- 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
% s0 _( C: I2 | t. {3 X6 bBoy Induced by Indirect Topical' b" O5 o) l& E- h7 N! \0 t, f S
Exposure to Testosterone
6 e2 ]" R- f8 K+ b) M! FSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2" i9 S. H5 X V: Q) M
and Kenneth R. Rettig, MD10 q# C a1 ]; |+ e$ \! E
Clinical Pediatrics% X9 h. u: u' x& I* ^8 W/ M
Volume 46 Number 6 G2 n) x9 K9 W" I
July 2007 540-543
2 j8 K2 A0 \- s. l% R* `7 @* p© 2007 Sage Publications7 {+ S6 M& n* E# m
10.1177/0009922806296651; A% Q- Q; z9 n3 j8 N5 r0 u4 X
http://clp.sagepub.com
; ]/ n& `' z( ^' n) n, J) C2 a/ c. lhosted at4 \/ z* P" {8 |! A
http://online.sagepub.com) w$ j" L5 F( L; q$ X% B
Precocious puberty in boys, central or peripheral,
2 ]( Q* u$ c0 C8 `# |! Fis a significant concern for physicians. Central5 _* }& S! g. Z7 @: O4 u
precocious puberty (CPP), which is mediated
+ C1 h4 D+ x7 E3 O* c' Z. fthrough the hypothalamic pituitary gonadal axis, has2 E3 l3 c3 `; u+ n- q8 r
a higher incidence of organic central nervous system
% C$ z) g# M: `% X, Q; ilesions in boys.1,2 Virilization in boys, as manifested- G; ~/ N1 h( j, I7 X( X) w
by enlargement of the penis, development of pubic
) d3 \- b& n" b- shair, and facial acne without enlargement of testi-5 V' b& q6 o1 l8 v" G
cles, suggests peripheral or pseudopuberty.1-3 We! [! v& b" y- e4 f8 x
report a 16-month-old boy who presented with the
( J2 b- |2 A; M3 Venlargement of the phallus and pubic hair develop-0 F8 G4 D1 J8 U, \( t; U
ment without testicular enlargement, which was due9 ^1 H; }7 H& U+ f
to the unintentional exposure to androgen gel used by
/ p: a+ s3 }! ?the father. The family initially concealed this infor-9 F. L. u6 w3 Y4 @
mation, resulting in an extensive work-up for this
) S5 U5 E$ o0 T$ L- U5 Z: [: lchild. Given the widespread and easy availability of
p. U& g7 a8 ?4 y* _testosterone gel and cream, we believe this is proba-
8 u# {% o+ I' B8 @3 y/ J, x- v. j# bbly more common than the rare case report in the: G* p& g% j& M6 p) `
literature.4' W3 D1 w5 \8 l( U
Patient Report0 t9 S1 K2 b6 U1 M1 T% P& {; f
A 16-month-old white child was referred to the9 T) ^! ? _, p6 i0 j! @5 s
endocrine clinic by his pediatrician with the concern/ j% ^" o2 y+ N' j6 I3 ~5 ?, x
of early sexual development. His mother noticed
: m; y( R/ S9 {8 {: Z `light colored pubic hair development when he was# _- t0 |& @% K" h
From the 1Division of Pediatric Endocrinology, 2University of
7 G5 `1 k- }9 N& a3 x" d7 gSouth Alabama Medical Center, Mobile, Alabama.
( r2 U( ?: J1 H. Z% w6 rAddress correspondence to: Samar K. Bhowmick, MD, FACE,
: x* Q8 }) i7 ^# K. MProfessor of Pediatrics, University of South Alabama, College of
" j: z8 M: y9 }5 z* G9 x; X# TMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;$ P: Z0 a( B& u8 E- J
e-mail: [email protected]. e, J M6 `3 E; G) p4 J `
about 6 to 7 months old, which progressively became
% I4 I1 F: ~5 f* edarker. She was also concerned about the enlarge-
+ a4 J$ K6 @: ?# `4 t* b, Fment of his penis and frequent erections. The child' h5 u* U/ w$ I q& U
was the product of a full-term normal delivery, with
5 ~' p% e( D0 u( E0 xa birth weight of 7 lb 14 oz, and birth length of: d, }# r0 O& W g; j# x+ ] ]' W2 b
20 inches. He was breast-fed throughout the first year' C" q( d. T( x3 @$ f. Z* S9 S
of life and was still receiving breast milk along with
$ a) q4 ?( G) D, l {solid food. He had no hospitalizations or surgery,* @9 D+ D) N7 y6 l3 m+ w9 k7 H8 |
and his psychosocial and psychomotor development
/ [* Y! W4 ~+ e. t0 N7 u7 v: [was age appropriate.
