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Sexual Precocity in a 16-Month-Old
0 M" c5 I, v6 B9 N, g( PBoy Induced by Indirect Topical( l( c% h8 @( j, ~ S
Exposure to Testosterone
5 A& |, {* d5 _" h7 p' a- {( tSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2& Q/ ^5 T5 `2 H" F
and Kenneth R. Rettig, MD1* k: d ], _+ t; L4 d3 S
Clinical Pediatrics
. D9 T2 T0 m4 S2 tVolume 46 Number 6( y# [% L( S8 I) {. C5 i
July 2007 540-543
" w" z7 ?7 G0 U8 n2 D* `© 2007 Sage Publications4 p2 `: i7 r) J* e0 q5 p
10.1177/0009922806296651( _ [ _" T9 W4 C* ?- E: A5 ^
http://clp.sagepub.com
; x& `$ U* `8 z2 Yhosted at( u8 p' \4 b5 ?8 Y
http://online.sagepub.com
- i1 E) _8 _ n8 }Precocious puberty in boys, central or peripheral,
4 O0 R1 z3 u0 X# a0 h" g9 R+ @is a significant concern for physicians. Central* m" v; c8 n7 Y9 `: d* M: c, B
precocious puberty (CPP), which is mediated4 _* T1 S, y9 f: g3 ~) i+ g) x" s
through the hypothalamic pituitary gonadal axis, has! J/ V/ d) c. `' ?
a higher incidence of organic central nervous system5 P. f$ r; S) ^, o, A$ x9 _6 R" n
lesions in boys.1,2 Virilization in boys, as manifested- K' D+ s+ o5 P4 L+ |
by enlargement of the penis, development of pubic
. ^+ i3 d) O# C* Whair, and facial acne without enlargement of testi-4 l9 y) e5 m/ c$ N1 Q: [
cles, suggests peripheral or pseudopuberty.1-3 We! I; K1 W' v6 _0 b
report a 16-month-old boy who presented with the
/ Q/ d* t& S( C1 |% Genlargement of the phallus and pubic hair develop-
# q1 M. P9 w) ^( Qment without testicular enlargement, which was due
8 @- i, l+ L; h- Dto the unintentional exposure to androgen gel used by
. t% A- t# m5 r/ o$ L! w) K5 rthe father. The family initially concealed this infor-2 o& L( x) a* E5 K3 R
mation, resulting in an extensive work-up for this
4 ~7 g9 T. d, j9 v4 D, ochild. Given the widespread and easy availability of$ U! ~ b8 c! Q" v" k- [" [& d' J
testosterone gel and cream, we believe this is proba-
3 @7 M5 W3 J6 L: n6 `8 ^bly more common than the rare case report in the
' T! a6 L- D4 A5 sliterature.4
; Z4 N& M# Z" LPatient Report* k Q4 E0 D ^. l
A 16-month-old white child was referred to the0 u! ]. N C9 O% O
endocrine clinic by his pediatrician with the concern
$ a0 l0 \3 D4 o& |4 Mof early sexual development. His mother noticed
7 w% N( h; O. i+ alight colored pubic hair development when he was3 V3 q3 q# W( p
From the 1Division of Pediatric Endocrinology, 2University of
4 z; ]1 |) D; J8 u+ SSouth Alabama Medical Center, Mobile, Alabama.1 E- r" M6 m$ P! N& I5 Y2 S$ J* ]
Address correspondence to: Samar K. Bhowmick, MD, FACE,! @! c) C5 }# ]( q! j6 N
Professor of Pediatrics, University of South Alabama, College of) O4 q8 {- o- S
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
0 t U& I' z$ X4 k! m* de-mail: [email protected].
