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Sexual Precocity in a 16-Month-Old
* O, c" w# y4 ?7 d6 MBoy Induced by Indirect Topical" c5 c; R/ W, Y" Z- j9 z5 p
Exposure to Testosterone
9 e6 l) m, P- f: s$ QSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2) Z: B$ t6 s3 j# f2 g- _) d
and Kenneth R. Rettig, MD1
6 c) d6 S4 {% E2 o* Q: \Clinical Pediatrics
: y- E) v- f+ k1 NVolume 46 Number 6
8 h8 ?- ~5 b/ |6 S6 }7 Z _July 2007 540-543
1 P. W- V4 z) E0 ]' e' X( ]& o4 h© 2007 Sage Publications0 B. A7 D9 C6 J0 R3 y
10.1177/0009922806296651$ |$ Y& R, b) I
http://clp.sagepub.com
# W. y' ]# n% u% e3 ]7 `hosted at
) y# X; p8 \+ `0 B$ h1 phttp://online.sagepub.com
( e- e* n8 N3 b& ]Precocious puberty in boys, central or peripheral,6 O6 J' Y2 }# y9 ~+ Z" d, e
is a significant concern for physicians. Central9 w* _( j- i. s' X7 Z) {$ t- A8 }$ F
precocious puberty (CPP), which is mediated( A( _8 ?1 o* h* P
through the hypothalamic pituitary gonadal axis, has
( K, @% t7 v( M |9 ua higher incidence of organic central nervous system
5 c" \6 ?% d8 w/ _/ llesions in boys.1,2 Virilization in boys, as manifested
9 y4 S9 d# y$ ~; {) Uby enlargement of the penis, development of pubic
6 b. g2 S7 D# W0 Xhair, and facial acne without enlargement of testi-% N9 ^- L& j1 k- C1 b: C
cles, suggests peripheral or pseudopuberty.1-3 We' T* C+ b, l7 q D
report a 16-month-old boy who presented with the
/ d4 F( K, B" O4 E# Penlargement of the phallus and pubic hair develop-3 O9 f/ N- D3 W7 o
ment without testicular enlargement, which was due$ y* O. \# h. ?3 H
to the unintentional exposure to androgen gel used by
6 | K+ m- t/ Athe father. The family initially concealed this infor-
" o& ]4 j+ k0 t! ]* O- gmation, resulting in an extensive work-up for this- k& F$ ]' h! o) l
child. Given the widespread and easy availability of& t D: Y. _* O7 V7 p! G
testosterone gel and cream, we believe this is proba-
2 d8 @: O& Q8 s; d* v) ^8 Rbly more common than the rare case report in the
" A9 z1 ~# B1 I& T) Pliterature.4
- f" l" @+ ?6 O+ K# jPatient Report
2 q, s+ Y. u: _9 [. K$ l( b( kA 16-month-old white child was referred to the% S# n- v# F8 Y% @$ \ i- \$ @& I1 U
endocrine clinic by his pediatrician with the concern$ _5 p9 a6 Z' n) L+ b
of early sexual development. His mother noticed
' G" E* S9 X3 e, B7 [light colored pubic hair development when he was
. B4 l- x: t- O4 r" FFrom the 1Division of Pediatric Endocrinology, 2University of4 n5 y* v/ U+ R
South Alabama Medical Center, Mobile, Alabama.' ~0 D: C4 a- F, c# G' K( w
Address correspondence to: Samar K. Bhowmick, MD, FACE,
/ b: k! a& f1 v) KProfessor of Pediatrics, University of South Alabama, College of3 r8 o5 P0 b, z$ L1 ^4 h' F
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;+ |, X; `2 V: ?/ s4 q+ h
e-mail: [email protected].
4 e+ k! `" r. P0 aabout 6 to 7 months old, which progressively became. t; R8 z* S. E! H4 S- y
darker. She was also concerned about the enlarge-
0 E* I( M& w% }+ Y/ f' r4 Vment of his penis and frequent erections. The child, K# i# V6 q+ ]: M
was the product of a full-term normal delivery, with# ]; X( D# ~/ k
a birth weight of 7 lb 14 oz, and birth length of3 r2 I8 Q" i+ b
20 inches. He was breast-fed throughout the first year/ }) m& O! [8 R' P! ~1 T! [* s; J
of life and was still receiving breast milk along with
+ N+ q0 E7 _- a7 D! e7 Y2 vsolid food. He had no hospitalizations or surgery," Z; x7 @: @2 d& ]6 ]+ G
and his psychosocial and psychomotor development! O4 S4 t7 N Q
was age appropriate.
