- 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
0 m. S2 l0 {& I" n) V! O- mBoy Induced by Indirect Topical5 |2 u" r) S* B4 l+ I/ ?- f
Exposure to Testosterone
9 a h8 L6 @# [! V3 G; A2 cSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2. Z/ j$ i2 j2 I: R7 o+ R$ J3 C
and Kenneth R. Rettig, MD1% N5 z+ W5 P @) f# m, B$ o) Q9 `
Clinical Pediatrics3 K- O: t7 f% h' a5 O: r3 V1 B
Volume 46 Number 65 ]7 }8 F& _6 j; f# a, F% ?9 u
July 2007 540-5437 A c) e3 b/ `# Z% p8 X) o+ J
© 2007 Sage Publications. f( S- w7 P7 p0 f; m h J7 N
10.1177/0009922806296651# F" k# D) g. i% q
http://clp.sagepub.com; q- A8 R% O1 N8 Y: a% R
hosted at) R" s0 L/ x0 a! Z8 ?) K G
http://online.sagepub.com0 o" e1 S$ X+ c+ M+ P( g
Precocious puberty in boys, central or peripheral,
2 u% k6 B) F0 \8 a* J2 ]1 _is a significant concern for physicians. Central
8 {4 Q; d" Z& o# f/ V; Wprecocious puberty (CPP), which is mediated7 c+ \& S8 W* d- [' w
through the hypothalamic pituitary gonadal axis, has0 E" g9 D4 H/ J/ @' G' P r- ^
a higher incidence of organic central nervous system5 C( D' P8 X5 k7 B
lesions in boys.1,2 Virilization in boys, as manifested7 f, @6 W1 p# F
by enlargement of the penis, development of pubic/ a: I3 e5 q& K3 v2 o; n
hair, and facial acne without enlargement of testi-
" N1 }3 e' X' L5 lcles, suggests peripheral or pseudopuberty.1-3 We$ M/ u" }5 M% Y2 u! {
report a 16-month-old boy who presented with the5 ?1 t$ w6 h9 J. n0 Q
enlargement of the phallus and pubic hair develop-! d8 B: \' w7 p$ e4 v! M
ment without testicular enlargement, which was due$ |3 p$ d; S# @% d/ \) }0 l5 G7 M; }2 L
to the unintentional exposure to androgen gel used by! s1 ]9 h* c1 u9 y. P
the father. The family initially concealed this infor-( l3 n6 C" w. d2 C& d
mation, resulting in an extensive work-up for this
; q, _8 f+ I& }* ?# nchild. Given the widespread and easy availability of! Z& y' O; n: Z z7 Q4 q+ \3 x
testosterone gel and cream, we believe this is proba-
: j# I) Z' |5 J$ Z. ]bly more common than the rare case report in the
; |. E& q; g- U1 a3 b9 V4 q( gliterature.4) v3 }$ D! k( v' I
Patient Report3 m& B0 j+ t1 a. r/ V8 a. a, ]; |
A 16-month-old white child was referred to the
" _" u. U h/ b7 X& w8 d' Aendocrine clinic by his pediatrician with the concern
# x; a# [/ T I6 h# \1 O7 Sof early sexual development. His mother noticed% i0 m. P5 L: V
light colored pubic hair development when he was" t4 J- n+ ?* Y, D& I4 f; q
From the 1Division of Pediatric Endocrinology, 2University of0 K/ k+ w2 k0 K( T+ l
South Alabama Medical Center, Mobile, Alabama.% @7 Y. A: i; a; C% \# U" m
Address correspondence to: Samar K. Bhowmick, MD, FACE,) M7 J0 ~- |+ h1 G% ?' i* N1 b1 }
Professor of Pediatrics, University of South Alabama, College of% A/ w# ^: t4 o: y
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;& l# B- M7 O$ O7 D4 a
e-mail: [email protected].! F$ H2 m) {. z3 H1 f
about 6 to 7 months old, which progressively became9 L; c- E& n7 q
darker. She was also concerned about the enlarge- [/ s6 Z, {0 h# n
ment of his penis and frequent erections. The child, q ^: S' ?1 ]" @
was the product of a full-term normal delivery, with
8 u" ^% ~; a5 p* |# ga birth weight of 7 lb 14 oz, and birth length of
* \" f8 M$ B' L" c7 A# f/ U! F3 H20 inches. He was breast-fed throughout the first year5 d, H& D6 K6 f# q" H7 `+ R
of life and was still receiving breast milk along with
* R& Q& K6 e8 t# @4 Bsolid food. He had no hospitalizations or surgery,
' W% Q! }9 \% U+ [' i2 j' ^and his psychosocial and psychomotor development
6 `+ I/ C, ]% A1 g0 c' U/ Qwas age appropriate.
