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Sexual Precocity in a 16-Month-Old. z$ q5 w, q' d1 z, H
Boy Induced by Indirect Topical2 b8 @; y% q: Z' l
Exposure to Testosterone" h1 N# ^6 F0 @1 m" L
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2) F" C% V' n" o2 N( T
and Kenneth R. Rettig, MD1
/ [6 J, M( u% @0 a/ q' lClinical Pediatrics
. Y& n& F% G/ w! `2 _7 UVolume 46 Number 6
$ I! K, B: u& XJuly 2007 540-543- H" F+ l. j5 B# z' _2 C
© 2007 Sage Publications
, z5 `% S1 F2 r% r10.1177/0009922806296651+ X$ y# m2 D; k
http://clp.sagepub.com
! z2 G7 x' j$ O" I7 z: o4 \6 R2 @hosted at
0 X* t3 ~2 W4 U! ~$ thttp://online.sagepub.com4 q* Q+ V) ?% ? S. g
Precocious puberty in boys, central or peripheral,; g5 n7 k. b8 T3 j$ l: l
is a significant concern for physicians. Central
: O Y% q" E- N( F) ^3 L8 \3 s7 s( Aprecocious puberty (CPP), which is mediated" r" _, Z+ q" O) K* q. j
through the hypothalamic pituitary gonadal axis, has
, k( V9 p. ?* I7 F. A6 l9 |4 Q# \5 ga higher incidence of organic central nervous system
! Y+ w. L4 f6 w, mlesions in boys.1,2 Virilization in boys, as manifested% |. k* B% X& e6 {
by enlargement of the penis, development of pubic
# b; Z, V% U- h4 b6 C( g. Jhair, and facial acne without enlargement of testi-
8 S! ]9 Q; G: R# }4 n$ tcles, suggests peripheral or pseudopuberty.1-3 We
. H' o' n+ k1 b" ~* n$ X/ qreport a 16-month-old boy who presented with the$ }7 |- w6 z* `1 N) l. o
enlargement of the phallus and pubic hair develop-
! ~9 Y; J& h3 S$ J n5 o, ]4 k/ yment without testicular enlargement, which was due) j6 h: G, w& ?. f! D
to the unintentional exposure to androgen gel used by
\3 J4 M* n, K5 Rthe father. The family initially concealed this infor-. E7 D( l2 N8 q) O
mation, resulting in an extensive work-up for this
% f: j: U P0 b# B8 G5 Q- W% Vchild. Given the widespread and easy availability of
. M* \; ]: R8 D0 Xtestosterone gel and cream, we believe this is proba-9 f9 f h. m& a0 W: F
bly more common than the rare case report in the9 z5 N- ?; l# f4 `) Q3 f" H
literature.4
4 j# E6 a- l7 N( v* T; EPatient Report
9 G+ L5 Z8 r/ B! l& ~& ^) XA 16-month-old white child was referred to the
8 l" F/ z9 I6 \0 lendocrine clinic by his pediatrician with the concern
/ }7 j# P. C/ q# _3 ?" n. Qof early sexual development. His mother noticed
- k7 W; c1 m+ I) b6 N& v: k* s' glight colored pubic hair development when he was
: c8 z% x4 ?6 RFrom the 1Division of Pediatric Endocrinology, 2University of$ e& x( V8 Y1 a9 U
South Alabama Medical Center, Mobile, Alabama.
