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Sexual Precocity in a 16-Month-Old
# q6 _5 o. \( U C1 O' A% Z! R& kBoy Induced by Indirect Topical
: d8 V" v* P7 KExposure to Testosterone4 |" R/ m% U9 h* s! h2 i
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
, y- n$ e- f/ _! `+ Yand Kenneth R. Rettig, MD1
9 V, ?$ p' [; m+ O+ oClinical Pediatrics
9 T5 C' a/ s/ K1 BVolume 46 Number 6
9 |/ w; i* e% q+ cJuly 2007 540-5430 u3 v/ S, T. E' X
© 2007 Sage Publications
8 \6 L3 | z( s: f6 q/ w10.1177/0009922806296651
. F4 D; ]) d- J. P8 j7 fhttp://clp.sagepub.com) n/ \) O# K. H, @& t
hosted at
& _! T& w1 ^# ?* P2 w/ ^7 f9 h4 A# Jhttp://online.sagepub.com
5 g$ C, ?# E1 A" I0 [" RPrecocious puberty in boys, central or peripheral,
1 @% e/ u0 y6 n1 [$ cis a significant concern for physicians. Central
" [/ W8 b4 Q' Y! u7 u ?6 vprecocious puberty (CPP), which is mediated
6 H* O- S( z9 K' kthrough the hypothalamic pituitary gonadal axis, has! p- O+ F/ Q6 m
a higher incidence of organic central nervous system& i) ^/ J: @( y5 k0 V7 \
lesions in boys.1,2 Virilization in boys, as manifested& ~, r0 W# k0 o0 n4 J9 P
by enlargement of the penis, development of pubic& V t" D7 J1 f7 w1 w
hair, and facial acne without enlargement of testi-" V" ^% @; U% `. j, C
cles, suggests peripheral or pseudopuberty.1-3 We
8 j& t/ ^9 a2 \8 P9 G+ ], V. rreport a 16-month-old boy who presented with the
# Q" `% \& R) T2 ?# jenlargement of the phallus and pubic hair develop-3 R( _* K3 x$ [( l7 \
ment without testicular enlargement, which was due& e2 V( g/ S! t* K) I! g
to the unintentional exposure to androgen gel used by
. D* v% Q0 [# s2 K, ?5 b0 }- ythe father. The family initially concealed this infor-
% g( i2 G9 J- E% P0 a" ?" `mation, resulting in an extensive work-up for this
4 K/ U% `9 w! D, K* U. K- }child. Given the widespread and easy availability of$ s& h/ R( A6 R4 c+ [( J& t! w
testosterone gel and cream, we believe this is proba-
6 _* E0 u7 ~' ^. }- u! W7 t7 m6 nbly more common than the rare case report in the9 r% ]! Z1 }+ |% v s
literature.4
: S2 @. `" d% K3 s5 L# l/ lPatient Report0 _6 M/ [- e# |% M! x
A 16-month-old white child was referred to the$ o, `- F: K6 Q5 `" t7 d, `
endocrine clinic by his pediatrician with the concern
9 Q6 S9 [' }8 E7 D5 j1 y- |' ?3 mof early sexual development. His mother noticed0 j2 v! |! Z( _0 B v" G
light colored pubic hair development when he was
9 J1 c I ^. F" PFrom the 1Division of Pediatric Endocrinology, 2University of
! R% T) x) q9 G7 J+ F& |% I) K3 W+ ISouth Alabama Medical Center, Mobile, Alabama.9 H& i$ I, }+ h+ l4 S' U) ^. e) O
Address correspondence to: Samar K. Bhowmick, MD, FACE,: w% Z/ j2 K R) ?# [. Z
Professor of Pediatrics, University of South Alabama, College of
4 \2 N: Z; ^6 |; Y5 r5 VMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
( r' N6 [9 W. ce-mail: [email protected].
