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Sexual Precocity in a 16-Month-Old1 R# l/ L& N. X  B
Boy Induced by Indirect Topical
+ a$ `2 n: l! f) p  x6 lExposure to Testosterone4 C3 x0 j2 m% D: M9 c; g
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
3 `0 x5 X# D# _and Kenneth R. Rettig, MD1
/ j; D( k  S  U/ O: O* {" Q7 [4 ?Clinical Pediatrics: P1 z. {9 j/ m8 _) u7 E
Volume 46 Number 6
4 ]5 q5 h5 P0 \; J6 ^; s! {July 2007 540-543% `' d. Z* N/ I. L4 Q6 n
© 2007 Sage Publications
; ?5 |- n9 x. S- h/ ]4 H10.1177/0009922806296651
1 G" c0 Q$ b7 z. T+ i' uhttp://clp.sagepub.com
8 P& S0 q( o. o& z1 J& P0 phosted at
* e  V, u6 H) Y! Q# X' q2 ^# Ghttp://online.sagepub.com
$ A0 o" a: V4 L: ~. _  zPrecocious puberty in boys, central or peripheral,6 p% a8 {* s$ |& Y  h% v( {, ^+ U7 J
is a significant concern for physicians. Central
8 m, w5 W! A2 }+ c6 e& o) C' m  iprecocious puberty (CPP), which is mediated
" j: D! ?) S3 C# g  Lthrough the hypothalamic pituitary gonadal axis, has
; T) v  U; ?) L7 u( Na higher incidence of organic central nervous system
# s& S1 {$ j7 e- jlesions in boys.1,2 Virilization in boys, as manifested( @! z+ G; F; [( Q
by enlargement of the penis, development of pubic
1 ~$ e1 }- q$ ?  s& S2 E. chair, and facial acne without enlargement of testi-
0 V% V0 i! P. d( e3 k( {cles, suggests peripheral or pseudopuberty.1-3 We4 j: [- f9 I7 ~3 |
report a 16-month-old boy who presented with the/ Z# G+ N; x) F0 s1 ]8 H! ~
enlargement of the phallus and pubic hair develop-
# C- w) U2 I* T7 o! xment without testicular enlargement, which was due$ @& ]  Z, U' u8 h1 g
to the unintentional exposure to androgen gel used by. S: o# {9 o9 X  Y# b$ k/ F
the father. The family initially concealed this infor-3 s  J. B" I# t! k  O
mation, resulting in an extensive work-up for this" s  M* `1 ~" e& }" ^0 `. t
child. Given the widespread and easy availability of
* @9 I' }% l  C9 |testosterone gel and cream, we believe this is proba-) }! g3 N; P9 U
bly more common than the rare case report in the
8 e; S$ z' ~( L4 aliterature.4
- A' A% }1 ?  ?$ @/ X2 d. d3 HPatient Report2 \/ U' [! A& V1 D) K' D1 a- m' F4 Q% c
A 16-month-old white child was referred to the
+ A) }; T& x5 \) w& {( W. e) q3 |endocrine clinic by his pediatrician with the concern
# [; \0 {6 g4 n4 ?8 Fof early sexual development. His mother noticed
. g( j3 k1 B6 K9 u5 x- Clight colored pubic hair development when he was( J2 `3 b- ?6 K$ v; f1 t
From the 1Division of Pediatric Endocrinology, 2University of' B- X2 s5 B2 P6 S5 I7 r) c
South Alabama Medical Center, Mobile, Alabama.% f( n# g+ o( S# j
Address correspondence to: Samar K. Bhowmick, MD, FACE,) Y* z& b! g. j# Z3 s- \
Professor of Pediatrics, University of South Alabama, College of. z) T0 b$ S& }4 h! l+ A+ {: F
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
1 v% E% b% @( O, Ie-mail: [email protected].
6 ~2 E1 A( X! N' P0 u5 nabout 6 to 7 months old, which progressively became
( s: \7 \! X( u+ |6 e* f) {% Hdarker. She was also concerned about the enlarge-
/ y' W6 c8 ]1 U8 p! J' P$ O: Q/ zment of his penis and frequent erections. The child  `, e. R( `: b
was the product of a full-term normal delivery, with
( O9 p; ?6 e4 Va birth weight of 7 lb 14 oz, and birth length of/ k) P$ O  w: E7 E9 u2 W
20 inches. He was breast-fed throughout the first year) z$ h& S. E# y& D* U; n7 x% p5 X
of life and was still receiving breast milk along with/ K" B# q' l0 X1 {
solid food. He had no hospitalizations or surgery,6 Z- }# M" p+ h" n1 A0 I8 E& c
and his psychosocial and psychomotor development( `2 J6 |; y7 e: |& w( h, a
was age appropriate.
7 \: N4 T7 |* e- f5 Q& ]( qThe family history was remarkable for the father,3 J1 R! L, ^8 z' B9 ~( y
who was diagnosed with hypothyroidism at age 16,
4 C! K9 c. o" n7 _9 p& C% s* _! Bwhich was treated with thyroxine. The father’s
3 G& a4 k- e1 q& y! i% Z# E6 Theight was 6 feet, and he went through a somewhat( d+ }+ K: H" F2 o, H/ V
early puberty and had stopped growing by age 14.
0 H  g* i  e, D( bThe father denied taking any other medication. The* _& X! f3 i. ?2 q6 y5 u
child’s mother was in good health. Her menarche! a- z1 N* o; s1 y4 s' a4 `
was at 11 years of age, and her height was at 5 feet5 M. T! ?* ?8 `& [" K. [
5 inches. There was no other family history of pre-: x! p# X/ B, L! u
cocious sexual development in the first-degree rela-
2 l# r7 O. m3 f0 Xtives. There were no siblings.
& n9 Q$ c- f, g7 pPhysical Examination7 v  t3 D4 f3 `8 h$ w  w
The physical examination revealed a very active,: l7 W% p6 ~' K5 s: {
playful, and healthy boy. The vital signs documented
. w' o* A" r5 y, x. W! }3 Pa blood pressure of 85/50 mm Hg, his length was
  Y5 N- ]! g- y90 cm (>97th percentile), and his weight was 14.4 kg
" I, G+ u' X% Y* p; q6 {. t(also >97th percentile). The observed yearly growth
' `! R' U) B+ _$ Nvelocity was 30 cm (12 inches). The examination of& }' G4 a( J4 o  l
the neck revealed no thyroid enlargement.
