- 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 03:27:02
|
顯示全部樓層
Sexual Precocity in a 16-Month-Old: t0 t4 D- r" Y
Boy Induced by Indirect Topical8 u+ {% P5 _5 b
Exposure to Testosterone
! E% b- |/ b2 t1 k+ x" C& X- G3 HSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2" C$ p) T9 B# j1 \/ V% L3 q
and Kenneth R. Rettig, MD1
4 A4 P" G! s* l$ fClinical Pediatrics
* v4 A- ~1 i N/ m, XVolume 46 Number 6
" u V: _1 |1 w; yJuly 2007 540-543) O* \: Q7 S; U5 N
© 2007 Sage Publications
2 Y, m; I" `4 b" y! z10.1177/0009922806296651
% q' A2 B) O1 ^: `, q D+ G* ~9 `) e3 hhttp://clp.sagepub.com$ X) n# l# J5 k' f6 ?8 ?2 Q' e: l. U
hosted at
. r5 q5 r3 P$ N! r0 }2 Uhttp://online.sagepub.com0 H8 B6 y' U4 [+ P7 ]8 q/ Z
Precocious puberty in boys, central or peripheral,$ e F0 w$ E5 }5 K( p6 e
is a significant concern for physicians. Central
! H& V. V* c/ Z" w) l9 Y* dprecocious puberty (CPP), which is mediated2 g/ Z4 b: b' \& S, K
through the hypothalamic pituitary gonadal axis, has
4 x* z# Q: c h3 A9 [a higher incidence of organic central nervous system1 W, P% R0 D1 J N
lesions in boys.1,2 Virilization in boys, as manifested2 w/ A! x8 B) l" Z' s" v
by enlargement of the penis, development of pubic- T+ H, |9 P8 P6 Z
hair, and facial acne without enlargement of testi-
0 z1 Y* e7 r3 x8 @cles, suggests peripheral or pseudopuberty.1-3 We
, ?# D8 w" q( V% X9 {report a 16-month-old boy who presented with the" L3 f. Q K# ~) w% V. m
enlargement of the phallus and pubic hair develop-7 X- S5 n. g* a: L# E8 b
ment without testicular enlargement, which was due* C# T4 K! u7 e+ C" r4 v* r3 M5 d" O
to the unintentional exposure to androgen gel used by
9 O$ E1 ?% ?5 v0 `the father. The family initially concealed this infor-
8 l w1 c4 @6 S6 u" B0 [6 mmation, resulting in an extensive work-up for this
1 g; z8 s- R; A% X& K" t7 _child. Given the widespread and easy availability of
. v: S% V! A9 V; etestosterone gel and cream, we believe this is proba-1 d$ R% J6 z; B* G6 f+ y4 X: i
bly more common than the rare case report in the9 X& O, U; E* u' J& V) d: ^
literature.4
3 }$ H5 I- j! T* i& v1 {3 i* LPatient Report
) x1 J5 d$ O; k& d+ ?5 S9 pA 16-month-old white child was referred to the( ^; [8 D5 i; A9 }, X. B2 K' g
endocrine clinic by his pediatrician with the concern1 H8 A H- A/ g9 u) ]# H! Z- a
of early sexual development. His mother noticed
1 y# {) k$ T- }2 w! S6 `light colored pubic hair development when he was
! B& j# {% \7 i( TFrom the 1Division of Pediatric Endocrinology, 2University of8 O- f& O/ n+ a! l
South Alabama Medical Center, Mobile, Alabama.9 y& C2 X" _9 o8 ^0 t
Address correspondence to: Samar K. Bhowmick, MD, FACE,( ` L8 \/ b% b3 D0 p+ D
Professor of Pediatrics, University of South Alabama, College of
& x0 Q( g3 P/ m# z) R7 IMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;/ ` f u q9 e# M" c
e-mail: [email protected]./ |$ ^. w; G$ ^6 q! f. ~
about 6 to 7 months old, which progressively became
% f. k- q+ B) r$ M9 `& f/ Ldarker. She was also concerned about the enlarge-. d( i* S- c y% E) O
ment of his penis and frequent erections. The child3 N0 x& V# ]/ ^. F
was the product of a full-term normal delivery, with
6 i7 S$ G1 x; y* {" C+ D/ B+ E6 C& Z9 Fa birth weight of 7 lb 14 oz, and birth length of
+ X4 z7 a# z5 Z, F: P. w20 inches. He was breast-fed throughout the first year
, m7 i9 B* {* I& jof life and was still receiving breast milk along with- b. |3 _$ X# r9 [4 f2 s1 j
solid food. He had no hospitalizations or surgery,8 K+ n3 Z3 c _% ^0 E
and his psychosocial and psychomotor development
- I: g3 _& x: h3 y- _; mwas age appropriate.
