- 註冊時間
- 2023-5-6
- 精華
- 在線時間
- 小時
- 米币
-
- 最後登錄
- 1970-1-1
|
發表於 2025-1-4 03:25:35
|
顯示全部樓層
Sexual Precocity in a 16-Month-Old* C9 U' N( Z8 ?
Boy Induced by Indirect Topical
; u, e* g6 \3 y) `, t ]) J: Y7 J8 fExposure to Testosterone# f) V+ _2 ~2 R& w, g
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2: O# w0 b; B0 y2 x! m: r
and Kenneth R. Rettig, MD1
) e. B( `/ j7 L* _5 U; iClinical Pediatrics! r. F. p9 s K
Volume 46 Number 6( l R: y* c& X, ^" H% c& n
July 2007 540-5433 x2 `$ T4 G& g5 Z) D) N
© 2007 Sage Publications& L( M" J& z; T4 w3 \5 R1 M% t
10.1177/0009922806296651
/ a/ I, T; z0 x+ |http://clp.sagepub.com$ a: U( Q2 o0 K+ ~% B
hosted at9 i& F* W8 O1 R2 }# s, ]$ r* V: R
http://online.sagepub.com( f1 r2 F2 l" t [) K
Precocious puberty in boys, central or peripheral,
1 k4 C. b. @% ^5 z7 M, N+ Tis a significant concern for physicians. Central
, { t) E$ t9 @; z2 `" J( o- Wprecocious puberty (CPP), which is mediated
1 T1 g6 Q( S2 |; G* I8 zthrough the hypothalamic pituitary gonadal axis, has
, M; S( _9 H7 Wa higher incidence of organic central nervous system
4 a# a+ |3 O- z! F, \lesions in boys.1,2 Virilization in boys, as manifested
! [" h9 p+ {6 g) k4 Uby enlargement of the penis, development of pubic# ?: d2 D7 e8 c4 O c- n! S
hair, and facial acne without enlargement of testi-
2 N4 z' b4 A5 D* scles, suggests peripheral or pseudopuberty.1-3 We+ s: |7 M& h I$ w
report a 16-month-old boy who presented with the" _* {$ d# P! m+ c3 B+ V, l
enlargement of the phallus and pubic hair develop-
- T3 l) d6 h! c' {7 ?( N& r8 B3 Z" Oment without testicular enlargement, which was due/ q7 L4 V! E, J, B* Z' [% @
to the unintentional exposure to androgen gel used by9 n& w! e+ k6 z4 e6 i% P
the father. The family initially concealed this infor-
1 \8 d& J' u8 H, pmation, resulting in an extensive work-up for this
g' ~" m* _" K2 r2 X" H2 Bchild. Given the widespread and easy availability of
, i0 b" b$ U5 G0 b0 Btestosterone gel and cream, we believe this is proba-! Z# u1 i; u1 [0 D
bly more common than the rare case report in the
5 D, i- N( @0 Lliterature.4
0 o* ?. {* g8 z- R s$ M _Patient Report: d; ?$ V5 b* G
A 16-month-old white child was referred to the
\! C8 r( E1 O, k% t; L' Cendocrine clinic by his pediatrician with the concern; M* m0 |2 s6 l! }! i; O
of early sexual development. His mother noticed
/ f, K+ s2 G `light colored pubic hair development when he was& j; d, i/ Q- ^
From the 1Division of Pediatric Endocrinology, 2University of
8 D* i$ G1 ?/ j5 d1 P$ qSouth Alabama Medical Center, Mobile, Alabama.
5 {) w) `/ h a+ |Address correspondence to: Samar K. Bhowmick, MD, FACE,
: e* |5 \" C$ G/ o) H! `, A9 w- BProfessor of Pediatrics, University of South Alabama, College of; Z9 I( c/ {1 G, A- t, N
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;) v. ^( C+ j/ A3 \6 ]5 h* S8 E
e-mail: [email protected].
