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Sexual Precocity in a 16-Month-Old) Z4 c; I/ i8 j1 q& K
Boy Induced by Indirect Topical
# {* B& v4 Z! a! ^3 Q5 b1 s' qExposure to Testosterone
9 X2 W- t4 P. U5 ? jSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
$ f1 l6 x+ m' A. w3 Aand Kenneth R. Rettig, MD1- o. r7 z: M, \, A! ~9 h
Clinical Pediatrics
! D$ Z& i+ O2 j, t8 {/ D( DVolume 46 Number 67 ]6 _" h. Z1 V( |! Y& _
July 2007 540-543
. |3 [6 T3 m' D# x: F" z- T© 2007 Sage Publications- W K0 J p3 @2 g
10.1177/0009922806296651: a1 C3 ^0 O" F' m0 \( j( Q7 E
http://clp.sagepub.com) x( T) K( S% ]) K6 c
hosted at! ^- R0 `# Y' u+ X
http://online.sagepub.com
% ?- b( n7 L" y' y! d* sPrecocious puberty in boys, central or peripheral,
5 Y: ]6 Y! f" h* @, wis a significant concern for physicians. Central
% _ E# Q3 f- N/ O( o" Nprecocious puberty (CPP), which is mediated: f% S- H1 U; ^9 ^1 t8 q' f" T
through the hypothalamic pituitary gonadal axis, has+ f+ a2 a1 o0 `: F9 G# a& @2 G
a higher incidence of organic central nervous system: [7 @0 C* C6 N4 S- c7 b
lesions in boys.1,2 Virilization in boys, as manifested- N8 M! p& e! m- P B& @1 l+ j
by enlargement of the penis, development of pubic
. Z5 f0 I% u3 Y# n! C# U7 thair, and facial acne without enlargement of testi-
4 g u0 p6 L! }7 _4 f' }cles, suggests peripheral or pseudopuberty.1-3 We
+ U+ _5 }4 b( e# d8 \5 N+ dreport a 16-month-old boy who presented with the
+ g, x$ @1 I& Q/ x# W7 p8 Denlargement of the phallus and pubic hair develop-) A& E0 X5 p, c" e P4 Y
ment without testicular enlargement, which was due
+ a8 Y6 r2 C: S/ Yto the unintentional exposure to androgen gel used by: p) x4 }5 g* E5 b
the father. The family initially concealed this infor-7 d' C; b+ B( q
mation, resulting in an extensive work-up for this
8 E% x9 n$ ?& a" bchild. Given the widespread and easy availability of
6 R7 R5 ?0 i* X9 c) h# {3 Ktestosterone gel and cream, we believe this is proba-/ |3 F/ |! u3 Z9 Q! G5 R! W$ Y
bly more common than the rare case report in the
8 R3 l2 j8 s7 l$ }literature.40 z, P8 M C' G6 }" e' _- {
Patient Report% b" B7 ?# P# l' _6 {, @
A 16-month-old white child was referred to the8 Y- v8 R. f6 W9 E9 D6 |' H% l' M
endocrine clinic by his pediatrician with the concern
7 x& J7 Z y$ _ ]of early sexual development. His mother noticed
0 T; Y8 |2 {9 r. j! I3 ulight colored pubic hair development when he was
- ]# C, O, H8 {+ M6 W# y6 LFrom the 1Division of Pediatric Endocrinology, 2University of
2 f/ r W7 u" p4 t3 ESouth Alabama Medical Center, Mobile, Alabama.8 O! u: X$ n1 e& I' L7 X
Address correspondence to: Samar K. Bhowmick, MD, FACE,
/ _" o- X5 q9 c8 u% D$ j# }Professor of Pediatrics, University of South Alabama, College of
2 J, q; ?# c" aMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;5 s8 y2 F1 h0 E& }7 v; m( t
e-mail: [email protected].
