- 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
$ A* Z3 }/ x, k. c. DBoy Induced by Indirect Topical
& K2 T% H+ h! M K! IExposure to Testosterone5 n6 @$ v9 T* v4 x
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,20 S6 T/ T. g3 B" B
and Kenneth R. Rettig, MD1
% s, U, N4 j- iClinical Pediatrics1 f: ^0 _4 A l
Volume 46 Number 6
" x$ K0 M2 ]& D9 d& BJuly 2007 540-543! `" {0 V: n4 T* v" E5 \' Y M
© 2007 Sage Publications4 M7 l0 s; e V: v: X
10.1177/0009922806296651
! n" G( j' k2 W" l3 l+ _http://clp.sagepub.com: } v8 m6 t. F9 f" ^2 x G( W3 A
hosted at& m$ k. p' s' V0 P2 s
http://online.sagepub.com
! W9 K. {6 |- b1 x/ J/ a' X b9 \Precocious puberty in boys, central or peripheral,
@2 H: F: m+ C' M) N( dis a significant concern for physicians. Central6 b1 [. H4 P+ Y
precocious puberty (CPP), which is mediated
1 a/ a0 r# _# I" d; e% Qthrough the hypothalamic pituitary gonadal axis, has
" Y$ P. l; y% z) p+ Wa higher incidence of organic central nervous system' l& f9 ]: O) f( G
lesions in boys.1,2 Virilization in boys, as manifested) Q1 ~7 z9 H# Z: ~ R' [* V
by enlargement of the penis, development of pubic- R1 W. i. h$ y( F* z$ c
hair, and facial acne without enlargement of testi-
7 y5 o: g( \$ p3 O" g2 k' _cles, suggests peripheral or pseudopuberty.1-3 We0 j# B) V3 t7 T6 b
report a 16-month-old boy who presented with the. f0 ~) e. A, A: U& v
enlargement of the phallus and pubic hair develop-
# \! a% y! Y9 E9 {* u0 n, N) K+ Vment without testicular enlargement, which was due; i" w6 W) ]/ j6 d% f! ?/ x
to the unintentional exposure to androgen gel used by4 y) b8 m7 U: [1 i# K
the father. The family initially concealed this infor-5 i5 F4 j" P1 n. X. l8 o
mation, resulting in an extensive work-up for this' t6 i4 C P/ B, {2 q' f( S
child. Given the widespread and easy availability of# m" L: R/ m6 e, \+ F% v0 s
testosterone gel and cream, we believe this is proba-
0 y; V2 ^2 u2 N( Z! v9 U0 ^' hbly more common than the rare case report in the
' R5 X) m9 a1 eliterature.4% ]9 t+ B# s+ u( b) B
Patient Report
" y% x ]5 r; ]7 q5 b9 cA 16-month-old white child was referred to the
1 o' S4 g$ T3 v0 Q4 z: S' M% _$ Sendocrine clinic by his pediatrician with the concern$ h5 m& {9 a9 }4 \- _% a" m7 S
of early sexual development. His mother noticed N A! z3 h+ z- s) b. X3 J3 t
light colored pubic hair development when he was0 c" z' d8 J3 o
From the 1Division of Pediatric Endocrinology, 2University of
6 H3 P8 d2 r% d3 JSouth Alabama Medical Center, Mobile, Alabama.1 G N( ]# i$ v* ]! h5 Y
Address correspondence to: Samar K. Bhowmick, MD, FACE,
A/ C; {$ g, [% C! [# MProfessor of Pediatrics, University of South Alabama, College of% u0 G7 q. @& P: ~9 r3 o- H' T
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
% i# P" d6 w0 v3 L D$ E( B, fe-mail: [email protected].* L& a) N; C2 r/ h
about 6 to 7 months old, which progressively became
7 E9 q ?# O1 B! q4 w0 wdarker. She was also concerned about the enlarge-7 J" W: B b) o( D$ H
ment of his penis and frequent erections. The child& y: {/ q- v: l& o
was the product of a full-term normal delivery, with2 y: Z @/ v& o- l2 S$ P) a/ ]
a birth weight of 7 lb 14 oz, and birth length of
; i7 `# v0 I& Q8 }: U( h20 inches. He was breast-fed throughout the first year0 m1 d/ `5 l1 N& S j
