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Sexual Precocity in a 16-Month-Old
5 j) A. t( k2 P% N) DBoy Induced by Indirect Topical
6 b3 V# x& {8 u; y0 \5 h+ ^Exposure to Testosterone
J0 v) v6 l' _; j: C4 f/ X8 s) RSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
( ^6 V% T' N$ S9 @) ^and Kenneth R. Rettig, MD1
; i" J' Z/ I& J2 L9 |( p+ K5 rClinical Pediatrics2 A' T) z! w* {) |5 c5 g
Volume 46 Number 6
% d2 V) U& G, f$ ]6 XJuly 2007 540-543
/ r& E4 ]7 p& o0 c' q* {2 _ D© 2007 Sage Publications( Z% r+ I: [+ ?
10.1177/0009922806296651
0 x1 p% w# X8 @# j. Vhttp://clp.sagepub.com
6 l2 i& J" N2 f( ~% ~# {- qhosted at( E& p) O5 { t- ~1 u
http://online.sagepub.com0 o' e: Y* H) ^' Q+ t ~2 L
Precocious puberty in boys, central or peripheral,
/ O: t9 }* f. s! o4 D4 E+ d( }is a significant concern for physicians. Central
; e) e8 Q9 P4 ~& @5 jprecocious puberty (CPP), which is mediated
" C# G, b; E! t$ @+ rthrough the hypothalamic pituitary gonadal axis, has. a2 U2 T1 {, e" j/ h' J3 v* v$ }
a higher incidence of organic central nervous system% j+ d. j/ k% `5 C5 N, J. | c0 s; t" {
lesions in boys.1,2 Virilization in boys, as manifested# I! p% c4 T+ k: P+ n9 c
by enlargement of the penis, development of pubic7 u. {7 ?* W( G2 e+ g T
hair, and facial acne without enlargement of testi-
: r7 ^+ S4 V! q8 G- Fcles, suggests peripheral or pseudopuberty.1-3 We% d9 y& \, J6 m7 W) w+ I% c
report a 16-month-old boy who presented with the$ l$ C. j4 ~+ X, R3 n- f
enlargement of the phallus and pubic hair develop-
& ?! L v) j8 f# X/ R. zment without testicular enlargement, which was due
1 F Q2 \, d/ c0 Vto the unintentional exposure to androgen gel used by: ~; a) W' Z, n/ l; x
the father. The family initially concealed this infor-% i3 ]; C r( E" N" h/ q
mation, resulting in an extensive work-up for this
/ a) `- w# N, [0 b/ T0 x Z! ?child. Given the widespread and easy availability of" I) ~9 W' O' P+ W
testosterone gel and cream, we believe this is proba- T0 y1 ^# [3 d* e! d& p# n5 g" v( n
bly more common than the rare case report in the
$ N$ m0 n' u% }literature.4 y1 T3 l Q/ h7 ]6 u4 v
Patient Report, T$ U/ w% |1 s5 I
A 16-month-old white child was referred to the
1 |1 R+ |$ V! H u( L; pendocrine clinic by his pediatrician with the concern
! i6 y$ n+ i+ c7 u& \of early sexual development. His mother noticed$ _5 k* U, ?9 Y% f9 l+ c
light colored pubic hair development when he was
6 B- d4 p' Y# I( G; x" KFrom the 1Division of Pediatric Endocrinology, 2University of
$ h+ ?8 ?2 M5 `: \South Alabama Medical Center, Mobile, Alabama.