( k4 ] X+ s8 k; m9 OThe family history was remarkable for the father," p0 b0 E$ b: c, }
who was diagnosed with hypothyroidism at age 16,7 h" e7 m) h- s$ {" I; Q
which was treated with thyroxine. The father’s& j6 I( l+ A3 o f3 a
height was 6 feet, and he went through a somewhat
$ |/ {; x# e! {" X0 c0 I4 P7 Qearly puberty and had stopped growing by age 14.- J. R: |6 |8 Y) z I
The father denied taking any other medication. The
$ o5 ]: {2 f0 Bchild’s mother was in good health. Her menarche
( e2 H' z$ Y7 u) s( _5 N, s. U) Gwas at 11 years of age, and her height was at 5 feet
* a# M' p; J, W8 l5 c; \8 o5 inches. There was no other family history of pre-
) |( ]; n7 u: H& V2 Vcocious sexual development in the first-degree rela- b9 q8 \0 n. W/ h+ V
tives. There were no siblings.
! q/ u' a( h8 ^/ ePhysical Examination
0 y# s! y U- R5 y. F* zThe physical examination revealed a very active,5 U! Z Q b! C% A
playful, and healthy boy. The vital signs documented* z: k6 A$ n+ |; J/ F/ U
a blood pressure of 85/50 mm Hg, his length was
/ U( q$ E3 T6 P" u6 ~$ L90 cm (>97th percentile), and his weight was 14.4 kg
0 M9 h: L- o# j3 V(also >97th percentile). The observed yearly growth
" I! E1 @6 w! o% V- Lvelocity was 30 cm (12 inches). The examination of
1 v& J3 k" B7 w' l% A7 j2 S- ?the neck revealed no thyroid enlargement.
. l' _5 T0 ?8 y& X$ S- d. eThe genitourinary examination was remarkable for
" `4 Y5 c* d2 }- ~enlargement of the penis, with a stretched length of b9 H0 X1 t2 I& a- G5 I/ ?6 K
8 cm and a width of 2 cm. The glans penis was very well( r( o: p5 G+ |3 q+ z
developed. The pubic hair was Tanner II, mostly around# |& T1 `7 W* W
540
/ a0 g! [8 J6 u+ lat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from4 a% K7 x6 R+ v
the base of the phallus and was dark and curled. The3 y4 F6 u4 | c' Z
testicular volume was prepubertal at 2 mL each.
5 `, t7 X4 H ]0 A8 kThe skin was moist and smooth and somewhat
$ K5 v& {6 h8 M- c$ Joily. No axillary hair was noted. There were no
! W | r4 y/ A. K" ~abnormal skin pigmentations or café-au-lait spots.. a0 b o1 j; }. V# ]( t
Neurologic evaluation showed deep tendon reflex 2++ g( N: x6 `: j u+ s% I) K
bilateral and symmetrical. There was no suggestion
( {6 w$ B4 ]& T- ?5 P) G! Oof papilledema.- M# y3 O& I6 J6 E# Y
Laboratory Evaluation& j0 [, X9 \5 l& \" y s& s
The bone age was consistent with 28 months by$ O- Q4 _# v I8 [3 M( `: W. i
using the standard of Greulich and Pyle at a chrono-
+ r% K8 s/ A# E. _" {! q u4 J, y( K$ Zlogic age of 16 months (advanced).5 Chromosomal9 G9 \. Z3 C# C" \3 {
karyotype was 46XY. The thyroid function test* V: m) Q. R5 C( P/ k
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
2 G( N: `8 l. n5 k: Z2 N, n$ q, L/ Nlating hormone level was 1.3 µIU/mL (both normal).: Y/ L/ D0 A- b/ X6 A) M
The concentrations of serum electrolytes, blood A/ \/ ?! \7 p' o) r6 V
urea nitrogen, creatinine, and calcium all were
- F) H& ~' S' t5 ]6 Kwithin normal range for his age. The concentration