- m: M2 C) N3 G! [2 S5 KThe family history was remarkable for the father,# p7 H* C G: _7 ]/ M4 k8 L/ T
who was diagnosed with hypothyroidism at age 16,
' ?' ~! L0 `& L" gwhich was treated with thyroxine. The father’s
) X) |5 g; r7 q5 [8 Dheight was 6 feet, and he went through a somewhat
" k* V0 v9 R7 ~9 A" Yearly puberty and had stopped growing by age 14.
4 R. |7 U4 n+ e, ~, B. YThe father denied taking any other medication. The
& [; t/ N4 b( k6 P8 j0 Hchild’s mother was in good health. Her menarche
, e$ J" a% T) s, H s' n* U s& twas at 11 years of age, and her height was at 5 feet* R! f' u8 {! i7 }6 f0 V
5 inches. There was no other family history of pre-2 s# \, @+ d5 E# _7 w" O: @* e
cocious sexual development in the first-degree rela-4 l4 V: I8 o8 c% b
tives. There were no siblings.
4 M; a' S7 P+ L9 i2 z7 w; w) bPhysical Examination
6 ^/ F7 N& f4 x) i- }/ @The physical examination revealed a very active,3 I6 n/ E! a% [ F; ^ ~
playful, and healthy boy. The vital signs documented
1 {1 ^4 W, C5 N8 j8 Q# f ka blood pressure of 85/50 mm Hg, his length was
( I3 U- X# ?$ ^) Q+ b8 x90 cm (>97th percentile), and his weight was 14.4 kg' {' y! O% k% Q, X j+ U( V }% q, `. P
(also >97th percentile). The observed yearly growth/ P( h, \( @; }
velocity was 30 cm (12 inches). The examination of* C! @- f7 `* T& Z$ ?
the neck revealed no thyroid enlargement.: e: b8 v& j; V _, J, Z/ Z& V
The genitourinary examination was remarkable for/ n7 g0 u! i) f& ~* b
enlargement of the penis, with a stretched length of5 m) y- ~2 Z; y6 U( f0 D% Q0 k1 k3 |
8 cm and a width of 2 cm. The glans penis was very well' D0 w a1 z9 p! ]& ^* c! @
developed. The pubic hair was Tanner II, mostly around3 r$ O6 L! \4 W8 U, ?3 U
540
; [0 m4 W5 {" Y) |) f. n6 n' Fat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from8 j$ `0 r, F/ A
the base of the phallus and was dark and curled. The
" G; R. y* r# L/ V2 Etesticular volume was prepubertal at 2 mL each.: w% N+ x# z2 ]
The skin was moist and smooth and somewhat
) d4 w- E( K2 M! A4 d1 m3 Roily. No axillary hair was noted. There were no
* ?# k, K* K U' W% S( i, mabnormal skin pigmentations or café-au-lait spots.
# ^, K. a" m) V7 J7 C1 L$ g2 q. PNeurologic evaluation showed deep tendon reflex 2+4 |8 L- q: w3 N f
bilateral and symmetrical. There was no suggestion
1 ^) K: G0 J7 G8 ~% X) ~of papilledema.# b6 W q$ ]. R# C J, ^( O
Laboratory Evaluation% h% ]4 w' X, S/ e
The bone age was consistent with 28 months by3 z J9 f; U4 q7 L8 y! @
using the standard of Greulich and Pyle at a chrono-
( r' |6 s; f; @- @" @/ V6 nlogic age of 16 months (advanced).5 Chromosomal$ K; f9 G( X! E
karyotype was 46XY. The thyroid function test
) ?- A% f" @- q" c. ~1 c" v: cshowed a free T4 of 1.69 ng/dL, and thyroid stimu-9 a2 Z" C6 S- Y8 b; E
lating hormone level was 1.3 µIU/mL (both normal).
