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Sexual Precocity in a 16-Month-Old
6 Q+ N. s5 [ p2 v; ~6 D1 jBoy Induced by Indirect Topical
( x1 K, C# r. y8 K- Z& ^7 [Exposure to Testosterone8 F$ }$ p8 g8 k# `0 \( h* V& ~
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
2 A" R6 @- e1 b% k8 V5 T& cand Kenneth R. Rettig, MD1
% y/ e- G( {1 d; `4 S* @% J9 PClinical Pediatrics
5 R" O* e. X/ N; i* |, qVolume 46 Number 6
6 v" Y4 H9 K' m$ l3 kJuly 2007 540-543
1 L: w& W0 x. c© 2007 Sage Publications- E- ~' `0 i; }, c* ]5 Y
10.1177/0009922806296651/ t* t j$ j1 Z4 A4 B' S% ~
http://clp.sagepub.com8 Z: \8 Z. d9 G+ v4 q
hosted at
# T( J8 ?- l4 T; ]2 Ohttp://online.sagepub.com
5 a9 a U7 Q' g, B3 H5 }Precocious puberty in boys, central or peripheral,; w- S& S1 @6 H9 C3 n1 t
is a significant concern for physicians. Central9 O2 m% r; d4 t
precocious puberty (CPP), which is mediated
, S$ B2 I! N1 E$ Fthrough the hypothalamic pituitary gonadal axis, has
$ ]8 U, t5 P9 Z& u% m) sa higher incidence of organic central nervous system
1 M# r5 e. e( Z% E- tlesions in boys.1,2 Virilization in boys, as manifested
, N7 ?, r4 Y/ M4 \2 c; u& t" X1 ?by enlargement of the penis, development of pubic
* k3 j" k$ P$ S6 A& j4 ihair, and facial acne without enlargement of testi-* A! q, q' \) Q/ O
cles, suggests peripheral or pseudopuberty.1-3 We
( h9 s3 E5 e+ ^( R: l6 Vreport a 16-month-old boy who presented with the# t" {1 D _ H& Z" z. s
enlargement of the phallus and pubic hair develop-! e C3 |3 {7 T8 \0 e8 f. B
ment without testicular enlargement, which was due
* v, s: z' T, _& [; rto the unintentional exposure to androgen gel used by4 s+ \- N7 Z* d8 V
the father. The family initially concealed this infor-8 Q! l! v7 E, ~% V. K
mation, resulting in an extensive work-up for this$ ~* E6 ?- q. Z) s$ m
child. Given the widespread and easy availability of
5 _% {0 a1 w5 `. J b2 Stestosterone gel and cream, we believe this is proba-
R! ?; `; f3 p9 p# T; O! Dbly more common than the rare case report in the( M! j3 j7 V( J- N7 y1 j$ Y
literature.4& |$ g$ |4 B# F! K- e) \
Patient Report' b8 b X4 ?' p2 r8 ^9 Z
A 16-month-old white child was referred to the
8 { `) y; T3 y$ `* Lendocrine clinic by his pediatrician with the concern1 W) J0 s# a1 Y, }6 a# ]4 r* q
of early sexual development. His mother noticed
Z/ E3 w% Z# |+ k# S+ Xlight colored pubic hair development when he was1 N' ^3 P o) ^" h9 p3 p3 i
From the 1Division of Pediatric Endocrinology, 2University of. [6 O8 p! s: \' `! r
South Alabama Medical Center, Mobile, Alabama.6 Z9 z* s7 g! O2 v C1 ^
Address correspondence to: Samar K. Bhowmick, MD, FACE,: ]7 o3 q2 H% ]0 b; @, u7 f* S( K
Professor of Pediatrics, University of South Alabama, College of( n( x* X) {' D
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;2 `/ } ]. K7 d4 u
e-mail: [email protected].- h' W0 F' H# q% I6 f6 [6 r
about 6 to 7 months old, which progressively became0 [+ ?; E& f" m7 g
darker. She was also concerned about the enlarge-" V" X8 x3 V& V1 a* t9 S3 c
ment of his penis and frequent erections. The child V% b" t: N! g" H) Y/ d2 ]
was the product of a full-term normal delivery, with
2 H7 J( ?; \# B6 S- Oa birth weight of 7 lb 14 oz, and birth length of4 i% p) t6 M! Z3 t3 s Q/ K
20 inches. He was breast-fed throughout the first year; q9 Q( I- q6 ^/ U% }
of life and was still receiving breast milk along with' G* ]; W' w0 S/ \
solid food. He had no hospitalizations or surgery,* T7 t: v+ ~' L- K3 @( ^
and his psychosocial and psychomotor development$ } q1 _0 R: f9 f# v
was age appropriate.