4 F2 W, R( Y4 ?' B3 H" D, Nof serum 17-hydroxyprogesterone was 16 ng/dL
, @1 t- Q( v; d) V8 y: t1 H5 B(normal, 3 to 90 ng/dL), androstenedione was 203 {( i: R" j6 I
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-+ c* f8 t) H1 ]5 {
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
( ?1 ^) p& j+ B( C! @) C& _1 J% Ldesoxycorticosterone was 4.3 ng/dL (normal, 7 to* R6 f8 V1 q5 T* d- b
49ng/dL), 11-desoxycortisol (specific compound S)
. G0 U& n6 S* a/ O, s( Q+ lwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-$ f _- c5 H. S B+ g7 U
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
) x" `. ~$ Q, W' M, h Htestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
0 g7 C* G' w2 b! [1 r5 fand β-human chorionic gonadotropin was less than/ E1 S' L) [$ Y4 L# X
5 mIU/mL (normal <5 mIU/mL). Serum follicular
# A: l2 O/ [$ ustimulating hormone and leuteinizing hormone7 B3 K: h8 W# Z1 i
concentrations were less than 0.05 mIU/mL
$ b' P' y1 Y& `! X: H3 N(prepubertal).
. ^) R n& \ r% P" eThe parents were notified about the laboratory9 c4 J4 W- G" ]& |" j, f
results and were informed that all of the tests were# C7 k/ ] F* Q# n, U: o1 p
normal except the testosterone level was high. The5 U1 Y, C6 I" T: B" a# j
follow-up visit was arranged within a few weeks to- b O! G/ u$ E! D
obtain testicular and abdominal sonograms; how-
5 b8 j9 `' C4 h" o) d7 \ever, the family did not return for 4 months.4 N# T/ D* V6 a0 l3 x. b
Physical examination at this time revealed that the. \3 |/ r. H# l& ^% S
child had grown 2.5 cm in 4 months and had gained" {4 N+ I9 c2 U# Z" Q' W8 v$ X
2 kg of weight. Physical examination remained
5 H2 k* P; h3 h! ]7 i) a" G& e; Vunchanged. Surprisingly, the pubic hair almost com-" }$ O9 i; _( o* J9 `3 X
pletely disappeared except for a few vellous hairs at
( U$ I# a7 F* y6 `! u4 Othe base of the phallus. Testicular volume was still 2
* L1 A: y" t$ h; m, T: HmL, and the size of the penis remained unchanged.
; Y x s4 Q, V! aThe mother also said that the boy was no longer hav-
& i% g! X' d# S5 P/ }$ y: Ding frequent erections.
9 r1 J$ P* l d2 ^Both parents were again questioned about use of
# J) ]1 H& G: Many ointment/creams that they may have applied to3 y; o8 A2 b; Y" w
the child’s skin. This time the father admitted the
+ o9 Q, E: m; ^& J7 xTopical Testosterone Exposure / Bhowmick et al 5413 e) A' C) `- Y6 j
use of testosterone gel twice daily that he was apply-
6 P3 o6 e( [! aing over his own shoulders, chest, and back area for! g9 }! H6 p( j* p4 v4 o
a year. The father also revealed he was embarrassed5 e9 Y. p6 c+ B+ a( ^6 e
to disclose that he was using a testosterone gel pre-. g% N8 p$ ^: R0 T
scribed by his family physician for decreased libido
_9 E/ i" O- s( ~! d7 asecondary to depression.
5 e1 C8 @5 L9 l) ZThe child slept in the same bed with parents.
( v6 ?: e n' G, IThe father would hug the baby and hold him on his6 E% Z5 a) B; B7 W2 r
chest for a considerable period of time, causing sig-& u9 b$ W% p P$ R$ U
nificant bare skin contact between baby and father.
