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Sexual Precocity in a 16-Month-Old
9 \2 \/ Q+ h0 S- x' }Boy Induced by Indirect Topical
) K: t. j( I5 a, zExposure to Testosterone
L" O' ~$ ]* a- h3 m2 r, ~- j2 MSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,25 }- d8 M! u0 e+ T0 l7 F
and Kenneth R. Rettig, MD1
, U3 X' Y K+ G3 K( nClinical Pediatrics
, k9 T+ @" b; r( n" C/ NVolume 46 Number 6
$ C) a9 |- ^7 z: vJuly 2007 540-543
- h( {2 o2 J$ v- ^& ?© 2007 Sage Publications
8 A Y7 l0 F/ D' x6 P10.1177/0009922806296651
7 W+ n% `0 _7 n: `& c4 x' g# bhttp://clp.sagepub.com3 }4 L6 Y% `4 r
hosted at
* H) ^, y% _$ [* B1 g4 w4 }http://online.sagepub.com7 s& c1 d. ^3 D- }" v6 E6 m
Precocious puberty in boys, central or peripheral,
+ T0 Z- z- T# F! c0 ]& d8 }is a significant concern for physicians. Central
0 Q) s. g% D; c# `( iprecocious puberty (CPP), which is mediated o, H# n5 S# f, K( ~: l
through the hypothalamic pituitary gonadal axis, has
& f) ]+ i& s6 {% Fa higher incidence of organic central nervous system2 ~( p! E0 c1 D" P/ Z
lesions in boys.1,2 Virilization in boys, as manifested) d+ k( s4 t- } Y+ p
by enlargement of the penis, development of pubic
. P( p* g$ S+ u: @( `hair, and facial acne without enlargement of testi-0 ~, C+ r# {( y
cles, suggests peripheral or pseudopuberty.1-3 We0 q9 V$ w2 e( \# s+ H+ A+ u
report a 16-month-old boy who presented with the
B, O o2 V# {/ v' e9 Zenlargement of the phallus and pubic hair develop-
s3 N: x- _1 D. C1 t% V4 Cment without testicular enlargement, which was due
) i) [, w; R! V/ K7 Lto the unintentional exposure to androgen gel used by" Y* O8 r' f* V2 C
the father. The family initially concealed this infor- e. a2 ?% n9 a$ U. i" @0 k7 ]
mation, resulting in an extensive work-up for this
; ]* Q; y( t/ B bchild. Given the widespread and easy availability of# ^& F8 `; L6 H
testosterone gel and cream, we believe this is proba-
9 B6 B3 X; S7 I1 o9 \: s Sbly more common than the rare case report in the
5 j+ g( T: u8 e& n6 D. h. p8 N0 i) Hliterature.4# x+ v/ K2 F* P, i) ?' T
Patient Report
' K. P+ F% H+ U$ @2 t, iA 16-month-old white child was referred to the
% [3 _' i4 F. @4 q7 O# ]# d8 w) J+ @endocrine clinic by his pediatrician with the concern# O' t/ ~8 a* W; P2 T; e* D$ r
of early sexual development. His mother noticed
3 E( S0 L9 J: t3 v8 p. H2 ?light colored pubic hair development when he was2 T/ @- V# k& s1 E1 u
From the 1Division of Pediatric Endocrinology, 2University of5 c7 A7 [4 S) x
South Alabama Medical Center, Mobile, Alabama.
0 C* ~" E# f. [! J' U4 qAddress correspondence to: Samar K. Bhowmick, MD, FACE,6 T, L& @7 D. Q
Professor of Pediatrics, University of South Alabama, College of9 E$ K' U; {& x1 u' t
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;& |+ c+ |3 Y5 O- c N* T
e-mail: [email protected].
* M8 r6 x5 p) Q6 H- g6 _about 6 to 7 months old, which progressively became
# C- Y( f1 \7 q# cdarker. She was also concerned about the enlarge-
% ~ h7 R( y& h8 A5 Jment of his penis and frequent erections. The child
* m, p, W, E9 y# U# w; E8 C' uwas the product of a full-term normal delivery, with
% A) U9 j8 g! G4 M8 \a birth weight of 7 lb 14 oz, and birth length of+ S/ ~7 q! r0 T
20 inches. He was breast-fed throughout the first year
* r$ G# V0 x" d# F7 k* V. T6 uof life and was still receiving breast milk along with
9 e. I5 X/ l+ e8 C0 j) Bsolid food. He had no hospitalizations or surgery,
+ u8 A: y/ f* E8 k$ ?8 X5 w1 band his psychosocial and psychomotor development
}+ d* e+ ]& D+ D6 J" C5 i0 owas age appropriate.
