繁體中文
不翻译
简体中文
English
繁體中文
日本語
한국어
切換到窄版

WK綜合論壇, WK综合论坛

 找回密碼
 立即注册
樓主: wk007

鄉下的妹子太便宜,一次四個都要了[12P]

[複製鏈接]
發表於 2025-1-4 03:25:35 | 顯示全部樓層
Sexual Precocity in a 16-Month-Old+ ?/ K; P( W( X$ R5 S) p' I+ ?
Boy Induced by Indirect Topical
$ H: _' {' |! iExposure to Testosterone
" j! R1 |0 c6 f8 ESamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2$ J, O6 s7 f9 f" B  q. X
and Kenneth R. Rettig, MD19 S+ s1 _8 L7 J
Clinical Pediatrics2 c; ~- s0 Z3 M% m
Volume 46 Number 6: Z1 w. Z9 |0 W0 i4 U$ k
July 2007 540-5437 f: {  O/ Y$ E! j# [
© 2007 Sage Publications
6 L; l: y. P: ^' i0 s9 x10.1177/0009922806296651
$ B# l* {& |2 p, G6 [+ uhttp://clp.sagepub.com6 x7 o/ Q' d+ t1 X2 w2 A
hosted at. s  a& ~, Y1 R( E
http://online.sagepub.com( s$ M4 r; v: |+ d; p
Precocious puberty in boys, central or peripheral,% X! S$ `6 l( i$ b& u# }  S  ^
is a significant concern for physicians. Central
1 V$ e  M2 f2 Kprecocious puberty (CPP), which is mediated
5 k; ~, k0 j, Bthrough the hypothalamic pituitary gonadal axis, has* \# S; @$ K! b6 C8 D3 t: E
a higher incidence of organic central nervous system
1 @: L9 b) b: Xlesions in boys.1,2 Virilization in boys, as manifested, s1 u# x% L: n" c! H! P4 Z' x( t$ f
by enlargement of the penis, development of pubic
, g1 P% q3 _. b) qhair, and facial acne without enlargement of testi-, L- j$ l# z$ P2 \4 G0 d
cles, suggests peripheral or pseudopuberty.1-3 We
3 Q1 U0 l( x; X$ i0 u5 I$ ~  Vreport a 16-month-old boy who presented with the
& ^0 }9 t% f5 T# l; w% `enlargement of the phallus and pubic hair develop-5 e( t; C% E. l
ment without testicular enlargement, which was due" w- j3 u  p) J) V- f, C
to the unintentional exposure to androgen gel used by, d- s+ v% K3 w
the father. The family initially concealed this infor-; Y. ^0 C) |( }1 Z" G
mation, resulting in an extensive work-up for this2 O4 }( T4 H2 Q! I$ `% i( T5 G9 E
child. Given the widespread and easy availability of
' o. z: E2 e; Q' r; \( \testosterone gel and cream, we believe this is proba-* q, [! K0 q+ H( l! ^; h* k
bly more common than the rare case report in the
" M% c8 i. M; qliterature.4
, y8 i: O  U4 t. k  RPatient Report
( t, x% T) |& u% N7 uA 16-month-old white child was referred to the
3 k4 j# t! D2 W6 W" y& ~. ]# ]endocrine clinic by his pediatrician with the concern) c% c* W# v1 w- l* W5 V
of early sexual development. His mother noticed2 R5 Y/ z2 R" P. b, D
light colored pubic hair development when he was
& w) |; z% \' uFrom the 1Division of Pediatric Endocrinology, 2University of
; O1 y7 K; w2 Z1 p, v0 U7 USouth Alabama Medical Center, Mobile, Alabama.
. k' Z5 U* P+ N: s0 s: a+ V6 b$ _Address correspondence to: Samar K. Bhowmick, MD, FACE," Z* A9 n% N) R
Professor of Pediatrics, University of South Alabama, College of
& B: T  u) D' x& r: a4 P( OMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
' p; g! T, ]( j  b) o. \6 o1 |e-mail: [email protected].
) E( k1 [% \+ O2 q6 O0 L4 cabout 6 to 7 months old, which progressively became
0 P6 a0 B, l# }' G9 @, Wdarker. She was also concerned about the enlarge-
+ d7 ]/ R4 b5 J+ O" ^6 rment of his penis and frequent erections. The child4 F) v9 O) p8 B1 d
was the product of a full-term normal delivery, with
& Z- r' G: M: G5 Aa birth weight of 7 lb 14 oz, and birth length of
3 ]* ], u3 b5 \20 inches. He was breast-fed throughout the first year: _; w7 Z# `; c! v8 j3 B. D
of life and was still receiving breast milk along with6 E$ N* s$ V- Q  |. f1 x4 d
solid food. He had no hospitalizations or surgery,
4 u* ?  Z; R4 G  z$ wand his psychosocial and psychomotor development
6 Y9 Y* A& [; C8 V' Xwas age appropriate.
" [6 l3 U7 ^9 @" a" g- F9 D' ]5 DThe family history was remarkable for the father,* G1 _7 J! m/ Q8 U- ]+ F9 A- X
who was diagnosed with hypothyroidism at age 16,
- _/ }( w, T3 _5 ?. Nwhich was treated with thyroxine. The father’s
, T# M. Q( d* Y! c. E& Vheight was 6 feet, and he went through a somewhat  n" o/ l- j5 x5 h  d1 r8 V
early puberty and had stopped growing by age 14.! u& k  ~, X4 O; V
The father denied taking any other medication. The8 [0 ^) z  G" G
child’s mother was in good health. Her menarche
- c0 }% N5 h" J4 @0 w$ {was at 11 years of age, and her height was at 5 feet* [; J, j% @* V: ^
5 inches. There was no other family history of pre-
4 ^; j. G& O0 Wcocious sexual development in the first-degree rela-
2 H" t0 r' u7 B$ @# ^- b; Q: ktives. There were no siblings.; x) ]4 Y5 Q+ L8 q% K. _
Physical Examination
( e0 w1 o# r0 F3 ]2 D' rThe physical examination revealed a very active,: F8 C4 l2 D  ^4 J
playful, and healthy boy. The vital signs documented
7 V$ ?, S9 f( _, p( U3 y5 Ia blood pressure of 85/50 mm Hg, his length was0 U) n4 h! g2 j/ n6 Z
90 cm (>97th percentile), and his weight was 14.4 kg4 V# W1 ]6 ~8 }  J
(also >97th percentile). The observed yearly growth
7 a4 p6 d  R1 B. r( Hvelocity was 30 cm (12 inches). The examination of
7 m3 a! }# A" M. X$ l% Uthe neck revealed no thyroid enlargement.
