- 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: m8 b; d' _: b8 W2 E& a, z
Boy Induced by Indirect Topical
$ j5 N; b# i- l9 l, ZExposure to Testosterone
1 W% N8 `3 H' ^8 V+ N' b9 T i; }- MSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
; u8 h: ]8 X9 K% `: b1 P, oand Kenneth R. Rettig, MD1# W% K% r$ H& l$ T1 Y
Clinical Pediatrics
- U- t3 k: ^3 F6 E2 x7 WVolume 46 Number 6; I# Q" g6 u) C2 \2 M9 F
July 2007 540-543
$ l, i% f6 o" u9 m% [1 O© 2007 Sage Publications# g) m% L- |2 k: ?
10.1177/0009922806296651
1 w0 f* A/ g6 c; y" E5 H7 _" U' whttp://clp.sagepub.com+ N8 S u1 ?; _9 |/ z) g6 I9 |
hosted at
' l) k' U4 W3 t" C1 J" W5 yhttp://online.sagepub.com8 K' K1 P0 G) O& b: e# S: i
Precocious puberty in boys, central or peripheral,
* R; S/ N" O9 m0 y. A5 bis a significant concern for physicians. Central9 V4 ^( [1 O4 E; D8 {
precocious puberty (CPP), which is mediated
7 d j' d. }; g0 l9 @( a. Sthrough the hypothalamic pituitary gonadal axis, has
# R1 @3 i4 X# c( _7 q4 W3 h D1 e0 ^! }a higher incidence of organic central nervous system
2 l; A- m1 B. k/ Klesions in boys.1,2 Virilization in boys, as manifested' A- E' g8 F9 V3 q* J V7 Q( G# }
by enlargement of the penis, development of pubic
2 y; @9 w% @8 u* y) Qhair, and facial acne without enlargement of testi-( g( ^' [5 _# |. W$ t# A2 o4 K/ M
cles, suggests peripheral or pseudopuberty.1-3 We- }" P- g0 z: _8 R. d
report a 16-month-old boy who presented with the+ C2 Q2 v8 o5 V2 a5 s
enlargement of the phallus and pubic hair develop-$ r, I5 N: R7 x* o
ment without testicular enlargement, which was due/ q/ U9 ?6 R/ l) w" B* A* x) w
to the unintentional exposure to androgen gel used by. }: B7 |$ X! ^) g% N
the father. The family initially concealed this infor-
3 i9 f6 m& N1 |mation, resulting in an extensive work-up for this
$ }2 o0 E) a- q( Uchild. Given the widespread and easy availability of: S3 v; k" u$ ]6 d
testosterone gel and cream, we believe this is proba-4 W, O1 f S. D" d. y4 P* f2 k% f
bly more common than the rare case report in the" B9 k" d2 N6 S+ s+ h* H
literature.4
6 t3 t1 M6 G+ a% r" lPatient Report
/ d3 y# r5 R4 c( `9 M- \A 16-month-old white child was referred to the' B4 K2 X6 W" d, S) y
endocrine clinic by his pediatrician with the concern; h. w+ ^8 L! S0 Z, L; e
of early sexual development. His mother noticed
/ m$ r9 S5 b1 U0 J& Ylight colored pubic hair development when he was/ y, E T' e+ _' z( b8 w! I5 `; Q
From the 1Division of Pediatric Endocrinology, 2University of' _) Z% Q1 }' U( l: v
South Alabama Medical Center, Mobile, Alabama.9 Q H& V C1 p' @6 P
Address correspondence to: Samar K. Bhowmick, MD, FACE,
5 e- b& h6 G* q s# t5 ?0 RProfessor of Pediatrics, University of South Alabama, College of
3 m* u: ]8 ]) DMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
. x+ N; Z. c3 {9 _8 `e-mail: [email protected].