0 [2 S0 J2 v) c( r6 uThe family history was remarkable for the father,
" L& N) _$ s- T% Y9 ~) wwho was diagnosed with hypothyroidism at age 16,
- |* Z) H! ~* s" owhich was treated with thyroxine. The father’s
" T& s& L4 G; k! Oheight was 6 feet, and he went through a somewhat
% Y6 ~9 A) K, K6 b F; nearly puberty and had stopped growing by age 14.
5 e7 \1 s: _, h- v. }6 W. I; K) bThe father denied taking any other medication. The9 `. S% n ^* O! h
child’s mother was in good health. Her menarche
$ ~" ?1 T2 l+ g/ }. o0 Q! I7 Awas at 11 years of age, and her height was at 5 feet
& o+ ?: L D$ E$ E- V5 inches. There was no other family history of pre-
6 h. W8 |. m2 L! xcocious sexual development in the first-degree rela-
^# l& A5 n- ~( Q! m1 |tives. There were no siblings.
, t" U3 i4 W+ W. s0 }Physical Examination
& c/ u% e8 p8 M9 LThe physical examination revealed a very active,+ M! H0 O$ R2 F
playful, and healthy boy. The vital signs documented
3 Z& G/ k! B# y" q1 Ka blood pressure of 85/50 mm Hg, his length was
+ _' c2 B" \! \0 q0 j* [90 cm (>97th percentile), and his weight was 14.4 kg- w6 R* M H4 ^& q8 Y) w- B
(also >97th percentile). The observed yearly growth: h" w% n# Y) U7 ^) ?
velocity was 30 cm (12 inches). The examination of1 K" @9 ^9 c/ j. B. F# J' x
the neck revealed no thyroid enlargement.
) l' U* @1 X/ s) I' z. s5 O/ WThe genitourinary examination was remarkable for% q$ e2 @$ ?+ u6 v! ]4 K
enlargement of the penis, with a stretched length of
0 E+ ?5 i" Q4 o, s. u% c$ @8 cm and a width of 2 cm. The glans penis was very well
) w; Y6 J" c2 [( {developed. The pubic hair was Tanner II, mostly around) U) z/ \- d, u7 @8 j
540
* ^: M. |. D' [at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
& ^ v( w) t9 `9 M5 q/ I/ Kthe base of the phallus and was dark and curled. The
* f; L; X% u. M6 R3 |3 |testicular volume was prepubertal at 2 mL each.3 g4 q b- C8 ?+ z r
The skin was moist and smooth and somewhat
. a9 [. R) J D* Yoily. No axillary hair was noted. There were no) t9 ^- t; |4 @
abnormal skin pigmentations or café-au-lait spots.9 i/ n! H8 `+ k. Q4 D/ x4 W
Neurologic evaluation showed deep tendon reflex 2+4 a! J% y! g; I7 c0 l- X7 ]* F. M% Y7 P
bilateral and symmetrical. There was no suggestion5 ^3 ~7 v; G, @* T' P
of papilledema.4 S0 f- `' F' o8 Q, I" O/ x5 n; l
Laboratory Evaluation
. ^5 u5 n0 z EThe bone age was consistent with 28 months by6 N- D9 r* A* A; |. o8 U
using the standard of Greulich and Pyle at a chrono-2 [/ ]& u+ K% R# Q3 y+ z; @% M& y
logic age of 16 months (advanced).5 Chromosomal
# {! O' j# H2 D7 ?1 U# Ukaryotype was 46XY. The thyroid function test3 V' o2 S" r9 P) ~" k, y
showed a free T4 of 1.69 ng/dL, and thyroid stimu- M: x, b; |% B& B
lating hormone level was 1.3 µIU/mL (both normal).