6 W* o2 D- S2 K2 h! AThe family history was remarkable for the father,& H+ ^3 ^8 F# W- U1 n( R: o
who was diagnosed with hypothyroidism at age 16,* V, b2 L4 J! N! y* j- r
which was treated with thyroxine. The father’s# k( P0 H; l& g7 b# N1 K) ]
height was 6 feet, and he went through a somewhat8 V. q& E; D9 |3 @' Q
early puberty and had stopped growing by age 14.
/ [! [2 P$ q* q8 n: H3 Q. EThe father denied taking any other medication. The, {, k$ Y/ r+ a( v
child’s mother was in good health. Her menarche
1 B! c* {+ F- r: @3 w. u4 ~, ]was at 11 years of age, and her height was at 5 feet! Q# O7 o& v4 ^6 w N
5 inches. There was no other family history of pre-, Q3 z8 [9 L- v; p: v
cocious sexual development in the first-degree rela-2 a! U" Z w/ l3 Z0 Q s
tives. There were no siblings.: c# u3 e- {5 i9 k w6 H
Physical Examination9 k& d& k5 P4 Z4 e" v9 h
The physical examination revealed a very active,2 s% H4 J$ [) N% i! Y
playful, and healthy boy. The vital signs documented
% y8 f0 _' T0 |1 Q4 V3 D8 p6 v- p: @a blood pressure of 85/50 mm Hg, his length was
/ ^+ ~2 A; M) Q, ~4 C90 cm (>97th percentile), and his weight was 14.4 kg: Z' G) F3 Q1 C8 O2 T& n$ C
(also >97th percentile). The observed yearly growth0 {4 M( @# ^/ x& C6 b! V4 I
velocity was 30 cm (12 inches). The examination of; a2 p z' N$ }4 B
the neck revealed no thyroid enlargement.6 y1 i; t2 \* Y! q% M# f
The genitourinary examination was remarkable for/ f% C: Z* B6 L& F
enlargement of the penis, with a stretched length of- d! ~1 o0 h, t; y# o2 A5 A
8 cm and a width of 2 cm. The glans penis was very well, d4 L8 a6 i5 o( {
developed. The pubic hair was Tanner II, mostly around
3 c1 L( Y+ |4 |0 ~: v5 D, [9 a540, B( G, a9 T* Q. _ f
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from/ e+ J$ Z- e) w) x% A. M
the base of the phallus and was dark and curled. The4 C3 H4 T: x1 ]) Y$ B2 H+ e3 d
testicular volume was prepubertal at 2 mL each.
; H* ~) J9 E; @7 NThe skin was moist and smooth and somewhat
1 ~. w3 K2 s) ]! D. ^" Z. }oily. No axillary hair was noted. There were no' n# F1 R* W% H2 U( ?- l+ K8 ^
abnormal skin pigmentations or café-au-lait spots., o: @! C- N$ n+ Q# d) C3 U. G/ J4 Z$ S
Neurologic evaluation showed deep tendon reflex 2+# `- S* k* D% U! M( v. x; L2 G
bilateral and symmetrical. There was no suggestion! Z4 w$ o' d( u6 E' R. o+ p4 \1 I3 X
of papilledema.