* n- f5 C! @$ habout 6 to 7 months old, which progressively became
& q9 M; C# N: [% u5 x$ odarker. She was also concerned about the enlarge-
$ s& k' n6 z1 k& o3 n2 c Yment of his penis and frequent erections. The child
8 ~( v b6 C# Zwas the product of a full-term normal delivery, with
# }/ H- J# D; [6 Da birth weight of 7 lb 14 oz, and birth length of
1 [/ a" L" F# }# D; o20 inches. He was breast-fed throughout the first year ]/ C% ]: Z& W" E x5 F
of life and was still receiving breast milk along with
! k8 `% v8 M4 c( `& d7 `* gsolid food. He had no hospitalizations or surgery,
, N Z6 ?* Y; j& w: a0 Eand his psychosocial and psychomotor development
0 R* B9 i. | qwas age appropriate." I( Y% o l; b
The family history was remarkable for the father,+ Z5 D( H0 Q$ T v. q
who was diagnosed with hypothyroidism at age 16,! Y# T9 q7 w6 P7 i; j
which was treated with thyroxine. The father’s% B/ Q/ F: G% E
height was 6 feet, and he went through a somewhat
+ n$ D! H) U8 Y$ M9 Oearly puberty and had stopped growing by age 14.
' X( T* d8 W: E' c7 }The father denied taking any other medication. The
& b! f0 N8 \- F' `# ^5 \, Ychild’s mother was in good health. Her menarche
5 v1 N" D+ b0 t, Z% Ywas at 11 years of age, and her height was at 5 feet
0 i. a7 q9 S+ ]1 z- H. f5 inches. There was no other family history of pre-3 x* ^8 S+ ~/ @1 ^! T a' ^' m# V
cocious sexual development in the first-degree rela-! H0 n. A2 v2 z7 _- z: V
tives. There were no siblings.
& a6 m) W* G8 J5 Q VPhysical Examination
; s" F! l1 p& Q1 o( AThe physical examination revealed a very active,
) S# a) C0 H" i% `playful, and healthy boy. The vital signs documented
; b: E$ J' I9 V* Xa blood pressure of 85/50 mm Hg, his length was: A. l* x& x0 C6 V" v! j$ V0 o) ^
90 cm (>97th percentile), and his weight was 14.4 kg
0 }& U7 e! J" a# L6 x+ L) v4 H(also >97th percentile). The observed yearly growth) l2 r- P7 X, p8 M8 i* \4 X
velocity was 30 cm (12 inches). The examination of4 k, s& z% a) x: n8 u/ T
the neck revealed no thyroid enlargement.
; \' b& T: D) EThe genitourinary examination was remarkable for/ q4 g" y2 R" {1 t+ N
enlargement of the penis, with a stretched length of
: J/ S8 v. e8 s* ~6 R, P8 cm and a width of 2 cm. The glans penis was very well
+ F( h L1 x- S5 ddeveloped. The pubic hair was Tanner II, mostly around
, [4 x! i: r; E7 o& X7 |0 p5401 @ }: x4 }, c. H8 Z3 i: v% z' i
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from8 `4 O0 b5 ?8 u1 Z, F
the base of the phallus and was dark and curled. The1 V/ n! \8 c7 t9 E* g6 }
testicular volume was prepubertal at 2 mL each.
7 y5 n) i6 `7 G% q# z1 xThe skin was moist and smooth and somewhat
/ @0 g! R+ G$ D& I" j/ _oily. No axillary hair was noted. There were no1 R) C- J, u0 U( S5 A
abnormal skin pigmentations or café-au-lait spots.% Y1 N8 r' Q: ?5 M, F+ W9 p
Neurologic evaluation showed deep tendon reflex 2+
; B* G7 P5 O" y: B c, {bilateral and symmetrical. There was no suggestion
; _8 i$ ^& ?8 p: Kof papilledema.% K) `, T9 Y- T; y# ^6 d
Laboratory Evaluation
3 j0 V3 d" L0 }3 `: B4 iThe bone age was consistent with 28 months by
$ ^! V5 e Y# [; N( L' V7 z' Wusing the standard of Greulich and Pyle at a chrono-$ h/ H( `/ x* X, t1 u, c/ b7 N$ p4 d0 I
logic age of 16 months (advanced).5 Chromosomal
+ R4 K {6 Q. w$ tkaryotype was 46XY. The thyroid function test
; E$ C' O3 g8 b7 ashowed a free T4 of 1.69 ng/dL, and thyroid stimu-9 M6 F5 g7 c D8 T