' y9 x" T( |8 t+ k( L- d/ FThe father also admitted that after the phone call,8 d& n$ z( S/ q
when he learned the testosterone level in the baby. E: p' K: k1 e. e0 Q0 ]
was high, he then read the product information
6 y S2 Y' B# y7 h; Rpacket and concluded that it was most likely the rea-6 j& H+ b6 G9 Y$ M/ |5 z
son for the child’s virilization. At that time, they
9 Q- r0 \7 [1 X+ g Ydecided to put the baby in a separate bed, and the- d/ I3 u2 |3 P7 k1 g" ?: J! E
father was not hugging him with bare skin and had+ G, ]" ?9 i W9 \
been using protective clothing. A repeat testosterone8 |+ C9 K: z: A7 A( @; R; L! @& n
test was ordered, but the family did not go to the7 \3 F# ]7 w. Y @3 q& F+ Q
laboratory to obtain the test.* n( Y+ ?3 g" F2 B
Discussion; ^' Y- m c8 p
Precocious puberty in boys is defined as secondary
. X: J2 o6 x8 j# R- \: t6 x- qsexual development before 9 years of age.1,4( y9 G$ o+ P& @7 _# k( |
Precocious puberty is termed as central (true) when8 X2 W2 W3 {2 b3 T: }" q
it is caused by the premature activation of hypo-% } d3 L- a4 H5 @
thalamic pituitary gonadal axis. CPP is more com-& m! b" r- W0 w* J4 W/ ~% I
mon in girls than in boys.1,3 Most boys with CPP
7 j0 h4 \* R7 \" M$ _may have a central nervous system lesion that is
4 ~5 @0 x. S& o. I6 p/ {0 eresponsible for the early activation of the hypothal-0 e7 O7 Z5 G1 }# H
amic pituitary gonadal axis.1-3 Thus, greater empha-7 v$ ?' U& i* x$ {; G& h R: C0 y
sis has been given to neuroradiologic imaging in
9 p. t3 e( E: W& [" lboys with precocious puberty. In addition to viril- Y! z, b% t' Y& w
ization, the clinical hallmark of CPP is the symmet-! X6 d9 G O# `& _
rical testicular growth secondary to stimulation by; l6 S3 P% p9 ]& }2 w) z4 v; u$ A
gonadotropins.1,3% F1 q- A- N$ Z
Gonadotropin-independent peripheral preco-' o/ \# t, Z, p- }6 i
cious puberty in boys also results from inappropriate
- O c9 ]1 r! Y5 T% @. l# s8 ~androgenic stimulation from either endogenous or
0 A# m3 ?- q+ W& o4 q5 r/ yexogenous sources, nonpituitary gonadotropin stim-8 d( j2 ?3 F/ w0 A" T) v+ p' A9 Y+ N
ulation, and rare activating mutations.3 Virilizing; {! J! M3 D9 \
congenital adrenal hyperplasia producing excessive& b, i: A. ~, E) B1 V( b
adrenal androgens is a common cause of precocious
0 S! }2 Z, j/ a* }5 ^2 {- Qpuberty in boys.3,4
P/ J2 @5 z0 y) h) i4 D5 x$ ~The most common form of congenital adrenal8 r( [+ J$ y) m5 H; h" }* G, h* ?: x
hyperplasia is the 21-hydroxylase enzyme deficiency.. F7 d. W @7 d) A, u
The 11-β hydroxylase deficiency may also result in
+ B+ d" E6 J( V" J* h' N4 q* X9 Iexcessive adrenal androgen production, and rarely,- \1 U2 S6 ?' J
an adrenal tumor may also cause adrenal androgen9 h: W4 r: s, T, h- X3 G5 d
excess.1,35 f/ ]& P L" N" \. B
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from( D! e, \! T$ Q( T+ x b3 J5 M
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007* x) K& H \1 n
A unique entity of male-limited gonadotropin-) Y/ k' X2 k/ y0 i8 X
independent precocious puberty, which is also known( A# K' X G! F
as testotoxicosis, may cause precocious puberty at a( x7 _& | }8 E! V# ?
