- 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
$ {" ^5 f" c& k9 NBoy Induced by Indirect Topical
6 X' J$ u7 e8 N6 g# {& I. LExposure to Testosterone
/ o! x9 ~$ y! I# g0 c9 cSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,28 f; V* c7 r8 Y3 E
and Kenneth R. Rettig, MD18 q& K6 @- R/ x# @3 }3 D2 K
Clinical Pediatrics
8 e0 Y; `% V* Y0 g8 H$ f0 vVolume 46 Number 6
3 S1 v; O! d }% i6 [July 2007 540-543% i6 K% T! T& g& G6 [( [1 M
© 2007 Sage Publications
3 n6 B- n9 r) O6 j8 Q& p4 m* R10.1177/0009922806296651
! y' O1 ~* j2 \2 L3 ahttp://clp.sagepub.com
0 X9 L5 S9 X) n( ]/ B. Y) x6 Vhosted at& V9 a4 |1 r; a. M5 p5 D
http://online.sagepub.com1 w, Y8 G' ^ L- `& e# o$ k% G
Precocious puberty in boys, central or peripheral," a; W1 @7 w# d1 m; k# {6 _8 I. L, x' V
is a significant concern for physicians. Central$ F* J- U$ p3 w) I# H/ N
precocious puberty (CPP), which is mediated: }, S$ |# c4 e) X# v! {' u: x
through the hypothalamic pituitary gonadal axis, has
2 [ c9 I2 ^$ h, {0 M# @2 t1 ma higher incidence of organic central nervous system3 Y0 C2 ~1 Y- q0 b* o3 O y
lesions in boys.1,2 Virilization in boys, as manifested
0 h0 C3 b6 U# D; I0 ^ uby enlargement of the penis, development of pubic$ D) I( ?* m0 J! V$ V
hair, and facial acne without enlargement of testi-3 \' [( q( v3 `; D+ e
cles, suggests peripheral or pseudopuberty.1-3 We+ c/ ^) O: _, y3 L
report a 16-month-old boy who presented with the
9 b( q1 A1 Y: qenlargement of the phallus and pubic hair develop-: _5 w. M# H7 @3 s+ M
ment without testicular enlargement, which was due
* I& v7 Y. t" b( m" B& yto the unintentional exposure to androgen gel used by- I) v, K. N8 y; n6 f9 |
the father. The family initially concealed this infor-8 g) k" k% i6 u1 B( l; W- K! E
mation, resulting in an extensive work-up for this/ ^. y: w. t4 V: T4 t
child. Given the widespread and easy availability of+ n8 O* {) q9 G# A
testosterone gel and cream, we believe this is proba-
2 z& e c; Y* D( R/ K6 e" S# N% Lbly more common than the rare case report in the0 {4 N. a0 ~0 i' s2 x; @
literature.4 L$ q; G0 b) }! u
Patient Report- e+ E& p# G3 y8 g' @/ v
A 16-month-old white child was referred to the
) ]; h" E& E1 u E- K% T1 Pendocrine clinic by his pediatrician with the concern; e6 R( {$ y+ z! I
of early sexual development. His mother noticed7 W9 ]9 x6 h% O! I9 I e9 u8 X' i' h
light colored pubic hair development when he was
+ B7 x9 G) G* `3 l+ q' }+ KFrom the 1Division of Pediatric Endocrinology, 2University of
( e1 q5 ^# P7 g+ s' USouth Alabama Medical Center, Mobile, Alabama.# @0 y* u8 i7 {3 O7 D' g
Address correspondence to: Samar K. Bhowmick, MD, FACE,
0 h, B6 G# q2 X3 Z% ^' s; jProfessor of Pediatrics, University of South Alabama, College of L2 H+ X E4 ]3 y3 s
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
5 T8 R% L. y* F7 R( X$ p1 v3 be-mail: [email protected].
& o9 Q# ]- @. t0 rabout 6 to 7 months old, which progressively became
" ?9 s: Q: z- ~: Q' zdarker. She was also concerned about the enlarge-
3 v# Y* d8 u/ W2 D- c- vment of his penis and frequent erections. The child
( J# I: ?: W) t- t: Rwas the product of a full-term normal delivery, with
6 b) c( p: l! h5 h6 |) j: V Ja birth weight of 7 lb 14 oz, and birth length of
6 K2 H; L6 v2 y L z% _20 inches. He was breast-fed throughout the first year
; G- t+ k1 _# \) M0 Pof life and was still receiving breast milk along with
, p1 p9 k0 j1 Vsolid food. He had no hospitalizations or surgery,
% I" h& K6 l$ n* ?& p8 f7 sand his psychosocial and psychomotor development
' U. t4 d& `7 v; ]was age appropriate.