9 U& _8 W+ w7 P" @The concentrations of serum electrolytes, blood! I' k% U- W. B) o
urea nitrogen, creatinine, and calcium all were
: {2 R7 [& c& k. W. M- O) fwithin normal range for his age. The concentration
% a6 x# c1 I! I; i/ gof serum 17-hydroxyprogesterone was 16 ng/dL
7 ]8 i3 b# l; X. I( g" b( e* `9 S(normal, 3 to 90 ng/dL), androstenedione was 20( k5 c; L$ K( f
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
l9 V% @* [2 k: w6 mterone was 38 ng/dL (normal, 50 to 760 ng/dL),) f' F# b6 X3 T7 Q0 {" z$ g
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
% F% G" u6 a" i8 `" c: z4 r1 f49ng/dL), 11-desoxycortisol (specific compound S)
$ t2 I% w- n) T5 twas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-& ]% i4 F \1 r; c
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total$ o8 G7 M- E* o9 B4 q; u
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),3 ~& U" q+ H0 o6 c8 _. D' m2 F
and β-human chorionic gonadotropin was less than+ x" Q2 d2 U. y5 ^
5 mIU/mL (normal <5 mIU/mL). Serum follicular% _) P w% d3 Y8 f* z
stimulating hormone and leuteinizing hormone! e3 `5 Y4 m1 b2 q' W6 a
concentrations were less than 0.05 mIU/mL
* }2 }; a; g( W3 [- ^(prepubertal).
# O. f, g) s% A7 e( _# RThe parents were notified about the laboratory
6 {, m! _9 f( I, e' H8 E# }results and were informed that all of the tests were% K4 i0 `6 l) M: D1 |$ u4 s
normal except the testosterone level was high. The8 A% Q, L! P: e" [* `
follow-up visit was arranged within a few weeks to
$ [0 D! ~# t, M& ^obtain testicular and abdominal sonograms; how-: L0 }( w& G! A r/ u% ^
ever, the family did not return for 4 months.5 ^" h; Z4 I! A
Physical examination at this time revealed that the# a7 D" G6 T7 z
child had grown 2.5 cm in 4 months and had gained
3 u, T4 J: `1 y2 kg of weight. Physical examination remained
- `4 w0 {7 H- t1 Q4 b0 I* ^0 g3 ?unchanged. Surprisingly, the pubic hair almost com-, S3 A2 Q3 v3 ^- t
pletely disappeared except for a few vellous hairs at
0 c8 H! {1 d) H! c) N- \the base of the phallus. Testicular volume was still 29 g6 D# ~$ g1 g6 Y
mL, and the size of the penis remained unchanged.
7 s) g# E* X# _0 P. b9 I& K4 h# PThe mother also said that the boy was no longer hav-3 k0 Y7 Y' U: F6 J2 x* G
ing frequent erections.
# i9 _$ j. J3 m. G. a4 G# e, W! jBoth parents were again questioned about use of, N5 k) h* u; B! F9 |: B3 O* s) f/ U
any ointment/creams that they may have applied to: {7 S) m6 Q9 W8 A
the child’s skin. This time the father admitted the4 W0 d( c0 x r
Topical Testosterone Exposure / Bhowmick et al 5413 T5 K. O$ \" X3 U9 E6 g
use of testosterone gel twice daily that he was apply-
4 X5 K6 b' N+ R1 \' Y9 T" [ing over his own shoulders, chest, and back area for+ B. S) Y9 g2 C$ C- n
a year. The father also revealed he was embarrassed
0 `: C. H' [1 k3 G( U1 l+ Uto disclose that he was using a testosterone gel pre-
2 M7 {9 N5 c5 R6 w4 T* Fscribed by his family physician for decreased libido, `5 P* B( x" e" E
secondary to depression.
" c% o; t( c) ?The child slept in the same bed with parents.
1 r( N/ Y F `: Z" vThe father would hug the baby and hold him on his1 Z5 s, U" k# f c/ |
chest for a considerable period of time, causing sig-
: `. J0 o3 d9 p/ g3 Fnificant bare skin contact between baby and father.