of life and was still receiving breast milk along with
% A$ A8 h# Y' fsolid food. He had no hospitalizations or surgery,
; l2 `+ P% y/ o: F a7 M Xand his psychosocial and psychomotor development
6 F& `1 B$ a7 _was age appropriate.
7 [) u- Q3 L; z/ U( A. g5 i- hThe family history was remarkable for the father,7 e1 L @6 @ w, u9 G
who was diagnosed with hypothyroidism at age 16,
6 n3 I. E( l( S6 m% X/ j$ Y% u4 Qwhich was treated with thyroxine. The father’s0 Z _4 ?6 B4 o" ?( r* _
height was 6 feet, and he went through a somewhat
2 p& v9 h7 x9 p' Uearly puberty and had stopped growing by age 14.
7 m) c4 F/ y- S2 ? cThe father denied taking any other medication. The
9 F% b9 u) M6 k5 k$ b5 H$ t% gchild’s mother was in good health. Her menarche6 Y1 V }/ f! l( Z/ }
was at 11 years of age, and her height was at 5 feet
0 Y6 T; \- a$ r0 Z5 `: E; E5 inches. There was no other family history of pre-
% |+ K7 C* m' vcocious sexual development in the first-degree rela-
+ p6 H5 Z1 Q+ F& @/ {# E- L. w6 ttives. There were no siblings.- V$ I1 I) z! j( b, E
Physical Examination. X X& v! Y7 [1 N! F; y7 f1 \, G
The physical examination revealed a very active," a$ t0 m+ C0 @+ C# X% b/ m
playful, and healthy boy. The vital signs documented! H. d& P6 ^& }- A d
a blood pressure of 85/50 mm Hg, his length was& m. ~2 T" R. R
90 cm (>97th percentile), and his weight was 14.4 kg/ f2 V% P9 k' j% [& t
(also >97th percentile). The observed yearly growth- e+ V! R7 h2 A& c! n7 @. L
velocity was 30 cm (12 inches). The examination of
) B9 w b: u5 L" z3 x+ Gthe neck revealed no thyroid enlargement., K% p$ j- x, v. `
The genitourinary examination was remarkable for
- M/ r0 C- s4 N4 q% a9 venlargement of the penis, with a stretched length of2 N$ c6 k; X- w
8 cm and a width of 2 cm. The glans penis was very well
& s o! `1 `6 [) I: _developed. The pubic hair was Tanner II, mostly around
) q# t s; t# `+ C- x8 N" K1 }5408 @: Y, x" q/ m* r" J r; k
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
3 L3 @2 u# G( Q* \, d' i/ g4 ithe base of the phallus and was dark and curled. The
: o5 I2 E# Z3 ptesticular volume was prepubertal at 2 mL each.6 }7 Q. _+ A. }- I5 z: _! k
The skin was moist and smooth and somewhat5 @4 v5 g8 h0 L# P3 K# ?5 G, i" j2 p
oily. No axillary hair was noted. There were no
* p! G1 n j& j3 z2 N3 Pabnormal skin pigmentations or café-au-lait spots.
+ r5 U9 ]+ f; c5 BNeurologic evaluation showed deep tendon reflex 2+
( l, n, V3 x, `9 k9 g" E# kbilateral and symmetrical. There was no suggestion
2 e( s2 K) j4 Z0 L( }% Gof papilledema." v: V y! o0 Y' L, ?