. J$ ?: C. L, L; W" W+ m4 `The family history was remarkable for the father,
0 X' L- [- L' Y% t# F, ?7 Twho was diagnosed with hypothyroidism at age 16,5 x6 V2 e/ A( i' \1 o8 D1 f
which was treated with thyroxine. The father’s+ m5 \. I9 N' e
height was 6 feet, and he went through a somewhat, j l1 \" X# U1 b
early puberty and had stopped growing by age 14.$ }5 _. W' E9 M* ^/ D0 t* T
The father denied taking any other medication. The
% \7 N2 q. g7 a& n4 b; ~* Bchild’s mother was in good health. Her menarche
% E4 {1 |# d4 |7 Mwas at 11 years of age, and her height was at 5 feet% r' b+ U, Y- j+ i4 H
5 inches. There was no other family history of pre-$ e% z% f! l) e; k+ `; G
cocious sexual development in the first-degree rela-" O5 X' X9 y( L
tives. There were no siblings.
" R8 N4 R9 m! [# @7 K4 \Physical Examination
9 E! d" [. U( P+ |) K+ YThe physical examination revealed a very active,
, Y' I. R5 ]1 s- r4 E% I1 q gplayful, and healthy boy. The vital signs documented
' j% S& t) L9 f% h, [8 Aa blood pressure of 85/50 mm Hg, his length was+ Z, E: c7 }! \& J: I- O3 X' e/ c
90 cm (>97th percentile), and his weight was 14.4 kg" t. X& S* o/ K+ e- y. k9 ^9 U
(also >97th percentile). The observed yearly growth8 B# L. d# O( s0 m6 T* ~7 ?. W8 Q
velocity was 30 cm (12 inches). The examination of( c! d S; _! o
the neck revealed no thyroid enlargement./ s# V: q$ I- R0 {
The genitourinary examination was remarkable for
; E7 b% W7 k/ s& O1 r senlargement of the penis, with a stretched length of$ ^0 i1 U, k, J0 J& k. s
8 cm and a width of 2 cm. The glans penis was very well, Z% a: ~0 m+ K, P- k/ v/ S
developed. The pubic hair was Tanner II, mostly around
2 Q x6 ^8 z2 f; P2 Z# @5403 F# x/ Q. k/ A: c( j
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
4 |* B9 S2 g( V' Othe base of the phallus and was dark and curled. The
7 u* | y7 C8 R/ g* i8 ?' ` d1 c) c+ D" Xtesticular volume was prepubertal at 2 mL each.
+ s( a' N) E; KThe skin was moist and smooth and somewhat# \9 y# \- D* @& b+ C- T3 l
oily. No axillary hair was noted. There were no
+ C3 ?& w1 k( T( K. ~0 t! M( ]( Sabnormal skin pigmentations or café-au-lait spots.) d8 }8 W3 r) U1 r
Neurologic evaluation showed deep tendon reflex 2+
# G, n- e% C1 E3 w# o% Bbilateral and symmetrical. There was no suggestion
, }3 R8 y/ _8 D3 r: }of papilledema.