: ^, z6 E: L6 r3 fAddress correspondence to: Samar K. Bhowmick, MD, FACE,
. J8 }/ Q! g2 hProfessor of Pediatrics, University of South Alabama, College of
$ l f. @% ]& |& A QMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;2 U0 T3 H% r! P- L* y) G5 A- H' P
e-mail: [email protected].9 W" P7 |. G' ]: Y
about 6 to 7 months old, which progressively became
! n5 E6 J# p) j( o4 ydarker. She was also concerned about the enlarge-+ Z4 v- o# O" [1 k
ment of his penis and frequent erections. The child
$ L, h* r4 o) J. g4 n3 F* B3 u. P; owas the product of a full-term normal delivery, with
, y. R* H8 t" y3 n) _a birth weight of 7 lb 14 oz, and birth length of2 M8 t& a5 R) @5 d2 `
20 inches. He was breast-fed throughout the first year5 X0 L; |. |8 _ j5 S1 ~; x) a' w+ D: z
of life and was still receiving breast milk along with
& d- | }4 m4 X1 [0 R- v t1 ssolid food. He had no hospitalizations or surgery, k6 [+ ^0 n; d+ A" R
and his psychosocial and psychomotor development
3 X6 }' S9 Z- e* T* A7 xwas age appropriate.# z# s! |$ p! u0 o5 |3 j
The family history was remarkable for the father,8 P; `2 }) i1 B/ X
who was diagnosed with hypothyroidism at age 16,
1 M0 w' [6 I; i; @7 j5 [which was treated with thyroxine. The father’s
% k2 N0 k5 z) }height was 6 feet, and he went through a somewhat' f; Y7 E3 x1 B! F$ y
early puberty and had stopped growing by age 14., c" m8 s" w( S- B' z
The father denied taking any other medication. The
; x7 n9 [, U) l" @. L1 nchild’s mother was in good health. Her menarche3 z, \5 ^! P/ [+ l. w6 a! J
was at 11 years of age, and her height was at 5 feet
. m) d! g" s' Y8 g+ E5 inches. There was no other family history of pre-
$ N' F! F% c* v) I' Xcocious sexual development in the first-degree rela-
- |9 t% J! R+ m; W6 o& d2 f E+ mtives. There were no siblings.
6 z, O, \7 U3 C. E9 @Physical Examination" L9 `0 |( G& {: r! F. ^8 J$ q
The physical examination revealed a very active,
" X) P. Q% s W" t- aplayful, and healthy boy. The vital signs documented1 U$ e; Y8 H/ q9 ^3 Q# q$ A
a blood pressure of 85/50 mm Hg, his length was
0 J' Q/ V m2 G7 u# G% z90 cm (>97th percentile), and his weight was 14.4 kg. b) X0 a7 G) s; W
(also >97th percentile). The observed yearly growth# J6 t0 {- u- q+ `' U7 K2 h$ O
velocity was 30 cm (12 inches). The examination of; y, j$ e+ t6 d! k
the neck revealed no thyroid enlargement.
4 R: |4 U: a. d) Q) mThe genitourinary examination was remarkable for
$ q& L2 P1 z/ }) H! ~enlargement of the penis, with a stretched length of# `$ G7 R- O8 Y' p3 f q4 m
8 cm and a width of 2 cm. The glans penis was very well. o9 F3 ? N# U! e" O
developed. The pubic hair was Tanner II, mostly around
4 g. k) F. N- e8 T3 z" E- M! W/ p h540* N9 O8 ^3 X- H$ _
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from# A4 k5 J0 a; l/ J: o0 O9 ?# D @
the base of the phallus and was dark and curled. The
8 g* d, C' X, \' U5 Q( V/ G" ^0 utesticular volume was prepubertal at 2 mL each.5 [1 L$ B1 ^2 @& Q7 H) R% a/ r
The skin was moist and smooth and somewhat$ t: Q. j s4 y5 x! Q) @' `
oily. No axillary hair was noted. There were no- t. u K/ _% {
abnormal skin pigmentations or café-au-lait spots. n1 H7 F! X) m/ a/ f% H
Neurologic evaluation showed deep tendon reflex 2+
6 D# Z1 g$ n f ~4 v3 v, abilateral and symmetrical. There was no suggestion
6 z5 | h- c& r9 V. \' {$ G2 l" N( Sof papilledema.' f+ D$ M5 U: a/ r" Y
Laboratory Evaluation* V6 K C8 K! N8 j7 D" q
The bone age was consistent with 28 months by
( b- ]3 _$ [3 b+ ]6 I4 T6 J. [! Pusing the standard of Greulich and Pyle at a chrono-
: t4 q3 X6 N& { j. ?" dlogic age of 16 months (advanced).5 Chromosomal
! Q/ k, q+ \* V5 H. \! Y; Ukaryotype was 46XY. The thyroid function test3 Y9 s ]& B1 {- q4 T! ]
showed a free T4 of 1.69 ng/dL, and thyroid stimu-& z! `4 B" o& K1 s% r6 B
lating hormone level was 1.3 µIU/mL (both normal).