# x7 ?+ ?+ R vabout 6 to 7 months old, which progressively became
2 u; E# [4 w+ S7 W8 }darker. She was also concerned about the enlarge-5 C" l' ]0 t e1 O( E, x; A
ment of his penis and frequent erections. The child
$ x) r7 E/ Z' \) {9 v* w- Swas the product of a full-term normal delivery, with$ t% E3 r. V8 \: K
a birth weight of 7 lb 14 oz, and birth length of
2 C; s# o8 S2 I- k20 inches. He was breast-fed throughout the first year( n9 C r* ? |" U) `
of life and was still receiving breast milk along with
/ l! d6 o8 d0 u4 u" }$ M- m- Nsolid food. He had no hospitalizations or surgery,
# B9 K [1 t* @5 {( _" a( iand his psychosocial and psychomotor development
% U2 b/ z( P2 owas age appropriate." z+ H' G% ~ z! x
The family history was remarkable for the father,4 X: l; K; _! }' O6 t1 d4 {
who was diagnosed with hypothyroidism at age 16,
6 C/ J9 I2 l9 z# cwhich was treated with thyroxine. The father’s
. o: A; B; V/ ?height was 6 feet, and he went through a somewhat" V' E, h$ K$ Z! B9 u3 r, h* `7 ^
early puberty and had stopped growing by age 14.
" y I+ R4 ^! D. ^7 X: y, zThe father denied taking any other medication. The2 a: ~1 B; ]! p+ C
child’s mother was in good health. Her menarche
0 k: }% I1 m; n5 s6 C7 fwas at 11 years of age, and her height was at 5 feet' x- K3 S. F1 p7 V- h
5 inches. There was no other family history of pre-
/ s3 N. h. `6 Q: B j B ncocious sexual development in the first-degree rela-6 r$ q0 B9 L! n- S9 V
tives. There were no siblings.& q$ V- p6 `% x/ [9 `
Physical Examination$ Q& {7 J ~& H3 u0 W
The physical examination revealed a very active,( g% v3 L2 j1 Z" ^5 w# O f3 j
playful, and healthy boy. The vital signs documented
0 K% g2 Q8 j7 u" s# Ra blood pressure of 85/50 mm Hg, his length was
3 M: T- ?' Z) G1 m90 cm (>97th percentile), and his weight was 14.4 kg" g* O0 y9 _7 ] {! A
(also >97th percentile). The observed yearly growth: h( Q! y" B5 |1 Z0 T, W/ l+ |+ o
velocity was 30 cm (12 inches). The examination of
/ Q; s& p* j6 O. Bthe neck revealed no thyroid enlargement.: f3 L/ v) P* i
The genitourinary examination was remarkable for& Q" U- x3 _9 l, L1 |# c ~
enlargement of the penis, with a stretched length of
* ]% L) _$ J2 G& D8 cm and a width of 2 cm. The glans penis was very well
1 d1 {3 y5 J" r( p2 f% G0 Tdeveloped. The pubic hair was Tanner II, mostly around
% |- K& k+ _6 @5407 w: R( ?: z( D. Q& P) V- K
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
! P( C8 f, G" ~the base of the phallus and was dark and curled. The5 S i7 e6 {7 c5 d* v1 v" q9 p1 y
testicular volume was prepubertal at 2 mL each.
# a: |6 h" w2 H | IThe skin was moist and smooth and somewhat; Z( ^ H0 C" N# c) b5 A
oily. No axillary hair was noted. There were no% U: h, @& B4 ]" t- G
abnormal skin pigmentations or café-au-lait spots.
6 d2 A, |; w$ e+ i7 Q% cNeurologic evaluation showed deep tendon reflex 2+
( R% r/ o$ w$ q, N B& [4 Hbilateral and symmetrical. There was no suggestion
$ T0 j6 I& q* N- ]4 e4 |2 l- c) c( cof papilledema.