" ]8 s4 p3 e5 w6 F2 |% ~" TThe genitourinary examination was remarkable for
9 f. }# M5 N. g" G" E1 q3 N2 Xenlargement of the penis, with a stretched length of& Y7 k5 N- d* M
8 cm and a width of 2 cm. The glans penis was very well6 S- s* }: i# x+ z& j- [  p4 j
developed. The pubic hair was Tanner II, mostly around: C- E' Q  a: p
540) w% F3 [7 f5 E( U! f8 A! ?4 Z
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from* N  q  D/ O" p; ]
the base of the phallus and was dark and curled. The
& g7 Z, N7 d, @  n6 b4 ltesticular volume was prepubertal at 2 mL each.- r2 t+ `/ L, \0 X9 x2 T6 a" d
The skin was moist and smooth and somewhat
4 u5 h+ c1 ]# U$ |! \+ m( P9 P( c' zoily. No axillary hair was noted. There were no
, T7 Q) G- u' x. I9 e! X5 T4 _/ Jabnormal skin pigmentations or café-au-lait spots.8 V- M* I( Z9 B5 D
Neurologic evaluation showed deep tendon reflex 2+8 s# \" ?% B# ?4 L5 `1 g
bilateral and symmetrical. There was no suggestion
* p3 g3 H* N; t3 v; Sof papilledema.
" n% ]' v3 V* w( P7 _Laboratory Evaluation- s2 |- e" _" U, R3 `3 j( o
The bone age was consistent with 28 months by
  h' O) b+ M. x* Qusing the standard of Greulich and Pyle at a chrono-$ I1 l! A6 y2 a% m0 B
logic age of 16 months (advanced).5 Chromosomal
6 q0 h# F# ~9 S0 B  Lkaryotype was 46XY. The thyroid function test8 d. |; d' Q) w0 Z
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
* \1 H& S% m9 C3 X( alating hormone level was 1.3 µIU/mL (both normal).
" L. \4 W* B- pThe concentrations of serum electrolytes, blood
6 S1 G2 q5 f: i; q6 ^urea nitrogen, creatinine, and calcium all were6 z) S3 Y  K* H$ U8 |; V# E
within normal range for his age. The concentration- @4 b3 b2 H' y$ q8 X: K5 @
of serum 17-hydroxyprogesterone was 16 ng/dL
! O% m" ?" K+ O(normal, 3 to 90 ng/dL), androstenedione was 20
  r4 P: K* Y- ?9 ~0 J* y3 Y& Bng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-$ o, Y3 G. F. M4 I( }
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
! t2 b( N9 X% v; n3 q& ldesoxycorticosterone was 4.3 ng/dL (normal, 7 to4 X* V. U' p* ^1 [% V
49ng/dL), 11-desoxycortisol (specific compound S): n+ t8 h: c6 U- N! H0 ?
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
/ u! i+ c( d. a" atisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
3 o6 ^* z  O4 L8 E5 `testosterone was 60 ng/dL (normal <3 to 10 ng/dL),$ K' B/ \# u- }
and β-human chorionic gonadotropin was less than% A8 ~- z: k8 H5 }
5 mIU/mL (normal <5 mIU/mL). Serum follicular7 _/ g: Z) U# V. N+ N$ ?
stimulating hormone and leuteinizing hormone
6 O. C' ?! _: s: M  @& uconcentrations were less than 0.05 mIU/mL
, b* [% B9 y* ?! H; N4 Y(prepubertal).
4 I$ W7 g" X. X$ C$ \The parents were notified about the laboratory
* h  t4 ^7 l0 hresults and were informed that all of the tests were
/ z( [8 _7 C! \+ E% `normal except the testosterone level was high. The
) u: X6 e" @+ d: Cfollow-up visit was arranged within a few weeks to
3 `' |- K  g0 R) B* g7 Tobtain testicular and abdominal sonograms; how-
3 z/ Z1 d0 j5 u' Iever, the family did not return for 4 months.
6 {1 h0 i  g6 [9 w! KPhysical examination at this time revealed that the
) a# ]& C6 C; N% w. Y+ |child had grown 2.5 cm in 4 months and had gained2 J" K  b; |2 W8 Y3 g! H& _) s( e
2 kg of weight. Physical examination remained
6 G% c6 I9 x3 e% R, wunchanged. Surprisingly, the pubic hair almost com-- z- F/ S1 `2 C: Y, l
pletely disappeared except for a few vellous hairs at
$ E* V. `4 C+ P$ d' i. G: k' ithe base of the phallus. Testicular volume was still 28 h" p) ?3 M, ~7 V7 Y
mL, and the size of the penis remained unchanged.
& q6 @. B% k4 O3 LThe mother also said that the boy was no longer hav-' E, M9 |, ]! r# U% D5 H% w
ing frequent erections.
7 t6 P2 i4 S" v2 G3 P' G. w8 EBoth parents were again questioned about use of
( k% G% L+ Y+ W! |% O, {) nany ointment/creams that they may have applied to) B2 n; X& p% W8 j' i
the child’s skin. This time the father admitted the, ]6 I+ b) S1 V( e+ ^. X4 P# ^: v7 u- t
Topical Testosterone Exposure / Bhowmick et al 541$ ]- k$ M: u8 @* h
use of testosterone gel twice daily that he was apply-
. I# o: ]" b: x7 ]! c- Ring over his own shoulders, chest, and back area for5 u% N6 g& I2 }0 F! r
a year. The father also revealed he was embarrassed9 h% ~. I. A& M
to disclose that he was using a testosterone gel pre-( j+ T1 _8 a/ o8 {
scribed by his family physician for decreased libido
, w, L. L1 `1 h, s0 L7 U( Nsecondary to depression.
" o# b0 L! q. e) S  ^/ A8 Y. UThe child slept in the same bed with parents.+ s% J3 T0 n6 F% j1 p% N: m& j
The father would hug the baby and hold him on his, J! b& N+ G* x0 {* A) N
chest for a considerable period of time, causing sig-
  k3 b8 O$ l% L0 ynificant bare skin contact between baby and father.