lating hormone level was 1.3 µIU/mL (both normal).8 z) N4 j% c4 [4 }+ k2 _
The concentrations of serum electrolytes, blood } L8 X* G4 x% J# j2 x
urea nitrogen, creatinine, and calcium all were
9 ^8 ]4 I6 S3 w2 q$ `- z0 Nwithin normal range for his age. The concentration
* ^( y4 G, I/ L# W9 ^1 G6 G, \of serum 17-hydroxyprogesterone was 16 ng/dL
& T, e* Q( h% [0 p9 q. G(normal, 3 to 90 ng/dL), androstenedione was 20
" u! Y( r$ |# y: `' j5 |ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-4 Q6 V: Z3 \' v! E/ c, n
terone was 38 ng/dL (normal, 50 to 760 ng/dL),9 H3 M4 q3 d3 ]* G8 N
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
5 x7 }+ f8 B- f49ng/dL), 11-desoxycortisol (specific compound S) m2 ~7 ^# v# I& j D/ c
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
1 V7 O2 T2 n" G! Rtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total: K G" E' d4 `0 ^
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
2 M+ V2 q& h" I7 x+ x! ]- wand β-human chorionic gonadotropin was less than9 @; \+ T n6 l- A, ]' G9 `7 K' s
5 mIU/mL (normal <5 mIU/mL). Serum follicular! D4 X# {! I- {$ t( O% o
stimulating hormone and leuteinizing hormone
" c8 l% f- W. [1 Sconcentrations were less than 0.05 mIU/mL( K& F6 {) }1 K0 _
(prepubertal).; v' ?/ t' I5 p0 s+ T
The parents were notified about the laboratory- {" P0 h' O. _/ q9 c. q
results and were informed that all of the tests were- }! t" X6 c" g" O/ |
normal except the testosterone level was high. The
7 V( [* ~. e; H$ R. o0 Rfollow-up visit was arranged within a few weeks to
* G5 ?# q! }. E" z. j5 Pobtain testicular and abdominal sonograms; how-/ y% H6 y1 R: E, q% D0 P4 [
ever, the family did not return for 4 months.
7 S" X0 ~ ^$ O3 }; F( A% QPhysical examination at this time revealed that the. A- h7 w2 x( I( m$ [
child had grown 2.5 cm in 4 months and had gained
0 a3 Y% {( s: Q2 kg of weight. Physical examination remained
# _- n4 A9 r0 Y0 v1 \3 K" junchanged. Surprisingly, the pubic hair almost com-& L1 X: ?4 p. x* _3 z' L' B2 f
pletely disappeared except for a few vellous hairs at; `9 H3 Z2 N- S8 _0 ], r" f4 J
the base of the phallus. Testicular volume was still 2+ T# r* B5 ]; u- d0 k1 x# r
mL, and the size of the penis remained unchanged.
9 P/ n! x, W9 R' |/ OThe mother also said that the boy was no longer hav-
5 J4 B0 ~" A+ Zing frequent erections.
4 l z" F: c1 h; }; TBoth parents were again questioned about use of) b4 y# H- Y7 Z
any ointment/creams that they may have applied to
4 p: ?, O0 f9 }: B& cthe child’s skin. This time the father admitted the# t3 W) m5 H; v, u w
Topical Testosterone Exposure / Bhowmick et al 541/ e- D( \7 z. \( T+ E) @, M
use of testosterone gel twice daily that he was apply-5 ]" p6 _& G, C8 O6 O2 i9 X
ing over his own shoulders, chest, and back area for
& x, R' P5 L( _ p0 }- x% na year. The father also revealed he was embarrassed$ ^9 C2 _4 z% l( ]: }5 A2 e
to disclose that he was using a testosterone gel pre-
4 [& P9 q7 h7 H) {- R" `scribed by his family physician for decreased libido! p4 P3 d* N% F1 i# r- x
secondary to depression.' l6 w7 U3 M! c8 u7 }& O* }6 F
The child slept in the same bed with parents.
) a. _4 }7 J" q4 M/ ^ H# VThe father would hug the baby and hold him on his
6 I+ d( N/ X% C& K1 R3 t# Qchest for a considerable period of time, causing sig-% [( Z; ^% w* ]- W/ @8 k) `
nificant bare skin contact between baby and father.
