- 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: Z6 \% e' L2 W% z
Boy Induced by Indirect Topical) [2 h5 O! E, Y3 e, f
Exposure to Testosterone J* c- k2 _7 V! p K- J
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
1 [+ P( [8 Q# J$ Z2 y% S" r% _and Kenneth R. Rettig, MD1) I, U4 J1 x+ j% l! M* l7 U7 R
Clinical Pediatrics
* J2 F5 U! V( `- aVolume 46 Number 6" _$ d8 N0 h/ G
July 2007 540-543: r; N, y- J5 I$ r/ }
© 2007 Sage Publications6 m6 n2 c; x1 f
10.1177/0009922806296651
: _. j9 v, q: W$ w+ k" Z. O2 u0 Lhttp://clp.sagepub.com; y' `. @- i$ @
hosted at" m) \/ l) d4 h8 S: \* r
http://online.sagepub.com' X \) ~" d _& s& H2 }( G
Precocious puberty in boys, central or peripheral,5 x8 V% y( y) D- D# \# M5 K
is a significant concern for physicians. Central1 c; |# C( V3 j: T/ M4 C+ S
precocious puberty (CPP), which is mediated
) z1 o- n! m: M8 uthrough the hypothalamic pituitary gonadal axis, has& ], d' a. _! Q& B1 C+ U3 F
a higher incidence of organic central nervous system
, O) L7 D' n0 I/ W8 `( x5 V4 ilesions in boys.1,2 Virilization in boys, as manifested$ c: J# o+ Z- z" x' b5 n' a$ p7 v
by enlargement of the penis, development of pubic
( Y1 `' }$ e; U1 nhair, and facial acne without enlargement of testi-- i- u* [1 ?: B$ ^
cles, suggests peripheral or pseudopuberty.1-3 We
5 d) w6 P( c& }) k; Wreport a 16-month-old boy who presented with the
' s6 _' v' A8 ?2 z! Wenlargement of the phallus and pubic hair develop-: N. j( T) T% b0 o9 p
ment without testicular enlargement, which was due
7 \ t* d5 e, u P Kto the unintentional exposure to androgen gel used by
8 \) @6 {/ b- K3 ^5 athe father. The family initially concealed this infor-( e2 v; P; b4 w# p, h
mation, resulting in an extensive work-up for this
8 X2 l7 H- @& ~% `! ]) E0 i- d; mchild. Given the widespread and easy availability of& T$ J8 x( n; Z2 K, U. X
testosterone gel and cream, we believe this is proba-
9 A5 b# f9 L6 I5 @/ N6 [# lbly more common than the rare case report in the/ s7 n u, \! W) U: C m
literature.44 b* M4 B: @5 H7 L" \( U
Patient Report
/ \6 F) d* r. s1 }A 16-month-old white child was referred to the8 B" D8 R/ q# D; q6 D) h2 `9 H
endocrine clinic by his pediatrician with the concern5 [3 Q J! ]' P5 G. Z* L
of early sexual development. His mother noticed" i+ N, {- X% a: ^
light colored pubic hair development when he was
: l' `8 d) a$ a5 YFrom the 1Division of Pediatric Endocrinology, 2University of
0 h/ F f$ |/ t2 w5 DSouth Alabama Medical Center, Mobile, Alabama.
# ]7 n1 z# _; K0 U/ Q) E, lAddress correspondence to: Samar K. Bhowmick, MD, FACE,$ I/ v, H+ K: A6 g! e: O1 Y
Professor of Pediatrics, University of South Alabama, College of6 ~( ^- b3 ]! x% \2 G+ }7 J
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
3 u2 _0 ]* d# A" Q3 je-mail: [email protected].3 a& |* F7 ?. T G8 P( Y! Y
about 6 to 7 months old, which progressively became# ^. k$ F! K! _3 ^7 x
darker. She was also concerned about the enlarge- x/ o, N9 E' ^ Q7 B5 d
ment of his penis and frequent erections. The child3 J. T; b$ ~0 q6 m# z
was the product of a full-term normal delivery, with2 X6 c8 m* m5 O
a birth weight of 7 lb 14 oz, and birth length of
) h( z, \0 o6 j h3 }# L, n20 inches. He was breast-fed throughout the first year# w2 V: A# U. k: {% Q
of life and was still receiving breast milk along with
5 I% o: v, ~3 N9 _* R% c- Nsolid food. He had no hospitalizations or surgery,% x+ w, M# j: _) E
and his psychosocial and psychomotor development( @$ h% Y6 o0 L* L, ^
was age appropriate.: B, q3 V2 p/ t9 i) _) {
The family history was remarkable for the father,
{ x' n5 b) L! X U" i- u3 X/ Pwho was diagnosed with hypothyroidism at age 16,8 \. L O- j- t( w( q
which was treated with thyroxine. The father’s
5 D; w; d: D' f G* eheight was 6 feet, and he went through a somewhat' s+ `0 _; P* T! ?! b* K; [8 b0 N
early puberty and had stopped growing by age 14.
