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Sexual Precocity in a 16-Month-Old
& @$ Y* w! @6 |# ~. {9 p/ RBoy Induced by Indirect Topical- B' j" ^1 U: i( k3 Z( ]9 o
Exposure to Testosterone/ S- V0 [! f9 _& d v) v3 \) {9 U
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
! b- E" G" k K( g6 ]) wand Kenneth R. Rettig, MD1
0 G& Y4 e- `5 V3 ]Clinical Pediatrics5 H E1 S( Z) C6 ], G
Volume 46 Number 6
0 B* v V9 i, J) P6 W+ S8 H6 UJuly 2007 540-543
, w, R1 W. d# Y; t+ q- R© 2007 Sage Publications- R% H! Z6 Y. [5 }- T( u2 \
10.1177/0009922806296651
2 C- U( s; R! e8 q$ d# [3 t$ Khttp://clp.sagepub.com" c/ T& v. o7 g! E" g' t( C
hosted at4 f3 `/ n3 {& k4 u( P$ @' ?
http://online.sagepub.com
1 ]" ]* h: p1 Z3 r4 k/ HPrecocious puberty in boys, central or peripheral,
& B/ G" C2 r H8 u7 C. D, u& lis a significant concern for physicians. Central
! U3 e0 z% G/ z$ ?precocious puberty (CPP), which is mediated6 g8 z ^: {, A% o) T
through the hypothalamic pituitary gonadal axis, has8 o2 t% }+ s# P% F7 j9 q
a higher incidence of organic central nervous system
M4 d! ]0 `* P$ k) M1 D! Plesions in boys.1,2 Virilization in boys, as manifested
5 d& F, L3 T7 c g# Oby enlargement of the penis, development of pubic
6 M" l: {4 O. Jhair, and facial acne without enlargement of testi-
. I) t: ~: Y9 ?cles, suggests peripheral or pseudopuberty.1-3 We
, K t8 V" W0 ureport a 16-month-old boy who presented with the W9 _2 r8 E K: I+ H
enlargement of the phallus and pubic hair develop-
4 m" \; e, ^- q! P9 wment without testicular enlargement, which was due
- u$ l/ Z6 s% u% ]to the unintentional exposure to androgen gel used by6 t" a1 L+ L3 T5 f! O. s) @
the father. The family initially concealed this infor-
, L' g3 m# e: Q9 i* _. Nmation, resulting in an extensive work-up for this
! w( u! Q! q! nchild. Given the widespread and easy availability of+ t4 P0 ~9 m6 F. n( G
testosterone gel and cream, we believe this is proba-
. i5 h. }7 q/ m" _, Q5 ]" zbly more common than the rare case report in the
c/ j4 ]& P5 E6 ?: Kliterature.41 D& X' Q- I0 {7 r5 }
Patient Report
& e' N( r' M, }' [' M+ e \ IA 16-month-old white child was referred to the
* C; R/ G6 Y/ r9 Q' Y( bendocrine clinic by his pediatrician with the concern
* z1 [$ J; N+ z! Y) dof early sexual development. His mother noticed4 U( m* y4 F+ A2 N; ?
light colored pubic hair development when he was! n" O" |# g2 }% O: j0 z
From the 1Division of Pediatric Endocrinology, 2University of& w6 g( \& u, t! ~
South Alabama Medical Center, Mobile, Alabama.