4 ~6 r( o' O- T, y1 N- m4 JLaboratory Evaluation
% ]" }8 C/ ~7 a4 ZThe bone age was consistent with 28 months by
" D B* Z& V! x; Xusing the standard of Greulich and Pyle at a chrono-
5 V+ X! g, [5 Z' flogic age of 16 months (advanced).5 Chromosomal
* U( f" g7 e- Z7 E, N0 okaryotype was 46XY. The thyroid function test
9 \. j K7 P1 V6 kshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
: [3 a: i$ \* k# \8 ^9 Dlating hormone level was 1.3 µIU/mL (both normal).: q+ H* k# J7 @# e E7 m
The concentrations of serum electrolytes, blood
( b+ Q" U7 ]' V5 c. X. y) ?urea nitrogen, creatinine, and calcium all were/ V& @, R& C. N
within normal range for his age. The concentration% @ n0 h, L( A) a
of serum 17-hydroxyprogesterone was 16 ng/dL
/ @# w8 K- e/ ?% t(normal, 3 to 90 ng/dL), androstenedione was 20
4 Y% A3 ?* m1 T6 A- h6 ?ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
3 n4 Z) g0 B4 {+ t$ n1 T3 u8 o7 Kterone was 38 ng/dL (normal, 50 to 760 ng/dL),! ^5 A0 o) s d2 u" w% i) M
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
0 M, r2 P( r% C5 t" Y7 \9 L49ng/dL), 11-desoxycortisol (specific compound S)& i7 m/ ?( L& h- v, L! R& N
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-, ?, p* `% v! w1 u( f+ y
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
' s7 z( J8 d: K5 r' l$ Ytestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
9 E2 m5 H# k+ Q% U) a) Jand β-human chorionic gonadotropin was less than
( A6 D! l* V. |2 H6 w5 mIU/mL (normal <5 mIU/mL). Serum follicular3 v, \3 H r+ G9 M' ]/ d
stimulating hormone and leuteinizing hormone% Z i; P9 S9 T. i
concentrations were less than 0.05 mIU/mL( c9 `7 D8 X8 N4 Z. N9 P) Z
(prepubertal).- a9 v" i, r( v9 T3 |0 ` B
The parents were notified about the laboratory
) `' i5 }+ \, m4 @4 rresults and were informed that all of the tests were$ P) j9 I% t& [4 N
normal except the testosterone level was high. The
; O: H/ Y* B$ J' ]follow-up visit was arranged within a few weeks to
. x4 w) C5 d9 m* [obtain testicular and abdominal sonograms; how-
# ~; [+ s+ u! ?; \* Eever, the family did not return for 4 months.; B: @/ n- a3 {% v; w0 R6 F
Physical examination at this time revealed that the$ Q. D @4 v- S
child had grown 2.5 cm in 4 months and had gained" x$ } K5 G0 F, T
2 kg of weight. Physical examination remained
; W2 @: a3 D6 I3 ^- q- T2 y' Cunchanged. Surprisingly, the pubic hair almost com-
: s% }6 }% q7 P, J/ b2 |' qpletely disappeared except for a few vellous hairs at6 U5 S2 r; y: E& k* a; T
the base of the phallus. Testicular volume was still 2
+ m. |; n6 j$ U# JmL, and the size of the penis remained unchanged.7 d% d& B- j9 t; F* ^9 z
The mother also said that the boy was no longer hav-
/ v5 ?; r6 G* M# D" G v+ ping frequent erections.
. X, `1 {' \2 S: j& ABoth parents were again questioned about use of8 V& P8 p+ I3 z' ^9 l
any ointment/creams that they may have applied to
1 Z/ V/ T" S3 ~* F1 l: \the child’s skin. This time the father admitted the
: S& [3 i# v( E9 z' MTopical Testosterone Exposure / Bhowmick et al 541
% m1 }: s$ Q0 l3 S+ vuse of testosterone gel twice daily that he was apply-( W0 D W. u4 o" i% m" K$ L
ing over his own shoulders, chest, and back area for
Q9 I3 {9 Y: e, X6 C# r) Na year. The father also revealed he was embarrassed
* U: X. a! _2 [: m* ?to disclose that he was using a testosterone gel pre-
# h4 t5 H: U3 \scribed by his family physician for decreased libido) e. H$ S- R" x
secondary to depression.- t% V: p/ H6 E) d+ Z
The child slept in the same bed with parents.4 E5 V: ^, N' l# j2 K
The father would hug the baby and hold him on his5 v# n9 f9 ?8 z- i& @/ B
chest for a considerable period of time, causing sig-
9 N, B% R! k2 @4 n" znificant bare skin contact between baby and father.! Q8 |. i% d) N; c8 b
The father also admitted that after the phone call,
' t' j9 o: [0 X5 W$ i' Swhen he learned the testosterone level in the baby( ?9 B9 l: g! F8 w3 l+ }
was high, he then read the product information
" r6 w9 d H+ m [6 Z) Bpacket and concluded that it was most likely the rea-
4 U# B0 M5 K( t' ason for the child’s virilization. At that time, they0 ?: N7 s: q; F, o
decided to put the baby in a separate bed, and the1 V' n& u, V4 ?! T0 v7 g) n- A+ ]
father was not hugging him with bare skin and had
; l$ y6 m* {8 f4 o, Gbeen using protective clothing. A repeat testosterone1 h$ f2 N* N0 K3 [' g
test was ordered, but the family did not go to the9 _' Z/ r m$ a, x% s7 i
laboratory to obtain the test.