+ K3 D' Y# I; aThe genitourinary examination was remarkable for& v; {/ D2 Y# [) c
enlargement of the penis, with a stretched length of
8 J, e% b1 f% F8 y: ?8 cm and a width of 2 cm. The glans penis was very well4 ^4 G3 w5 T, l! I
developed. The pubic hair was Tanner II, mostly around
4 N3 x# p9 T" d2 r* z9 Y540
$ n* G, ~7 Y1 L: ^5 T/ bat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
" k# R1 ^& b+ F3 sthe base of the phallus and was dark and curled. The
3 s2 Q0 @% @; a! g1 ~testicular volume was prepubertal at 2 mL each.1 l8 i  F. I. F5 M9 Q9 j
The skin was moist and smooth and somewhat6 I6 w5 K( j- J2 H2 Y
oily. No axillary hair was noted. There were no
/ l7 ]; w* n" }9 G4 q) T4 h! Fabnormal skin pigmentations or café-au-lait spots./ o) J. _& E" E" V' Q: j% v  u
Neurologic evaluation showed deep tendon reflex 2+# l- G8 G; S* h* G
bilateral and symmetrical. There was no suggestion, ~7 X4 z2 j$ l# m+ M. t8 l8 R
of papilledema.
% A$ ^9 o  p0 O. b+ P) mLaboratory Evaluation
, e+ K3 z" R" n6 V1 zThe bone age was consistent with 28 months by
: g6 [# _# l8 l, M# p1 ?6 iusing the standard of Greulich and Pyle at a chrono-
9 U; e0 g) @6 n, {logic age of 16 months (advanced).5 Chromosomal2 y8 n# v2 d6 v4 V# J; s. b2 x
karyotype was 46XY. The thyroid function test) v; \* G8 z. |1 w2 d
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
5 Z7 m( }5 ~, U; {; G& |1 U, Ulating hormone level was 1.3 µIU/mL (both normal).; r! ]6 D7 j( b
The concentrations of serum electrolytes, blood2 y7 Y4 Y- G$ I3 w6 c' Q, y
urea nitrogen, creatinine, and calcium all were! P; w4 H4 r9 q' H6 D
within normal range for his age. The concentration: R1 }! @' Z# V
of serum 17-hydroxyprogesterone was 16 ng/dL+ f7 i) U% s6 s- n( d
(normal, 3 to 90 ng/dL), androstenedione was 20
- i4 E# J' }& f  H  C. Cng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
3 ?* b; |, N7 D0 d6 v; lterone was 38 ng/dL (normal, 50 to 760 ng/dL),+ @- [4 `& D, {6 V0 G, n
desoxycorticosterone was 4.3 ng/dL (normal, 7 to3 \6 Z2 h- |: A# f% T3 o; ]& T- L
49ng/dL), 11-desoxycortisol (specific compound S)
9 i0 b3 n" P! t  M* ^7 ewas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
) H+ r+ z$ M: I) ~tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
. x: B  L# _, a* n, F: i! \" K5 I* p2 btestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
; _; t; ]8 E4 t# _) O9 jand β-human chorionic gonadotropin was less than
) v9 f; E0 T6 }4 J5 mIU/mL (normal <5 mIU/mL). Serum follicular0 K9 Q3 P! n6 P2 M1 X' k% e5 m
stimulating hormone and leuteinizing hormone
8 r% N/ {7 _, L+ O/ dconcentrations were less than 0.05 mIU/mL
3 D  t+ ?1 V+ x" J$ t% m2 u& a(prepubertal).# s+ J* C% n3 Z0 V" E4 r& _1 D
The parents were notified about the laboratory4 F* W/ c% g0 q2 V5 B! k
results and were informed that all of the tests were
. N9 s5 P" [6 U! ^normal except the testosterone level was high. The) s3 n& N+ ~7 E4 \, M
follow-up visit was arranged within a few weeks to! Q' q! M5 H0 K( E1 O) M( V
obtain testicular and abdominal sonograms; how-7 J6 J' t' s: w+ u/ X6 H% n2 \
ever, the family did not return for 4 months.! L) c1 Q2 M2 t4 V! \; |* v
Physical examination at this time revealed that the: M7 Z' N( \& q" |0 Y
child had grown 2.5 cm in 4 months and had gained- R0 {9 \# g  S" e+ C2 }  K
2 kg of weight. Physical examination remained
7 F6 a- r9 g) Gunchanged. Surprisingly, the pubic hair almost com-) D' n; U5 e0 a+ F$ ]
pletely disappeared except for a few vellous hairs at% U5 l+ n/ p/ D
the base of the phallus. Testicular volume was still 2
" r9 n. r  `9 k  O3 _mL, and the size of the penis remained unchanged.2 R$ E4 A' N4 d6 S* r
The mother also said that the boy was no longer hav-; U# H0 }+ C3 f" U0 f
ing frequent erections.( n5 ^0 I4 Z2 E0 @+ w6 A$ V
Both parents were again questioned about use of5 J9 @2 b. t4 m: E" |" O7 V) ?
any ointment/creams that they may have applied to
) p$ W5 j9 t* n8 mthe child’s skin. This time the father admitted the
0 x+ _6 c5 q& Z3 D4 F8 QTopical Testosterone Exposure / Bhowmick et al 541
& C$ v( e+ g% V: Puse of testosterone gel twice daily that he was apply-# Z2 C- F! s4 o. t
ing over his own shoulders, chest, and back area for
+ D/ E+ R' [( R$ ]8 M+ ]a year. The father also revealed he was embarrassed
) b0 X5 |' L  k' }& w/ Hto disclose that he was using a testosterone gel pre-+ Y0 B0 X% }  P, V& D* }3 g- y4 }
scribed by his family physician for decreased libido
- W3 e% G; D4 V6 h( [7 Qsecondary to depression.7 o6 V1 _$ |( b3 |# Z
The child slept in the same bed with parents.' ]0 }8 S  r2 ?" x
The father would hug the baby and hold him on his
: p5 g1 I; A8 achest for a considerable period of time, causing sig-
( N3 Z, d' `* }( \* |: ^) }; ^nificant bare skin contact between baby and father.
