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Sexual Precocity in a 16-Month-Old
1 I' |: `- S8 `& X3 r8 \Boy Induced by Indirect Topical
8 P. ~3 D! b: WExposure to Testosterone
/ M! T3 m" O- E* G$ J% x: RSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,24 W0 `# k& W- g7 q& {
and Kenneth R. Rettig, MD1
! D' m( G: m& H( m9 pClinical Pediatrics3 K' [# U8 `4 c# {. S
Volume 46 Number 64 _! s V$ Z9 `; t' g/ \
July 2007 540-543
) ~9 G- w2 x0 |© 2007 Sage Publications" d. F7 K1 u+ q) U( E
10.1177/00099228062966513 j% l) Q5 F' N! }1 y
http://clp.sagepub.com
, {5 `, h h0 C+ dhosted at
* L5 B) K0 b1 v+ e8 h0 k9 W6 M/ shttp://online.sagepub.com6 C6 L" ?# B) X+ w* _) a; p
Precocious puberty in boys, central or peripheral,4 s; \' X! W/ a- [* L
is a significant concern for physicians. Central
9 z6 C* X; M6 t2 ^$ Sprecocious puberty (CPP), which is mediated _4 Q% I0 g# [& L. t/ j
through the hypothalamic pituitary gonadal axis, has1 F# ]1 {% p2 u( s* ]$ W
a higher incidence of organic central nervous system
9 F" j7 Z; a4 m" d6 jlesions in boys.1,2 Virilization in boys, as manifested; d+ C, x* l# b/ C# ?7 Q, j* T
by enlargement of the penis, development of pubic- G* Q8 E& H: R2 L3 `/ G. ?
hair, and facial acne without enlargement of testi-5 d! y5 d% f: S5 Y4 N; F
cles, suggests peripheral or pseudopuberty.1-3 We
0 z8 B: F5 G/ ]report a 16-month-old boy who presented with the
2 o* }* T6 \3 H$ |) r' w& I8 fenlargement of the phallus and pubic hair develop-
" a a! T! \) I( @0 kment without testicular enlargement, which was due2 K7 v; U- }. M( f2 f$ ~, `( D
to the unintentional exposure to androgen gel used by
6 \% R# I& M/ p; |) F6 D+ Ythe father. The family initially concealed this infor-
+ Y6 F. K& r) t0 u% ^1 ?+ B, ~3 f$ E* C* Wmation, resulting in an extensive work-up for this
6 |# P, x3 T: _/ \' f: bchild. Given the widespread and easy availability of
4 E* s" `/ f x' P- V' c, `" }testosterone gel and cream, we believe this is proba-
* X6 D2 `2 E0 F4 kbly more common than the rare case report in the/ G6 H- U; ]$ @' j: P6 L
literature.47 q3 R( n9 O6 u
Patient Report
9 E; y4 d) c9 s+ {A 16-month-old white child was referred to the/ `4 N$ Z) g9 u @
endocrine clinic by his pediatrician with the concern
e$ n6 ]! s( hof early sexual development. His mother noticed" p1 m, ]1 n2 F
light colored pubic hair development when he was
E+ `* j( Q: R$ ]0 sFrom the 1Division of Pediatric Endocrinology, 2University of" Y2 R9 T" P1 R( l. h# y8 l
South Alabama Medical Center, Mobile, Alabama.
6 v, Y6 b. K* F2 w" r2 `4 MAddress correspondence to: Samar K. Bhowmick, MD, FACE,5 z; X& t0 [! ?! x
Professor of Pediatrics, University of South Alabama, College of
0 ]% {. j' ~& S0 xMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;" Y( ]: | j/ ]. d
e-mail: [email protected].
9 S" V, ], U V+ T# ^! f4 Nabout 6 to 7 months old, which progressively became. [- F" y1 H w# `' ~
darker. She was also concerned about the enlarge-: S1 d) r4 E9 F2 R
ment of his penis and frequent erections. The child0 A9 Q) I$ g& a( O9 ]
was the product of a full-term normal delivery, with! y% }: d E. S: |
a birth weight of 7 lb 14 oz, and birth length of
7 n. f% u) M d+ y2 a20 inches. He was breast-fed throughout the first year. F5 m4 W/ j2 _7 w; g8 v
of life and was still receiving breast milk along with
9 t, i8 z1 Q; y2 f$ psolid food. He had no hospitalizations or surgery,
1 w6 I. ^& @& `+ D5 u6 y; nand his psychosocial and psychomotor development
$ e7 m$ G2 n9 c2 q" O) i4 Awas age appropriate.