6 H& |0 \ ]& S' i- A; C1 @Address correspondence to: Samar K. Bhowmick, MD, FACE,% j8 ?7 r' _( o; r
Professor of Pediatrics, University of South Alabama, College of2 m* _$ \# h' s6 c0 d. U
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
@, Q |4 t& z3 T. f( e8 he-mail: [email protected]./ K$ s( C4 J$ g* `
about 6 to 7 months old, which progressively became
F- n' ?! Q! x6 edarker. She was also concerned about the enlarge-
/ S; n3 L: ?; ^2 ~# Z' D+ c1 Vment of his penis and frequent erections. The child, T6 k" _7 u" p8 t% h& p) N- U9 x. i
was the product of a full-term normal delivery, with
" a# O- R5 ^! p6 e9 sa birth weight of 7 lb 14 oz, and birth length of
$ q- |$ V" z) p7 X20 inches. He was breast-fed throughout the first year
3 d2 ~9 `* \+ H# d8 ^' e6 nof life and was still receiving breast milk along with3 z% q& R/ Z! {1 z
solid food. He had no hospitalizations or surgery,
* u, W Z) N( `) h" k& t0 h9 Vand his psychosocial and psychomotor development
$ R2 Q/ u; ~0 Pwas age appropriate. p4 z- A6 m! K1 N9 P
The family history was remarkable for the father,5 j5 Z p8 j: O& j
who was diagnosed with hypothyroidism at age 16,+ c! A! s, P! p% h
which was treated with thyroxine. The father’s
; z6 x1 C3 S0 \4 p4 A7 z, mheight was 6 feet, and he went through a somewhat8 R1 B* g' Y) U. Q
early puberty and had stopped growing by age 14.0 Y5 S5 W, ~; x7 W! ^' Y! o7 e* q
The father denied taking any other medication. The
0 U, i6 s% l! B8 X1 @- rchild’s mother was in good health. Her menarche2 L* e2 C, `+ L& X
was at 11 years of age, and her height was at 5 feet
" r& a: b9 t7 W V% ]4 x/ t1 M& Q5 inches. There was no other family history of pre-
+ a v; A# K2 r5 ^ u' ncocious sexual development in the first-degree rela-; m. a6 `" t+ ?
tives. There were no siblings.
* ^* b* H; f. s/ S7 r% k; t1 {Physical Examination
$ C* r9 O3 L4 I0 b5 qThe physical examination revealed a very active,
1 W7 g# v% \ O% ]9 Aplayful, and healthy boy. The vital signs documented
& @" U3 ]5 H! k6 F- X' Xa blood pressure of 85/50 mm Hg, his length was: H1 |& Z+ [: P* S/ x# t! i
90 cm (>97th percentile), and his weight was 14.4 kg1 D' Q; Q0 E' l3 x( {4 k* i
(also >97th percentile). The observed yearly growth) Z2 R9 j+ g% D% _# J$ E
velocity was 30 cm (12 inches). The examination of. r/ N/ y& s3 G/ T% N8 _0 h% {0 E
the neck revealed no thyroid enlargement./ Y! z. ^5 D$ @5 M: C- u
The genitourinary examination was remarkable for( }8 d: N" c. L& A# q3 C
enlargement of the penis, with a stretched length of, N- H& ?7 q! X9 L2 C+ N* S' j1 D
8 cm and a width of 2 cm. The glans penis was very well( G, ^' J) y% n1 s9 z* j9 M1 B3 \6 }
developed. The pubic hair was Tanner II, mostly around) l7 I" p" N+ T
540
2 ?8 z* l1 g' X' L+ J+ oat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
( W a- @+ Z# W" h2 f5 w1 r$ Q* q9 Uthe base of the phallus and was dark and curled. The0 P! K$ w( \: I- X
testicular volume was prepubertal at 2 mL each. F' a" D8 @' m$ L3 E# F4 p* M
The skin was moist and smooth and somewhat
& T9 f9 N4 Y' u8 T& J4 {, Ioily. No axillary hair was noted. There were no& r8 d+ q; J3 I
abnormal skin pigmentations or café-au-lait spots.