) e; W' l% S) X1 N }5 d# L: `# Labout 6 to 7 months old, which progressively became
" a% G7 W0 }* h. O* cdarker. She was also concerned about the enlarge-% ?6 @+ L l+ t
ment of his penis and frequent erections. The child1 O% N6 F+ V' n
was the product of a full-term normal delivery, with
3 n5 Y8 {( K! k5 W: m n1 G* L; Va birth weight of 7 lb 14 oz, and birth length of- ]7 x! V) L4 X" L: k" v
20 inches. He was breast-fed throughout the first year
/ a0 c$ r+ @+ {. F+ wof life and was still receiving breast milk along with
/ z4 w. Q7 X7 @+ T5 f4 K7 nsolid food. He had no hospitalizations or surgery,
8 _) o) r) U; W, Iand his psychosocial and psychomotor development
4 \1 e! ~% j( W0 a. G9 r9 M/ Swas age appropriate. ?. u3 V7 X/ J3 l( \* N: }
The family history was remarkable for the father,, V7 h, P7 C- g) m! {
who was diagnosed with hypothyroidism at age 16,! c! j$ H1 O" _5 n0 z& @
which was treated with thyroxine. The father’s) `$ Y0 a/ o4 V
height was 6 feet, and he went through a somewhat
8 u! ^" ^7 i2 C, f6 j$ hearly puberty and had stopped growing by age 14.
: o$ U" O+ \) k N# ]The father denied taking any other medication. The$ q. |) l) [1 t2 ^
child’s mother was in good health. Her menarche
* U0 Y+ L j t8 }2 vwas at 11 years of age, and her height was at 5 feet+ z8 f( l1 u& P+ q: Q
5 inches. There was no other family history of pre-/ v/ s% S2 T/ q6 x' I
cocious sexual development in the first-degree rela-* d. o2 }; O. ~9 ]
tives. There were no siblings.
: F" W8 U0 i6 qPhysical Examination& _1 H5 G5 g9 S8 B% P+ T
The physical examination revealed a very active,
# r4 g/ Z; b$ ?: O. X( Dplayful, and healthy boy. The vital signs documented
8 ?4 U5 A7 T5 {; J0 @0 m+ va blood pressure of 85/50 mm Hg, his length was8 l- k) C6 H' m W
90 cm (>97th percentile), and his weight was 14.4 kg2 _' I; Q5 {; N1 D* h6 N
(also >97th percentile). The observed yearly growth$ Z8 V* i7 q! v9 _5 C; F1 b
velocity was 30 cm (12 inches). The examination of/ J4 t8 ~. Z( x
the neck revealed no thyroid enlargement.% X1 J' {+ T! b/ i4 c
The genitourinary examination was remarkable for
L* O! C! I0 s9 [enlargement of the penis, with a stretched length of
% q5 J6 d) l3 s& C) d$ `! N% U- j8 cm and a width of 2 cm. The glans penis was very well
7 |) {$ Y4 k4 ^" P; Jdeveloped. The pubic hair was Tanner II, mostly around
+ s2 m H. `( T% h. K; N- a# p/ F% U540
' p* r; g5 y. [& {at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
+ T+ I, X/ E x qthe base of the phallus and was dark and curled. The
: V7 C: _, i+ J4 ftesticular volume was prepubertal at 2 mL each.
, `* q) F( Y+ NThe skin was moist and smooth and somewhat
! |/ K. c' p- ^. ?# M3 _oily. No axillary hair was noted. There were no1 H8 d; z1 X) p
abnormal skin pigmentations or café-au-lait spots./ ~7 u# O0 S, U4 l, x' i/ L
Neurologic evaluation showed deep tendon reflex 2+9 Y9 R X) ~& W S
bilateral and symmetrical. There was no suggestion( j+ ^9 p9 n" X
of papilledema.