Laboratory Evaluation
$ o5 T/ v8 H/ j. CThe bone age was consistent with 28 months by: R; X+ H5 \6 Y9 O7 v0 S/ k2 X0 h: _
using the standard of Greulich and Pyle at a chrono-
- F0 W' F8 |1 g: tlogic age of 16 months (advanced).5 Chromosomal
# y2 \* t9 J" b6 Ekaryotype was 46XY. The thyroid function test M# k9 E. Y. U6 o
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
v0 o6 S# i2 J6 J0 n- clating hormone level was 1.3 µIU/mL (both normal).+ @( N0 i1 ]' y* I3 V$ t' k
The concentrations of serum electrolytes, blood
( U- S# V& T3 P jurea nitrogen, creatinine, and calcium all were
% _* W# i3 u" x# H5 Y' s. Twithin normal range for his age. The concentration- K, s4 ~% A: }( b0 _
of serum 17-hydroxyprogesterone was 16 ng/dL& G2 [1 L% C1 Z7 Y
(normal, 3 to 90 ng/dL), androstenedione was 20
8 u, x8 t8 p% R7 |" Ong/dL (normal, 18 to 80 ng/dL), dehydroepiandros-' M9 m2 ]- ~. ?2 e0 q5 m
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
+ e& ]6 {6 e3 ^: O/ }4 \desoxycorticosterone was 4.3 ng/dL (normal, 7 to
: E) r7 f5 C1 `( j9 W49ng/dL), 11-desoxycortisol (specific compound S). X! D% h0 b. G. r
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
# N9 w# _8 q' @4 ^0 }% ^) Y7 xtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
+ T. p5 E( K: p6 K& S5 P1 ]2 Ntestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
: \! ` [* l0 s3 e2 H- u D2 rand β-human chorionic gonadotropin was less than; S) g! ~) A b
5 mIU/mL (normal <5 mIU/mL). Serum follicular( ]' @. i& F) X& Z" l1 v
stimulating hormone and leuteinizing hormone
2 n5 t# G% p/ K" g: p bconcentrations were less than 0.05 mIU/mL
/ G4 G" ?. n# n$ f4 t. `(prepubertal).& @7 O# T0 r+ @- ]
The parents were notified about the laboratory
2 e! v. M& T8 G0 W U5 f; mresults and were informed that all of the tests were
3 b0 b1 `0 e, Inormal except the testosterone level was high. The
/ f d- k1 c: Q* H1 V& Ifollow-up visit was arranged within a few weeks to* K6 y0 w$ G5 T
obtain testicular and abdominal sonograms; how-0 j4 \ [# v& U* L1 n
ever, the family did not return for 4 months.9 L2 _+ ], F" Y
Physical examination at this time revealed that the
1 {* y3 L, H( ^4 {" ?$ _child had grown 2.5 cm in 4 months and had gained
+ y9 a" g4 @5 [! _6 s! Z, q2 kg of weight. Physical examination remained
' d5 ~; y7 v% v9 U, F* T( Runchanged. Surprisingly, the pubic hair almost com-* ?4 Y/ C. G. H" g7 d
pletely disappeared except for a few vellous hairs at
! ~/ r i9 z: ?4 gthe base of the phallus. Testicular volume was still 2: \& a& S8 @& g, N' ?6 y+ Q
mL, and the size of the penis remained unchanged.
/ X- s% x$ }& g- G! u! `5 a3 q8 WThe mother also said that the boy was no longer hav-
- y/ X6 T y1 iing frequent erections.0 A4 k0 _! ~; g. h l9 c
Both parents were again questioned about use of
6 e; X" ~" \# F( F8 [+ D( N$ _any ointment/creams that they may have applied to
- _$ g u; V& g a7 X& H* Hthe child’s skin. This time the father admitted the
" v0 T9 a+ g3 O0 I0 STopical Testosterone Exposure / Bhowmick et al 5415 |) Z1 t0 v/ N
use of testosterone gel twice daily that he was apply-7 j! H% O m% b5 N5 Q! O3 s
ing over his own shoulders, chest, and back area for- T. P6 B$ j( e5 L) \2 C5 `7 |
a year. The father also revealed he was embarrassed9 S9 S" [/ n* R. p: J( X6 x
to disclose that he was using a testosterone gel pre-# q8 ?" s+ o; Z
scribed by his family physician for decreased libido
& U: r, ~( D- O6 v/ J1 Nsecondary to depression.
9 x6 ?5 j9 f$ VThe child slept in the same bed with parents.
