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Sexual Precocity in a 16-Month-Old
3 M/ z# R$ S7 I6 [Boy Induced by Indirect Topical4 B& b7 m+ j, [6 i' ^- a7 c- {
Exposure to Testosterone' W4 ?+ u! N9 A2 I6 e: F
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
# h" H6 G- P7 C1 xand Kenneth R. Rettig, MD13 d) }% |- T  s
Clinical Pediatrics
6 W- ~+ b- W1 e; q/ F( }( k9 j4 XVolume 46 Number 6
/ d( M$ v- j  P/ d+ dJuly 2007 540-543  u: O8 |2 L" P+ X
© 2007 Sage Publications
0 I5 b9 r1 @. M# e$ t4 @& M10.1177/0009922806296651
( P) R7 ]: u) q) L8 e! Y0 Zhttp://clp.sagepub.com
: U* c' _1 ]* w0 }3 F: w/ bhosted at; G6 G0 g5 F# V: s4 `- S, T  y" @
http://online.sagepub.com
" A9 Q3 i3 E) NPrecocious puberty in boys, central or peripheral,5 b7 K$ |/ \& ^8 o: [
is a significant concern for physicians. Central5 A/ r- z4 o2 Y% I9 _
precocious puberty (CPP), which is mediated3 v. U  l  Y5 H) x2 Y% Y9 ?
through the hypothalamic pituitary gonadal axis, has$ H0 v+ ]( v4 d- V' f
a higher incidence of organic central nervous system
' Z; w! {6 s! ?: slesions in boys.1,2 Virilization in boys, as manifested
' U7 @4 f$ @( e, m& ~" iby enlargement of the penis, development of pubic' g7 B8 S# [) Z, [, B7 Q
hair, and facial acne without enlargement of testi-
8 `# c/ v1 _6 v" X1 ^cles, suggests peripheral or pseudopuberty.1-3 We
6 P* w6 u$ M& d3 L' E9 ?report a 16-month-old boy who presented with the
* I( C0 n( G" fenlargement of the phallus and pubic hair develop-/ c$ g% p7 f) C* B2 x1 n6 D
ment without testicular enlargement, which was due6 y9 j5 y/ \( U  g. W
to the unintentional exposure to androgen gel used by7 ]" ]- o/ m; x. v5 V% E
the father. The family initially concealed this infor-3 B1 u7 Y1 j/ o: j3 P7 C; i! A. m
mation, resulting in an extensive work-up for this
2 w7 ~+ }3 q; ?  {% ~# j8 w* d' lchild. Given the widespread and easy availability of) l: u4 q: B% q! I3 u
testosterone gel and cream, we believe this is proba-
' p; x  n% s1 I6 qbly more common than the rare case report in the9 B+ \4 o; T! Z; t" i  h; _! q
literature.4% ?' R- T0 i5 U
Patient Report* O* H6 I5 I  y/ l) m: h
A 16-month-old white child was referred to the
7 H7 S5 A, r! q, {endocrine clinic by his pediatrician with the concern$ L: _5 U% V5 _$ t
of early sexual development. His mother noticed: b* S( i, F/ p6 v  o' S8 `
light colored pubic hair development when he was
9 t$ K- ^) C3 I9 S4 fFrom the 1Division of Pediatric Endocrinology, 2University of
8 `: }# `2 ~% a7 l. W; ]6 t2 |- CSouth Alabama Medical Center, Mobile, Alabama.
% F2 Y" _% l9 x& o- q5 r+ LAddress correspondence to: Samar K. Bhowmick, MD, FACE,0 y& o1 |4 I! z
Professor of Pediatrics, University of South Alabama, College of1 a" [8 z9 y; L4 {; D% J$ c- w
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
) o( Q- d0 m: z3 Y3 Me-mail: [email protected].) k# n4 C- |+ {0 H! K
about 6 to 7 months old, which progressively became: F5 E% F7 A; z7 \
darker. She was also concerned about the enlarge-
6 f' G* g$ P1 B# ament of his penis and frequent erections. The child
) `9 G8 ^/ D- j. X- _8 N, k+ Kwas the product of a full-term normal delivery, with! M% m/ b! @: V) U6 Z6 C  A
a birth weight of 7 lb 14 oz, and birth length of# a7 w$ ?! D% J2 p3 |  r$ F# U
20 inches. He was breast-fed throughout the first year
' q  P2 H" |! ]; qof life and was still receiving breast milk along with# n, Q$ T, X' Z0 d7 c1 U( n
solid food. He had no hospitalizations or surgery,0 h; G% T7 ~0 a2 M
and his psychosocial and psychomotor development
) s/ f7 b6 v+ n' h6 D  Hwas age appropriate.: p, n  ^* U9 y8 [& j8 \. R
The family history was remarkable for the father,  C1 d" w8 a, _0 U5 t0 j
who was diagnosed with hypothyroidism at age 16,, G, z6 k: `! r: y  @2 `' }8 a
which was treated with thyroxine. The father’s! D$ q1 v! P# ]
height was 6 feet, and he went through a somewhat$ {# T- G: K0 \* b& v4 F
early puberty and had stopped growing by age 14.
3 F& V" a1 H9 w) JThe father denied taking any other medication. The
( ~$ t( p9 v3 g4 B/ }& dchild’s mother was in good health. Her menarche
% A0 R6 u( N% ~. _6 w3 Wwas at 11 years of age, and her height was at 5 feet7 ~0 g- M2 M# E
5 inches. There was no other family history of pre-3 B5 d, H' E5 d! H) n  t
cocious sexual development in the first-degree rela-- \: D) R% V4 ?
tives. There were no siblings.1 l/ B; ]! M5 ]4 v. Y3 U
Physical Examination
$ G( p0 V: t8 wThe physical examination revealed a very active,  |6 L. _1 M" u: ~
playful, and healthy boy. The vital signs documented
) [5 S" x- Y, F+ B) E+ X  |a blood pressure of 85/50 mm Hg, his length was
! Q3 _) F" L' y' G& R, b+ T9 M% R" @90 cm (>97th percentile), and his weight was 14.4 kg8 f$ D2 L$ f  n0 ~* P9 ~: m7 i
(also >97th percentile). The observed yearly growth. r+ z! G; S. P6 \/ p5 K+ ~
velocity was 30 cm (12 inches). The examination of7 _( @# O8 v+ n+ ]. c* w
the neck revealed no thyroid enlargement.