( {5 w6 N8 N, L) A" m5 fLaboratory Evaluation4 q) _ c- P2 j( ?. n' D
The bone age was consistent with 28 months by
& \! Q; d8 A" ]3 \ |8 \3 nusing the standard of Greulich and Pyle at a chrono-" W& ^, d- r5 [$ L, I4 ]) ?9 U
logic age of 16 months (advanced).5 Chromosomal3 y S. f0 Y9 l, j' h0 W
karyotype was 46XY. The thyroid function test% }' v. {4 u- {( J0 ]# _+ m* G7 b
showed a free T4 of 1.69 ng/dL, and thyroid stimu-" C1 F' P% r# j
lating hormone level was 1.3 µIU/mL (both normal).- G3 `: p8 c/ S$ E7 d$ z
The concentrations of serum electrolytes, blood
& I6 Q5 Y6 B p. M6 gurea nitrogen, creatinine, and calcium all were
, f+ D+ ~$ W5 _3 \within normal range for his age. The concentration; w* Y6 p* ]0 X2 k; _- b$ J
of serum 17-hydroxyprogesterone was 16 ng/dL+ X" S% e- X* c/ N- W- C
(normal, 3 to 90 ng/dL), androstenedione was 20
; ]% l% E, u: {; e( nng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
+ J, Z3 p$ Y; ~. r0 M% ~terone was 38 ng/dL (normal, 50 to 760 ng/dL),. r* D- l6 P7 k$ Q/ Q$ ^
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
$ @: Z" J( ?; A. Z& W49ng/dL), 11-desoxycortisol (specific compound S)8 O2 V7 `- n# e
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-! v" g; P* N0 T; r! F
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total$ t( c/ U6 [6 {3 W2 l( M4 F% U2 Q
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),) F* y0 m0 S! |4 t% w& S- t, @
and β-human chorionic gonadotropin was less than
( O0 }( ` W1 |8 e9 L! d- k- ]- H5 mIU/mL (normal <5 mIU/mL). Serum follicular9 i% l6 L& y+ v X# [
stimulating hormone and leuteinizing hormone
/ X: b; I5 [( o: U; N1 Zconcentrations were less than 0.05 mIU/mL/ t- {& V8 y4 m
(prepubertal)." t- z. R$ D+ O5 O* p* O1 H
The parents were notified about the laboratory
! ]" ]+ _- n& q ]6 @results and were informed that all of the tests were
8 @# t6 X; r% Y% Z2 S# g2 snormal except the testosterone level was high. The8 G8 k" N' q, z% X
follow-up visit was arranged within a few weeks to; D9 K- c, Y/ K$ E' }/ V1 B
obtain testicular and abdominal sonograms; how-3 L! A4 W$ I9 s3 m$ ^1 D
ever, the family did not return for 4 months.( j" g: u/ ?) Z* i% S2 B3 b
Physical examination at this time revealed that the
0 N5 x3 A) o! E- y) H% p( {; p8 Z; X$ ]child had grown 2.5 cm in 4 months and had gained1 H) D/ W2 N" c
2 kg of weight. Physical examination remained
2 D) u7 o* J( n' f+ T. {unchanged. Surprisingly, the pubic hair almost com-% r1 Q2 m5 k6 H! W
pletely disappeared except for a few vellous hairs at
# s0 @8 F4 Q$ A; {) A7 Tthe base of the phallus. Testicular volume was still 21 S# ]! F8 E$ r, V: \+ x, f
mL, and the size of the penis remained unchanged.
. q# O9 l2 b, n$ d+ ^# iThe mother also said that the boy was no longer hav-
3 C, [6 ~7 P" t2 ping frequent erections.* x- z8 l5 O5 O% I* u7 b! J9 G
Both parents were again questioned about use of
; H1 S/ C+ A( C( tany ointment/creams that they may have applied to8 z' y+ ^) I2 B5 I7 c
the child’s skin. This time the father admitted the7 m! b- M4 x1 r5 C" b7 S
Topical Testosterone Exposure / Bhowmick et al 541
8 {. m4 _9 v: i( {1 ^use of testosterone gel twice daily that he was apply-
4 e4 ^( S$ L5 P0 P$ |, p" e( _* ?ing over his own shoulders, chest, and back area for7 Y( ?6 {1 Y% A+ x. w
a year. The father also revealed he was embarrassed+ o2 L1 n1 U! c# ^& K" }
to disclose that he was using a testosterone gel pre-
: q' n+ ~+ D% Wscribed by his family physician for decreased libido
$ k+ `% w; S- B# s( x9 N$ nsecondary to depression.7 t9 G" a6 l6 A
The child slept in the same bed with parents.! C( R8 U. _6 `' e1 V; Z3 R
The father would hug the baby and hold him on his, M; l) L3 z* O
chest for a considerable period of time, causing sig-, y. X' ]; T4 F
nificant bare skin contact between baby and father.