! d0 i+ |5 ?, N: s7 @- AThe family history was remarkable for the father, q- V& S* E U
who was diagnosed with hypothyroidism at age 16,
' u. R+ V+ Z* Rwhich was treated with thyroxine. The father’s
* @7 Z: ?$ }$ h4 I, Xheight was 6 feet, and he went through a somewhat" ?; [9 {- j& x3 g8 M
early puberty and had stopped growing by age 14.: ^2 T- R t7 B! O7 S
The father denied taking any other medication. The! d9 l& n# q1 S$ O2 e
child’s mother was in good health. Her menarche6 Y4 v4 J& X1 }# J6 A' v
was at 11 years of age, and her height was at 5 feet
: o, C* F2 I/ I2 T+ m- K5 inches. There was no other family history of pre-) w1 y9 C; v% c* p
cocious sexual development in the first-degree rela-
8 g- l/ X, J; d1 `- c1 ntives. There were no siblings.% f6 O! G( j& g$ x
Physical Examination) c# f7 ^4 _, Y X3 ~3 p
The physical examination revealed a very active,
+ N3 m& l4 d9 V5 Vplayful, and healthy boy. The vital signs documented. X# {; N4 w4 p
a blood pressure of 85/50 mm Hg, his length was
2 N8 ]: ]+ f# Y6 z; u2 W90 cm (>97th percentile), and his weight was 14.4 kg& Y6 F+ `1 l- S
(also >97th percentile). The observed yearly growth
2 q/ m* h }' V3 T6 z7 j- dvelocity was 30 cm (12 inches). The examination of
5 h$ x5 j- |; Kthe neck revealed no thyroid enlargement.* h3 c1 j5 `) F2 }
The genitourinary examination was remarkable for
- m$ @2 n9 a) h7 p }: A5 R) menlargement of the penis, with a stretched length of
/ \* f) R6 q7 J( F9 g8 g& Y8 cm and a width of 2 cm. The glans penis was very well
6 H' X5 i3 [0 `$ M6 Q; |developed. The pubic hair was Tanner II, mostly around/ [; X9 a) s. A# W8 D' N
540% r8 V* _- B9 p6 R
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
+ g* n v* a# M3 q+ @! ?the base of the phallus and was dark and curled. The/ D+ A+ P0 l. z
testicular volume was prepubertal at 2 mL each.
, [; m7 `6 d+ e. h, QThe skin was moist and smooth and somewhat
6 i2 \; R" [% u$ _- C% u' Doily. No axillary hair was noted. There were no) R* L; j; u. V( f
abnormal skin pigmentations or café-au-lait spots.3 h) I( t4 a Y2 G
Neurologic evaluation showed deep tendon reflex 2++ x: k) H( ^- l7 s0 P! n
bilateral and symmetrical. There was no suggestion
$ D% e N. n. e) R2 M. sof papilledema. `+ g0 {0 U4 R8 K
Laboratory Evaluation& u* A% R5 E8 d, g( I, ~# e2 ^
The bone age was consistent with 28 months by# u$ k* I" @9 N7 Q. `# P! V, l9 H
using the standard of Greulich and Pyle at a chrono-& ]7 o; h8 L+ B2 V
logic age of 16 months (advanced).5 Chromosomal3 Q& S, a6 w& M! H$ ]* O* e) [
karyotype was 46XY. The thyroid function test
5 [" t+ i$ j" v) s% p6 bshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
) {; r/ o2 O; o2 h t7 t( `' Dlating hormone level was 1.3 µIU/mL (both normal).+ _+ T" i" j. t. v
The concentrations of serum electrolytes, blood# o& q* O. M1 b7 V" n! m
urea nitrogen, creatinine, and calcium all were: ^2 D) f' W. u# E7 W3 I4 z( o! Q