5 E( T" u2 j f( J. iLaboratory Evaluation/ y7 ?+ a6 N9 A
The bone age was consistent with 28 months by+ N& @4 G7 \3 j' q) |/ Z2 i
using the standard of Greulich and Pyle at a chrono-
8 _( B" M' }6 W+ x5 dlogic age of 16 months (advanced).5 Chromosomal
6 v/ U' @( Z7 `/ a5 vkaryotype was 46XY. The thyroid function test
% g. g+ ?9 K/ U; ?" f, Q4 D) l, Nshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
1 P6 [7 U4 y+ n0 P2 J4 Hlating hormone level was 1.3 µIU/mL (both normal).: T7 v$ c; n0 c8 }4 e% k
The concentrations of serum electrolytes, blood
+ |5 s: h; l1 {# h6 j0 aurea nitrogen, creatinine, and calcium all were' R) P' V8 U6 e
within normal range for his age. The concentration+ J" X* `* E# U, u
of serum 17-hydroxyprogesterone was 16 ng/dL
' Y1 n/ ~! ^1 V" L z- ]+ ?/ d(normal, 3 to 90 ng/dL), androstenedione was 20$ Y+ u! r- w* j
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-5 ?' G+ x [7 N( K) {+ N) x6 F" [
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
5 G# C% [. B* k" }+ wdesoxycorticosterone was 4.3 ng/dL (normal, 7 to
# M; @2 t5 R9 d49ng/dL), 11-desoxycortisol (specific compound S)
- E% i2 G Q; l8 f" qwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-0 G5 P( ]3 l: L$ r; n9 g
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total) i* r% X" F( L0 f& ^7 q7 V0 c- j5 Y
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
% E. X! W( |) D3 R0 i) a; _; Dand β-human chorionic gonadotropin was less than; v: b9 l) G8 T
5 mIU/mL (normal <5 mIU/mL). Serum follicular
& Z4 ~5 x* P6 u" [- g9 v$ fstimulating hormone and leuteinizing hormone
# a. s8 T. k: m, T$ Tconcentrations were less than 0.05 mIU/mL
4 s, [$ m; {' G( s. |: ~(prepubertal).1 }& O/ {# s' T& X
The parents were notified about the laboratory2 |8 @0 O# J4 ^0 ?: C8 j2 h
results and were informed that all of the tests were1 O P1 V2 U* E3 ^
normal except the testosterone level was high. The4 I( Z" h* | B7 `# {
follow-up visit was arranged within a few weeks to
) }4 ~$ x) C1 |4 D2 d4 J' _obtain testicular and abdominal sonograms; how-
7 q: N3 U- S+ a! d8 f) X% _2 d* u& uever, the family did not return for 4 months.3 n- e8 I* M1 @2 w8 N% `" L
Physical examination at this time revealed that the
$ o2 [2 G+ V1 o. Ychild had grown 2.5 cm in 4 months and had gained
4 ^4 e' U. h2 A; e5 u3 D& x& ?2 G2 kg of weight. Physical examination remained
7 Q6 |( F6 X' Z G: N6 iunchanged. Surprisingly, the pubic hair almost com-, q N, R1 t! i- |+ I
pletely disappeared except for a few vellous hairs at
& Z, n5 L8 y/ k8 }9 x0 S1 c+ v9 fthe base of the phallus. Testicular volume was still 2! y1 D! [$ E+ w5 B
mL, and the size of the penis remained unchanged.; W& ^# A' {) @6 }' |2 v
The mother also said that the boy was no longer hav-
1 _5 m) z! W }6 Z4 Hing frequent erections.' p( B& T2 @' f% Y3 B, K% J! F
Both parents were again questioned about use of j$ v- I* j' o$ ^
any ointment/creams that they may have applied to
6 D L3 @4 K: ~9 y0 Wthe child’s skin. This time the father admitted the/ O; j! _% b) V7 O
Topical Testosterone Exposure / Bhowmick et al 541% v* Y9 g! G* {. V# m, m0 f
use of testosterone gel twice daily that he was apply-
4 I r& H( k6 X5 ying over his own shoulders, chest, and back area for
' g/ p4 n* n/ N7 _2 Va year. The father also revealed he was embarrassed
* U: t$ z* V2 |, D, I5 T2 u& {+ rto disclose that he was using a testosterone gel pre-
, ~6 g( E& ^5 F! i' hscribed by his family physician for decreased libido% K6 w- F! P! w
secondary to depression.) K1 ~; O" \! T
The child slept in the same bed with parents.
+ D; Y# {% S( p0 ]: ]& o' P' LThe father would hug the baby and hold him on his* _6 }. S+ ^7 q0 Z
chest for a considerable period of time, causing sig-" r5 r* p7 M$ q1 [
nificant bare skin contact between baby and father.
