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Sexual Precocity in a 16-Month-Old
* Z" b! j0 Z, S, h& _Boy Induced by Indirect Topical: V/ W+ U" v. u; Z. I- W4 Y  O1 m/ J
Exposure to Testosterone
* B6 z$ g. k' n2 s1 o) XSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
; `# j1 H, l7 P* F' eand Kenneth R. Rettig, MD16 \$ l- t/ O; b! H5 ^9 W! h; k
Clinical Pediatrics
* a0 U: m& ~# `1 jVolume 46 Number 6
! U- S6 r& J! _3 a) CJuly 2007 540-5434 t- }8 S: }! U0 q" H
© 2007 Sage Publications1 n3 C! f4 I5 E* d: f6 z  U/ R
10.1177/0009922806296651
5 a% w9 L7 g$ Y/ B1 B8 M* Fhttp://clp.sagepub.com2 N! a2 D6 q. @) x+ e* ~' F' S
hosted at, x% Y. a* d2 L, }8 D. _$ u  _6 B
http://online.sagepub.com
+ P6 ?& y+ x' g! z: j& I2 zPrecocious puberty in boys, central or peripheral,
7 h$ }- X  V& G; n  y% Dis a significant concern for physicians. Central0 t& f) b( c7 Y
precocious puberty (CPP), which is mediated9 T9 H- W/ x+ F/ a9 h* E' z. O: |6 j
through the hypothalamic pituitary gonadal axis, has
5 a' W" S, d5 ?( ja higher incidence of organic central nervous system3 l3 A/ M; K; i' l% }/ L9 H6 W9 l
lesions in boys.1,2 Virilization in boys, as manifested
- F3 ?/ j: O& ?4 r  h; b1 |, p8 Nby enlargement of the penis, development of pubic
/ `4 l  r% m+ l7 z) @& j$ y. hhair, and facial acne without enlargement of testi-- l$ s. w4 O" z
cles, suggests peripheral or pseudopuberty.1-3 We8 y5 Q# [2 p' d8 x- F& Q' f0 h
report a 16-month-old boy who presented with the3 i) g! u7 ?+ W' C
enlargement of the phallus and pubic hair develop-6 U8 g2 y' H( T) F' @) g* H
ment without testicular enlargement, which was due/ H, |# {3 n# A$ F( x; N* L7 E" J
to the unintentional exposure to androgen gel used by; H$ N3 ]; {# H
the father. The family initially concealed this infor-! t0 Y8 d% w% X0 A( s
mation, resulting in an extensive work-up for this$ D& w: |; V# f2 X' U3 k0 {" q. d
child. Given the widespread and easy availability of
7 V, [7 n. ?# C+ T$ J8 \: dtestosterone gel and cream, we believe this is proba-1 B& ?9 l' `/ d0 A1 \- A
bly more common than the rare case report in the
# T9 v; \# \3 |3 lliterature.4/ Z! t, [  J- n8 y
Patient Report- I& h* u0 g* p! T% h: I- e0 f
A 16-month-old white child was referred to the
) @6 z! C6 H$ |4 N# zendocrine clinic by his pediatrician with the concern: X3 x- J# y7 O: `7 T  M0 t) S
of early sexual development. His mother noticed
, p( q$ N5 W# U* F1 u; Nlight colored pubic hair development when he was
3 F; }. y  [% r3 A, w. d+ VFrom the 1Division of Pediatric Endocrinology, 2University of9 Q: c- z7 @0 }! g" {
South Alabama Medical Center, Mobile, Alabama.) y1 ^" o7 e9 T% c8 L* d( X: `
Address correspondence to: Samar K. Bhowmick, MD, FACE,$ K  m) f; i. s8 W7 w
Professor of Pediatrics, University of South Alabama, College of
) _  u& H8 C# ]: Z4 O. O" LMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;; }8 W' e- ~+ P# U# M% Q' Y
e-mail: [email protected]." ^& k9 K3 a  @& W, j, v
about 6 to 7 months old, which progressively became7 L) a. P1 s0 K0 H% Y
darker. She was also concerned about the enlarge-
/ N' F# E2 o* w2 Q' s0 B$ l, H0 sment of his penis and frequent erections. The child
2 Q  Q( T" a4 d) j! O& z6 Ywas the product of a full-term normal delivery, with8 I, T' }0 |- f* ?" I
a birth weight of 7 lb 14 oz, and birth length of
% C/ Y" e2 j6 |9 E' Z% o/ N& {20 inches. He was breast-fed throughout the first year
, y: h- Y6 {9 E5 _) Y1 F. {of life and was still receiving breast milk along with
6 E3 f! m2 ]& O6 z4 m8 H- Gsolid food. He had no hospitalizations or surgery,
# k3 ~6 e- D- d' A6 Zand his psychosocial and psychomotor development. U, u3 _: C( h4 L; ]* V/ s
was age appropriate.
7 Y) ]7 Y- B) z! EThe family history was remarkable for the father,1 K5 a( t0 z5 J7 H6 s  x' Z
who was diagnosed with hypothyroidism at age 16,
( }) p, R: }: I4 \which was treated with thyroxine. The father’s2 B0 x- \/ a/ p/ ]4 B
height was 6 feet, and he went through a somewhat7 [: U* f$ X5 D+ ~
early puberty and had stopped growing by age 14.
) Z* ~5 S; T+ f8 ~The father denied taking any other medication. The1 O3 z5 j! h" x1 x
child’s mother was in good health. Her menarche
8 M" F7 o; }4 a0 _- f# p7 [; n1 C3 o5 twas at 11 years of age, and her height was at 5 feet
% D, ]* a6 P# q& t5 inches. There was no other family history of pre-0 K# e6 i& L( V
cocious sexual development in the first-degree rela-
3 r7 r! f5 i1 U1 Q2 ^" Ftives. There were no siblings.' f( G8 a. K2 p* L: }- E; L- D2 @
Physical Examination
) G% |- G) b: s! wThe physical examination revealed a very active,
8 ^4 r+ w0 v; {" dplayful, and healthy boy. The vital signs documented
3 m! V  m. `# D1 Ea blood pressure of 85/50 mm Hg, his length was
2 Y$ G/ j* E, u3 U90 cm (>97th percentile), and his weight was 14.4 kg/ B2 W6 ?0 v4 a$ I& ?( E
(also >97th percentile). The observed yearly growth* K. E6 j4 L# P$ y/ ^
velocity was 30 cm (12 inches). The examination of
( b2 t  L( A7 s5 n& C7 Jthe neck revealed no thyroid enlargement.