6 J, Q( T5 Y! yNeurologic evaluation showed deep tendon reflex 2+ }& o7 w+ u0 W9 g+ T7 _) i1 C
bilateral and symmetrical. There was no suggestion! ]9 u6 q% l8 K: c' F
of papilledema. d3 z" Z$ U/ w& T p. r
Laboratory Evaluation
) s1 J7 B7 K/ l: U! H6 JThe bone age was consistent with 28 months by
3 `7 N+ q2 G q( B, j; V" Nusing the standard of Greulich and Pyle at a chrono-! E' \+ | z0 q0 C
logic age of 16 months (advanced).5 Chromosomal
9 k6 k3 Z% u6 Ekaryotype was 46XY. The thyroid function test
4 T3 b2 f8 @5 ?; L5 p9 jshowed a free T4 of 1.69 ng/dL, and thyroid stimu-1 h s0 I9 g! {2 e
lating hormone level was 1.3 µIU/mL (both normal)." B/ X3 \1 H; g9 V ^4 y
The concentrations of serum electrolytes, blood7 f# w7 x# D, R% X( T3 x8 Z3 }
urea nitrogen, creatinine, and calcium all were
8 |4 i. D* c h+ Z9 Awithin normal range for his age. The concentration0 F. B* M1 D6 |! G5 w
of serum 17-hydroxyprogesterone was 16 ng/dL' c# E& R, F- N8 w/ Y5 f
(normal, 3 to 90 ng/dL), androstenedione was 20, a) Q7 T* d$ q9 |9 \% ]# K; k
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-- J0 j% M0 i# i) o' U& L/ c
terone was 38 ng/dL (normal, 50 to 760 ng/dL),- R4 g7 X5 `( S6 t/ g( e$ x
desoxycorticosterone was 4.3 ng/dL (normal, 7 to4 E& a. D" p: p% S0 H
49ng/dL), 11-desoxycortisol (specific compound S)
5 Z- ]. y& o9 F2 @0 ~was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-- h0 w$ T- @% |9 q+ A
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total1 n9 q4 h/ [: j
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
1 L! U4 ~, v) P! sand β-human chorionic gonadotropin was less than& A# x; S+ h5 h# A. O) ~
5 mIU/mL (normal <5 mIU/mL). Serum follicular
3 }. ]! O5 a, E% _4 bstimulating hormone and leuteinizing hormone% z9 a; ~0 ^) G4 A, X5 b
concentrations were less than 0.05 mIU/mL0 ]! P- @$ w- }0 Z$ Q
(prepubertal).
* h8 C3 ?6 ?6 N9 ~3 {0 K1 u/ CThe parents were notified about the laboratory
, j7 f+ a$ R( A" {* oresults and were informed that all of the tests were
3 t* t' x5 I7 ~# \4 W9 tnormal except the testosterone level was high. The
; V! b) e5 [! r- sfollow-up visit was arranged within a few weeks to$ h0 v) n$ i1 V9 D* n8 G
obtain testicular and abdominal sonograms; how-2 B& n. g- p9 U. L- }
ever, the family did not return for 4 months., B) o$ W( C, t2 O* c" v
Physical examination at this time revealed that the
- N& J2 ?6 c0 _8 g' `child had grown 2.5 cm in 4 months and had gained
7 \0 \1 t5 M# m; @9 t+ m2 kg of weight. Physical examination remained
$ h V& c4 J; G" {unchanged. Surprisingly, the pubic hair almost com-- i+ A( k/ N2 s: U6 ~
pletely disappeared except for a few vellous hairs at
$ D" y7 h2 S$ f A& @& E+ }the base of the phallus. Testicular volume was still 22 q% `' B! I6 b7 A' ?
mL, and the size of the penis remained unchanged.
* I! I4 g* o+ W LThe mother also said that the boy was no longer hav-0 i+ O/ _" @. E" h- ^5 n c
ing frequent erections.
5 X& U$ C. l& h3 T" v* q& T9 tBoth parents were again questioned about use of
0 c* e! B; ~; |, i- g- g9 rany ointment/creams that they may have applied to& n( Q* F; ~7 w! c
the child’s skin. This time the father admitted the
# L) A3 _% `' B6 R1 s* s4 }Topical Testosterone Exposure / Bhowmick et al 541
! h9 ~- K- P2 N# ]; kuse of testosterone gel twice daily that he was apply-% [' ` Q& u a: f% C3 ^" Z
ing over his own shoulders, chest, and back area for* Q* g0 S# D5 B* M
a year. The father also revealed he was embarrassed
4 `" G) A; x2 J, Ato disclose that he was using a testosterone gel pre-* k3 U9 f4 @ R8 |' Z5 \& w. Z# w
scribed by his family physician for decreased libido& w4 D: C& ?' g) J6 ~
secondary to depression.
& W K" L/ d) f$ E0 lThe child slept in the same bed with parents.
