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Sexual Precocity in a 16-Month-Old
1 B" A" ?' M& N+ NBoy Induced by Indirect Topical/ {+ A5 l$ @# d0 q& `& `+ p$ ?
Exposure to Testosterone9 i% U8 V! ~1 G
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2' t8 L T( @0 g1 l& H, X! I# W; ]
and Kenneth R. Rettig, MD1
/ `& F0 k; I. P8 kClinical Pediatrics) K) k+ B9 h% U+ g9 y! I' \4 s
Volume 46 Number 6
2 s: l `7 E5 c# ?/ K' e- sJuly 2007 540-543# W0 `9 T5 w0 w) I N
© 2007 Sage Publications
/ X8 K6 z8 x8 l* P3 X10.1177/0009922806296651
/ v3 @5 z1 z9 U8 b9 `http://clp.sagepub.com
& _: M7 K( k' h, s: d; J% m3 ^6 J. H8 chosted at8 U _# X. F* o/ r& Y
http://online.sagepub.com
7 l& H$ r$ o" c1 Z; l* u+ u H! BPrecocious puberty in boys, central or peripheral,
: W; R& T: e* H; w) pis a significant concern for physicians. Central9 i' j' A f1 K8 Z
precocious puberty (CPP), which is mediated
3 e6 N0 O: R7 ?1 H8 w/ J) qthrough the hypothalamic pituitary gonadal axis, has. z0 {5 _4 v3 d$ t. E
a higher incidence of organic central nervous system, g% w: l. R D
lesions in boys.1,2 Virilization in boys, as manifested v9 q3 o7 G; [: L
by enlargement of the penis, development of pubic8 x! |8 g: u( G T- `( E2 ~
hair, and facial acne without enlargement of testi-
O, }8 V1 u* u6 Z5 R4 ~) ycles, suggests peripheral or pseudopuberty.1-3 We% a9 r& a' E* _7 z& ?3 [
report a 16-month-old boy who presented with the" }& \( ]+ R- ~4 |: X- c0 d
enlargement of the phallus and pubic hair develop-
% _/ {7 Y# O }ment without testicular enlargement, which was due0 ^* S: C3 I% u" ]2 e+ _/ Q
to the unintentional exposure to androgen gel used by
5 v! ~" e- r7 C6 G6 u, Mthe father. The family initially concealed this infor-0 t; |; o4 Q. d) x" B. x
mation, resulting in an extensive work-up for this
h- f7 Y, M+ l b, F; `child. Given the widespread and easy availability of/ a' ^& n2 v* x( K$ Z
testosterone gel and cream, we believe this is proba-
- G( @6 W h/ d7 G: `bly more common than the rare case report in the
0 a& ~& Q( w- U2 l; r' sliterature.4 ?3 U, o5 Y/ `
Patient Report ~1 a7 R. w+ ^# k9 d1 }
A 16-month-old white child was referred to the! J: ~1 ]" {4 e G B6 r+ Q, F
endocrine clinic by his pediatrician with the concern3 o7 B5 B3 @, W/ I
of early sexual development. His mother noticed7 ^$ b* H- R7 `% A1 Z% M: n
light colored pubic hair development when he was% a* d" b/ D0 r! b1 m8 H
From the 1Division of Pediatric Endocrinology, 2University of0 t3 S/ o/ ~8 m9 o7 j* y9 @
South Alabama Medical Center, Mobile, Alabama.
4 x; l: U, M) u6 r4 pAddress correspondence to: Samar K. Bhowmick, MD, FACE,
% }; }6 B% f! \8 ?Professor of Pediatrics, University of South Alabama, College of! r% H3 \0 c( ?9 M
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
9 q8 t4 R- c9 P. a6 S0 t6 he-mail: [email protected].3 Q, }. {! O4 ^6 K' o
about 6 to 7 months old, which progressively became; ^6 Z" b% I" @8 V2 j2 D/ E" x) O
darker. She was also concerned about the enlarge-( v/ {/ j# x3 {0 C4 V: P" u; N
ment of his penis and frequent erections. The child0 ?! V6 v, y" a) [
was the product of a full-term normal delivery, with
* `# N3 s8 O) v" Sa birth weight of 7 lb 14 oz, and birth length of& X. [: \2 @( _9 e+ {) \
20 inches. He was breast-fed throughout the first year$ t; h) d' l* k) S) C
of life and was still receiving breast milk along with" J: H: m% q) u& _2 G5 r) R
solid food. He had no hospitalizations or surgery,! ?+ C, D8 a( z. j* {6 G
and his psychosocial and psychomotor development
# R7 P7 S8 `5 k0 B5 t0 T( V. @7 |was age appropriate. }+ ~+ L: n+ L& q# }; r
The family history was remarkable for the father,
* T: c* U4 N) ]6 ~9 c0 xwho was diagnosed with hypothyroidism at age 16,! C' Q; h) z8 K. y1 ]* |
which was treated with thyroxine. The father’s8 W) s- |3 h2 W9 n% p F
height was 6 feet, and he went through a somewhat" \+ O m0 f2 T$ i
early puberty and had stopped growing by age 14.