1 R5 B6 k+ j( a( U. b1 CThe father denied taking any other medication. The. t6 O1 w F8 L0 b
child’s mother was in good health. Her menarche
7 b Y! H# A. A; Z5 q' [% }was at 11 years of age, and her height was at 5 feet
/ _) ?% p" J- v' T# n+ y7 w5 inches. There was no other family history of pre-
9 ^; l4 R7 c6 a0 P( zcocious sexual development in the first-degree rela-
1 C4 t- ]" Z- ~, Y1 t7 K: O/ e3 stives. There were no siblings.+ c/ S) E8 ^- w" b
Physical Examination
& v4 m* S% H+ W# z/ \The physical examination revealed a very active,3 y, |5 e: Q2 ~4 Q) W" H
playful, and healthy boy. The vital signs documented% F, k$ I0 ^' j% k# l4 r
a blood pressure of 85/50 mm Hg, his length was, o) H* X# M5 G$ Z' |
90 cm (>97th percentile), and his weight was 14.4 kg
/ G6 ]% R) _ F. n. [4 n. [- m& L8 L(also >97th percentile). The observed yearly growth& R- C4 v6 d }1 v( y
velocity was 30 cm (12 inches). The examination of
, l% J# P; s( w$ U4 \- pthe neck revealed no thyroid enlargement.
' t: F2 t8 A. O( V7 @6 XThe genitourinary examination was remarkable for
& t8 z$ X0 X+ h/ C9 ?7 cenlargement of the penis, with a stretched length of" b. d2 o$ H) x- O9 l3 j
8 cm and a width of 2 cm. The glans penis was very well! u5 A, h& C% n$ |) ~& t A
developed. The pubic hair was Tanner II, mostly around, Y# \$ u" }: X! F
540& F/ ]$ ?: D. @7 s7 x
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from3 }3 P; a0 X9 A3 ~% j
the base of the phallus and was dark and curled. The
, K# D4 i5 O$ ~) ^6 [testicular volume was prepubertal at 2 mL each.
h8 P) s, j$ ~4 i w' B# d2 `The skin was moist and smooth and somewhat
# U# X o) P- r* A1 toily. No axillary hair was noted. There were no
, |+ t: s" d3 `& S( M! T9 G1 vabnormal skin pigmentations or café-au-lait spots.! f' L6 m5 a, j# _. K
Neurologic evaluation showed deep tendon reflex 2+5 i1 [" r1 H3 ]% X# ^4 \
bilateral and symmetrical. There was no suggestion
& U% G. x% C! S, Y$ y3 G1 fof papilledema.8 L& X' W+ Z8 W v4 S
Laboratory Evaluation$ b, b# }. m. v/ S, j4 P1 v
The bone age was consistent with 28 months by
9 D* R& X& k7 K/ Ausing the standard of Greulich and Pyle at a chrono-
3 l7 E- {' p8 \) }; k/ Slogic age of 16 months (advanced).5 Chromosomal
k8 ]% N! ?& v* gkaryotype was 46XY. The thyroid function test
' }! b3 N. R) i1 d% n1 K* X5 Oshowed a free T4 of 1.69 ng/dL, and thyroid stimu-; K9 ^: `: o1 S2 ?5 {
lating hormone level was 1.3 µIU/mL (both normal).) q/ G6 ~. x0 T: l; J; p
The concentrations of serum electrolytes, blood6 `$ O2 v& i2 T, k% y
urea nitrogen, creatinine, and calcium all were# x3 f$ r' E. X7 A" v4 @
within normal range for his age. The concentration
4 i5 T! S) d7 n6 ^: m5 q/ ]2 kof serum 17-hydroxyprogesterone was 16 ng/dL
+ K, C# E$ T5 F3 I, d(normal, 3 to 90 ng/dL), androstenedione was 20
8 X5 m/ m" Q7 |9 ]* h. | tng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-2 h+ e- c: K9 M& S) D" M+ z