( r! Z& D) [0 f# [& O8 M. qabout 6 to 7 months old, which progressively became
$ h- Y, }1 v0 k, n8 w: A: hdarker. She was also concerned about the enlarge-9 u9 f8 x Z* i" S
ment of his penis and frequent erections. The child
( `; `6 Y8 d0 d5 P! _was the product of a full-term normal delivery, with
* p: I5 l7 `& Q+ ga birth weight of 7 lb 14 oz, and birth length of
& k. ?! c6 A" v9 @+ [! b20 inches. He was breast-fed throughout the first year
4 t7 v; m( j) ~& w0 Z; Iof life and was still receiving breast milk along with
: V3 g0 F; c. ysolid food. He had no hospitalizations or surgery,, g. Z9 p6 y/ O3 f% f7 i: i$ l/ I- t
and his psychosocial and psychomotor development2 }5 V) |9 R& u9 k, D7 ~! D8 E* o4 v
was age appropriate.5 u/ @8 u& n/ {# k ` X$ @
The family history was remarkable for the father,
2 }$ t+ J. l+ ?* Q6 `/ B% lwho was diagnosed with hypothyroidism at age 16, y% c3 e4 j# Z+ Z8 T" d
which was treated with thyroxine. The father’s$ Q5 i, G: n, z" f
height was 6 feet, and he went through a somewhat( N) ^ i5 S7 [3 H1 _
early puberty and had stopped growing by age 14.+ j( M: U( _& y) |6 I
The father denied taking any other medication. The
$ R. }# H! _/ h' h: uchild’s mother was in good health. Her menarche
. N( ]. X5 \$ O) a7 `6 p( Q& W) I" mwas at 11 years of age, and her height was at 5 feet* H9 r& B9 R8 H
5 inches. There was no other family history of pre-
/ v h2 x; c, {1 J jcocious sexual development in the first-degree rela-
9 C2 F7 q' H' c3 L0 N& Utives. There were no siblings.
0 l) S& c! {) U: m# q yPhysical Examination4 E" @2 X* G$ p/ |- G
The physical examination revealed a very active,
0 I" f. y6 e2 Pplayful, and healthy boy. The vital signs documented% P! T! m# b3 [6 B& U, B3 B9 c5 I
a blood pressure of 85/50 mm Hg, his length was- [% i6 f ] W+ c
90 cm (>97th percentile), and his weight was 14.4 kg
& O+ i0 \( M s ?(also >97th percentile). The observed yearly growth8 w `* m& ~1 b- n: e. \
velocity was 30 cm (12 inches). The examination of5 E: @% C, p. G$ J" k+ m
the neck revealed no thyroid enlargement.) t% \+ r- t7 L) f9 a
The genitourinary examination was remarkable for, V, _! a8 g5 z2 \, e+ R
enlargement of the penis, with a stretched length of7 t. e+ Z- W& [
8 cm and a width of 2 cm. The glans penis was very well/ a3 p1 b8 T7 e6 m8 Q3 r4 i, K/ Y
developed. The pubic hair was Tanner II, mostly around5 ~5 E- C0 f+ }1 G2 |0 y4 } ?
540' i1 W, c( W, Z5 v3 J! x
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from( ^, \, A2 W: [5 ?+ d% c
the base of the phallus and was dark and curled. The
0 Z1 q1 O$ a9 l! _8 O jtesticular volume was prepubertal at 2 mL each.2 z( s4 x( `; d5 `
The skin was moist and smooth and somewhat
, F5 ~' @& e7 Q9 eoily. No axillary hair was noted. There were no4 @5 ]! @, A1 r- ]" N! ]
abnormal skin pigmentations or café-au-lait spots.
& D+ u6 y' S! K- h, w+ uNeurologic evaluation showed deep tendon reflex 2+/ n4 E' z& y- p+ }7 J W, S
bilateral and symmetrical. There was no suggestion0 m6 p, y7 G& u [
of papilledema.
