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Sexual Precocity in a 16-Month-Old
1 h) x- p8 t4 U6 K, i+ n' M$ WBoy Induced by Indirect Topical& H. a7 M" X) y% [
Exposure to Testosterone
7 d; ^; Q4 h3 I, @' iSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
+ `1 R! F7 J& m3 r- F3 P; v; xand Kenneth R. Rettig, MD1
( Y! W% ]* G- i( S# I& QClinical Pediatrics
3 Z! U" G; l$ l7 u- F3 OVolume 46 Number 68 a' I- }! S4 a* o) G Q( G
July 2007 540-543
0 v& k0 Q' _$ o: G© 2007 Sage Publications
" a( |) c8 L- X* l10.1177/0009922806296651
- E3 w$ o. q& Whttp://clp.sagepub.com! |- \! R" ?% ]. i" w; z2 \2 Q- F
hosted at( K- C# U8 i( Q I0 Z0 {0 Z
http://online.sagepub.com& F# e* z) q* x- j
Precocious puberty in boys, central or peripheral,
/ c5 F0 ^* R, i- b) J8 Kis a significant concern for physicians. Central) K, w3 w; W: ]% R( \) N# _/ H
precocious puberty (CPP), which is mediated
/ w* s! g# w( m% C' ?$ k( ithrough the hypothalamic pituitary gonadal axis, has; `( i: a( l Q" I! ]9 }
a higher incidence of organic central nervous system# r* G# l& m- d7 r
lesions in boys.1,2 Virilization in boys, as manifested, d, l4 h4 x( _/ {
by enlargement of the penis, development of pubic
7 Q, U7 J6 l0 o* [ f* m+ Dhair, and facial acne without enlargement of testi-
' l* E% Z% H0 `# r8 |) p- l( D& f1 T, Ncles, suggests peripheral or pseudopuberty.1-3 We
' ^# O) v6 [8 n1 yreport a 16-month-old boy who presented with the6 w* y# D& T C" v; U3 b) G
enlargement of the phallus and pubic hair develop-
( g6 r: Q# ^1 \ment without testicular enlargement, which was due
6 i; d4 g# q+ }( U/ rto the unintentional exposure to androgen gel used by
$ k0 {$ F) i& l- \! f; jthe father. The family initially concealed this infor-% i% l* P/ C7 V- F+ y1 r
mation, resulting in an extensive work-up for this
7 d% _+ u' e3 D+ \+ J D/ ?, xchild. Given the widespread and easy availability of8 Y! p4 T# _ W4 r( J; ?
testosterone gel and cream, we believe this is proba-
$ T" f ^. f+ Lbly more common than the rare case report in the
! g8 [9 O' ?! `4 |1 D8 j; \- t( Mliterature.4$ C) g" s& ?* C/ E; ?; g4 V$ m
Patient Report8 J' @2 R# p8 |: p. D1 y
A 16-month-old white child was referred to the4 n& F' w1 C% a+ {% v. {6 u6 h: [* ^
endocrine clinic by his pediatrician with the concern4 [. n4 A6 T2 ]
of early sexual development. His mother noticed
; H# l3 p5 u4 z; A, klight colored pubic hair development when he was& Y/ G- S, W5 h/ }
From the 1Division of Pediatric Endocrinology, 2University of# M7 u5 d* ?( H$ s, x
South Alabama Medical Center, Mobile, Alabama.
4 J2 [! f8 f* g9 M2 G) F: \8 x7 IAddress correspondence to: Samar K. Bhowmick, MD, FACE,7 @! T1 M% X9 R. y: U: d
Professor of Pediatrics, University of South Alabama, College of
% Q0 j0 s$ L" P* B1 i8 W" \4 y5 MMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
7 P( b9 o* t( G% D1 Y$ c+ fe-mail: [email protected].; X8 o+ Z6 e" x0 U1 E
about 6 to 7 months old, which progressively became5 r/ X, j2 `1 |# c1 @! N/ a8 z( ]+ L
darker. She was also concerned about the enlarge-( Y: x8 u$ _8 T4 `- f; t
ment of his penis and frequent erections. The child
) l( C* U3 A" O: j7 J( H) |' ?was the product of a full-term normal delivery, with% d% x3 l: s) F, P
a birth weight of 7 lb 14 oz, and birth length of
& p) G! t% k* l- ~7 A# W20 inches. He was breast-fed throughout the first year, D, j2 q( ?7 C) r* i# e
of life and was still receiving breast milk along with
3 g3 n$ Q- M" }- K+ R0 ^solid food. He had no hospitalizations or surgery,
! |3 D) J: a3 M1 y$ {and his psychosocial and psychomotor development2 C3 Q; G7 W$ j6 m" H
was age appropriate.