1 M6 f( q/ o% ]about 6 to 7 months old, which progressively became! r( |% o6 }0 e+ b
darker. She was also concerned about the enlarge-
' M! X# W5 @" e( o: J! c Qment of his penis and frequent erections. The child
+ R+ _+ {4 W# |+ c+ cwas the product of a full-term normal delivery, with# `7 y- L* B9 Q6 I, T/ l
a birth weight of 7 lb 14 oz, and birth length of7 A3 _# U* W2 x4 E
20 inches. He was breast-fed throughout the first year7 Q4 d" S, i# x$ F7 j2 Y
of life and was still receiving breast milk along with
& i6 h; k/ ]% X4 G1 msolid food. He had no hospitalizations or surgery,
# a f7 A( e# W3 `( M! Aand his psychosocial and psychomotor development
) x" k' N5 u; E1 l7 l! ?was age appropriate.8 A7 C9 u( r; `4 x$ W% \
The family history was remarkable for the father,8 `7 a+ t1 P+ x! ^0 C8 ^: ~ [
who was diagnosed with hypothyroidism at age 16,
2 X; A% r {! b. \which was treated with thyroxine. The father’s/ j0 o# h$ `/ K& b* W+ W9 d
height was 6 feet, and he went through a somewhat+ u; z ~( m, m k$ L( X; y
early puberty and had stopped growing by age 14.
, L. R& V% j% a# o, C; [5 FThe father denied taking any other medication. The P: r% b! c, w7 z; u, G
child’s mother was in good health. Her menarche$ @7 f' l8 X& E1 I9 \$ E- ]/ S# [
was at 11 years of age, and her height was at 5 feet) ]0 @6 N; a* |3 Y" G L
5 inches. There was no other family history of pre-
( Y, {/ b/ h$ s& M3 Y# z3 tcocious sexual development in the first-degree rela-6 T$ M F" K0 T) ~2 d
tives. There were no siblings.* Q# j: a) p1 y( L
Physical Examination
3 l/ G5 O/ G d+ x5 n4 VThe physical examination revealed a very active,
2 d+ L5 X6 R) y% ?% Jplayful, and healthy boy. The vital signs documented! u5 ?: E& `) ~ y# h1 N
a blood pressure of 85/50 mm Hg, his length was
3 U/ V: X1 x0 p( ~% U" e90 cm (>97th percentile), and his weight was 14.4 kg$ J$ r+ T( l; |
(also >97th percentile). The observed yearly growth d9 d A. f) j# M6 q8 A2 A( C* M
velocity was 30 cm (12 inches). The examination of
. ^. X, Z+ E% ~" r; l" K9 |5 xthe neck revealed no thyroid enlargement. |2 S, j. u5 f; k
The genitourinary examination was remarkable for+ X/ Q: h) R) M# z0 h1 t! h
enlargement of the penis, with a stretched length of
$ a8 f$ `1 x; ], t' c9 D8 cm and a width of 2 cm. The glans penis was very well
7 o: i; \$ E, h" p! Hdeveloped. The pubic hair was Tanner II, mostly around
4 B& {+ v7 h) x2 X540
* H, G0 ~- ^( G* Uat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from& _# c- f1 h4 v, l
the base of the phallus and was dark and curled. The
# X$ ]& Q# L4 ?; h6 |1 |$ itesticular volume was prepubertal at 2 mL each.
, O7 c' O" i- E1 Z* p) l8 lThe skin was moist and smooth and somewhat. Q0 b% L) \, E% c7 W% e4 x
oily. No axillary hair was noted. There were no6 f+ M) U/ S. @* H- ~
abnormal skin pigmentations or café-au-lait spots.
^: c9 l, {3 H1 D3 c4 mNeurologic evaluation showed deep tendon reflex 2+
+ u8 x$ A8 `. m7 |: A! `: d$ ybilateral and symmetrical. There was no suggestion
- t P1 w0 {% w, c8 Z3 gof papilledema.+ y7 j, K! G/ X( \4 y' k
Laboratory Evaluation8 `: J1 n! W5 t- W8 P* {( j |
The bone age was consistent with 28 months by
4 s9 d. v3 g: G' A; h: Ousing the standard of Greulich and Pyle at a chrono-. }8 O; B; d' k; f6 ^% x
logic age of 16 months (advanced).5 Chromosomal. m, X( T' i( a# K
karyotype was 46XY. The thyroid function test/ w+ j7 ~2 p" Z2 t( M
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
4 h" d# i8 ~0 q8 [4 zlating hormone level was 1.3 µIU/mL (both normal).