within normal range for his age. The concentration
( Z& }0 L+ K) H$ B4 @7 U7 E5 H3 gof serum 17-hydroxyprogesterone was 16 ng/dL# y$ H2 k# v2 T; G
(normal, 3 to 90 ng/dL), androstenedione was 204 q$ s$ v3 G# e D& c
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-& q( b0 M% f R+ A; Y
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
3 t+ u9 O* ^- P ?! cdesoxycorticosterone was 4.3 ng/dL (normal, 7 to# Y% _0 ~' p4 |6 y1 m5 H% Y
49ng/dL), 11-desoxycortisol (specific compound S)% W2 D+ S" H0 B8 a/ Z$ P1 b! {
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
& _! R. h: K5 v8 w; e& utisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
6 Y+ F! \' _; ~, q" vtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
2 N, p! [, Q( F4 }1 Wand β-human chorionic gonadotropin was less than
! V/ N2 r+ ^' ^7 E5 mIU/mL (normal <5 mIU/mL). Serum follicular% ^0 u3 o2 s6 n1 {
stimulating hormone and leuteinizing hormone1 k, Y ]9 |) t7 ~ m
concentrations were less than 0.05 mIU/mL# |* {: w# z# q% e
(prepubertal).
# Z! N( E6 P. e4 {* Y. CThe parents were notified about the laboratory
+ ]1 s: S0 A2 F+ l( ]# q# }$ vresults and were informed that all of the tests were
, Z! u1 Z. ]0 O3 H! Ynormal except the testosterone level was high. The
' |3 `+ S+ p$ f: g. m4 {5 hfollow-up visit was arranged within a few weeks to2 `# Y0 n& J4 F4 E' e
obtain testicular and abdominal sonograms; how-& c: L6 f7 b5 @+ ]
ever, the family did not return for 4 months.+ @! w- o8 F2 V
Physical examination at this time revealed that the4 T& N g4 b5 Y& j0 c
child had grown 2.5 cm in 4 months and had gained" ?5 v2 _9 d" Y- r/ T% N
2 kg of weight. Physical examination remained
4 u9 p7 I9 r" nunchanged. Surprisingly, the pubic hair almost com-# t& W' m; M: f; Y6 L$ ]8 w
pletely disappeared except for a few vellous hairs at; T, }4 w5 i0 x9 n% r% H8 [
the base of the phallus. Testicular volume was still 2
/ g9 Q6 R$ _4 umL, and the size of the penis remained unchanged.
+ N ]6 y% p$ m' O2 Z. }/ i! XThe mother also said that the boy was no longer hav-3 j. [- z- v* G
ing frequent erections.
6 @3 ^/ Z/ y2 `- l8 i! O3 N# B/ WBoth parents were again questioned about use of. L6 ~! R- U1 x$ f# ^) A' Q* w( ?
any ointment/creams that they may have applied to5 i+ e! L! n, x
the child’s skin. This time the father admitted the
4 F8 Q; C8 x2 R8 f3 M0 RTopical Testosterone Exposure / Bhowmick et al 5411 n- [. c% `6 P0 W6 ?( R
use of testosterone gel twice daily that he was apply-
- f' s2 q+ E% u$ R$ `2 }ing over his own shoulders, chest, and back area for9 {) N2 C C$ w
a year. The father also revealed he was embarrassed
# \# m( o+ R) J z# Cto disclose that he was using a testosterone gel pre-
" q; `% _( |; i- I2 \4 Z6 hscribed by his family physician for decreased libido
" C' Y# q; Z3 \' X' g! d+ `secondary to depression.