3 v0 P2 D6 U& u5 k& x9 i: GThe family history was remarkable for the father,
$ l; B# f0 L1 {- r, h5 z5 a1 hwho was diagnosed with hypothyroidism at age 16,& Z, _* W( `+ |& \
which was treated with thyroxine. The father’s1 d: [" S* R" |0 Y5 R0 [/ e
height was 6 feet, and he went through a somewhat& k5 ] ]: g/ J; M& J1 W! n: _: G
early puberty and had stopped growing by age 14.
1 m1 N1 ]/ x6 C/ Z, XThe father denied taking any other medication. The ?& i4 j% q' }9 j* T. b0 h
child’s mother was in good health. Her menarche! _1 Z2 a( I5 d0 B1 @5 ^) Y
was at 11 years of age, and her height was at 5 feet
# N3 c2 G$ d' p2 Y5 inches. There was no other family history of pre-( M5 Z$ X; ?, X9 |. x; p
cocious sexual development in the first-degree rela-! o+ P) {7 e" L/ W3 e/ @5 J: o; v# F: s
tives. There were no siblings.( @( g: B! x+ X7 k0 @% V
Physical Examination0 z1 ^5 \) d* Y P" s% r; [
The physical examination revealed a very active,2 _# w) e+ y3 ~ D# b. q/ o0 `8 W; T k
playful, and healthy boy. The vital signs documented" q3 f8 n9 f6 p) ? h4 P
a blood pressure of 85/50 mm Hg, his length was
& j1 x( w9 z! O7 x4 W1 J90 cm (>97th percentile), and his weight was 14.4 kg
6 J" k: D5 o& ]6 e* J+ K8 R; e(also >97th percentile). The observed yearly growth
' x1 B2 M3 Y0 t+ ~velocity was 30 cm (12 inches). The examination of
/ e/ T/ @9 f: J0 X& U% g" ~the neck revealed no thyroid enlargement.
) N d: W, U" x/ m( f: y8 }The genitourinary examination was remarkable for+ s2 l2 W- c( B9 J0 H3 `
enlargement of the penis, with a stretched length of
- }+ c! g: G; F4 }2 u8 cm and a width of 2 cm. The glans penis was very well0 i4 L3 f+ L' D5 A4 G
developed. The pubic hair was Tanner II, mostly around
5 p$ X- e" k6 ^$ i6 j2 n540, ^" }# ]6 Y- h) V. g: ~0 e4 {* `
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
( o, G: l( }8 q# w4 `* `the base of the phallus and was dark and curled. The
2 A+ X3 p. W9 y& vtesticular volume was prepubertal at 2 mL each.
4 S3 G, r- k eThe skin was moist and smooth and somewhat& Q7 T, d2 @ P
oily. No axillary hair was noted. There were no" r' C/ l% H) S) ?5 z, Y
abnormal skin pigmentations or café-au-lait spots.5 H4 A/ f( ?$ L
Neurologic evaluation showed deep tendon reflex 2+8 T; r- b. j1 Q
bilateral and symmetrical. There was no suggestion# Z% ^ k% n0 [# U4 }/ A3 h
of papilledema.
# T7 D! }6 X5 d. A, sLaboratory Evaluation
. D. P& B2 i8 U( } }( E+ _The bone age was consistent with 28 months by z1 y0 w6 y, `; J1 l# {
using the standard of Greulich and Pyle at a chrono-! @- a" h. p* P8 H( Z3 x
logic age of 16 months (advanced).5 Chromosomal" i8 h; e) J* _2 z
karyotype was 46XY. The thyroid function test9 Y1 q6 S3 n8 \5 Z& w
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
8 {& `& U) A8 H/ flating hormone level was 1.3 µIU/mL (both normal).