$ z6 i% i% l' q; Z- d8 z: @/ G$ GThe father also admitted that after the phone call,
8 q1 `; A. g0 `9 v% ? a% N4 lwhen he learned the testosterone level in the baby! \( C* w, Y. y, w# ~; u
was high, he then read the product information9 x, }% R9 h, t3 M( p! M& [
packet and concluded that it was most likely the rea-
+ g2 l' \ G" i8 Json for the child’s virilization. At that time, they
6 u0 h: Q" T1 \, adecided to put the baby in a separate bed, and the
% o2 N, p$ G. S% o- Q1 Jfather was not hugging him with bare skin and had
( M. o4 w4 R" R8 C7 O" _8 kbeen using protective clothing. A repeat testosterone
, Q$ H. M6 S! R8 A$ c9 atest was ordered, but the family did not go to the5 v9 v6 G) U( C# j0 d9 ]/ `* |
laboratory to obtain the test. N! S0 D5 U: P; {; P
Discussion3 p# Q" O4 P* s6 h: `
Precocious puberty in boys is defined as secondary% X$ e. T% \' e. s0 N8 |: i" D# Y
sexual development before 9 years of age.1,4
7 ~+ D% m ]2 F3 i! i( W' p3 HPrecocious puberty is termed as central (true) when! P: o4 z& _7 n
it is caused by the premature activation of hypo-
: d) {, O$ G: q1 J" A/ C/ {! cthalamic pituitary gonadal axis. CPP is more com-! M. `( V3 G! F$ D: f. `# e
mon in girls than in boys.1,3 Most boys with CPP9 O6 E. n( x! Y3 E2 P; b9 ]3 l
may have a central nervous system lesion that is2 R( }; J; E$ @0 T1 C/ a
responsible for the early activation of the hypothal-: m( g" Y' i1 g9 L/ K
amic pituitary gonadal axis.1-3 Thus, greater empha-
+ C% h8 o+ E0 Z, S% Hsis has been given to neuroradiologic imaging in y+ B+ \9 ]8 k" `) i
boys with precocious puberty. In addition to viril-; @1 d5 u5 p, ]9 L" V
ization, the clinical hallmark of CPP is the symmet-! O/ j ` C4 n3 c$ k3 ~
rical testicular growth secondary to stimulation by
9 f0 m6 w: B+ x3 s- T2 m; f) kgonadotropins.1,3" ] c8 R3 Y8 `/ a' n
Gonadotropin-independent peripheral preco-
+ M: S( P( ~- Q8 l: p2 Kcious puberty in boys also results from inappropriate
/ _9 T0 ~2 N) Q# ]& fandrogenic stimulation from either endogenous or
$ e ^- i( A) B$ T1 x! @2 k7 aexogenous sources, nonpituitary gonadotropin stim-) ?& Y3 c1 W; L& y1 M0 G$ Y! S
ulation, and rare activating mutations.3 Virilizing) ^/ z; z5 @4 l/ c) a
congenital adrenal hyperplasia producing excessive
/ D6 q3 j) L) o Nadrenal androgens is a common cause of precocious9 P0 |' J( s0 J$ y3 L7 G
puberty in boys.3,4" Q+ h, d0 ~: w% I0 k; y; q
The most common form of congenital adrenal
6 J1 n( y9 H5 d) N6 h- I5 b$ T; ghyperplasia is the 21-hydroxylase enzyme deficiency.& h, ] x) S8 x6 W+ V5 \5 G# W
The 11-β hydroxylase deficiency may also result in; X7 B9 ]) X% W5 j
excessive adrenal androgen production, and rarely,
( ^# N9 E5 t$ Zan adrenal tumor may also cause adrenal androgen
0 O# g0 Y8 Q( d- ~: _: S" eexcess.1,35 i5 l& K$ t# c
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from; M2 q2 H% R: }8 k( d2 x: }
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
9 J5 z5 Y" U0 BA unique entity of male-limited gonadotropin-
( K- H: Q0 l8 U7 e; Sindependent precocious puberty, which is also known
1 w) e6 s$ j5 ]as testotoxicosis, may cause precocious puberty at a
6 h% k7 m% B. j) y9 gvery young age. The physical findings in these boys" Z9 p2 F3 _" u. ~
with this disorder are full pubertal development,2 a9 I2 P8 p/ e7 s* ~1 j
including bilateral testicular growth, similar to boys# u! x. m, `5 s" b. d" m
with CPP. The gonadotropin levels in this disorder
9 O, c3 N" b$ R' a% J1 w/ kare suppressed to prepubertal levels and do not show
: s; l1 d9 E( u* Y2 N4 |. apubertal response of gonadotropin after gonadotropin-# g( p- |4 a- j
releasing hormone stimulation. This is a sex-linked
+ j$ R# ^. l/ u) {* Q; i/ A9 Lautosomal dominant disorder that affects only* l, ^5 Z# n7 B4 h4 A4 w, t
males; therefore, other male members of the family1 ^. Z( h4 K7 k8 f2 Q
may have similar precocious puberty.3/ U, o4 F* \$ v+ A& y) g- t8 i