+ ?1 S. s# h* }, ~0 I' a0 u# DThe father also admitted that after the phone call,1 q% c& y4 ^! \1 W
when he learned the testosterone level in the baby
' P l# n; Y& Z& Ewas high, he then read the product information" k3 H0 o& g4 P- r
packet and concluded that it was most likely the rea-
! X* f- |" y- J" d* json for the child’s virilization. At that time, they
4 V, y$ A- |: g. {7 ?# Ydecided to put the baby in a separate bed, and the
! J) P5 k" |9 K! Kfather was not hugging him with bare skin and had8 ]: P( Z+ k2 |4 m& W! x) ~
been using protective clothing. A repeat testosterone1 L: R/ W2 j( h- k0 U3 I
test was ordered, but the family did not go to the( G8 ?- T0 A9 H4 \2 L# {1 f
laboratory to obtain the test.; x7 j/ q9 \5 C& B! d
Discussion: M' N9 i1 M! H8 `6 `2 x' `" F& j
Precocious puberty in boys is defined as secondary, X4 Y$ Z5 ]& E
sexual development before 9 years of age.1,4
8 j5 B/ p$ U9 |Precocious puberty is termed as central (true) when7 Z3 o* H+ K% n. r* `
it is caused by the premature activation of hypo-
9 [" q! [, `/ z0 ]6 Sthalamic pituitary gonadal axis. CPP is more com-9 U) o; C& r$ w! s
mon in girls than in boys.1,3 Most boys with CPP+ B& K3 g! e, I2 H: P
may have a central nervous system lesion that is
" B: O3 Q6 u; |9 T w- Y# presponsible for the early activation of the hypothal-
0 R4 g# q8 Q \9 }+ T1 ]' r! Qamic pituitary gonadal axis.1-3 Thus, greater empha-
# B4 x; c. u* Y0 O$ v* @- qsis has been given to neuroradiologic imaging in
) L N+ _' `/ j0 j6 T2 Z- Lboys with precocious puberty. In addition to viril-
# N2 x8 e1 n A9 R) bization, the clinical hallmark of CPP is the symmet-& S) c% X( M. |; g* e
rical testicular growth secondary to stimulation by
; m% x) N2 D- |/ Agonadotropins.1,37 R6 c$ T* l4 Q% @3 A. Z1 T
Gonadotropin-independent peripheral preco-$ K. M& k+ o L4 Y; S2 S
cious puberty in boys also results from inappropriate" X8 ^" W. v) q& \
androgenic stimulation from either endogenous or
( V+ ~ R! J' }* L" N- Lexogenous sources, nonpituitary gonadotropin stim-# p+ D8 e0 H* T% q
ulation, and rare activating mutations.3 Virilizing' Y3 |3 N# h% A3 ]
congenital adrenal hyperplasia producing excessive1 r, W% e3 u6 x' F# i8 r8 {
adrenal androgens is a common cause of precocious
4 ]$ P% ^, K/ j9 A, o5 Ipuberty in boys.3,4
% b4 I1 V5 {+ H1 V9 }The most common form of congenital adrenal
6 [+ g1 A6 T9 H% P; O6 Ohyperplasia is the 21-hydroxylase enzyme deficiency.
) I( U3 x3 i: oThe 11-β hydroxylase deficiency may also result in& x" ~# t4 f( Q. }
excessive adrenal androgen production, and rarely,
$ a6 V7 \1 N; [ X- kan adrenal tumor may also cause adrenal androgen+ e: H8 M7 R% S4 Z, w
excess.1,3
$ U" P, t% W* I" ~at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from+ j$ W: k/ L1 j# t2 C: g# ^- ^
542 Clinical Pediatrics / Vol. 46, No. 6, July 20076 E, Z9 r5 z5 r8 G& I
A unique entity of male-limited gonadotropin-- @, i) m( @2 U/ ?- e" Q
independent precocious puberty, which is also known
+ A. H" S9 B: F, ras testotoxicosis, may cause precocious puberty at a
) a- ~+ @6 i$ `8 m+ N. Ivery young age. The physical findings in these boys: H% w' n. [4 {! ]' C8 o
with this disorder are full pubertal development,
( w: p6 q, Z6 d4 Z3 Cincluding bilateral testicular growth, similar to boys1 F4 f4 X1 x2 L& }
with CPP. The gonadotropin levels in this disorder
( d S' |5 `3 {/ M$ i0 pare suppressed to prepubertal levels and do not show) H% T& j( T* I, g
pubertal response of gonadotropin after gonadotropin-- D$ K# R* d0 ~# T6 H
releasing hormone stimulation. This is a sex-linked
8 H8 W/ v% U* D4 |' }autosomal dominant disorder that affects only6 H- p+ d6 t) c; K
males; therefore, other male members of the family$ U) l4 ^/ Z$ `
may have similar precocious puberty.3
+ s* { v/ [- _8 d. `. v2 o+ i" AIn our patient, physical examination was incon-