, k t% |! }, z) F# m0 @The concentrations of serum electrolytes, blood w, ]2 F* \) m% }7 r
urea nitrogen, creatinine, and calcium all were% h8 K1 i! l( [0 D
within normal range for his age. The concentration
6 h# b' ]( D6 _% m# Q7 Jof serum 17-hydroxyprogesterone was 16 ng/dL
( d1 R6 B0 V, _2 ]; W(normal, 3 to 90 ng/dL), androstenedione was 20
4 L, D( j& n! {/ j0 N4 ?ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
5 q3 p% S. b6 K" B3 U2 {" \terone was 38 ng/dL (normal, 50 to 760 ng/dL),
- \4 d; R( F7 P3 X/ [7 x. ]desoxycorticosterone was 4.3 ng/dL (normal, 7 to* d: }5 l {! n. B: N% C+ `
49ng/dL), 11-desoxycortisol (specific compound S)
6 @0 E' p- `2 Pwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-- ^8 k9 E# u: N: W4 R1 p! \1 E8 f
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total: [& e* A5 Z6 F/ l! Y3 J
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),4 I! P* d g- j# p1 ]
and β-human chorionic gonadotropin was less than
4 @+ h- K8 E. P% \2 @9 M( P7 b4 l5 mIU/mL (normal <5 mIU/mL). Serum follicular
( |1 w, \9 H9 w* _5 s4 @7 Gstimulating hormone and leuteinizing hormone$ j' q; A, }% e0 k- h$ g: v
concentrations were less than 0.05 mIU/mL
5 E3 ], F' J. F1 D3 u4 k: ~(prepubertal).$ |2 s% [3 \$ G# d/ o
The parents were notified about the laboratory
$ W& C. Y2 \1 b- |" g3 q( Jresults and were informed that all of the tests were, v# x, ~ F3 ~3 R1 k- _& }; h
normal except the testosterone level was high. The
/ K$ K4 N4 ]' Afollow-up visit was arranged within a few weeks to
6 x5 v0 e7 v1 y, U+ hobtain testicular and abdominal sonograms; how-7 i3 l F" A) X$ o/ l2 r3 V
ever, the family did not return for 4 months.
0 `% Q% o& A/ v- m# h- SPhysical examination at this time revealed that the* ^/ t1 h; ^* m5 t% C
child had grown 2.5 cm in 4 months and had gained5 f: {* D' o$ h4 @2 {5 h' U$ t5 y
2 kg of weight. Physical examination remained% U! d/ J/ z/ Q" n+ S4 v
unchanged. Surprisingly, the pubic hair almost com-- ]; J4 ?6 z q& p7 a
pletely disappeared except for a few vellous hairs at
4 y2 T8 `/ G5 k' ^the base of the phallus. Testicular volume was still 2
' T7 e. u: |# v1 F; `, v' ?mL, and the size of the penis remained unchanged.1 k5 b/ \5 n M0 B4 C
The mother also said that the boy was no longer hav-
3 @+ X9 u5 q7 e$ ^/ }- j1 Hing frequent erections.
; Q0 h$ e3 ] u+ |Both parents were again questioned about use of
/ V, J) H7 J4 Z, ^3 nany ointment/creams that they may have applied to) S2 G# {) ]! ~& K* U3 D
the child’s skin. This time the father admitted the. x r8 C ]9 C
Topical Testosterone Exposure / Bhowmick et al 5410 c1 v1 y5 ~1 u2 L
use of testosterone gel twice daily that he was apply-- H& O% _. w8 k
ing over his own shoulders, chest, and back area for7 {: M8 ~/ Q" r1 X7 U/ V
a year. The father also revealed he was embarrassed) l; W+ I, z% u) ], H
to disclose that he was using a testosterone gel pre-0 o+ O/ [- j$ [* @1 a C: g1 N8 b
scribed by his family physician for decreased libido, h) i& x; Q. u/ ]
secondary to depression.
7 z8 i8 c0 m3 L( |; D4 e bThe child slept in the same bed with parents.
; Y& x) j& c# E0 G7 T! x8 eThe father would hug the baby and hold him on his
# S4 J3 l8 G0 h8 O4 ?9 zchest for a considerable period of time, causing sig-# {2 E$ y- N# H I6 \
nificant bare skin contact between baby and father.