5 s5 m; B! Y6 U) c: P4 f2 X+ f8 RLaboratory Evaluation0 @9 P" Z! y& h3 H G
The bone age was consistent with 28 months by5 C7 N; n5 K9 \5 v( y
using the standard of Greulich and Pyle at a chrono-7 D8 o: L% J* h8 R
logic age of 16 months (advanced).5 Chromosomal
5 k0 v% u# Z+ h: i( ?2 |. k/ ckaryotype was 46XY. The thyroid function test
6 f$ U; a0 ?0 R7 }3 x5 Qshowed a free T4 of 1.69 ng/dL, and thyroid stimu-' w; U( o8 }% f, \0 W9 T
lating hormone level was 1.3 µIU/mL (both normal).$ x% Z0 O! x: v$ n' [
The concentrations of serum electrolytes, blood
9 o _% H5 {' B0 r. h4 eurea nitrogen, creatinine, and calcium all were0 s* E, t+ S% @+ s
within normal range for his age. The concentration
2 j$ d6 L" K$ Q+ w% E0 pof serum 17-hydroxyprogesterone was 16 ng/dL
1 ]4 Z$ ?, D8 Y. L( w(normal, 3 to 90 ng/dL), androstenedione was 20. ^- ^; t0 k- W$ I
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
5 H4 [* {+ T9 w% t0 |terone was 38 ng/dL (normal, 50 to 760 ng/dL),, Q! J1 w" A z! p# T
desoxycorticosterone was 4.3 ng/dL (normal, 7 to- k+ O& t( F$ w8 H S3 x
49ng/dL), 11-desoxycortisol (specific compound S)
/ l0 K5 {; S2 i; c4 ^1 nwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
5 T6 M4 D0 ]: \1 ^; Ptisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
8 x$ v# d* k J% B7 A% J3 m2 Dtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),; B$ e H* ]; u% V; h: C, ]. e
and β-human chorionic gonadotropin was less than- n* ~6 M: y. G7 o- s
5 mIU/mL (normal <5 mIU/mL). Serum follicular9 V+ v+ w! W1 L4 n; a9 y
stimulating hormone and leuteinizing hormone
+ R* C) ^! H/ Pconcentrations were less than 0.05 mIU/mL
2 ], u3 z8 z) b9 j3 f* X(prepubertal).
3 h9 y V }0 X/ N! R3 F+ ?4 YThe parents were notified about the laboratory+ W6 T: s# l& u' I( m% Y
results and were informed that all of the tests were7 R; H2 _8 O' R( `
normal except the testosterone level was high. The, G. L- ~+ {6 g2 F) x! g5 T
follow-up visit was arranged within a few weeks to
3 H+ g. i% X6 ]. U1 S. {( sobtain testicular and abdominal sonograms; how-
4 J- S' \( S9 s: }$ xever, the family did not return for 4 months.
1 K9 F) r" g1 wPhysical examination at this time revealed that the
`7 h9 a, ]" B3 |( J9 R, k( hchild had grown 2.5 cm in 4 months and had gained
( v2 {6 v% B- A' \* z; j" w2 kg of weight. Physical examination remained+ a+ V T, X) Z/ e! d0 m
unchanged. Surprisingly, the pubic hair almost com-
* U/ g/ [" M6 ]. I3 X7 \" n: hpletely disappeared except for a few vellous hairs at7 z- g* E% d' c. l( |
the base of the phallus. Testicular volume was still 29 v4 Q6 v3 E0 H" O
mL, and the size of the penis remained unchanged.2 `# z1 |1 w% M p$ ^( C
The mother also said that the boy was no longer hav-
6 n; P. t) P8 h0 _ K2 c" hing frequent erections.4 k5 ], { P( y1 [; n! ~
Both parents were again questioned about use of; V6 V- Y9 B+ d6 x
any ointment/creams that they may have applied to, N. b/ L: @$ O8 D* j
the child’s skin. This time the father admitted the
* d# `* J1 `, B0 q( W4 L( WTopical Testosterone Exposure / Bhowmick et al 541