3 m  E: G9 ^* ZThe genitourinary examination was remarkable for8 g% a. j! ?/ e+ K1 I; `) s
enlargement of the penis, with a stretched length of* z1 x: E8 {' k. R+ q
8 cm and a width of 2 cm. The glans penis was very well: V. M% H  n2 D' b
developed. The pubic hair was Tanner II, mostly around
" w/ I  k# g/ i/ `: r' J3 D540
; n1 E6 E; E) b) B* fat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
6 i, D9 v5 ^  z& B: l7 x0 Fthe base of the phallus and was dark and curled. The9 `, C! V6 H& P5 n
testicular volume was prepubertal at 2 mL each.7 q# ?1 h$ W  g" Z
The skin was moist and smooth and somewhat
& v* _4 K5 j- R4 e' noily. No axillary hair was noted. There were no
( L- p* U, N+ z- n+ T' W# Gabnormal skin pigmentations or café-au-lait spots.$ O3 U; E& f( b( t
Neurologic evaluation showed deep tendon reflex 2+
2 k( r  h  [5 I% G2 p! \3 Tbilateral and symmetrical. There was no suggestion( ?& C8 d, a- U) M1 H. B
of papilledema.
" A6 b' d7 b* b7 [Laboratory Evaluation
8 h* s" w/ P& WThe bone age was consistent with 28 months by* @; z$ Y+ y; J7 |( K
using the standard of Greulich and Pyle at a chrono-
1 U# F: @3 c2 C5 G; a* u9 alogic age of 16 months (advanced).5 Chromosomal
$ B( J' F4 k; i! U% r9 Kkaryotype was 46XY. The thyroid function test8 q1 C8 q( H( K8 G+ O
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
$ R3 P8 ]  j2 u# Q, zlating hormone level was 1.3 µIU/mL (both normal).
' h; ^/ B; O' e9 I" N& a; lThe concentrations of serum electrolytes, blood# b; {% ~  I% |+ j0 Y* }' P3 ?. @
urea nitrogen, creatinine, and calcium all were
3 [; r! J$ e# W* nwithin normal range for his age. The concentration. _# o+ v( w4 Y2 \+ @) k% N4 C3 y
of serum 17-hydroxyprogesterone was 16 ng/dL; |9 b! c+ ^9 E: |. d3 `
(normal, 3 to 90 ng/dL), androstenedione was 20
7 U2 a5 z! @1 h. x/ ?  ?8 P6 |ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-! o* }, \! M& W: f" T# I/ f& _
terone was 38 ng/dL (normal, 50 to 760 ng/dL),3 U( X5 j6 t3 ^- S, H: `: m
desoxycorticosterone was 4.3 ng/dL (normal, 7 to- g# c' C3 `/ T6 g, L2 n7 a. l
49ng/dL), 11-desoxycortisol (specific compound S)
3 I& N. H& `- S& \0 iwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
2 k1 `, R1 ~  ptisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
/ [' C) l7 h+ Z: @testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
4 u# p6 [9 }4 X# l$ s3 land β-human chorionic gonadotropin was less than, ~- H1 b/ w& S/ W. y
5 mIU/mL (normal <5 mIU/mL). Serum follicular
* L; y6 }& ^5 ^" d4 X  h$ Tstimulating hormone and leuteinizing hormone) }9 Q5 y' }  z: h  @0 I
concentrations were less than 0.05 mIU/mL2 g* Q$ ^; w/ u+ l' j
(prepubertal).5 p7 g4 ^5 ]$ ~5 A, h0 w
The parents were notified about the laboratory" Z+ Z0 O, \9 b9 l
results and were informed that all of the tests were
1 u$ W# q" J! s2 {normal except the testosterone level was high. The
/ V/ ]/ [2 D6 q0 x! wfollow-up visit was arranged within a few weeks to" A" u' q; R: _0 _+ U. ?+ K4 G
obtain testicular and abdominal sonograms; how-
* S7 A+ {1 S5 z. \0 R4 e4 i0 Iever, the family did not return for 4 months.
* h( _5 i. B) K% H7 LPhysical examination at this time revealed that the
' k# p6 j& C( z; J3 Z, Q2 Dchild had grown 2.5 cm in 4 months and had gained- l2 ~/ k9 o9 ~9 Q
2 kg of weight. Physical examination remained) C3 W# Q- P* h/ L
unchanged. Surprisingly, the pubic hair almost com-. x; A4 x5 z5 r$ Y2 I7 g. L: c
pletely disappeared except for a few vellous hairs at  n& X) ?( D4 V4 B' e  |5 K2 K5 ]  X  ]
the base of the phallus. Testicular volume was still 2
" Q# p5 Z+ \" `& \. p. [# p1 K: zmL, and the size of the penis remained unchanged.3 x+ _' Z) j) q5 `4 p! _' }3 E8 q
The mother also said that the boy was no longer hav-$ _8 C- U* K7 i+ U$ t# c/ V! b  C3 D
ing frequent erections.& I! `) `8 s% |
Both parents were again questioned about use of
( h( o; Z; q3 J* @! u4 Xany ointment/creams that they may have applied to
; I% E: P% N- ^$ h$ o% Fthe child’s skin. This time the father admitted the) c, i- G4 P0 ]+ b
Topical Testosterone Exposure / Bhowmick et al 541
3 n+ F, o) B2 @; N8 iuse of testosterone gel twice daily that he was apply-' T4 y. K2 d6 u, H: Y) S
ing over his own shoulders, chest, and back area for" M! W+ V  K) v. F7 f! Z$ D
a year. The father also revealed he was embarrassed% l- M" t  H/ v- ]% m0 O
to disclose that he was using a testosterone gel pre-
$ U8 p; T3 D7 W. m3 s* s0 I6 t1 ]+ bscribed by his family physician for decreased libido6 [0 i% B  w( c, o6 j
secondary to depression.+ v) l( C0 J& A( k
The child slept in the same bed with parents.5 |0 l+ k4 x+ C* b2 d2 a4 X+ y  o
The father would hug the baby and hold him on his
1 j' c; ~% W, Q/ Lchest for a considerable period of time, causing sig-6 o4 ~9 D1 A2 w
nificant bare skin contact between baby and father.