! G6 h) F1 z; ~% oThe father denied taking any other medication. The
$ k6 j- Y* T+ d3 c' R6 a9 e" ?% Lchild’s mother was in good health. Her menarche
+ X3 t: ]/ o. C1 t" K1 b. ywas at 11 years of age, and her height was at 5 feet( I: F$ e' Y6 L4 F4 E( r3 _
5 inches. There was no other family history of pre-
( J' S5 _ _+ X% j2 J- ?cocious sexual development in the first-degree rela-
7 T5 [! I1 [, Z+ Z- _' atives. There were no siblings., ^1 M; `, V/ Y7 F( s! L3 s
Physical Examination
" G6 e5 ]# Q& Y9 j" HThe physical examination revealed a very active,
, ^8 n A3 p: y4 p* p7 Zplayful, and healthy boy. The vital signs documented
' h& y- e: D, ^9 s7 _, E; \) qa blood pressure of 85/50 mm Hg, his length was
0 i: z: W: a I: ]. {- ^90 cm (>97th percentile), and his weight was 14.4 kg. w7 D- r9 J2 J& N0 [5 V
(also >97th percentile). The observed yearly growth
9 _) W2 c' l7 r. |velocity was 30 cm (12 inches). The examination of7 y9 c& ]4 `+ {" I/ l
the neck revealed no thyroid enlargement.& F9 P. D3 W4 W3 ?6 F5 i; U
The genitourinary examination was remarkable for
$ k" [+ P8 N% u2 Aenlargement of the penis, with a stretched length of" @% U& T; J( K/ X9 o
8 cm and a width of 2 cm. The glans penis was very well+ `+ S# Y8 p+ [, D: Z7 }$ ?
developed. The pubic hair was Tanner II, mostly around7 ^! u8 N0 W& L. k- W
540
) p9 }: ?2 D5 q3 Q" J/ Uat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from0 B2 ]; N, J0 K& k+ w
the base of the phallus and was dark and curled. The
7 i7 g- O/ [& vtesticular volume was prepubertal at 2 mL each.# u l& n9 ]; B0 Z7 w4 W
The skin was moist and smooth and somewhat
5 A t6 F) f0 \1 e# t4 `oily. No axillary hair was noted. There were no
$ I4 Q0 L) C5 wabnormal skin pigmentations or café-au-lait spots.
1 c5 n, m! h9 g0 d6 `2 M1 u' yNeurologic evaluation showed deep tendon reflex 2+5 K% {, b5 |9 z r0 h8 h: x/ L