/ G5 Z# |2 }$ m# l; NThe father also admitted that after the phone call,
2 X! h9 N4 p/ z. M, F+ |when he learned the testosterone level in the baby. l) @- ?: e0 B* V
was high, he then read the product information
% [0 U9 c: a$ Zpacket and concluded that it was most likely the rea-& ^; d8 k8 T, |/ x. n0 Y
son for the child’s virilization. At that time, they
4 F) s2 a- _# X5 h' H& l9 [/ q+ g! Pdecided to put the baby in a separate bed, and the& \9 }9 _ E: ^/ k) a/ x
father was not hugging him with bare skin and had
+ K3 x, ~/ h6 V9 {: m; Q1 wbeen using protective clothing. A repeat testosterone; s( ]: Y! L& W, n
test was ordered, but the family did not go to the
3 j N4 ^7 U' A3 n4 J7 plaboratory to obtain the test.
, V, H# j! w: V% v" V, P8 ^Discussion
8 V; G; _; W3 W) p2 `% XPrecocious puberty in boys is defined as secondary5 L, q5 K/ l" ^+ @+ M" P+ ~
sexual development before 9 years of age.1,4
9 p. ?8 h6 j2 ?Precocious puberty is termed as central (true) when
0 D; H3 Y7 l# D9 G& p, ^8 ^8 Dit is caused by the premature activation of hypo- Q7 k# _9 D" d' e( `8 f" |
thalamic pituitary gonadal axis. CPP is more com-; |. H- z0 s8 Q4 X8 F
mon in girls than in boys.1,3 Most boys with CPP
8 N8 A; `3 I" H2 C$ b+ C4 c9 wmay have a central nervous system lesion that is
5 L9 F- Q4 P: m3 w; F, \8 ]responsible for the early activation of the hypothal-
( c+ f( j! t0 Q' S! m9 vamic pituitary gonadal axis.1-3 Thus, greater empha-
+ Q' Y# i1 L5 P3 z1 wsis has been given to neuroradiologic imaging in M1 j1 R( K" m8 H0 f5 u1 d
boys with precocious puberty. In addition to viril-
. C0 }0 |/ n; t0 h: Lization, the clinical hallmark of CPP is the symmet-6 B% l. g5 t0 L3 m/ g5 R( M, M
rical testicular growth secondary to stimulation by4 i5 N0 a/ K/ T: m9 a X0 ~
gonadotropins.1,3
) u6 L$ w. @5 i) u* _( I; IGonadotropin-independent peripheral preco-
8 t* j3 Q( I5 T% E0 S( Bcious puberty in boys also results from inappropriate
3 \6 @5 F- _7 Z) Landrogenic stimulation from either endogenous or
; x. t# t9 D: |8 I; m* Kexogenous sources, nonpituitary gonadotropin stim-2 K: K& k. z$ N, z3 a" S6 l
ulation, and rare activating mutations.3 Virilizing
3 U2 U! H+ T4 W0 D7 R$ ycongenital adrenal hyperplasia producing excessive
* ?( H- _" J! j n: G7 \adrenal androgens is a common cause of precocious) V6 N" i/ \* W0 D& n/ A/ _
puberty in boys.3,4# k2 C3 g0 s7 A. _! ]$ C
The most common form of congenital adrenal: u- ^4 ]' V) P5 y
hyperplasia is the 21-hydroxylase enzyme deficiency.; C! k; }: a: G& D1 J2 Y
The 11-β hydroxylase deficiency may also result in1 i9 y3 C1 O7 s0 j9 F+ J; B/ I, X
excessive adrenal androgen production, and rarely,
& {6 X, |* C0 K7 X# c/ e& Can adrenal tumor may also cause adrenal androgen8 R, v" @% p5 j4 Z, Y. @+ s& l7 ?3 r
excess.1,3$ p* a( B. j9 n3 a
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
4 I& E# [$ Z4 G' r! A3 ~" e542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
! H0 h+ i$ x$ L* B: B% G* ~A unique entity of male-limited gonadotropin-% O8 M7 c r. @( x7 n, [
independent precocious puberty, which is also known% ~! B2 T0 L# |9 O5 e( i( E- p
as testotoxicosis, may cause precocious puberty at a
' E/ J/ u! _0 F1 X0 S! {# tvery young age. The physical findings in these boys
; a5 H0 }$ P& P( n9 J7 E7 Iwith this disorder are full pubertal development,