, g9 b% c: C# ?4 }The father also admitted that after the phone call,
* z: e. M1 j3 hwhen he learned the testosterone level in the baby" E+ Y- \1 U5 X& L" k  P. i' w
was high, he then read the product information
/ m6 ~+ L. D0 o2 Wpacket and concluded that it was most likely the rea-
% B! o( x( K, rson for the child’s virilization. At that time, they6 {: {; G  {& m3 R: ^0 O1 @1 A5 {- u
decided to put the baby in a separate bed, and the
) @7 }+ m* W+ _  u3 ^/ Dfather was not hugging him with bare skin and had
; i6 Q* q; q5 `# W- \; {+ wbeen using protective clothing. A repeat testosterone
; T2 k, D2 q4 M1 p: Utest was ordered, but the family did not go to the
* C, Z% Z, K- P% _laboratory to obtain the test.
8 l& K3 D! b: E9 q: M! v6 sDiscussion: ^( O- M  o: d) i" _! c) P6 _- F
Precocious puberty in boys is defined as secondary+ t% m- f( E+ X) H) A+ s0 o" y. Y
sexual development before 9 years of age.1,4# U$ E' ~  Q, v$ f; \9 G& {
Precocious puberty is termed as central (true) when
: R9 d' V- a8 V' c, F; G( Fit is caused by the premature activation of hypo-/ |9 F; z6 |! K, ?' _; W
thalamic pituitary gonadal axis. CPP is more com-7 W( l) j% f( J4 G1 Q
mon in girls than in boys.1,3 Most boys with CPP
) I" E# I: C0 `+ z4 m8 ~may have a central nervous system lesion that is$ q& B6 o5 `: b  ]8 g
responsible for the early activation of the hypothal-
0 a8 S1 Q8 X( S* [7 d: \! X% ~9 Jamic pituitary gonadal axis.1-3 Thus, greater empha-1 `5 C8 ^- u/ z$ o
sis has been given to neuroradiologic imaging in( ~3 p7 o; k3 V1 i: m
boys with precocious puberty. In addition to viril-/ ?' c' C( U7 @4 k& j
ization, the clinical hallmark of CPP is the symmet-8 R$ x8 E' j2 f0 v, K" D
rical testicular growth secondary to stimulation by
! k, Q" l' }0 L4 A( ~gonadotropins.1,33 T' |! [( D$ z+ H
Gonadotropin-independent peripheral preco-0 A( k: a* ?7 M" k% V- \8 l, @! k
cious puberty in boys also results from inappropriate* k! ?6 E' C, k+ L* z
androgenic stimulation from either endogenous or; @& P' v6 n) d; Q
exogenous sources, nonpituitary gonadotropin stim-+ J+ Y' ^" q- H$ q( B3 H. o
ulation, and rare activating mutations.3 Virilizing
: c: Y1 w  [: r" y( T/ Z$ {congenital adrenal hyperplasia producing excessive. F2 N. Z. [" n5 @1 |9 d
adrenal androgens is a common cause of precocious
% ~8 F" \1 d8 N1 T! t4 l! Xpuberty in boys.3,4
' Q& w: q2 n4 s8 [: i' o" QThe most common form of congenital adrenal
" {* i4 V: T% H9 |% hhyperplasia is the 21-hydroxylase enzyme deficiency.) R  Z2 I7 E" a2 J( Y% F
The 11-β hydroxylase deficiency may also result in
, f  e& ^& N/ h* w8 r& d4 {" v4 |excessive adrenal androgen production, and rarely,
2 B' F# @' Q; Dan adrenal tumor may also cause adrenal androgen9 x7 Y- O( @8 E
excess.1,3; l5 e, S) G; G% Y
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from9 F2 T4 L/ l1 s, }( J
542 Clinical Pediatrics / Vol. 46, No. 6, July 20076 D$ {5 t' G* ^+ C
A unique entity of male-limited gonadotropin-$ o8 S, k! s& C1 H
independent precocious puberty, which is also known
5 B, |& E* r/ _4 Z, n: [as testotoxicosis, may cause precocious puberty at a9 O0 }  [! W7 `- A" D- P- I
very young age. The physical findings in these boys
9 q% l, Q$ t* H+ f6 ?with this disorder are full pubertal development,; W5 J4 C8 }+ C+ Z
including bilateral testicular growth, similar to boys
' ?- k1 r/ A6 o% ]  S6 Qwith CPP. The gonadotropin levels in this disorder3 B8 j; E6 M3 A" @4 q6 E
are suppressed to prepubertal levels and do not show
/ c0 F( v$ m& W$ l( I( W+ Tpubertal response of gonadotropin after gonadotropin-7 P2 S, q5 C# {
releasing hormone stimulation. This is a sex-linked$ U: J2 c) I' s
autosomal dominant disorder that affects only
% @9 B8 Q: k! g$ t8 Qmales; therefore, other male members of the family
' E/ B& z, k7 \2 lmay have similar precocious puberty.3$ R6 q( a: Z3 c% T
In our patient, physical examination was incon-; ]! d" ]* s0 M) ?3 g
sistent with true precocious puberty since his testi-+ X4 T$ b: l/ C4 Y1 A
cles were prepubertal in size. However, testotoxicosis" _9 {, e2 i- j! e3 j  o6 P0 U4 g
was in the differential diagnosis because his father$ E' R$ B; S- o4 F" x& b, ]7 l
started puberty somewhat early, and occasionally,4 d& y0 J: ?. F! h5 {' A
testicular enlargement is not that evident in the: w- E( ~. `' G' [
beginning of this process.1 In the absence of a neg-
* v7 X# i3 |+ wative initial history of androgen exposure, our1 E  @4 U2 d% X! [& f7 z! o! |
biggest concern was virilizing adrenal hyperplasia,5 r* A/ q* L3 H& i: M7 H8 _
either 21-hydroxylase deficiency or 11-β hydroxylase6 f" A1 ?3 C8 G( z: Q
deficiency. Those diagnoses were excluded by find-/ w; f. p6 ^- Y6 q9 n  X5 E
ing the normal level of adrenal steroids.