+ @& [9 m1 t1 \The concentrations of serum electrolytes, blood
|) E1 V3 Z5 u7 Vurea nitrogen, creatinine, and calcium all were
8 Y; L4 o( `% D _5 W& P, Cwithin normal range for his age. The concentration) }, Z2 _2 V7 E' ]$ ?# L
of serum 17-hydroxyprogesterone was 16 ng/dL F9 b0 { O. v, ^5 z X) ?
(normal, 3 to 90 ng/dL), androstenedione was 20( R9 K* Q# W3 l" M2 I: v
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
. p* n, B; q7 m6 t8 ^& h7 }5 [terone was 38 ng/dL (normal, 50 to 760 ng/dL),
( g1 p" M$ `: A+ `' M b9 Ddesoxycorticosterone was 4.3 ng/dL (normal, 7 to
) v' P5 U+ N+ j. V) f0 j49ng/dL), 11-desoxycortisol (specific compound S)" y, k% `$ Q& R
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-: _" [ ^3 G H, M
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
. t% W* y( P, M0 t4 ?0 ctestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
5 h6 D% H0 O% ?, i9 K V3 A: Hand β-human chorionic gonadotropin was less than
, j: V+ S( e$ P4 o0 ~" s, m5 mIU/mL (normal <5 mIU/mL). Serum follicular/ C4 m8 V& L# q+ [# J, V
stimulating hormone and leuteinizing hormone
! m8 v0 X3 H f, X2 fconcentrations were less than 0.05 mIU/mL' i0 j6 O& Z7 h1 ~, G1 M
(prepubertal).* [/ b9 H" n1 u
The parents were notified about the laboratory
1 \" [4 @1 t# _9 ^1 B5 Z: b Aresults and were informed that all of the tests were, L6 q" W R' C' P+ d' ]
normal except the testosterone level was high. The- B) L4 H1 e2 l6 j0 B: D. ^, C
follow-up visit was arranged within a few weeks to
+ [8 h* X" A% F ~( yobtain testicular and abdominal sonograms; how-
" Y7 w3 m5 `" t; Jever, the family did not return for 4 months.
# t( H* D9 }. G0 ?' y0 zPhysical examination at this time revealed that the
6 n U9 K' b4 @3 i# F9 Bchild had grown 2.5 cm in 4 months and had gained/ Q' ~; Y3 E; L' e7 R/ |3 A% L
2 kg of weight. Physical examination remained9 r- ?+ T7 q4 ?# _. ^2 p$ B
unchanged. Surprisingly, the pubic hair almost com-
7 m- r Y% f# ?9 _7 [& O9 Opletely disappeared except for a few vellous hairs at! v, M/ Q! {" Q* y5 v+ N, ~
the base of the phallus. Testicular volume was still 2
0 o1 w3 D) E9 B S0 M RmL, and the size of the penis remained unchanged." L$ Z4 q/ M8 ?6 _
The mother also said that the boy was no longer hav-) r! P) ^1 s/ G: P
ing frequent erections.* i, Z1 z$ O" c# b- r! [% e& I
Both parents were again questioned about use of" Q! N! D! ~% i" x, n( q
any ointment/creams that they may have applied to0 f" E) _& k- b( M2 Q1 J3 e9 r; i4 O
the child’s skin. This time the father admitted the, Z9 Z, d7 x S* D4 r4 u+ v+ f9 N
Topical Testosterone Exposure / Bhowmick et al 541
& g9 [8 v6 s. u2 l2 k& _use of testosterone gel twice daily that he was apply-
: o: r6 b7 ? S2 ?/ ling over his own shoulders, chest, and back area for/ [3 |6 Z" x. j( D4 {
a year. The father also revealed he was embarrassed
0 r$ q4 _) Z8 A8 @% H. [9 ^to disclose that he was using a testosterone gel pre-$ v+ M$ [ U: w4 x u5 V
scribed by his family physician for decreased libido
) Q# [ `8 f# A. I- {' D% Msecondary to depression.
; ~7 x2 V {5 ^9 K; s' f: M3 qThe child slept in the same bed with parents.