- c5 E+ }- F* ^5 ~The concentrations of serum electrolytes, blood
% |8 W, F$ F/ _1 ^urea nitrogen, creatinine, and calcium all were: W" h6 a4 ^# V' @+ a
within normal range for his age. The concentration6 Z7 z s1 W# P9 x2 {: H! i7 h$ f$ a
of serum 17-hydroxyprogesterone was 16 ng/dL* _- p, g4 }1 P8 M" Y* H. ~
(normal, 3 to 90 ng/dL), androstenedione was 20: a- ]! t7 a0 P/ h5 n8 u, f
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros- x- o$ V# |) i; q, y. X9 ?
terone was 38 ng/dL (normal, 50 to 760 ng/dL),$ W8 H# }- [9 E! d1 e/ @
desoxycorticosterone was 4.3 ng/dL (normal, 7 to0 W" \' T: F- W9 c1 h' a
49ng/dL), 11-desoxycortisol (specific compound S)
' ~ ?1 U' T& O) F3 [9 m% q- uwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
: m R5 p: N7 P( O( ftisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
# Q1 ^8 j7 @/ l4 Etestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
/ i) ~ q* M3 z+ Zand β-human chorionic gonadotropin was less than7 H6 ?) S* i. w X, D
5 mIU/mL (normal <5 mIU/mL). Serum follicular% d# O1 e8 o ]* s5 _
stimulating hormone and leuteinizing hormone
( Z% H6 J; y" L" ^6 }concentrations were less than 0.05 mIU/mL
: _+ e) E7 }% e; r9 ?, ^4 ~ r(prepubertal).
: ^2 Z9 S1 P! c- O0 p$ h) a7 r8 y1 |7 TThe parents were notified about the laboratory' o) X7 G2 A Z3 ^
results and were informed that all of the tests were
" V) _3 _ O* A, \normal except the testosterone level was high. The! @( ^% \1 Y$ x; ]: {. ~
follow-up visit was arranged within a few weeks to: R {) I- I t0 @
obtain testicular and abdominal sonograms; how-- M4 Z% i( N4 W. G7 T' g0 K+ F
ever, the family did not return for 4 months.7 E- R/ L8 a3 x
Physical examination at this time revealed that the
( @4 k% n" H( {) Qchild had grown 2.5 cm in 4 months and had gained
1 b! b; d$ L8 ^) Y4 N1 K) k0 B2 kg of weight. Physical examination remained
A. Y* q1 o, w8 i* D4 Tunchanged. Surprisingly, the pubic hair almost com-
8 D5 F2 v/ `# ?" ppletely disappeared except for a few vellous hairs at2 d3 M, w' A0 i5 r
the base of the phallus. Testicular volume was still 2% R" n* i- V `, s( N5 M* [
mL, and the size of the penis remained unchanged.1 u B( T& ]; K; P0 w$ q& O/ w
The mother also said that the boy was no longer hav-
, N$ a- J8 w! C# z/ n3 n {9 g5 hing frequent erections.2 X: W7 h/ a% y: M2 z4 D8 ^" {
Both parents were again questioned about use of
$ V/ h- @& r; K( G% a* S0 Y" vany ointment/creams that they may have applied to
1 l% d: E3 p, o" `the child’s skin. This time the father admitted the
3 y6 P5 n& Y+ NTopical Testosterone Exposure / Bhowmick et al 541
7 O6 l0 R( R \- t9 E" wuse of testosterone gel twice daily that he was apply-: @% e) j: t" [% {" k
ing over his own shoulders, chest, and back area for
1 v- U3 L* U# t5 p# Sa year. The father also revealed he was embarrassed9 |) r: {; f( Z9 V( m9 M
to disclose that he was using a testosterone gel pre-4 ~7 {8 `/ j& g0 V7 W
scribed by his family physician for decreased libido
8 J; s: H4 {. H+ z* K& ^secondary to depression.1 x6 P7 B* N2 ]. g
The child slept in the same bed with parents.