. I1 h& L- x. I, k; V* NThe father also admitted that after the phone call,) g' \, _* G( G; \2 a; J: b$ e7 J
when he learned the testosterone level in the baby
8 T1 p' ?: G! ^+ ?5 R5 c- rwas high, he then read the product information, F0 Y3 q; J2 l7 b3 E* \1 A
packet and concluded that it was most likely the rea-0 C& l; j/ d; E5 x# H/ |
son for the child’s virilization. At that time, they; Y% Z5 x8 l5 f! k6 P+ b
decided to put the baby in a separate bed, and the
- u/ Y* c' f2 v) a$ y* D3 F2 [father was not hugging him with bare skin and had
: g$ ~0 E6 u% z" e/ ~been using protective clothing. A repeat testosterone5 e) R" m# v6 h" W" f, C
test was ordered, but the family did not go to the
8 O9 O4 i, F5 a2 C( v" ulaboratory to obtain the test.5 F* d' R8 z; [+ M3 }$ z  d
Discussion
& d) c: @8 N/ l: V" ~  m  a0 m" gPrecocious puberty in boys is defined as secondary
- t/ ^( ~% ]& vsexual development before 9 years of age.1,4
7 M7 k) W5 T' YPrecocious puberty is termed as central (true) when! N* U% w3 a0 g, t. m  G
it is caused by the premature activation of hypo-. m/ n6 k' _( U' u) X
thalamic pituitary gonadal axis. CPP is more com-
( p5 }6 t+ |/ |. S6 i) M" K( _/ Jmon in girls than in boys.1,3 Most boys with CPP% b! u/ l; K4 Z( U/ I
may have a central nervous system lesion that is
2 n' m( s7 `9 U, G$ p, q" ?responsible for the early activation of the hypothal-
, M$ u$ u6 r6 l+ K! Famic pituitary gonadal axis.1-3 Thus, greater empha-
1 `4 B3 Y4 ~$ C0 z7 C2 @2 ~sis has been given to neuroradiologic imaging in+ Y8 B" v7 B" y3 N7 j! [6 X
boys with precocious puberty. In addition to viril-
4 c! Y; z: Z, ]ization, the clinical hallmark of CPP is the symmet-
1 c( x9 h5 Y/ n' yrical testicular growth secondary to stimulation by
% s1 ]$ R7 f3 X0 g, A5 C1 |, f: fgonadotropins.1,3; \2 W- i8 |% B
Gonadotropin-independent peripheral preco-
' D% d" q9 d8 ]' {( s7 s8 c: Hcious puberty in boys also results from inappropriate# N, E4 b6 K2 v0 c
androgenic stimulation from either endogenous or
4 F+ ?, L$ w- v0 z2 S9 u: Jexogenous sources, nonpituitary gonadotropin stim-
, N, b  i0 y6 n7 e& x9 F5 oulation, and rare activating mutations.3 Virilizing, C, c2 m4 p+ r. c3 x  c
congenital adrenal hyperplasia producing excessive- f! W& t/ w7 k& F7 J9 r
adrenal androgens is a common cause of precocious4 r( S. ~" I& A& v
puberty in boys.3,4
. l: |& @( J; A1 G+ R6 `9 S5 a/ EThe most common form of congenital adrenal
* I  B. b* ]- N5 Y* W2 X7 Ihyperplasia is the 21-hydroxylase enzyme deficiency.1 r1 L3 h$ |/ e3 {, W
The 11-β hydroxylase deficiency may also result in0 V8 u5 @& L% |8 D5 D' q
excessive adrenal androgen production, and rarely,
; r: P- [" H: R, W8 U# ban adrenal tumor may also cause adrenal androgen) R+ I2 P5 B" `9 a8 ~. m
excess.1,3
4 L1 m1 A7 \0 i9 {7 Wat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
  Y3 D: j, z' R542 Clinical Pediatrics / Vol. 46, No. 6, July 20074 ~5 ?& `, o9 o9 y  I/ c) r
A unique entity of male-limited gonadotropin-. ^- f: X' ~2 M8 s' C
independent precocious puberty, which is also known5 h4 H7 w0 ?0 K! y
as testotoxicosis, may cause precocious puberty at a
. M$ d0 C; X: }4 D- dvery young age. The physical findings in these boys
" k/ O* t" W1 swith this disorder are full pubertal development,4 H! Y# k% f6 L. K! ?1 N
including bilateral testicular growth, similar to boys
2 |2 O6 r! Z$ W, `1 k5 Owith CPP. The gonadotropin levels in this disorder
2 z6 _" b1 R8 z  Mare suppressed to prepubertal levels and do not show
7 z- ]2 n# u( A  P1 E5 I  E6 xpubertal response of gonadotropin after gonadotropin-. ~$ A+ X, q' d$ t  v
releasing hormone stimulation. This is a sex-linked9 d3 o( @& q) @8 }' d9 `
autosomal dominant disorder that affects only
3 j  x8 M% _# E, E. pmales; therefore, other male members of the family
! E/ `0 @$ {& I, L# e0 n1 w* ?may have similar precocious puberty.3
+ G) U3 y+ |& }2 p; u8 B$ R* uIn our patient, physical examination was incon-
9 y4 t) e; B2 L9 k/ }sistent with true precocious puberty since his testi-
' {0 O, W$ R  Jcles were prepubertal in size. However, testotoxicosis
7 i! L6 w$ m% b) G9 w4 k. q5 P4 Rwas in the differential diagnosis because his father
" P/ T; a8 R7 }0 c2 g& y3 Y- ostarted puberty somewhat early, and occasionally,1 i6 `# p& z0 G$ Q/ y/ p( @
testicular enlargement is not that evident in the( A2 T- ~; M6 S
beginning of this process.1 In the absence of a neg-
( g! Y9 F. t' h! aative initial history of androgen exposure, our5 V( [+ {( o& p! k
biggest concern was virilizing adrenal hyperplasia,, [1 W7 t7 P0 L' P0 o7 Q
either 21-hydroxylase deficiency or 11-β hydroxylase
# x; c( F- O& wdeficiency. Those diagnoses were excluded by find-
7 T: g( a% R. K0 P- cing the normal level of adrenal steroids.5 j; b0 n* a5 r% p2 o0 F8 {
The diagnosis of exogenous androgens was strongly
1 e# W% [( R% x2 v1 Rsuspected in a follow-up visit after 4 months because
1 }) Z. O7 I; `7 u& o. O5 Ythe physical examination revealed the complete disap-
( c2 i) |2 m; f+ b9 \pearance of pubic hair, normal growth velocity, and5 Q1 K& s) g. q3 B% d: z
decreased erections. The father admitted using a testos-
. f+ Z! P# J3 I+ sterone gel, which he concealed at first visit. He was8 X. B1 G5 }( M) m8 j$ F
using it rather frequently, twice a day. The Physicians’2 A8 ~$ }" r3 j/ [
Desk Reference, or package insert of this product, gel or  a4 ?; p- V6 d) ^9 A! K  I  z  ~
cream, cautions about dermal testosterone transfer to
  w3 e" d# v1 ~5 }( Xunprotected females through direct skin exposure.