* ], E5 B) A& c% NThe father would hug the baby and hold him on his' ^& l* @" ?% \# k" a( X1 ?
chest for a considerable period of time, causing sig-
1 M% W2 `: P. W. vnificant bare skin contact between baby and father.
: |' b" Y6 B& p# {, vThe father also admitted that after the phone call,% I% w: B J9 N9 s9 P
when he learned the testosterone level in the baby
1 [. a; d4 c; @ {3 Vwas high, he then read the product information+ r1 t! a) ?1 u$ i' n
packet and concluded that it was most likely the rea-
& [( I6 @$ m, M" S% Z i$ V1 tson for the child’s virilization. At that time, they
" Z: i. s6 u, ?8 m% kdecided to put the baby in a separate bed, and the" } ~3 e8 v: z% d. H8 j
father was not hugging him with bare skin and had9 X2 O6 D7 I) X
been using protective clothing. A repeat testosterone" G W: P+ Y" B. x4 \
test was ordered, but the family did not go to the
- d( i2 b" |# U8 I5 Zlaboratory to obtain the test.
; _& C, e8 }7 F. [& R; z" g, BDiscussion- C; R/ j6 \7 `
Precocious puberty in boys is defined as secondary
" j, I2 a: Q% z- [sexual development before 9 years of age.1,48 h( n! K. ~. {
Precocious puberty is termed as central (true) when( V7 C1 p& V3 _1 W, K/ z
it is caused by the premature activation of hypo-4 a! m- d: u" v* w" s2 Q) O* Q2 y2 z
thalamic pituitary gonadal axis. CPP is more com-3 X' l a6 L, |8 z/ V+ F
mon in girls than in boys.1,3 Most boys with CPP
( E3 [! T' J% |( c, ~) dmay have a central nervous system lesion that is
$ @& i/ C. b8 }9 }: M! Oresponsible for the early activation of the hypothal-
: L7 E$ [6 Q: u7 g. _amic pituitary gonadal axis.1-3 Thus, greater empha- u ]8 d8 \- _& J
sis has been given to neuroradiologic imaging in
+ N% ^* c4 W+ \' \1 vboys with precocious puberty. In addition to viril-
9 w9 C5 h" c3 E5 F! S# r$ [ization, the clinical hallmark of CPP is the symmet-
% ]! q/ o1 x! L0 ^6 Urical testicular growth secondary to stimulation by( o2 A0 F1 L V; c
gonadotropins.1,3
/ Y% n7 E9 N2 Y e' t( K1 V$ bGonadotropin-independent peripheral preco-
7 I+ x+ ^5 x; |: }1 Fcious puberty in boys also results from inappropriate
2 P f s; m8 Y. m; L _- J. Iandrogenic stimulation from either endogenous or
l8 ^9 o ?2 X7 o9 p! j2 _exogenous sources, nonpituitary gonadotropin stim-
+ t* ~; }& _" L+ h2 @* C7 e) sulation, and rare activating mutations.3 Virilizing
, H0 r! b( A- s4 E: `congenital adrenal hyperplasia producing excessive) G% K4 P3 N8 ?. i5 W) u' A: y
adrenal androgens is a common cause of precocious0 p5 {+ Q1 T) z9 i/ @
puberty in boys.3,4" d0 y2 N- H+ Q i
The most common form of congenital adrenal
1 c1 A% o: b7 [2 ahyperplasia is the 21-hydroxylase enzyme deficiency.+ k) i" h/ f) O1 d) S! K
The 11-β hydroxylase deficiency may also result in
: J1 b, y1 Y* J( o; @excessive adrenal androgen production, and rarely,% ?' t' n# \/ {: u. h
an adrenal tumor may also cause adrenal androgen
3 X& K; |& {6 I2 z4 `0 T: Qexcess.1,38 e @. b8 |8 b3 N
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from9 h9 `% h' m1 o l% N& G: V
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007! ]" J% v- l* |; ^( V/ X
A unique entity of male-limited gonadotropin-9 R* U) P% q, x0 O/ V
independent precocious puberty, which is also known
9 I5 g7 K4 L0 ]) P9 V8 Pas testotoxicosis, may cause precocious puberty at a- j" [; U# n) O: p# @( U
very young age. The physical findings in these boys; A: p9 A' W( p4 D5 F
with this disorder are full pubertal development,
8 |" Z7 P0 b: S$ u3 N/ lincluding bilateral testicular growth, similar to boys