3 b) l) m; c' w; a% q9 SThe father also admitted that after the phone call,3 T  b; [' Z+ j
when he learned the testosterone level in the baby
4 `3 h( G* w+ o# Y) l$ @; qwas high, he then read the product information8 u# I. O4 e( Q1 p( a( C% Q+ M
packet and concluded that it was most likely the rea-$ N/ \# e) O" ?. h/ f& [
son for the child’s virilization. At that time, they9 ?& \% D; a* E0 O$ l6 W
decided to put the baby in a separate bed, and the5 `: A# F( M! N9 i& y7 ~+ m
father was not hugging him with bare skin and had
  Y+ F2 V0 X" u. z. c1 y0 Hbeen using protective clothing. A repeat testosterone
" L+ V, {2 k) K7 b# A4 `1 a6 Stest was ordered, but the family did not go to the
/ g4 ?7 _6 t  A3 m' f! _1 C  B5 elaboratory to obtain the test.5 ^; N9 Q; ^: o  M$ {
Discussion# O# x1 N2 G$ W
Precocious puberty in boys is defined as secondary
; j# F' W7 m0 W8 P; ]sexual development before 9 years of age.1,4
7 {6 ?# I4 w! F/ @Precocious puberty is termed as central (true) when
, |' H# R6 ^5 _- l2 C2 O' ]( w8 }it is caused by the premature activation of hypo-
: z9 V! N" ?( [, Q( kthalamic pituitary gonadal axis. CPP is more com-% t2 U& G2 y0 \5 |# f
mon in girls than in boys.1,3 Most boys with CPP
7 e4 T+ r. O% g( Q" y7 q) X' Smay have a central nervous system lesion that is
' h1 x& I4 {  K" l3 s6 J; Y. vresponsible for the early activation of the hypothal-
$ q  e' \, d$ @  l/ Eamic pituitary gonadal axis.1-3 Thus, greater empha-
, ^# d% a# g% G( W  B" t6 q5 P# |sis has been given to neuroradiologic imaging in, s. f1 J* k5 Q. |! a, Q+ J( f3 L
boys with precocious puberty. In addition to viril-7 V. T/ L! z1 p: @: K
ization, the clinical hallmark of CPP is the symmet-
+ G9 m- _+ B5 L: Z5 G9 W; l' f; crical testicular growth secondary to stimulation by
! P( n( o0 C: x. V0 T6 x8 m" M/ b+ kgonadotropins.1,3
! p' T! j# n! k) x5 KGonadotropin-independent peripheral preco-
6 @+ h- h* g% F" a; vcious puberty in boys also results from inappropriate% b( i3 w8 z0 K# P) h
androgenic stimulation from either endogenous or
" j( T' x5 J  r- d+ [* pexogenous sources, nonpituitary gonadotropin stim-
2 A  o( W6 y7 x& mulation, and rare activating mutations.3 Virilizing
  Z8 ]: z: D# a- d1 dcongenital adrenal hyperplasia producing excessive
  Z# E: N! U) k. p) u* V; u6 B" _adrenal androgens is a common cause of precocious
. g& w1 \+ p$ q0 W  Y' zpuberty in boys.3,4
& e  ?& Y$ P: r. k+ \The most common form of congenital adrenal
- c* y# k7 b- W* p+ X0 L% v  }hyperplasia is the 21-hydroxylase enzyme deficiency.
9 ?4 d( s" V; J8 I0 }& tThe 11-β hydroxylase deficiency may also result in
0 E; O. R- D% X. Jexcessive adrenal androgen production, and rarely,5 A4 a  ?' n/ M; T& P# }
an adrenal tumor may also cause adrenal androgen# X6 }) n) I- i4 b+ O% @8 g6 m2 e
excess.1,3  Y: ]. i, ], Y. r
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
5 a7 O; P% x( G2 [  b542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
# V5 o1 r6 G3 ~2 ]) v& VA unique entity of male-limited gonadotropin-
/ l8 X0 ^, a! g! o3 ^0 I) Findependent precocious puberty, which is also known
6 R! q" T# R) r* L, }as testotoxicosis, may cause precocious puberty at a
/ g; {) G8 Q/ y) }1 H: {& p' `very young age. The physical findings in these boys8 D1 a1 B3 M+ x1 x' v; ]
with this disorder are full pubertal development,
' S5 ]2 S% f' M$ hincluding bilateral testicular growth, similar to boys' [0 P6 d9 G' X3 {
with CPP. The gonadotropin levels in this disorder2 T' @" d8 z# K5 e* V6 V' @
are suppressed to prepubertal levels and do not show+ n/ {9 ~* Y3 p5 M
pubertal response of gonadotropin after gonadotropin-
3 k3 s/ b: t; I- hreleasing hormone stimulation. This is a sex-linked0 |" o; y3 U% k+ N; m
autosomal dominant disorder that affects only
# k- f0 X; A- j. v, d9 m9 X7 Zmales; therefore, other male members of the family
6 R) g) w: A! M; S6 Amay have similar precocious puberty.30 N8 p3 l3 C- m
In our patient, physical examination was incon-
5 O3 T5 w9 r0 |; i3 v0 ]/ L' Fsistent with true precocious puberty since his testi-1 @1 x: v  \5 ~, r3 B/ Z
cles were prepubertal in size. However, testotoxicosis
$ [, v* N8 n! V( Z% O" b$ Twas in the differential diagnosis because his father  d, x. m8 G0 L" b2 f
started puberty somewhat early, and occasionally,
2 G7 g: s6 N4 r* ^2 {# itesticular enlargement is not that evident in the
9 N* X; n) L5 a; Zbeginning of this process.1 In the absence of a neg-, v9 {5 w" t/ t7 ?  y6 C' T
ative initial history of androgen exposure, our
- ?& J. P! D  q7 S% P8 ~biggest concern was virilizing adrenal hyperplasia,
4 P. u+ S3 t+ B- neither 21-hydroxylase deficiency or 11-β hydroxylase
- I- r) L& f  ?7 g4 fdeficiency. Those diagnoses were excluded by find-
( l0 {( u+ U- `$ ^6 King the normal level of adrenal steroids.
2 g7 E9 `3 [8 c. P6 ^The diagnosis of exogenous androgens was strongly/ G' @' O- P9 {$ |1 Y6 [/ j
suspected in a follow-up visit after 4 months because1 C) S* p  c" a
the physical examination revealed the complete disap-3 z8 L9 ~; L$ j' i/ t3 }: Y9 }
pearance of pubic hair, normal growth velocity, and
4 C4 c% q( W0 v( Rdecreased erections. The father admitted using a testos-
+ i/ G  t3 w9 wterone gel, which he concealed at first visit. He was! ^1 b; M- c5 C0 r7 v
using it rather frequently, twice a day. The Physicians’
4 [: q: _5 B4 a+ M) EDesk Reference, or package insert of this product, gel or
! w8 ?, O+ l9 tcream, cautions about dermal testosterone transfer to
$ {( A" R. g' Sunprotected females through direct skin exposure.