1 T. i0 b7 L- d$ VThe father also admitted that after the phone call,; ~- |' ~6 D3 k' k
when he learned the testosterone level in the baby$ W0 D" v6 Z) s! n+ B* E0 s4 z
was high, he then read the product information4 j3 `2 t0 R- a' z+ A+ u5 ^
packet and concluded that it was most likely the rea-. K% S2 u" l. ^/ \4 o& s
son for the child’s virilization. At that time, they
3 @* S: @% i. e+ Ddecided to put the baby in a separate bed, and the
% p) ]! i" m S$ C3 y! k+ s: k! Bfather was not hugging him with bare skin and had; \, o9 z z. K7 O& R
been using protective clothing. A repeat testosterone
- {. {/ m# J; G" I- S. a% Ttest was ordered, but the family did not go to the
) }" }( N% Z; A9 V9 ~0 l$ W, Tlaboratory to obtain the test.: F/ b6 W6 S+ e+ x( t( E
Discussion5 r" s0 T {% C2 `
Precocious puberty in boys is defined as secondary
% U. e. H3 | w9 c3 y) }sexual development before 9 years of age.1,4" [- [* i2 x6 R
Precocious puberty is termed as central (true) when
) Y K* W' I1 y- P3 R1 Yit is caused by the premature activation of hypo-
+ c0 X1 K' n) Z2 E7 Z5 X# A3 pthalamic pituitary gonadal axis. CPP is more com-* G# l$ A, f5 A! B4 I4 n
mon in girls than in boys.1,3 Most boys with CPP' p0 s6 G- E. d& q1 t0 I1 L/ y* L
may have a central nervous system lesion that is
5 T/ D3 p6 q% D6 Oresponsible for the early activation of the hypothal-
9 E) K/ U9 Y+ H+ z; w: ?) Vamic pituitary gonadal axis.1-3 Thus, greater empha-
! v8 n8 J. u- g/ Z9 R/ h& Jsis has been given to neuroradiologic imaging in
% c: ~" c' o, r' P9 \# }4 ~/ wboys with precocious puberty. In addition to viril-8 e9 R. Z' U+ m% T J5 X+ b! J
ization, the clinical hallmark of CPP is the symmet-
, |, j8 A3 b* b1 Erical testicular growth secondary to stimulation by
8 j! g! L2 s5 {. L3 ygonadotropins.1,37 T0 m" V# u! u% J# |6 k* v" z1 C
Gonadotropin-independent peripheral preco-6 _4 P+ l* C/ w! Z( b0 }8 v: \6 F
cious puberty in boys also results from inappropriate, b* g9 m/ i) J* t
androgenic stimulation from either endogenous or
- E( D- O" [2 ]" {0 H$ F, [5 j3 }/ aexogenous sources, nonpituitary gonadotropin stim-" E. y* G0 y6 D* @. B
ulation, and rare activating mutations.3 Virilizing h0 o$ q& x1 t0 }1 Z
congenital adrenal hyperplasia producing excessive
3 c* @ t, i- x" \. T6 E/ ~adrenal androgens is a common cause of precocious" k! E$ S# O" z# R- q( ?
puberty in boys.3,4
+ I- G5 X( q, m* ]1 pThe most common form of congenital adrenal$ P1 f2 V3 p- Y9 x' R' h
hyperplasia is the 21-hydroxylase enzyme deficiency.. K9 k! \ J* `
The 11-β hydroxylase deficiency may also result in
& i$ }9 j: Y% Eexcessive adrenal androgen production, and rarely,1 G' B& j( A' Z
an adrenal tumor may also cause adrenal androgen5 T8 f& D9 _5 J3 d5 @7 r
excess.1,3" z* m5 s9 C; r w7 q/ A
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
8 r* ?0 m1 E: u6 I D! S% j542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
6 y0 P. U ]& n% {' K VA unique entity of male-limited gonadotropin-: l. p1 A* x0 s
independent precocious puberty, which is also known
$ Y1 N$ ^9 D7 }7 B% kas testotoxicosis, may cause precocious puberty at a