; J0 D" P5 H* N, {1 B1 A8 {/ zThe genitourinary examination was remarkable for2 M. V1 s! W5 _
enlargement of the penis, with a stretched length of
2 p* X1 _4 M3 Q8 cm and a width of 2 cm. The glans penis was very well% A3 V& b+ F0 d# \1 H' J+ q. V
developed. The pubic hair was Tanner II, mostly around
  C  `7 F  |1 A( @% y3 o540" w" S( R5 S* Y/ r; ]
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
) [9 g; o- p7 R. b+ h4 a  d- D( fthe base of the phallus and was dark and curled. The
! j/ }% b) t( f: u+ o3 j7 Etesticular volume was prepubertal at 2 mL each.
" L/ D5 e+ g7 v& hThe skin was moist and smooth and somewhat/ R. m& _7 |1 ?% R
oily. No axillary hair was noted. There were no
' r- w, E5 c) T+ p! ~/ kabnormal skin pigmentations or café-au-lait spots.
. l! d+ ~1 k# z9 c; aNeurologic evaluation showed deep tendon reflex 2+
8 y& R8 V/ r% y5 cbilateral and symmetrical. There was no suggestion( D0 B3 M. G% a! ~* @( N2 o
of papilledema.
" T% i" f: S, W9 O1 K0 YLaboratory Evaluation
' o8 E5 @7 T; s7 K  L& ~  v4 \3 FThe bone age was consistent with 28 months by: w* o8 q1 {: F6 t
using the standard of Greulich and Pyle at a chrono-  H0 X2 K+ W7 d3 Z6 L
logic age of 16 months (advanced).5 Chromosomal
  c' X  U& G6 d# Akaryotype was 46XY. The thyroid function test
0 V9 Z0 E6 I8 qshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
9 q5 G* |. _# b! Z* M8 e. F9 T" Alating hormone level was 1.3 µIU/mL (both normal).( i  a) `" ~9 E  z
The concentrations of serum electrolytes, blood6 |1 ?5 _: a2 p! x! m
urea nitrogen, creatinine, and calcium all were" t7 o( ]; u; Q4 ]4 b, Y5 a
within normal range for his age. The concentration5 i) t+ Z1 w; o' [9 v
of serum 17-hydroxyprogesterone was 16 ng/dL
, s' q$ G9 C$ T* x. A(normal, 3 to 90 ng/dL), androstenedione was 208 _% f; U. a1 r6 H$ e
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
. w. t! S9 I- |. p  B% Z, tterone was 38 ng/dL (normal, 50 to 760 ng/dL),
3 g. ~0 X9 P' g, R1 B7 Q0 t5 ]* Tdesoxycorticosterone was 4.3 ng/dL (normal, 7 to; O$ p  D- }/ _2 _
49ng/dL), 11-desoxycortisol (specific compound S)) _! m9 u: X5 ]4 l* C
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-, g( }9 V; _2 d) G! W% i+ z1 s1 `
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
' @! K& D& K, F, R  G: J* gtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),- v4 v6 y7 e* N+ G$ z  g3 J
and β-human chorionic gonadotropin was less than- l5 u2 N5 S" @# N/ x1 T& ~
5 mIU/mL (normal <5 mIU/mL). Serum follicular3 [$ j/ u* r3 E5 r* J
stimulating hormone and leuteinizing hormone) |5 f, l& s( F4 u( H2 Q2 _
concentrations were less than 0.05 mIU/mL
2 R5 e7 T( m7 T9 U(prepubertal).4 M4 G9 [5 W& [* f, g$ R
The parents were notified about the laboratory
3 N8 s; M6 V5 H8 h- x5 \% Uresults and were informed that all of the tests were; w8 y! C/ t2 t+ t/ M8 k5 @
normal except the testosterone level was high. The
( q3 \( O. \8 L9 w& Z! }2 A$ lfollow-up visit was arranged within a few weeks to
+ B8 r8 e! F$ G3 S: t$ aobtain testicular and abdominal sonograms; how-
$ S! c+ |! {1 n( Cever, the family did not return for 4 months.
; M* o0 @9 w# Z# B" fPhysical examination at this time revealed that the$ s0 {* K2 d3 |+ ^: {5 I" B$ V2 T
child had grown 2.5 cm in 4 months and had gained
7 i% R- `* H/ \. E: Z: ]3 u" o' u" h2 kg of weight. Physical examination remained
5 b/ u4 q7 T* p' @4 z" t( j9 Cunchanged. Surprisingly, the pubic hair almost com-/ R. G' A2 x) I  V& ?
pletely disappeared except for a few vellous hairs at
: M: d' d3 x; m$ i+ d/ Q0 Uthe base of the phallus. Testicular volume was still 2
! Y% b. j* e: m) r/ qmL, and the size of the penis remained unchanged.4 J' \2 W( f( h
The mother also said that the boy was no longer hav-, L# ~) W* D% t6 W. i
ing frequent erections.$ F- f5 G5 j  D9 i% K1 Q- I- W
Both parents were again questioned about use of
; X0 e  z* E/ t0 y' Oany ointment/creams that they may have applied to
4 c/ C$ m3 O  z4 e, H9 c, Pthe child’s skin. This time the father admitted the
  D- \6 f2 K( N; G/ rTopical Testosterone Exposure / Bhowmick et al 541
' i% U0 l8 v3 {  Tuse of testosterone gel twice daily that he was apply-
4 Z, v3 F% |1 s: h4 ~, T6 h# `ing over his own shoulders, chest, and back area for3 U$ m1 r. N; b
a year. The father also revealed he was embarrassed
# ]' C, l/ a" T; A7 pto disclose that he was using a testosterone gel pre-! _! f- X% o5 \- A
scribed by his family physician for decreased libido
3 W( T7 [; r8 zsecondary to depression.
4 z! ~& K( V; k! q  |The child slept in the same bed with parents.