terone was 38 ng/dL (normal, 50 to 760 ng/dL),) d" c3 {9 H0 Y3 `, u* y
desoxycorticosterone was 4.3 ng/dL (normal, 7 to$ j$ e! q5 `1 r( m+ M1 G
49ng/dL), 11-desoxycortisol (specific compound S)5 @% k- y1 Y2 `0 C1 ^- d: a( h
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-2 b, ?/ t# |0 _( n0 p+ V
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total0 [2 F( a. Z. D# W" q8 S- n
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),( ]8 u5 m; @8 A: N
and β-human chorionic gonadotropin was less than$ F5 h: D# A( z h) |6 ~4 I
5 mIU/mL (normal <5 mIU/mL). Serum follicular. z4 f* H( ?3 z
stimulating hormone and leuteinizing hormone9 f, i( I2 f+ o$ p7 K; F
concentrations were less than 0.05 mIU/mL
7 k& V- r, E4 U4 ~( \6 W n(prepubertal).
" X! D% m& i* R1 o8 v: P2 ]/ MThe parents were notified about the laboratory
: @ X- {3 P+ J! ^- z1 N0 j8 Tresults and were informed that all of the tests were
9 ^" W, r' N; j, H9 y7 F {normal except the testosterone level was high. The
3 `3 P1 M( o1 u; I+ T/ e x( \follow-up visit was arranged within a few weeks to; y; V% i0 L; H
obtain testicular and abdominal sonograms; how-& w. K1 U( t& y" K# \
ever, the family did not return for 4 months.9 J; S6 f* X, }+ ]. B* Z+ S6 |- ?
Physical examination at this time revealed that the; ^" i3 Y2 I* G4 H" |1 v
child had grown 2.5 cm in 4 months and had gained
/ Y# g5 Q$ {0 [* {5 i2 N2 kg of weight. Physical examination remained* P4 M; D8 s% T. }
unchanged. Surprisingly, the pubic hair almost com-
9 x+ T9 d$ l; Hpletely disappeared except for a few vellous hairs at( T. h9 Y# X) q* c: X
the base of the phallus. Testicular volume was still 29 j1 `/ r& J( }$ a2 \) N, P
mL, and the size of the penis remained unchanged.- E' k Y, c" F% y
The mother also said that the boy was no longer hav-+ B% f! Q, p. M: E1 Y6 r' J+ c
ing frequent erections.
7 L7 k' Y% }* |8 }! v5 B- u3 C' rBoth parents were again questioned about use of7 Z$ @- X1 b0 l$ o+ H/ I: l
any ointment/creams that they may have applied to8 r/ v1 W0 U: ?' A. r
the child’s skin. This time the father admitted the1 `( ?+ @6 ^! i1 B" S% Y% `; H2 @% p$ Y
Topical Testosterone Exposure / Bhowmick et al 541
9 s" |/ n1 N- t# B0 w. Z$ Iuse of testosterone gel twice daily that he was apply-( p7 Q( T2 y% p- S& L
ing over his own shoulders, chest, and back area for4 [5 q/ V$ f% g f" g
a year. The father also revealed he was embarrassed
' {3 b, C4 h' S3 N+ eto disclose that he was using a testosterone gel pre-
4 b; U1 S9 D- q5 ?( [6 gscribed by his family physician for decreased libido5 H# q, C" \# F' g) ~# O
secondary to depression.) L6 y: n* _) v. x* y
The child slept in the same bed with parents.
( g4 C% A, s1 Q1 D. g1 aThe father would hug the baby and hold him on his- ^, j$ Q s* c! j6 _
chest for a considerable period of time, causing sig-
/ K5 o6 ^" O# v% M. ~, v+ hnificant bare skin contact between baby and father.