5 X: R! z& M0 h; L- VLaboratory Evaluation/ p [* Z0 _" a; i) {
The bone age was consistent with 28 months by) }# @7 C6 U3 M0 g
using the standard of Greulich and Pyle at a chrono-9 I( f+ {. R: [) D/ D* r4 ?6 v
logic age of 16 months (advanced).5 Chromosomal6 O4 r: K; z( j) C0 N" v* l# x7 A
karyotype was 46XY. The thyroid function test, R& S8 Z8 ?; `$ q: H5 K
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
/ s2 C8 a# V M; ^( p7 Alating hormone level was 1.3 µIU/mL (both normal).% z) h0 g( G( q
The concentrations of serum electrolytes, blood* d) A, O! X) }9 e) U
urea nitrogen, creatinine, and calcium all were
1 a" l: t8 a: r% w) v3 Swithin normal range for his age. The concentration6 b* V) X: o% ]4 V# C) w7 M
of serum 17-hydroxyprogesterone was 16 ng/dL9 e2 r+ w, @! l+ X a
(normal, 3 to 90 ng/dL), androstenedione was 20/ K e' S% Q4 }( }
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
5 P; h9 |. i3 T& u* g) rterone was 38 ng/dL (normal, 50 to 760 ng/dL),
) A: O) X4 H. L/ p5 ]% \desoxycorticosterone was 4.3 ng/dL (normal, 7 to
$ z _- m! Z1 C49ng/dL), 11-desoxycortisol (specific compound S)
r+ f; g% G6 s; ^' g; Q5 n" rwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
1 _5 b, }, J4 Y% k* Itisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
; h Q" k( `9 \' H% u2 [8 Qtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
4 X% G) v$ f( a7 ^and β-human chorionic gonadotropin was less than9 q. G G" F& H2 g
5 mIU/mL (normal <5 mIU/mL). Serum follicular
$ N1 V% ~" J) U1 z; `stimulating hormone and leuteinizing hormone
5 X& z4 ~7 d, q6 r( G! Kconcentrations were less than 0.05 mIU/mL1 \. Y6 c0 i; ~0 o
(prepubertal).* k( K; `" ^% d/ Z
The parents were notified about the laboratory6 Q- O! c0 ]8 s0 V: F9 \& w
results and were informed that all of the tests were! f: v. e6 E" Q& ^, k2 S' X
normal except the testosterone level was high. The; {6 w) e% C! m& e
follow-up visit was arranged within a few weeks to% `% m( z1 c* l ^7 _+ w
obtain testicular and abdominal sonograms; how-! \1 _8 t6 V% j2 i1 ]- [' P1 ]1 _
ever, the family did not return for 4 months./ o @. C N9 Q2 e; Y
Physical examination at this time revealed that the7 k& C( k0 E/ M- P& D \8 _0 i
child had grown 2.5 cm in 4 months and had gained# E% G' d ^$ ]1 U
2 kg of weight. Physical examination remained
6 r3 d$ _) @/ sunchanged. Surprisingly, the pubic hair almost com-
0 D1 _3 `# _9 A9 l# N* e6 qpletely disappeared except for a few vellous hairs at$ I+ n, J4 u. t! w5 I4 V: c7 J) J
the base of the phallus. Testicular volume was still 2
# c! B1 g/ H( h( SmL, and the size of the penis remained unchanged.1 a P$ H% a/ W* p
The mother also said that the boy was no longer hav-
8 ^# ]+ I1 l+ I0 \; ~ing frequent erections.
6 c1 j4 m( ^1 ]3 [4 C9 S' aBoth parents were again questioned about use of
' r2 S8 f+ G2 U! l1 G Many ointment/creams that they may have applied to5 F+ H8 X) _# V7 z
the child’s skin. This time the father admitted the
" w; `% g$ R- H. H3 oTopical Testosterone Exposure / Bhowmick et al 5417 f" N2 X$ }8 U% X, s1 Q
use of testosterone gel twice daily that he was apply-& B, c! W. S' `0 t# G( ~
ing over his own shoulders, chest, and back area for
( Z8 W: g# O. J, F3 ^& \0 ca year. The father also revealed he was embarrassed; W2 p% s" B1 D. ~
to disclose that he was using a testosterone gel pre-, L% b; I& I$ `1 I9 _
scribed by his family physician for decreased libido0 |; Y9 a0 E9 E& A9 A' J& k& K
secondary to depression.$ f. R8 |$ \4 f' G; K9 }
The child slept in the same bed with parents.