1 T/ }# ~1 G7 q8 b% {The family history was remarkable for the father,
% E9 H5 w; z d& V, [; F% a9 Jwho was diagnosed with hypothyroidism at age 16,* |, i! A$ [- W- d
which was treated with thyroxine. The father’s
# g& `9 E/ x5 ?1 |; mheight was 6 feet, and he went through a somewhat. z0 d& e0 X" r' F
early puberty and had stopped growing by age 14.
0 @4 r8 c# A" k1 U5 }4 \The father denied taking any other medication. The
0 p( h; w7 I5 X$ V7 j2 Rchild’s mother was in good health. Her menarche" V) ?( m" b! \/ h
was at 11 years of age, and her height was at 5 feet
4 `- R% o4 Z' k( S Y5 inches. There was no other family history of pre-
1 t3 g! `3 I% K1 v# n# T9 acocious sexual development in the first-degree rela-
/ Q% _" b4 f- o* V' Y- `tives. There were no siblings.& p; r# _$ F# u) D6 Y
Physical Examination
7 v9 M) ~- v; i% _, `8 OThe physical examination revealed a very active,
6 T; v6 \4 r2 Y: D% b, j9 u/ h- aplayful, and healthy boy. The vital signs documented/ f5 }$ @3 R2 P& y+ w, m
a blood pressure of 85/50 mm Hg, his length was% t, O9 @5 D- X* b
90 cm (>97th percentile), and his weight was 14.4 kg% c/ b# t7 `' @! E
(also >97th percentile). The observed yearly growth/ T* ]' j. [, o: P: ^2 Z3 s
velocity was 30 cm (12 inches). The examination of
" K" p2 }8 X! I* {the neck revealed no thyroid enlargement.
5 e: m+ x% V. y% DThe genitourinary examination was remarkable for
" {/ \$ o3 |8 Henlargement of the penis, with a stretched length of) v1 d& w) u: `
8 cm and a width of 2 cm. The glans penis was very well
4 O* s. }: J! H( ? s# I, jdeveloped. The pubic hair was Tanner II, mostly around, K% D* O6 }& Y2 [0 s# n' C0 |
540
9 }9 c) U3 y" t3 xat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
' G9 j$ Q0 {' f. n5 Ethe base of the phallus and was dark and curled. The
, `( a! v- F( i# T2 n" G; Q* btesticular volume was prepubertal at 2 mL each.
& b* S3 @- ?4 k: D0 i" l$ a; mThe skin was moist and smooth and somewhat. P A$ w( D. o% {
oily. No axillary hair was noted. There were no
5 H9 H( s, |3 Habnormal skin pigmentations or café-au-lait spots.% y6 x1 v6 S, {/ o; O7 U1 s
Neurologic evaluation showed deep tendon reflex 2+
3 l0 u4 [: d& {9 E0 abilateral and symmetrical. There was no suggestion
. T, J5 }3 F7 W# E3 h4 Zof papilledema.
; D: k& A2 C% `8 y# J+ y, f4 mLaboratory Evaluation; ]. u) B7 K2 u* {' X
The bone age was consistent with 28 months by0 m! u4 N; _+ b
using the standard of Greulich and Pyle at a chrono-6 U7 B1 _5 H) H) o" W' b
logic age of 16 months (advanced).5 Chromosomal9 Q/ I* W" Z4 z1 a1 T
karyotype was 46XY. The thyroid function test2 q9 U$ F S4 g3 F
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
. e. ?2 a/ u# K( L: m! k) @lating hormone level was 1.3 µIU/mL (both normal).