In our patient, physical examination was incon-8 s" {. l* J$ J+ I$ P
sistent with true precocious puberty since his testi-- n) x7 K' z1 K1 ^
cles were prepubertal in size. However, testotoxicosis R9 O, w; V7 U5 a L* U
was in the differential diagnosis because his father
! u5 `- h" Y" P! S( i8 @5 j/ Qstarted puberty somewhat early, and occasionally,1 I# k! W+ C0 ^+ T8 h& y ^* j; ]0 K" w
testicular enlargement is not that evident in the
6 K4 V0 B; I7 \) R/ w/ ibeginning of this process.1 In the absence of a neg-. r4 ]9 e+ i2 T5 L- D1 c
ative initial history of androgen exposure, our
+ I5 Y# _! z( h, qbiggest concern was virilizing adrenal hyperplasia,* H) G+ }! V, ^" l2 I
either 21-hydroxylase deficiency or 11-β hydroxylase* h5 Z2 J, z. n0 E" H( N
deficiency. Those diagnoses were excluded by find-1 ^9 x* P! ?" F; o! B8 O0 k7 ~8 f) ^
ing the normal level of adrenal steroids.0 t1 b3 H& W# E6 r; z- b; f
The diagnosis of exogenous androgens was strongly9 ? r2 W2 m" ^4 T2 R! i
suspected in a follow-up visit after 4 months because0 P* b1 R5 b4 F9 T7 x
the physical examination revealed the complete disap-7 D5 }1 g: V" w v8 \; }1 k
pearance of pubic hair, normal growth velocity, and
; h$ ?5 z" T3 I8 |; D- jdecreased erections. The father admitted using a testos-
8 z) u& R* J% P8 L4 w; pterone gel, which he concealed at first visit. He was
7 f" J1 z! g) j: Gusing it rather frequently, twice a day. The Physicians’& m! ]2 G M0 ?. L
Desk Reference, or package insert of this product, gel or# \4 a4 T" O0 }: _
cream, cautions about dermal testosterone transfer to
* J: o/ }( y8 s0 a* g7 vunprotected females through direct skin exposure.
9 o7 Q$ f' r6 S8 x# TSerum testosterone level was found to be 2 times the6 Y" H7 ?: O: t& d9 F
baseline value in those females who were exposed to# y. {: Q1 N# \ S
even 15 minutes of direct skin contact with their male
* P8 a, r+ X2 o8 d! h& a2 spartners.6 However, when a shirt covered the applica-& N9 a D! I. }' A
tion site, this testosterone transfer was prevented.3 b9 o& n2 _$ w, P2 \6 A
Our patient’s testosterone level was 60 ng/mL,* H( F! Q$ j2 E5 y% }
which was clearly high. Some studies suggest that; q: w9 c) w. E
dermal conversion of testosterone to dihydrotestos-0 Z, c' a- y6 G" X" x+ I
terone, which is a more potent metabolite, is more
- c! M3 ~/ L; r5 D; Xactive in young children exposed to testosterone
; Q+ p# D5 \* g `exogenously7; however, we did not measure a dihy-
! O! m: \: Q% i3 C0 R. L7 M& Pdrotestosterone level in our patient. In addition to* u* T. H7 [ \, Y. ^0 f* _) Z
virilization, exposure to exogenous testosterone in
! @: }9 m+ y) j: Kchildren results in an increase in growth velocity and* A% {- Y- K2 ?; N v/ @
advanced bone age, as seen in our patient.2 {# S; h5 P" O, D9 X- o
The long-term effect of androgen exposure during9 q4 w9 D: C' s0 E2 Z. v
early childhood on pubertal development and final7 Z* R; e3 }0 b- G
adult height are not fully known and always remain$ s* h1 p, U- e# w$ K" B0 n4 @
a concern. Children treated with short-term testos-
" D$ z; J9 Y' g* v# Q7 W" Wterone injection or topical androgen may exhibit some" P3 Z) _; g+ @3 i4 n; i
acceleration of the skeletal maturation; however, after
# k9 w. H, K* u' O- Scessation of treatment, the rate of bone maturation* H$ g8 k: j8 S" v
decelerates and gradually returns to normal.8,9$ z# @5 H0 C+ h' ~/ X, E
There are conflicting reports and controversy
! Y$ t6 L$ S/ ]over the effect of early androgen exposure on adult3 G8 |! t( \, S4 A7 ]9 F8 c
penile length.10,11 Some reports suggest subnormal
1 N! a* r9 Z/ L. B% kadult penile length, apparently because of downreg-& s8 v7 y s, i! \7 ~* U# L
ulation of androgen receptor number.10,12 However,1 @' c; G9 g$ k. u) R
Sutherland et al13 did not find a correlation between
& p( G; A9 ]/ w5 \. o2 W3 F4 u6 ychildhood testosterone exposure and reduced adult1 E/ Y7 q$ ]( X: |
penile length in clinical studies.