+ k! L/ H$ n. ~  _The diagnosis of exogenous androgens was strongly
5 w: h' g& e# [  [  F* Bsuspected in a follow-up visit after 4 months because
) z) Z' I" x" D# _" V* y. Rthe physical examination revealed the complete disap-9 S- J2 C' p$ t5 k" m; `
pearance of pubic hair, normal growth velocity, and
  l; z1 h1 q4 B  w! adecreased erections. The father admitted using a testos-  S5 W. T5 r- R, n& r8 a
terone gel, which he concealed at first visit. He was
# \& b9 p2 }' u, fusing it rather frequently, twice a day. The Physicians’5 C; d, [- O% d9 m! g9 Q
Desk Reference, or package insert of this product, gel or
5 K' R  d9 t. v4 Dcream, cautions about dermal testosterone transfer to
% d9 r$ i2 D, m) T% g' k; [$ F# dunprotected females through direct skin exposure.2 |8 w+ y! B7 D! @4 s+ H
Serum testosterone level was found to be 2 times the
) i& f+ Y% N! G9 M; s3 qbaseline value in those females who were exposed to
7 i0 }6 I9 b9 m) _; F  Eeven 15 minutes of direct skin contact with their male
9 ?% b8 x' V" ?# z+ Y: w7 y9 jpartners.6 However, when a shirt covered the applica-5 p) E3 c) _0 u3 r5 C( h$ X% \* Y
tion site, this testosterone transfer was prevented.8 D" c% q; ~( U4 a
Our patient’s testosterone level was 60 ng/mL,
' i  W6 a# ]7 \8 j+ uwhich was clearly high. Some studies suggest that( ]; x( m8 g7 D' f! j, v1 K
dermal conversion of testosterone to dihydrotestos-
" h6 J3 a  ]1 d! n! B- H4 F  m7 f7 Kterone, which is a more potent metabolite, is more
* I& j. Y4 O- A9 O0 a$ X  Qactive in young children exposed to testosterone6 g4 k0 Y3 \* a9 x$ a
exogenously7; however, we did not measure a dihy-7 O( j) m8 }4 u$ M
drotestosterone level in our patient. In addition to
, c2 \. q6 L  X% ]virilization, exposure to exogenous testosterone in
3 P! N0 \# ?0 o% R( l0 h# mchildren results in an increase in growth velocity and
/ P9 w) c4 c2 T  {advanced bone age, as seen in our patient.+ X* E3 B5 g* f% x. x2 N4 j+ Y) r
The long-term effect of androgen exposure during2 m4 u% W! g, M# G
early childhood on pubertal development and final, `5 G- p, g3 E0 i" k, c9 }) w2 P
adult height are not fully known and always remain
: z* S8 J. p0 d+ Q' E0 X! B2 ia concern. Children treated with short-term testos-6 e- r; o3 M8 Y' W3 y, D  u- h. V
terone injection or topical androgen may exhibit some
9 Z2 o" j3 q# n5 Q  Q7 [7 E6 sacceleration of the skeletal maturation; however, after
4 S  ~) j2 P$ I, Ocessation of treatment, the rate of bone maturation1 b( m& u) ]- t( z" ~
decelerates and gradually returns to normal.8,90 T% q( O' w, n- D- q) d
There are conflicting reports and controversy
  E6 K& R9 O* E; s/ p! d: n3 Xover the effect of early androgen exposure on adult
$ S4 x+ s6 F) p+ @7 j4 i0 M# D  zpenile length.10,11 Some reports suggest subnormal& F6 `2 D% }) {( O2 ~, u
adult penile length, apparently because of downreg-& j8 @4 l3 g4 w$ x$ s, }1 [
ulation of androgen receptor number.10,12 However,
7 _1 |8 u& ^4 ]1 P) l9 r/ ~Sutherland et al13 did not find a correlation between: k# Z; X. M1 b, P
childhood testosterone exposure and reduced adult
2 n; O6 [! F, g4 I: Z' F1 t6 Npenile length in clinical studies.) H( u" ~6 t  G" q- D7 C# @
Nonetheless, we do not believe our patient is
( |/ z2 R- |# g. b5 jgoing to experience any of the untoward effects from% \  i) F) A/ j0 z7 B1 P7 c
testosterone exposure as mentioned earlier because
* D) @6 y: B5 a( g, f& dthe exposure was not for a prolonged period of time.
8 _, D7 H; [* _) `Although the bone age was advanced at the time of
. K3 P8 o! p* L8 C& Ddiagnosis, the child had a normal growth velocity at* S& W1 K2 B0 R  Z2 k7 M
the follow-up visit. It is hoped that his final adult
9 \) j+ Z8 P2 T3 T1 P! theight will not be affected.
1 x2 U. i+ j7 X3 q5 JAlthough rarely reported, the widespread avail-
% k9 b- ^; C& f0 B3 Jability of androgen products in our society may
. a- O- h) |5 ~' ?+ L: mindeed cause more virilization in male or female7 |( H" d% _8 B0 N; A  w* E
children than one would realize. Exposure to andro-9 @  N# h, f2 t9 G7 w
gen products must be considered and specific ques-
/ o% p+ h+ m7 b2 ltioning about the use of a testosterone product or& ^& \+ R. w& o; s2 g9 M! ?" A# Y! b
gel should be asked of the family members during. J/ n9 Q& B, x1 p7 {* V- o
the evaluation of any children who present with vir-0 f  _5 F$ f* _
ilization or peripheral precocious puberty. The diag-! {' g, h5 \0 D+ f5 L: G! d
nosis can be established by just a few tests and by
6 [" b. m7 l- uappropriate history. The inability to obtain such a
0 m: z9 M! H; C' \6 K: Nhistory, or failure to ask the specific questions, may1 K2 X: l0 c- P3 y2 a/ i3 x5 K' K
result in extensive, unnecessary, and expensive; `5 M3 O/ l, Z! A( O5 S
investigation. The primary care physician should be
: s- ~" L1 F  D" N& Q+ baware of this fact, because most of these children
, z' f5 g6 H) H0 D5 Xmay initially present in their practice. The Physicians’
) F. R* b& J2 R4 F4 m. WDesk Reference and package insert should also put a
; A0 }# i% O: I* E9 @warning about the virilizing effect on a male or
- \0 {5 v' k5 p8 W/ U3 I" b( mfemale child who might come in contact with some-
* h3 K7 q' O* G* pone using any of these products.9 L- C: f3 @3 g/ S
References
! L+ |+ o  e" \. z; W  B+ q1. Styne DM. The testes: disorder of sexual differentiation, \& m+ X( L- q' S* \5 M
and puberty in the male. In: Sperling MA, ed. Pediatric3 C4 e( D/ t8 |- `
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;- W& G8 V% A: f' v
2002: 565-628.