0 V" m( k A- kThe concentrations of serum electrolytes, blood* q! R6 ]+ ?& z! s2 X8 ] v
urea nitrogen, creatinine, and calcium all were! V n0 g1 {1 Z/ ?% \" S& r' t
within normal range for his age. The concentration
' N0 k7 F9 d5 t0 ~2 o1 qof serum 17-hydroxyprogesterone was 16 ng/dL
4 C( O, W3 e# |8 y& _(normal, 3 to 90 ng/dL), androstenedione was 20
* n" j. v* I- i. H; H8 I5 U, ung/dL (normal, 18 to 80 ng/dL), dehydroepiandros-* F: b8 c6 a$ n8 b8 `
terone was 38 ng/dL (normal, 50 to 760 ng/dL),4 A2 ?. {% R0 l
desoxycorticosterone was 4.3 ng/dL (normal, 7 to: d* q) X @- n
49ng/dL), 11-desoxycortisol (specific compound S)
4 o" x- g, p/ d5 B# uwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
: A1 ?8 [& A; t+ J. h" wtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
7 ~1 j3 s m& v4 Mtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),- E' \/ B P \0 W! X7 C2 c( P [
and β-human chorionic gonadotropin was less than4 D. u% J' R. L; m& y Q
5 mIU/mL (normal <5 mIU/mL). Serum follicular
0 Q! l# p$ D" Y, N6 M7 ?" }9 x1 ystimulating hormone and leuteinizing hormone
' a3 Y ?+ `, F! ~. A( w( v5 lconcentrations were less than 0.05 mIU/mL
4 w! n" h& P- N# y9 z/ P% q4 |(prepubertal).
8 R. `1 S& ]% P6 G. f% s9 R+ ]The parents were notified about the laboratory0 `% N! @2 c8 v
results and were informed that all of the tests were
+ q5 ~( g+ E4 z5 d3 Onormal except the testosterone level was high. The
) c6 H C! K5 K- V. C3 h0 h( Q: S- Gfollow-up visit was arranged within a few weeks to
4 g3 h: m {, p& Z6 {obtain testicular and abdominal sonograms; how- X8 N9 y% r9 J9 k& x" s
ever, the family did not return for 4 months.
& Z3 n2 R# J. _7 } R' m6 F# ePhysical examination at this time revealed that the- N) H9 m4 }! N+ A9 M w8 h0 y
child had grown 2.5 cm in 4 months and had gained; W5 s0 f5 J! g
2 kg of weight. Physical examination remained
1 d3 O# [2 Z2 D- Ounchanged. Surprisingly, the pubic hair almost com-
% ]2 v) v) g9 G! o! p4 Cpletely disappeared except for a few vellous hairs at
" s+ f+ X2 U8 q! Ythe base of the phallus. Testicular volume was still 2
* G' c3 P# x6 A4 y( |mL, and the size of the penis remained unchanged.
* W, \& r! s6 g) m [) nThe mother also said that the boy was no longer hav-
8 u7 M/ D ^0 y# ~) ^3 v/ V4 \$ r. ying frequent erections.
4 A6 N+ c3 b( P7 `0 i7 \ c2 uBoth parents were again questioned about use of
* R7 E( Z$ O: x# W+ `any ointment/creams that they may have applied to
0 I& O# q, D' L; t' q; xthe child’s skin. This time the father admitted the1 u: E) q" F- ~1 F$ `/ Q
Topical Testosterone Exposure / Bhowmick et al 541
9 U' Q8 g& {1 G% Q5 w/ H k. d- ~use of testosterone gel twice daily that he was apply-, D' z. _2 r4 f
ing over his own shoulders, chest, and back area for* C" h y0 b! L& B6 V$ w% }& \
a year. The father also revealed he was embarrassed2 g- S \$ y- G# X0 h2 D: f
to disclose that he was using a testosterone gel pre-# P1 \5 H; f8 m4 L3 Y5 t
scribed by his family physician for decreased libido0 U2 | g3 C* Z, _- A
secondary to depression.& w' s% u/ g5 {! _1 ^ T8 w X$ p/ q0 O
The child slept in the same bed with parents.
7 K, a h& K( v# [, {( s, AThe father would hug the baby and hold him on his
& Z) S9 T" F3 B% E5 ]+ p: ?chest for a considerable period of time, causing sig-
' k% Q9 X- e0 ~0 ]nificant bare skin contact between baby and father.