p6 O! A0 E# J( K# D/ c7 L6 \, YAddress correspondence to: Samar K. Bhowmick, MD, FACE,
2 j$ E% X. `+ X% r7 P+ b! `5 SProfessor of Pediatrics, University of South Alabama, College of
3 x- l% B! U$ W* P: eMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
) f: g: c- U/ x9 {9 Q2 ee-mail: [email protected].2 u; K1 B1 \' K/ r
about 6 to 7 months old, which progressively became
! T9 p/ j" ? H8 F4 F7 udarker. She was also concerned about the enlarge-) D4 u) v- w+ L, E) K0 z
ment of his penis and frequent erections. The child
4 c+ f( ~. Y" [7 C; I# L$ ?4 ]' T1 nwas the product of a full-term normal delivery, with
2 F2 v t& R6 q! [- k: i) ua birth weight of 7 lb 14 oz, and birth length of
. M# s$ C! X" z2 U5 G ?20 inches. He was breast-fed throughout the first year
# Q$ i5 F0 I5 W# rof life and was still receiving breast milk along with
& Y4 i& W5 Y |! fsolid food. He had no hospitalizations or surgery,
- }6 H3 K: C4 H& D, }2 Nand his psychosocial and psychomotor development
% W' _/ Y' x' r5 H4 C) r' Xwas age appropriate.$ ?" m$ r% F" q' d7 h: ~! j9 v9 ~
The family history was remarkable for the father,! k) t' f$ J/ z& f D
who was diagnosed with hypothyroidism at age 16,8 b+ P! _2 W* P, o; P
which was treated with thyroxine. The father’s' E3 ^4 C; v/ Y, }/ G
height was 6 feet, and he went through a somewhat
7 P9 E8 U; o" j% F- ^$ Zearly puberty and had stopped growing by age 14.. j; e g3 l- i1 M/ T) m
The father denied taking any other medication. The0 n2 [5 a" B8 U1 k; r
child’s mother was in good health. Her menarche; s0 J. |; c& F- f5 N+ ~- B2 ?; c
was at 11 years of age, and her height was at 5 feet
$ O, z5 E2 V7 \: j5 inches. There was no other family history of pre-
8 C/ Z- ?8 p% O' n' ~cocious sexual development in the first-degree rela-$ {7 d+ n/ e, w7 H
tives. There were no siblings.
4 e% v" m* R+ _Physical Examination
( y$ r) u) y; r+ lThe physical examination revealed a very active,/ r( X2 Z3 ~8 K. g9 | [
playful, and healthy boy. The vital signs documented
8 S: Y5 p- J' b. g; w) `- {a blood pressure of 85/50 mm Hg, his length was
! {: O, q9 k) [9 r8 I90 cm (>97th percentile), and his weight was 14.4 kg
" H4 b. L: s3 H) I8 D' E(also >97th percentile). The observed yearly growth
: ? S3 ]5 h! }* Tvelocity was 30 cm (12 inches). The examination of
5 q9 k: m U; Ythe neck revealed no thyroid enlargement.% L* V' ]: S5 o2 i
The genitourinary examination was remarkable for
9 t/ v% ` P, y7 c- b% ^enlargement of the penis, with a stretched length of2 p6 @4 y* B& }0 |
8 cm and a width of 2 cm. The glans penis was very well
1 R& \( z5 i( Z( ddeveloped. The pubic hair was Tanner II, mostly around4 Z, ~% a% J& Z0 I
540 a7 K3 s8 c8 I* t
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from+ U8 M+ P5 b; R7 H7 ~
the base of the phallus and was dark and curled. The7 l0 R: D: D/ Z
testicular volume was prepubertal at 2 mL each.+ l% X1 v4 \% _* T% ^0 C! [0 ]
The skin was moist and smooth and somewhat8 T, y, J! X2 g; a
oily. No axillary hair was noted. There were no5 M5 v! a7 y) o; u
abnormal skin pigmentations or café-au-lait spots.+ B, n) ~ ]5 z h
Neurologic evaluation showed deep tendon reflex 2+
, L% U0 y6 [" N/ K6 nbilateral and symmetrical. There was no suggestion
/ m4 }# G: w3 y( A3 d' D9 iof papilledema.
: m: x$ B& X! S" A( k1 {) gLaboratory Evaluation
9 B9 d2 k, s3 F- O ]8 v$ F. pThe bone age was consistent with 28 months by
[5 H! x/ T' U% Jusing the standard of Greulich and Pyle at a chrono-9 \9 }7 e9 n5 _* S9 x+ q' M# h# E; h
logic age of 16 months (advanced).5 Chromosomal
- C, S5 u& g' V% K: D/ p; m# h2 xkaryotype was 46XY. The thyroid function test+ J6 V0 {' x5 K7 { b7 }7 F- x
showed a free T4 of 1.69 ng/dL, and thyroid stimu-/ d8 t9 @+ O3 Q0 L
lating hormone level was 1.3 µIU/mL (both normal).