. D' K: O! N& n9 XThe father also admitted that after the phone call,
8 _+ h3 O8 W2 x* J! z5 lwhen he learned the testosterone level in the baby
' F% C v) P$ k1 M5 [1 ]was high, he then read the product information3 Q6 A1 F4 v& k$ ~( U
packet and concluded that it was most likely the rea-: G' ^. t) s! X) l/ ~
son for the child’s virilization. At that time, they
( ]. j( H$ \: q) E; e, ddecided to put the baby in a separate bed, and the
- Q3 f, `; B! j1 J" dfather was not hugging him with bare skin and had) X( X% s8 L( m# r, r9 K
been using protective clothing. A repeat testosterone
7 b# j: r. N+ }8 h) e0 n- J; {test was ordered, but the family did not go to the
, p! \6 }$ A% p' Q: m" nlaboratory to obtain the test." r8 Q# y1 P, I [6 A7 @
Discussion
& P3 _* ~' Q, d" WPrecocious puberty in boys is defined as secondary& ?8 D/ _. l: z' p) M8 Z0 W* h
sexual development before 9 years of age.1,4
$ S- n2 ?' B/ B! s' @7 D0 ZPrecocious puberty is termed as central (true) when
/ V2 B8 L' l C3 C) ?. _it is caused by the premature activation of hypo-
% ^' d1 p) g+ ^6 P$ ~1 ?* |% I5 c& gthalamic pituitary gonadal axis. CPP is more com-/ D( U! P+ j2 a; Y4 `3 z
mon in girls than in boys.1,3 Most boys with CPP
& G" U3 u/ x# s+ Rmay have a central nervous system lesion that is
' T6 s6 y: e" U! e6 o# h. F2 e2 lresponsible for the early activation of the hypothal-$ k% ?( D e( P
amic pituitary gonadal axis.1-3 Thus, greater empha-4 H- i* |$ G3 {* S/ l) ~9 V
sis has been given to neuroradiologic imaging in2 P, T: D9 u, t, `
boys with precocious puberty. In addition to viril-
8 v, a& T8 H: }4 q4 R+ F- U# Jization, the clinical hallmark of CPP is the symmet-: q$ E% b! X2 U. f4 \( E
rical testicular growth secondary to stimulation by
q$ o6 I+ z" @: D! p. P( J, egonadotropins.1,3
i, n0 U& s: {1 qGonadotropin-independent peripheral preco-
6 W8 j, P" k* C$ j4 }$ E6 Pcious puberty in boys also results from inappropriate) U- l6 M" X" ~, I: D! w* d7 c
androgenic stimulation from either endogenous or8 C# ~, ^/ _: c0 A4 R
exogenous sources, nonpituitary gonadotropin stim-
9 b" M/ G5 t4 j+ I7 Tulation, and rare activating mutations.3 Virilizing2 R) s7 z4 Q* n- w
congenital adrenal hyperplasia producing excessive9 B! k; K7 m( w
adrenal androgens is a common cause of precocious/ z/ _6 p' R ^, o5 X
puberty in boys.3,4
- A$ L9 p5 e9 o1 a$ d+ E. x. F6 MThe most common form of congenital adrenal% n2 O) K* p1 H
hyperplasia is the 21-hydroxylase enzyme deficiency.3 N0 j, S+ J& k% A+ P4 e9 K. c
The 11-β hydroxylase deficiency may also result in
% W4 U% f) s( n& `# rexcessive adrenal androgen production, and rarely,' F4 T: Z8 D7 ?) Y2 M
an adrenal tumor may also cause adrenal androgen
. r5 t/ d2 e1 ~3 p J7 fexcess.1,30 F3 @- Z! {$ ^4 _3 T* @/ k' b
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
' M. R s$ V6 k* ?542 Clinical Pediatrics / Vol. 46, No. 6, July 2007* e9 ?; q" O5 Z, X
A unique entity of male-limited gonadotropin-
6 X1 G+ V- [$ z& A0 Cindependent precocious puberty, which is also known4 K) r0 v) |/ v b
as testotoxicosis, may cause precocious puberty at a6 i; d+ D' u& J9 |) @4 f
very young age. The physical findings in these boys
4 k# k8 O; r# ?4 G0 H) C! N% ~with this disorder are full pubertal development,