. j# E. k8 A. H4 `3 K1 V8 LThe father would hug the baby and hold him on his# D4 l$ \/ ?& P/ I% r3 k6 S4 F, y
chest for a considerable period of time, causing sig-% N7 k8 {7 H: i$ G% P7 |! d! j
nificant bare skin contact between baby and father." k0 y! j1 L& x) f7 |3 a
The father also admitted that after the phone call,+ e& w3 O$ C" e1 `( q
when he learned the testosterone level in the baby
% e" R* g' _4 @" Swas high, he then read the product information4 g+ x r1 I W6 B4 p# i F3 T
packet and concluded that it was most likely the rea-
. x* V/ X9 v; L. E( m/ }# a$ c8 [0 kson for the child’s virilization. At that time, they0 Q; z g0 {" H) z0 R
decided to put the baby in a separate bed, and the8 x2 i& s. |& E Z, v5 i
father was not hugging him with bare skin and had
1 S$ c i5 p/ D% vbeen using protective clothing. A repeat testosterone
* J$ R" c/ l% [3 ?8 W) ]% Q; Atest was ordered, but the family did not go to the. n; h0 Q9 f9 m7 J; C
laboratory to obtain the test.
; Z# d5 q5 w8 U* oDiscussion
2 ?& {/ |/ J: L5 mPrecocious puberty in boys is defined as secondary
0 r/ S' F( k6 c* E$ K9 |- @sexual development before 9 years of age.1,4
6 d( l2 C) Z/ V+ s |0 v! tPrecocious puberty is termed as central (true) when ~5 k( q; K, T
it is caused by the premature activation of hypo-
9 \$ {* V8 |& b' ^ Z8 n* M5 \% c# {thalamic pituitary gonadal axis. CPP is more com-
4 V ?# u* ^! K k6 v3 q- g7 amon in girls than in boys.1,3 Most boys with CPP
8 p4 _5 _1 X# A7 Z, s! p) ^may have a central nervous system lesion that is/ i7 m* O% Y. p! o1 }! U6 n. p
responsible for the early activation of the hypothal-5 g! h- E j# F0 A9 r; m6 s# ?6 g
amic pituitary gonadal axis.1-3 Thus, greater empha-+ z- K& r8 X5 ]( U0 C) v
sis has been given to neuroradiologic imaging in. d- b" n) [# E- a" i' y+ c: {: K
boys with precocious puberty. In addition to viril-: T5 G3 S( F7 I
ization, the clinical hallmark of CPP is the symmet-% b, K/ o* W7 A+ p
rical testicular growth secondary to stimulation by
' `- U" o2 P) ?gonadotropins.1,3" s9 X8 T2 P" m; [0 l, v$ e
Gonadotropin-independent peripheral preco-1 z. X; Y& c. t% X: O0 C
cious puberty in boys also results from inappropriate& |1 r( v, i! _; m; U" O, v
androgenic stimulation from either endogenous or. Q$ `3 Y0 ]/ w* f! y8 A
exogenous sources, nonpituitary gonadotropin stim-8 o0 p5 h. D9 _' x% b4 O
ulation, and rare activating mutations.3 Virilizing/ I1 b. O4 @8 L$ c$ S- o, a4 G
congenital adrenal hyperplasia producing excessive
& m/ Y7 M1 j+ S' o% Y1 h0 Madrenal androgens is a common cause of precocious" A( X* A3 S7 \* G
puberty in boys.3,4# R' e& [9 Q; C; K z
The most common form of congenital adrenal) f0 O3 R m' b6 ~
hyperplasia is the 21-hydroxylase enzyme deficiency.