- I0 t! C" }( w+ K$ T. [- O, EThe concentrations of serum electrolytes, blood
6 H9 L6 Z! v: b1 ~- eurea nitrogen, creatinine, and calcium all were
6 Q; d0 E6 Y9 h6 V* N; I% Rwithin normal range for his age. The concentration( E; }) I/ n' H
of serum 17-hydroxyprogesterone was 16 ng/dL9 ~" @' b1 Y: Q' L
(normal, 3 to 90 ng/dL), androstenedione was 20
7 U `1 p$ [; [( v- hng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
& p+ R2 W! B2 i- Cterone was 38 ng/dL (normal, 50 to 760 ng/dL),
6 f5 h% _' F5 I- q5 K1 [* ?0 Fdesoxycorticosterone was 4.3 ng/dL (normal, 7 to S+ Y# g" D! H- R w& V
49ng/dL), 11-desoxycortisol (specific compound S)
/ ?, {. k3 ~' F3 p" v" s4 q( gwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
! }3 G8 S1 g; \ s* y$ Etisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
+ Z& B. p: y0 N/ D, S8 ntestosterone was 60 ng/dL (normal <3 to 10 ng/dL),3 c0 q! v" X! P! A8 j5 \
and β-human chorionic gonadotropin was less than6 s- V9 k& h$ J7 i4 k# c$ O
5 mIU/mL (normal <5 mIU/mL). Serum follicular
# {! L. |$ P, ustimulating hormone and leuteinizing hormone0 S; Q+ X0 I! M4 h: y
concentrations were less than 0.05 mIU/mL9 ?- N# x* M/ J1 N8 u& r! s# a
(prepubertal).$ [) r1 f9 v) t, ^ j3 s
The parents were notified about the laboratory
. U* u/ K. X2 B2 e& Xresults and were informed that all of the tests were2 H' \# W7 r1 a+ {9 _
normal except the testosterone level was high. The+ D( S5 k/ d. x7 |
follow-up visit was arranged within a few weeks to' G# Q( {$ h- p3 W* k8 a B' Z7 n
obtain testicular and abdominal sonograms; how-
: h5 m% E/ h; ?8 V. T. sever, the family did not return for 4 months.
, I3 z5 \6 Z/ K- xPhysical examination at this time revealed that the
% ^8 F! P/ e. B) Hchild had grown 2.5 cm in 4 months and had gained
2 g$ I9 \$ p$ o4 D5 h. r, W9 D2 kg of weight. Physical examination remained
- t9 \( }+ O+ p5 Q. {% i. Hunchanged. Surprisingly, the pubic hair almost com-
* T3 N: n7 [4 t* u& S! _5 H1 Vpletely disappeared except for a few vellous hairs at& E1 o1 d$ G+ W/ J3 O
the base of the phallus. Testicular volume was still 2
]- D1 F& W8 c4 r* t3 rmL, and the size of the penis remained unchanged.
- e6 ^8 E4 J9 z& W; TThe mother also said that the boy was no longer hav-
2 q; n& z$ u+ H8 p" K! j$ A4 D# V, oing frequent erections.5 R: D% z' F8 ~7 r/ A$ o
Both parents were again questioned about use of
' P, L! v6 B+ [8 k* p! Dany ointment/creams that they may have applied to
' y, l6 Z/ n9 `* `( \the child’s skin. This time the father admitted the
# A# ^' r" C% d1 Q3 e, c2 ATopical Testosterone Exposure / Bhowmick et al 541
7 Q% Y8 w# q+ O- |& [1 r muse of testosterone gel twice daily that he was apply-+ z# Y6 F7 B- R8 P6 \9 b$ R
ing over his own shoulders, chest, and back area for# @6 V1 `4 T3 ^( z) J
a year. The father also revealed he was embarrassed
! O0 I$ R! d6 @8 ?: ?" Nto disclose that he was using a testosterone gel pre-" Z2 O2 u7 g* `) h, z
scribed by his family physician for decreased libido9 P# I3 R2 G: p
secondary to depression.
4 i0 f# O: U2 E5 f; `: HThe child slept in the same bed with parents.
- h& c! t, B9 L7 R% z* @The father would hug the baby and hold him on his5 J' [ G( y# n+ L! J- O& {
chest for a considerable period of time, causing sig-. r% A. h8 P6 W1 r. a- B, L) d. x8 V
nificant bare skin contact between baby and father.