1 |$ G7 g6 j. i) JThe father would hug the baby and hold him on his
2 j6 r# F' O, hchest for a considerable period of time, causing sig-0 p+ p$ E4 P8 ]# Y! l
nificant bare skin contact between baby and father." ]& |8 Y( J% ?! c7 A- y
The father also admitted that after the phone call,0 l/ c8 U9 K i8 A. T9 b
when he learned the testosterone level in the baby
0 W' L) m; a3 ~8 \( V/ _* v: d; a; `% U ^0 Vwas high, he then read the product information) b" i1 P: f# m& W
packet and concluded that it was most likely the rea-
- }% L0 u5 p% _2 p0 Xson for the child’s virilization. At that time, they: R( ?3 K/ |: G- Z0 g' `, e
decided to put the baby in a separate bed, and the
# D' ^; D: D& d8 kfather was not hugging him with bare skin and had
) h+ a1 k& g z3 [: Sbeen using protective clothing. A repeat testosterone
( s7 M6 b1 z1 T) z9 V: p# c5 a3 p3 stest was ordered, but the family did not go to the
8 j6 ]: n: E; y& ~% p, X& Slaboratory to obtain the test.
2 h% Y% w$ F8 h( ~; [( g2 kDiscussion7 K9 s+ _9 U; u$ x) x$ O7 I$ N
Precocious puberty in boys is defined as secondary8 F/ X2 a9 P$ j& I
sexual development before 9 years of age.1,4
: s# Z G2 k4 R, H5 \* v& ]Precocious puberty is termed as central (true) when) u; k4 ]& {1 s
it is caused by the premature activation of hypo- O, {4 k' h8 A3 H' U9 l
thalamic pituitary gonadal axis. CPP is more com-
5 ?& o* Y) g: {mon in girls than in boys.1,3 Most boys with CPP
% I+ N# d! z- g* }+ tmay have a central nervous system lesion that is1 T. s/ _9 s$ O! `9 E
responsible for the early activation of the hypothal-6 Z" g1 N$ |' p3 b
amic pituitary gonadal axis.1-3 Thus, greater empha-4 A5 E% y- N# k0 c$ \) F2 p5 o
sis has been given to neuroradiologic imaging in
% w1 }" v4 V8 {; R+ y! ?! jboys with precocious puberty. In addition to viril-! z2 M2 d! y, I P! t/ [! u
ization, the clinical hallmark of CPP is the symmet-# O, d: j0 n4 w7 Q! q+ K3 v" G
rical testicular growth secondary to stimulation by
* N5 o3 A4 N( c2 C% [ V8 t/ Y ugonadotropins.1,3
# d, w9 R/ X$ }( `7 j9 VGonadotropin-independent peripheral preco-
; m+ t* L* k. ]8 n; p) `cious puberty in boys also results from inappropriate. P+ P6 P. f3 m
androgenic stimulation from either endogenous or
0 H3 N$ U/ h0 a, @2 bexogenous sources, nonpituitary gonadotropin stim-
$ H, w" r2 L& Tulation, and rare activating mutations.3 Virilizing
9 r9 a& b' A! Mcongenital adrenal hyperplasia producing excessive
. n) T- D7 ~/ }, V1 _4 ^* k6 padrenal androgens is a common cause of precocious
: b q) N8 l+ ]+ c' s; H. d* g# xpuberty in boys.3,4
* r/ g4 @+ _% l5 w3 _, CThe most common form of congenital adrenal
$ R; Y# J2 S# hhyperplasia is the 21-hydroxylase enzyme deficiency.) U3 e$ j" ?, u" T0 ~; F' V8 g$ v
The 11-β hydroxylase deficiency may also result in O/ T6 y9 Z, z+ l8 s
excessive adrenal androgen production, and rarely,
5 J$ Y6 r0 {& H4 M# v& o3 }* T: dan adrenal tumor may also cause adrenal androgen5 D* K% S' k" c' \
excess.1,31 U4 w, L1 E' {. z% V! k6 I/ v. {
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from) H' c0 C3 I, q
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007 N/ Q$ z* V" y) h3 d$ _
A unique entity of male-limited gonadotropin-
/ O8 m. l& e0 _$ T; Aindependent precocious puberty, which is also known
' g/ f! y% v% m3 q# q% Cas testotoxicosis, may cause precocious puberty at a
3 R2 F5 ]' d+ overy young age. The physical findings in these boys
& A, h: L% i( S, qwith this disorder are full pubertal development,4 H$ a, {1 \) \2 ?