5 G2 p- U# }! z2 n: M5 q' A9 }sistent with true precocious puberty since his testi-5 K, D9 u" C) `/ z3 I) k: l
cles were prepubertal in size. However, testotoxicosis
- }1 m% p; R) n- q5 Wwas in the differential diagnosis because his father
0 Z: N6 B+ D% L" ?$ k9 qstarted puberty somewhat early, and occasionally,
4 x# [+ o5 _0 n, Ztesticular enlargement is not that evident in the
8 I( @$ [( S( p, _1 d6 Bbeginning of this process.1 In the absence of a neg-
& X9 G# u5 c# D( _/ I/ Pative initial history of androgen exposure, our$ g6 F3 u1 g3 J& C' g6 K3 u4 I
biggest concern was virilizing adrenal hyperplasia,
1 x1 @3 ^( o. s, w1 ?either 21-hydroxylase deficiency or 11-β hydroxylase5 t% x8 f! l4 a3 u1 C
deficiency. Those diagnoses were excluded by find-% ~7 N7 N1 M( I) t8 @
ing the normal level of adrenal steroids.
6 h; y0 L* d! O4 m. x* e% }2 RThe diagnosis of exogenous androgens was strongly; w* e0 Q; i+ }* e! l( K
suspected in a follow-up visit after 4 months because
3 Z* [1 k% T2 z8 D3 c1 V' gthe physical examination revealed the complete disap-
* Z" `0 D' w( B4 `$ Npearance of pubic hair, normal growth velocity, and! ]9 n/ m5 J! X5 I
decreased erections. The father admitted using a testos-
* @' P# s/ z0 Nterone gel, which he concealed at first visit. He was
+ K3 z# T, M2 k( |using it rather frequently, twice a day. The Physicians’
( A S* Z) S$ a5 g+ P3 {Desk Reference, or package insert of this product, gel or& c: {* P* O# Y# @0 W+ |
cream, cautions about dermal testosterone transfer to( r/ @: Y7 i0 ]/ U% G6 b
unprotected females through direct skin exposure.
0 C% D' G5 g, R1 u& ?Serum testosterone level was found to be 2 times the4 x% {: |. U6 x: _: A; L
baseline value in those females who were exposed to
; e# \) `( l, f! B% `( h+ l0 M& geven 15 minutes of direct skin contact with their male
5 j+ y3 l2 r1 ?9 ]. {. spartners.6 However, when a shirt covered the applica-. Y. o' T7 w' Y% U- C6 y
tion site, this testosterone transfer was prevented.
0 x) h1 `- K- E% n9 xOur patient’s testosterone level was 60 ng/mL,0 n7 [$ S7 E0 n% g; h. q
which was clearly high. Some studies suggest that% d0 o' }/ R9 N1 X( _3 f* D! V
dermal conversion of testosterone to dihydrotestos-
0 h% d! P. f; {9 Mterone, which is a more potent metabolite, is more
" y) T: D! @3 N9 T! \/ k' Ractive in young children exposed to testosterone
( i Q. D: r3 A5 }exogenously7; however, we did not measure a dihy-& Q- a6 h3 S* ^8 J! T
drotestosterone level in our patient. In addition to
k; L' O! g* ?9 t4 c, U! `virilization, exposure to exogenous testosterone in5 q: i4 n4 i* R$ N. b: U: A
children results in an increase in growth velocity and4 P; e( B- l9 T* c$ ?( v
advanced bone age, as seen in our patient.5 u8 |0 j' r% i" @$ @: v1 @
The long-term effect of androgen exposure during
0 ^0 u/ O1 n$ G$ e8 h( G6 B6 i7 Tearly childhood on pubertal development and final
! M. w3 f5 B+ X, [; o! u/ s# sadult height are not fully known and always remain/ @3 ]0 b5 t/ `6 `
a concern. Children treated with short-term testos-
" E0 ]+ L; s* z" nterone injection or topical androgen may exhibit some# q3 c+ l8 n6 @- q4 z5 k; S0 [9 Q' J7 @
acceleration of the skeletal maturation; however, after5 O4 |3 t; @4 ~; O, H& X, ^2 o6 Z5 I
cessation of treatment, the rate of bone maturation
+ K, s$ S# t- f; }, |decelerates and gradually returns to normal.8,9& K* l* `# k# ^$ {9 ~, I
There are conflicting reports and controversy
/ E; m$ @( S" ~& I( }9 Hover the effect of early androgen exposure on adult
' a/ n- [$ i9 Y* l, g$ n6 Hpenile length.10,11 Some reports suggest subnormal# T+ f g r! O0 |5 k
adult penile length, apparently because of downreg-: a S6 ]( j `, Z4 }- A; d
ulation of androgen receptor number.10,12 However,
: ?: u- M7 P3 q# }Sutherland et al13 did not find a correlation between" X, h) G5 C0 c: w5 W" n4 z
childhood testosterone exposure and reduced adult
5 \6 W5 T9 f' D8 Npenile length in clinical studies.