) ]4 [8 k  h& {The father would hug the baby and hold him on his1 n% j6 b& ?! K- p
chest for a considerable period of time, causing sig-
2 F% H' k6 s$ w, I  l* Y. snificant bare skin contact between baby and father.
  A' Z, P: M* T9 H3 W8 N$ gThe father also admitted that after the phone call,/ z! p( _/ p% h, [7 Q; U
when he learned the testosterone level in the baby; c4 U; z2 K0 }* g2 A* E) I
was high, he then read the product information1 `1 e, C. S* I5 m5 N  e8 Z
packet and concluded that it was most likely the rea-. W( W: s5 u+ M  m. k3 i6 h
son for the child’s virilization. At that time, they
! ^& Z1 v) \8 g- ?1 W+ y; Q: bdecided to put the baby in a separate bed, and the+ _, @+ _9 D5 b/ G+ F
father was not hugging him with bare skin and had
* d8 J5 b) S3 Wbeen using protective clothing. A repeat testosterone
) k; Z( q$ }$ m4 ~6 J& ytest was ordered, but the family did not go to the# G% }( a7 W% [
laboratory to obtain the test.
8 c0 ^3 r* F2 U, X- GDiscussion" l3 o: ?; |& a$ V5 H
Precocious puberty in boys is defined as secondary
$ H! v) E$ M0 a) ~sexual development before 9 years of age.1,4$ W% g  M  ~. C; S0 ]' L7 w
Precocious puberty is termed as central (true) when6 n6 P0 M' W" w5 a& ?8 V
it is caused by the premature activation of hypo-) t) p4 M; u- g+ b+ g! z5 L
thalamic pituitary gonadal axis. CPP is more com-
3 U5 \) u: V7 }8 F4 ]- smon in girls than in boys.1,3 Most boys with CPP
0 ^- @2 G0 r1 ~- c; t. \+ `* rmay have a central nervous system lesion that is6 i' L8 C- r) F* p3 z
responsible for the early activation of the hypothal-
9 @0 I( v9 w* Gamic pituitary gonadal axis.1-3 Thus, greater empha-" n% I7 f* X  ]4 P1 ]. `9 Q% Q
sis has been given to neuroradiologic imaging in4 C; X# Z! }0 L7 n4 q
boys with precocious puberty. In addition to viril-& N2 j/ X0 J. ?+ B5 X
ization, the clinical hallmark of CPP is the symmet-3 X# h& F$ I6 G7 ?' R  A, w8 E
rical testicular growth secondary to stimulation by
3 l5 {% ^9 a& h5 \' Ygonadotropins.1,3' q: d3 @" G( {+ e5 q. [( Y
Gonadotropin-independent peripheral preco-
9 I% |3 _$ X  H3 }& tcious puberty in boys also results from inappropriate
, R# b  e  A1 d$ d7 E. L$ mandrogenic stimulation from either endogenous or
" V/ a; F  [' z9 n+ p# w6 }exogenous sources, nonpituitary gonadotropin stim-5 U3 u* X# e  d$ U: t( X
ulation, and rare activating mutations.3 Virilizing
* y$ k+ m' x6 rcongenital adrenal hyperplasia producing excessive
4 o1 \1 b. _) {4 V9 B. n# G% @adrenal androgens is a common cause of precocious7 {0 ^* |. U5 a& w9 p( ?4 L4 i
puberty in boys.3,4
: V" ]& j- i3 \9 b  m. @The most common form of congenital adrenal
+ z: S1 N6 ]% H2 [5 ghyperplasia is the 21-hydroxylase enzyme deficiency.
" V0 `1 g/ ~  ?, wThe 11-β hydroxylase deficiency may also result in+ d% x! ~# z, R, G5 g( ^4 _
excessive adrenal androgen production, and rarely,3 o" Z1 N$ E6 ~! ?7 p7 M
an adrenal tumor may also cause adrenal androgen
& `, ~- }$ Z  Kexcess.1,3
1 v. r/ |3 v& U6 W, `4 `- M% Z5 E: fat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from* E  ], b- ?  {3 I  [, g
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007) Z5 l1 o$ f2 ]8 d2 a
A unique entity of male-limited gonadotropin-& ~( O7 _" V; g! v
independent precocious puberty, which is also known) a4 H& T: s7 \; f
as testotoxicosis, may cause precocious puberty at a$ ~5 |, u9 @5 y: M1 u/ M- w  g  |
very young age. The physical findings in these boys
" x1 M" h# r0 v. \: ^7 r% Ywith this disorder are full pubertal development,
" f9 g/ ?4 H8 y" r* r$ p) Bincluding bilateral testicular growth, similar to boys5 ]. D+ D8 K! q, h
with CPP. The gonadotropin levels in this disorder* l* G: l5 E9 v6 G* @% A0 ]
are suppressed to prepubertal levels and do not show
. a* g' T" R, Q7 L, wpubertal response of gonadotropin after gonadotropin-& M2 k+ ?4 ?2 Z4 N& K/ E0 Z
releasing hormone stimulation. This is a sex-linked6 P+ ?. B- P0 ]
autosomal dominant disorder that affects only  |* h1 ]% f" H3 F8 @
males; therefore, other male members of the family
$ N$ p5 J5 N7 _2 n% F$ Zmay have similar precocious puberty.3" ^  o  A$ I0 k( p6 c! t. J
In our patient, physical examination was incon-, b4 p6 X4 B  r9 h! |+ p
sistent with true precocious puberty since his testi-0 E4 ^( c! P! r1 ^2 j
cles were prepubertal in size. However, testotoxicosis: }/ B' v" A8 d! ~/ I% R+ W
was in the differential diagnosis because his father5 c. @3 \  g$ V- Q, }% J% q
started puberty somewhat early, and occasionally,
! Z4 D# s8 Z9 o) N( K- T- _" i  c2 l0 ?testicular enlargement is not that evident in the
$ G% B7 U5 U/ ^beginning of this process.1 In the absence of a neg-. @1 C! o# {( T* \
ative initial history of androgen exposure, our3 R( [* P3 N) d$ o- \- M8 a* p
biggest concern was virilizing adrenal hyperplasia,; f( V$ R9 C6 H9 _1 g1 t
either 21-hydroxylase deficiency or 11-β hydroxylase
( Y9 C8 [, |- q- i. d5 e% J. Ddeficiency. Those diagnoses were excluded by find-" ?8 g1 H, b( ]/ B$ `- b6 i
ing the normal level of adrenal steroids.& g1 h# {7 U3 A5 R
The diagnosis of exogenous androgens was strongly( ]4 P  k+ S( P7 U. t8 P5 p( b
suspected in a follow-up visit after 4 months because) X1 C: S1 ?. `5 H; m' P
the physical examination revealed the complete disap-: P  }; I' }5 K9 F) ?* D7 i) Y
pearance of pubic hair, normal growth velocity, and
7 ?7 W3 G' [( ]; x1 b5 kdecreased erections. The father admitted using a testos-7 K6 c8 r, l5 X1 w% ?& Z/ ~- X, g0 M
terone gel, which he concealed at first visit. He was' c" |7 }$ O" F0 B
using it rather frequently, twice a day. The Physicians’
0 s6 B( ?3 M0 h. G  h' UDesk Reference, or package insert of this product, gel or
! W8 D8 y% `- ?' ~cream, cautions about dermal testosterone transfer to& s6 E; t6 L% _1 D5 x! [) h& _
unprotected females through direct skin exposure.3 P6 u5 ?6 O% B' u: i
Serum testosterone level was found to be 2 times the! t( I/ A, a* f) Q2 Y& z
baseline value in those females who were exposed to6 D& I( n, B; e
even 15 minutes of direct skin contact with their male
2 [: r* Y. H+ C: g# U4 Hpartners.6 However, when a shirt covered the applica-2 r7 n/ W3 s" i3 `# H! \
tion site, this testosterone transfer was prevented.