bilateral and symmetrical. There was no suggestion
9 X2 B( m8 ?$ ?3 k. hof papilledema.
6 q. ?& |7 @1 ^5 ^) A4 E3 k0 \5 C6 uLaboratory Evaluation9 @3 n6 I+ f' u7 y
The bone age was consistent with 28 months by, \0 `. c+ Q3 |
using the standard of Greulich and Pyle at a chrono-) R* `' O4 H2 P x8 G: j1 L
logic age of 16 months (advanced).5 Chromosomal
2 ~/ B" L5 D0 L; M% okaryotype was 46XY. The thyroid function test
8 d6 z/ O) u6 |showed a free T4 of 1.69 ng/dL, and thyroid stimu-+ C7 d: l0 R+ g) [; O! ]
lating hormone level was 1.3 µIU/mL (both normal)., D7 P4 K5 F: F& h: {3 i, T
The concentrations of serum electrolytes, blood
+ l9 v: r8 J1 Q, U7 Ourea nitrogen, creatinine, and calcium all were
% b: d- R1 K7 g- Ewithin normal range for his age. The concentration
$ d; \5 _: h- B5 aof serum 17-hydroxyprogesterone was 16 ng/dL
2 A! G% z& `% v. `1 X" H(normal, 3 to 90 ng/dL), androstenedione was 208 G4 P/ P) ~+ D' H
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
# h2 s) L7 i& [ R3 G& wterone was 38 ng/dL (normal, 50 to 760 ng/dL),4 Z1 v% J: o9 T" T
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
# f3 L0 C& I2 p: g7 f# f m7 _49ng/dL), 11-desoxycortisol (specific compound S); Q+ ?! y9 s8 I z
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
$ Z( y! X5 P" ^: V) [! F" {tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total, _ @, S& v7 L. p O% I
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
' p' M2 l# F2 Band β-human chorionic gonadotropin was less than! p$ `: C5 N" q' i2 u' |( M0 H
5 mIU/mL (normal <5 mIU/mL). Serum follicular
0 I$ u, H. |1 ?& U. Y4 hstimulating hormone and leuteinizing hormone* [ d$ z2 O# N; v& H) D
concentrations were less than 0.05 mIU/mL# `7 S8 C+ V5 L3 e
(prepubertal).
* \: ]# k. N/ k) C# dThe parents were notified about the laboratory* U! Z& m' ~0 R8 P( Q: X4 v7 N' T: d
results and were informed that all of the tests were
# F/ A, {3 y2 Jnormal except the testosterone level was high. The
; J* I! \- f; k# @ Y7 W \' Bfollow-up visit was arranged within a few weeks to' D% s2 c* J3 t2 e
obtain testicular and abdominal sonograms; how-3 ]" b/ I0 {/ ^3 t# v7 j
ever, the family did not return for 4 months.( f5 \( b: o& p' l
Physical examination at this time revealed that the
8 l# M6 l, J! f" G4 n# D! Ochild had grown 2.5 cm in 4 months and had gained# A- Y) q6 s: D5 }
2 kg of weight. Physical examination remained6 @# m! M- d- s$ O% _6 ^
unchanged. Surprisingly, the pubic hair almost com-
5 j9 l) N3 `: J; J9 S1 ] E# Cpletely disappeared except for a few vellous hairs at% X& Q! W+ ]6 r) P: W
the base of the phallus. Testicular volume was still 2
' v' {" S- }; k5 ?# y% @9 i# O* ymL, and the size of the penis remained unchanged.
8 t/ j7 {$ C3 fThe mother also said that the boy was no longer hav-
* ^" d; J6 n+ G# O g- jing frequent erections.: x: z- L8 @% v2 c3 x7 ~
Both parents were again questioned about use of5 a/ I& W3 {6 N+ O+ n' @6 j
any ointment/creams that they may have applied to7 `. ^" E7 ]; C A; w$ f
the child’s skin. This time the father admitted the% A0 A; Y0 N0 z; L* I0 n2 f4 w
Topical Testosterone Exposure / Bhowmick et al 541
8 v$ i0 o* @/ puse of testosterone gel twice daily that he was apply-# _& M% F; B# W6 ~
ing over his own shoulders, chest, and back area for
; m& `( h$ a6 J; p4 n+ X2 ~a year. The father also revealed he was embarrassed/ k& X# G$ @! \) x! j& q
to disclose that he was using a testosterone gel pre-
# ^7 m$ {* p5 ~scribed by his family physician for decreased libido& S3 K) F/ @& ?4 K# |3 _
secondary to depression.' g) ^ V4 v- K3 ?
