 N9 f" q# c4 qacceleration of the skeletal maturation; however, after) S1 a4 x6 y& m" u0 \5 r5 _
cessation of treatment, the rate of bone maturation( Q3 C' N A' k1 x1 e
decelerates and gradually returns to normal.8,9' P5 y! C2 |" F
There are conflicting reports and controversy2 z/ b2 y, N/ \
over the effect of early androgen exposure on adult1 Z! [% X* p5 G* Y2 |. D
penile length.10,11 Some reports suggest subnormal
) R' T. L2 t7 i9 T* B& g, ^adult penile length, apparently because of downreg-1 Z- l% O i% v h0 P0 U/ G9 l
ulation of androgen receptor number.10,12 However,2 ~* x- K" u$ z/ w; i. R0 `
Sutherland et al13 did not find a correlation between
( d/ k( h: \ O! ~2 @: J ichildhood testosterone exposure and reduced adult* d h& ?0 L/ }, [/ r- z7 d& l
penile length in clinical studies.
" v, P4 V7 A) U2 g: TNonetheless, we do not believe our patient is
2 K+ Q; x/ c- }) Vgoing to experience any of the untoward effects from& ^5 k* c, M( @ u$ b
testosterone exposure as mentioned earlier because
2 m( u, ~# n, d9 Fthe exposure was not for a prolonged period of time.6 e3 a3 \. _& q
Although the bone age was advanced at the time of8 }4 w! h I* A" f" B
diagnosis, the child had a normal growth velocity at. h6 x( t6 A0 r
the follow-up visit. It is hoped that his final adult
" S/ I: U) a o Y$ |+ S/ @1 Nheight will not be affected.8 }2 ]; b" }! \
Although rarely reported, the widespread avail-- O; V# X6 ~0 e( a" i' b" R+ p" i
ability of androgen products in our society may
) P) c- T* _3 B Tindeed cause more virilization in male or female
- K. u( W' T; O0 w" X: X' w$ tchildren than one would realize. Exposure to andro-
$ o% P3 a" J+ r( P9 Jgen products must be considered and specific ques-
% i: S& L# c2 W9 g' O i# ptioning about the use of a testosterone product or
% |, |6 i9 W( E& Ngel should be asked of the family members during% j; x. H4 R/ k. ~; f
the evaluation of any children who present with vir-8 @6 X7 W4 e( b$ I
ilization or peripheral precocious puberty. The diag-2 M" k+ ]8 C" ^" u# `& @# Y
nosis can be established by just a few tests and by) p8 _! K- h8 }' J! m6 a# y7 C# ]
appropriate history. The inability to obtain such a
3 x+ v, o& f2 T: k3 h; Thistory, or failure to ask the specific questions, may
2 R* W5 m4 X+ I* dresult in extensive, unnecessary, and expensive6 w7 ^: f1 P2 c6 s$ d. H
investigation. The primary care physician should be9 l& W/ {5 \0 q d
aware of this fact, because most of these children
; C2 q: B0 d: f( Z. m# f [may initially present in their practice. The Physicians’
4 O+ q: g% m2 [' V. E' rDesk Reference and package insert should also put a
/ |/ l# h- u; F# ]1 t& _warning about the virilizing effect on a male or6 S' ~" V: \3 [% t. g! x
female child who might come in contact with some-( @7 g) I* d% ~) D$ U3 k, {2 o
one using any of these products.
& x/ @2 [/ ~9 X( w# @8 J/ ?# P8 XReferences" u: {- {. C# h: S* C4 ~* K
1. Styne DM. The testes: disorder of sexual differentiation
' W) b9 n# Y, b5 f nand puberty in the male. In: Sperling MA, ed. Pediatric/ c/ G( Y' T' q0 u. {9 O
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;/ l, v% M2 c& E% q3 r
2002: 565-628.
2 U, `9 u' \6 R! R5 h3 b2 D; R. c2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious! ^( k( {7 j9 c; ^, k+ V. B8 f
puberty in children with tumours of the suprasellar pineal |
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