3 K' A0 X' n: _* Q8 Z$ x& f* Z' A. \including bilateral testicular growth, similar to boys
: o0 m5 C1 `$ M- O: uwith CPP. The gonadotropin levels in this disorder
: F: Y( c- r0 }2 a; t, C5 o+ Lare suppressed to prepubertal levels and do not show' X2 F# M3 u% B9 T4 d. `
pubertal response of gonadotropin after gonadotropin- c( v6 r8 s* ]- o B; c1 M3 M
releasing hormone stimulation. This is a sex-linked3 E, I, B1 ^2 b7 y+ [$ R
autosomal dominant disorder that affects only
3 f; m R2 o3 \# e6 Y* A+ Z& Kmales; therefore, other male members of the family: i. o; Z+ b3 ~1 w$ w
may have similar precocious puberty.3* _' r8 N& q0 R! `
In our patient, physical examination was incon-
6 j w3 W2 }/ e! [sistent with true precocious puberty since his testi-) Q; ~ n1 ~5 f) [- R5 m# X! e
cles were prepubertal in size. However, testotoxicosis
1 O# C. B% W6 T& Y6 @+ S) pwas in the differential diagnosis because his father
4 J& D3 R* ?2 E o. Pstarted puberty somewhat early, and occasionally,
; d6 X( F. y; m6 `. a8 w% @( rtesticular enlargement is not that evident in the, G$ p e! E5 W0 f5 K
beginning of this process.1 In the absence of a neg-
" x* |1 F" ]' N& h0 [2 V3 h5 W, Sative initial history of androgen exposure, our6 E9 X8 L2 x0 ]: U' a" L5 R: {
biggest concern was virilizing adrenal hyperplasia,2 ]9 I6 X7 v' s7 D+ G i! z+ U
either 21-hydroxylase deficiency or 11-β hydroxylase
& `3 M0 \8 z# W% ideficiency. Those diagnoses were excluded by find-& H- j0 D6 ?9 U
ing the normal level of adrenal steroids.
* l' a* `1 ]- C- @The diagnosis of exogenous androgens was strongly9 `8 `5 s& N3 P+ g
suspected in a follow-up visit after 4 months because
' `' H9 u) k! R( x$ L% O, c4 Kthe physical examination revealed the complete disap-+ o! q! Z* Q9 o5 Y4 J
pearance of pubic hair, normal growth velocity, and
, z* d! |" u5 s; i; ~6 tdecreased erections. The father admitted using a testos-
. n8 p6 N/ B& bterone gel, which he concealed at first visit. He was2 p1 u4 ~/ o+ U9 ~
using it rather frequently, twice a day. The Physicians’
% U8 M5 X `7 \' r* }; NDesk Reference, or package insert of this product, gel or
5 N% h2 ?6 ?+ ~& x. D/ ~# rcream, cautions about dermal testosterone transfer to
9 ]4 H1 t+ T/ {6 s( f9 bunprotected females through direct skin exposure.
# s$ C' T4 _3 \( A. Q1 a( NSerum testosterone level was found to be 2 times the+ G, w/ a. _& B" h4 W, A: M
baseline value in those females who were exposed to' R2 \8 x! p- W# V- N" J5 K- g
even 15 minutes of direct skin contact with their male6 Y8 q; {( f8 k/ l/ i- K9 B
partners.6 However, when a shirt covered the applica-3 I( g O+ C1 i2 S }( e$ y1 U
tion site, this testosterone transfer was prevented. K$ m: y+ @7 N b" I! P8 P' Z
Our patient’s testosterone level was 60 ng/mL,
* h1 B6 D- R0 Z) u# Owhich was clearly high. Some studies suggest that
; Q2 m) v+ ]3 n2 @, {: Udermal conversion of testosterone to dihydrotestos-
! G: Q4 h$ [, [# v, y5 x2 P5 _terone, which is a more potent metabolite, is more
& x# a4 n( T# Tactive in young children exposed to testosterone
$ r- D4 b! F2 z' A. [4 oexogenously7; however, we did not measure a dihy-
4 c$ M+ q ?$ z- {6 @# D. Udrotestosterone level in our patient. In addition to* _: q; q; C) h' e2 u
virilization, exposure to exogenous testosterone in
% P( t4 \/ \. |children results in an increase in growth velocity and
' G* O% `' s' a9 C! jadvanced bone age, as seen in our patient.