: L$ T5 |- g% `. fuse of testosterone gel twice daily that he was apply-
, t/ N7 r! A, n2 f( ning over his own shoulders, chest, and back area for8 G7 N2 ^5 G6 @9 W& d
a year. The father also revealed he was embarrassed
# m' F( m) {/ gto disclose that he was using a testosterone gel pre-! m" s" K/ T6 E( k; a3 N+ w
scribed by his family physician for decreased libido
3 ~* I! k/ v! ?8 X0 m) t) c Gsecondary to depression.: c1 ]" W# D8 q$ g( Y# \
The child slept in the same bed with parents.. {2 [$ h4 A* B0 X) A* n
The father would hug the baby and hold him on his
$ @$ r1 T/ a J' g; @5 mchest for a considerable period of time, causing sig-4 ^! `# |/ u h3 x
nificant bare skin contact between baby and father.4 V# R6 W+ x! p. t- M% b
The father also admitted that after the phone call,
$ W( P0 K% ?% H) q& z3 e2 \when he learned the testosterone level in the baby4 P# X9 s& K) f% T9 ~! C' w
was high, he then read the product information/ y; o5 R$ x$ r7 m
packet and concluded that it was most likely the rea-/ D4 f! Y# p5 Z& U- B S r0 o
son for the child’s virilization. At that time, they4 q$ e$ q& r: |3 R6 D
decided to put the baby in a separate bed, and the6 C+ Z- z v6 }* F' O& Y
father was not hugging him with bare skin and had
- |- I, d& q L) o8 a, L! Ubeen using protective clothing. A repeat testosterone" f' F6 ~1 x: {' C5 X% B
test was ordered, but the family did not go to the" z& a0 V; C* S
laboratory to obtain the test.) m C+ [' D5 Z1 O
Discussion
1 u$ V) S3 G+ }4 {5 A# lPrecocious puberty in boys is defined as secondary* {5 e# k: L9 |6 ^6 F; x8 n
sexual development before 9 years of age.1,4
9 T2 R; T6 K0 oPrecocious puberty is termed as central (true) when
0 C1 ^0 ~0 ]% e# Kit is caused by the premature activation of hypo-2 o6 f; D6 l' H. ^4 [
thalamic pituitary gonadal axis. CPP is more com-
4 J/ O9 Q1 n/ @' bmon in girls than in boys.1,3 Most boys with CPP( _, q8 k. i' I2 ]4 I" t m) ]$ r
may have a central nervous system lesion that is" s4 y5 J" I. q$ K
responsible for the early activation of the hypothal-
9 x! i9 `5 o8 [1 c, ~; [$ |amic pituitary gonadal axis.1-3 Thus, greater empha-/ }( c, Z+ x. Y3 k( f
sis has been given to neuroradiologic imaging in
+ x9 `4 M6 S/ r4 a% H& c9 nboys with precocious puberty. In addition to viril-4 n9 y6 A& ?8 t! q
ization, the clinical hallmark of CPP is the symmet-% C4 Q- s, w* z7 b
rical testicular growth secondary to stimulation by
* ~5 _( \1 v( k; K) Zgonadotropins.1,3/ h. D% u' j) N, q3 R' t
Gonadotropin-independent peripheral preco-
( u# ^" e2 k1 v @/ U4 ~7 Hcious puberty in boys also results from inappropriate$ A; C2 A% p) B+ e: [
androgenic stimulation from either endogenous or
1 f. I) f, q+ z5 u! R |exogenous sources, nonpituitary gonadotropin stim-
* u! o) V# q' Oulation, and rare activating mutations.3 Virilizing
1 ^' L( `9 Z) Hcongenital adrenal hyperplasia producing excessive
( B( h% j# b7 ^adrenal androgens is a common cause of precocious, s" O# s1 L2 k
puberty in boys.3,4' B& v9 U) m% T6 z+ R
The most common form of congenital adrenal
& f% f/ {7 z$ u+ h" a& n- Ohyperplasia is the 21-hydroxylase enzyme deficiency.