- [& o- I/ s' k% z ^7 I: Twith CPP. The gonadotropin levels in this disorder& d& x" x; s( P( I
are suppressed to prepubertal levels and do not show
' r. [1 }( ^6 z7 v; |pubertal response of gonadotropin after gonadotropin-; O8 _% K7 q3 F3 Z# ? W d$ z5 C( r
releasing hormone stimulation. This is a sex-linked
: Q0 E7 y# |2 S0 xautosomal dominant disorder that affects only
1 L) a }" H: S5 s; Pmales; therefore, other male members of the family
3 a) v, K/ ?3 y- v: |may have similar precocious puberty.3- P/ x- n5 |9 u& k; e8 \7 z. M* n e
In our patient, physical examination was incon-
. O. u3 {/ G: L: |- z% }7 r) ]sistent with true precocious puberty since his testi-
Y, R' h3 m5 Fcles were prepubertal in size. However, testotoxicosis
. T3 L2 k4 L- C# Vwas in the differential diagnosis because his father
# x7 {" B, H0 p8 o. g- J, H$ Y+ jstarted puberty somewhat early, and occasionally,
0 K8 J) o$ j- T) gtesticular enlargement is not that evident in the
6 I8 F) K" A8 D0 o, a% D4 w% cbeginning of this process.1 In the absence of a neg-/ ?. y; ~# a* h: m! J% P2 W0 N& t
ative initial history of androgen exposure, our/ Y1 t) c1 P: B9 k
biggest concern was virilizing adrenal hyperplasia,
2 L4 F" t- v3 p6 weither 21-hydroxylase deficiency or 11-β hydroxylase* j% Z2 @) h8 B& C( V
deficiency. Those diagnoses were excluded by find-4 p O! d5 s$ Z5 R
ing the normal level of adrenal steroids.
* p' R4 }. N, f- S4 pThe diagnosis of exogenous androgens was strongly9 ^; `! o, S3 X7 b' Q, R
suspected in a follow-up visit after 4 months because6 p: e& }6 ?) Q! E# }' V: e: k
the physical examination revealed the complete disap-- P- V8 J% p+ d) j- r/ ^( {0 |$ |
pearance of pubic hair, normal growth velocity, and. ^5 x2 W5 p' D
decreased erections. The father admitted using a testos-; b! q, F, `" c' H+ \8 s {# j
terone gel, which he concealed at first visit. He was
( Z$ c" ~' S* D0 ]8 u) Dusing it rather frequently, twice a day. The Physicians’
8 ~0 ?1 p. S$ m( |5 @. o0 PDesk Reference, or package insert of this product, gel or. C& V) G9 Z- G# t7 [, l$ _
cream, cautions about dermal testosterone transfer to
- x8 j( ?/ M' n/ funprotected females through direct skin exposure.
) C. V. {( X6 g) A( E( u5 J! {Serum testosterone level was found to be 2 times the. ]# s6 x# Z$ } z. D2 O
baseline value in those females who were exposed to/ I' f0 L% Y7 b3 K3 I$ f2 M
even 15 minutes of direct skin contact with their male& r. B P- C( X4 x" D% ~# ]+ T
partners.6 However, when a shirt covered the applica-
( P# `& j( s8 m( Z/ Ktion site, this testosterone transfer was prevented." j- H# w. x, U
Our patient’s testosterone level was 60 ng/mL,
1 i: q+ ?5 ?! o1 V7 u) ]# |& pwhich was clearly high. Some studies suggest that- Z' ]. ~, x! U7 j6 n }
dermal conversion of testosterone to dihydrotestos-
, c/ Y4 d+ p- L) Q4 uterone, which is a more potent metabolite, is more0 Q% L" D: {5 O
active in young children exposed to testosterone5 e% k2 j7 D1 U( G0 Z& D0 `/ ]9 [ \
exogenously7; however, we did not measure a dihy-
; t$ _7 v) L# k0 d& c: ]drotestosterone level in our patient. In addition to1 k' C) f* T: ]3 ^% E2 I! l
virilization, exposure to exogenous testosterone in
, `: z& ~4 Q4 h' o8 T! {$ jchildren results in an increase in growth velocity and! M$ y- A R$ B* |1 q: {# Q
advanced bone age, as seen in our patient.( Z) d8 d( T) N+ ~# m; [; \
The long-term effect of androgen exposure during7 c% c- S( n5 f6 L* O
early childhood on pubertal development and final
+ ], H4 [3 |& p! Q) F: Iadult height are not fully known and always remain