) i/ `9 z- ^/ U9 x2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious7 G; h; y; w4 s! f' z& L* _
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
1 B* X* o$ y. z' gBoy Induced by Indirect Topical
2 ]- s; d  f8 _% x! B7 nExposure to Testosterone& q/ c/ q" T! A0 n
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2" m) y( x3 I7 k
and Kenneth R. Rettig, MD1
$ i3 a& j6 c- d% g; o, uClinical Pediatrics
1 A. t  e$ w3 U# J  i  wVolume 46 Number 6
$ b7 v5 W' C* `8 E) z2 F8 g( \July 2007 540-543
; ^  K# H! h2 m+ o( @© 2007 Sage Publications
/ Q& h0 Q2 a' s; g9 h10.1177/0009922806296651
% \5 g) `5 ~: |" S6 Dhttp://clp.sagepub.com
2 ^9 M3 t0 c" Q* U, f* B3 \/ V4 Rhosted at9 h" l4 _5 d# h7 I/ n- {" A
http://online.sagepub.com' m- B+ E; u" e; ]
Precocious puberty in boys, central or peripheral,
9 P, |$ \2 o8 X3 G9 kis a significant concern for physicians. Central
: S! i9 p5 @8 |" G/ J* qprecocious puberty (CPP), which is mediated! m* P- R% l$ g
through the hypothalamic pituitary gonadal axis, has0 |0 D5 R/ B1 x' f* [
a higher incidence of organic central nervous system
* t- j! z7 G- V0 ^3 J5 _5 Slesions in boys.1,2 Virilization in boys, as manifested
' i& n: V9 X# [3 @' J* cby enlargement of the penis, development of pubic
; d& J0 Z% Y# U3 K0 ^' Uhair, and facial acne without enlargement of testi-7 J" p/ A. n" n, e: T7 H0 W3 `: M
cles, suggests peripheral or pseudopuberty.1-3 We: R/ r: q, {# Q- U9 V# ^3 Q/ `, b* u
report a 16-month-old boy who presented with the' f5 J/ w/ q+ I9 l& Z* a
enlargement of the phallus and pubic hair develop-
- w; ?4 d' k) y( ?- Qment without testicular enlargement, which was due7 g* ~* c9 W( |1 p, F) b. ~
to the unintentional exposure to androgen gel used by9 d) `; {- Y  M
the father. The family initially concealed this infor-, v* U( I5 T5 I- ]4 T+ r$ f, D" L8 R
mation, resulting in an extensive work-up for this
' `$ y' q+ O1 {, n- mchild. Given the widespread and easy availability of
% a  m! b, X& R8 ptestosterone gel and cream, we believe this is proba-/ |0 }2 _: a. U3 o# }2 ~
bly more common than the rare case report in the9 {' v; X& F5 `3 ?% e3 N9 T; @
literature.42 }% o% g# L( R. W2 x( R& ^
Patient Report- r" ^3 @+ o( _8 G% w; @( o* {
A 16-month-old white child was referred to the( d$ N, I0 ]5 H; F
endocrine clinic by his pediatrician with the concern& F  G2 x$ s; i3 q9 u
of early sexual development. His mother noticed
, ?+ J; N: {4 M: r6 ]7 X8 m* \light colored pubic hair development when he was: k# t. W' V# t" @' `
From the 1Division of Pediatric Endocrinology, 2University of
) i& V5 d% G: m/ ?0 JSouth Alabama Medical Center, Mobile, Alabama.5 y4 D0 l' z2 ~
Address correspondence to: Samar K. Bhowmick, MD, FACE,
8 p6 G3 t3 q  T6 y6 `9 @1 LProfessor of Pediatrics, University of South Alabama, College of* i6 c. z  C4 n- x, V
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
+ e  g) q8 y% U  Z% fe-mail: [email protected].
8 M8 z# W( j# R% L  x! t1 ]about 6 to 7 months old, which progressively became
2 X: |1 V- D( j% T, e( B4 [darker. She was also concerned about the enlarge-
4 i& ^9 n2 o8 q' @5 ~ment of his penis and frequent erections. The child
9 q8 O" P& I' z# N8 |- zwas the product of a full-term normal delivery, with
9 j1 O' w' `7 ~1 t, S: e, va birth weight of 7 lb 14 oz, and birth length of  k$ o" q0 f" P  s
20 inches. He was breast-fed throughout the first year+ H0 J; V  B5 e
of life and was still receiving breast milk along with
5 E2 S* _9 o: u) ^( S. h' o) k* isolid food. He had no hospitalizations or surgery,
' m: ~& S# ^2 ?2 {8 m8 B* O* T7 Pand his psychosocial and psychomotor development- H. p" }* T( _
was age appropriate.
6 V. ?/ M3 S) z, I( t- ^  RThe family history was remarkable for the father,* j8 }4 O) C# o. `. w3 u9 I
who was diagnosed with hypothyroidism at age 16,4 e0 @- D* ?% d2 s
which was treated with thyroxine. The father’s
8 W' h5 o2 L! E) q2 D2 I6 dheight was 6 feet, and he went through a somewhat
1 n) {# g" R+ w3 hearly puberty and had stopped growing by age 14.
* W% P9 |+ d6 S% {" w; r3 O7 HThe father denied taking any other medication. The/ I( L0 Y  W; @( ^+ Q# J
child’s mother was in good health. Her menarche+ c. G1 e" J8 z3 Z3 I5 \* e
was at 11 years of age, and her height was at 5 feet. E2 i) B; ]0 P4 r5 Y! K* t
5 inches. There was no other family history of pre-' c# j! ^2 `2 E& Y1 G0 I
cocious sexual development in the first-degree rela-/ {) q( m2 O5 Z9 }" c* S
tives. There were no siblings.