- h6 Y, N, j, A" G8 @- a- A9 b' LThe family history was remarkable for the father,
5 y f' e) {" d0 v8 S% B/ Rwho was diagnosed with hypothyroidism at age 16,
) N1 b8 [% K$ q( xwhich was treated with thyroxine. The father’s
4 e M$ y j/ n2 S% ~9 P; \5 G7 Pheight was 6 feet, and he went through a somewhat$ s' L# x7 ?: q/ A- a' F" d) @
early puberty and had stopped growing by age 14.
1 u. e1 r: b0 R6 f- jThe father denied taking any other medication. The1 p; _$ }5 q0 i
child’s mother was in good health. Her menarche
7 y( i) @ P1 }7 t8 V2 k; H* d( swas at 11 years of age, and her height was at 5 feet
5 A3 c6 {# n2 I. b5 inches. There was no other family history of pre-
N# K: e- J1 p I, Dcocious sexual development in the first-degree rela-
1 h% b! d6 u, [. d' k5 V2 Q7 H. itives. There were no siblings.
/ G2 o7 X [& o9 V9 |Physical Examination( y! M+ E( S( Y) m3 p' S
The physical examination revealed a very active,' K" k% F" s( ?# J
playful, and healthy boy. The vital signs documented
* v' X1 Y' T5 F1 S) V8 o' ta blood pressure of 85/50 mm Hg, his length was( S. K/ s4 W' v$ M9 \( b+ S; g+ w& U
90 cm (>97th percentile), and his weight was 14.4 kg7 G$ ]' H9 s4 G2 O# _
(also >97th percentile). The observed yearly growth$ Y. D" n* R2 V
velocity was 30 cm (12 inches). The examination of
* H. @2 ?2 u- Q4 f2 g0 q( C8 \" }the neck revealed no thyroid enlargement.
) M; D) s, r- C# Z7 RThe genitourinary examination was remarkable for
; g6 H( \/ s4 L8 Eenlargement of the penis, with a stretched length of0 z! ^4 c$ ^$ j
8 cm and a width of 2 cm. The glans penis was very well
$ [$ [/ ^; h2 T' m& I! kdeveloped. The pubic hair was Tanner II, mostly around
( m# U. {5 k. q5 a: h540
- w! _8 v0 T @8 H: L; Nat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from. A# g% B+ Z% d& [ r5 g
the base of the phallus and was dark and curled. The2 g9 n1 a, T3 c w9 _% P* S. X
testicular volume was prepubertal at 2 mL each.
# v9 @0 f1 I: \5 { D: g' bThe skin was moist and smooth and somewhat
& ? p. x8 l: A6 B) c! N% y8 woily. No axillary hair was noted. There were no, Y% _$ |$ h: L, ]
abnormal skin pigmentations or café-au-lait spots.