very young age. The physical findings in these boys3 z; [8 ?/ I4 W
with this disorder are full pubertal development,: x8 b# P7 a3 W+ d5 D% ^, ]9 Y; e2 q
including bilateral testicular growth, similar to boys$ B( n6 u6 \4 r$ Q) C
with CPP. The gonadotropin levels in this disorder
4 c+ p9 i0 M% b) F9 W8 F; T: e, yare suppressed to prepubertal levels and do not show) V) s/ t; m" j- h. H- ^
pubertal response of gonadotropin after gonadotropin-4 l) @0 p+ Q5 D$ C
releasing hormone stimulation. This is a sex-linked
7 K T# _8 z, o! u B* m- B6 Q8 [autosomal dominant disorder that affects only4 {& N) N! l; D- z
males; therefore, other male members of the family
% \! K$ X# X2 A) X; L( S$ T! Y9 smay have similar precocious puberty.3
$ R9 @6 u5 r" b7 Y6 @, A/ eIn our patient, physical examination was incon-
, G" k! O( v. F2 R$ y$ Bsistent with true precocious puberty since his testi-) [. |' @/ A+ C& c: `* `6 a
cles were prepubertal in size. However, testotoxicosis, ^9 N. H) J1 i4 S
was in the differential diagnosis because his father1 ~( C- q: ^: t- F4 t0 W
started puberty somewhat early, and occasionally,
+ n3 S2 r+ M2 c9 C; Wtesticular enlargement is not that evident in the3 D) q- ^: E& k$ s
beginning of this process.1 In the absence of a neg-
, n$ {2 @0 Y4 Q" P0 o( _ative initial history of androgen exposure, our
9 u: H, A9 W' E% g2 D4 }biggest concern was virilizing adrenal hyperplasia,& ^4 ~$ v O2 a% H7 P# P
either 21-hydroxylase deficiency or 11-β hydroxylase7 `9 X, i0 j7 g! P$ G& C) D4 d+ u
deficiency. Those diagnoses were excluded by find-
" G, S& O0 {/ |ing the normal level of adrenal steroids.6 [" q) ~; |5 F# u: x
The diagnosis of exogenous androgens was strongly. |' W9 d, ~! Y P4 g' B
suspected in a follow-up visit after 4 months because
& D: z3 W! y" X% V: L6 A7 ?the physical examination revealed the complete disap-- P4 M7 ~4 z1 w$ [
pearance of pubic hair, normal growth velocity, and/ z1 d* i$ l6 a9 v& g* O. V* w8 K. w
decreased erections. The father admitted using a testos-5 ~1 R/ W1 s2 k; K) L0 n4 C$ D
terone gel, which he concealed at first visit. He was p/ ?7 f: w# Z8 E$ n/ {# r
using it rather frequently, twice a day. The Physicians’
; w* z0 h w/ X$ IDesk Reference, or package insert of this product, gel or
# V! @, x9 E' pcream, cautions about dermal testosterone transfer to4 B8 e' h) j" n; [; u6 p+ u
unprotected females through direct skin exposure.
( g* ]7 L' W' M- ]Serum testosterone level was found to be 2 times the7 {" {% o+ p' R" C1 ^& q
baseline value in those females who were exposed to
3 r7 d- Y& |9 e; H0 Veven 15 minutes of direct skin contact with their male6 E! X% V& d/ O! P, o/ D
partners.6 However, when a shirt covered the applica-7 x' u6 D2 I& c' n- I0 j1 V: f9 O
tion site, this testosterone transfer was prevented.% K W# c, g: W- @" T
Our patient’s testosterone level was 60 ng/mL,
. d2 T; p L P d% |0 S7 e1 R8 zwhich was clearly high. Some studies suggest that
+ ?6 n! W0 {; V) T9 Q' }) vdermal conversion of testosterone to dihydrotestos-
4 [, T: l+ x, F3 [! g H3 dterone, which is a more potent metabolite, is more
2 [. H7 B3 }1 x2 a# l1 R; K6 cactive in young children exposed to testosterone
7 D- n8 \: {( r, ]exogenously7; however, we did not measure a dihy-4 q4 U( X. C3 L! d0 s" X) C4 v
drotestosterone level in our patient. In addition to
- ~/ Z! s, g/ y& i2 E: R/ g2 Jvirilization, exposure to exogenous testosterone in
* `0 c5 J/ Z4 R) Jchildren results in an increase in growth velocity and
8 p, O; [+ @; R& madvanced bone age, as seen in our patient.