8 v1 O' ]$ u( m mincluding bilateral testicular growth, similar to boys7 o6 ~; U+ c% v' W
with CPP. The gonadotropin levels in this disorder
2 b1 O |7 b' x) Jare suppressed to prepubertal levels and do not show
5 k8 M' P, b' e+ g- t" Qpubertal response of gonadotropin after gonadotropin-
8 n: I% i/ ^/ O- `releasing hormone stimulation. This is a sex-linked
; V' ^7 ?; j7 Y6 P6 A3 eautosomal dominant disorder that affects only
) G+ }+ O4 t+ h! |- ~! \0 imales; therefore, other male members of the family9 O* _- t4 x/ P1 p, a
may have similar precocious puberty.3- Q8 j$ `. e/ |- \
In our patient, physical examination was incon-* k2 v' s# K; z2 {( ^
sistent with true precocious puberty since his testi-
! ?" o+ K) X" }cles were prepubertal in size. However, testotoxicosis1 K, e/ m; |+ R5 D! r6 w# ?& ?/ C
was in the differential diagnosis because his father1 }) g' z. m+ F n# h
started puberty somewhat early, and occasionally,
5 @6 Q0 F# I% M0 i- d3 Q2 Wtesticular enlargement is not that evident in the2 T, ~! A' w, X# ^/ B- a1 s
beginning of this process.1 In the absence of a neg-
3 ]: B+ v* j* `3 }7 f p% eative initial history of androgen exposure, our" x8 U$ t; ]% f4 V$ r$ p% J% n( k7 t
biggest concern was virilizing adrenal hyperplasia,
: M6 s$ G: B& e* ]) T$ a5 ^either 21-hydroxylase deficiency or 11-β hydroxylase5 E# U: v8 m* @& |% m n" c
deficiency. Those diagnoses were excluded by find-. D0 ], B; C. o% L8 G
ing the normal level of adrenal steroids.4 R; _2 A8 F; j' S
The diagnosis of exogenous androgens was strongly7 i+ `" G. i. A9 C, Z* W% M
suspected in a follow-up visit after 4 months because. m; e) b" \+ v6 c8 M
the physical examination revealed the complete disap-
; ~ v2 r$ N; g% O/ cpearance of pubic hair, normal growth velocity, and: A" V: {) g, B4 [2 W; e
decreased erections. The father admitted using a testos-5 T3 n2 L) a) S7 B9 f5 D
terone gel, which he concealed at first visit. He was
8 U# g" p9 T: J. {+ Eusing it rather frequently, twice a day. The Physicians’
$ k( ]9 g. k) g+ G% W4 R, ?Desk Reference, or package insert of this product, gel or0 m% l" x$ w/ T/ S/ T
cream, cautions about dermal testosterone transfer to
& b- D: T" ], Uunprotected females through direct skin exposure.; C; c, q' ?* G
Serum testosterone level was found to be 2 times the
4 g5 v7 |4 O4 Ibaseline value in those females who were exposed to# N4 M7 \+ ~$ j) j7 v$ j+ Z1 u
even 15 minutes of direct skin contact with their male) A& _, M2 A2 [' q+ M$ @' ]. u
partners.6 However, when a shirt covered the applica-
, t4 x( m& Q! a. Ption site, this testosterone transfer was prevented.
: e# S1 H: C% ]/ f3 o# NOur patient’s testosterone level was 60 ng/mL,- `1 }, K/ e/ T8 D C% q
which was clearly high. Some studies suggest that
& v$ l3 \6 Y3 W4 Mdermal conversion of testosterone to dihydrotestos-
1 q" h: B# G+ d7 T1 s I- E2 r; _terone, which is a more potent metabolite, is more
: s6 _! J! g9 y) n: }- W. E: _active in young children exposed to testosterone3 A6 l% |8 ?/ o5 L( ?7 \/ I1 T; s
exogenously7; however, we did not measure a dihy-
' B5 y* s0 p: ?& }6 y1 T* V0 ldrotestosterone level in our patient. In addition to( I. c& G5 z/ m5 Y' G5 t2 t. q
virilization, exposure to exogenous testosterone in$ J' D+ H$ |, s1 ?