: R5 {) t6 ?- t VNeurologic evaluation showed deep tendon reflex 2+# J) D0 K, c: y' N7 P1 a$ z
bilateral and symmetrical. There was no suggestion
7 g% B( Y M2 ?" D" |5 pof papilledema.: s- F) z: l2 v$ E( s# D
Laboratory Evaluation
- ]+ q& X( u& x; Y) DThe bone age was consistent with 28 months by
. q( J% v8 ?. xusing the standard of Greulich and Pyle at a chrono-+ t9 V/ h1 @+ }% X- {8 b
logic age of 16 months (advanced).5 Chromosomal1 R/ {, X) G; \, A: \. l) M
karyotype was 46XY. The thyroid function test% R( e Q* n! q' l8 ^
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
, F) S/ E! R% U! \- p+ H m, e: Plating hormone level was 1.3 µIU/mL (both normal).- Z$ J1 p! w1 ? ^
The concentrations of serum electrolytes, blood
. v3 A5 u v. X( }urea nitrogen, creatinine, and calcium all were
# V& b& t) P- V0 hwithin normal range for his age. The concentration5 B6 r" c' [/ |6 q" q) R; U
of serum 17-hydroxyprogesterone was 16 ng/dL
# r3 j8 E4 x7 u1 X* Y ? j(normal, 3 to 90 ng/dL), androstenedione was 20! o+ n, Z5 P5 m; X
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-. u4 ]' ~: X7 W) {! u! B
terone was 38 ng/dL (normal, 50 to 760 ng/dL),6 M+ H; B7 {; E2 V$ s5 j
desoxycorticosterone was 4.3 ng/dL (normal, 7 to; e$ `; }; d1 z' q
49ng/dL), 11-desoxycortisol (specific compound S)
" L' d: O! V, d3 Kwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-8 N; e5 n1 W& n, p3 z
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
3 ~6 J O. D5 W$ f8 `1 wtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),# K) P; L9 a6 O2 A: X1 E6 a
and β-human chorionic gonadotropin was less than
5 h! V. [3 Y; n' E' z1 N' h5 mIU/mL (normal <5 mIU/mL). Serum follicular
: o& |, b& E4 }7 I% ^& vstimulating hormone and leuteinizing hormone
" T6 s' ^ h* vconcentrations were less than 0.05 mIU/mL) \2 p; F8 L) s+ h8 K; r
(prepubertal).( t+ a; K7 J/ ^- s+ D& V y* V
The parents were notified about the laboratory
* J7 h2 Z2 p; k! e% U7 N+ Lresults and were informed that all of the tests were5 J* x1 L6 D; x" ], e/ U
normal except the testosterone level was high. The4 n: M9 j! C7 n- M* i+ f/ y9 G
follow-up visit was arranged within a few weeks to
$ b# T( h u' i% D6 k- p e2 |obtain testicular and abdominal sonograms; how-
, T% K- C; t* Z! b, `8 s* C: e% Kever, the family did not return for 4 months.
' ~! Y$ Z( ]# kPhysical examination at this time revealed that the8 M. [" X# i, z
child had grown 2.5 cm in 4 months and had gained
/ w. C7 i( H: V N g! F) ~2 kg of weight. Physical examination remained. `0 i ]( F/ |2 m
unchanged. Surprisingly, the pubic hair almost com-
9 I& ]) v! A* m& l' D) P' cpletely disappeared except for a few vellous hairs at+ t; B }& q: F R) A% \' m
the base of the phallus. Testicular volume was still 2) G9 u& `1 @; C( [* O& D' R
mL, and the size of the penis remained unchanged.
8 G/ K' A; L: M+ J, o( O% ^The mother also said that the boy was no longer hav-8 ?. L$ u: Z/ q- n. m9 D
ing frequent erections.
; C; d+ O0 ~# \- Z- Y- ~Both parents were again questioned about use of
: H: U9 ~" e, z: w. X# tany ointment/creams that they may have applied to
# ?9 ]) X7 K5 |% m! N5 D* {the child’s skin. This time the father admitted the
6 j% {7 b" n( g o* cTopical Testosterone Exposure / Bhowmick et al 541 D" e- R6 P1 l% L' x5 b
use of testosterone gel twice daily that he was apply-
5 f5 _+ H# C! ]! Aing over his own shoulders, chest, and back area for
$ X, M- l. z& \0 T' ~1 ]' B2 Na year. The father also revealed he was embarrassed
$ w4 b$ @3 D1 d; mto disclose that he was using a testosterone gel pre-; @ J. K. a! T/ N
scribed by his family physician for decreased libido0 l. o1 b6 U2 s3 \5 l: ?7 b M
secondary to depression.0 I3 N: k2 T- F$ Y5 a) W9 m
The child slept in the same bed with parents.
* Q+ C! z/ r0 G% UThe father would hug the baby and hold him on his
# F) I4 m7 q! `) `% [chest for a considerable period of time, causing sig-( S3 P0 T1 L. M1 U( r
nificant bare skin contact between baby and father.