3 \3 W5 H4 _( ^( f1 N5 K' LSerum testosterone level was found to be 2 times the: U) r$ e, F( B# o: f* u* y
baseline value in those females who were exposed to
* t4 X" s) L. e" o6 K/ q0 Peven 15 minutes of direct skin contact with their male
  h: z( j$ }7 y, ?& _partners.6 However, when a shirt covered the applica-7 Z4 z1 K* A- a( S7 \. E6 q
tion site, this testosterone transfer was prevented.
' G* u/ V0 ~7 c8 Z' U# ZOur patient’s testosterone level was 60 ng/mL,( x0 J  l5 b& _% d! g
which was clearly high. Some studies suggest that; K, Z5 f! J# ]" `$ z) h
dermal conversion of testosterone to dihydrotestos-9 a3 O5 L; P3 {4 ^
terone, which is a more potent metabolite, is more0 D$ p$ c& a8 P- d, H+ N( f
active in young children exposed to testosterone
4 X) b* ]- X. o5 l! K0 q, |) Fexogenously7; however, we did not measure a dihy-6 \! I* f, h+ [
drotestosterone level in our patient. In addition to7 x1 x! c) x5 ~2 D5 N( X3 p
virilization, exposure to exogenous testosterone in
/ b$ r1 [0 i+ achildren results in an increase in growth velocity and
4 M# v4 a  H% O) A  A+ ?advanced bone age, as seen in our patient.0 c, ]% p9 S7 N$ N' K0 ]& e
The long-term effect of androgen exposure during1 h- A& P' g+ J2 ?" t6 h
early childhood on pubertal development and final
2 O/ W( o$ d1 v/ F" A" n* y- madult height are not fully known and always remain- I# u* a& v6 m. l
a concern. Children treated with short-term testos-4 }# ~; b# }6 U' E& c. \) p
terone injection or topical androgen may exhibit some
6 Z5 ~/ ?/ q" R- R8 e& u, eacceleration of the skeletal maturation; however, after
( _9 p5 G4 L# w$ q8 f* V: Scessation of treatment, the rate of bone maturation
6 \6 Q% Y" P$ Xdecelerates and gradually returns to normal.8,92 v; T: X0 S5 F; o4 ^6 M# b7 G8 f3 E
There are conflicting reports and controversy2 E, q; ]& m5 p* E5 F
over the effect of early androgen exposure on adult
: \, F" W9 {$ j3 Jpenile length.10,11 Some reports suggest subnormal
4 e) S" T& r/ @2 `7 g6 E, oadult penile length, apparently because of downreg-
. F7 {7 \! b/ A" B# E7 j5 Wulation of androgen receptor number.10,12 However,
% c. x) I9 V6 VSutherland et al13 did not find a correlation between: E- l2 @7 e! o  s" O* }
childhood testosterone exposure and reduced adult
. T5 D; Q% I2 W* F2 U9 Hpenile length in clinical studies." d# \1 W" c- k- D$ s( I' ?
Nonetheless, we do not believe our patient is
  J1 ~/ d- r) U3 N+ fgoing to experience any of the untoward effects from( V( V4 A% N- H
testosterone exposure as mentioned earlier because) K2 V4 ~! ]0 Q( O
the exposure was not for a prolonged period of time.
5 }& U4 x. L3 ]% BAlthough the bone age was advanced at the time of
, M  p- \' @0 S0 Q3 ^5 B) c7 cdiagnosis, the child had a normal growth velocity at3 T- `1 J6 d" R  u9 a9 z, M
the follow-up visit. It is hoped that his final adult
1 F* z% c1 g. w/ |) o0 E9 xheight will not be affected.
4 w4 ]7 q6 O# K, ]5 fAlthough rarely reported, the widespread avail-
! C2 U8 T" v7 w. s0 Gability of androgen products in our society may+ d) c4 _! A3 i3 c- X
indeed cause more virilization in male or female# K' [5 S7 N& `
children than one would realize. Exposure to andro-3 B9 R6 T  m2 M1 r+ T
gen products must be considered and specific ques-7 g: h& d  H; _) ?: k6 ^$ B
tioning about the use of a testosterone product or
- q. y6 f6 N8 z) l5 Hgel should be asked of the family members during
1 ^6 G0 i5 x% B0 F9 C0 T' gthe evaluation of any children who present with vir-( j. [: D+ B; G& ?& a
ilization or peripheral precocious puberty. The diag-" \9 T  d+ u+ O% r
nosis can be established by just a few tests and by1 B. v8 d6 Q# ~# A) p0 g: j
appropriate history. The inability to obtain such a# ?/ _  Y5 K8 \6 S
history, or failure to ask the specific questions, may' I- q& f" P3 Z) ^
result in extensive, unnecessary, and expensive
* \$ ?; `6 m  r' Einvestigation. The primary care physician should be5 q3 l3 t4 v* v- X2 T" N
aware of this fact, because most of these children" E2 [  V- D7 Q( Z2 I# @
may initially present in their practice. The Physicians’
, u# \4 F8 W9 w( n0 dDesk Reference and package insert should also put a' w1 x* d/ x6 |' G0 _- X/ O
warning about the virilizing effect on a male or
5 Y& ?/ [7 v0 s& p7 Y% ffemale child who might come in contact with some-
7 N' x" K7 Z5 l9 W' H$ vone using any of these products.0 q/ h# _, ^6 ~, t4 H- @: j
References
5 K, x# {+ H; ~) N3 M4 S' s0 z1. Styne DM. The testes: disorder of sexual differentiation/ l/ l$ m9 o$ g$ S
and puberty in the male. In: Sperling MA, ed. Pediatric2 b4 y( E9 X  }; f
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;, ?! o6 @. Q3 C
2002: 565-628.