5 Z8 r5 K$ O+ x1 XOur patient’s testosterone level was 60 ng/mL,6 z8 F$ x/ i9 r, l  g. W
which was clearly high. Some studies suggest that+ x) W) z, i! i3 K' J  H$ L
dermal conversion of testosterone to dihydrotestos-. J* t6 K6 E0 ^( ]; w5 b: h* `
terone, which is a more potent metabolite, is more. w% m/ K2 I- ?8 N. N+ W( u
active in young children exposed to testosterone
+ A- H: h5 A) wexogenously7; however, we did not measure a dihy-0 i: B* T7 ?# B- R; T% J
drotestosterone level in our patient. In addition to
1 u. r4 ~+ A" {8 o7 S+ ~' @virilization, exposure to exogenous testosterone in/ w& f6 I) _2 K6 j
children results in an increase in growth velocity and
' |8 a1 N- x( y5 k; p% Gadvanced bone age, as seen in our patient.
3 V! S% Y* j( N& w6 \The long-term effect of androgen exposure during9 O0 \) B- I' k* f. k, s' u: x
early childhood on pubertal development and final. }" [& S! h; ~8 q* w
adult height are not fully known and always remain
8 x( Z: A: {2 t3 N1 Fa concern. Children treated with short-term testos-2 f" R' x3 }& t7 x; b
terone injection or topical androgen may exhibit some
3 L0 m! A' s9 }# F+ N  [/ u, Xacceleration of the skeletal maturation; however, after# m1 x1 f& H, a3 i0 Z0 e
cessation of treatment, the rate of bone maturation
/ b2 x5 R, D1 N) @+ Xdecelerates and gradually returns to normal.8,9
! T; F1 x3 X- JThere are conflicting reports and controversy
6 o, R  e3 N  |8 y; Y+ Jover the effect of early androgen exposure on adult
$ p$ |" e. H( H: O; Mpenile length.10,11 Some reports suggest subnormal% d0 c8 F# |8 x
adult penile length, apparently because of downreg-0 a. g* t! w5 ?( {
ulation of androgen receptor number.10,12 However,! o+ S. O2 n4 u' X  R0 Y3 ]
Sutherland et al13 did not find a correlation between, E7 _7 |+ V. a- c
childhood testosterone exposure and reduced adult: |* p; A; f. V0 L( B" |( ~
penile length in clinical studies.
" T' f. m& p7 s- I) R8 eNonetheless, we do not believe our patient is
4 f" X1 t" m1 F# vgoing to experience any of the untoward effects from
2 J: c* C' l+ i5 ctestosterone exposure as mentioned earlier because
1 f) e% B/ V3 Rthe exposure was not for a prolonged period of time.- v- h( j3 @0 a$ |% e: l% R1 t
Although the bone age was advanced at the time of
3 F# n2 V$ B/ e- _' k  Udiagnosis, the child had a normal growth velocity at
% ~( n/ T( m- L3 o# A8 B& vthe follow-up visit. It is hoped that his final adult# ^7 l  m9 s$ C8 a; h% p* r) S' t
height will not be affected.+ |+ f, d" B1 B" U- q4 H
Although rarely reported, the widespread avail-
7 T( p+ U9 U' \% u$ R% k* h. kability of androgen products in our society may0 f) d$ t/ U  G; b
indeed cause more virilization in male or female* v8 D7 _. z" J0 l' h- M
children than one would realize. Exposure to andro-0 J. M* E6 k6 g/ z5 g
gen products must be considered and specific ques-
, e  N' i2 b3 ]: wtioning about the use of a testosterone product or8 y% e7 W8 ~& ]: {3 c" Z- v' W
gel should be asked of the family members during' F- a9 g5 d$ _1 s1 _( |" X
the evaluation of any children who present with vir-
2 Q3 o6 @1 X2 t- `% x" Filization or peripheral precocious puberty. The diag-
0 x3 z" ]' c) K: D1 |; Hnosis can be established by just a few tests and by
! [* z4 Q- f5 \: Bappropriate history. The inability to obtain such a
4 Y4 p  J1 _+ t8 \history, or failure to ask the specific questions, may$ k4 w4 u" n8 X9 R. a" {7 X, F
result in extensive, unnecessary, and expensive3 T+ w1 w- J" m$ @
investigation. The primary care physician should be; \$ I. g9 o" e! z9 P2 E; V0 K3 }
aware of this fact, because most of these children' O8 }1 B2 ^8 W6 ^  C
may initially present in their practice. The Physicians’
4 F7 N% ]6 o; P( {0 VDesk Reference and package insert should also put a
6 I7 d/ N  X/ ~* d( Qwarning about the virilizing effect on a male or
" C2 d$ v- e0 j3 lfemale child who might come in contact with some-- j3 a" ~1 c7 o3 a' k7 Z7 [
one using any of these products.2 h' M2 d8 r) c$ x# e
References
& }+ D8 B! f3 W, j' E1. Styne DM. The testes: disorder of sexual differentiation
& ^' B. l$ Y" C) Fand puberty in the male. In: Sperling MA, ed. Pediatric2 f- [( _1 ]- J5 m; Z* l
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
/ i1 }; U" s/ K9 A! \% H) G2002: 565-628.