( Z& V! w' u; p4 f! dThe concentrations of serum electrolytes, blood
7 U& u! d" `* m: W2 q, k( lurea nitrogen, creatinine, and calcium all were
9 n; a" s; ]. t0 n4 k% dwithin normal range for his age. The concentration
5 W3 t! O( t( Q6 X- R1 Kof serum 17-hydroxyprogesterone was 16 ng/dL- r, b) m+ \7 n- Y) |# H4 W
(normal, 3 to 90 ng/dL), androstenedione was 20 ? _9 n5 Q$ m" Z, x
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
8 K" t( U4 D/ g* rterone was 38 ng/dL (normal, 50 to 760 ng/dL),$ t, ]/ C7 O8 a3 r {5 s( U( Q$ }
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
) B' r5 j$ [. d4 J8 w% V49ng/dL), 11-desoxycortisol (specific compound S)
q2 ^& H& b2 s4 F7 c/ |* Hwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
# M3 X. a" s# w& o( ntisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
/ x# l+ {9 e# Z4 z% G8 u$ ?: N/ |testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
& @" F* k. ]5 T- jand β-human chorionic gonadotropin was less than
1 j ], K1 R( q% i; k) g5 mIU/mL (normal <5 mIU/mL). Serum follicular( N$ A: { c6 c3 \, f' ]" P
stimulating hormone and leuteinizing hormone* o( y8 Z! [# b/ I/ a; u5 C
concentrations were less than 0.05 mIU/mL
! u9 I# `# R' d9 j# [# ]/ Z(prepubertal).* s K( \$ |6 E. A9 y
The parents were notified about the laboratory6 d& q: f" d0 |$ B# t" j7 a& k6 {
results and were informed that all of the tests were5 n' q* ~. i8 S5 _. d
normal except the testosterone level was high. The) A2 {0 h7 O' H
follow-up visit was arranged within a few weeks to
7 G, u0 w \# a; y7 P2 c5 J+ Tobtain testicular and abdominal sonograms; how-
6 |6 @* D5 c. X {ever, the family did not return for 4 months.
6 z6 M! G" N& K1 I; H1 v# C! FPhysical examination at this time revealed that the
: I0 i1 l" W8 K7 kchild had grown 2.5 cm in 4 months and had gained; P. @5 y: o$ G. N
2 kg of weight. Physical examination remained
7 |2 L9 U2 u% a3 {2 y* f, V& Dunchanged. Surprisingly, the pubic hair almost com-
( w4 I- e6 r6 |! R& g) ~' fpletely disappeared except for a few vellous hairs at* ^0 d+ v* A1 K8 D5 o
the base of the phallus. Testicular volume was still 2# j3 B( S: E8 O6 |! B% C
mL, and the size of the penis remained unchanged.
4 J( H2 C. ^2 _5 vThe mother also said that the boy was no longer hav-
% e( m7 ]( X% L5 H5 M" C/ Q" S+ Iing frequent erections.5 g. C l) `3 I/ Q. w
Both parents were again questioned about use of v) G+ ^1 o' M: J. N' q
any ointment/creams that they may have applied to# w2 p8 \- {8 d0 Z6 }7 K6 Y, }
the child’s skin. This time the father admitted the
9 z% O+ G* A6 M! v9 I9 Q/ ]Topical Testosterone Exposure / Bhowmick et al 5412 O, h: K: e. J3 q7 t+ Q1 k
use of testosterone gel twice daily that he was apply-
# [& V, k N! E) Q- |! iing over his own shoulders, chest, and back area for
3 s& K# |2 t' e5 Y) ka year. The father also revealed he was embarrassed
$ \ \ G% P" R- w& Dto disclose that he was using a testosterone gel pre-
2 E0 W, I/ c E$ f( Fscribed by his family physician for decreased libido
% a4 C6 B1 a" x% ]7 Asecondary to depression. ^2 y, b; {1 x1 f' |/ a
The child slept in the same bed with parents.
5 l0 X4 B2 _1 S" fThe father would hug the baby and hold him on his) t3 O( S$ D. u
chest for a considerable period of time, causing sig-/ `7 R! T3 o& o! E
nificant bare skin contact between baby and father.
+ l/ }* b8 [% E" L( rThe father also admitted that after the phone call,
* q4 Z F( r$ @7 u) \8 Qwhen he learned the testosterone level in the baby
3 M+ x2 _1 ^# }. y0 G9 ^! M6 y, |was high, he then read the product information. U: Z3 }8 H, i4 m$ z* O
packet and concluded that it was most likely the rea-9 H9 g( O. z( K2 q; l1 Z
son for the child’s virilization. At that time, they4 _* l5 \% l. d
decided to put the baby in a separate bed, and the
9 S. F6 `+ a& k; [father was not hugging him with bare skin and had1 ?, k4 L* R( H* {1 d: e
been using protective clothing. A repeat testosterone
; o5 u, n! A- w; f; Btest was ordered, but the family did not go to the
+ g0 X( b$ P0 N u% M6 m1 rlaboratory to obtain the test.