) I/ v  I! |8 ^( I* F& uSerum testosterone level was found to be 2 times the% g, c$ p3 ^! K5 X) V
baseline value in those females who were exposed to
' `* s1 N- C" T  n0 T. R- ~+ F* \2 Aeven 15 minutes of direct skin contact with their male
! G: m; u4 T: rpartners.6 However, when a shirt covered the applica-$ ~& m- ^4 I# h- P$ C$ n6 Z6 K
tion site, this testosterone transfer was prevented.0 I  U4 Y3 U" S" n0 j) p  @
Our patient’s testosterone level was 60 ng/mL,
& T: @5 n, u+ r, Q6 vwhich was clearly high. Some studies suggest that
* h4 p/ X. H' U, y! W: n' `/ n. I, odermal conversion of testosterone to dihydrotestos-
* B/ l8 @8 [* d1 `% |2 q& uterone, which is a more potent metabolite, is more
# d' J/ ^' d. tactive in young children exposed to testosterone
# p' t: m4 X9 J  W: Yexogenously7; however, we did not measure a dihy-
3 |' C1 y, O2 {' ddrotestosterone level in our patient. In addition to
7 ^, Q" n' C2 |/ F/ z! G( \) vvirilization, exposure to exogenous testosterone in! ]6 E. k' @) e0 U2 J- B
children results in an increase in growth velocity and
3 [  G' A& E0 J. M% {5 y* ~5 C5 Xadvanced bone age, as seen in our patient.% d4 ^/ d! t: l. o
The long-term effect of androgen exposure during
& P7 S8 M' {& `' q# c# F8 i. I: _early childhood on pubertal development and final
# o" C3 K9 e( R2 j$ padult height are not fully known and always remain
) w7 ^) a9 c$ g5 n# q7 c" Q5 g; ka concern. Children treated with short-term testos-
. M' `. Z6 J7 ]/ N) R9 u0 Nterone injection or topical androgen may exhibit some
9 L" c8 w2 a5 s; v8 X4 W, r, }acceleration of the skeletal maturation; however, after* t5 m/ a) G0 A; d/ `. L
cessation of treatment, the rate of bone maturation
4 M, p' q; [* Q- u" y# n! s; w. Odecelerates and gradually returns to normal.8,9
/ w" A7 F: T3 w5 c3 LThere are conflicting reports and controversy
: Z: d. a. j- O9 Y' _/ `over the effect of early androgen exposure on adult
7 H( P+ r# A4 B5 D) W3 r" Upenile length.10,11 Some reports suggest subnormal. L2 E3 ~) n9 ~
adult penile length, apparently because of downreg-3 E6 V7 I7 c1 ?$ k7 ^0 w6 {
ulation of androgen receptor number.10,12 However,
% q8 W3 f8 N9 u/ CSutherland et al13 did not find a correlation between# X5 D: N( ]& b& T7 s' W3 F2 Z
childhood testosterone exposure and reduced adult' B8 V6 T/ \! W/ u0 ~
penile length in clinical studies.
) H6 D. [, v! @Nonetheless, we do not believe our patient is, q8 a/ g0 y  h8 i9 z0 H0 U
going to experience any of the untoward effects from
1 P& I% K( N; C  g8 Y  N8 f" \testosterone exposure as mentioned earlier because( n# o0 h% \/ `" S" R$ L4 s
the exposure was not for a prolonged period of time.( V; f8 M& r2 y- Q- j
Although the bone age was advanced at the time of8 N- n4 C9 R5 \- O7 L/ F
diagnosis, the child had a normal growth velocity at6 y) r3 k) }& |; I& A. K1 f
the follow-up visit. It is hoped that his final adult
" e: d: @2 B& e5 kheight will not be affected.
, ?, M0 x" H; _5 X/ [, W" ~0 EAlthough rarely reported, the widespread avail-
" d8 L+ Z5 f5 l8 m8 I! Hability of androgen products in our society may
6 q8 b3 t1 ^% o- |( H. V4 g  ^2 gindeed cause more virilization in male or female% n) U! B: v7 i3 ^2 H
children than one would realize. Exposure to andro-
, k# M7 B; }5 z- {) n2 [/ bgen products must be considered and specific ques-/ S5 Y' L6 i" d1 K( u6 n& }
tioning about the use of a testosterone product or
- V9 p, f4 Y0 r2 egel should be asked of the family members during, |# Y6 H* r/ f- W" }# Y+ S- l
the evaluation of any children who present with vir-+ k1 W6 u' T: g4 Y  N
ilization or peripheral precocious puberty. The diag-
0 s9 z0 l* k: G; x8 Z+ \nosis can be established by just a few tests and by  v# X: y( \' l! ^! @9 c
appropriate history. The inability to obtain such a# r/ ?9 v( N( ?" H7 V
history, or failure to ask the specific questions, may
; C  L& b$ Z0 `result in extensive, unnecessary, and expensive5 a  L2 {5 Y  V6 m
investigation. The primary care physician should be  P; ?+ ~! @' I. {2 f- L
aware of this fact, because most of these children
8 `! R& m8 L0 w2 w# u9 Hmay initially present in their practice. The Physicians’
6 ?3 e4 q5 R: o0 k( p% @9 ]: s# eDesk Reference and package insert should also put a
. b  C9 `: @2 x) A4 Wwarning about the virilizing effect on a male or
* n8 Y, i) Q; C3 {: vfemale child who might come in contact with some-
4 W. L) g" \: V) ]% i: done using any of these products.6 n7 _) V" q; ?$ f
References
: e# {/ @/ W1 Y* o# V4 _9 |, y1. Styne DM. The testes: disorder of sexual differentiation' I$ X8 s- \1 f6 I
and puberty in the male. In: Sperling MA, ed. Pediatric9 w4 r0 T# {+ _3 A1 w
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;3 R0 E, a9 D0 r
2002: 565-628.