& j- A" D6 l3 m0 |: E, P2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
" R" R- n8 B2 @  |: s, b# lpuberty 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) R+ ?* O& v( ]6 o( p
Boy Induced by Indirect Topical$ i- J* \" n* }$ ~. ?+ Q
Exposure to Testosterone: x* R8 L( j! `" j3 R* J9 t5 X3 D
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
( N; u/ c7 f9 `6 Wand Kenneth R. Rettig, MD1
7 V! B7 o( B4 U' jClinical Pediatrics5 T4 j+ y6 V, ^2 b
Volume 46 Number 6& X# D# ?7 p) W$ C, _3 H! H/ A
July 2007 540-543
2 ]) `, r( b4 w) I) e© 2007 Sage Publications
- f3 y# p; E, f' D10.1177/0009922806296651" u9 [5 I) i, z( c9 a7 y
http://clp.sagepub.com0 h# X, R2 L7 l) o" ~
hosted at
! }& Y: Q  E- u' D  p% h0 Z7 vhttp://online.sagepub.com
! H1 b/ D; @( d6 ^4 OPrecocious puberty in boys, central or peripheral,
* M3 x6 Z' u5 f, K. }0 p% K+ nis a significant concern for physicians. Central
5 j1 D* C: u* z8 b7 wprecocious puberty (CPP), which is mediated
2 C% @6 F$ H* Y$ [4 P5 Bthrough the hypothalamic pituitary gonadal axis, has! r+ c# \' t5 l
a higher incidence of organic central nervous system7 u, }* h1 q6 v( `* p0 ], w8 Q2 o
lesions in boys.1,2 Virilization in boys, as manifested
- g, r% A& I, |- Hby enlargement of the penis, development of pubic
2 a' K: |% G6 R. \; a* t4 Q) bhair, and facial acne without enlargement of testi-
* G' T8 R2 \7 g8 r- ecles, suggests peripheral or pseudopuberty.1-3 We7 \( I1 E' d* D
report a 16-month-old boy who presented with the
, `' w& U# ^. s6 M4 a: Tenlargement of the phallus and pubic hair develop-) S  A) Y" h  g4 J* d$ T/ T
ment without testicular enlargement, which was due6 F2 n& W, {" l' z" E
to the unintentional exposure to androgen gel used by1 s6 q1 D+ o0 @& `
the father. The family initially concealed this infor-. w- @8 j0 K, C. e
mation, resulting in an extensive work-up for this: p% [$ g2 h4 c9 y6 ]' a. [, H3 M
child. Given the widespread and easy availability of
1 ]! t, r3 m% m7 Htestosterone gel and cream, we believe this is proba-
7 _0 y; Q* P, gbly more common than the rare case report in the- ^2 L* D. w0 k" A$ o
literature.4
. F3 x7 a% J3 v. g) [; z. B2 Z5 sPatient Report
: y+ l! [/ o# CA 16-month-old white child was referred to the
5 U3 E( |; @7 p" ?5 z8 wendocrine clinic by his pediatrician with the concern
- s0 n6 c. |" F+ A- c8 _of early sexual development. His mother noticed6 x" [) q& b/ H, w) Q% a% W9 t
light colored pubic hair development when he was6 g) P3 G& _7 q' q/ _
From the 1Division of Pediatric Endocrinology, 2University of& [0 x, @8 N6 }* ^: z; v4 o
South Alabama Medical Center, Mobile, Alabama.
4 M  r0 p# ?6 O' @7 v+ v. nAddress correspondence to: Samar K. Bhowmick, MD, FACE,
( o8 y. n! _* i" T" o/ kProfessor of Pediatrics, University of South Alabama, College of
' R. Q5 Y$ V5 {6 x7 CMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;& ?0 H& C/ w& f4 _+ z1 M8 R
e-mail: [email protected].# i2 e' D* z8 p% S  u. ]) j; r
about 6 to 7 months old, which progressively became
: {% H' [( O' ddarker. She was also concerned about the enlarge-4 s, R2 X% c. a4 i0 E
ment of his penis and frequent erections. The child
: p2 d7 F3 m- g  u( e! s1 T% B3 |  E) Swas the product of a full-term normal delivery, with7 v/ r7 F" X- M+ b  Y9 S- D
a birth weight of 7 lb 14 oz, and birth length of
3 W9 B! h' b1 U) P6 J- `. C20 inches. He was breast-fed throughout the first year% v7 ~6 C3 p0 G- W5 |
of life and was still receiving breast milk along with
$ C$ f. y& z7 c: f) h7 |9 M. A3 ksolid food. He had no hospitalizations or surgery,+ Z$ l9 W3 n4 p, P
and his psychosocial and psychomotor development' n* v* e* ^, q# R4 Z  g1 q7 q
was age appropriate.9 H$ m& i; d1 U3 y+ A
The family history was remarkable for the father,2 S0 d, X; W- u5 q
who was diagnosed with hypothyroidism at age 16,$ H4 r4 F( |3 H& Z7 R9 p
which was treated with thyroxine. The father’s! L" |! z0 w+ K; f3 L) q
height was 6 feet, and he went through a somewhat
% Z5 ^8 b/ p/ b. t5 r0 q0 Uearly puberty and had stopped growing by age 14./ H% ^9 x8 [- S( N* b
The father denied taking any other medication. The
1 C( W( y+ Z! g6 z5 I$ nchild’s mother was in good health. Her menarche
3 g, G& e7 F  o5 @" a; O4 p' awas at 11 years of age, and her height was at 5 feet
9 q! h. c$ g6 [$ G; |( c2 Q5 inches. There was no other family history of pre-0 e$ M) Z1 W- @# r6 {+ R
cocious sexual development in the first-degree rela-
' v! Y* ?& G4 G3 Xtives. There were no siblings.  ^+ O  O" _8 j
Physical Examination: u; ?0 F2 ^1 P( E9 E1 b4 A& m: S. C
The physical examination revealed a very active,/ R+ o2 _8 N. X6 K6 n( u( |; Y8 Y7 J
playful, and healthy boy. The vital signs documented
3 L& H. I/ T( E1 N3 E4 j0 pa blood pressure of 85/50 mm Hg, his length was
' b& n9 j! z, _3 S90 cm (>97th percentile), and his weight was 14.4 kg
2 k9 k6 _( g  E% K. g0 T(also >97th percentile). The observed yearly growth9 n' X( c$ o% \
velocity was 30 cm (12 inches). The examination of8 p8 L1 j' ^% x1 ?" q; W* W# d
the neck revealed no thyroid enlargement.' o' L' y+ O) |6 v+ }3 t
The genitourinary examination was remarkable for, U1 H1 m7 [, ]; x7 e5 C. |
enlargement of the penis, with a stretched length of
3 ^5 S! R2 g6 |8 cm and a width of 2 cm. The glans penis was very well
/ z# c( J- A4 C( g9 L0 odeveloped. The pubic hair was Tanner II, mostly around/ z2 [* p, K, `( l; [- o
540! l2 U  o) Z: l& I0 T
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
: ^+ r1 \5 S. G( n! Athe base of the phallus and was dark and curled. The2 r2 V: x! \8 D1 _8 d% X
testicular volume was prepubertal at 2 mL each.  d9 ?* F/ g2 B5 d2 h
The skin was moist and smooth and somewhat# d* p9 ?' E3 ~! I8 R6 t
oily. No axillary hair was noted. There were no
+ B, \4 B3 M" y  L# J! S  oabnormal skin pigmentations or café-au-lait spots.