7 r" z3 s# G1 n( v, i. p- gDiscussion" |6 p1 `+ ]. o$ w( n% c% z+ d" T" P
Precocious puberty in boys is defined as secondary/ n. U5 }) J+ G' f' ^) f! a" A2 Y8 Y
sexual development before 9 years of age.1,4
5 |4 c/ b4 _1 Y, d% ^ fPrecocious puberty is termed as central (true) when5 d3 [+ y% D R3 _% b7 S+ \
it is caused by the premature activation of hypo-( Z5 g' x, M' C2 t
thalamic pituitary gonadal axis. CPP is more com-. X) o8 m: Q3 B* W9 i9 z
mon in girls than in boys.1,3 Most boys with CPP
2 o1 c% e1 s/ X9 P2 Q7 d: Zmay have a central nervous system lesion that is5 i/ b, c/ ?5 a8 U f
responsible for the early activation of the hypothal-
! N: v+ V5 L9 B$ bamic pituitary gonadal axis.1-3 Thus, greater empha-# k' ?0 |' X z' N3 ?# ]" a- o
sis has been given to neuroradiologic imaging in
% d4 t5 O. \# q( O* \boys with precocious puberty. In addition to viril-
9 A) P0 o& i& |3 j+ d* f wization, the clinical hallmark of CPP is the symmet-
# Y8 c, o# D# A j2 Grical testicular growth secondary to stimulation by/ S' K3 P1 c: f Z! l9 ~
gonadotropins.1,3% e+ i) I5 J8 _! f- v8 H
Gonadotropin-independent peripheral preco-
8 g5 p; D& o- G6 q" x% {# ~: I3 [cious puberty in boys also results from inappropriate
1 ~! r/ K* e- A, S3 y& L2 U4 h' Landrogenic stimulation from either endogenous or) m# {) J2 `0 X+ e* q! S
exogenous sources, nonpituitary gonadotropin stim-
4 a8 P$ o; `% Y( ?! o1 F4 Y. {ulation, and rare activating mutations.3 Virilizing. ]+ D! H& R: L
congenital adrenal hyperplasia producing excessive
( w3 r E3 O* _! h q4 H eadrenal androgens is a common cause of precocious. b/ h1 {7 [! K
puberty in boys.3,4- X9 N/ ^& e; i0 ~' c' _
The most common form of congenital adrenal
, [- C/ Z# q0 a7 s N* y& Chyperplasia is the 21-hydroxylase enzyme deficiency. c! p6 @" V7 m8 U: |9 t
The 11-β hydroxylase deficiency may also result in0 T# N7 J: j" _; D b
excessive adrenal androgen production, and rarely,
9 n: R1 e+ C+ o+ |8 H" ?an adrenal tumor may also cause adrenal androgen5 P: T3 A0 w" h) }: m
excess.1,3
. c& j, v4 M% ^; gat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
2 ^. }+ g% D# \0 C: D5 s1 h) O542 Clinical Pediatrics / Vol. 46, No. 6, July 2007$ x A8 |5 d% p" [% b. E; n
A unique entity of male-limited gonadotropin-3 O: D* ^+ n8 D3 b @4 ?" v5 D
independent precocious puberty, which is also known
; q/ g3 T7 h7 L' B: x6 fas testotoxicosis, may cause precocious puberty at a
( T7 v( V1 }2 c% y) z. S6 i, Lvery young age. The physical findings in these boys' c/ U: I# Y$ @' Y; |
with this disorder are full pubertal development,
% t) t' }0 R9 W ?9 qincluding bilateral testicular growth, similar to boys& I" [) Y8 r0 u" |
with CPP. The gonadotropin levels in this disorder
) Q9 t# }; f- Q; a; Kare suppressed to prepubertal levels and do not show
* U9 E0 w, ^( Fpubertal response of gonadotropin after gonadotropin-
# ?% F0 G7 N: i" H- a" Y0 l( Kreleasing hormone stimulation. This is a sex-linked
$ \8 N3 O4 A" i% N4 D# N( I# C3 mautosomal dominant disorder that affects only
- X7 t, C6 A1 K! n; _, Imales; therefore, other male members of the family: E7 ~2 r1 z+ T8 V9 k' ~
may have similar precocious puberty.3% N3 M. n: n3 U1 ?4 ?2 G
In our patient, physical examination was incon-) H( ^3 R& Y- m( M) x
sistent with true precocious puberty since his testi-8 a: r6 u, i8 i$ Y. ^" g
cles were prepubertal in size. However, testotoxicosis
! N5 h1 M; M( L2 ^' {was in the differential diagnosis because his father/ Y- v7 {" O' {0 V
started puberty somewhat early, and occasionally,
3 Z+ t; ]. u* q& Xtesticular enlargement is not that evident in the
9 d; b" D) f: ~& \. q/ r q0 Y, y/ Pbeginning of this process.1 In the absence of a neg-
1 m6 D! e" c Gative initial history of androgen exposure, our
+ U' l3 p* B! g) _9 O1 \: Obiggest concern was virilizing adrenal hyperplasia,; N9 V$ S" E: ?