& g* k1 O" b9 s$ B; q2 g" e# f3 GDiscussion- |; F: }1 L0 [/ w1 i
Precocious puberty in boys is defined as secondary# _, L Q0 }/ l+ K+ p2 N
sexual development before 9 years of age.1,4. c8 s3 {- {! T+ I6 V
Precocious puberty is termed as central (true) when
! l" S$ n) n& z* e$ H8 ]it is caused by the premature activation of hypo-# Y8 G, A7 M% d; F0 ~. x" x
thalamic pituitary gonadal axis. CPP is more com-$ T4 \9 ^5 R6 A, e; i: [' }
mon in girls than in boys.1,3 Most boys with CPP
8 J0 B/ r) ^0 n* Tmay have a central nervous system lesion that is
" A' ^7 f9 H5 w5 bresponsible for the early activation of the hypothal-) v6 m0 A. b4 @! j
amic pituitary gonadal axis.1-3 Thus, greater empha-* l4 `; B6 W6 x, C
sis has been given to neuroradiologic imaging in4 h, T& T( z% G7 t. p
boys with precocious puberty. In addition to viril- X2 A" K6 F& F5 w- L3 o
ization, the clinical hallmark of CPP is the symmet-
8 o& g0 a5 {* a5 _rical testicular growth secondary to stimulation by( I2 O2 e& z0 _; q. W0 @1 ]
gonadotropins.1,3
( T- ~" W! }) y7 L/ }9 k! G# LGonadotropin-independent peripheral preco-5 P H. ~9 A" O* V
cious puberty in boys also results from inappropriate* @6 P, Q; }7 A; H, T% c# c5 h2 S; @
androgenic stimulation from either endogenous or4 l* @$ E+ G( E* n
exogenous sources, nonpituitary gonadotropin stim-$ z/ t' E0 p3 Z. P0 F7 W% e# r& d/ G
ulation, and rare activating mutations.3 Virilizing& |8 f& j/ ]2 k c. t
congenital adrenal hyperplasia producing excessive. K7 @3 v( R/ w- K
adrenal androgens is a common cause of precocious+ j; R( M2 f: `
puberty in boys.3,4
( v7 ~8 i; [; FThe most common form of congenital adrenal/ |& X# n) y. C
hyperplasia is the 21-hydroxylase enzyme deficiency.' d( G F2 G" y( M+ C# D1 F
The 11-β hydroxylase deficiency may also result in4 E @) Y& `* t1 M7 c7 g( e
excessive adrenal androgen production, and rarely,
# C8 s5 X2 `# G4 K. {5 xan adrenal tumor may also cause adrenal androgen
# X9 t, y, C' Y2 Texcess.1,3% R+ q1 v% Z7 {" p3 D* j) h4 Q. T
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from) q) U+ H: X; b: E9 ^
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007& m$ m& \( _1 X) ~2 b
A unique entity of male-limited gonadotropin-6 X/ M1 H9 I3 [: d* v2 c& E
independent precocious puberty, which is also known+ L' o2 i1 `! K& B0 M b
as testotoxicosis, may cause precocious puberty at a2 x# _ q. i( N, W) D( t' H
very young age. The physical findings in these boys: B% g6 A' e- }+ @3 S9 d6 T
with this disorder are full pubertal development,
6 I/ s1 ~& r8 e% b2 B7 x: Vincluding bilateral testicular growth, similar to boys& b5 {" ^# w1 E! q' r Z
with CPP. The gonadotropin levels in this disorder; S' D' T9 R, y4 i) S+ O, K
are suppressed to prepubertal levels and do not show: L/ q6 r/ T! y* }
pubertal response of gonadotropin after gonadotropin-
^1 D! s$ _" sreleasing hormone stimulation. This is a sex-linked
! o: V ^# O1 d3 F: s) qautosomal dominant disorder that affects only) H+ l/ Q+ X3 ?+ F
males; therefore, other male members of the family
6 F; v6 c1 c; p/ xmay have similar precocious puberty.3
4 S! ~. K j0 t D# _; S# G% oIn our patient, physical examination was incon-
9 Q; ^5 a( [$ ^4 v, C; D" Qsistent with true precocious puberty since his testi-
- A, `; e+ a6 ?( \& \cles were prepubertal in size. However, testotoxicosis
1 k/ q8 {0 \& G0 [# D$ L9 Ywas in the differential diagnosis because his father
4 v) w& V1 X: W- }4 l X4 ~5 t4 ?started puberty somewhat early, and occasionally,1 ]/ F( b8 S& K# ]- h. Q D