& e) }0 E: m; {" E* g0 j* c& k4 FNeurologic evaluation showed deep tendon reflex 2+
8 ~2 F8 c5 i  k% cbilateral and symmetrical. There was no suggestion6 }, \; f* A" V7 ~$ x
of papilledema.. p0 G! e* k5 S8 c$ c: I" R3 H+ o
Laboratory Evaluation) k$ J- x) x5 y7 l
The bone age was consistent with 28 months by' C* Z0 j, d7 V7 y" Y
using the standard of Greulich and Pyle at a chrono-
% Z; M3 }( ]9 E( I' i# V3 ]) @4 nlogic age of 16 months (advanced).5 Chromosomal
3 @4 X( z. \" Wkaryotype was 46XY. The thyroid function test6 a( m4 S& l- q+ R+ V
showed a free T4 of 1.69 ng/dL, and thyroid stimu-  L2 i# o; D) f3 g' X# z) w/ ~
lating hormone level was 1.3 µIU/mL (both normal).2 ^- m2 [4 o; D' Q& x
The concentrations of serum electrolytes, blood; b5 ^8 ~: l% c5 n/ w( y2 v5 n
urea nitrogen, creatinine, and calcium all were
0 V  T3 K) ~( Cwithin normal range for his age. The concentration6 q$ c* G8 h, Y$ o$ W/ y9 c4 X
of serum 17-hydroxyprogesterone was 16 ng/dL
. N. s) A5 k5 h% B# T(normal, 3 to 90 ng/dL), androstenedione was 20
, D  {& i7 I7 Q/ A8 Eng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-+ L( U. T' z5 M; B/ ?7 ?0 ~/ D( c$ X
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
, E, Z% ?" }0 i  B" N  `desoxycorticosterone was 4.3 ng/dL (normal, 7 to
2 j& j$ a. Y! T, u49ng/dL), 11-desoxycortisol (specific compound S)
& P9 g  j4 [" @8 twas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
! F! z0 s* D, L( t8 Htisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
6 s, k' G9 I0 |, S  y* u' ]testosterone was 60 ng/dL (normal <3 to 10 ng/dL),2 I. T( [0 n' {2 q" m+ e, g' N9 d# p
and β-human chorionic gonadotropin was less than
) N. L6 }7 |# K3 {$ M0 |3 C; r5 mIU/mL (normal <5 mIU/mL). Serum follicular
* n! \+ s6 V3 ?" G7 Tstimulating hormone and leuteinizing hormone7 C, Y* o5 Q( \0 J  A
concentrations were less than 0.05 mIU/mL
4 u: @$ A$ |1 N& U3 A  @(prepubertal).
2 p5 I; A7 z- y/ AThe parents were notified about the laboratory# E# i+ `8 B' Y% R' q
results and were informed that all of the tests were
+ w( w; M$ i2 v2 Hnormal except the testosterone level was high. The. C9 o1 O/ E# T( s- I" N! p" v
follow-up visit was arranged within a few weeks to1 A+ v9 r- W  ]& ^9 ?
obtain testicular and abdominal sonograms; how-. x, |5 V( l- o: w; H3 G
ever, the family did not return for 4 months.
2 V# {8 Q* U: [* E' WPhysical examination at this time revealed that the  e+ V9 Q* p) x# J
child had grown 2.5 cm in 4 months and had gained( K3 @$ i- g+ j. Q
2 kg of weight. Physical examination remained
& u) }+ F' Y9 N6 L  \$ Runchanged. Surprisingly, the pubic hair almost com-4 R. p3 [5 ^- k4 s# Q& a. ^' z
pletely disappeared except for a few vellous hairs at
4 w" j% P; X+ N/ x  |7 o( Q8 `- Bthe base of the phallus. Testicular volume was still 21 c5 k2 s7 p  Y; g# X' b( |
mL, and the size of the penis remained unchanged.' _1 t* Y3 d+ \: d8 T+ {0 e0 Y. Z: o
The mother also said that the boy was no longer hav-5 n) ]8 L0 f1 Y0 ?) I8 }
ing frequent erections.4 m* r1 z0 U( `7 P
Both parents were again questioned about use of$ `3 T# o  h' G3 f6 w7 ], W
any ointment/creams that they may have applied to/ v% P, Q- n# S* W7 U
the child’s skin. This time the father admitted the
( C4 b1 y  H1 B% p; m; O/ f9 kTopical Testosterone Exposure / Bhowmick et al 5413 z( M/ R8 o; S. }5 ?) v
use of testosterone gel twice daily that he was apply-
/ h6 U) B2 t% G4 [ing over his own shoulders, chest, and back area for  Q4 k* t' I) H1 S! a
a year. The father also revealed he was embarrassed+ E0 T  ]0 T1 o; e
to disclose that he was using a testosterone gel pre-) G2 N; m  I. z
scribed by his family physician for decreased libido
4 O5 N- R3 o: lsecondary to depression.
" k7 U# M* p% W0 V' C. J9 [The child slept in the same bed with parents.