1 |2 f# u/ g9 ~The father also admitted that after the phone call,
1 e- r1 E# }, m& owhen he learned the testosterone level in the baby3 S6 h3 ~, r; G" p
was high, he then read the product information$ q1 Y% \8 ?! z7 Z3 a1 Q% k( R
packet and concluded that it was most likely the rea-
& _8 V0 H$ B6 h' d. T) B& Pson for the child’s virilization. At that time, they4 v6 y4 z9 _6 Z7 S) Y8 }' Z
decided to put the baby in a separate bed, and the0 \$ \" ~! ? C# e& q
father was not hugging him with bare skin and had
5 E# E9 I2 F4 Z5 w5 i! D7 e3 qbeen using protective clothing. A repeat testosterone6 F' ]4 w- y1 Y# n9 t A7 V
test was ordered, but the family did not go to the
# {* I6 [& J! Z; u2 z& g" M* x, ?laboratory to obtain the test.
6 M. H# T6 a' VDiscussion
6 ?; P+ x8 u5 ?' Y# V) M$ ^Precocious puberty in boys is defined as secondary0 y) A( B6 d. f+ e4 n
sexual development before 9 years of age.1,4
# ]% a5 Q1 c9 U A& W3 S! ~Precocious puberty is termed as central (true) when C6 f1 i7 X& _8 q+ q6 S
it is caused by the premature activation of hypo-
- g) M' Q! C; L x, ythalamic pituitary gonadal axis. CPP is more com-. R1 p, Z+ p% T- e5 I" |
mon in girls than in boys.1,3 Most boys with CPP; r+ J0 ^: _9 o2 A
may have a central nervous system lesion that is
) ]8 F/ D0 z6 i- q( }& @- [5 Lresponsible for the early activation of the hypothal-
1 G1 f2 B" A0 L4 S. D- p5 u4 V+ Camic pituitary gonadal axis.1-3 Thus, greater empha-
1 F W( r% O- p: d5 lsis has been given to neuroradiologic imaging in+ _. H. o. j8 n$ f, h, U8 B
boys with precocious puberty. In addition to viril-& `- i+ w3 H- Y
ization, the clinical hallmark of CPP is the symmet-
9 i! s0 X( V7 \6 h5 rrical testicular growth secondary to stimulation by ?; h+ f* c0 Y, A, i! b
gonadotropins.1,3
' Y# @9 J& _ u1 a7 p# G+ m$ }Gonadotropin-independent peripheral preco-
# {: W% |) u# fcious puberty in boys also results from inappropriate
0 @4 v0 p2 G9 V5 r8 a- Jandrogenic stimulation from either endogenous or- A, ~' k% U& P
exogenous sources, nonpituitary gonadotropin stim-3 ^/ X) ?4 [' t8 s, V6 o4 y
ulation, and rare activating mutations.3 Virilizing
, ?4 Y: N6 [4 d' E u1 Q* y, Xcongenital adrenal hyperplasia producing excessive. W/ Y6 Q, t" g1 [' S0 u/ L
adrenal androgens is a common cause of precocious
* u/ P4 B+ i" y; k* {puberty in boys.3,4
6 R4 o! I9 F+ o/ JThe most common form of congenital adrenal2 T) L a5 d- j% u$ ^- T2 P" u; ]
hyperplasia is the 21-hydroxylase enzyme deficiency.