6 n% m# o: ?& K9 D# w k8 JThe child slept in the same bed with parents.( D- j4 P. F4 j" y
The father would hug the baby and hold him on his* z- r: s: o9 t
chest for a considerable period of time, causing sig-
6 T0 n% {, V3 e3 Z* o) G/ ^nificant bare skin contact between baby and father.1 s& S+ h! f5 a2 x) ]+ G8 Y$ n
The father also admitted that after the phone call,5 S2 ?& F" c! A P
when he learned the testosterone level in the baby
0 ~2 G, _1 ^/ L- p6 C5 Uwas high, he then read the product information
- v' H/ F$ V, g* z0 mpacket and concluded that it was most likely the rea-
3 y+ _" Q; P0 K* h8 zson for the child’s virilization. At that time, they
! C1 p' b1 E5 B2 D) [; A' Bdecided to put the baby in a separate bed, and the6 G/ _$ C9 ]2 W$ L; }
father was not hugging him with bare skin and had
3 S; A' l* t; G& p) Nbeen using protective clothing. A repeat testosterone
) l: f( H3 H/ k ftest was ordered, but the family did not go to the$ L1 G) t$ a; l/ d5 u' `
laboratory to obtain the test.
$ P; O% r- r, g1 |7 F" @ W8 ?3 qDiscussion c3 y4 G N9 g7 y
Precocious puberty in boys is defined as secondary
1 D7 Q+ h2 ]! A9 v# r: qsexual development before 9 years of age.1,4
" X+ k. D# V: T$ v9 nPrecocious puberty is termed as central (true) when
! f% d: a- L1 K+ J8 {* git is caused by the premature activation of hypo-6 ?8 |6 X& p) y( \$ d0 S0 x. u
thalamic pituitary gonadal axis. CPP is more com-
' C7 ?" E4 i4 x# {9 Umon in girls than in boys.1,3 Most boys with CPP
; L9 z+ N1 ]+ ]! nmay have a central nervous system lesion that is2 @) v7 `; k3 J4 ]
responsible for the early activation of the hypothal-+ l; u( |- _ q: T5 @1 V
amic pituitary gonadal axis.1-3 Thus, greater empha-& t" K% G9 |" Z6 E- D
sis has been given to neuroradiologic imaging in
" H- _; u5 {- X' z5 d" E: `1 I. o: fboys with precocious puberty. In addition to viril-- k" S( T& ?6 J% l( y) x/ |
ization, the clinical hallmark of CPP is the symmet-
5 |5 Y$ Q. R( J0 i# jrical testicular growth secondary to stimulation by# p, z" T& o; Y3 v6 s& K) k
gonadotropins.1,31 o0 j2 j# i% t3 k
Gonadotropin-independent peripheral preco-
# Y. Y2 G; {" k1 e* Ecious puberty in boys also results from inappropriate
$ e; I: K& n) D( u# vandrogenic stimulation from either endogenous or
, V! V, S, X* ~2 G) z: j& _( ~: xexogenous sources, nonpituitary gonadotropin stim-3 Z/ D/ a, |! L% F5 ]0 i
ulation, and rare activating mutations.3 Virilizing- z, t" j ]# v& j* A
congenital adrenal hyperplasia producing excessive" b$ d- m$ x* m( F+ X7 }' ]
adrenal androgens is a common cause of precocious+ r+ ~0 B3 o' ]6 {" P/ v, S
puberty in boys.3,4$ G* F! |" s, x3 ?/ D ?
The most common form of congenital adrenal$ h! E6 p ]8 Q+ I+ d; i8 B
hyperplasia is the 21-hydroxylase enzyme deficiency.
. V9 w4 C9 p) ^The 11-β hydroxylase deficiency may also result in2 R5 \4 _/ h8 K. ?
