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
VIP精品區,資源無限好賺金任務區,輕松賺金幣
加入VIP,享受高級特權宣傳賺金又升級,超級棒
Sexual Precocity in a 16-Month-Old- `) s& e. f: m1 {; p# S
Boy Induced by Indirect Topical
  T5 u0 Q/ P  H( \Exposure to Testosterone/ @- K+ B, B" v; M4 w* b7 D% ^
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2" V7 v* |, r/ S$ U
and Kenneth R. Rettig, MD1
  I  v  p# K2 V+ }0 {Clinical Pediatrics
; A5 [" [" S, ?/ W8 M' N7 {! BVolume 46 Number 6
- c! m9 n8 c' J' W4 I; @1 [) @July 2007 540-543
7 {4 D; {& X2 O- @# d© 2007 Sage Publications
9 @7 Y( H" W, [8 }10.1177/00099228062966518 a( F3 \1 n( q- z/ v5 E9 `% s
http://clp.sagepub.com& \+ G, ?& ]. G5 d1 w* C! N+ \
hosted at. u) j9 m$ C" a* B# Y+ G: @1 W
http://online.sagepub.com4 u3 \$ X$ w- \
Precocious puberty in boys, central or peripheral,% G" S+ i" g4 ]5 f! ^4 K
is a significant concern for physicians. Central
( B% p- m5 M: N2 S1 g( Q) P( Oprecocious puberty (CPP), which is mediated) H: y/ W, g. C+ m( W$ F& m% S5 }
through the hypothalamic pituitary gonadal axis, has
+ X6 b6 T' X) E) c$ b5 N( h1 Va higher incidence of organic central nervous system; r% Y& ?- S: i# g! `4 ^
lesions in boys.1,2 Virilization in boys, as manifested
* N  a: {3 x5 C8 \by enlargement of the penis, development of pubic
" q% o+ p/ n: ~$ v+ G4 A) o- Dhair, and facial acne without enlargement of testi-
! d/ G- j) l3 V' K9 `cles, suggests peripheral or pseudopuberty.1-3 We
& S8 m, M( g6 U: Z8 |4 m' M; Ureport a 16-month-old boy who presented with the5 V9 D& @# \4 R
enlargement of the phallus and pubic hair develop-
. A* S! G( P" S( k6 H+ g" a  Xment without testicular enlargement, which was due. [* t8 ]% z8 e; M+ G: B
to the unintentional exposure to androgen gel used by! X) @$ [# |$ I1 x
the father. The family initially concealed this infor-
1 |: y2 k: W# b( w& A  S& |! [mation, resulting in an extensive work-up for this% V1 c" C" [9 N5 r
child. Given the widespread and easy availability of
0 ^1 b* J, W7 S  \testosterone gel and cream, we believe this is proba-
9 D( @. j' |# _& g, xbly more common than the rare case report in the
- [; {7 Z- g6 Cliterature.4
8 L: o' U' o1 @$ G0 P( B; {* o, W7 a: WPatient Report5 l# l9 Y  Q2 ]
A 16-month-old white child was referred to the
4 Z$ H% x* U9 `1 |) yendocrine clinic by his pediatrician with the concern
: u  p. j& {, ^  \! O0 cof early sexual development. His mother noticed
8 w0 W  m# R; ?light colored pubic hair development when he was8 k! g$ ?; o3 {% ]
From the 1Division of Pediatric Endocrinology, 2University of
9 p% l  M  |3 O! _South Alabama Medical Center, Mobile, Alabama./ h' P( B* S* Z3 `
Address correspondence to: Samar K. Bhowmick, MD, FACE,+ k: B9 X5 H9 ~' k( s" B! i* j
Professor of Pediatrics, University of South Alabama, College of
& R1 ]0 Y% b+ \( p, n& qMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;, d7 ^  [2 K$ K/ J2 Y. @: W
e-mail: [email protected].