The child slept in the same bed with parents.% |$ @" C2 H/ e/ m( n- L8 {
The father would hug the baby and hold him on his( ]: {9 e9 C) S& n- x# ?4 z
chest for a considerable period of time, causing sig-
' \; ?2 z6 P! X3 Mnificant bare skin contact between baby and father./ P4 p: k2 P6 I, }3 ^* c5 [: w
The father also admitted that after the phone call," D* k' w4 A, ^. M4 i! I
when he learned the testosterone level in the baby
. D# R0 p: z) |5 l9 {" Y( ^1 r2 Gwas high, he then read the product information6 b: Y) f* E- h2 R! I5 i. z+ r; X6 F
packet and concluded that it was most likely the rea-/ C' M6 W$ v* r- ^; E1 x c
son for the child’s virilization. At that time, they
5 I' w- y. |8 v8 x$ V) Ndecided to put the baby in a separate bed, and the) {, P0 B+ L; J- v+ `
father was not hugging him with bare skin and had
+ ~# Z9 N/ L1 C) e2 K) obeen using protective clothing. A repeat testosterone
8 R& H1 n6 a3 B% T$ R* @test was ordered, but the family did not go to the
9 k9 x' x& \6 s P% A8 S3 f5 ] t0 |laboratory to obtain the test.1 @- a& X; w- l" \% i( {
Discussion
5 o9 l6 n& s, B7 ?, |. k" o/ q) xPrecocious puberty in boys is defined as secondary
, }: I/ h- Q+ E2 l3 _sexual development before 9 years of age.1,4
) `& p; l# w z/ m' B# i+ jPrecocious puberty is termed as central (true) when
, q) r; w* h1 j7 \; M4 U* S: ~it is caused by the premature activation of hypo-/ }: l, [6 B, f9 n: f0 E
thalamic pituitary gonadal axis. CPP is more com-; H. @% F# B0 G" C c8 n, C
mon in girls than in boys.1,3 Most boys with CPP
0 V) X; i2 T1 ?2 Mmay have a central nervous system lesion that is$ H" `5 u* q7 b4 v
responsible for the early activation of the hypothal-
X! q. U% l4 B! Z* hamic pituitary gonadal axis.1-3 Thus, greater empha-
! A0 N9 l$ L7 b! z& Y* x2 tsis has been given to neuroradiologic imaging in6 H `9 `! t7 L) _
boys with precocious puberty. In addition to viril-
" r" B7 u# c( x! D8 \2 eization, the clinical hallmark of CPP is the symmet-/ ? w4 ]5 e$ }, z, o" U* [
rical testicular growth secondary to stimulation by
: F( C5 O8 [4 s* ~4 jgonadotropins.1,3+ A! u8 m) l; ~7 p5 _$ w
Gonadotropin-independent peripheral preco-- }0 C/ C8 Z' e
cious puberty in boys also results from inappropriate1 ~' T- R* {5 f% Y' Q4 r; D e3 F
androgenic stimulation from either endogenous or
* t. O3 j9 b, y+ `9 Yexogenous sources, nonpituitary gonadotropin stim-
: B, v2 }/ }$ x; l. Pulation, and rare activating mutations.3 Virilizing
( I9 v; ~8 l2 k& ?congenital adrenal hyperplasia producing excessive' W) Z9 L5 [ R" q% r6 O
adrenal androgens is a common cause of precocious
: k6 L; I% O; M, i" L6 e: f6 b8 Gpuberty in boys.3,4
6 C. Z$ Q/ f& s; e4 I5 s8 o# aThe most common form of congenital adrenal; Q; m# l. C8 C5 l/ ?8 y. B
hyperplasia is the 21-hydroxylase enzyme deficiency.