children results in an increase in growth velocity and/ y! \9 J- X5 t' b9 O
advanced bone age, as seen in our patient.; W1 x7 `; e$ y+ ]
The long-term effect of androgen exposure during
0 X5 T' M! m/ s8 a/ o" V2 f: B- ~early childhood on pubertal development and final
- ]( }, J2 n- Qadult height are not fully known and always remain6 a& h/ M* L& D5 L
a concern. Children treated with short-term testos-1 N/ N6 l/ _ U) Q3 t8 v, @/ B" l8 b
terone injection or topical androgen may exhibit some& Q. X6 h6 O4 F1 j
acceleration of the skeletal maturation; however, after
% F: P$ t$ Z( _6 @2 j- Y( {! |6 Hcessation of treatment, the rate of bone maturation
$ a" e5 X, o$ W( w0 _' ^- r2 l( ndecelerates and gradually returns to normal.8,9
# n7 a( H2 h! B( hThere are conflicting reports and controversy) L! y( c. Y; Q1 Q; q' O4 @" J
over the effect of early androgen exposure on adult1 u+ G4 h% m9 u7 ?- V+ ^, B
penile length.10,11 Some reports suggest subnormal
S- t+ S' z1 s! F( C6 x1 T0 N& {/ hadult penile length, apparently because of downreg-1 @4 r8 v) M, V. C+ F: Y" n
ulation of androgen receptor number.10,12 However,& j7 j( U$ X* u( W- K8 C
Sutherland et al13 did not find a correlation between4 c% c, H) C5 s9 [. c
childhood testosterone exposure and reduced adult/ ]/ A3 V$ i" a$ I
penile length in clinical studies.8 L" v$ {8 r# z3 ^4 o
Nonetheless, we do not believe our patient is3 a2 t8 x% N$ F8 j# ], Y3 B" f
going to experience any of the untoward effects from0 S' h0 |- s# u+ f) T0 {; A+ w& X
testosterone exposure as mentioned earlier because$ J: ^8 C u) \# ~. b, K+ X, J
the exposure was not for a prolonged period of time.
% q: [# E1 J6 F; RAlthough the bone age was advanced at the time of
. B) r3 }' f, h/ Q% U: a+ n: m4 o& |% y Adiagnosis, the child had a normal growth velocity at
! a3 r' I/ O) I) }1 Ethe follow-up visit. It is hoped that his final adult
6 ^5 w0 ? [0 s2 ~7 ?3 |/ @. dheight will not be affected.
( s- A5 Y& a2 Q% M) M& [& eAlthough rarely reported, the widespread avail-8 G5 \8 \0 q4 m! n; y |( F& r
ability of androgen products in our society may( B9 B. i4 e4 X
indeed cause more virilization in male or female
( i8 K# m" l1 }: L& x8 @children than one would realize. Exposure to andro-
: u1 U+ k; R5 ?( Y. sgen products must be considered and specific ques-$ L) ]. R/ [) T) ~$ [
tioning about the use of a testosterone product or
0 Y) K4 U! u9 M/ e; o8 ogel should be asked of the family members during
# r5 }- x5 c3 s, n5 athe evaluation of any children who present with vir-6 z- q. P/ w: Y- G* m0 D2 o
ilization or peripheral precocious puberty. The diag-7 G x; ^8 M" j( ?0 h) R9 H# `
nosis can be established by just a few tests and by
7 I. L8 c# E' q. B2 c; Tappropriate history. The inability to obtain such a1 X S& P* V' r9 Y' d
history, or failure to ask the specific questions, may J6 E1 M5 F" S/ p1 e( F
result in extensive, unnecessary, and expensive: I* z7 a$ b0 o4 a& F& _
investigation. The primary care physician should be
B, N! h* F! ^5 Qaware of this fact, because most of these children0 F9 E5 V7 L9 W5 N; D- G
may initially present in their practice. The Physicians’
) l( H- O4 f3 _( I( g9 C& c; dDesk Reference and package insert should also put a
3 C3 B2 S. G5 b, s9 ` wwarning about the virilizing effect on a male or
$ `3 T4 h: Z( Ofemale child who might come in contact with some-
" H+ `) E0 {' S8 m8 h5 tone using any of these products.
' _7 m% K$ ^- f- p5 k5 p. w* uReferences$ I( m" ~" T a5 f6 x3 ^2 M$ L: \
1. Styne DM. The testes: disorder of sexual differentiation
4 \, ?# K( _) Hand puberty in the male. In: Sperling MA, ed. Pediatric
$ ^ ?+ b* p1 G, |& ]3 a( QEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
, U! W8 j9 M3 j, j2002: 565-628.2 g1 ?* X. v9 i4 ?2 \, \3 Q
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
) A" I ~- W1 _$ l* ypuberty in children with tumours of the suprasellar pineal |
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