testicular enlargement is not that evident in the
- ]8 C4 T! G4 u6 Wbeginning of this process.1 In the absence of a neg-
. s* z3 X+ R5 sative initial history of androgen exposure, our
& h* v. h+ y+ n6 ?1 _( ebiggest concern was virilizing adrenal hyperplasia,; ?0 @, G2 d6 g2 b. N6 `8 |" F
either 21-hydroxylase deficiency or 11-β hydroxylase
1 `2 k$ p9 B" u, y+ Jdeficiency. Those diagnoses were excluded by find-
' b# L/ e4 c! W! ]7 Ring the normal level of adrenal steroids.0 ?4 m. O; P) A9 n
The diagnosis of exogenous androgens was strongly( G$ W! z0 c- _- t. [& ]% _
suspected in a follow-up visit after 4 months because0 F: l% K' y: R2 G; s7 g: P- S2 I
the physical examination revealed the complete disap-
* m+ J: L6 b, y- B2 Epearance of pubic hair, normal growth velocity, and7 C! M2 `& q# B0 Y% K
decreased erections. The father admitted using a testos-
2 w/ t$ f: Q3 x1 Yterone gel, which he concealed at first visit. He was3 L5 J( u! z: {, E* H' \
using it rather frequently, twice a day. The Physicians’& I& P0 y( H1 F7 q) ?
Desk Reference, or package insert of this product, gel or
; \, a6 C* o& s+ ]1 [% j0 acream, cautions about dermal testosterone transfer to* c. J6 X8 @' I, p$ }
unprotected females through direct skin exposure.. U9 |1 C O' V+ z E/ @
Serum testosterone level was found to be 2 times the6 w. s( z. P# _& ^4 q3 k
baseline value in those females who were exposed to
8 a$ b+ W& g5 p' T: l" beven 15 minutes of direct skin contact with their male1 Q& i+ d3 @6 O, T8 |$ `, }8 B
partners.6 However, when a shirt covered the applica-
' y' Q2 j' `6 i: C' Xtion site, this testosterone transfer was prevented.: Y6 L! g8 m% e& i
Our patient’s testosterone level was 60 ng/mL,
; k2 y5 P; p1 Q% X7 @* Z& \6 P! rwhich was clearly high. Some studies suggest that
& M8 A( T2 g- v9 c9 Cdermal conversion of testosterone to dihydrotestos-0 d$ z( ] I2 {. s
terone, which is a more potent metabolite, is more
T! b' s6 j; ~/ _4 F$ j* cactive in young children exposed to testosterone
; V- P7 j0 ?- M( Kexogenously7; however, we did not measure a dihy-( V# _6 Z! V' {4 `6 z. E
drotestosterone level in our patient. In addition to
9 F3 W3 h7 p0 |. U2 Nvirilization, exposure to exogenous testosterone in0 g* V# x0 ]1 r& Y: @
children results in an increase in growth velocity and
6 @* |8 }" n- z V0 uadvanced bone age, as seen in our patient.. n r- a2 ^- u/ L. y0 K, J3 y
The long-term effect of androgen exposure during
% v4 o+ Y e2 L$ o8 m8 Hearly childhood on pubertal development and final
) P/ m, u1 \& b4 Vadult height are not fully known and always remain( X) B: j# w$ o0 u* h
a concern. Children treated with short-term testos-& r Z6 A% |7 {5 f" B
terone injection or topical androgen may exhibit some
' _ o, \6 e; {9 ~acceleration of the skeletal maturation; however, after
: k5 e5 T! X& l. qcessation of treatment, the rate of bone maturation
2 t$ N) o3 D9 E! { P/ q- qdecelerates and gradually returns to normal.8,9
' B! e. u) y: i fThere are conflicting reports and controversy: y7 o0 g4 a1 n5 r3 H) c
over the effect of early androgen exposure on adult
+ m6 C+ d g' E) \& t; Y, Gpenile length.10,11 Some reports suggest subnormal, `' }; X9 y ]
adult penile length, apparently because of downreg-) i3 T; Q# }" m q* }3 \/ A
ulation of androgen receptor number.10,12 However,
7 V( ^! F2 N+ W* {/ hSutherland et al13 did not find a correlation between
: Y l+ m ~. g1 {; W2 E2 [/ S: S2 u2 Mchildhood testosterone exposure and reduced adult
4 d# z# J, x: xpenile length in clinical studies.