. m. i: _. N# N) CThe long-term effect of androgen exposure during# E }* i0 w H. C- y
early childhood on pubertal development and final
8 v8 |- U x4 g1 hadult height are not fully known and always remain7 G& A( g! h3 ^: n: D6 \; o
a concern. Children treated with short-term testos-! l' u9 M) k" |* n( \& i- ?2 ^* R
terone injection or topical androgen may exhibit some0 A9 y* p/ l+ ]5 H' g# z ^& y
acceleration of the skeletal maturation; however, after
! `. ~: {8 U f3 ?% n/ v4 o7 e( {5 \0 Qcessation of treatment, the rate of bone maturation$ g4 U1 I8 o: Z5 j4 j
decelerates and gradually returns to normal.8,9
, m! l% i. l7 m" e: f& d/ ]* y# i; OThere are conflicting reports and controversy
' ]+ [ k% f/ X) nover the effect of early androgen exposure on adult
3 K, \& ^- x4 a# y9 x9 \penile length.10,11 Some reports suggest subnormal4 `" |/ \1 B2 a! @" |4 `$ @5 R
adult penile length, apparently because of downreg-
+ ?0 U* m; Z: V" u1 Z- j4 x. {0 dulation of androgen receptor number.10,12 However,
7 n) \1 z6 w4 W2 \$ lSutherland et al13 did not find a correlation between! J* |2 a3 m% m, q) R
childhood testosterone exposure and reduced adult
4 a* z+ [, I. W& j lpenile length in clinical studies.
. T1 g; r3 j2 I8 x7 Q: ]Nonetheless, we do not believe our patient is8 {7 [% A1 a& \# o
going to experience any of the untoward effects from* \6 x+ ~& A" c+ F. S) g
testosterone exposure as mentioned earlier because
4 `) u, ]0 J* g: s* Othe exposure was not for a prolonged period of time.
: W' V1 @$ j. i$ G# K; WAlthough the bone age was advanced at the time of
0 r b+ b. M4 q- N. G! h3 h- j; Fdiagnosis, the child had a normal growth velocity at- s- a6 t. ]7 J; P' h7 I
the follow-up visit. It is hoped that his final adult
$ n8 J: y! V7 A3 @' G4 Dheight will not be affected.+ ?8 c7 ?$ V3 D. u
Although rarely reported, the widespread avail-0 W1 y5 M/ M' K: j2 o% K
ability of androgen products in our society may
]2 f. t& p; [( w4 N) ^( hindeed cause more virilization in male or female
8 B' H* U/ W+ g2 schildren than one would realize. Exposure to andro-" E$ k- L8 o. l; [( e P
gen products must be considered and specific ques-% t( O5 @# |& o3 @- g& H
tioning about the use of a testosterone product or
; j+ e3 n0 c. ugel should be asked of the family members during( T% i# {. c8 {
the evaluation of any children who present with vir-+ p* V* r, o0 N# D8 S
ilization or peripheral precocious puberty. The diag-
4 o8 w, Y0 O/ Y; D& O2 `1 xnosis can be established by just a few tests and by
7 }6 j% Q$ F7 B# Sappropriate history. The inability to obtain such a" y! \ F# n% f# Z4 @) Z
history, or failure to ask the specific questions, may9 A' V% {4 n" r5 @
result in extensive, unnecessary, and expensive+ T$ [3 B/ A4 ] ?' Y% ^
investigation. The primary care physician should be0 F5 Y }4 d: j$ d) q( d
aware of this fact, because most of these children
& f* k, u1 H! C$ B, P2 x, Wmay initially present in their practice. The Physicians’, k0 c; j2 r( J7 k
Desk Reference and package insert should also put a8 F6 P. S; G, }# ^+ P
warning about the virilizing effect on a male or, ^* j+ d" E$ i' U1 C
female child who might come in contact with some-
9 F1 E& C) `1 ~( h" m0 N' E! mone using any of these products.) Q% W* M2 H s4 w7 q+ c: ?
References
6 O1 H& i$ X: `9 v$ M5 E1 u$ l6 W1. Styne DM. The testes: disorder of sexual differentiation2 N7 O) b. s1 g1 S1 w
and puberty in the male. In: Sperling MA, ed. Pediatric
% j$ k5 m' D/ E7 ]" b1 D& zEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
( d2 M% o% g: ]2 l$ Z4 b% O8 B2002: 565-628.
, ~) z( }& V/ |6 A3 W6 W2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
# l o$ g+ o8 U fpuberty in children with tumours of the suprasellar pineal |
|