2 z; @: N; j: C% u" {9 a2 @* W2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious' \9 C& l) F9 H0 H
puberty in children with tumours of the suprasellar pineal
發表於 2025-1-4 03:27:02 | 顯示全部樓層
Sexual Precocity in a 16-Month-Old+ B8 [% C% K! J  v1 s: C2 y
Boy Induced by Indirect Topical7 a1 h4 b+ C) M
Exposure to Testosterone* z' M: T, q) H/ b6 F/ D
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
" k$ ^( z& y3 a: Cand Kenneth R. Rettig, MD1+ E7 n4 B& N  _/ `
Clinical Pediatrics
0 W. n9 A  E# \% I& i( t' \Volume 46 Number 6
$ y0 p5 r( i" b3 a# \6 TJuly 2007 540-543
1 w0 a4 E! a8 e1 F" c9 U0 S* T© 2007 Sage Publications
; B  A( X, _  U7 {; F! N: Y10.1177/0009922806296651
/ t( a0 T; y6 B/ A8 S0 I5 [% ]http://clp.sagepub.com+ f' x+ @: E" w8 ?
hosted at
4 x: J! A/ U, S9 Khttp://online.sagepub.com
+ t/ \3 c. S- X. oPrecocious puberty in boys, central or peripheral,' {  ~4 U8 t9 k( N8 @# z+ @
is a significant concern for physicians. Central
6 v- F; T  W& }* h! Yprecocious puberty (CPP), which is mediated6 o) V( s) `% \& \* S; o
through the hypothalamic pituitary gonadal axis, has7 t$ z) J* l- O( h/ ?" }' f$ k
a higher incidence of organic central nervous system4 [8 c. u4 K0 |5 T# Y' R
lesions in boys.1,2 Virilization in boys, as manifested8 `0 r* n+ [) P& j0 F8 }/ a
by enlargement of the penis, development of pubic+ s% [* x0 d8 h, O  ~* b2 V
hair, and facial acne without enlargement of testi-) A4 ?) S1 ^; Q0 M: Q% d
cles, suggests peripheral or pseudopuberty.1-3 We% k* _0 O0 D: m9 j' b
report a 16-month-old boy who presented with the
7 o6 {! |' R3 I' P' Zenlargement of the phallus and pubic hair develop-0 @0 j  J/ E! W# _
ment without testicular enlargement, which was due
9 }2 D3 @, ]/ j5 Kto the unintentional exposure to androgen gel used by1 Z7 P/ }, U% j
the father. The family initially concealed this infor-
7 P4 V! g1 e- W# z" W6 Hmation, resulting in an extensive work-up for this- J, W- a- [8 R) L+ G7 x
child. Given the widespread and easy availability of1 P  Q0 W$ `" S3 j0 l
testosterone gel and cream, we believe this is proba-+ g1 b/ r6 r* Y2 q% }  T  F$ }
bly more common than the rare case report in the
' h! k9 A0 x8 z1 q1 s9 Cliterature.4" G: P; k0 D# x% e8 B& z9 |
Patient Report
/ x4 |9 ?2 O( E% v/ d. QA 16-month-old white child was referred to the7 }. X. b' b/ C/ [+ K  Q
endocrine clinic by his pediatrician with the concern
1 ~2 b5 R1 U' j5 I0 l/ j; t! Oof early sexual development. His mother noticed
! t! K6 A7 T3 x$ h3 j" }light colored pubic hair development when he was
% [: Y# x# R6 e, S7 R  v9 m* I. dFrom the 1Division of Pediatric Endocrinology, 2University of
2 K6 B5 J9 J, I; b0 y3 ~South Alabama Medical Center, Mobile, Alabama.) h9 Q$ H* ?$ Z- K# Q. K7 g+ X1 s0 H
Address correspondence to: Samar K. Bhowmick, MD, FACE,
. m" [7 L3 u4 F9 zProfessor of Pediatrics, University of South Alabama, College of# S0 K. I" G+ L
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
1 H! c1 `7 _5 z; W) Y. A6 Z  le-mail: [email protected].
2 I, k! ?. l! ^about 6 to 7 months old, which progressively became* S& T; W1 _! U7 j# M% ]& h5 \1 k
darker. She was also concerned about the enlarge-0 k# j. g" m5 {0 P; Y
ment of his penis and frequent erections. The child# w" Q9 y% @8 `* p; a
was the product of a full-term normal delivery, with
4 a; B. X. p  K5 v2 }% na birth weight of 7 lb 14 oz, and birth length of
5 d! k& t6 c6 S% q9 l20 inches. He was breast-fed throughout the first year* h4 J1 R9 }9 {- J
of life and was still receiving breast milk along with/ S1 n: k2 N* O! W4 K9 q% j) W0 F
solid food. He had no hospitalizations or surgery,5 Y5 @6 d# J0 i) ?+ {. Q
and his psychosocial and psychomotor development; v2 U, {! r) N/ j* U  \3 m( _, H
was age appropriate.
& j4 L& Y2 {& m2 G4 Y) J9 ]7 w: VThe family history was remarkable for the father,
. X. r% h, y$ xwho was diagnosed with hypothyroidism at age 16,
, [. a- I$ t$ W, E; k0 Qwhich was treated with thyroxine. The father’s. P. @+ |; d! b* Z6 `+ Z- v
height was 6 feet, and he went through a somewhat
! `" Z6 F6 A" v$ ?7 x2 Nearly puberty and had stopped growing by age 14.( M6 j0 F( I4 l5 Z) w
The father denied taking any other medication. The
; D" T  |5 p! Q7 ^/ Bchild’s mother was in good health. Her menarche  ^# _' \/ _5 C# W$ h; V) g
was at 11 years of age, and her height was at 5 feet9 ^1 h8 h4 q) H; E6 |/ M
5 inches. There was no other family history of pre-
7 O& s4 _! A: a% c, V3 |) ?cocious sexual development in the first-degree rela-
5 S% k2 q9 d$ m# V( r- V) otives. There were no siblings.2 `0 @9 E5 o% m$ _! K
Physical Examination
+ |" _! Q0 _( Q+ h8 J+ B  ^The physical examination revealed a very active,; }. w4 i) [3 C8 }/ ?2 \
playful, and healthy boy. The vital signs documented* A0 V1 P) R( o  q
a blood pressure of 85/50 mm Hg, his length was3 Y3 h8 ~3 l# ~& t$ ?5 I8 X4 J: D8 D1 k
90 cm (>97th percentile), and his weight was 14.4 kg+ ]2 y: \8 f6 ?+ k! l2 K+ w1 q) U  R
(also >97th percentile). The observed yearly growth
  `% k' Z2 N* Qvelocity was 30 cm (12 inches). The examination of
& E; x4 k- S6 j: @the neck revealed no thyroid enlargement.