1 r/ e% y2 P- h* U) O5 I( APhysical Examination
7 k  e, E9 n- M% ?3 I: B- AThe physical examination revealed a very active,
0 ]) u; Q2 F9 s8 tplayful, and healthy boy. The vital signs documented
1 a2 Y' N6 C& f- c* Y/ aa blood pressure of 85/50 mm Hg, his length was
' ~$ ]- n9 ]: c/ ]& ^90 cm (>97th percentile), and his weight was 14.4 kg
3 g* \; ~- K' I5 d- c/ N(also >97th percentile). The observed yearly growth6 r! f1 k" _& T3 e( W: k' W6 L8 d
velocity was 30 cm (12 inches). The examination of
7 E& I) M+ I! w, {6 \/ k. K% Y* ithe neck revealed no thyroid enlargement.
5 D$ E" k  U& d' B% lThe genitourinary examination was remarkable for" Z5 S2 ~9 n- ?# Q. e
enlargement of the penis, with a stretched length of
' G% D/ U; q) q8 cm and a width of 2 cm. The glans penis was very well
7 f5 Y$ R* D5 F) q' d4 U" t. ]developed. The pubic hair was Tanner II, mostly around$ e' L9 R' i5 P" v0 S# `9 E
540
3 {. t6 J) R8 p, E2 [at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
& Z+ t& v: m3 W9 nthe base of the phallus and was dark and curled. The4 M' `4 n5 {+ `' ?7 m
testicular volume was prepubertal at 2 mL each.5 O+ W- X" t5 p
The skin was moist and smooth and somewhat
! K( `8 @! X: Moily. No axillary hair was noted. There were no
# f* q( k( @% b4 p8 Pabnormal skin pigmentations or café-au-lait spots.
/ t$ h9 c! g* B) |$ }Neurologic evaluation showed deep tendon reflex 2+) f3 Y0 i! Q" o( ^. S5 R; K+ g0 Z
bilateral and symmetrical. There was no suggestion
0 C+ Z) Z) r" Z4 F6 i  pof papilledema.2 V. h/ ]& B/ O* N" L6 G+ w% G
Laboratory Evaluation! Y8 Y8 e0 a- q/ |$ u
The bone age was consistent with 28 months by! X2 ~4 L9 V/ l; V
using the standard of Greulich and Pyle at a chrono-
2 Y6 B5 @  m1 D6 Clogic age of 16 months (advanced).5 Chromosomal# ^+ h  @: c# E9 E) r% m
karyotype was 46XY. The thyroid function test: d& K  W' z! x" T: h( \" u, {
showed a free T4 of 1.69 ng/dL, and thyroid stimu-& @) i& _) }0 U2 t
lating hormone level was 1.3 µIU/mL (both normal).
5 O" j+ Z" |& Y; a# L2 a0 y. |The concentrations of serum electrolytes, blood
. C6 J. H( I; f* |+ kurea nitrogen, creatinine, and calcium all were7 ^6 u  m, ]* G2 C) ]
within normal range for his age. The concentration
" h7 U  ^; c; I  E1 Qof serum 17-hydroxyprogesterone was 16 ng/dL$ ^4 U: V1 H, i8 K
(normal, 3 to 90 ng/dL), androstenedione was 20) u) Z" e: ]; m$ A# Z9 e* S
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
% ?* I# ~3 Q2 v4 c$ ]terone was 38 ng/dL (normal, 50 to 760 ng/dL),# Q6 x: n" X% M7 ^# @
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
/ n/ n% N' p$ x* @( e2 w. P49ng/dL), 11-desoxycortisol (specific compound S)9 W% H5 Y  @% g7 e  r* g
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-7 U# H; z# {6 _; o
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
4 C( o" N) E) ztestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
, ]7 |1 L. `! M9 F+ d, S" C* @and β-human chorionic gonadotropin was less than
, p" _7 |/ H- y' p5 mIU/mL (normal <5 mIU/mL). Serum follicular* M, a9 j' u9 V4 z% P8 y
stimulating hormone and leuteinizing hormone
4 {$ u7 \8 i  [$ R2 }5 P& Mconcentrations were less than 0.05 mIU/mL$ n" K2 O2 M+ I1 q7 I/ Z
(prepubertal).5 p) s7 L7 b$ k% A& l
The parents were notified about the laboratory3 Q. b9 v( ^4 |/ F0 y/ `
results and were informed that all of the tests were
# ~4 S9 W6 w7 F/ W7 r' dnormal except the testosterone level was high. The
( {! Z0 M1 k3 `8 M( Ifollow-up visit was arranged within a few weeks to
: a. O( P' j1 R6 \2 Tobtain testicular and abdominal sonograms; how-7 H0 z" a. d% ?  Z0 f
ever, the family did not return for 4 months.
5 t$ w4 q8 g+ H4 F- xPhysical examination at this time revealed that the
+ U3 j! U! v6 v/ n, F, O9 f4 \child had grown 2.5 cm in 4 months and had gained( `  m! s) v$ |0 h: V
2 kg of weight. Physical examination remained
# U$ [6 ]' U0 D3 Q* i( a4 nunchanged. Surprisingly, the pubic hair almost com-* L; [# [+ C) f' H8 F
pletely disappeared except for a few vellous hairs at
" K4 N  e) \0 @- T) f  xthe base of the phallus. Testicular volume was still 2
, o9 F" ]/ z9 O# }- m1 a# F) bmL, and the size of the penis remained unchanged.
5 f2 h/ K0 I' l: o3 LThe mother also said that the boy was no longer hav-# x) a+ U/ J' t# @- H5 S4 O% i/ ?' [3 e
ing frequent erections.) m4 A1 Q( G, z0 N
Both parents were again questioned about use of
3 B1 r. K( Y* T& _0 t) I! Oany ointment/creams that they may have applied to
# W3 n" P- m* {& V* I- k: H, Othe child’s skin. This time the father admitted the
2 p& N& \# a  |Topical Testosterone Exposure / Bhowmick et al 5412 m, ^# _, x! L- J8 v
use of testosterone gel twice daily that he was apply-( {( e9 p! z. ?1 X$ L% K
ing over his own shoulders, chest, and back area for# ?! }$ H  r8 z" |# j7 |) w% z, e3 B
a year. The father also revealed he was embarrassed
+ Z% a8 k4 I7 |9 T2 X, J5 J% b( @to disclose that he was using a testosterone gel pre-8 ?. W, f& S9 B
scribed by his family physician for decreased libido3 f, r" N5 L$ f
secondary to depression.
# f% |& `& w: v0 }% O  KThe child slept in the same bed with parents.3 T5 b  {; N3 @2 U* U
The father would hug the baby and hold him on his' n, c  y( Z% j8 x6 e+ E
chest for a considerable period of time, causing sig-. l6 k6 t  l' E9 r0 Y5 D5 H
nificant bare skin contact between baby and father.* h% f! \3 G% T- `  g1 H
The father also admitted that after the phone call,
) q& o8 G/ ~6 w8 c" p4 Mwhen he learned the testosterone level in the baby
6 v; t8 c8 ?& x" ]; k1 C- wwas high, he then read the product information3 s/ @2 ^) ^% Z5 E; R6 c
packet and concluded that it was most likely the rea-; u1 J+ `: E( s9 i' _6 J
son for the child’s virilization. At that time, they
/ X8 s0 t2 x7 ?8 Ndecided to put the baby in a separate bed, and the1 [5 f" a- J+ C6 b* ~3 A5 i8 ]7 `
father was not hugging him with bare skin and had; c7 v* m1 d; @( r5 [
been using protective clothing. A repeat testosterone. G1 K- D! H$ B4 Q
test was ordered, but the family did not go to the
; N9 [, V9 U9 `. _) \laboratory to obtain the test.