excessive adrenal androgen production, and rarely,
* p( @7 q1 w5 J6 q; J0 ]) {8 ban adrenal tumor may also cause adrenal androgen
) K# H5 m) e0 H# `. W( @excess.1,3% b$ K) _9 w8 K$ C7 W. ~
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from, p# S! @+ j, k D N( R) K& |
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
. f& b) b2 q( b) qA unique entity of male-limited gonadotropin-
- M7 y+ S- ^9 \0 w$ _% yindependent precocious puberty, which is also known
9 o$ S6 i) y m- Z9 A1 l5 Was testotoxicosis, may cause precocious puberty at a0 w" T3 K% [( X- h
very young age. The physical findings in these boys
/ j& Y+ S/ ]1 u) Hwith this disorder are full pubertal development,7 e; a4 J# S) e& c. }" b+ n
including bilateral testicular growth, similar to boys2 n9 d" o! i$ c& Q: ^+ n [
with CPP. The gonadotropin levels in this disorder
3 S$ ?+ Q* n+ Mare suppressed to prepubertal levels and do not show2 P3 Y) X& s; R
pubertal response of gonadotropin after gonadotropin-' o# Q1 R% t" z; X7 B) ]
releasing hormone stimulation. This is a sex-linked& H2 {- c( o) A7 ~) G$ j
autosomal dominant disorder that affects only5 S8 y8 C0 k, _) J! K
males; therefore, other male members of the family
7 \( v& V8 }3 b- G! w! t3 umay have similar precocious puberty.3
9 Q; z6 Q: w2 \& rIn our patient, physical examination was incon-% d! Z/ O5 g+ q3 Q
sistent with true precocious puberty since his testi-! w" P) K4 b5 m* M. ^* W4 t [
cles were prepubertal in size. However, testotoxicosis! G, k( i5 v# Z5 i4 }
was in the differential diagnosis because his father7 c4 H+ j/ ^0 m% @8 c6 k
started puberty somewhat early, and occasionally,0 k. o" I M* u5 q8 ^* E% z
testicular enlargement is not that evident in the$ u% d: p5 y9 d, m" H9 {
beginning of this process.1 In the absence of a neg-
2 v+ V. P# m) s+ X7 W) R Sative initial history of androgen exposure, our
9 R% m( b6 s2 I2 s# m9 Vbiggest concern was virilizing adrenal hyperplasia, T7 z- W9 T2 Z* P4 Y5 `3 H+ H
either 21-hydroxylase deficiency or 11-β hydroxylase
6 ^! H. s, J7 ?% @deficiency. Those diagnoses were excluded by find-& G5 J; | o# M) e) [
ing the normal level of adrenal steroids.) [9 m( p7 u3 T& U1 C
The diagnosis of exogenous androgens was strongly
8 t9 F- M1 Q j9 dsuspected in a follow-up visit after 4 months because( g E; a& u& p0 f$ B
the physical examination revealed the complete disap-
& t, a2 g% {2 G, u' y0 apearance of pubic hair, normal growth velocity, and
+ O8 l/ V. t% O0 d5 ^decreased erections. The father admitted using a testos-- r+ A+ j! W$ q ^. G8 O
terone gel, which he concealed at first visit. He was3 v: h" \/ ~: { F4 i2 r; D/ {. Z6 v# E
using it rather frequently, twice a day. The Physicians’; M- v4 R% z* X
Desk Reference, or package insert of this product, gel or
% U0 W$ Y6 g$ \5 \0 R0 [cream, cautions about dermal testosterone transfer to! W9 X$ f3 ]' L, Q& E
unprotected females through direct skin exposure.
. X7 W2 j" T: E6 X8 [, OSerum testosterone level was found to be 2 times the$ s* r; R, N, s
baseline value in those females who were exposed to
2 t) s* E, j* A- |even 15 minutes of direct skin contact with their male' t" C7 z I4 u$ H
partners.6 However, when a shirt covered the applica-. k9 d" ]* l; k$ d' S
tion site, this testosterone transfer was prevented.8 v" c; {% R4 o) L' K$ n
Our patient’s testosterone level was 60 ng/mL,
# U1 p( s7 d/ y+ } `( xwhich was clearly high. Some studies suggest that D) \2 S2 t0 y, {( A
dermal conversion of testosterone to dihydrotestos-$ p( P9 n6 d( K' ^" t# L
terone, which is a more potent metabolite, is more
Y! ?6 ]! C+ ~8 ~. Cactive in young children exposed to testosterone3 A! R& d2 U9 f
exogenously7; however, we did not measure a dihy-$ p4 ?$ d- t" W1 W$ e! ~9 B
drotestosterone level in our patient. In addition to
6 {( L. t- z ^+ `0 w4 w0 Q# w8 Wvirilization, exposure to exogenous testosterone in; s- l( {6 L1 ?$ C7 K0 S- G* B
children results in an increase in growth velocity and
$ l* {/ z1 Z6 U# Badvanced bone age, as seen in our patient.' |7 Q( i- r5 [6 X# K9 _+ E" a
The long-term effect of androgen exposure during4 H/ Q" X5 W& R5 s
early childhood on pubertal development and final
& o, E0 u' p+ f8 D4 e8 e5 uadult height are not fully known and always remain7 Y' ?5 C* M$ o- L9 y9 n% D
a concern. Children treated with short-term testos-1 `3 P5 H+ g7 ~ j- u8 ]% H
terone injection or topical androgen may exhibit some# C- {7 i3 `) r y0 A# C3 x& x
acceleration of the skeletal maturation; however, after
/ k* V- `+ ]' ~& T5 b: x# ocessation of treatment, the rate of bone maturation# c5 \5 [ G, R" T+ ?; E
decelerates and gradually returns to normal.8,98 W: l g# O" x. F! X
There are conflicting reports and controversy0 Z5 s6 m8 E$ M( m& Q
over the effect of early androgen exposure on adult
9 T, m2 v, \5 _/ D& ipenile length.10,11 Some reports suggest subnormal
3 e$ b8 _8 Z& {; U3 I. i& h ~" n$ X; radult penile length, apparently because of downreg-1 O- o4 b1 P& y
ulation of androgen receptor number.10,12 However,; ]" w; Y' _6 H6 b: ^8 B' T" U
Sutherland et al13 did not find a correlation between
6 C( B2 ^ X# ?: T! Vchildhood testosterone exposure and reduced adult" g( [9 @# d1 K6 `( i
penile length in clinical studies.