9 ?- }& {/ g, Z* i: UThe father also admitted that after the phone call,
8 f1 l0 e; L$ ]when he learned the testosterone level in the baby
, P" u, B* j2 n" ]& Uwas high, he then read the product information5 J5 f7 H" i& y
packet and concluded that it was most likely the rea-
( X1 p- V3 s% Y2 qson for the child’s virilization. At that time, they. y% o% k+ _- j' V5 P8 d
decided to put the baby in a separate bed, and the# s, k: E0 A/ Q. ^$ o$ b# O
father was not hugging him with bare skin and had
R' d7 M: \0 Ibeen using protective clothing. A repeat testosterone
8 s, r5 y( S+ j' N6 f- S* D" f' a. ~test was ordered, but the family did not go to the& H9 N# S9 u' D0 W& A# f
laboratory to obtain the test.
& i* z! [0 z1 n# z# jDiscussion' I0 z' r2 @& [1 }5 Z2 O/ V( R
Precocious puberty in boys is defined as secondary
, R3 l& e0 x4 r) n/ l' Qsexual development before 9 years of age.1,4# t. l9 B1 d2 v1 s
Precocious puberty is termed as central (true) when4 U+ m$ M C, \& M. q# R; b
it is caused by the premature activation of hypo-1 Q/ o8 B7 g7 t+ g3 Z6 R. N4 p
thalamic pituitary gonadal axis. CPP is more com-+ z+ f+ i. o H9 l/ v$ B$ ^
mon in girls than in boys.1,3 Most boys with CPP
' x5 I* y" Y# n- m. r6 zmay have a central nervous system lesion that is5 S" n ?- [* d$ I8 h
responsible for the early activation of the hypothal-
1 f5 R- J1 ]2 p: l0 X0 @amic pituitary gonadal axis.1-3 Thus, greater empha-" d4 @- L G2 _" R) ]8 ]# ?6 d
sis has been given to neuroradiologic imaging in" A* z" }% ~1 F0 c
boys with precocious puberty. In addition to viril-" v$ c; N9 x0 o( g/ O
ization, the clinical hallmark of CPP is the symmet-
3 R5 R" d8 ~1 orical testicular growth secondary to stimulation by. c; _3 x! L. V& X! w
gonadotropins.1,3
' ]1 W% R$ ]* ?$ \Gonadotropin-independent peripheral preco-
$ Y& N$ P) t7 B, q6 x8 A' w) u& N# ecious puberty in boys also results from inappropriate
( O0 ?0 i; l* _, N0 bandrogenic stimulation from either endogenous or
* e9 X5 ~& e# T8 X# L0 W5 t( Jexogenous sources, nonpituitary gonadotropin stim-
4 Y2 f4 T" O) P$ Y/ O! Nulation, and rare activating mutations.3 Virilizing4 n2 ?8 w% l; x
congenital adrenal hyperplasia producing excessive3 g3 ]6 y: v. v8 F
adrenal androgens is a common cause of precocious3 I9 G3 h, J2 G& `$ j W# i- k# O
puberty in boys.3,48 ?4 y0 I8 e$ h7 z2 i v2 I& M9 g
The most common form of congenital adrenal
0 g0 V% m* e2 M9 {- _: d% z, Zhyperplasia is the 21-hydroxylase enzyme deficiency.2 W( f& x3 V9 S- E
The 11-β hydroxylase deficiency may also result in! E$ K' m% C* e. ~! x8 o% A
excessive adrenal androgen production, and rarely, F' y3 R Q3 |4 A% B
an adrenal tumor may also cause adrenal androgen" B& @! ^5 S& S$ _
excess.1,3
& `5 W4 [$ q5 y- ~2 W. p! Pat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
% ~. |- U: t3 Z% I: t' g6 q3 R542 Clinical Pediatrics / Vol. 46, No. 6, July 2007$ x6 p) d. c" E q% n) H
A unique entity of male-limited gonadotropin-
5 V: {+ k5 b! G9 @independent precocious puberty, which is also known1 J9 x5 [9 Z2 \
as testotoxicosis, may cause precocious puberty at a
) F) K- d& @+ W2 ?( Lvery young age. The physical findings in these boys
1 x" u( V* o# _6 E/ f, _( W4 bwith this disorder are full pubertal development,, x6 |/ \- V7 w4 E7 h% e* L6 D
including bilateral testicular growth, similar to boys2 A7 \" s6 B% p( K( l- Q