; Y6 X0 X5 Z4 A [+ m5 ENonetheless, we do not believe our patient is9 l$ W9 J6 c; D' G1 Y4 F9 T0 E5 Z
going to experience any of the untoward effects from3 @) I; R1 Q6 c \- ?( Y# r6 V
testosterone exposure as mentioned earlier because/ G1 q" V! p% u1 \3 N9 N C
the exposure was not for a prolonged period of time.
' `. h9 k& Q& qAlthough the bone age was advanced at the time of9 L5 g! e2 U$ k
diagnosis, the child had a normal growth velocity at
- X8 d2 q2 Q w' ythe follow-up visit. It is hoped that his final adult7 b9 \0 y" v/ } ~# Y S/ q7 u
height will not be affected.% H, |. o" A6 a I9 }
Although rarely reported, the widespread avail-2 t6 `' U+ b/ A0 q" i8 {: O
ability of androgen products in our society may# u- A, y! X8 _- V& ^+ o
indeed cause more virilization in male or female
8 c. v/ G, ]( ]5 Vchildren than one would realize. Exposure to andro-. W7 [6 S+ p: R9 I. S) ]+ r1 g: Q0 r6 Y
gen products must be considered and specific ques-! v3 G# k9 J, q b
tioning about the use of a testosterone product or
3 {$ ^. E7 @$ c Kgel should be asked of the family members during9 \7 W& I* D7 E2 Z0 j; a
the evaluation of any children who present with vir- i# G! A8 S, K* @9 k- T
ilization or peripheral precocious puberty. The diag-. k0 m7 L2 h! s) }( w
nosis can be established by just a few tests and by4 P" m2 ~% g' K* V6 M& @" w
appropriate history. The inability to obtain such a& x0 J0 p3 @' t/ D, [. E% ]% i/ V1 u
history, or failure to ask the specific questions, may
+ P$ A( Y9 ~7 X- Yresult in extensive, unnecessary, and expensive, n- t1 g- @3 L4 R0 _4 g, G
investigation. The primary care physician should be
$ X2 R4 h$ Z1 T& I& |) taware of this fact, because most of these children
3 z# B; } T- J% l: y" omay initially present in their practice. The Physicians’
|. I. y0 R8 [8 s- wDesk Reference and package insert should also put a8 F3 o& _ W2 {% M, J0 I
warning about the virilizing effect on a male or
& r/ n& O) F& U* v3 E# e( Afemale child who might come in contact with some-
3 k# S8 {4 a) N1 k( @1 v3 m5 |one using any of these products.
+ [+ k. X) C8 y- b& c9 G0 F# NReferences$ D! f, F5 R- H3 q8 L
1. Styne DM. The testes: disorder of sexual differentiation; ? C& H* [" o+ n: f/ L; B9 y
and puberty in the male. In: Sperling MA, ed. Pediatric8 u% O/ h2 J* m' t; n" P9 R
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
; v+ d; j% e; C& @2002: 565-628.
9 Z4 p' R/ l: L' H% c* R2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious- Z1 F/ t/ r/ d# g2 p9 Z4 p6 ?
puberty in children with tumours of the suprasellar pineal |
|