. x. t; e! _+ S( g4 E& WThe father also admitted that after the phone call,
& y: O5 d4 C6 z" t8 Bwhen he learned the testosterone level in the baby
/ h- P! r8 o! l8 a) R8 p) X* ^& Kwas high, he then read the product information7 ^3 t2 `9 @4 {+ i# D5 @* T
packet and concluded that it was most likely the rea-
6 ~( E) N/ ^* g+ Json for the child’s virilization. At that time, they
* C8 w0 L7 n% {! N# Gdecided to put the baby in a separate bed, and the
+ |1 T4 p. r, w0 f# \father was not hugging him with bare skin and had
9 U$ {# i$ Z; ?1 obeen using protective clothing. A repeat testosterone
+ @" q5 e# i% _, J1 `1 c! j" Atest was ordered, but the family did not go to the
' {4 @4 U4 t, a2 Dlaboratory to obtain the test.
3 K }% Q+ U- c! [0 I( f1 R5 TDiscussion0 v2 y1 }4 B) Y6 _4 o2 E L0 A
Precocious puberty in boys is defined as secondary
/ R" p. z% ` ~, p' @ ~; ~sexual development before 9 years of age.1,4
6 N9 D; A: u. y! J, XPrecocious puberty is termed as central (true) when) I! E4 Q% G( z- j# |1 U2 L- e0 Q
it is caused by the premature activation of hypo-7 u5 L2 Y2 B! H1 K6 l. H( ]* v
thalamic pituitary gonadal axis. CPP is more com-
( Q1 I1 W( u4 A0 m9 {) K4 ]mon in girls than in boys.1,3 Most boys with CPP7 v7 d" |6 Y# E0 S4 m. O$ N' u
may have a central nervous system lesion that is
/ v0 X& |/ s* A: Fresponsible for the early activation of the hypothal-
- X( Q0 c) r+ jamic pituitary gonadal axis.1-3 Thus, greater empha- \1 e. ^* a4 z# H/ Y8 I
sis has been given to neuroradiologic imaging in
j! x- R- a; T" P1 u( K2 ]boys with precocious puberty. In addition to viril-
# H/ i' `5 l- H9 {4 eization, the clinical hallmark of CPP is the symmet-& d% o2 X/ j- u$ e) ]
rical testicular growth secondary to stimulation by& \: k- h$ m7 K* ?9 ?
gonadotropins.1,37 }, b* d5 z5 e1 n
Gonadotropin-independent peripheral preco-3 s- Z( _- _8 b; k
cious puberty in boys also results from inappropriate
2 t# A. a2 d. u2 q" gandrogenic stimulation from either endogenous or
4 @! k& u* v5 V4 Rexogenous sources, nonpituitary gonadotropin stim-
7 I$ {5 D/ n. r! E* r& `/ T, nulation, and rare activating mutations.3 Virilizing, A V1 H1 m# ~2 q/ b4 a# ]7 T" ?
congenital adrenal hyperplasia producing excessive
" M+ N7 } Y1 P$ h* a/ h Q2 u# k2 Badrenal androgens is a common cause of precocious
8 S f5 {! t) `# [! L$ ?puberty in boys.3,49 G) u" |' b0 w$ N
The most common form of congenital adrenal
; C) p; p c! v( N; F0 ~hyperplasia is the 21-hydroxylase enzyme deficiency.