% q+ a# \1 Q- C* Y5 w6 M2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious/ j' I  t$ K; ^2 q1 F
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$ V; n0 [' Q& G
Boy Induced by Indirect Topical
2 l- H& b  ?& T0 `4 B' M- Q: [# wExposure to Testosterone
) h) z' s( O- ]Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2* N  K9 n5 ]0 P5 n3 f7 D6 e- Y
and Kenneth R. Rettig, MD1
- S9 I- B; @5 |5 m$ ^: ~+ \6 eClinical Pediatrics1 I# S6 g7 F7 W* T
Volume 46 Number 6
, \7 @2 p8 k, L' `% P) BJuly 2007 540-543
" o/ `# W% @! z2 n# K% ]© 2007 Sage Publications
% g) O1 A7 ^8 c1 Y* e10.1177/0009922806296651& K6 m/ U7 [( M: k& M5 }9 V
http://clp.sagepub.com9 }7 T* M6 {" E6 u
hosted at
; n: W+ z* G& j4 U8 |: ~1 Fhttp://online.sagepub.com/ F# ?  H3 V* I+ Z0 Z  Q' o
Precocious puberty in boys, central or peripheral,
8 ?; X: u) K7 nis a significant concern for physicians. Central2 _  p9 G3 r3 R& f
precocious puberty (CPP), which is mediated
. J/ K* G8 U; q& G/ T* V0 Z9 Rthrough the hypothalamic pituitary gonadal axis, has- h# h0 S! z: W$ d
a higher incidence of organic central nervous system
5 L; B# o' }! i* Llesions in boys.1,2 Virilization in boys, as manifested( k  N* `4 b, U- n, G! K8 n9 D
by enlargement of the penis, development of pubic, x) x5 h8 E& m: x# P, G9 A
hair, and facial acne without enlargement of testi-
0 P* K/ r6 H% S* G8 \cles, suggests peripheral or pseudopuberty.1-3 We% c2 T6 g$ x! E+ g9 T
report a 16-month-old boy who presented with the/ W& E' f1 z2 D/ h$ \+ b# O4 m0 B
enlargement of the phallus and pubic hair develop-5 N: j7 ?( q" t$ R( A) t. a* d
ment without testicular enlargement, which was due  @0 r' |2 b& O% \- m
to the unintentional exposure to androgen gel used by* ]# ]3 v; n( K  Y- Z
the father. The family initially concealed this infor-
. \/ c# [2 d5 {  ~mation, resulting in an extensive work-up for this7 |' f3 j0 R" S5 z1 @: C
child. Given the widespread and easy availability of5 a8 V6 Z1 d$ K+ _
testosterone gel and cream, we believe this is proba-
. ~. B5 W4 P, j( }7 y# Wbly more common than the rare case report in the
' w. P* I6 R+ A. z4 D; N/ q' Nliterature.4
. [& M5 `3 d. M2 R6 d6 sPatient Report
6 W; r, v4 }! @/ T$ MA 16-month-old white child was referred to the7 d/ }7 ~5 v6 x
endocrine clinic by his pediatrician with the concern/ b! H# I( i# ]+ `# C* p, a% y
of early sexual development. His mother noticed
# |+ l2 X9 b) y( o; s3 ilight colored pubic hair development when he was0 s  ]7 i/ I) ?. A/ H' |
From the 1Division of Pediatric Endocrinology, 2University of- [; t% n3 ~( @2 ~* n
South Alabama Medical Center, Mobile, Alabama.
* A2 K  `2 C( k) [; ~Address correspondence to: Samar K. Bhowmick, MD, FACE,+ I$ g. r0 z  m2 D" ?$ S- r
Professor of Pediatrics, University of South Alabama, College of: S, j9 d& {, u
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
: [; |  q8 x$ b) @& N& }2 d: a# re-mail: [email protected].
" b0 n4 L% n* C( O2 [about 6 to 7 months old, which progressively became/ x4 i7 l# W6 Y5 s9 d/ l
darker. She was also concerned about the enlarge-
5 ^$ o3 s6 Q& f9 m! Ument of his penis and frequent erections. The child6 j/ x5 i) A& B
was the product of a full-term normal delivery, with
' p4 @) E6 A0 ?% k: Za birth weight of 7 lb 14 oz, and birth length of
/ j6 g- j) `3 o- C# L# e20 inches. He was breast-fed throughout the first year) p; y$ q6 M9 N
of life and was still receiving breast milk along with) ~4 f( {- _) F7 |, K
solid food. He had no hospitalizations or surgery,
1 S+ I( _* K9 F. J# c* F' Gand his psychosocial and psychomotor development
9 j7 F7 O  Y/ i$ q6 ^was age appropriate.& E1 Q7 q, G" m8 `
The family history was remarkable for the father,7 J# N; v/ {' V. {
who was diagnosed with hypothyroidism at age 16,8 m# I. g  L( M- v' D$ C, H* r
which was treated with thyroxine. The father’s
5 K: R* y- G' nheight was 6 feet, and he went through a somewhat! V6 `) Q9 s. `" W1 j9 t2 n
early puberty and had stopped growing by age 14.
* q! u- C7 r1 B; x" @$ @2 QThe father denied taking any other medication. The# z6 A9 W4 Y2 p. t* v
child’s mother was in good health. Her menarche8 W3 Q0 T! G4 R+ Q
was at 11 years of age, and her height was at 5 feet
" ^9 w, Y* ~: h; W$ [1 B5 inches. There was no other family history of pre-
" L. L+ m8 R. i% gcocious sexual development in the first-degree rela-- y& R7 X2 A" ?, T3 Z
tives. There were no siblings.3 {4 a6 R1 \5 M
Physical Examination
( \, g) J, U( t- H8 Z: tThe physical examination revealed a very active,
6 c0 w1 L+ S4 v% Cplayful, and healthy boy. The vital signs documented5 u* x2 L# M3 f9 q: Y7 h' s
a blood pressure of 85/50 mm Hg, his length was2 u- X5 \6 @( H) k
90 cm (>97th percentile), and his weight was 14.4 kg
& y4 u7 E3 R& d& E4 ^/ x(also >97th percentile). The observed yearly growth& M  s1 W9 [5 O4 a! T5 }+ t
velocity was 30 cm (12 inches). The examination of8 p  Y1 q% \# `# Q
the neck revealed no thyroid enlargement.