5 i1 @2 {' W0 K8 GThe genitourinary examination was remarkable for& |0 J0 l4 y0 l
enlargement of the penis, with a stretched length of
/ P7 y) m( N% O9 v% g7 t8 cm and a width of 2 cm. The glans penis was very well
7 F1 ]: S) d" _4 jdeveloped. The pubic hair was Tanner II, mostly around0 n( o% Z1 w9 A- Y+ V5 m5 o
540% l  O: i+ Z# t8 p3 n
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
" {! I( g1 j. m3 K% ~# ?the base of the phallus and was dark and curled. The) M" T. G7 w& K* o; S- t6 |( Z
testicular volume was prepubertal at 2 mL each.
! R3 q3 ~" U9 D+ S5 @The skin was moist and smooth and somewhat, E; p7 [" N* m+ K
oily. No axillary hair was noted. There were no
% s9 J9 `9 S" q' xabnormal skin pigmentations or café-au-lait spots.0 s2 T( K( }. D5 \* ^$ T* f: v, Z
Neurologic evaluation showed deep tendon reflex 2+2 \; ~" e: L0 X2 K, v
bilateral and symmetrical. There was no suggestion
* Y: ~1 S" {2 ~3 Wof papilledema.
5 z8 B8 Y- d+ _, h- }4 H* M7 SLaboratory Evaluation  k: Z# \  _8 I9 a2 ?! e
The bone age was consistent with 28 months by
9 F$ Q7 O/ M1 U. G9 _using the standard of Greulich and Pyle at a chrono-+ M" |& }' |8 B
logic age of 16 months (advanced).5 Chromosomal, q; G4 a( O8 ?2 H" N/ a- o
karyotype was 46XY. The thyroid function test+ m. }3 T8 [& o1 d
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
% f- f2 D2 F  k2 Klating hormone level was 1.3 µIU/mL (both normal).. z5 G* E$ o! m
The concentrations of serum electrolytes, blood! _& ~/ S- [+ o" ]8 {
urea nitrogen, creatinine, and calcium all were
& I5 Z$ n3 W9 O, m# Xwithin normal range for his age. The concentration- U! S% ^* H' O" `7 E+ L
of serum 17-hydroxyprogesterone was 16 ng/dL
( @: t/ G4 r& u: n, `(normal, 3 to 90 ng/dL), androstenedione was 202 y: l; E3 `! B  {% i
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
; \- j( M4 F2 h% y' w: m( X7 f5 [& @8 Fterone was 38 ng/dL (normal, 50 to 760 ng/dL),
/ m! w& b, d! ?* d% T! a0 R) d0 D# Fdesoxycorticosterone was 4.3 ng/dL (normal, 7 to
; E- F5 Z2 \0 L4 V# f" L! N49ng/dL), 11-desoxycortisol (specific compound S)7 _0 I5 b1 I0 W, y# D+ Q; g
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
2 k& ^( f( `. ?# Htisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total. }' z7 X+ U; s* ^1 \# {
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
/ d9 ]* t2 M3 s7 yand β-human chorionic gonadotropin was less than
. p  U& e6 s" ~& B( W5 mIU/mL (normal <5 mIU/mL). Serum follicular4 W+ ]& M2 D% @
stimulating hormone and leuteinizing hormone
% A+ Q2 Z0 v8 ]. y) @1 fconcentrations were less than 0.05 mIU/mL
/ M3 z; q5 M, ?  v(prepubertal).
; a( p- z! Q7 c0 C& uThe parents were notified about the laboratory
5 j, \9 U* |1 C' q8 ?results and were informed that all of the tests were3 i+ E7 e, U& P: z/ W* x0 k
normal except the testosterone level was high. The( b4 a( Z9 Y1 [0 U( x4 X; Z
follow-up visit was arranged within a few weeks to
4 `! [5 p6 B2 m: x4 \; wobtain testicular and abdominal sonograms; how-
% l( Y5 A! P; ^ever, the family did not return for 4 months." @7 k, }8 W. y, `% s0 w3 L6 i1 l
Physical examination at this time revealed that the
0 d  L+ N5 l$ U$ a- Echild had grown 2.5 cm in 4 months and had gained
$ U: J1 w% d" M0 }! g2 kg of weight. Physical examination remained
2 f- s* k9 ?4 u' N/ A) Bunchanged. Surprisingly, the pubic hair almost com-! t' u& {2 }+ h9 d: f
pletely disappeared except for a few vellous hairs at
0 M* q/ x) x  g6 ^; B  }: x- e. g) Hthe base of the phallus. Testicular volume was still 2, a5 r+ _: w. V# s
mL, and the size of the penis remained unchanged.
1 B+ [5 f7 F) Z5 U3 i/ j  UThe mother also said that the boy was no longer hav-
$ Y" \" a2 R1 S. y; I  U: Zing frequent erections.
: N* N) v, p0 w: ~Both parents were again questioned about use of- h5 @: ]# p$ h- E" d; w
any ointment/creams that they may have applied to
7 w! \- b4 k6 M9 o" m* S# z4 Jthe child’s skin. This time the father admitted the
8 C- q2 }8 x% [% wTopical Testosterone Exposure / Bhowmick et al 541/ A) o4 \" c* U
use of testosterone gel twice daily that he was apply-
8 r) l+ C. T! }+ ^- N7 d6 Ting over his own shoulders, chest, and back area for2 H# U& n3 N, u/ l8 @
a year. The father also revealed he was embarrassed
# c$ I0 {: L' b7 F' [6 m1 ?to disclose that he was using a testosterone gel pre-, T- j) p2 E" g8 h2 q. w3 O" |
scribed by his family physician for decreased libido
" b5 ~' x% p8 D/ }& \7 B( V5 B" ysecondary to depression.  [3 Z+ p, I7 W& K4 q
The child slept in the same bed with parents.
# @8 ?: r3 `8 N: `! t' T1 iThe father would hug the baby and hold him on his
" W/ w7 I+ M, Y! ?6 \; i) Rchest for a considerable period of time, causing sig-" [3 B" L3 R1 j8 |
nificant bare skin contact between baby and father.