8 @6 R- Q/ ]( Q+ A) uThe 11-β hydroxylase deficiency may also result in( U: P# e7 N6 |5 ^2 _. ]! T
excessive adrenal androgen production, and rarely,9 O: @, j/ W3 w/ y
an adrenal tumor may also cause adrenal androgen
' J) c1 M4 B8 D7 ]4 @7 F8 texcess.1,3
& R2 T% `5 T$ @. J6 Wat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from7 S# h' O0 K6 l/ D0 {% k
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007/ I% ~: n( k6 B! G/ \
A unique entity of male-limited gonadotropin-
& p; A5 t( E1 D7 mindependent precocious puberty, which is also known% V, K5 w! F2 f
as testotoxicosis, may cause precocious puberty at a
3 g1 J8 D. C8 l! D4 l% C- @; ~very young age. The physical findings in these boys
5 Q9 n3 n; O) j/ g) {with this disorder are full pubertal development,
0 I3 U& Z. M/ xincluding bilateral testicular growth, similar to boys$ u/ T2 w( u& b4 P; o
with CPP. The gonadotropin levels in this disorder
/ e- f- x0 {# Y: n, Yare suppressed to prepubertal levels and do not show( R2 o g' o8 Z# l
pubertal response of gonadotropin after gonadotropin-
2 q( _& _7 w4 H( N( treleasing hormone stimulation. This is a sex-linked
% T# \- m3 e/ ?4 vautosomal dominant disorder that affects only) m s' F w" H& w
males; therefore, other male members of the family7 T# H- J* n& s! b, S: P: p
may have similar precocious puberty.37 W0 C2 k0 [! n3 z* t! U, |: K5 A
In our patient, physical examination was incon-' i, D+ t/ n- F: z/ _
sistent with true precocious puberty since his testi-
: K( z& x' U9 U: @! x- m# l' Ucles were prepubertal in size. However, testotoxicosis7 X" t8 z; `8 J9 `
was in the differential diagnosis because his father
( L& g0 `; o+ F5 p$ Tstarted puberty somewhat early, and occasionally,
2 a1 e) ~- W" E" gtesticular enlargement is not that evident in the9 x: {/ W ]) J$ T- ?5 S
beginning of this process.1 In the absence of a neg-
6 C; H( G) X, n6 Rative initial history of androgen exposure, our4 P( G# Y8 Z; n% U" Z* s1 p
biggest concern was virilizing adrenal hyperplasia,
1 v( q g2 W+ @6 U+ j. \3 d; g3 veither 21-hydroxylase deficiency or 11-β hydroxylase+ w8 J+ g% d- l
deficiency. Those diagnoses were excluded by find-
9 ?% `% H# Y6 r% H, Ring the normal level of adrenal steroids.# |1 c% s$ J9 z. N4 X: @3 j. K# v
The diagnosis of exogenous androgens was strongly [2 j" E: t' y8 E1 o2 R
suspected in a follow-up visit after 4 months because0 p, @3 _ x4 |
the physical examination revealed the complete disap-
( D: ]* D4 u2 l6 Ypearance of pubic hair, normal growth velocity, and4 v, ] j: U4 N
decreased erections. The father admitted using a testos-: [/ _" J6 \3 k0 S
terone gel, which he concealed at first visit. He was) Y) s/ _; [' h9 x6 }
using it rather frequently, twice a day. The Physicians’" O# V1 v) e7 u" g3 ?: n
Desk Reference, or package insert of this product, gel or
; g/ [( C! t4 ]. ]9 fcream, cautions about dermal testosterone transfer to
# p' o( o: D' ]; G$ G+ A, O% Junprotected females through direct skin exposure.. n) F, |* N5 Z& P6 X2 o5 A" M6 ?$ z
Serum testosterone level was found to be 2 times the
6 j" U' h4 L( g" @3 W3 F% gbaseline value in those females who were exposed to
5 b( c% L, c% Z; E! u' f+ f) {even 15 minutes of direct skin contact with their male4 x" Y t+ f" j
partners.6 However, when a shirt covered the applica-7 a* s v) ^, q$ J8 e1 P
tion site, this testosterone transfer was prevented.