/ S6 u7 U) z4 zThe 11-β hydroxylase deficiency may also result in4 O# |5 b# I, ^" n/ n; P1 Q; n
excessive adrenal androgen production, and rarely,0 G- p3 _+ N# Q1 i, l3 X7 z$ D, r
an adrenal tumor may also cause adrenal androgen, h: ]" u( Y0 y& b7 g: R/ _
excess.1,37 d2 b% Y: q7 G6 l
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
* [5 N( R5 K1 Y( ~' R6 S5 j1 l5 P542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
+ S+ s5 ^+ ~1 H" }A unique entity of male-limited gonadotropin-. b7 Z9 d1 J# M* Q% i
independent precocious puberty, which is also known
* ?& g$ E4 C3 o! Y1 }0 l# l) Das testotoxicosis, may cause precocious puberty at a, z' D8 `" w/ y, f* w
very young age. The physical findings in these boys
n+ }. x1 s# q) ^8 awith this disorder are full pubertal development," l1 Q. O) i1 T2 W& A
including bilateral testicular growth, similar to boys
$ X8 C2 B; P0 q; X5 Q6 C" d1 G6 F6 rwith CPP. The gonadotropin levels in this disorder
2 ~1 ~' B* L/ S; K2 p* O0 ]are suppressed to prepubertal levels and do not show
- W: U T. W- s" r: Kpubertal response of gonadotropin after gonadotropin-
$ }4 q9 T; o. s7 O% t# Lreleasing hormone stimulation. This is a sex-linked
( L4 \" r$ g% R. U% k5 c; a. F; W: vautosomal dominant disorder that affects only
! |% g" E- L3 \males; therefore, other male members of the family
$ e( c* A7 X& }/ T' m* y) Y5 Bmay have similar precocious puberty.3" m0 r$ A; Z* H+ H7 _- `
In our patient, physical examination was incon-$ Q3 [! \: ~. z, ^/ h& R- r3 o
sistent with true precocious puberty since his testi-$ r- l1 `+ t( `+ n$ A
cles were prepubertal in size. However, testotoxicosis
}2 t9 c& z t8 Swas in the differential diagnosis because his father! M8 _* D6 w( k! C8 j
started puberty somewhat early, and occasionally,
* {# X: b' F* V" @testicular enlargement is not that evident in the
- z2 S8 W( f9 e2 H. s3 E( { zbeginning of this process.1 In the absence of a neg-
3 j, m+ e: o6 I* L( I1 \9 g4 Z( O/ ?4 vative initial history of androgen exposure, our
& W6 ^7 m' d; k8 q3 Ubiggest concern was virilizing adrenal hyperplasia,
- m+ E& o/ B+ K2 I5 j! O" |# beither 21-hydroxylase deficiency or 11-β hydroxylase
; R; B" k0 N! ~( |+ a3 c8 Rdeficiency. Those diagnoses were excluded by find-
/ I0 u' g# e% z! r% C" fing the normal level of adrenal steroids.! H. l/ b) O9 q- @
The diagnosis of exogenous androgens was strongly5 @; x, F. S' _# ?* l# J Z
suspected in a follow-up visit after 4 months because4 v; A$ k# c2 h
the physical examination revealed the complete disap-
" z2 d6 G( w- K2 X0 ypearance of pubic hair, normal growth velocity, and
9 E0 F3 p4 J. |decreased erections. The father admitted using a testos-
6 a0 c, X8 F* N. hterone gel, which he concealed at first visit. He was
4 E( F' V I, Ausing it rather frequently, twice a day. The Physicians’ ^3 X$ J D0 ^/ J* i J
Desk Reference, or package insert of this product, gel or+ a, N2 o/ ~# r: `9 S6 B
cream, cautions about dermal testosterone transfer to
3 Z$ A: c$ n' Y7 b j! B. Zunprotected females through direct skin exposure.9 O1 @5 f( r* M, H: @0 v o
Serum testosterone level was found to be 2 times the
) z' B, J) G4 F9 \baseline value in those females who were exposed to
5 W. @0 h" u. ^' `even 15 minutes of direct skin contact with their male
1 ~- N4 o) c f! Z. cpartners.6 However, when a shirt covered the applica-
* L1 H; W5 p% Ttion site, this testosterone transfer was prevented.3 F0 }& E1 X5 f7 \8 \- [
Our patient’s testosterone level was 60 ng/mL,& ?- C4 ?5 a) O" t7 q: O0 v
which was clearly high. Some studies suggest that
8 j. k7 ] h8 ]5 b6 hdermal conversion of testosterone to dihydrotestos-
6 i6 A w2 H( Q3 {6 tterone, which is a more potent metabolite, is more
* S9 B) C0 A: R: hactive in young children exposed to testosterone
( Z8 e+ ?% K& ^0 S: aexogenously7; however, we did not measure a dihy-
* l2 g0 W) G8 r1 _' F, [; Kdrotestosterone level in our patient. In addition to
" m( ]4 s7 l J2 G; e0 e( N% tvirilization, exposure to exogenous testosterone in
! J5 p5 T6 ?9 |; |4 L* K0 bchildren results in an increase in growth velocity and
) N( E5 k2 S% E; R% M+ |advanced bone age, as seen in our patient.