4 Z" f7 ~0 b4 S1 K! m0 ~1 `* zThe father also admitted that after the phone call,
/ P& e0 Y: h) ?5 xwhen he learned the testosterone level in the baby# l, U* [* |% R- s' i. R  ~$ q
was high, he then read the product information  J- h; I9 ~: @; c1 L- S' r
packet and concluded that it was most likely the rea-. D8 A( u: K' K+ q7 C# ~# Y
son for the child’s virilization. At that time, they
4 m, ^& g% J# {- Pdecided to put the baby in a separate bed, and the$ c& X6 i0 I# y" ^( m4 j
father was not hugging him with bare skin and had/ x1 K) P$ J- M8 T
been using protective clothing. A repeat testosterone6 T# S5 Q0 p. e& q6 s
test was ordered, but the family did not go to the2 V& `& J3 K& z& t/ M) v* ]
laboratory to obtain the test.# T+ j% H4 l! T6 I% m" {* d3 x
Discussion
0 t3 L# D/ y+ B$ Q, O$ f! Z# P) QPrecocious puberty in boys is defined as secondary2 m5 y+ E2 X& X/ b6 d& |
sexual development before 9 years of age.1,4# {/ l4 N2 ~/ A5 S
Precocious puberty is termed as central (true) when( y2 v6 M4 C- h
it is caused by the premature activation of hypo-
/ v0 [3 P! r& ?6 W4 C9 j8 Hthalamic pituitary gonadal axis. CPP is more com-) F1 R7 E5 E9 ^2 R$ W
mon in girls than in boys.1,3 Most boys with CPP
0 L4 H2 J$ Y/ G! gmay have a central nervous system lesion that is
$ o: l9 D6 ?* N/ W. gresponsible for the early activation of the hypothal-, O6 p1 D1 Y% [: d$ o. E
amic pituitary gonadal axis.1-3 Thus, greater empha-
( ?+ i0 Y3 d1 H' O$ ]7 `% x2 [sis has been given to neuroradiologic imaging in
+ y/ O* i/ N) }3 W; Tboys with precocious puberty. In addition to viril-
: S- R1 @: c: b2 C1 U! wization, the clinical hallmark of CPP is the symmet-
; X  J5 G6 R- Rrical testicular growth secondary to stimulation by
3 c  J3 Q! K/ t; |! E& ?' O4 `gonadotropins.1,3
2 x; |: h+ y/ VGonadotropin-independent peripheral preco-4 q* B  l9 S% H  i# B9 C
cious puberty in boys also results from inappropriate
# n4 k  O6 r8 `( i/ q) Q: Q- randrogenic stimulation from either endogenous or
% ?4 G- p9 ]6 p1 i( A3 iexogenous sources, nonpituitary gonadotropin stim-+ J$ X* _0 U  N/ x& A) H* K$ F, n
ulation, and rare activating mutations.3 Virilizing
9 O  ?  i, Y& }$ `/ @! u4 m( Vcongenital adrenal hyperplasia producing excessive
: w' \5 J+ m1 R6 H- J/ jadrenal androgens is a common cause of precocious
6 j6 F2 a7 ~- G. _. i  Hpuberty in boys.3,4# W& z' k, v& H" v' c
The most common form of congenital adrenal
- f; n7 `* x/ H$ f! P# `4 p1 Ohyperplasia is the 21-hydroxylase enzyme deficiency." W! J0 i0 q4 q4 D6 ^6 \' i0 Z
The 11-β hydroxylase deficiency may also result in) F$ E. x4 J) I
excessive adrenal androgen production, and rarely,- b8 ?; t1 M* p
an adrenal tumor may also cause adrenal androgen
: v1 C: ]/ h' a$ N0 fexcess.1,39 Z5 V0 }. P% u% f6 h; C# r
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from& S6 L: C0 ]7 }6 h3 L5 H
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
/ `2 d9 D0 k* m: SA unique entity of male-limited gonadotropin-
0 B3 j" l. s  t7 }+ Mindependent precocious puberty, which is also known! p0 d9 c3 t9 z9 m! z- n
as testotoxicosis, may cause precocious puberty at a
4 L. E% W: x4 V0 K0 b7 ^3 h) \very young age. The physical findings in these boys" ?7 Z3 l4 O  K7 I; n
with this disorder are full pubertal development,
  t- ]1 t& `9 f% _* E2 Mincluding bilateral testicular growth, similar to boys
5 x5 ^7 r, C- t- K7 c1 p( \# Qwith CPP. The gonadotropin levels in this disorder% c) Q. e9 m( ]+ \& p. ]9 Y4 v
are suppressed to prepubertal levels and do not show
( ^( ~8 K! z* A$ ?pubertal response of gonadotropin after gonadotropin-* n. Q: A+ K& M$ Q4 Q
releasing hormone stimulation. This is a sex-linked3 h/ x" v9 `, p9 H
autosomal dominant disorder that affects only* O4 e9 R2 u3 f+ y0 E
males; therefore, other male members of the family
9 S9 s3 y: t4 S) Wmay have similar precocious puberty.3  ^' t" @+ j- p: l
In our patient, physical examination was incon-1 k0 j" j" r) U. J- {
sistent with true precocious puberty since his testi-+ |# K4 H; g, a# H, J0 }
cles were prepubertal in size. However, testotoxicosis
! u. m+ G1 g2 _" ^6 v* cwas in the differential diagnosis because his father% |4 W5 m0 j9 ^% t! j) L! s! [9 @% z
started puberty somewhat early, and occasionally,
; Z+ H+ B- r* D9 Z; w+ j+ h; Otesticular enlargement is not that evident in the
" x9 E& i3 G( Y9 ybeginning of this process.1 In the absence of a neg-4 i; l7 r4 X) [' I