$ Y$ D/ W8 [8 H4 yThe 11-β hydroxylase deficiency may also result in' g m7 a, i f: ]
excessive adrenal androgen production, and rarely,
# ^; n1 Q2 X6 F" ean adrenal tumor may also cause adrenal androgen
7 m @4 H. o* z* `3 hexcess.1,33 \9 i/ Z; D- V7 K& z
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from* d. T @8 g3 ^7 x7 t
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007% O8 m" M6 u) D+ Q7 Y9 y6 j; J
A unique entity of male-limited gonadotropin-# ~* A( p4 y0 I7 g( p- z8 }
independent precocious puberty, which is also known4 K3 w9 B4 n4 }6 P1 |" Q; f* O
as testotoxicosis, may cause precocious puberty at a
2 }" U2 t5 X5 G6 o7 mvery young age. The physical findings in these boys
- z) P7 A9 {1 }- Z2 g/ O$ [with this disorder are full pubertal development, `/ [" s$ r; C* f
including bilateral testicular growth, similar to boys, B% k) C8 S# s( R
with CPP. The gonadotropin levels in this disorder5 o0 H, g1 r t4 }& }; A; Z T
are suppressed to prepubertal levels and do not show1 c1 l: M) a2 D1 s# k
pubertal response of gonadotropin after gonadotropin-
* j2 m( |$ ?1 k9 |2 creleasing hormone stimulation. This is a sex-linked) X- R+ A+ ^! J8 z7 I2 D. ^
autosomal dominant disorder that affects only6 M% X# y0 A/ s) G) Z$ `% E: _
males; therefore, other male members of the family
1 O O' D" W M+ Pmay have similar precocious puberty.3: ^: ?- w$ Q" L/ L6 x& [0 K& g
In our patient, physical examination was incon-4 v" w H' q3 ]7 O+ `: M$ ~9 {
sistent with true precocious puberty since his testi-
, E$ Z e/ P1 U+ n% V# i7 Ccles were prepubertal in size. However, testotoxicosis1 D8 D- l# i7 | W/ C( h
was in the differential diagnosis because his father
0 I& n) D6 _" P, b A% Tstarted puberty somewhat early, and occasionally,9 x8 W& z. K U' L
testicular enlargement is not that evident in the) p$ u) r5 H% |" A- z
beginning of this process.1 In the absence of a neg-
! M; D6 C0 p$ M$ ?ative initial history of androgen exposure, our, X' o( r: Q' }- t* B/ V
biggest concern was virilizing adrenal hyperplasia,
% Y" o4 P" I2 H, Oeither 21-hydroxylase deficiency or 11-β hydroxylase
- ^. p0 @) k+ a7 X4 D5 f, wdeficiency. Those diagnoses were excluded by find-3 x4 f1 d4 s+ ~- A" `! M
ing the normal level of adrenal steroids.5 s7 Z9 @1 A9 a' ?$ d) I
The diagnosis of exogenous androgens was strongly
, t( P7 H- F( N8 k9 v! l9 |suspected in a follow-up visit after 4 months because
5 O3 h/ i; ]( |* l5 j+ Wthe physical examination revealed the complete disap-
1 e8 r' K# m/ E# e+ D$ Rpearance of pubic hair, normal growth velocity, and9 R2 K( X$ s, e: W( V# c$ S' {+ |
decreased erections. The father admitted using a testos-
9 O( F5 w# s, d# p* Tterone gel, which he concealed at first visit. He was
& z; _# V. z* o4 _' Yusing it rather frequently, twice a day. The Physicians’& y y, j* z( t0 H
Desk Reference, or package insert of this product, gel or
5 M2 u( N! n) F8 ycream, cautions about dermal testosterone transfer to
+ H7 D% M n3 v, P7 sunprotected females through direct skin exposure.
, n' m5 g: |- v8 P- |Serum testosterone level was found to be 2 times the
7 \- E! {# \: Jbaseline value in those females who were exposed to
( a& k' z! B+ G* p+ m8 H" geven 15 minutes of direct skin contact with their male
% |: O, |; {7 _1 Q$ ^partners.6 However, when a shirt covered the applica-' J; ^& j+ H) |: L5 l7 A* h) p
tion site, this testosterone transfer was prevented.
1 V$ A0 G5 K* Z0 D" z9 g5 {$ KOur patient’s testosterone level was 60 ng/mL,
, ` \) r4 C) e7 y9 f! k6 P& X" uwhich was clearly high. Some studies suggest that6 B" ]- U4 ?& I! Z" ]* y9 a
dermal conversion of testosterone to dihydrotestos-' @" l8 |: W* c' y1 Q
terone, which is a more potent metabolite, is more
& h% v8 @9 o2 b: y9 [! [- k0 {active in young children exposed to testosterone
/ J8 ?- q0 Q% F" G4 Yexogenously7; however, we did not measure a dihy-
: k2 s4 ~0 p$ k7 adrotestosterone level in our patient. In addition to
7 Q9 J" Z T9 hvirilization, exposure to exogenous testosterone in2 k1 M, p0 u3 G: q2 F
children results in an increase in growth velocity and! ^- i& A: B% k! q* L" |' C( P6 }
advanced bone age, as seen in our patient.) ?7 }% \& D3 Z; q: ]) d% e Q: g
The long-term effect of androgen exposure during, x& G) }" _& W! w% l2 h/ m- p
early childhood on pubertal development and final) L* j" Q: |5 x: P4 ]. A Q% W# I( y
adult height are not fully known and always remain" K! E# p: v9 F# [
a concern. Children treated with short-term testos-* u2 K9 A- S' f% ^- h0 T; f
terone injection or topical androgen may exhibit some
& |# H3 n& G" _) a8 Racceleration of the skeletal maturation; however, after
# ^0 V: _; H+ w" [3 B5 @) Jcessation of treatment, the rate of bone maturation
$ f' q( ?+ R2 o h3 q( b2 P& vdecelerates and gradually returns to normal.8,9' {# z: V4 ?: J$ B% y
There are conflicting reports and controversy5 ]& g1 r' k8 w3 _% O
over the effect of early androgen exposure on adult$ a6 X2 x0 }* T$ r1 v8 Z! K) @" n' w
penile length.10,11 Some reports suggest subnormal
4 K' M2 p- R2 U A# {/ G* Yadult penile length, apparently because of downreg-
+ I' p. H L" P) T( r7 Qulation of androgen receptor number.10,12 However,
$ x" N+ I% q- j; vSutherland et al13 did not find a correlation between! ?$ n/ \1 g1 O$ ^+ V
childhood testosterone exposure and reduced adult7 Y4 e4 Z+ V0 j( ^9 P" `
penile length in clinical studies.