. a4 J( o) u8 k3 T' Q6 r3 t( z3 yDiscussion1 x' F0 {+ X3 Z' L
Precocious puberty in boys is defined as secondary
( u/ I  j; N$ y7 Q3 Rsexual development before 9 years of age.1,4
  ~; m1 i7 |# r: \9 J5 P+ U% k. ]Precocious puberty is termed as central (true) when
# d+ G: d, ?" i! N+ Wit is caused by the premature activation of hypo-
0 s5 S/ |% y1 s% Nthalamic pituitary gonadal axis. CPP is more com-
4 o1 C* E9 N' `& t! S! i7 zmon in girls than in boys.1,3 Most boys with CPP
3 g0 b4 _& @6 K. L1 q! Smay have a central nervous system lesion that is' s- g$ X. o* _- [$ f+ h
responsible for the early activation of the hypothal-4 }+ q. M" p/ Y5 r
amic pituitary gonadal axis.1-3 Thus, greater empha-0 S& k8 i: r7 v) g! X
sis has been given to neuroradiologic imaging in
1 T$ p5 @9 ]% o1 `7 p- N% J4 nboys with precocious puberty. In addition to viril-
+ z- s7 T. V& B3 Y( n! Tization, the clinical hallmark of CPP is the symmet-
  e9 m- m5 r# k# d; {rical testicular growth secondary to stimulation by
3 _0 L) W# ]1 p9 L  \gonadotropins.1,3
, [* S% |+ e" U/ M) E9 QGonadotropin-independent peripheral preco-; O/ c) Y; T9 l% Q
cious puberty in boys also results from inappropriate
0 L& e4 t7 j1 X% L& \) Landrogenic stimulation from either endogenous or0 B6 B6 t" s: a0 E* B. s  R
exogenous sources, nonpituitary gonadotropin stim-
+ S- V7 [0 k- e- ^# z* Kulation, and rare activating mutations.3 Virilizing; I. W+ O  _7 h5 S( [
congenital adrenal hyperplasia producing excessive
$ u/ ^5 ^" i+ Q/ ~* wadrenal androgens is a common cause of precocious4 i: K# i" a/ }) F+ f2 f5 l8 W# a
puberty in boys.3,4, Y" B+ B! [/ S- P' L
The most common form of congenital adrenal* v! N, P8 R, D+ H* B) }
hyperplasia is the 21-hydroxylase enzyme deficiency.3 B7 k8 i. t  y5 m5 d
The 11-β hydroxylase deficiency may also result in
" m$ [! i" W5 g: S: q  o- Bexcessive adrenal androgen production, and rarely,
/ e4 \) r9 E3 E: `an adrenal tumor may also cause adrenal androgen
. ?4 a+ [- d+ L7 H" Yexcess.1,3
. d1 d2 N5 `: h6 U. F8 I6 Lat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from7 Z% {2 \3 ]9 Q" {+ k  |$ u  X
542 Clinical Pediatrics / Vol. 46, No. 6, July 20074 o+ {5 C: q+ d0 s3 e/ C4 F
A unique entity of male-limited gonadotropin-
6 q  Z2 H% C( T  Q3 o( B+ bindependent precocious puberty, which is also known' T, F6 ^. ]6 K# }  j3 n
as testotoxicosis, may cause precocious puberty at a
% H. M. q: F, d$ P4 k. ~very young age. The physical findings in these boys6 g6 @& E/ `% R* A7 p( a
with this disorder are full pubertal development,7 i" W: [# G0 q6 d( \& J! H# d9 b. P
including bilateral testicular growth, similar to boys
, y9 O, l, V& D; Y" T# N* Y1 Swith CPP. The gonadotropin levels in this disorder0 T* c3 i- Q. |: N5 P3 S
are suppressed to prepubertal levels and do not show! |. y9 |6 w) T4 h: ^7 g) M
pubertal response of gonadotropin after gonadotropin-
* f* H5 ?5 e6 {! ^1 yreleasing hormone stimulation. This is a sex-linked
+ c8 t2 R! W' Fautosomal dominant disorder that affects only2 q# @. u6 _1 i% J- c# s
males; therefore, other male members of the family
3 c- E0 h% _1 _3 b5 a: b3 [may have similar precocious puberty.3
$ g) u# B* w8 uIn our patient, physical examination was incon-
- l  |" e  b( _sistent with true precocious puberty since his testi-
$ i; Y& K+ X6 X) x$ D+ w% Ecles were prepubertal in size. However, testotoxicosis
$ M# a! A* f& O0 ~, ]7 ?  F6 ?. Wwas in the differential diagnosis because his father
4 _* O9 C& }& U5 }4 vstarted puberty somewhat early, and occasionally,! H+ c6 j' ]- o3 n# M
testicular enlargement is not that evident in the
% q0 c* j4 I6 _+ t6 \beginning of this process.1 In the absence of a neg-
8 k' u( |2 {% ~$ n0 vative initial history of androgen exposure, our
" o9 V8 ~6 U/ f& G1 gbiggest concern was virilizing adrenal hyperplasia,7 Y8 ~4 g3 K% \5 U1 l5 m& e
either 21-hydroxylase deficiency or 11-β hydroxylase
; G* V8 i7 u3 P6 j  `deficiency. Those diagnoses were excluded by find-0 m' y4 ?; ?1 s8 r. w
ing the normal level of adrenal steroids.- f  w: f6 R, H( l1 `5 P
The diagnosis of exogenous androgens was strongly
. i9 G0 B* L) [! T9 o0 J$ ~1 Xsuspected in a follow-up visit after 4 months because
' I# u/ F2 E# @the physical examination revealed the complete disap-
9 i0 ]! }3 \5 Y2 e+ o& ?: d, ]- Ppearance of pubic hair, normal growth velocity, and" f3 K4 U( `; y/ D1 a
decreased erections. The father admitted using a testos-4 q/ r/ O$ {. f% W
terone gel, which he concealed at first visit. He was2 s* x1 e* Q# ^* c; k
using it rather frequently, twice a day. The Physicians’
( Y5 T1 m" S* l1 g) W: @Desk Reference, or package insert of this product, gel or5 M  \! K( ~) B
cream, cautions about dermal testosterone transfer to
- P; ^/ q, z8 V) a. Z: V9 W! Aunprotected females through direct skin exposure.5 u: G; T" B3 l4 _2 c) p; K& i$ }
Serum testosterone level was found to be 2 times the
" R1 B. V2 f5 L( R# Hbaseline value in those females who were exposed to
2 k: f- K; \% |, L2 @even 15 minutes of direct skin contact with their male5 X# r  o; C6 Z. W+ x* P2 g; ?0 f
partners.6 However, when a shirt covered the applica-) ]# \9 n; Z* r! E. @7 S/ H
tion site, this testosterone transfer was prevented.) a! X4 B! E: r, {3 K. k
Our patient’s testosterone level was 60 ng/mL,+ B" S. h7 g2 [+ N1 ^7 k. |+ f* c
which was clearly high. Some studies suggest that% `; p: T. N1 ]* d0 [
dermal conversion of testosterone to dihydrotestos-6 K' H; Y; K! K8 n1 Y8 R0 x
terone, which is a more potent metabolite, is more" L* \: T  W5 g3 z$ s
active in young children exposed to testosterone$ `: q+ |, {" r5 Y3 l* V* S7 j
exogenously7; however, we did not measure a dihy-  E8 J" Q, ]1 ^* a
drotestosterone level in our patient. In addition to. d- g( r: w! j3 \
virilization, exposure to exogenous testosterone in- t- X) L' E( F% p- |
children results in an increase in growth velocity and
; V9 o& Z8 ?9 n2 N. Sadvanced bone age, as seen in our patient.