. o, m" ]7 d4 O( z5 D8 t8 OOur patient’s testosterone level was 60 ng/mL,. L9 _% O; L- p' ]: ]4 l
which was clearly high. Some studies suggest that* @/ }7 n7 C U
dermal conversion of testosterone to dihydrotestos-0 ?+ X! k6 ]+ m' k% F
terone, which is a more potent metabolite, is more; P7 W$ Z" B; \& l6 y f
active in young children exposed to testosterone
, l3 F' i8 P, u' B# uexogenously7; however, we did not measure a dihy-
% r! K, J( G) F, ndrotestosterone level in our patient. In addition to# W8 m* l) ~3 R
virilization, exposure to exogenous testosterone in
% Q* t4 I$ K7 Q: Achildren results in an increase in growth velocity and
# ]+ m9 i1 U) A" Eadvanced bone age, as seen in our patient.& h' Z$ w- `: l, g2 O, R* v
The long-term effect of androgen exposure during
& V6 R" s# f. p( d# i& c4 Eearly childhood on pubertal development and final
4 n2 E0 i# w4 x- z+ P/ G* D8 Badult height are not fully known and always remain
$ ?5 p4 E( `& l; S2 qa concern. Children treated with short-term testos-" J, P2 G8 Q6 ~5 {8 E9 P
terone injection or topical androgen may exhibit some7 ?7 }! N7 Z6 u3 z8 L5 m
acceleration of the skeletal maturation; however, after/ R6 b5 E( w: P# y, p3 [7 b
cessation of treatment, the rate of bone maturation _0 V9 _7 ^, } q
decelerates and gradually returns to normal.8,9
; k$ H% q4 l0 l" ?2 |# X# VThere are conflicting reports and controversy
$ f* W3 w7 T8 V$ H$ W( k {) Jover the effect of early androgen exposure on adult
: G$ a% Q9 ?' ]% S" p- m, epenile length.10,11 Some reports suggest subnormal
" c# X% e P" Dadult penile length, apparently because of downreg-" _7 C8 @1 u. b c: E
ulation of androgen receptor number.10,12 However, l( y' h0 w$ N; F# [3 h) ~) O
Sutherland et al13 did not find a correlation between, e* q/ i" T$ [. V7 y" y/ {: l
childhood testosterone exposure and reduced adult
$ x+ e# l+ J f9 p1 a# f) {penile length in clinical studies.
8 ^+ ^ G/ H7 ~$ ]. CNonetheless, we do not believe our patient is
% F q1 w9 d5 t9 R: Sgoing to experience any of the untoward effects from
0 {8 B6 r- H, ttestosterone exposure as mentioned earlier because2 P8 P* l( L C d" q2 T
the exposure was not for a prolonged period of time.
1 j: ?% F; |# n1 w3 bAlthough the bone age was advanced at the time of
. P- e$ x6 D! P x# Q: [3 Adiagnosis, the child had a normal growth velocity at
- Y4 @$ c$ G; v; y' X6 I% O/ Ithe follow-up visit. It is hoped that his final adult
* L9 @$ }& M$ qheight will not be affected.; y' G5 }8 F: ` T& @0 T0 J2 [
Although rarely reported, the widespread avail-
& C4 Y4 @# Z5 oability of androgen products in our society may5 o2 i: J" D& y" S: [* N! V/ \
indeed cause more virilization in male or female
, ]( @1 H! @& A3 T3 d2 lchildren than one would realize. Exposure to andro-
: `9 n/ u8 h7 egen products must be considered and specific ques-
9 w& X7 \+ F: p; h# {+ Wtioning about the use of a testosterone product or, ~# u% y+ O3 g) I
gel should be asked of the family members during
e7 [5 @. p4 w1 ]the evaluation of any children who present with vir-3 V& ?0 T' m. U( @/ A; P ^
ilization or peripheral precocious puberty. The diag-
" {; g% b' F1 I! A+ o t* jnosis can be established by just a few tests and by
, t8 ^" y7 ^- _6 ?7 B7 ?% ]# X6 sappropriate history. The inability to obtain such a
( |1 |3 @& W9 V- ?4 t5 Xhistory, or failure to ask the specific questions, may/ i! m. I5 s. y7 z4 C8 ~) L7 _
result in extensive, unnecessary, and expensive
' E3 Q1 z/ p/ A2 [+ Q5 O" _investigation. The primary care physician should be
' A' @# O3 B. caware of this fact, because most of these children
8 e) C0 M7 O% O* s; {3 dmay initially present in their practice. The Physicians’
3 C& G8 D5 f& |Desk Reference and package insert should also put a
5 x1 O8 m( M6 c7 Q2 f, Z3 E% nwarning about the virilizing effect on a male or
" c8 C& X5 z+ K2 vfemale child who might come in contact with some-; B9 ]* H. l: O: ]
one using any of these products.
* a4 y; j( {1 X Y0 p$ Z% a& g7 NReferences* ~; ?, J0 u. ?' V+ F! f
1. Styne DM. The testes: disorder of sexual differentiation1 U! r* d4 \8 u' r
and puberty in the male. In: Sperling MA, ed. Pediatric8 [/ y* `3 A/ \0 n! w2 x6 j
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
* S( n! r1 i& @2002: 565-628.
4 l& H- r1 D& I2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious0 ]1 q( W: _' B
puberty in children with tumours of the suprasellar pineal |
|