with CPP. The gonadotropin levels in this disorder
9 N0 Y- i0 [. B; x9 [# aare suppressed to prepubertal levels and do not show- F# u# l/ Q6 ]5 U! N2 O8 d
pubertal response of gonadotropin after gonadotropin-! K) d( [- `" R. m; k
releasing hormone stimulation. This is a sex-linked
5 y" k( @6 r* j2 J9 oautosomal dominant disorder that affects only' m9 O' h# H" ~& S3 o' A
males; therefore, other male members of the family
8 f( [. H$ M0 _* I0 D. B6 rmay have similar precocious puberty.3+ G+ ]% G- a. r" i) c. R
In our patient, physical examination was incon-) J( d1 f1 N7 V6 H
sistent with true precocious puberty since his testi-
# n/ m/ R& B: I' v4 e/ I& xcles were prepubertal in size. However, testotoxicosis
0 T* L" n2 ?4 Q6 N# Vwas in the differential diagnosis because his father
0 G) g1 q) t8 {( V9 e, D5 V# istarted puberty somewhat early, and occasionally,( y; n, J# h1 v% o- q
testicular enlargement is not that evident in the% e0 P* s) _) O) X" V
beginning of this process.1 In the absence of a neg-
5 \/ n; t2 c2 hative initial history of androgen exposure, our. w) K3 g# f E6 m; `# J: K; N1 I; T
biggest concern was virilizing adrenal hyperplasia,
4 K# P7 N9 g( E+ {5 \1 jeither 21-hydroxylase deficiency or 11-β hydroxylase
9 d$ `, A5 V' [deficiency. Those diagnoses were excluded by find-
0 Y' p) c5 A7 h+ qing the normal level of adrenal steroids.* @' O5 x9 O) H* R3 ]% M0 l: D" S
The diagnosis of exogenous androgens was strongly9 x) C3 Y1 q- C( E9 d1 o
suspected in a follow-up visit after 4 months because# p4 t+ Z6 q* g$ X! R
the physical examination revealed the complete disap-
' ^7 o% ?& O" e: K1 mpearance of pubic hair, normal growth velocity, and
4 B; ?, o& O5 h) a" xdecreased erections. The father admitted using a testos-
9 `6 ^- o7 ?7 E% T) e \1 N; }/ oterone gel, which he concealed at first visit. He was( u, T$ x |3 u% h j
using it rather frequently, twice a day. The Physicians’ c. t/ O9 L" ~9 g& y5 U9 ]
Desk Reference, or package insert of this product, gel or8 l! _- ^9 U; A) e
cream, cautions about dermal testosterone transfer to% v( D) a& Y7 d
unprotected females through direct skin exposure.
) z8 G, u8 S; `1 A' s2 o2 iSerum testosterone level was found to be 2 times the. r0 N3 S6 K" w
baseline value in those females who were exposed to
9 _8 C8 X R$ h( z v0 I4 Xeven 15 minutes of direct skin contact with their male
% b& ?. M: }( M1 U- }$ l% @: ?) z! @partners.6 However, when a shirt covered the applica-' W* x7 W1 w. X+ ?; c
tion site, this testosterone transfer was prevented.& F8 m% x6 \$ z, G
Our patient’s testosterone level was 60 ng/mL,( z- |" U# Y2 Z, }' t
which was clearly high. Some studies suggest that' }' |2 X: R- D9 B
dermal conversion of testosterone to dihydrotestos-8 h5 x/ V6 W# z( u9 W* }
terone, which is a more potent metabolite, is more: g# D2 `' F1 E' Q0 r* B
active in young children exposed to testosterone/ D5 v2 C$ J/ d7 }; _7 F/ J0 Z( x
exogenously7; however, we did not measure a dihy-
4 k9 n9 _3 `& c2 T8 y! B& w- j" gdrotestosterone level in our patient. In addition to
% C% b2 Q6 v+ Q* Jvirilization, exposure to exogenous testosterone in* [/ A$ e1 I) a, j4 B S
children results in an increase in growth velocity and: ^9 j g& G" D0 m. U% P7 C( r7 U
advanced bone age, as seen in our patient.