% n/ E1 j- h. ^& @The genitourinary examination was remarkable for
6 {  _: K+ K- H7 B! l1 M3 venlargement of the penis, with a stretched length of7 A/ G8 x# Q4 K/ `" g; q
8 cm and a width of 2 cm. The glans penis was very well2 k0 c( }' b! m) ^& g
developed. The pubic hair was Tanner II, mostly around9 h7 z& z' x; j9 G; j# i6 j+ Q7 P
540
5 ]  x1 d- [  i: z/ ?, tat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
& L' `+ M, S2 [! S) uthe base of the phallus and was dark and curled. The
! V7 X) y  C, h, }testicular volume was prepubertal at 2 mL each.
% O  y: T- \4 z" ZThe skin was moist and smooth and somewhat8 B( G9 ^. ?0 h
oily. No axillary hair was noted. There were no) i* ]+ I- r0 i% O, Z3 p' G
abnormal skin pigmentations or café-au-lait spots.# g6 I7 V! c% s3 d  O' S
Neurologic evaluation showed deep tendon reflex 2+
5 `/ |7 L. S! Y- @bilateral and symmetrical. There was no suggestion
3 z! M0 t' d8 J7 x% O4 O" Pof papilledema.
) i  [) e% ], x1 w1 l0 qLaboratory Evaluation% G; u5 h5 V- o$ O
The bone age was consistent with 28 months by' p4 _% ~; ~% j: x! R+ X
using the standard of Greulich and Pyle at a chrono-4 k" G2 U# Z- _+ ]
logic age of 16 months (advanced).5 Chromosomal3 S* o# @4 K9 c  g! k3 k
karyotype was 46XY. The thyroid function test
& p: R/ L, j$ ?9 i" K& n% Lshowed a free T4 of 1.69 ng/dL, and thyroid stimu-4 W2 |: ^* m# M8 c
lating hormone level was 1.3 µIU/mL (both normal).) x3 K4 r  x  Y4 P
The concentrations of serum electrolytes, blood4 a8 `: [7 W+ ^. ?
urea nitrogen, creatinine, and calcium all were
# V3 |; G' ~: Z5 H$ c& @! [within normal range for his age. The concentration/ I& F8 k: b( D8 a2 f
of serum 17-hydroxyprogesterone was 16 ng/dL
' N9 f/ \* |% S) L! ~- ~0 |(normal, 3 to 90 ng/dL), androstenedione was 20
, O' K, x2 d. P$ Y2 ]3 G3 v6 Ung/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
- j9 v) @9 T! H) Z- R! Uterone was 38 ng/dL (normal, 50 to 760 ng/dL),3 k9 G" l4 T) C7 W7 E: _
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
5 ?0 G. |( O- w- @" d3 q49ng/dL), 11-desoxycortisol (specific compound S)- `0 N. M+ {  J' L2 {9 U
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-; ?) o2 o2 [) [! B- d
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
  G* p+ a' L; {6 y3 j8 ]5 }6 gtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),6 t0 ~! c; G% O: x3 v8 G5 ]  t$ [8 s
and β-human chorionic gonadotropin was less than9 {! g5 B- h- L4 j+ P4 T
5 mIU/mL (normal <5 mIU/mL). Serum follicular) v  a$ u+ h% ^3 ?+ k
stimulating hormone and leuteinizing hormone# ?; @: W; w6 d" @& y4 W' ]! Y- l
concentrations were less than 0.05 mIU/mL/ _/ i9 P; P# B/ X  h- B% d
(prepubertal).& ?, t/ q; W7 d5 m. ^/ S2 a4 @. t* H
The parents were notified about the laboratory
$ I, n4 G! X" _% ~# G5 |results and were informed that all of the tests were
4 w0 U2 D5 J4 U& ^, \. r$ |normal except the testosterone level was high. The3 Z, Q3 O7 U, x4 C9 n
follow-up visit was arranged within a few weeks to' s4 B, V; r1 A) g) x7 K
obtain testicular and abdominal sonograms; how-
2 |2 o0 M6 A- K+ @. Yever, the family did not return for 4 months.! p2 \/ a$ x% m/ y4 T
Physical examination at this time revealed that the
6 t+ t  H+ Z5 Q, D1 x- _2 Uchild had grown 2.5 cm in 4 months and had gained& x* z  T% B( q- T9 s
2 kg of weight. Physical examination remained( |+ A0 u( V; W4 `+ U, \
unchanged. Surprisingly, the pubic hair almost com-
) S) ^& F7 y$ G5 i) gpletely disappeared except for a few vellous hairs at
& F+ @) G/ V7 P2 ?9 L5 p) gthe base of the phallus. Testicular volume was still 2
! w# Q% g9 u* R  }" E% C0 j8 omL, and the size of the penis remained unchanged./ u/ ~3 `' L6 K  |7 S" `+ l
The mother also said that the boy was no longer hav-/ _$ {! l3 C* ?( [2 u
ing frequent erections.  N: ]; I) |/ Y' `: j$ M% G
Both parents were again questioned about use of5 o& i4 O& K& D0 S
any ointment/creams that they may have applied to) I8 a5 u/ o* L0 k& N5 c
the child’s skin. This time the father admitted the
  E: k5 U' [3 gTopical Testosterone Exposure / Bhowmick et al 541, e  {" B  p. A
use of testosterone gel twice daily that he was apply-) F, }& _8 w' `9 U! B) X% E0 l  u
ing over his own shoulders, chest, and back area for
$ m4 F5 K3 N( }$ Xa year. The father also revealed he was embarrassed
3 `. B  S4 Y! ]to disclose that he was using a testosterone gel pre-' n% v: S& Y3 M6 {# n4 l0 Z
scribed by his family physician for decreased libido
1 n% n% r, j3 x" ~8 V1 Isecondary to depression.
+ U1 a% W/ K1 }0 r/ U7 N3 c3 A  qThe child slept in the same bed with parents.