including bilateral testicular growth, similar to boys
! r+ D* `0 T* H. \6 D4 |with CPP. The gonadotropin levels in this disorder
6 \" I# Z& P2 v1 gare suppressed to prepubertal levels and do not show8 ?* R0 y8 O' ^. s5 J; \8 h
pubertal response of gonadotropin after gonadotropin-, ?( V0 G7 a" n/ |
releasing hormone stimulation. This is a sex-linked. Z4 G6 e: D7 f% M4 m6 r' V
autosomal dominant disorder that affects only& d, p1 n+ w0 P& c# M/ v. I
males; therefore, other male members of the family! f- }& i7 g0 P
may have similar precocious puberty.3- w7 \3 I3 ?3 _# ]' [* D! t4 K
In our patient, physical examination was incon-0 [3 E2 e9 \8 L/ [& q
sistent with true precocious puberty since his testi-
: K) J1 _0 n/ ecles were prepubertal in size. However, testotoxicosis
1 `/ c2 ]$ ~5 \2 z6 }was in the differential diagnosis because his father
5 o1 Y% f8 c* ^/ G; F( Istarted puberty somewhat early, and occasionally,1 X8 b* R3 S' I* L8 W8 p
testicular enlargement is not that evident in the4 f4 _2 Z$ x7 s& h0 g
beginning of this process.1 In the absence of a neg-+ F. W- i9 W7 c9 I* b. Y
ative initial history of androgen exposure, our* w m2 e1 m- J0 g% ?
biggest concern was virilizing adrenal hyperplasia,9 ~+ m+ M* Y8 @2 u4 B# c
either 21-hydroxylase deficiency or 11-β hydroxylase
, o# _1 X* t( z# Z" K! Hdeficiency. Those diagnoses were excluded by find-: }4 o: e5 {& |8 i# p
ing the normal level of adrenal steroids.
* M, Z0 P+ a$ s" mThe diagnosis of exogenous androgens was strongly
- \4 X6 ^$ s& ]- E _suspected in a follow-up visit after 4 months because; j, y. |0 W# C$ Z0 z
the physical examination revealed the complete disap-# i7 i' f/ j5 p9 G& ~, ~' `
pearance of pubic hair, normal growth velocity, and
2 u' s" [7 R2 |* X( i d# W4 `decreased erections. The father admitted using a testos-
( s' s, ]: F8 K3 S$ \8 |terone gel, which he concealed at first visit. He was3 l! B; N* c4 V: Q
using it rather frequently, twice a day. The Physicians’
1 K/ m0 m a" r3 u/ e1 d, BDesk Reference, or package insert of this product, gel or0 o9 S+ G! V3 `2 h
cream, cautions about dermal testosterone transfer to
7 J0 l8 ^' D8 b' Vunprotected females through direct skin exposure.
% |& [5 }9 b* q6 ~4 l0 X' h* WSerum testosterone level was found to be 2 times the
, k$ R) {% G" |: ^& K h7 Mbaseline value in those females who were exposed to$ L8 M" \. G$ c+ \" K& x9 c7 V
even 15 minutes of direct skin contact with their male
7 A) X' \' `& X! l6 Q% Epartners.6 However, when a shirt covered the applica-6 [* F3 ^* C% `; ~& a( i8 F! L
tion site, this testosterone transfer was prevented.