B5 [9 n7 m% v4 v: u1 LThe father would hug the baby and hold him on his
! d3 Q- x+ }/ w& s: Rchest for a considerable period of time, causing sig-
: r, r) }+ E9 _/ i) anificant bare skin contact between baby and father.8 z( ?, R4 u1 g
The father also admitted that after the phone call,6 x5 i% `0 t3 ?$ g
when he learned the testosterone level in the baby
$ V8 Q* E: }! X) Z& Owas high, he then read the product information
/ l: u+ ]+ q; b" ]6 `- {6 Spacket and concluded that it was most likely the rea-5 c$ p. j0 O# @+ ]2 Z5 L
son for the child’s virilization. At that time, they
$ G5 e0 Z4 v+ @1 P& \- l0 y* Vdecided to put the baby in a separate bed, and the
8 ]( N- A6 I) d. jfather was not hugging him with bare skin and had: |. r! ~7 o$ ^
been using protective clothing. A repeat testosterone, p5 O8 X# i+ h9 A1 ]( X5 H
test was ordered, but the family did not go to the! S a# G" S; o( y. y' o7 J8 ^' Y
laboratory to obtain the test.' Z, K2 P* j3 h. z
Discussion
% P' a6 Y& z, V5 X* nPrecocious puberty in boys is defined as secondary; y4 C8 q6 w& B2 B# T, c
sexual development before 9 years of age.1,4
I/ ~+ P0 t8 MPrecocious puberty is termed as central (true) when
$ T5 Y' _7 K1 E2 Bit is caused by the premature activation of hypo-
. k6 o0 V+ J5 a3 T2 F& t, ^( L' Pthalamic pituitary gonadal axis. CPP is more com-
8 ~; y2 k. |% r5 T/ X$ s$ Nmon in girls than in boys.1,3 Most boys with CPP
: ~/ v' {5 [' ]3 H, V2 w+ q! f6 C: {may have a central nervous system lesion that is2 a P" f& }- {
responsible for the early activation of the hypothal-
) H2 o" R3 |# f4 ?: @amic pituitary gonadal axis.1-3 Thus, greater empha-
' l% [. M3 t: w( X2 R0 msis has been given to neuroradiologic imaging in$ P3 n3 b% ~& Q' _
boys with precocious puberty. In addition to viril-
8 w0 Y) e$ ^) i% @& Eization, the clinical hallmark of CPP is the symmet-+ u5 r+ k# c4 d' @7 u2 i+ K( J& |
rical testicular growth secondary to stimulation by
( |: h7 `( S/ h5 Q# m# I! j5 k9 Ugonadotropins.1,3
$ l" M+ {% B9 n' WGonadotropin-independent peripheral preco-3 D; J+ h" Z& u R6 O/ F g6 {
cious puberty in boys also results from inappropriate
1 a9 U9 k5 X) {& A# W/ Oandrogenic stimulation from either endogenous or' U, V) s# V( b5 @+ c% w4 p
exogenous sources, nonpituitary gonadotropin stim-3 Y, F6 C$ R; `4 S" U* ^
ulation, and rare activating mutations.3 Virilizing
0 c; s4 E7 G Gcongenital adrenal hyperplasia producing excessive
0 r% O U% i d. Ladrenal androgens is a common cause of precocious" D: Z9 ?' b2 }( L
puberty in boys.3,4+ f; z' d. d& K7 A
The most common form of congenital adrenal
4 Z+ L' t$ R" J7 Vhyperplasia is the 21-hydroxylase enzyme deficiency.9 z4 F1 k: x3 M& W: d. ]
The 11-β hydroxylase deficiency may also result in
! ?# s, ?3 b$ Lexcessive adrenal androgen production, and rarely,
$ w" C1 j+ _! Oan adrenal tumor may also cause adrenal androgen G3 N: @3 J+ M0 E' y- h7 p
excess.1,3
, ?, G: |1 Z8 q+ K. \at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
! Y+ P& L+ z. R3 [0 C+ L542 Clinical Pediatrics / Vol. 46, No. 6, July 2007! M. U* Y) \+ Q2 x2 u6 \
A unique entity of male-limited gonadotropin-% @" C" [/ [% x' f
independent precocious puberty, which is also known
/ Y$ D7 e3 O6 _2 K# las testotoxicosis, may cause precocious puberty at a1 x' A5 |; P* T1 a6 y
very young age. The physical findings in these boys/ ^! o- I* r; Y% A& X+ l- L