% s+ F9 S) y: Y) ^) g: H" u" U, sThe 11-β hydroxylase deficiency may also result in' ~0 h, G, Y3 O/ a- l
excessive adrenal androgen production, and rarely,
' |' J* S2 h! O8 g9 yan adrenal tumor may also cause adrenal androgen
4 R- p2 C2 r4 ]9 `- _* \excess.1,3
9 {1 U& U9 W2 b3 ~1 ]& @& Gat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
0 }+ ~) w3 O, |$ w- r# U542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
' A5 m5 E/ ^- ^A unique entity of male-limited gonadotropin-& F) q! r+ W7 y3 n8 J
independent precocious puberty, which is also known1 N) v" p" s7 b
as testotoxicosis, may cause precocious puberty at a
* M$ C8 `" l6 ~5 x" Cvery young age. The physical findings in these boys
; L6 Z0 _) L# T [9 g# Qwith this disorder are full pubertal development,4 c! q& b) g ~, M0 ^
including bilateral testicular growth, similar to boys
4 ]7 k- u6 ]0 y+ Xwith CPP. The gonadotropin levels in this disorder
7 b( r$ Z0 M/ r; B6 V9 Rare suppressed to prepubertal levels and do not show* I% [0 a6 Y0 Y* v7 a3 E: I
pubertal response of gonadotropin after gonadotropin-
* L% g: e e4 Ereleasing hormone stimulation. This is a sex-linked
6 M0 Y- I7 @/ Qautosomal dominant disorder that affects only! |) o2 Z; Q, d
males; therefore, other male members of the family: z( \! C6 e$ Y0 A L; ?/ o
may have similar precocious puberty.3; O- Y4 m+ A0 ^/ Q
In our patient, physical examination was incon-1 Q: Y: D& R1 t1 l# D
sistent with true precocious puberty since his testi-
) d8 y" B/ ]4 p5 [- s/ A7 b: a& j0 xcles were prepubertal in size. However, testotoxicosis
# N% D) A/ f- `was in the differential diagnosis because his father7 H1 q, Q8 j+ v7 R' h
started puberty somewhat early, and occasionally,
7 D* a( k2 l6 R% e; `. i5 ^testicular enlargement is not that evident in the
9 S' @, E$ b1 \beginning of this process.1 In the absence of a neg-9 j9 E5 t" h* E" y3 M7 Q5 s9 Q- J7 m
ative initial history of androgen exposure, our2 w0 p p. `5 }5 z+ G% z
biggest concern was virilizing adrenal hyperplasia,
" M! d4 U- e# Veither 21-hydroxylase deficiency or 11-β hydroxylase
( {5 D0 ?) f& A- I( k$ V2 u% ]- Ndeficiency. Those diagnoses were excluded by find-
) T Z& v3 R$ R$ T$ Ging the normal level of adrenal steroids.
9 D5 P( {, |, f; ^( WThe diagnosis of exogenous androgens was strongly" H* a) ^7 o' b! W# z+ b5 v
suspected in a follow-up visit after 4 months because
* x- p1 x1 @# i1 o5 k) g6 Sthe physical examination revealed the complete disap-
D0 j: V- ?! v+ ~pearance of pubic hair, normal growth velocity, and3 z2 Y, Q2 ^; I. J- j! Y
decreased erections. The father admitted using a testos-
; |$ b) X7 b( L6 ~% Iterone gel, which he concealed at first visit. He was: ?% t9 X C0 v* h n$ R/ R% `
using it rather frequently, twice a day. The Physicians’0 i/ J! z; w9 Q& Y, I/ E3 P
Desk Reference, or package insert of this product, gel or# W G0 M3 K Q& a( @# t% D- N/ S7 a
cream, cautions about dermal testosterone transfer to
! t A2 Q0 p! j! }& p7 ^+ r$ Lunprotected females through direct skin exposure.$ S) @4 E8 i# j
Serum testosterone level was found to be 2 times the
4 R3 \6 v# M; ~baseline value in those females who were exposed to0 _' `5 M l5 Z9 I
even 15 minutes of direct skin contact with their male; s7 s9 V9 C' u( ^
partners.6 However, when a shirt covered the applica-. N2 U7 K; M1 U9 G# J9 N& h
tion site, this testosterone transfer was prevented.