5 B* d+ D8 u* AThe father would hug the baby and hold him on his1 C- q) {, X' J
chest for a considerable period of time, causing sig-. R4 x. u( j: X/ ^  `: y4 k
nificant bare skin contact between baby and father.) k8 b3 ?  z$ w8 J  H
The father also admitted that after the phone call,
, R" l4 c- p2 F  Z& X4 mwhen he learned the testosterone level in the baby
3 N: _" H; u4 z) [! g/ A( qwas high, he then read the product information
) _6 S3 G; g0 Fpacket and concluded that it was most likely the rea-6 m! d4 T; h! y+ f% ?1 x
son for the child’s virilization. At that time, they
, @7 P9 N$ y- E2 \9 e7 ndecided to put the baby in a separate bed, and the
& z1 I2 h# w, G7 vfather was not hugging him with bare skin and had2 Q' i' H4 Y9 N- g
been using protective clothing. A repeat testosterone5 T5 g, f- Z. p7 h# q
test was ordered, but the family did not go to the9 d; j; l+ x. [1 p
laboratory to obtain the test.7 I8 E( w# {- c
Discussion/ X. T7 t7 n( F! I  H& A. h
Precocious puberty in boys is defined as secondary* r+ M) G4 z& B4 R$ s
sexual development before 9 years of age.1,4
. ?: v9 _1 I! J: ^Precocious puberty is termed as central (true) when+ y5 e2 S7 B8 w$ D! a5 _) |: S
it is caused by the premature activation of hypo-$ s  }8 i: E- `- S9 f4 A! N$ l) F
thalamic pituitary gonadal axis. CPP is more com-
! S9 L7 E% W1 O9 m- V3 {( Zmon in girls than in boys.1,3 Most boys with CPP
; U+ z; E$ C$ r: s( j1 R2 rmay have a central nervous system lesion that is
; V8 Z) H& q1 w) {responsible for the early activation of the hypothal-3 [+ `% G; K/ i2 k1 D
amic pituitary gonadal axis.1-3 Thus, greater empha-
. D8 T' p7 B: e: f* [sis has been given to neuroradiologic imaging in8 d# ^/ [$ G" y
boys with precocious puberty. In addition to viril-
* s" d* |; a" x. O7 Oization, the clinical hallmark of CPP is the symmet-
. }9 c; m. s' ^) Arical testicular growth secondary to stimulation by
& d1 E: C; e; I+ P; k2 Q6 Ngonadotropins.1,34 S0 ]& w9 n8 |- L+ E2 H
Gonadotropin-independent peripheral preco-& E1 c  s( I; a. I4 @' G
cious puberty in boys also results from inappropriate4 r( {  h8 d- \0 f7 U
androgenic stimulation from either endogenous or+ M& f# g( i& U$ C- e( V, N' a4 d0 o0 n
exogenous sources, nonpituitary gonadotropin stim-
" i! ]2 [+ E6 Bulation, and rare activating mutations.3 Virilizing3 Q6 c0 `% @5 T4 I9 S0 s) Z- e
congenital adrenal hyperplasia producing excessive
7 l) A/ }6 y+ V0 |adrenal androgens is a common cause of precocious  l0 i: F% x8 g  M
puberty in boys.3,4
0 h% X) k5 y3 v- `0 SThe most common form of congenital adrenal7 d" Z% n$ U5 W" J2 Z9 Q. Y/ C
hyperplasia is the 21-hydroxylase enzyme deficiency.) [0 p: Q4 b+ x8 G9 ~4 Z
The 11-β hydroxylase deficiency may also result in  ]; f+ s* S. q% h
excessive adrenal androgen production, and rarely,
" g, [- E: J* ~- Nan adrenal tumor may also cause adrenal androgen3 f4 d' c5 T% D0 C( o! j. q  C
excess.1,3) V( G3 m7 k& M3 N
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from1 L  l. [1 R( k7 A! X! z
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
0 }1 D: l' l/ i# ]% n. u9 ?A unique entity of male-limited gonadotropin-
; z: ~. P9 k6 m  H( Qindependent precocious puberty, which is also known. i& Q3 M$ \, {( o2 m. ^. t
as testotoxicosis, may cause precocious puberty at a7 m9 D2 E" q+ P% d
very young age. The physical findings in these boys
4 z$ p% K* I1 J0 R. E. u& L9 q, ?4 `with this disorder are full pubertal development,+ L7 s9 q9 b; J1 |" W
including bilateral testicular growth, similar to boys
, h2 F$ B- [8 Awith CPP. The gonadotropin levels in this disorder7 s/ A1 X5 ~% E% ^3 {
are suppressed to prepubertal levels and do not show( b2 z2 n0 i/ V, E! _1 Y/ e; ]
pubertal response of gonadotropin after gonadotropin-$ a5 O& J' Z6 H, o' j
releasing hormone stimulation. This is a sex-linked
, r7 B) f0 Q7 G" ~; \2 n; ^autosomal dominant disorder that affects only
* l( @* }  R3 zmales; therefore, other male members of the family
; }/ M8 Q  c6 D3 f; \( xmay have similar precocious puberty.3
! m6 c+ {2 @) W: }6 F$ VIn our patient, physical examination was incon-6 ^7 d+ Z% I( Q9 o& a# d
sistent with true precocious puberty since his testi-
& d7 d. M! e" ucles were prepubertal in size. However, testotoxicosis5 b+ f% ]8 R; W" U" `- z
was in the differential diagnosis because his father( H$ f8 {+ s. `9 [  v
started puberty somewhat early, and occasionally,5 x5 g& @# ^( U8 T  y* k: o# \, L- q
testicular enlargement is not that evident in the  n0 V% j  ?6 v: t
beginning of this process.1 In the absence of a neg-# S# K- d/ {( K+ U0 |
ative initial history of androgen exposure, our
: H7 [# A- u6 B1 Q/ g' Vbiggest concern was virilizing adrenal hyperplasia,; a0 u1 I4 U( r; y( i- P
either 21-hydroxylase deficiency or 11-β hydroxylase5 W( P$ a6 ^' @# Q% l$ {1 G8 y
deficiency. Those diagnoses were excluded by find-' v- y. r5 Q6 }% G/ G* O
ing the normal level of adrenal steroids.