* d+ Y$ \* r" }+ i3 a: M4 D$ H3 s3 vThe father also admitted that after the phone call,5 D) F: I6 `# |: e) y+ U
when he learned the testosterone level in the baby3 |' ]1 H" P% q4 o6 k0 \
was high, he then read the product information
) j+ L8 y, _1 B/ s# E; [packet and concluded that it was most likely the rea-) Q' f* y% C3 ~. J* Q7 W/ l
son for the child’s virilization. At that time, they
) v7 a e/ @4 V% h) R K! J# udecided to put the baby in a separate bed, and the
2 J2 ? Z# e( `) ]0 E) l$ Jfather was not hugging him with bare skin and had2 w' p @. A; h: c ?6 O. z, k& z
been using protective clothing. A repeat testosterone
' |& y8 |! P9 Ltest was ordered, but the family did not go to the) H, K; P6 l" D+ T! n7 x
laboratory to obtain the test.
$ f) ]- c9 H% u) FDiscussion
: c8 C5 z0 J5 O) U, }( ~' zPrecocious puberty in boys is defined as secondary* L7 G+ P+ \8 b8 U
sexual development before 9 years of age.1,4. `8 d* T/ L5 P) K
Precocious puberty is termed as central (true) when
# I) g1 G. R1 Z6 p# I$ o* B& u/ Oit is caused by the premature activation of hypo-
; c% v% P# }. c$ w) ?9 x7 hthalamic pituitary gonadal axis. CPP is more com-
2 n4 ]/ R; k- [0 F+ _% i Smon in girls than in boys.1,3 Most boys with CPP2 p Z2 R* }& C8 a$ b2 n8 K6 F
may have a central nervous system lesion that is: a. f( M' ^# v# W6 {
responsible for the early activation of the hypothal-
$ a: O1 W- P h. c, I# lamic pituitary gonadal axis.1-3 Thus, greater empha-+ i( E) q0 Y5 n( c7 ?1 Z1 P- g
sis has been given to neuroradiologic imaging in
# H' R" F+ g5 bboys with precocious puberty. In addition to viril-
2 S1 D" U8 |4 x8 k3 zization, the clinical hallmark of CPP is the symmet-
5 u# h7 s2 r: jrical testicular growth secondary to stimulation by
- y" b* B1 r: d: J% o! ^+ Hgonadotropins.1,3
2 c$ L( c9 f7 J2 |: K, MGonadotropin-independent peripheral preco-
+ j( c$ a$ y4 x, F+ ~3 Jcious puberty in boys also results from inappropriate
, d! _( o, F" H# K7 S+ F4 Mandrogenic stimulation from either endogenous or
0 I" K2 w) \& h# o+ yexogenous sources, nonpituitary gonadotropin stim-
+ k: z+ r6 p' i2 Uulation, and rare activating mutations.3 Virilizing0 m8 H, a. `5 P( ^# ^
congenital adrenal hyperplasia producing excessive0 z1 n. p! ^' {. t
adrenal androgens is a common cause of precocious
. V+ p1 J8 Z$ G9 Bpuberty in boys.3,4
( S: v/ @* O [( jThe most common form of congenital adrenal
% `9 o) N4 x7 O0 t5 W5 A- l! {; Q- Shyperplasia is the 21-hydroxylase enzyme deficiency.
0 Y% R) v3 C3 l, LThe 11-β hydroxylase deficiency may also result in
7 L) _( q7 C! ?4 S8 x% Gexcessive adrenal androgen production, and rarely,
0 k: A& E5 L1 |/ z3 r# w* zan adrenal tumor may also cause adrenal androgen+ _- ]" _8 E' g, P) n8 C
excess.1,39 Q9 ^* [: c( |* z
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
4 S8 G# i1 T# g& Z' _( v0 `. Q542 Clinical Pediatrics / Vol. 46, No. 6, July 2007: C7 N1 G& _; }0 ]% |0 Y. |0 R
A unique entity of male-limited gonadotropin-
, V% a( r7 a; h5 }+ c8 Iindependent precocious puberty, which is also known9 J* v& X _4 ~) j
as testotoxicosis, may cause precocious puberty at a
% R+ Q: o) k* I( lvery young age. The physical findings in these boys
% u7 V& m8 m. K- U/ ^2 q; y; swith this disorder are full pubertal development,
. ~7 N$ ~8 J, o7 nincluding bilateral testicular growth, similar to boys0 V3 w6 b; A8 `