with this disorder are full pubertal development,
& p) y8 Y$ C7 o. ~including bilateral testicular growth, similar to boys4 E/ E, a* x; U2 e/ F
with CPP. The gonadotropin levels in this disorder
* O! E; e$ _7 a% u* care suppressed to prepubertal levels and do not show2 J9 k5 r% v. u# Z" ~2 Y2 j8 S
pubertal response of gonadotropin after gonadotropin-
^6 W4 Z; N. N% yreleasing hormone stimulation. This is a sex-linked
1 \5 C; e* d0 i& b3 u7 lautosomal dominant disorder that affects only
) h* l( Z: W; \% {males; therefore, other male members of the family
( h$ d* j% Z2 M& z7 E8 Pmay have similar precocious puberty.36 u* [/ M9 K8 z3 {; V; V
In our patient, physical examination was incon-
" N' i6 t8 x1 f( S4 r. Lsistent with true precocious puberty since his testi-
1 p! q# z7 l# lcles were prepubertal in size. However, testotoxicosis
6 l3 D( a0 U; i+ ?" w( fwas in the differential diagnosis because his father
8 z: [& R5 W9 q. d Bstarted puberty somewhat early, and occasionally,
4 Q- k& z8 l- P1 q, v! [6 ^$ Atesticular enlargement is not that evident in the
. F" y+ z4 ~% r& ebeginning of this process.1 In the absence of a neg-
0 X8 t7 P+ T9 I1 ]0 hative initial history of androgen exposure, our
$ ? i B6 ]$ v; abiggest concern was virilizing adrenal hyperplasia,5 u" _$ } |2 F% ] |) E
either 21-hydroxylase deficiency or 11-β hydroxylase
4 B1 `* o. X' ?, sdeficiency. Those diagnoses were excluded by find-5 P1 G: B, e5 \# n5 ]. M
ing the normal level of adrenal steroids.6 Z+ Y7 F$ B: k! W. s# l0 j- t s
The diagnosis of exogenous androgens was strongly; P: a) I" W! e/ e" J" j
suspected in a follow-up visit after 4 months because' _& i9 G0 O0 f2 i5 g
the physical examination revealed the complete disap-
+ g0 K6 I/ k9 i" l' V- cpearance of pubic hair, normal growth velocity, and6 Z) b# V' d' V& B
decreased erections. The father admitted using a testos-: o8 u' c' f! f/ T
terone gel, which he concealed at first visit. He was) `" V4 j! `3 U$ v
using it rather frequently, twice a day. The Physicians’
. j- \( \3 J5 K$ Q5 w2 ~+ _( BDesk Reference, or package insert of this product, gel or
]. O5 u8 @$ d, N/ K. o0 @5 B5 lcream, cautions about dermal testosterone transfer to
4 U( w+ m, x, l9 Lunprotected females through direct skin exposure.
3 P3 B0 D9 U2 V) Z% h" O* Z4 I) cSerum testosterone level was found to be 2 times the5 T$ v# u; e, U+ h4 m
baseline value in those females who were exposed to
' ?4 _$ i4 b) |# S, ^even 15 minutes of direct skin contact with their male
& M* Y4 C2 Z; M o5 E; Dpartners.6 However, when a shirt covered the applica-
4 P$ p6 f: H' e: g, rtion site, this testosterone transfer was prevented.3 y8 f- H; \; j9 B
Our patient’s testosterone level was 60 ng/mL,
+ W3 b0 K# O7 {7 Q- h1 l- G+ Kwhich was clearly high. Some studies suggest that0 m; p% l. _$ }8 S5 Z
dermal conversion of testosterone to dihydrotestos-
) F1 t. [ v8 ~/ gterone, which is a more potent metabolite, is more/ |; X2 ~9 g' ]! B D$ |
active in young children exposed to testosterone
! H( P) z) w! I# \exogenously7; however, we did not measure a dihy-3 q+ O1 w: N& O( f2 F! c
drotestosterone level in our patient. In addition to
* Q: P- |! a5 f- Y9 q9 tvirilization, exposure to exogenous testosterone in/ c: z. p4 c7 W" ~# z$ t
children results in an increase in growth velocity and
@: `, }. D% N% f8 Z) \- fadvanced bone age, as seen in our patient.