" ^6 `$ u8 \4 E ^9 BThe 11-β hydroxylase deficiency may also result in
4 c* L9 U- k- c. P0 kexcessive adrenal androgen production, and rarely,+ c+ E- z$ v3 l- l: F
an adrenal tumor may also cause adrenal androgen
0 r1 f$ V; x: t8 O$ A6 o; p( iexcess.1,39 j! h7 ?) }0 @4 U9 j8 |: t
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
) E5 N! V( g+ \. o542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
8 E6 _ m# n/ u( @! f% a" E" aA unique entity of male-limited gonadotropin-
n0 k( y; T2 a* c3 I4 ~9 qindependent precocious puberty, which is also known! B( n: `: f; e$ P. X: f
as testotoxicosis, may cause precocious puberty at a
3 t, v" A5 l7 ]" R$ w8 {very young age. The physical findings in these boys
% Y3 Y' u1 r9 X, awith this disorder are full pubertal development,! V: U& Z, q! B
including bilateral testicular growth, similar to boys3 e* K$ ^. b8 ^$ |+ ^
with CPP. The gonadotropin levels in this disorder; T/ n! e( L; ~8 W; b& r6 p
are suppressed to prepubertal levels and do not show
1 {# f0 x: p- ]6 z6 Opubertal response of gonadotropin after gonadotropin-
6 ~6 S0 Z+ T3 @4 kreleasing hormone stimulation. This is a sex-linked/ B; y3 A/ W+ P% F
autosomal dominant disorder that affects only- F% z' I/ a1 [5 ^
males; therefore, other male members of the family
9 \ L* k& f3 v3 t3 a6 y/ ~9 nmay have similar precocious puberty.3& z: W; K z8 H' u$ o" j( A
In our patient, physical examination was incon-
5 A& @; _- B) _+ ^1 jsistent with true precocious puberty since his testi-& t5 _: H2 L5 x9 d* y J
cles were prepubertal in size. However, testotoxicosis
( I; |. ~5 u+ D3 x) W+ v/ C6 owas in the differential diagnosis because his father H, Q4 p6 ~- Y" B
started puberty somewhat early, and occasionally,( l8 V9 n2 j3 `& S; O: U' n, K
testicular enlargement is not that evident in the" U8 J: Z+ ]& l/ s+ p! J( u
beginning of this process.1 In the absence of a neg-
. g2 a9 t6 O8 D! P/ S6 @ative initial history of androgen exposure, our4 _: _! z5 @8 S% Z& s8 P
biggest concern was virilizing adrenal hyperplasia,+ z5 t, j g" d# X+ _6 n) x2 C! A& \
either 21-hydroxylase deficiency or 11-β hydroxylase- E7 O7 |6 E2 I+ ]/ {0 q; }1 w% U t
deficiency. Those diagnoses were excluded by find-* c$ v1 e( K2 c+ c P
ing the normal level of adrenal steroids.
% N, ~, t# u$ b* j* R$ SThe diagnosis of exogenous androgens was strongly7 {# r8 o7 h2 p7 ]
suspected in a follow-up visit after 4 months because4 V. S) k2 ^) A5 M E" l$ A6 ^
the physical examination revealed the complete disap-2 O+ Y% L* i V' h E+ C! z; R
pearance of pubic hair, normal growth velocity, and
- x$ t6 }; g, Rdecreased erections. The father admitted using a testos-6 {$ U* p2 i3 q# Z: B3 E }' v
terone gel, which he concealed at first visit. He was
. W6 F8 E& G7 p/ ` ?% iusing it rather frequently, twice a day. The Physicians’
( Z6 X& O3 N9 O, F/ }Desk Reference, or package insert of this product, gel or, ?4 \% b2 E* |7 i$ F
cream, cautions about dermal testosterone transfer to- D' k. h9 G1 M+ Q; t
unprotected females through direct skin exposure.2 F. j1 n/ @4 \2 X% O- P% Z
Serum testosterone level was found to be 2 times the
- W: N! _7 C c# V) \1 lbaseline value in those females who were exposed to1 q! z, [ W2 O3 O: ^% \
even 15 minutes of direct skin contact with their male# l4 w+ Q% K& W2 o9 c0 @7 H
partners.6 However, when a shirt covered the applica-
4 ^) x8 E5 g# s; E" xtion site, this testosterone transfer was prevented.8 P! F) x/ x+ m" v: ^5 F
Our patient’s testosterone level was 60 ng/mL,
6 y" L4 l/ @% \1 ]which was clearly high. Some studies suggest that
0 P- L: t9 T! W) I( wdermal conversion of testosterone to dihydrotestos-6 O7 {, E& U" s0 Z( W
terone, which is a more potent metabolite, is more2 r# {+ `8 d6 P: p3 e
active in young children exposed to testosterone
, w* k2 i0 P) f0 H/ O9 S+ Dexogenously7; however, we did not measure a dihy-
/ k" r: {& g4 u6 x4 |/ Ndrotestosterone level in our patient. In addition to% i# s# f# z. A8 M: f& ~7 z
virilization, exposure to exogenous testosterone in
2 R! D% F" c2 C* V6 ]5 Ichildren results in an increase in growth velocity and9 u6 A0 [0 E" C
advanced bone age, as seen in our patient.