with CPP. The gonadotropin levels in this disorder8 k O: v$ Z# N5 p; a& P
are suppressed to prepubertal levels and do not show; M1 Y3 N4 k( B' Q2 n+ t# }
pubertal response of gonadotropin after gonadotropin-
% P, C+ K$ Z* v. w; Creleasing hormone stimulation. This is a sex-linked
7 A1 u/ w u5 a2 x5 m+ u- z& iautosomal dominant disorder that affects only
$ `* m) D5 i/ x* Cmales; therefore, other male members of the family
5 ~: h0 b, z# tmay have similar precocious puberty.3
- q1 B* n4 T5 q3 EIn our patient, physical examination was incon-
/ @# [* |% D7 ?; f* D" ^9 j8 lsistent with true precocious puberty since his testi-
6 S' p, [; p1 K8 y3 C6 G: q! G8 ?cles were prepubertal in size. However, testotoxicosis
! |, u5 ?3 [ G0 @, E8 w. _was in the differential diagnosis because his father
' v, N. L- ^1 l+ P& mstarted puberty somewhat early, and occasionally,
8 H0 W5 d( |6 R, G0 v- u% ]testicular enlargement is not that evident in the% i- d' E# r* p7 b
beginning of this process.1 In the absence of a neg-
: ^" q, Z! |+ \! Fative initial history of androgen exposure, our/ U6 S/ M( v% }
biggest concern was virilizing adrenal hyperplasia,- y6 S# [6 o! H+ V7 _
either 21-hydroxylase deficiency or 11-β hydroxylase5 Y% x: G: x! M; Z+ e
deficiency. Those diagnoses were excluded by find-
G+ S- Z1 ^9 K+ A3 u$ _# Wing the normal level of adrenal steroids.
7 M% U3 @. X- u! J, I$ fThe diagnosis of exogenous androgens was strongly" o) U0 u' R4 U t. y8 q
suspected in a follow-up visit after 4 months because
* j6 M( n/ T4 a u' Pthe physical examination revealed the complete disap- b8 m$ W6 h6 {. I* j4 q
pearance of pubic hair, normal growth velocity, and
8 B% k; m& Z& i6 Z, u. `. M! y( ^decreased erections. The father admitted using a testos-- U- I% _# c6 ]' F0 ] C
terone gel, which he concealed at first visit. He was! W$ e7 t( J1 w4 e
using it rather frequently, twice a day. The Physicians’
# B% d& D6 i$ z3 M$ i6 m. U1 y+ d( tDesk Reference, or package insert of this product, gel or
2 L- L; C. ` X/ ~5 x) l/ p6 D- j! Bcream, cautions about dermal testosterone transfer to, I* ?( J$ j8 a2 C7 M
unprotected females through direct skin exposure.! y; g7 q2 m: P. b7 z/ W/ _0 D' A
Serum testosterone level was found to be 2 times the
( L/ i* j1 H" [' H& k ebaseline value in those females who were exposed to$ r7 t" d* C4 \/ p# D/ I( V
even 15 minutes of direct skin contact with their male8 S1 L1 J) |3 x7 a" ~$ _* [
partners.6 However, when a shirt covered the applica-
+ K" m8 ?5 n4 x. T& Z! A- Ltion site, this testosterone transfer was prevented.7 F, E7 A" \7 O, ]. ~" A
Our patient’s testosterone level was 60 ng/mL," @+ G, W: n7 j! p7 D6 ^
which was clearly high. Some studies suggest that& Q& W, x5 a/ ?
dermal conversion of testosterone to dihydrotestos-
) `' n) Y# |" O8 `# u0 uterone, which is a more potent metabolite, is more
5 w- Q0 Z/ t% T; Aactive in young children exposed to testosterone2 K) P" i! f3 T$ | a
exogenously7; however, we did not measure a dihy-9 ?, U, \ \8 B: X) M8 @6 K
drotestosterone level in our patient. In addition to) w4 }0 m1 h$ z& b
virilization, exposure to exogenous testosterone in
$ m; c8 \& i, R3 ?, _! j+ ^0 O' nchildren results in an increase in growth velocity and ?* K% Z5 ]* F
advanced bone age, as seen in our patient.