4 R1 l% t$ g p* q9 A, g6 vNonetheless, we do not believe our patient is
* u2 o$ f' v$ p4 Ygoing to experience any of the untoward effects from/ v4 m2 f; V$ O' x
testosterone exposure as mentioned earlier because
6 C. y4 M! V' d' ^3 ?4 N' Ithe exposure was not for a prolonged period of time.
# g5 T( A1 h/ _' m; F# x$ nAlthough the bone age was advanced at the time of! F) s [, X; X, e* }
diagnosis, the child had a normal growth velocity at. Q) A* D% B8 a
the follow-up visit. It is hoped that his final adult
. g$ x1 m/ t x/ z, C: Cheight will not be affected.$ d: \8 Z* e; b
Although rarely reported, the widespread avail-
0 f8 D$ e+ |) ^3 I |: O( F% P V# cability of androgen products in our society may
2 C( u7 j' l& p( a$ Hindeed cause more virilization in male or female
! V& G& b5 M0 o- e' K0 U/ fchildren than one would realize. Exposure to andro-
$ s7 ]" _( `, ]7 [7 o. z! Z6 egen products must be considered and specific ques-
4 W3 k+ I6 ~$ j8 [tioning about the use of a testosterone product or5 _$ r3 [! e5 }
gel should be asked of the family members during! j4 n0 g: j+ [4 |5 }' r; E+ [
the evaluation of any children who present with vir-0 u: p" L5 |/ R: z+ f5 ?9 z* }# }
ilization or peripheral precocious puberty. The diag-) U# [6 y& s; B5 L
nosis can be established by just a few tests and by
8 p5 x* B! K: f2 `6 yappropriate history. The inability to obtain such a: K" h" P# B* c" D' w2 o! s7 j
history, or failure to ask the specific questions, may& j& `' t$ p& u& m
result in extensive, unnecessary, and expensive
! X: c! N6 j2 \3 p. D) N7 Rinvestigation. The primary care physician should be6 G8 h8 E! d2 e. R3 A4 o, |: X
aware of this fact, because most of these children
( E% ?" o) m2 F, R0 tmay initially present in their practice. The Physicians’3 r) j, \; Y5 l3 C; ~6 N; f9 A
Desk Reference and package insert should also put a
, ^1 l; W, d; b1 X( N+ R7 fwarning about the virilizing effect on a male or6 M! w8 J3 }: Z! E; A6 ?& ?
female child who might come in contact with some-
2 Y) S4 C2 R0 E* hone using any of these products.) t# V! {+ c$ p# A" ?. m
References
7 F, [$ K9 c! Y. P( r. ^1. Styne DM. The testes: disorder of sexual differentiation
8 ?" u& V3 t3 Xand puberty in the male. In: Sperling MA, ed. Pediatric
7 ?: \" H) w! u9 U9 q. fEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
1 n+ H: p' S! u' |2002: 565-628.- w7 F/ B8 h8 k' _6 p4 C2 y. H
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious: R1 f# B9 K& z g! I
puberty in children with tumours of the suprasellar pineal |
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