4 U& M- I8 g+ J4 }# cThe father would hug the baby and hold him on his
6 s4 n, w, I5 d8 q9 Mchest for a considerable period of time, causing sig-9 G% |- l* m d7 [% \9 r
nificant bare skin contact between baby and father.9 F. w# ?2 m7 u+ K# j
The father also admitted that after the phone call,
5 ` \7 i( ` j7 i& L4 \7 iwhen he learned the testosterone level in the baby, v; T# J/ P1 ?4 l
was high, he then read the product information
. O- `6 C$ a' s* @% b0 w( `packet and concluded that it was most likely the rea-, y0 p* |2 t6 c8 M2 }7 X
son for the child’s virilization. At that time, they J3 ^5 L8 I6 _2 L9 U- ^
decided to put the baby in a separate bed, and the
9 a4 l8 t8 X2 I2 Ffather was not hugging him with bare skin and had
0 z; o: Z" _! Xbeen using protective clothing. A repeat testosterone
7 T$ n3 m; ^' h) { T, ztest was ordered, but the family did not go to the
. D8 f7 [( ~3 g u- W5 |* M; ^ _( R' xlaboratory to obtain the test.6 o- C0 ?/ k! h( b; x& [1 D
Discussion
6 H( `% q8 e: L+ xPrecocious puberty in boys is defined as secondary
2 w5 h ?; M) s% \sexual development before 9 years of age.1,43 d& ?$ X/ B/ L# L% R
Precocious puberty is termed as central (true) when7 e! ~4 p; a8 I0 n' a
it is caused by the premature activation of hypo-
. b. t3 R! }+ B) u( Ythalamic pituitary gonadal axis. CPP is more com-+ A5 l: \- q& T" Y* R. w% m
mon in girls than in boys.1,3 Most boys with CPP6 R& e% r( Y- G" D' d% ]; m. F
may have a central nervous system lesion that is3 I- i5 ?5 J0 ]$ ~/ E# r, x# H
responsible for the early activation of the hypothal-
' h& k# {0 g3 J) s2 b' |+ h/ qamic pituitary gonadal axis.1-3 Thus, greater empha-