ative initial history of androgen exposure, our! ~) B& R( B" C/ _/ V9 ^
biggest concern was virilizing adrenal hyperplasia,2 W% ?2 d' K) s5 v1 O
either 21-hydroxylase deficiency or 11-β hydroxylase
# Q3 C0 S2 L) V9 edeficiency. Those diagnoses were excluded by find-
0 A3 R4 m2 Q! Ting the normal level of adrenal steroids.
; O) D6 C8 w& Q  i" M7 UThe diagnosis of exogenous androgens was strongly
' U$ S8 I; A; b+ N6 {suspected in a follow-up visit after 4 months because
& e2 q9 r  {8 r0 f1 gthe physical examination revealed the complete disap-3 c: _1 {  d/ H( q7 @
pearance of pubic hair, normal growth velocity, and) A. l6 [3 o$ L5 K" b9 t
decreased erections. The father admitted using a testos-* J9 L% o5 }. ^
terone gel, which he concealed at first visit. He was" e% M/ d1 H, K* e3 {
using it rather frequently, twice a day. The Physicians’
1 ]; E5 d/ ^7 x; M; lDesk Reference, or package insert of this product, gel or
% x) ?$ h  S( dcream, cautions about dermal testosterone transfer to
: E, }% L* J9 v" a# }, b6 Q. r. eunprotected females through direct skin exposure.1 O2 P% a- y2 v) r
Serum testosterone level was found to be 2 times the4 ^1 `9 S! {$ E( H1 Z
baseline value in those females who were exposed to# h/ M  A' c' b4 y3 p& b
even 15 minutes of direct skin contact with their male$ O- ~1 _* D' ?, D1 W
partners.6 However, when a shirt covered the applica-2 o  A" k. w' O0 l
tion site, this testosterone transfer was prevented.# {, ~9 U' v( z1 Y, T
Our patient’s testosterone level was 60 ng/mL,
6 \3 O" t  C' }$ \6 hwhich was clearly high. Some studies suggest that, J% Q% Q8 h1 {* K" c
dermal conversion of testosterone to dihydrotestos-. h& t2 K$ b) @/ i. r. O
terone, which is a more potent metabolite, is more" `- O1 ~# J' J
active in young children exposed to testosterone
. `) z# T. x4 V5 {, [4 a0 x  O3 iexogenously7; however, we did not measure a dihy-! {+ {' I: m$ w9 p% o3 D
drotestosterone level in our patient. In addition to
# R' q9 j- {3 n5 X* ?& Gvirilization, exposure to exogenous testosterone in
" p9 b  _( O$ ]5 p. fchildren results in an increase in growth velocity and# d1 k; P" ^- d
advanced bone age, as seen in our patient.
9 J3 \2 U6 V. @) `$ xThe long-term effect of androgen exposure during
; ]0 H/ T6 G9 G+ j$ K: i+ l. D6 bearly childhood on pubertal development and final
9 D9 V0 _# J( b7 m2 Q: iadult height are not fully known and always remain5 O8 D$ d# O( O2 r1 |1 J
a concern. Children treated with short-term testos-
" }  {8 m+ j) Bterone injection or topical androgen may exhibit some
, n7 ]- Q/ S2 c$ A5 ~acceleration of the skeletal maturation; however, after
2 D* M$ ^/ q, @+ j* X0 O& _" j  Scessation of treatment, the rate of bone maturation% u% @+ w8 J- F; u; E6 a
decelerates and gradually returns to normal.8,9
6 c9 F$ ^  Y) C$ YThere are conflicting reports and controversy
8 h! |* e6 O0 J  `( A2 g9 Wover the effect of early androgen exposure on adult3 D7 b7 x+ i) q1 I1 @* i
penile length.10,11 Some reports suggest subnormal
+ E' M$ k/ r) P  zadult penile length, apparently because of downreg-6 T, q8 R5 k' N) T
ulation of androgen receptor number.10,12 However,
) A, X8 b& q# P. }4 f( z) Q# FSutherland et al13 did not find a correlation between" U+ ~1 m$ ?; Z2 E" p
childhood testosterone exposure and reduced adult
$ p- K! x5 q( O) i* R* H, Qpenile length in clinical studies.
# c$ l; n8 s7 B5 aNonetheless, we do not believe our patient is
$ X. H7 F' W5 G7 Y" T0 fgoing to experience any of the untoward effects from+ G+ u- Q/ I' P$ u
testosterone exposure as mentioned earlier because
, |/ ]# Q  Q& M, Ythe exposure was not for a prolonged period of time." \; Q' H* R% r6 r4 @. G( ?
Although the bone age was advanced at the time of2 k, j4 D$ ^; S% o
diagnosis, the child had a normal growth velocity at
9 X8 B; q$ P' Y1 ^# ^1 j5 @the follow-up visit. It is hoped that his final adult& T' ?) K5 ^+ K0 Z8 _* K, W; S# D6 e
height will not be affected.
5 A+ Z3 q! l* yAlthough rarely reported, the widespread avail-
0 B1 R- I4 C. H7 |# R* ~6 uability of androgen products in our society may- ~6 M8 b! h4 e) O
indeed cause more virilization in male or female, L7 T) F$ a' j3 C; G# s6 V
children than one would realize. Exposure to andro-( @  U, A! Y/ t9 [+ U3 [
gen products must be considered and specific ques-
1 f# O" p8 @0 s% n% g' V3 Ztioning about the use of a testosterone product or
, {9 a: Y5 c/ q4 T, v& bgel should be asked of the family members during, i) ]. _: s+ _: @4 D
the evaluation of any children who present with vir-
# d) Z* S* s2 C6 C4 }+ h( nilization or peripheral precocious puberty. The diag-
1 {& ^- r+ X( hnosis can be established by just a few tests and by
! O- R- @( o- i7 L7 V0 K4 r3 \appropriate history. The inability to obtain such a. o! q( Y, m5 l$ W# A& e6 M
history, or failure to ask the specific questions, may
" i& w  z3 y7 P7 I7 X- E6 R: jresult in extensive, unnecessary, and expensive, `8 `0 r9 T: q' i! M: g
investigation. The primary care physician should be0 k/ |; N' `8 L2 [
aware of this fact, because most of these children8 a+ t: w. X. n" g0 W; z
may initially present in their practice. The Physicians’
2 R. M$ a& h8 p5 ^# XDesk Reference and package insert should also put a
# R0 Y. ~/ z" q; ~% Qwarning about the virilizing effect on a male or, k% ~' Q( |3 I! ^1 o- ?$ l, \
female child who might come in contact with some-+ `2 P1 h7 F6 E. F
one using any of these products.
% a1 P& F. j& p! ~$ \References4 L& E. u  a7 q; n( ]1 y7 C+ E
1. Styne DM. The testes: disorder of sexual differentiation
8 @# e) W' w4 A4 sand puberty in the male. In: Sperling MA, ed. Pediatric6 V# C1 G8 E% N( U
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
2 `- T4 R2 x6 {1 Y2002: 565-628./ f8 y: F1 t+ K1 u' x
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious, G( m4 M" g# t4 N
puberty in children with tumours of the suprasellar pineal
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女厕偷拍辅导班主任尿尿老师的逼很嫩还有一点
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( A& g+ u" O  p$ U精妙絕倫的精品,感謝啊!期待你更多更好的創作哦!
發表於 2025-3-11 12:31:56 | 顯示全部樓層
么好吧v进化过程就回国参加发uft成就和;哦i回来就好v科技股份兄弟人的 路由公开vu个v库每年b
發表於 2025-4-8 11:10:25 | 顯示全部樓層
精妙絕倫的精品,感謝啊!期待你更多更好的創作哦!
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