6 H% _$ y6 [- `6 s, N V7 ZOur patient’s testosterone level was 60 ng/mL,, {5 l( a: O, q$ m' N1 E' z
which was clearly high. Some studies suggest that
. S- I3 _0 W9 ]7 y: udermal conversion of testosterone to dihydrotestos-# U1 Z) @( `/ Q3 j+ a
terone, which is a more potent metabolite, is more
, ]/ w2 {. B/ E, zactive in young children exposed to testosterone2 f, j+ N0 O3 }0 W g1 e4 Z7 q! O
exogenously7; however, we did not measure a dihy-
8 K7 g8 Q& H; Jdrotestosterone level in our patient. In addition to7 Y% G0 r6 Z% ~ i! M
virilization, exposure to exogenous testosterone in# V# V0 a* L7 l: ?+ y8 H9 d& I; X
children results in an increase in growth velocity and/ ]) g8 k* q: X/ [; H$ S
advanced bone age, as seen in our patient.( T& Q6 I# }- K5 ?9 H& J
The long-term effect of androgen exposure during. H7 z3 Y8 l$ e5 Q4 N
early childhood on pubertal development and final
" D. m( }4 q# Z! W. `5 J7 Y: c8 ^adult height are not fully known and always remain
- z$ Z' H# f# t1 ~8 W. ` t* Za concern. Children treated with short-term testos-, I1 }: b( f) J% S# W' N9 E
terone injection or topical androgen may exhibit some: {& L( M! A2 Y% c7 u5 a+ P2 ^0 `
acceleration of the skeletal maturation; however, after
3 W& c! d6 a9 F, A/ I. b, ^' \cessation of treatment, the rate of bone maturation/ K7 |! P3 A: M4 d) g* b; x
decelerates and gradually returns to normal.8,9' z1 _0 o- q. _( }# i
There are conflicting reports and controversy# Z& ]4 s% o/ j* l
over the effect of early androgen exposure on adult
( C F9 Q9 Q- A2 V3 |8 y( Wpenile length.10,11 Some reports suggest subnormal; R' G0 L# k b0 B
adult penile length, apparently because of downreg-
. i, v6 d) f' Y: A5 t6 _ulation of androgen receptor number.10,12 However," o8 [0 K" Y+ R" t5 q9 t8 |
Sutherland et al13 did not find a correlation between
, z1 e4 a1 R9 [childhood testosterone exposure and reduced adult
/ L8 d! |1 ^$ L# q2 J! [# D5 cpenile length in clinical studies.; [# n2 c; g4 p: a0 W
Nonetheless, we do not believe our patient is5 T, r, n/ `5 F q# ~ L% y
going to experience any of the untoward effects from
, f! ?. H" R6 P$ S1 c3 P, n+ O6 k9 S% |testosterone exposure as mentioned earlier because: T: F& @+ V! Y0 d0 R! O
the exposure was not for a prolonged period of time.' M# b: ~3 L& W
Although the bone age was advanced at the time of/ u7 z6 E' `" m3 L) l. d( j
diagnosis, the child had a normal growth velocity at$ D" {' P0 i/ ]. b/ H
the follow-up visit. It is hoped that his final adult
& \* E' D! F( l" l6 I( j: Xheight will not be affected.
9 y# D+ R: |7 o( iAlthough rarely reported, the widespread avail-
. B1 [# M9 M+ v7 t$ l5 Bability of androgen products in our society may, z7 K0 C, E/ I2 n' Q# }. m! Z
indeed cause more virilization in male or female
. r9 A0 N0 S6 ychildren than one would realize. Exposure to andro-1 _/ g" ~ m" }: {
gen products must be considered and specific ques-0 e9 `% ~' E6 A
tioning about the use of a testosterone product or
C. |5 c7 b% w2 l2 Igel should be asked of the family members during
, v( g5 P0 s! k; Dthe evaluation of any children who present with vir-
Y+ [' c( n8 _+ } _5 e& D' Y$ yilization or peripheral precocious puberty. The diag-3 f- S# N4 n6 X3 f
nosis can be established by just a few tests and by
3 }- q* j7 }5 \+ Z r9 ]6 Xappropriate history. The inability to obtain such a- L# ^; ^* ^1 S. |3 ]
history, or failure to ask the specific questions, may
/ _. h2 ?7 S0 O a( Vresult in extensive, unnecessary, and expensive& i8 M3 ~0 Q4 ?9 k6 g
investigation. The primary care physician should be1 W) N9 V/ V, _& ~* _1 x
aware of this fact, because most of these children0 M0 w; g! k+ u* i1 ?0 |0 |) r
may initially present in their practice. The Physicians’. q8 R# W z6 Q9 g, }4 w; P% A
Desk Reference and package insert should also put a, {$ s" r0 T' h% N
warning about the virilizing effect on a male or
! Q- y9 s0 \. b1 Sfemale child who might come in contact with some-
( W5 y5 |4 M/ k- U% Xone using any of these products., x E3 d9 e& ~8 K# B" H
References
1 P9 A7 A$ U* e" d+ |9 d1. Styne DM. The testes: disorder of sexual differentiation1 A5 K4 M8 p' H) }
and puberty in the male. In: Sperling MA, ed. Pediatric
5 P6 J% s8 [# H; rEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;6 D7 y& ?4 I. A: Q5 J+ p: ^
2002: 565-628.
. U8 P- E: c& h( J) `2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
: ?! X5 s# |& Y3 K" R/ B4 r4 w" Dpuberty in children with tumours of the suprasellar pineal |
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