. |2 i& p3 Z p% GThe long-term effect of androgen exposure during
! R) X6 Z2 m$ l5 u0 [( iearly childhood on pubertal development and final. ~( ?7 N. s8 G6 d
adult height are not fully known and always remain# t) ]) q" C i( E' g
a concern. Children treated with short-term testos-6 P. z; C& N. A. { ~! J6 x
terone injection or topical androgen may exhibit some( O* G: _, J- i* u7 V
acceleration of the skeletal maturation; however, after
2 j9 g3 K) K) k, V9 r3 y$ A" C, x& U8 Ccessation of treatment, the rate of bone maturation. M9 b5 D, O, K- @2 I: V
decelerates and gradually returns to normal.8,9% i- y/ d! Q/ g
There are conflicting reports and controversy
) c/ K! x3 ^& X1 D9 k1 F/ Uover the effect of early androgen exposure on adult5 v) `, x1 g- \) s1 X( \
penile length.10,11 Some reports suggest subnormal9 { y2 T5 y# C" [! f
adult penile length, apparently because of downreg-5 e8 p0 E% y7 C E Y/ b7 ]
ulation of androgen receptor number.10,12 However,. |6 G+ K7 q Q( J, O# _1 Q
Sutherland et al13 did not find a correlation between
6 z' B6 |; ?5 |childhood testosterone exposure and reduced adult
w$ M2 _9 ~1 N) Q( O5 |penile length in clinical studies.
6 X, g" |+ W/ \- lNonetheless, we do not believe our patient is0 W# c( {" z, B! F# m6 U: f
going to experience any of the untoward effects from
3 W& J3 O& `, |3 }0 _ ~) v/ J- z) Xtestosterone exposure as mentioned earlier because
5 V5 Z6 d8 @; H. F. u- tthe exposure was not for a prolonged period of time.5 W3 M8 r6 l; a; P0 M+ l( o
Although the bone age was advanced at the time of
: [8 c2 [# D( Q1 Xdiagnosis, the child had a normal growth velocity at
3 C @6 _4 }; B. M1 ?5 Jthe follow-up visit. It is hoped that his final adult7 }5 \5 x m. g! u
height will not be affected.9 i8 v, K5 ~1 G- o
Although rarely reported, the widespread avail-+ h/ d7 m# H$ U: k5 N
ability of androgen products in our society may
1 K' J& A m! A* Tindeed cause more virilization in male or female- A8 v# c$ T- F! ~( ?9 d3 D7 ^
children than one would realize. Exposure to andro-
5 ]& }$ R; T1 G0 S# q. z" [$ agen products must be considered and specific ques-$ q. @7 j. ?, h& c& @
tioning about the use of a testosterone product or* s; s3 L8 q% ~2 \) r4 D
gel should be asked of the family members during! j/ E3 |& D6 x& m3 f
the evaluation of any children who present with vir-3 Z0 B. }# Y& C- X0 L0 g' j
ilization or peripheral precocious puberty. The diag-( t0 i2 |5 W6 r) s- v, _
nosis can be established by just a few tests and by) V+ }) T' @; V# u/ m+ e
appropriate history. The inability to obtain such a
6 t$ p/ e2 y, P" f0 u0 e7 Uhistory, or failure to ask the specific questions, may8 y: v5 {8 N8 d' g
result in extensive, unnecessary, and expensive
" z. Z( g+ o/ ~investigation. The primary care physician should be& |, I- n1 l0 t# ]
aware of this fact, because most of these children- b0 M/ E3 ^+ `5 J" _. t! s% O
may initially present in their practice. The Physicians’5 M2 ]( f2 c; F2 h$ Z- ^) U
Desk Reference and package insert should also put a+ H1 Z, ^5 ?6 P) @8 | U$ @1 g$ i7 I* C
warning about the virilizing effect on a male or' `( w7 o. d$ @$ `6 W0 o3 B* W
female child who might come in contact with some-
8 k: s: a" k& y6 l- ]one using any of these products.
( z9 A5 K8 w( w( u. `References
4 D* X5 F% u2 m7 S1. Styne DM. The testes: disorder of sexual differentiation
2 g8 J- Z8 O: F( jand puberty in the male. In: Sperling MA, ed. Pediatric9 ]0 U" N8 G- l/ W y
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
: n/ V8 P* }% K2002: 565-628.& Y, u/ H/ z, a$ Y" x S, [5 M
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious# |7 N5 l9 }6 [, g2 l7 J9 K
puberty in children with tumours of the suprasellar pineal |
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