! ~, `9 l5 {1 n5 d. g# NThe long-term effect of androgen exposure during- m! A8 x% F6 {. }2 S
early childhood on pubertal development and final
9 i3 ^* T! y/ J3 Y- o- j$ Hadult height are not fully known and always remain& p4 [7 o, G, |. H# H# V
a concern. Children treated with short-term testos-, F' d* s% c% y5 M; ~9 c2 X
terone injection or topical androgen may exhibit some
: m& @4 R- S) c' }acceleration of the skeletal maturation; however, after* A+ z w+ f) e5 o7 g3 H& {8 A, G
cessation of treatment, the rate of bone maturation7 T2 z9 Q- A% [1 ]
decelerates and gradually returns to normal.8,95 I1 v' Z3 c/ @+ U% ^* M; L
There are conflicting reports and controversy9 A! f5 Z! q/ \% T
over the effect of early androgen exposure on adult
: q @; I* s3 K3 S. ?penile length.10,11 Some reports suggest subnormal: r2 F9 ?3 B6 a) b4 r! D/ D* s
adult penile length, apparently because of downreg- N( k {2 z; Y {5 z; Y
ulation of androgen receptor number.10,12 However,. |3 F7 f- E, R0 t
Sutherland et al13 did not find a correlation between: M5 p! p8 O% q% d
childhood testosterone exposure and reduced adult
. o( d3 n5 J3 r7 h, d& I! jpenile length in clinical studies.
1 Q3 _- l- C- p! nNonetheless, we do not believe our patient is4 F. T* B) G+ p4 T
going to experience any of the untoward effects from8 d* v* B6 ?6 O* {8 P7 I
testosterone exposure as mentioned earlier because4 @$ W N$ p( l ]& L2 x
the exposure was not for a prolonged period of time.
/ Y$ Z+ F. M0 w; p" u2 RAlthough the bone age was advanced at the time of3 q" ?7 J3 I) h6 g
diagnosis, the child had a normal growth velocity at% ~& e5 s$ Q1 M B& ?+ \8 ]
the follow-up visit. It is hoped that his final adult: Q0 ~2 I' d$ s
height will not be affected. w( k5 j9 v$ B7 B( k
Although rarely reported, the widespread avail-. f, w/ S3 Y7 N
ability of androgen products in our society may
- S. r& D8 j& tindeed cause more virilization in male or female$ N. ? j) N; [
children than one would realize. Exposure to andro-4 f( E) H0 d! W" s- A/ {
gen products must be considered and specific ques-3 D% E# D k9 J4 n/ R2 N( R
tioning about the use of a testosterone product or
. u n/ G' u3 Q3 i6 \gel should be asked of the family members during
' |) K2 @- N' b, ^+ Kthe evaluation of any children who present with vir-
; X# l& n4 G8 Nilization or peripheral precocious puberty. The diag-6 E; v( ?5 E q2 `$ b- C6 r
nosis can be established by just a few tests and by
) m* s5 B0 ^1 i+ C1 fappropriate history. The inability to obtain such a5 v+ I6 V% L, Y1 `: V
history, or failure to ask the specific questions, may# ]8 U* t' @( G
result in extensive, unnecessary, and expensive+ ?7 ?, s2 O& x& T
investigation. The primary care physician should be, e! u9 P( N0 C. N5 \7 V9 E
aware of this fact, because most of these children; z' q9 n+ [; W. Z9 h9 k
may initially present in their practice. The Physicians’3 m6 a5 Z3 \9 e
Desk Reference and package insert should also put a
: g. O$ k, `! \1 r# A6 [warning about the virilizing effect on a male or' l" t, o P( N' F) x1 E
female child who might come in contact with some-
" f' q( L1 S3 k) Y3 N+ xone using any of these products.6 v- A% s+ i5 q
References
% i8 s, V7 p& p7 x0 d8 [& p1. Styne DM. The testes: disorder of sexual differentiation
( Q: }$ Z1 h/ _0 v2 dand puberty in the male. In: Sperling MA, ed. Pediatric# @' n5 f: x1 U' j" X
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
7 G5 d$ Q- ~# A. v% r) p$ e* F+ @2002: 565-628.
4 E c5 }% Q: I! W3 x# L1 B2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
+ x7 C1 V- o: L+ \3 i2 M6 ~puberty in children with tumours of the suprasellar pineal |
|