7 L3 R0 v- M3 K5 P, @6 u4 Qvery young age. The physical findings in these boys: R3 M/ a0 [1 w, w4 h& y8 }+ F
with this disorder are full pubertal development,
- y& a2 @8 ~( Aincluding bilateral testicular growth, similar to boys
/ [# ^" N+ t. m9 Owith CPP. The gonadotropin levels in this disorder
2 o* b5 Y6 V% v0 Nare suppressed to prepubertal levels and do not show" s" u9 i, e4 [+ @9 h
pubertal response of gonadotropin after gonadotropin-
0 b1 P1 j. |4 u2 |0 `9 }releasing hormone stimulation. This is a sex-linked/ P: o" v) P, q7 u) g0 k) d4 H6 v
autosomal dominant disorder that affects only
$ c3 U5 q( J& V- @5 K1 y3 i* tmales; therefore, other male members of the family
/ W6 H! ?2 G( r" }may have similar precocious puberty.3: x8 ?8 P4 Y; { Z: G
In our patient, physical examination was incon-0 y) q( L* z/ J0 ^4 T
sistent with true precocious puberty since his testi-/ ^" C3 J1 f# I( a9 q/ C; t
cles were prepubertal in size. However, testotoxicosis: i2 X' P+ _1 B# B! Z X
was in the differential diagnosis because his father
8 x3 d1 c$ x1 o, M6 bstarted puberty somewhat early, and occasionally,! j/ L) \4 O" \$ l7 X$ B
testicular enlargement is not that evident in the
4 X8 C' d. R& L- O3 @beginning of this process.1 In the absence of a neg-
$ b' U' V. [ d7 ^; [& a2 zative initial history of androgen exposure, our
5 E! A2 S: B6 c" R( p- R8 K+ zbiggest concern was virilizing adrenal hyperplasia,
, r; Q+ e% e! S3 keither 21-hydroxylase deficiency or 11-β hydroxylase# Q% l6 V% A( @$ j, `! R+ J
deficiency. Those diagnoses were excluded by find-
/ C6 ]: v4 ?# E$ q0 W( wing the normal level of adrenal steroids.
* O, r6 e5 J/ e: sThe diagnosis of exogenous androgens was strongly
4 q f0 X1 ^% x1 Wsuspected in a follow-up visit after 4 months because
U/ `! v* X- H0 Q% ]# [& ~the physical examination revealed the complete disap-
( o6 c7 @1 |, A# kpearance of pubic hair, normal growth velocity, and' n/ H4 [( @9 O" C1 k( ^, O M
decreased erections. The father admitted using a testos-
- f8 ~8 Y- U- [- j1 J6 Oterone gel, which he concealed at first visit. He was, c( X) N5 s) t
using it rather frequently, twice a day. The Physicians’
9 \: g0 D1 R- N( \+ Q. rDesk Reference, or package insert of this product, gel or
- F7 W2 n9 b5 ?! P& D9 qcream, cautions about dermal testosterone transfer to
0 @' L6 g+ t% W4 B! d$ X6 bunprotected females through direct skin exposure.2 y8 ^3 K- k" |# @0 R4 C
Serum testosterone level was found to be 2 times the
3 N9 ^# E& T6 T2 `: v, ~9 |* T [) x* ^baseline value in those females who were exposed to6 y4 @: X0 x# X* K
even 15 minutes of direct skin contact with their male
]$ L' X& @5 `2 u! ?0 opartners.6 However, when a shirt covered the applica-
/ R8 r2 ]3 v" V# n0 Jtion site, this testosterone transfer was prevented.7 Z8 V2 G" m+ C, k* M8 `, m
Our patient’s testosterone level was 60 ng/mL," ?9 g; ?; @5 c5 M; C
which was clearly high. Some studies suggest that
/ z' B# L; }( b% |; y6 Q7 Wdermal conversion of testosterone to dihydrotestos-* k4 u- q7 B2 i3 R' ^5 H/ E
terone, which is a more potent metabolite, is more" r7 G% i1 h# @7 R# A
active in young children exposed to testosterone' v$ S4 Z2 V: J+ ?