1 m$ s9 I" |2 ?The diagnosis of exogenous androgens was strongly
+ p; @  j2 s: |2 a. i% @suspected in a follow-up visit after 4 months because
, Q$ _  c3 D+ R  @the physical examination revealed the complete disap-- k' \4 P. G( _0 W% B/ [* o
pearance of pubic hair, normal growth velocity, and
5 S3 k+ I( t% d$ O8 rdecreased erections. The father admitted using a testos-
" l2 l# \7 g8 L/ Vterone gel, which he concealed at first visit. He was
) c+ d% L, T! Wusing it rather frequently, twice a day. The Physicians’
; q9 f# z: Y- r. Z$ c1 |Desk Reference, or package insert of this product, gel or
$ }8 y2 S7 T: X2 Z7 vcream, cautions about dermal testosterone transfer to
6 L) Y' B$ q9 p- L9 ounprotected females through direct skin exposure.
. v. S1 ?- H/ rSerum testosterone level was found to be 2 times the, K! L# {9 G$ c& {* L, u
baseline value in those females who were exposed to  `2 K/ I" I/ D1 f, i# K$ _
even 15 minutes of direct skin contact with their male
) j0 K1 b; k- J5 `7 mpartners.6 However, when a shirt covered the applica-- M! }. a% j- M5 Y- h; M! d
tion site, this testosterone transfer was prevented.
; h( r- K4 Y! k" e+ j$ ]Our patient’s testosterone level was 60 ng/mL,9 L* f, d3 e9 m- P
which was clearly high. Some studies suggest that
' n# B. `# s3 }dermal conversion of testosterone to dihydrotestos-4 R; U! c) i3 E' Y9 t( A) h* \
terone, which is a more potent metabolite, is more
* K. K7 P4 P' {3 a" i) yactive in young children exposed to testosterone
- V1 c+ y1 [& E5 O, J* Gexogenously7; however, we did not measure a dihy-5 A/ D: [: E) x, F: n) e6 H: D  D
drotestosterone level in our patient. In addition to
$ d& C; r6 y' N; D6 }3 j7 gvirilization, exposure to exogenous testosterone in
: F1 J4 i; n. O# Kchildren results in an increase in growth velocity and9 _- c9 T6 c  T$ N
advanced bone age, as seen in our patient.0 l9 A, }1 q4 @, D
The long-term effect of androgen exposure during) L$ H( b; k( Y2 p3 ^* y
early childhood on pubertal development and final& K4 d, s9 {% O  ~5 F
adult height are not fully known and always remain9 |# b; Y' D. k- E" g
a concern. Children treated with short-term testos-/ ~5 J2 ?0 \7 C2 _& `$ ?2 D
terone injection or topical androgen may exhibit some
9 H$ ^7 g/ P  q5 y$ R+ Jacceleration of the skeletal maturation; however, after( }- \0 U" d$ K( z2 |% I
cessation of treatment, the rate of bone maturation& g; a! U1 T+ i! C: I
decelerates and gradually returns to normal.8,9; Q2 q, `0 \0 Q6 D: q
There are conflicting reports and controversy
& z% C, l; z( v) M1 w. ]over the effect of early androgen exposure on adult0 \, _2 }+ q6 a$ F6 N
penile length.10,11 Some reports suggest subnormal6 o7 T. {& Q) b$ A, A) R6 Q
adult penile length, apparently because of downreg-
" E" ]  F& e6 {ulation of androgen receptor number.10,12 However,# J0 E7 Z3 i5 b* |
Sutherland et al13 did not find a correlation between
3 u* r% S. w  K* L2 Wchildhood testosterone exposure and reduced adult2 ^( l- h8 r! F- B% n7 L
penile length in clinical studies.% t8 d$ r; N) i/ o
Nonetheless, we do not believe our patient is  T5 u* e6 y) m# T1 @  s$ ^/ x# j
going to experience any of the untoward effects from
9 a! D$ s& E0 \9 G# @testosterone exposure as mentioned earlier because
/ ~8 V, Y, k' D; R- U+ }0 kthe exposure was not for a prolonged period of time.
9 y) U7 J5 s0 t1 ^/ z7 J! k9 oAlthough the bone age was advanced at the time of( j+ R- S' }5 t; c
diagnosis, the child had a normal growth velocity at1 V+ B8 ~! ^7 y6 l$ n" U6 _
the follow-up visit. It is hoped that his final adult& W3 T, y* i! t/ Z
height will not be affected.
; h9 Z0 z4 ~' A) _( U, L. YAlthough rarely reported, the widespread avail-
0 n+ Z9 U4 [+ {+ t. J( a; j6 |ability of androgen products in our society may0 c- f0 E+ Z: n' q. h: {! V
indeed cause more virilization in male or female( h+ \0 O6 Z7 z+ Q. Q# j
children than one would realize. Exposure to andro-
8 q7 w# c$ r/ E+ Cgen products must be considered and specific ques-
/ c; `# v( h8 f! l5 v( _# R. stioning about the use of a testosterone product or5 N. ^" k& R/ \0 h, t
gel should be asked of the family members during
" \; w) z& r, h  U$ E. {the evaluation of any children who present with vir-
; [4 Q- g7 E& m* V7 _- dilization or peripheral precocious puberty. The diag-
/ z8 ^8 z+ y: }* }; p- o7 Mnosis can be established by just a few tests and by( m$ }9 w% ~8 w! h1 M& w
appropriate history. The inability to obtain such a8 N5 Y5 `1 W+ b& B$ V1 L
history, or failure to ask the specific questions, may
1 b, J: R0 y% F% l3 ?) Tresult in extensive, unnecessary, and expensive
  s/ S- T; D% A, L3 Minvestigation. The primary care physician should be2 [$ _  U6 m2 d0 e! ]* f
aware of this fact, because most of these children
. `6 y1 s1 ?8 ~, O4 ^7 H# ]1 X+ Bmay initially present in their practice. The Physicians’
/ T! x% U- @, `& W9 g. YDesk Reference and package insert should also put a
' e4 z5 e9 F$ s5 h9 _! w. m8 Zwarning about the virilizing effect on a male or! O& T9 ]& M6 j0 n# N" p1 O" X
female child who might come in contact with some-- \# f# E5 ?- i# k
one using any of these products.: k7 j' m5 d! _; V* m1 B
References
: G  d6 L, J! c% H, o1. Styne DM. The testes: disorder of sexual differentiation
& ?/ w) Y5 J0 _, land puberty in the male. In: Sperling MA, ed. Pediatric
# v% _. ^1 `  H. BEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
! H; u7 X& N  w: q; T. Y2002: 565-628.
$ c! B, B5 B+ W# ~+ S2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious" s  ?: U( x4 y6 M4 S  D% R( r8 A
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

( V+ m: K2 S. K) Z/ Q! F$ r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!
您需要登錄後才可以回帖 登錄 | 立即注册

本版積分規則


快速回復 返回頂部 返回列表