* D" q& y( @, n8 ^. g* TThe long-term effect of androgen exposure during' Z( ^5 y2 a- g' ?7 T
early childhood on pubertal development and final
. h. Q' b( m& |, iadult height are not fully known and always remain
" y7 P p4 R& w4 k3 X! m* S Wa concern. Children treated with short-term testos-
+ p; O* O, }. U, Zterone injection or topical androgen may exhibit some3 m. P L5 ?- t$ H+ w
acceleration of the skeletal maturation; however, after
7 {4 B# \/ T+ M r* ycessation of treatment, the rate of bone maturation! d( D8 m" [% [
decelerates and gradually returns to normal.8,9
+ N: q" s3 o% i: iThere are conflicting reports and controversy1 M/ T" Y, ~$ f
over the effect of early androgen exposure on adult
8 R( f$ i W" t0 Z0 n, x4 P( v; ?penile length.10,11 Some reports suggest subnormal) {5 P: D& J) F1 s
adult penile length, apparently because of downreg-4 c# i% w4 A v& [9 ?* |! {! y, ?8 G; B
ulation of androgen receptor number.10,12 However,
; p. @( K e' j+ W; KSutherland et al13 did not find a correlation between
& j. H" m0 J( D# ^+ l, echildhood testosterone exposure and reduced adult& r. f4 G3 I6 ^4 C
penile length in clinical studies.% ^3 W8 a0 g, n4 _9 f, c
Nonetheless, we do not believe our patient is
5 x) f/ T* e) D/ V7 ngoing to experience any of the untoward effects from; `+ t2 T. r" g+ m9 v% _0 n [, V
testosterone exposure as mentioned earlier because
8 v; A+ _& v* e* k; Ithe exposure was not for a prolonged period of time.
. U2 M9 ?/ v. l! M4 QAlthough the bone age was advanced at the time of
0 }( \: M5 x/ _$ ediagnosis, the child had a normal growth velocity at
% n. w% G! D8 x, zthe follow-up visit. It is hoped that his final adult. B; L( m# u6 B9 t: U: P9 w
height will not be affected.7 }: G+ y+ }9 o7 V x h7 ^
Although rarely reported, the widespread avail-/ X( N+ x7 d% K$ C0 N3 [2 a' G% o
ability of androgen products in our society may6 s" j- B0 _0 Z) Q
indeed cause more virilization in male or female8 K/ t" F) e7 l8 G N" n" d. U' W5 u
children than one would realize. Exposure to andro-
e2 C) |! n0 Qgen products must be considered and specific ques-
* Z; v( g- \' l8 [, M- x) wtioning about the use of a testosterone product or3 v7 X1 ?' g! S$ b- f
gel should be asked of the family members during( H, h( r/ k3 T+ M+ \8 A
the evaluation of any children who present with vir-1 h4 W; T/ E- I9 T/ C- [$ A2 c/ h) n$ [
ilization or peripheral precocious puberty. The diag-! O; g+ E6 }9 [0 G2 Z
nosis can be established by just a few tests and by
' N6 P5 k2 p* @$ `appropriate history. The inability to obtain such a, I# b3 @* K* X I$ x4 X
history, or failure to ask the specific questions, may6 d0 d2 h1 Q7 G/ |2 d' R
result in extensive, unnecessary, and expensive
* w) v' I4 X3 `4 |7 N0 cinvestigation. The primary care physician should be
6 D# b1 y* f b8 zaware of this fact, because most of these children' B! E, k c$ s( y/ \" J
may initially present in their practice. The Physicians’
7 s5 J9 F$ \- |Desk Reference and package insert should also put a
: `! B+ U6 ~( D1 q0 Wwarning about the virilizing effect on a male or
# T, i$ b$ t7 j5 [female child who might come in contact with some-
* a! W5 c8 ?% i/ k" jone using any of these products.; L( T0 g' r; x, ~" H- N
References) G7 t# A" i5 ?7 Y
1. Styne DM. The testes: disorder of sexual differentiation' h' z6 k* D: k
and puberty in the male. In: Sperling MA, ed. Pediatric
; e% S* B' ?6 k$ P, i9 {Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;, T* e: k7 O! E( [1 m( h# ^
2002: 565-628.
) w X" j. {& r/ ^) w7 \2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious2 `6 P7 T# R, [2 ]6 c' l
puberty in children with tumours of the suprasellar pineal |
|