( Q8 g) X0 }2 m3 kThe long-term effect of androgen exposure during( U( ~8 u; y1 D" M* u' R" T1 X
early childhood on pubertal development and final2 { v5 P6 O0 z! p
adult height are not fully known and always remain) b% m' b+ p) G) F* c
a concern. Children treated with short-term testos-
! _8 H) U$ M- S4 k) lterone injection or topical androgen may exhibit some& z$ v" t6 B1 l* d3 W) ^ t
acceleration of the skeletal maturation; however, after# O3 s& P& Y3 r: s( j
cessation of treatment, the rate of bone maturation, y: p! ]; g& j! O' o# G
decelerates and gradually returns to normal.8,93 E1 Y* H& \3 G
There are conflicting reports and controversy
- g+ P8 g$ a- }7 Z5 dover the effect of early androgen exposure on adult
. Q+ `& y3 ^( w2 s6 w# L0 hpenile length.10,11 Some reports suggest subnormal
# u* Z- M0 P1 C) `) ]adult penile length, apparently because of downreg-
- W' `% Z4 `( b6 e6 Q6 }% T+ Z- aulation of androgen receptor number.10,12 However,
, V7 A+ V6 b8 ?/ c6 u0 x' b4 NSutherland et al13 did not find a correlation between
+ }# I' S4 A: z! Vchildhood testosterone exposure and reduced adult
% b, \9 `( J1 H( ^! x u" gpenile length in clinical studies.
0 ]' B; `, v: c6 U+ f5 }( ^Nonetheless, we do not believe our patient is
$ j) I0 I' g1 @7 X& `& Lgoing to experience any of the untoward effects from9 h; o& S3 b7 w* x+ {
testosterone exposure as mentioned earlier because
$ g( l' v+ w f3 T" V pthe exposure was not for a prolonged period of time.
7 u7 J; X1 u: ]Although the bone age was advanced at the time of
7 A8 J G, }# l$ A5 ^4 ^" ndiagnosis, the child had a normal growth velocity at5 p5 f4 J" A8 y) f6 D Z+ z
the follow-up visit. It is hoped that his final adult
6 v8 y/ d6 `* K6 ^( Y9 w Kheight will not be affected.& o" H7 \& T- `+ N8 P% ~2 k
Although rarely reported, the widespread avail-
6 y. F* G+ G" Jability of androgen products in our society may
2 X4 U, F# r! h7 X0 a+ m2 u findeed cause more virilization in male or female
O9 ]( I& C8 m5 ^) H$ S$ ]! E8 N" gchildren than one would realize. Exposure to andro-
! [/ e( y: l' z" F# x3 F& u# _gen products must be considered and specific ques-
- B# f3 q4 ]8 L; t) ^$ qtioning about the use of a testosterone product or) G3 q6 E: t. I$ i* m
gel should be asked of the family members during' t! r, G& l7 Z" T7 k
the evaluation of any children who present with vir-/ Z( X3 `3 t& q) a3 t4 Y" K' ?
ilization or peripheral precocious puberty. The diag-
1 W; {% [' G. }9 g& i, znosis can be established by just a few tests and by
- ~ w5 O1 D; U) u9 jappropriate history. The inability to obtain such a! P3 _, ~( N6 k$ p5 k2 b3 H
history, or failure to ask the specific questions, may( K" I5 A! S" o+ o+ s
result in extensive, unnecessary, and expensive
- y4 b: w" b) L/ b+ sinvestigation. The primary care physician should be5 p* }% c2 g5 R+ L+ S! m# ^: h
aware of this fact, because most of these children+ N8 v7 s6 _0 V* y6 o# _) A
may initially present in their practice. The Physicians’
$ V+ t/ S3 h1 V8 k* n; n- ?- ~Desk Reference and package insert should also put a% f5 M6 G% Q# V, k. ?! Z+ ~$ g! ?
warning about the virilizing effect on a male or
$ z C) u( `4 a7 nfemale child who might come in contact with some-
' f; J/ I1 D! None using any of these products.! x) K- X2 ]! _% ]/ H6 A
References
) R( E6 N* X: Y! z4 X+ G+ r1. Styne DM. The testes: disorder of sexual differentiation
4 |) z# V, B6 r* xand puberty in the male. In: Sperling MA, ed. Pediatric1 q' K5 w0 `# k T0 t1 \
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
; ] _7 z/ K" o1 k. h T7 Y) G1 B+ v% B2002: 565-628.
2 @, [0 u. n& L o5 @2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious2 @3 L6 j2 _" s8 W* u7 O) Y
puberty in children with tumours of the suprasellar pineal |
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