: ^! `' t& }6 n7 QNonetheless, we do not believe our patient is3 K p# T! P, ` ], D5 s# i6 O z
going to experience any of the untoward effects from
% }: p1 S) ?; N3 M' K. B! r9 D$ R3 f' dtestosterone exposure as mentioned earlier because {2 P9 [! F# F! e
the exposure was not for a prolonged period of time.: u! _ F' c. E, U1 |& d' h) w8 n
Although the bone age was advanced at the time of
- I! J. B, E6 ^9 ?2 U6 D, V' Udiagnosis, the child had a normal growth velocity at& ^/ r9 O/ e! j/ P C* d( C
the follow-up visit. It is hoped that his final adult
1 E- f2 x3 x3 t& m( g$ Qheight will not be affected.
% m( u0 R) O7 [+ J$ s5 W" e* tAlthough rarely reported, the widespread avail-
* ]+ a: A4 U1 E( F4 uability of androgen products in our society may
, f/ [( b* v4 y, m7 }' Aindeed cause more virilization in male or female
: t8 [" ?& B$ U/ z' s) ychildren than one would realize. Exposure to andro-
3 v/ A) u* I% Ygen products must be considered and specific ques-
' B! `* u1 C* r" I8 H# jtioning about the use of a testosterone product or
+ ^& \& e9 w! P5 d+ q6 v6 L$ U I4 z/ |gel should be asked of the family members during. |+ s# M) }- h0 v
the evaluation of any children who present with vir-
0 a$ ?$ f( L2 E* u. A( Bilization or peripheral precocious puberty. The diag-
. O, R2 E6 L% x. _- p# Knosis can be established by just a few tests and by
1 e3 Y& j: O+ D/ x( H# N: `' dappropriate history. The inability to obtain such a4 c5 ?) h* q( q6 ?
history, or failure to ask the specific questions, may s- t7 c5 P ^" s
result in extensive, unnecessary, and expensive3 H$ M- q/ N/ X4 B# q
investigation. The primary care physician should be
# S' ?; W& R0 e" saware of this fact, because most of these children5 X( ~6 Q" u, s1 w. S; C. ~( a
may initially present in their practice. The Physicians’
8 f) |6 j" Z3 ]Desk Reference and package insert should also put a
- u( `; L' g! n m4 O xwarning about the virilizing effect on a male or) y7 |4 f4 I& ?2 ]4 Q5 e
female child who might come in contact with some-
6 }% ]# g; p) O! c+ k( V0 Gone using any of these products.
6 }0 O) I! V3 I# W. p: k$ }References. y, }, y4 X- Z$ b/ w4 n/ Z
1. Styne DM. The testes: disorder of sexual differentiation" X, x' }% B6 @: j; T
and puberty in the male. In: Sperling MA, ed. Pediatric
+ ?8 y _: Y3 _1 }1 v1 pEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
5 F4 D) K3 s0 _6 l2002: 565-628.
, ?- r9 o, Q% h6 L+ g8 g# [2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
q0 A6 F& E+ ^. U/ N5 |3 jpuberty in children with tumours of the suprasellar pineal |
|