either 21-hydroxylase deficiency or 11-β hydroxylase
8 \. k$ n( x4 Wdeficiency. Those diagnoses were excluded by find-
' @6 O- {' ]/ [. M4 V' ~( j# xing the normal level of adrenal steroids.: a4 b) c; j! F5 b+ P9 u# ]- {
The diagnosis of exogenous androgens was strongly4 v& `" `7 `3 L& p1 |' A2 y
suspected in a follow-up visit after 4 months because
' A8 B8 s6 b5 \, a* [ rthe physical examination revealed the complete disap-
3 Q6 M0 ~4 m* Y! \: Z dpearance of pubic hair, normal growth velocity, and
1 t' `& ]- X+ k/ G' \0 J. }decreased erections. The father admitted using a testos-
2 \5 V+ [5 }; J) Qterone gel, which he concealed at first visit. He was
9 E5 ]/ q5 l( F1 J, y! [: [using it rather frequently, twice a day. The Physicians’
' s8 L* y; t, l5 B6 H& Y- U: fDesk Reference, or package insert of this product, gel or- A) @/ b$ \$ l8 o; H
cream, cautions about dermal testosterone transfer to+ [7 O3 c* ~9 n3 i0 G
unprotected females through direct skin exposure.8 Q2 i' T4 Y8 b
Serum testosterone level was found to be 2 times the
( Y/ z1 o" v* q, @& Qbaseline value in those females who were exposed to7 h0 Q G, P6 K- M- b: p
even 15 minutes of direct skin contact with their male
% p1 h0 p5 n1 Wpartners.6 However, when a shirt covered the applica-
% I1 u0 t& e, ^0 i' \% a6 wtion site, this testosterone transfer was prevented.) o" }% p) [" M. l
Our patient’s testosterone level was 60 ng/mL,: u% q9 E7 ~/ e+ i' P: S8 w y
which was clearly high. Some studies suggest that: M: h K6 C; V& m
dermal conversion of testosterone to dihydrotestos-* G& A! W* c4 U
terone, which is a more potent metabolite, is more
8 u/ s( k, s4 a. ^, g6 @$ c$ }active in young children exposed to testosterone4 o8 d9 b6 ?; H Y7 R* Y
exogenously7; however, we did not measure a dihy-# ~! V8 _. h8 R( z
drotestosterone level in our patient. In addition to1 y& R0 ?; u5 i$ a0 i) [
virilization, exposure to exogenous testosterone in
% e& g9 V. W: o ^. P# H% z) P8 vchildren results in an increase in growth velocity and+ ~7 D2 \% m6 H. C0 T0 ?. A' n+ F4 D
advanced bone age, as seen in our patient.