+ l3 T* j$ Q& N H! Z5 n, n* H' ka concern. Children treated with short-term testos-
: l! I! o9 l# M0 }! N1 c0 J E& oterone injection or topical androgen may exhibit some
; y% L/ E' T3 i- b& h7 Pacceleration of the skeletal maturation; however, after
8 f- K1 k/ o! j1 V$ Vcessation of treatment, the rate of bone maturation
; t+ D3 Y- r, Jdecelerates and gradually returns to normal.8,9
& y- ~ H# G! `# w, |3 S/ ~4 MThere are conflicting reports and controversy
8 a7 s: ?! C z. r, f+ n5 nover the effect of early androgen exposure on adult8 \# l- f! S/ a, h8 J$ _; `6 ^& r
penile length.10,11 Some reports suggest subnormal
7 ? r7 P( Y) q# U- J& Z# Z" y7 radult penile length, apparently because of downreg-, x9 Y4 _) K* }1 f1 Z, O1 y' Y
ulation of androgen receptor number.10,12 However, [/ U" l z0 |5 P
Sutherland et al13 did not find a correlation between% e1 x5 V6 q# v7 O A
childhood testosterone exposure and reduced adult
) v& [# B: j) s% f/ \& bpenile length in clinical studies.5 I5 @; V0 v* e Z6 _8 Q+ I" a1 t, U
Nonetheless, we do not believe our patient is" X& l5 s! a( K$ ^
going to experience any of the untoward effects from, O" z2 Q* x0 O1 E' e
testosterone exposure as mentioned earlier because
0 L% d' [6 P* e5 X% wthe exposure was not for a prolonged period of time.
3 K0 D1 G; u5 v( v' PAlthough the bone age was advanced at the time of
+ J4 l; W( ~; O F/ u4 b/ p/ Kdiagnosis, the child had a normal growth velocity at
. r( `" W( O/ I5 C" t% X( ythe follow-up visit. It is hoped that his final adult
; u. ~- `" f( q" a( Cheight will not be affected.
& y$ q8 U; y, w* FAlthough rarely reported, the widespread avail-
1 p3 x2 h$ `- h% \: D0 M1 V8 Gability of androgen products in our society may
, T& g* b# i" z6 r# ?% K) ^( h$ Windeed cause more virilization in male or female
9 N, D3 ~( F5 bchildren than one would realize. Exposure to andro-: X6 @4 ]: f7 J$ l
gen products must be considered and specific ques-( n$ t6 x/ O0 f+ r( B2 Z9 _* u
tioning about the use of a testosterone product or+ T( x5 u! o. o& s0 G3 `( [1 o0 U
gel should be asked of the family members during5 K9 X' o6 p1 ^; l- g" \# X& r
the evaluation of any children who present with vir-1 `4 I7 W T7 M
ilization or peripheral precocious puberty. The diag-
: e8 q" o8 k1 C. q/ H# x' Pnosis can be established by just a few tests and by
8 s3 n; X2 N K) L9 E3 A* cappropriate history. The inability to obtain such a
: b; r( a, e: g# R9 `. R/ khistory, or failure to ask the specific questions, may, D$ c {! K; ^# d6 G& w: X
result in extensive, unnecessary, and expensive
% ~5 \; X; ~* V6 o. uinvestigation. The primary care physician should be; @* I) x, i: ?% f$ R, Q6 C
aware of this fact, because most of these children
1 h6 `. x, s( jmay initially present in their practice. The Physicians’
5 ~, j* V/ |, j. U4 qDesk Reference and package insert should also put a
7 p, S. l' @, N5 W) X; Q, awarning about the virilizing effect on a male or/ d# ^* ^0 P7 z- v! o
female child who might come in contact with some-
6 B' z, Q: u3 J$ C% S7 uone using any of these products.4 y1 x3 v9 |. ]
References
) e* ~& i) w5 U- I M+ |3 V1. Styne DM. The testes: disorder of sexual differentiation8 x* x v) ?$ }
and puberty in the male. In: Sperling MA, ed. Pediatric( ~0 P' T) y$ H" w. z) p
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
, k& {' Z5 s) P+ s2002: 565-628.
* s& f6 e1 {! L5 s, w2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious, \. y' O+ i- P7 {
puberty in children with tumours of the suprasellar pineal |
|