, ~* p7 D- E9 x1 r9 Q ^1 }* ~# m0 vNonetheless, we do not believe our patient is. x# N* P) k9 k9 i3 T
going to experience any of the untoward effects from
' J/ h3 D5 a5 itestosterone exposure as mentioned earlier because v, a) s. H2 B3 c! V% k) w# W
the exposure was not for a prolonged period of time.! E# t! } A0 I4 u
Although the bone age was advanced at the time of/ m; ~( j7 |7 _8 W: A
diagnosis, the child had a normal growth velocity at
( b* x( L# N; g8 d5 R6 l8 }! W4 tthe follow-up visit. It is hoped that his final adult% x, H) l2 B5 R. E- ]
height will not be affected.# z& q6 E* Y# P- a0 e: m+ X7 E
Although rarely reported, the widespread avail-) i& M. u+ Q3 |. ]8 ?; ^
ability of androgen products in our society may; \ X: d& i# g
indeed cause more virilization in male or female
$ [4 k/ j6 I7 |8 i. Uchildren than one would realize. Exposure to andro-# O' C* W3 p) V9 ^
gen products must be considered and specific ques-
7 z2 Z' ~: t1 s2 N \) q2 stioning about the use of a testosterone product or/ ]+ o0 u4 l; }2 E( y
gel should be asked of the family members during
3 i6 p& h/ e$ L+ D9 z, g+ rthe evaluation of any children who present with vir-3 i @" M1 Y: A9 v5 `/ |
ilization or peripheral precocious puberty. The diag-
$ T6 j9 H7 {+ g: O6 |nosis can be established by just a few tests and by
: {/ G4 r2 f5 O M# O% a! vappropriate history. The inability to obtain such a8 h, e' }4 x8 u- r7 g
history, or failure to ask the specific questions, may
@3 [# [; }( T" ^& tresult in extensive, unnecessary, and expensive
: I" ]3 R. d* e5 b4 y; Kinvestigation. The primary care physician should be
* E; }# f$ x7 l$ N7 gaware of this fact, because most of these children% d1 q) T( u. f% U( q) L
may initially present in their practice. The Physicians’6 r* g' R n2 N/ g6 G7 c) a8 V
Desk Reference and package insert should also put a$ N! G9 Y8 H4 m% `( C) h5 p# L2 g# b
warning about the virilizing effect on a male or
9 H i4 U5 D1 V; g9 @female child who might come in contact with some-
# M/ P9 R& N: F% {one using any of these products.
5 e, p- H/ N* _' O, X4 YReferences! A5 i* l# g- X" d7 u2 y
1. Styne DM. The testes: disorder of sexual differentiation" R! J: U1 k! Q; O! o- o1 {6 N( c9 e
and puberty in the male. In: Sperling MA, ed. Pediatric
! }! n: w7 W* @7 g+ E- ?Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;# ]9 M: S# R- M' D9 f4 z
2002: 565-628.
6 x0 v7 E3 l: [4 N3 ~/ R2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious$ z4 x7 D/ F. I4 _. s
puberty in children with tumours of the suprasellar pineal |
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