1 C& H2 [; _! n) O2 @ Y) d( gsis has been given to neuroradiologic imaging in1 Z% N; M5 I4 u* K, b" b$ A- \
boys with precocious puberty. In addition to viril-
7 Z7 w( N, L& ?) sization, the clinical hallmark of CPP is the symmet-0 \; L# T. U9 h/ I7 ]7 J: v
rical testicular growth secondary to stimulation by
# Z& N: f# o9 @$ {gonadotropins.1,3
" ~4 ]- P1 J. V" _Gonadotropin-independent peripheral preco-
9 N! a, q: {' N3 D& P; R7 Mcious puberty in boys also results from inappropriate) Y' ~! o0 G. Q1 Q9 _4 O
androgenic stimulation from either endogenous or* @- W( K. W9 Q! F" E) r
exogenous sources, nonpituitary gonadotropin stim-9 Y8 j8 _" w% H( ^* M6 |. C
ulation, and rare activating mutations.3 Virilizing: j# l `- @4 }% L% @% g
congenital adrenal hyperplasia producing excessive ?8 ~* } K2 C; `) L& U$ j, N
adrenal androgens is a common cause of precocious. i. a$ t& O( Q; d; |) J% _
puberty in boys.3,4
1 e7 i7 z8 }6 L/ T, _) c% BThe most common form of congenital adrenal
2 N& q5 _. I u' G8 Ehyperplasia is the 21-hydroxylase enzyme deficiency.
1 T5 x6 r. ^ Q2 e) V* F/ j$ S1 ?The 11-β hydroxylase deficiency may also result in' e+ N3 [3 P+ I
excessive adrenal androgen production, and rarely,
5 v6 d i4 a! W& p @. }2 R3 ban adrenal tumor may also cause adrenal androgen+ X- h5 k. S0 V( G
excess.1,3
" O4 V" H& H7 W! ], `( k2 U% k" Tat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from5 W Z& ~& o2 R. X7 A, m. n
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
! n5 h8 A0 d: N3 P. IA unique entity of male-limited gonadotropin-4 Y% k0 r# A9 ]) q4 r, S1 u4 d6 q
independent precocious puberty, which is also known _3 m- M& E7 \5 p
as testotoxicosis, may cause precocious puberty at a$ [: n5 j4 M. ~# t0 c
very young age. The physical findings in these boys9 }# t, ~6 _2 p! ^! y
with this disorder are full pubertal development,. K7 h# ]7 S3 s3 \2 W' N: F) s% ~
including bilateral testicular growth, similar to boys! [( g9 Z }4 K0 h
with CPP. The gonadotropin levels in this disorder
! ^& f; u- m4 n7 H3 ?are suppressed to prepubertal levels and do not show! y. t" f* d' i% E
pubertal response of gonadotropin after gonadotropin-
2 m& n" X5 o+ C, K5 ereleasing hormone stimulation. This is a sex-linked2 ?2 B: M+ T) @! H# E
autosomal dominant disorder that affects only
9 Z$ z0 v4 o% a( b: P+ P( Dmales; therefore, other male members of the family
3 f) y* C# t7 |: r0 Qmay have similar precocious puberty.3
5 W3 i/ z; U# X# NIn our patient, physical examination was incon-
! K a. H/ X9 L& k0 V- |! |/ c9 W# osistent with true precocious puberty since his testi-1 x! z9 f' A, j' F- {: U% n e
cles were prepubertal in size. However, testotoxicosis6 I8 n! }+ E$ d. e
was in the differential diagnosis because his father+ f4 @* z3 n) w5 r: h; k1 G# y
started puberty somewhat early, and occasionally,
- v# E7 R) i$ e7 \ u3 S0 K- otesticular enlargement is not that evident in the
0 D1 w; P' \5 C: Q5 }beginning of this process.1 In the absence of a neg-
9 n: C' p6 `; t& p" u6 I: r- z* y1 @ative initial history of androgen exposure, our
, G2 G* N! t. o& V2 vbiggest concern was virilizing adrenal hyperplasia,4 J7 q8 g/ H2 y
either 21-hydroxylase deficiency or 11-β hydroxylase
! Q- q# [5 x% L5 {- `( G4 z1 ddeficiency. Those diagnoses were excluded by find-' _) X5 i8 j( I# R7 {
ing the normal level of adrenal steroids.
' v3 m. V4 H$ n6 p+ _2 \6 EThe diagnosis of exogenous androgens was strongly$ G; n% d- M: R- D9 g# A8 d
suspected in a follow-up visit after 4 months because: K( |0 z% F9 Y. n
the physical examination revealed the complete disap-
2 H3 M4 h6 B3 w+ R1 Hpearance of pubic hair, normal growth velocity, and. J1 s6 S+ v2 v+ o9 R/ T8 m
decreased erections. The father admitted using a testos-6 i4 ]+ {9 X0 `% t. B, ~
terone gel, which he concealed at first visit. He was ~, y* Z; D* t% \. G
using it rather frequently, twice a day. The Physicians’
& a5 ^- m, X: i' L# @1 rDesk Reference, or package insert of this product, gel or& `: }+ r; X6 p) @7 J
cream, cautions about dermal testosterone transfer to
5 P, e- J" @% m& d- Junprotected females through direct skin exposure.
) @5 @+ ^* ~0 sSerum testosterone level was found to be 2 times the; R( N9 o$ H0 o
baseline value in those females who were exposed to8 n7 [" M- B H% L' X8 E5 q
even 15 minutes of direct skin contact with their male8 d" R& {+ ?. c8 W
partners.6 However, when a shirt covered the applica-- c6 ~$ ]. m* s
tion site, this testosterone transfer was prevented.