7 n* F# f0 X: v( S/ J; pNonetheless, we do not believe our patient is: n8 o/ b$ M; u0 q2 m5 [: y
going to experience any of the untoward effects from7 o* H* X& o$ g+ e
testosterone exposure as mentioned earlier because
/ y0 Z& L9 c2 q: cthe exposure was not for a prolonged period of time.4 l9 C$ G! J4 \ S" E4 z
Although the bone age was advanced at the time of- L" s }( {9 X1 G& B
diagnosis, the child had a normal growth velocity at
0 d* h3 B9 ^- k3 `; Qthe follow-up visit. It is hoped that his final adult: `3 e0 \7 }0 U( E p
height will not be affected.
# ~% p& h! n" [1 F5 [. v( hAlthough rarely reported, the widespread avail-5 `! |! ^1 G( T; I; C
ability of androgen products in our society may
3 B0 g# t, V. R! Jindeed cause more virilization in male or female, Z. ^% d: w& Y/ X' J
children than one would realize. Exposure to andro-
" L1 J# X! m( i/ X! i- Vgen products must be considered and specific ques-
6 F- ^+ d9 D9 M3 q% l+ ]0 i) Mtioning about the use of a testosterone product or8 F( C/ f8 |; e0 g c/ q
gel should be asked of the family members during
' o7 n0 H4 M. V9 [. _the evaluation of any children who present with vir-
) j; ]/ W! d8 {0 q) u1 W3 Ailization or peripheral precocious puberty. The diag-+ S. p2 I. O2 V9 E/ m
nosis can be established by just a few tests and by
( n* L' ^( j9 A* _. F: b3 X0 S( Pappropriate history. The inability to obtain such a
) F) D: }9 ~& i# r. L1 }2 ]& nhistory, or failure to ask the specific questions, may& w6 z, G" ?7 x3 ]% v
result in extensive, unnecessary, and expensive* M: U$ V$ m0 q
investigation. The primary care physician should be
: L0 _ ? @( r: q- Vaware of this fact, because most of these children
' a/ B: M# C6 ]may initially present in their practice. The Physicians’
* @; T" K6 b5 d2 Q# B7 ]( \Desk Reference and package insert should also put a
0 l c0 W5 E" H& R: Y" m% Kwarning about the virilizing effect on a male or
( i% ?+ K5 I. t# afemale child who might come in contact with some-# t q) \$ B) s, b7 f* Z, e; z6 m ^
one using any of these products.
/ _8 C! |! s8 ^5 } zReferences
: x3 h% j5 J% v2 {0 \% C1. Styne DM. The testes: disorder of sexual differentiation2 B4 I+ C6 q6 w ?/ V! n
and puberty in the male. In: Sperling MA, ed. Pediatric/ y8 Q Y6 m7 I8 W2 b
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
/ `" ~3 `* R( L7 Q/ f' b/ }2002: 565-628.; u- W7 `, @' f5 q6 A! k1 b
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious& v: X1 C( ^/ H0 \
puberty in children with tumours of the suprasellar pineal |
|