exogenously7; however, we did not measure a dihy-! e! v8 _6 W& \+ r1 e) h
drotestosterone level in our patient. In addition to7 C }8 w: \) W/ r; Y
virilization, exposure to exogenous testosterone in% E7 I6 a7 Q6 ~2 S7 V8 j
children results in an increase in growth velocity and
6 h# P, s1 ?& }advanced bone age, as seen in our patient.1 x/ L, G* u$ r( a6 ?6 z! B6 E
The long-term effect of androgen exposure during% }" C& f8 ~/ T0 C
early childhood on pubertal development and final: S K+ m! @" @' P: S
adult height are not fully known and always remain
; {) t$ c. H% B; I$ Xa concern. Children treated with short-term testos-. {! f+ }0 n9 W" \$ E
terone injection or topical androgen may exhibit some- S0 l& z7 f8 A4 i& y+ @, u0 C" m
acceleration of the skeletal maturation; however, after
1 y( h* X& \1 M, icessation of treatment, the rate of bone maturation/ n. @$ f% v1 A( a# C
decelerates and gradually returns to normal.8,98 R9 H1 E8 R' V
There are conflicting reports and controversy
1 X$ Z! x6 V! Q& f; b$ gover the effect of early androgen exposure on adult* v0 X/ K3 g; {
penile length.10,11 Some reports suggest subnormal
, N4 F: F. d; }/ ^5 Z; N3 c/ Dadult penile length, apparently because of downreg-
+ H* o/ ^ E) l8 {ulation of androgen receptor number.10,12 However,
M! I, i7 x O/ K4 b8 \8 D, a7 iSutherland et al13 did not find a correlation between/ A. B4 v7 i R+ X
childhood testosterone exposure and reduced adult
, _9 C' y; h; spenile length in clinical studies./ n8 j% T( R& e+ f0 e
Nonetheless, we do not believe our patient is
' o; a4 p. @- S- ?going to experience any of the untoward effects from0 u+ f' a [+ z6 u) w5 I
testosterone exposure as mentioned earlier because9 h3 ^1 r+ o! g% C }" x. U" B
the exposure was not for a prolonged period of time.
5 R# _, a9 G9 f* q, _! ?' {Although the bone age was advanced at the time of
7 |4 d$ d" q9 n( bdiagnosis, the child had a normal growth velocity at
, v! |* W) d1 \4 vthe follow-up visit. It is hoped that his final adult
9 y1 _- ]) {; Fheight will not be affected., `9 R6 \9 ?. _9 q% p
Although rarely reported, the widespread avail-* C! B+ z# h4 G4 |
ability of androgen products in our society may# }* z! [& c. q2 E* s" a6 T
indeed cause more virilization in male or female5 O6 S' A6 e+ W( }6 j/ I6 @0 L6 E
children than one would realize. Exposure to andro-
* ?! w" a8 {: A$ _gen products must be considered and specific ques-
$ n ^( x$ M" P5 Ktioning about the use of a testosterone product or+ o3 V& C! K, L+ n7 @4 ~
gel should be asked of the family members during
! D: { u/ i8 U' x; }the evaluation of any children who present with vir-$ C# |+ R) [1 T9 e) _
ilization or peripheral precocious puberty. The diag-
+ T( r; D9 e$ Znosis can be established by just a few tests and by
3 Q7 H% N; ~4 t3 Dappropriate history. The inability to obtain such a6 ]0 O* x6 a( S4 c1 w9 ~ \) o
history, or failure to ask the specific questions, may/ o7 M1 Z- ]( e5 Q6 ~$ Z! v
result in extensive, unnecessary, and expensive
9 B0 a- _7 `* w9 T3 K5 [& einvestigation. The primary care physician should be
9 m0 u: `9 j" C) i9 E% _8 b# a; }aware of this fact, because most of these children
# D# |" F* J9 {' f- a' fmay initially present in their practice. The Physicians’/ {) u, X" a4 r0 s9 m+ `
Desk Reference and package insert should also put a& P9 I5 k: S; n1 k( B
warning about the virilizing effect on a male or7 B/ H6 \6 v9 c; h$ ` B B- o: B
female child who might come in contact with some-
: N( Y1 k. R% x* a. K" x# A6 Pone using any of these products.
7 ^+ _ K* R0 p' KReferences
7 @+ u* K6 i. P+ ?8 Z$ |* T1. Styne DM. The testes: disorder of sexual differentiation
: A5 }; z7 T% Q% v, B8 l5 sand puberty in the male. In: Sperling MA, ed. Pediatric
8 M, I8 U1 o. Z9 ZEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;, ^) q+ w9 }* G: n0 \
2002: 565-628.
/ `" b/ D/ L1 n3 ?9 a/ j$ I2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
& v$ Z) |7 p8 Q$ F0 t5 Cpuberty in children with tumours of the suprasellar pineal |
|