t% o3 z+ O, `/ I. f' H# o$ s6 H4 OThe long-term effect of androgen exposure during
; N b$ G7 |$ G5 v' }: a- Bearly childhood on pubertal development and final
$ c4 T' O* c1 V3 S7 wadult height are not fully known and always remain) r, v' ?/ q/ \( ]
a concern. Children treated with short-term testos-' V- X( X2 G; A2 `: _# Z
terone injection or topical androgen may exhibit some
) | m; K g' N$ w3 \acceleration of the skeletal maturation; however, after: B0 _6 V7 \ Z, I
cessation of treatment, the rate of bone maturation
7 I+ ^8 {1 d" A2 }- f5 ?* p/ Fdecelerates and gradually returns to normal.8,9
. x3 f4 ^; ~0 W3 T: `1 k! u/ j( iThere are conflicting reports and controversy
, x f6 a" V, l2 F7 Y1 U9 mover the effect of early androgen exposure on adult
+ L$ c! t; _. N" e0 p6 i I, ?penile length.10,11 Some reports suggest subnormal
5 `- l* K+ Y' R. cadult penile length, apparently because of downreg-
1 e* m! p0 T, S0 J5 p$ m, b; x) Mulation of androgen receptor number.10,12 However,
* z! G) }* S, f& s5 j/ xSutherland et al13 did not find a correlation between9 T" N- h6 k" m; |. ]. `% G6 C1 }
childhood testosterone exposure and reduced adult
8 M1 a% E$ }' w% T; M+ A" ]. I+ Ppenile length in clinical studies.0 k$ n0 ]3 R' X
Nonetheless, we do not believe our patient is
4 ], u. d* q- v4 l) egoing to experience any of the untoward effects from
+ k- A1 B# x6 R) }0 ^+ e4 xtestosterone exposure as mentioned earlier because
! F2 Z# J }2 T5 L8 Cthe exposure was not for a prolonged period of time.( a, f" b- L4 `9 Q4 P) X0 W
Although the bone age was advanced at the time of
; V& _9 j _$ X8 B5 |diagnosis, the child had a normal growth velocity at. G$ a% T% v, }( U4 M* |
the follow-up visit. It is hoped that his final adult
) [, `# [, }, dheight will not be affected.
: x9 H/ D2 R% Y. ~4 i0 OAlthough rarely reported, the widespread avail-
# w& ?" g6 {) H6 E: a* \9 ]ability of androgen products in our society may* J9 Y' A1 _8 w8 u; T$ s) i5 C
indeed cause more virilization in male or female Z/ l9 O5 T' e1 [$ K2 w9 e
children than one would realize. Exposure to andro-4 p1 N+ L A4 ] \3 \4 a
gen products must be considered and specific ques-. m: Y2 c" _+ `8 W7 ~; J
tioning about the use of a testosterone product or% U8 q0 S+ i+ m! D" @5 t
gel should be asked of the family members during- c* }# l$ v% J2 |
the evaluation of any children who present with vir-
% N" V7 K: t% k8 }ilization or peripheral precocious puberty. The diag-
9 w7 }4 h1 _* S* t4 L9 vnosis can be established by just a few tests and by% V2 m, ^2 l& F
appropriate history. The inability to obtain such a7 T) \' m" S% _4 b; k9 r5 E+ H
history, or failure to ask the specific questions, may2 a6 M$ x/ G5 b. ]" H+ F/ r; x) z2 I
result in extensive, unnecessary, and expensive x% u* r- U- q& j- i' ?& Z
investigation. The primary care physician should be9 J1 B. ]+ Z E4 f5 F! T0 l
aware of this fact, because most of these children- q/ a5 B9 A5 d2 h- M5 w4 r
may initially present in their practice. The Physicians’
5 ~" _1 G+ Y/ G- f, G4 Y) |Desk Reference and package insert should also put a
! ] Z' I( `# z* Vwarning about the virilizing effect on a male or
0 g1 n/ M6 @6 G9 m; v0 l' Cfemale child who might come in contact with some-" B8 k* {. v/ S0 V* _( B, a8 r$ @( W
one using any of these products.
1 l& L" `. [- Z5 F6 zReferences p# P& @$ K4 D! N2 k' `, x. a
1. Styne DM. The testes: disorder of sexual differentiation3 r, `8 V: Y/ f; G; F X
and puberty in the male. In: Sperling MA, ed. Pediatric
0 b5 X0 D8 Y5 q" SEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
# h+ p$ ^- s# Z1 L7 K2002: 565-628.
( @( I* s/ _& x7 a& d$ {) |# g2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious. S& p7 E1 }# w6 {% u
puberty in children with tumours of the suprasellar pineal |
|