. v8 ]& ^1 s( m% z  [  YThe long-term effect of androgen exposure during+ D. _- J& X+ P! v
early childhood on pubertal development and final7 h0 E. s5 o1 l. K7 M
adult height are not fully known and always remain
# u) D, R4 g' s- b: ]- l& c" `a concern. Children treated with short-term testos-
4 O& o& H5 K/ _terone injection or topical androgen may exhibit some3 n3 w" H/ n$ z/ W& y
acceleration of the skeletal maturation; however, after
9 `. g8 h+ g+ e, g5 kcessation of treatment, the rate of bone maturation
5 z- x% _# W8 F$ t2 g7 Adecelerates and gradually returns to normal.8,9
! r; T4 P) @/ K- i. yThere are conflicting reports and controversy
+ B3 }. O2 t  I9 v+ O8 gover the effect of early androgen exposure on adult: J! n; O0 u# J% V, v0 [" L; A
penile length.10,11 Some reports suggest subnormal% g; n0 C. g  o% a0 b+ a
adult penile length, apparently because of downreg-& d9 l9 |! }- y0 j& l9 ^2 k, C
ulation of androgen receptor number.10,12 However,
7 m6 I2 M8 w: {# `Sutherland et al13 did not find a correlation between
. L' f+ r" J. d9 `* {0 r) m& Echildhood testosterone exposure and reduced adult+ V2 N' z9 ~: F* N+ Y9 I/ Z
penile length in clinical studies.
5 j! D; I# P8 cNonetheless, we do not believe our patient is
2 |  ^  B/ O1 z; h: \3 C8 H& |4 fgoing to experience any of the untoward effects from
+ E! |- E' z! r, T* Gtestosterone exposure as mentioned earlier because
5 H$ Y' @$ d) R5 L: I, Dthe exposure was not for a prolonged period of time.
& r% X. n7 c; K/ t* S& K0 [Although the bone age was advanced at the time of- j: O" N) {! y9 L% _
diagnosis, the child had a normal growth velocity at" i. Q1 X; c  \! S, T" I  S
the follow-up visit. It is hoped that his final adult
! j# q( l' F8 pheight will not be affected.' ~% U/ H2 {! ^1 b: `. }
Although rarely reported, the widespread avail-- u, D& T+ v1 \. T* {0 ~0 D) w
ability of androgen products in our society may
; I. O/ I# t+ |indeed cause more virilization in male or female
( Y, r/ U' s/ |* q& E8 r8 dchildren than one would realize. Exposure to andro-
( t; n, {4 t# K' `6 P1 Egen products must be considered and specific ques-& L/ m: P9 X, l( z
tioning about the use of a testosterone product or
; u! k3 T; k1 ugel should be asked of the family members during- R* O7 i5 ]5 S/ b' ~# a0 h
the evaluation of any children who present with vir-) O3 A. H" j5 H: @/ y3 @6 T3 r% ^
ilization or peripheral precocious puberty. The diag-3 f. `4 C! I( h6 c3 V1 O
nosis can be established by just a few tests and by  h& `+ R7 w& p2 z
appropriate history. The inability to obtain such a9 x' \# W. @9 R$ v# s
history, or failure to ask the specific questions, may) R* ?( E9 Y) c; i8 @7 [: [
result in extensive, unnecessary, and expensive$ \4 _% B. O+ X: Q2 X; K) P  @
investigation. The primary care physician should be$ O, ?( |/ S0 P3 @
aware of this fact, because most of these children+ P4 Z$ j1 X+ k/ l4 r# B
may initially present in their practice. The Physicians’
. V1 o7 Y0 k) g3 W5 BDesk Reference and package insert should also put a
4 h7 F8 u* D$ B5 S- q2 S' i) ~warning about the virilizing effect on a male or
* U( N7 f' K% l( ]; f- ?female child who might come in contact with some-" a- T0 S. F, z% H2 u8 F; @" d* @
one using any of these products.6 d% \# n4 K# s
References! a  F+ a6 v' U$ \9 g
1. Styne DM. The testes: disorder of sexual differentiation
+ t, z# S( K3 b; A$ N' A+ Gand puberty in the male. In: Sperling MA, ed. Pediatric
! B0 G# s8 E$ oEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
8 M. B5 S% a1 B- `* _- }. D$ u2002: 565-628.0 e2 ^- }: U' Y! [: O
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious. H( Y( J0 O, F7 Z0 M4 k0 a) M$ n
puberty in children with tumours of the suprasellar pineal
發表於 2025-1-11 22:18:01 | 顯示全部樓層
女厕偷拍辅导班主任尿尿老师的逼很嫩还有一点
發表於 2025-1-17 16:31:39 | 顯示全部樓層
4个什么样的?
發表於 2025-1-19 02:41:05 | 顯示全部樓層

, _# L7 W; N4 k9 M% k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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