! {& Y. g. t: j. s7 _Our patient’s testosterone level was 60 ng/mL,. r% R' Z1 R4 z. ~0 }% j, S: p; d3 L
which was clearly high. Some studies suggest that9 M7 N$ p$ p* O
dermal conversion of testosterone to dihydrotestos-
: J# I: F6 j7 R9 |& @terone, which is a more potent metabolite, is more: m7 T3 I# E+ i% t! q' Q! B
active in young children exposed to testosterone' m# v; x0 j$ s) q
exogenously7; however, we did not measure a dihy-
, ]- ~: J5 g4 S2 _+ Kdrotestosterone level in our patient. In addition to
3 K8 V5 |2 w6 e4 |, X% \virilization, exposure to exogenous testosterone in
1 x; @% p+ E, tchildren results in an increase in growth velocity and. V5 n! r4 {; f( c
advanced bone age, as seen in our patient.3 h, r# H: f7 w; W0 f, l& D! J1 A/ y
The long-term effect of androgen exposure during5 v' q4 q3 W& {# j$ |
early childhood on pubertal development and final- E# Q' U5 ^6 z/ I. S) l
adult height are not fully known and always remain
; [; \' q! Z3 Z S8 Wa concern. Children treated with short-term testos-
$ H4 z; b7 v' Y* v% K* d7 Bterone injection or topical androgen may exhibit some
- K$ b" i* g- n7 Z7 k& Z5 Iacceleration of the skeletal maturation; however, after9 V$ [, s9 C$ `1 j4 w' c
cessation of treatment, the rate of bone maturation- |7 @# \4 `! t0 v" o% }) A
decelerates and gradually returns to normal.8,9- S/ W# g Z. F9 {( \0 l5 g! w
There are conflicting reports and controversy
6 X2 M2 G5 O3 O9 M' {, d0 {5 _over the effect of early androgen exposure on adult
, q- ^! n2 U/ f9 F2 P: V. ^penile length.10,11 Some reports suggest subnormal
) z3 P$ X2 [; M7 p7 V* aadult penile length, apparently because of downreg-
0 F5 j7 K7 Y* ?6 b4 c# iulation of androgen receptor number.10,12 However,8 c. q7 L" L+ ^. R7 s: x9 Z+ v8 U
Sutherland et al13 did not find a correlation between3 b4 {; r: N/ ^ z
childhood testosterone exposure and reduced adult
' m3 O# y8 T6 K) y P4 o- I# v5 S- {penile length in clinical studies." ? g8 R8 a f/ q" s# g
Nonetheless, we do not believe our patient is5 o9 ?' z% t+ c9 p# ^) _1 S
going to experience any of the untoward effects from
- p& J' L6 l1 Gtestosterone exposure as mentioned earlier because
* M! {1 c: Z6 l+ T$ \2 m6 {the exposure was not for a prolonged period of time.
# J4 q/ j8 m* F7 R# FAlthough the bone age was advanced at the time of( f# G0 [2 _0 g: T/ `7 O
diagnosis, the child had a normal growth velocity at
5 Z% A, }" O3 z$ wthe follow-up visit. It is hoped that his final adult
4 {3 k* v6 H0 K9 @0 v9 zheight will not be affected.
; H `9 L3 \7 @9 t- ZAlthough rarely reported, the widespread avail-2 y. P8 }; B" Y$ q \: v
ability of androgen products in our society may
0 V3 L" F% t6 F0 Nindeed cause more virilization in male or female& `3 U- f6 a; B( A2 `+ g* n) x' a
children than one would realize. Exposure to andro- g- O; H& k$ ?1 T
gen products must be considered and specific ques-
. @) ?, Y0 a. ytioning about the use of a testosterone product or
& w) _$ i9 V, n0 G+ s4 k/ c* {$ igel should be asked of the family members during
% p' K9 j% h. R0 t$ ~- O6 E* ythe evaluation of any children who present with vir-' U# d( D) O, h8 ~/ Q' d9 D
ilization or peripheral precocious puberty. The diag-4 _+ I j0 ^3 }, c
nosis can be established by just a few tests and by0 A- Z2 c; ?- f! ?+ n+ q" Y
appropriate history. The inability to obtain such a, |; z, E: K+ t. O6 n2 e/ k4 d" U; G
history, or failure to ask the specific questions, may
2 `- \8 L# P4 P0 q; Gresult in extensive, unnecessary, and expensive# r; G7 \. `" k% o# `
investigation. The primary care physician should be
! `* s. u; F! }1 P. ^aware of this fact, because most of these children
* |* t/ z$ Z9 c( d- ]may initially present in their practice. The Physicians’
9 `0 |- A% P# R/ |Desk Reference and package insert should also put a
6 t* A! ?& M5 y" S# N2 f" Owarning about the virilizing effect on a male or, y J" o& X8 k* @# t( f3 f
female child who might come in contact with some-: _' N/ |7 V2 v9 J# ^0 q" D
one using any of these products.7 G0 v' G+ R8 r: x( @
References
' p) K5 n6 q+ O5 e, C6 `! B1. Styne DM. The testes: disorder of sexual differentiation: c7 }6 f2 U* O7 ^. X
and puberty in the male. In: Sperling MA, ed. Pediatric
9 C% q) k( t% CEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;! X* a: g. D* a, M& [
2002: 565-628. H7 N% X3 x u, c$ O5 D& P' W
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
8 z x% S) s$ c# ^( epuberty in children with tumours of the suprasellar pineal |
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