. g: c& R0 F( x" A. s; wThe long-term effect of androgen exposure during
: O+ I* E% P! dearly childhood on pubertal development and final4 J* C: w8 u: s
adult height are not fully known and always remain
* r* n- D5 {# k% r+ m- _a concern. Children treated with short-term testos-
, {: z+ W4 X( w5 T5 n7 Rterone injection or topical androgen may exhibit some
5 [- V: n4 Z! d* a" @acceleration of the skeletal maturation; however, after# E6 {! H" ?4 k0 S2 W" p1 u
cessation of treatment, the rate of bone maturation
/ g4 v7 h3 e- t/ w8 Y9 ydecelerates and gradually returns to normal.8,9
" q/ m& d. Q) l% B# W- k8 X6 ?There are conflicting reports and controversy3 B( W. z/ h; ^( Y; E! i
over the effect of early androgen exposure on adult
# g5 x& h) G7 L* Tpenile length.10,11 Some reports suggest subnormal
# j5 M" A; U! p8 f. S+ Ladult penile length, apparently because of downreg-, b. k( k$ K5 R R2 y5 S
ulation of androgen receptor number.10,12 However,( _& n4 d, M8 m3 ]/ K A
Sutherland et al13 did not find a correlation between2 Y( z* w& {6 M# P6 u5 w
childhood testosterone exposure and reduced adult' s5 z4 T# S! p% d0 o
penile length in clinical studies.
O$ Y8 d7 r* o5 d a9 CNonetheless, we do not believe our patient is
$ O# x0 T$ D0 p- T% i) ]3 ?! ?) pgoing to experience any of the untoward effects from4 v9 @( C7 c' A$ P3 S
testosterone exposure as mentioned earlier because9 b; G5 k4 ^7 b5 C2 [. s2 ]' K
the exposure was not for a prolonged period of time.3 g) o1 ~# p' C' {/ o% _
Although the bone age was advanced at the time of6 S4 F; K$ \9 F! w
diagnosis, the child had a normal growth velocity at% D4 z9 W0 |# Y, L
the follow-up visit. It is hoped that his final adult* [7 ]1 \! H. n; W& k2 T0 B; I
height will not be affected.3 u+ d/ g! w% h
Although rarely reported, the widespread avail-
: o7 N% _$ A( @" w/ ~7 O3 _3 J T0 C: s5 Mability of androgen products in our society may
/ S" v0 C, R% n, L1 c0 iindeed cause more virilization in male or female
1 U1 Q! J& ^# K% |' b: c# W& vchildren than one would realize. Exposure to andro-
' q+ g; g2 [, C* \; _! Wgen products must be considered and specific ques-
) P0 H9 G }+ L0 K; E# Etioning about the use of a testosterone product or
, b3 o3 E ~6 e7 L* h; agel should be asked of the family members during: C- K' d7 W+ C$ m
the evaluation of any children who present with vir-
/ S7 {! Q8 _, i+ U( Zilization or peripheral precocious puberty. The diag-' N4 A) ~( o) y
nosis can be established by just a few tests and by0 G/ j: g6 C3 a( \6 P
appropriate history. The inability to obtain such a" Q1 }1 q& R0 E$ d3 p
history, or failure to ask the specific questions, may: M" r3 Y& u- e. }3 A
result in extensive, unnecessary, and expensive
, H- X/ D3 n0 `; V0 y! ^1 rinvestigation. The primary care physician should be
% R/ j5 h1 F q* @" s$ n$ u' R* daware of this fact, because most of these children6 Z; f# n1 j! F4 N. E+ ~! J' z
may initially present in their practice. The Physicians’
% w' v% K6 L" X# Z5 y& ~, M4 jDesk Reference and package insert should also put a
; c9 D9 Z2 }9 _3 g/ Q/ c6 T( @2 Ywarning about the virilizing effect on a male or
/ E* `, e5 n3 ]* `female child who might come in contact with some-/ d4 _# O5 N( @! z( ], _
one using any of these products.
: C2 c2 U7 v& U2 cReferences
4 x5 a, T8 J/ Q; X+ M- d1. Styne DM. The testes: disorder of sexual differentiation
. H$ k- T9 G9 G% y8 T% S, T7 W8 _and puberty in the male. In: Sperling MA, ed. Pediatric! [4 b s* ^3 I& V5 f' h N, i' i6 ]
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;' T8 S' u' l4 O0 v' P/ i
2002: 565-628.
9 W- u0 c# Y: s% q- d9 ~6 \2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious: B) p: C) p) X }9 c) Q, x; ? J# L1 e
puberty in children with tumours of the suprasellar pineal |
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