/ \1 S5 C& P8 h, ^* W# B0 I1 ROur patient’s testosterone level was 60 ng/mL,
( h) D c. p: y* w Nwhich was clearly high. Some studies suggest that+ G: P+ b5 \+ Z) q( T, T
dermal conversion of testosterone to dihydrotestos-
% ^% L1 \, f' S2 a7 {2 iterone, which is a more potent metabolite, is more* B: w# E" Y e4 r0 z1 }# M" n
active in young children exposed to testosterone
" {7 P" j2 C2 E5 |2 Y/ _( jexogenously7; however, we did not measure a dihy-, K& X$ ^' V: Z) ~2 {( |
drotestosterone level in our patient. In addition to
) [( H$ q, O" a, ^$ J; s9 Kvirilization, exposure to exogenous testosterone in/ c' L" ^1 B* G8 Z+ w! m
children results in an increase in growth velocity and. {# G; c. m/ R, X- y! I* c% [
advanced bone age, as seen in our patient." {" X1 T4 i( b7 o
The long-term effect of androgen exposure during
8 n/ i$ q# {: B! Iearly childhood on pubertal development and final0 E0 h. a1 d8 h: i1 |+ ~6 H- B9 }1 I$ q
adult height are not fully known and always remain
7 y& A% w8 q5 y# r% k9 ka concern. Children treated with short-term testos-
. N; H' Z" i/ B& dterone injection or topical androgen may exhibit some
1 \: }5 y" T! w f X+ |acceleration of the skeletal maturation; however, after( }4 D! |' u! `4 ]) N& L
cessation of treatment, the rate of bone maturation
3 s; A; P: r% n" x4 ?. s r1 ]6 x" ndecelerates and gradually returns to normal.8,9
2 ~5 U2 U1 T8 o& K7 \There are conflicting reports and controversy
4 Z$ ]) D0 \. K7 h5 I- ]over the effect of early androgen exposure on adult1 H8 _" p- v: O+ @* N" F
penile length.10,11 Some reports suggest subnormal
7 }1 s8 |2 }- e$ r( r, f3 Sadult penile length, apparently because of downreg-3 n7 f6 T5 R |+ B
ulation of androgen receptor number.10,12 However,
1 `& ?+ g4 J+ A$ R( P( c& Z# lSutherland et al13 did not find a correlation between
) L0 R6 l/ X& dchildhood testosterone exposure and reduced adult7 S$ ?2 w- f/ [! F. \5 i
penile length in clinical studies.
/ b0 R5 G' Y: v5 i( LNonetheless, we do not believe our patient is
) J% r6 p6 U9 r) W! W+ ]# ]going to experience any of the untoward effects from% p* }5 d& k9 u7 m
testosterone exposure as mentioned earlier because% l& ~$ E4 Y, F5 q
the exposure was not for a prolonged period of time.
: n' ^) M7 ]$ d; C3 |5 ?Although the bone age was advanced at the time of7 t& v$ V! @$ ? ]4 u) ]4 q8 C
diagnosis, the child had a normal growth velocity at
; n& x2 k/ _9 f+ Jthe follow-up visit. It is hoped that his final adult
. G F& t6 _9 g. c' N7 hheight will not be affected.8 I% ?8 u6 |; S" l
Although rarely reported, the widespread avail-& z* s9 `& V2 i: b
ability of androgen products in our society may- v- }* g, H1 Y3 t$ z! g) ^8 i# l
indeed cause more virilization in male or female
1 x0 ~) G9 A8 m! C4 F+ bchildren than one would realize. Exposure to andro-. r5 Z0 [5 G: u) v! {
gen products must be considered and specific ques-. _0 b5 C6 Y) v3 q& E8 H* E* g" U
tioning about the use of a testosterone product or
1 B6 T+ x8 y0 {1 K+ Pgel should be asked of the family members during
) k+ ^- Y+ @: d* w" }+ V' M8 U$ Cthe evaluation of any children who present with vir-9 A+ _6 U3 F, w8 A
ilization or peripheral precocious puberty. The diag-2 z. j7 \7 D3 d3 \: v
nosis can be established by just a few tests and by* h# F' G) K/ k o$ w* D5 n- J
appropriate history. The inability to obtain such a
4 s& p* Q$ k5 N! e% d1 v, G# G/ _history, or failure to ask the specific questions, may; J9 l8 S5 Z) y
result in extensive, unnecessary, and expensive. a: n. t9 g& v5 r- T% L
investigation. The primary care physician should be7 S% z) K; I0 p6 h9 J
aware of this fact, because most of these children6 } E* e4 }/ Z# C
may initially present in their practice. The Physicians’
! f- C$ O; T) i& [5 n$ SDesk Reference and package insert should also put a
! S' ]9 z) u9 @warning about the virilizing effect on a male or* L$ j# s" f8 ?4 ]( E
female child who might come in contact with some-. E% V+ g& b# D( X5 d
one using any of these products.
* J @! Z' V5 S4 k9 [- t! PReferences1 H& X" y( D- W/ p- J
1. Styne DM. The testes: disorder of sexual differentiation
- Y, w, p% j% rand puberty in the male. In: Sperling MA, ed. Pediatric+ j/ t+ G5 a7 g6 ?
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
$ G0 U* e1 m# E/ H; C2002: 565-628.
- r* E: D4 y* }$ r* n2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious. ~! X: S2 d' z% L
puberty in children with tumours of the suprasellar pineal |
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