( F% F1 W0 B- p+ OThe father would hug the baby and hold him on his6 Z( m3 M5 A! O4 _/ C. T7 e1 J
chest for a considerable period of time, causing sig-/ y: {3 r& l) e# W1 g# s0 C. i
nificant bare skin contact between baby and father.$ D; u7 |0 p4 i( F8 {& d$ R) k: }
The father also admitted that after the phone call,
0 v0 P, `) ^4 ^, U/ R. K9 Owhen he learned the testosterone level in the baby
  U) z  m* B/ r+ R: Hwas high, he then read the product information
# D4 t4 f: L9 L5 p2 S! e# s" Bpacket and concluded that it was most likely the rea-
8 y/ x) k/ D* Y) I9 s' ison for the child’s virilization. At that time, they3 C$ K/ Z0 L8 g; T8 ?" @
decided to put the baby in a separate bed, and the- A) ]0 V% T( F+ D- Q
father was not hugging him with bare skin and had
# Q/ a4 v: E* Z" xbeen using protective clothing. A repeat testosterone
4 c* ]* d% ]( V& ^test was ordered, but the family did not go to the! l  z2 d/ E' z* R5 h6 v
laboratory to obtain the test.
1 j1 k0 F) c3 C0 r; ZDiscussion
7 Y/ x3 R. `( v/ v% q! V( VPrecocious puberty in boys is defined as secondary- z: Y! l: Z$ d" ?, C
sexual development before 9 years of age.1,4
* A5 Q' R/ F# Q2 _  BPrecocious puberty is termed as central (true) when- M) K( c* _0 [" H" P
it is caused by the premature activation of hypo-% A3 C8 a# e1 J8 V* }* v5 z
thalamic pituitary gonadal axis. CPP is more com-
' V  }/ P) k" Wmon in girls than in boys.1,3 Most boys with CPP
0 s* y, z3 ?! N/ G  c; v( e! jmay have a central nervous system lesion that is/ M0 {9 {5 _; W5 {' ~% d( N
responsible for the early activation of the hypothal-1 x& X: a; J9 B0 }
amic pituitary gonadal axis.1-3 Thus, greater empha-
; Q  Z, z# m5 osis has been given to neuroradiologic imaging in( P2 \$ H7 x8 J/ Z0 c* q2 @  X" `/ h
boys with precocious puberty. In addition to viril-
7 ^* L& e: J/ ~5 Y4 H3 k; ~! |1 `) lization, the clinical hallmark of CPP is the symmet-
+ R2 X0 b* q7 jrical testicular growth secondary to stimulation by+ l* A1 G2 }( @4 F! L
gonadotropins.1,3( y5 h- T# s6 i) Y* n: f) O
Gonadotropin-independent peripheral preco-
# C2 K  U* c: J; t: Kcious puberty in boys also results from inappropriate: m4 K4 w- m. Q& c5 I
androgenic stimulation from either endogenous or
! [9 e2 j0 Q/ y- M5 Y  Cexogenous sources, nonpituitary gonadotropin stim-3 U6 \1 B) {) G- H( s( ]+ P, o% `
ulation, and rare activating mutations.3 Virilizing
0 }4 V5 C5 g* V5 r' Ccongenital adrenal hyperplasia producing excessive8 c- j7 V* H4 G- l
adrenal androgens is a common cause of precocious
  o+ M: k9 @/ A1 M( f3 R* V6 ^puberty in boys.3,4( t) N" z$ o4 C9 k" E5 @# ]5 H7 Z5 l
The most common form of congenital adrenal, k  [/ j: I0 z4 q& K% c" M  I, q& t
hyperplasia is the 21-hydroxylase enzyme deficiency.% p( E$ Z: [" g' f' c; J( X
The 11-β hydroxylase deficiency may also result in. }  F  a+ ]" I0 T4 T/ s2 V1 W
excessive adrenal androgen production, and rarely,& \: a5 J6 T" B
an adrenal tumor may also cause adrenal androgen5 C6 J% `+ E( [. i% T0 c
excess.1,3& Q$ @. y% i( U# h
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
, L+ c1 ~1 u3 \( T8 `. T  w542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
" j$ d+ F* [. M! r8 YA unique entity of male-limited gonadotropin-) v! Z& I3 P( ^, t8 x0 ]6 e
independent precocious puberty, which is also known
3 H- f( r8 X- q" A0 ^, S6 kas testotoxicosis, may cause precocious puberty at a3 ?3 D& k$ O- r% f, |) A
very young age. The physical findings in these boys
% c+ _9 j+ `- J! H' |with this disorder are full pubertal development,: H/ H6 y4 j. L$ r
including bilateral testicular growth, similar to boys0 p+ a" E8 i, a6 u! s
with CPP. The gonadotropin levels in this disorder) X2 P: H# Z  }- H( F2 b; ^' ^
are suppressed to prepubertal levels and do not show
) P5 T7 g, ~0 e! zpubertal response of gonadotropin after gonadotropin-: r4 L$ _1 q4 m2 w
releasing hormone stimulation. This is a sex-linked
7 r7 E& y7 L2 Kautosomal dominant disorder that affects only
9 ]. J3 m. F9 v6 ?; bmales; therefore, other male members of the family0 J  E& Z. [: {. x/ E
may have similar precocious puberty.33 i$ O, [" @0 j8 F
In our patient, physical examination was incon-
& r* S+ v' K- f" c9 H) [sistent with true precocious puberty since his testi-; Y# s6 r. w3 ^4 o& ?0 H* R
cles were prepubertal in size. However, testotoxicosis  C, L$ y: V, j
was in the differential diagnosis because his father
1 S  H* \; B7 A# Estarted puberty somewhat early, and occasionally,1 g1 d% B7 n* \
testicular enlargement is not that evident in the  M# m' u+ N$ I7 S) Y1 {, ^
beginning of this process.1 In the absence of a neg-* k: O" b0 N* j: F9 g4 U
ative initial history of androgen exposure, our
) T; A7 R/ Y, B2 I. N  ]7 G5 F8 Gbiggest concern was virilizing adrenal hyperplasia,
& Z7 T, H. ~/ `& D6 zeither 21-hydroxylase deficiency or 11-β hydroxylase
" N; T0 U  j6 u  S' k$ ?deficiency. Those diagnoses were excluded by find-
# A. _. D/ i9 g3 h1 Xing the normal level of adrenal steroids.% U9 Q3 n, ^  r5 }& q
The diagnosis of exogenous androgens was strongly' M$ A8 K  C2 c
suspected in a follow-up visit after 4 months because7 W$ \1 b' [: \- m
the physical examination revealed the complete disap-
8 z2 \; L! {3 J: |" g7 {pearance of pubic hair, normal growth velocity, and( v8 z4 K# K  a: ^1 v
decreased erections. The father admitted using a testos-3 A) q$ P! R# j2 g5 f9 V4 s6 L
terone gel, which he concealed at first visit. He was
9 R( t2 M' R: [0 A& Q  b. _using it rather frequently, twice a day. The Physicians’
2 U0 }7 S( g+ D- ~* aDesk Reference, or package insert of this product, gel or3 C2 ~) z0 [) Z& M4 d
cream, cautions about dermal testosterone transfer to
4 K8 z2 z& y  A, q; i6 v; |) x$ nunprotected females through direct skin exposure.4 x) Z) m, }% g1 a1 O
Serum testosterone level was found to be 2 times the
7 ?2 k" U9 u/ q5 b8 Zbaseline value in those females who were exposed to
0 V, h1 {" s, |7 k$ b1 veven 15 minutes of direct skin contact with their male
: s2 o4 ~3 k& q& @6 `% _partners.6 However, when a shirt covered the applica-2 o* C& R0 z6 `+ @0 D
tion site, this testosterone transfer was prevented.