6 Y( b! K6 F; y0 PThe long-term effect of androgen exposure during3 s T7 x# E' k
early childhood on pubertal development and final0 C6 Y) D i V: P* |" J% L9 D
adult height are not fully known and always remain: @- Q C7 v$ @# ?
a concern. Children treated with short-term testos-
! O$ S/ m- p2 J8 tterone injection or topical androgen may exhibit some4 I" d& o2 a) G2 K0 p7 R
acceleration of the skeletal maturation; however, after
9 Q7 F( [) y6 R2 h+ v! S- icessation of treatment, the rate of bone maturation6 N. w- Z6 n( t$ ?+ p8 `
decelerates and gradually returns to normal.8,9
" S1 z% y( Z0 o4 {% mThere are conflicting reports and controversy
) h0 x( k$ {, u' U3 a; u2 \! xover the effect of early androgen exposure on adult
/ l; k3 V' U* y2 |penile length.10,11 Some reports suggest subnormal
8 X7 `* n( Z$ q0 r) B& hadult penile length, apparently because of downreg-0 D) [( W5 l+ s6 i1 r/ H8 u! h6 L8 C
ulation of androgen receptor number.10,12 However,
, F: v# q' ]+ `# s1 HSutherland et al13 did not find a correlation between' S) j% G1 q9 @/ z2 ?8 M" u" E
childhood testosterone exposure and reduced adult
; Q6 D& d8 a' z! V. Q9 r0 upenile length in clinical studies.3 ^& a& [, W/ U8 M* ~0 S8 S
Nonetheless, we do not believe our patient is
. X) ~5 U6 [. g- k& Q dgoing to experience any of the untoward effects from5 Q( `' s1 H# K( \% y
testosterone exposure as mentioned earlier because9 ^8 o$ F/ g; U! I7 j
the exposure was not for a prolonged period of time.
7 Y8 z: A4 f: {9 \2 m bAlthough the bone age was advanced at the time of
" I0 J9 K7 U) K2 F2 W: j0 |" _diagnosis, the child had a normal growth velocity at( [# X; ?: ?: k2 Q
the follow-up visit. It is hoped that his final adult5 \' P. t9 S l1 T
height will not be affected.8 p, X2 T. r! z `8 \$ [
Although rarely reported, the widespread avail-
- ?, C5 ?2 I# z- dability of androgen products in our society may( a6 C; P) B( ~/ d6 _
indeed cause more virilization in male or female
/ v, v1 t, L; e! D# H4 U O5 @children than one would realize. Exposure to andro-
' n& x1 `+ k. r, i. tgen products must be considered and specific ques-# x# x7 c" q6 M( A( t1 M$ N8 ?; p
tioning about the use of a testosterone product or( n& e! e9 D L( Y
gel should be asked of the family members during
' O0 N$ l1 U& I8 k* T/ e i3 Pthe evaluation of any children who present with vir-
( e4 Q+ F% c! c+ q0 oilization or peripheral precocious puberty. The diag-
. ?6 [% `( Y5 jnosis can be established by just a few tests and by
; {8 J# R' {! P% pappropriate history. The inability to obtain such a5 F" L" w& H% z( B* u# H% ~2 ?: N
history, or failure to ask the specific questions, may
% t- }, D/ f# R* Oresult in extensive, unnecessary, and expensive
/ }/ o, p0 B" ginvestigation. The primary care physician should be
8 S2 y# j: V' |0 i" Qaware of this fact, because most of these children7 N; t) d* d. ]" y+ T" i& K2 B
may initially present in their practice. The Physicians’/ ]5 I: o) m8 J s. t5 `6 d
Desk Reference and package insert should also put a
% j) [# @; y; e! swarning about the virilizing effect on a male or2 h/ h0 x! T' O9 J/ D
female child who might come in contact with some-
* t, a) e9 V' R( _' D8 X- kone using any of these products., D, t5 q( G1 C
References8 F% N; V1 [: {( w* [
1. Styne DM. The testes: disorder of sexual differentiation5 o5 e$ U! x$ y
and puberty in the male. In: Sperling MA, ed. Pediatric% \% V& [5 D& ?" |( [! w9 S
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
+ \: {: J6 Q- X: l% ?% C+ Y; w2002: 565-628.0 q, A( K; N, r7 y
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious3 e0 H. ^6 j% k/ G: T
puberty in children with tumours of the suprasellar pineal |
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