! v# v! f" T9 J- O9 r, r9 F; @7 QOur patient’s testosterone level was 60 ng/mL,
7 a5 V1 h3 r  C; ~* q3 q1 e( ~& Dwhich was clearly high. Some studies suggest that
# R' r2 s3 }. M% q9 }% V# x4 \dermal conversion of testosterone to dihydrotestos-
; B$ s  C" ?* Z* S- \- I4 {terone, which is a more potent metabolite, is more
8 R* K$ m- s$ A8 w/ J0 n  b2 Hactive in young children exposed to testosterone, u7 e, W5 g  @
exogenously7; however, we did not measure a dihy-
. v$ c4 b8 M7 C$ N8 |, d* Xdrotestosterone level in our patient. In addition to' m% L6 T' K: D8 v% L: w: g& ]2 D
virilization, exposure to exogenous testosterone in
( K* V. P* d! s' W. Fchildren results in an increase in growth velocity and
0 \# C! K2 r  qadvanced bone age, as seen in our patient.* D" K* b: {5 Z& x0 ?0 G
The long-term effect of androgen exposure during
& V' P8 }6 C# x( }$ b) H; kearly childhood on pubertal development and final
0 k$ T' z! P+ Ladult height are not fully known and always remain# n  Y% N9 ~+ C6 v; W) A
a concern. Children treated with short-term testos-( }" Z$ e# j* _) u
terone injection or topical androgen may exhibit some
  P9 r( A( e/ a/ a/ t# M, o6 m6 Xacceleration of the skeletal maturation; however, after' M+ m# z% @& Z6 S( @/ h; s
cessation of treatment, the rate of bone maturation. m7 [! R2 }. A) d+ [8 A; o+ ?
decelerates and gradually returns to normal.8,9& I& u) o) O9 f' y" v5 o
There are conflicting reports and controversy
$ K: M! W0 X0 B' B+ zover the effect of early androgen exposure on adult
& Q  u1 K* H; d3 l0 M! Dpenile length.10,11 Some reports suggest subnormal
; R" O# k$ z) w* [. P% X3 X- c) [, r3 Sadult penile length, apparently because of downreg-
! H. f) E, E. W+ P. dulation of androgen receptor number.10,12 However,, y0 Q4 y' k+ `# ~( _. T
Sutherland et al13 did not find a correlation between" A4 I% ~. X/ A5 ?; b
childhood testosterone exposure and reduced adult7 R% \! ~/ Q* f2 A/ U1 U) ~$ D2 D) a
penile length in clinical studies.& c7 v) t  K2 K; Q  X
Nonetheless, we do not believe our patient is
4 I; K, |+ H7 T, ~! w+ c: dgoing to experience any of the untoward effects from( F$ S3 D$ x' a& V* d; Z3 C
testosterone exposure as mentioned earlier because
6 v% q4 y8 Y+ L5 Ythe exposure was not for a prolonged period of time.
4 a2 o0 B/ j4 S: j2 }! D4 {Although the bone age was advanced at the time of
- m' l# q+ z3 @/ l/ i, `: {2 m8 `diagnosis, the child had a normal growth velocity at
9 a* O; P  y, }- Zthe follow-up visit. It is hoped that his final adult, f8 f0 c9 G8 k+ M6 A, N
height will not be affected.. k/ Z  n/ s) [
Although rarely reported, the widespread avail-
6 Z7 y% S3 n! F( w1 R+ H) T2 ?: iability of androgen products in our society may
, ^( R9 @* Z; Aindeed cause more virilization in male or female
6 ]: a% m" ~% |! a. F: `children than one would realize. Exposure to andro-2 ?' z' d  b# ?
gen products must be considered and specific ques-6 Q2 E/ O4 M1 a: L/ M( s
tioning about the use of a testosterone product or1 \7 Q& I3 b$ @* y# M" N" K7 W3 i5 g
gel should be asked of the family members during( m  I% p% |4 v+ I" F
the evaluation of any children who present with vir-
& p2 O, l6 o* Wilization or peripheral precocious puberty. The diag-
4 x4 \3 V8 Z6 }7 b- O/ B3 ?nosis can be established by just a few tests and by
; \6 Q8 ]4 v1 `& k2 Z( a& H7 Lappropriate history. The inability to obtain such a
+ }- I* n3 L& W" @) ~7 }6 |history, or failure to ask the specific questions, may
; X) A4 }! h2 g4 Aresult in extensive, unnecessary, and expensive. }& g6 d: |2 ?4 J
investigation. The primary care physician should be) [8 e6 k; c$ K7 o7 S
aware of this fact, because most of these children
  J, X' ~$ E! u" j; }may initially present in their practice. The Physicians’# V, X+ P5 S0 [, \4 N
Desk Reference and package insert should also put a
* e+ e6 e) f9 \warning about the virilizing effect on a male or% i4 C, e) }7 T% u, |* e
female child who might come in contact with some-
7 @5 S% p$ k3 P( N& l) C; Qone using any of these products.; L0 D6 W2 Q# P: |1 p1 N
References5 q+ [# k- r, e( m5 \
1. Styne DM. The testes: disorder of sexual differentiation0 J- a% V0 p. w. H, m3 \
and puberty in the male. In: Sperling MA, ed. Pediatric
5 ]. A  t0 E* s) K- zEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;5 I4 ^  f, p' c6 k
2002: 565-628.
6 ~& Z7 o  M8 ], G0 f8 _2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
: y+ v- D6 @* B& \8 `. {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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4个什么样的?
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  M# X4 b* n# G, I3 D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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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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