: P% Y# O+ ~0 Mabout 6 to 7 months old, which progressively became1 G: ]! v1 M3 h3 j: q2 @
darker. She was also concerned about the enlarge-5 }1 n" W5 \- W+ ?9 j9 |+ |
ment of his penis and frequent erections. The child  D4 Z. ~' I: m7 H. p5 R( n
was the product of a full-term normal delivery, with, g4 v% [# s: u, c2 D- I+ c& A
a birth weight of 7 lb 14 oz, and birth length of
, m3 h3 g" n. [2 c$ e0 g20 inches. He was breast-fed throughout the first year
* B  i( B" Y: F! j" Sof life and was still receiving breast milk along with; K4 R7 J6 Q) v' @
solid food. He had no hospitalizations or surgery,
' L7 N+ ~! W5 s0 |and his psychosocial and psychomotor development2 ^  d3 y( S# @" {& l0 ^5 n) h
was age appropriate.
3 R/ Z+ X( S  B& mThe family history was remarkable for the father,
% H9 b# ?, M! Hwho was diagnosed with hypothyroidism at age 16,
9 k$ |: K1 ]: p; A8 Uwhich was treated with thyroxine. The father’s
* D2 g3 u- F- C7 p( x1 ^0 _  Vheight was 6 feet, and he went through a somewhat; a! T" f" k, o( q
early puberty and had stopped growing by age 14.1 D; ?8 w! k6 ?4 ]
The father denied taking any other medication. The
  h5 S' m' `/ e2 P& K4 X8 {% xchild’s mother was in good health. Her menarche
- W! K% t1 [. i2 Q8 y: Mwas at 11 years of age, and her height was at 5 feet9 K$ p! c6 W0 K. i, L
5 inches. There was no other family history of pre-
1 N8 m8 `! q/ K) \0 Y% {" `; }% }2 h+ ococious sexual development in the first-degree rela-& N0 r  o0 Z. @! O' Z7 u% l
tives. There were no siblings.
5 x4 M$ Q# p* R* J. F# zPhysical Examination9 H7 q6 e$ c5 n* I+ q
The physical examination revealed a very active,
7 w& \( a1 n$ O( E0 h8 Xplayful, and healthy boy. The vital signs documented: v: o! |7 e, `  K$ g2 }" D3 w
a blood pressure of 85/50 mm Hg, his length was% `! T  \. I; K, X% I$ v( K
90 cm (>97th percentile), and his weight was 14.4 kg
/ D4 t( F0 F1 A9 D5 A' p, w(also >97th percentile). The observed yearly growth% k0 ^% t' o! v- k7 k# P9 n% _
velocity was 30 cm (12 inches). The examination of# Y" H/ u( L2 `, a0 J
the neck revealed no thyroid enlargement.' R& [! j) l7 V& i. g* Q# w$ \& F
The genitourinary examination was remarkable for
# d/ K, A' C) u% m* qenlargement of the penis, with a stretched length of, i, s' {! u3 M: O- e8 {/ S
8 cm and a width of 2 cm. The glans penis was very well
* f, f+ b7 Y4 h/ Y' gdeveloped. The pubic hair was Tanner II, mostly around9 `8 I4 }: S/ f% e# v! d2 G. ~8 a4 |
5405 V/ g- E8 E6 g9 ?; H: B, d: H- |
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from$ R) e" B3 f6 [+ u% r- i
the base of the phallus and was dark and curled. The5 m1 F+ L* f5 y
testicular volume was prepubertal at 2 mL each.9 p/ Y2 R4 U- @+ j6 ]6 r  I
The skin was moist and smooth and somewhat
. N% w4 T: r7 r4 Xoily. No axillary hair was noted. There were no- J% m  m3 ]" p. Z
abnormal skin pigmentations or café-au-lait spots.
+ l! b$ Y6 Z: ]: N" oNeurologic evaluation showed deep tendon reflex 2+" _& N" R; w6 b( y
bilateral and symmetrical. There was no suggestion
- L/ Q& Z7 n& ?- i. l  j- e, yof papilledema., P+ L- i* K1 G
Laboratory Evaluation' w: R# r7 ^3 u! ]( Z
The bone age was consistent with 28 months by" Z  [7 O  P4 O& y) k
using the standard of Greulich and Pyle at a chrono-& m- j' J! I' ]0 J6 W. Y
logic age of 16 months (advanced).5 Chromosomal
" b3 r. _& e, [9 A( O: ikaryotype was 46XY. The thyroid function test% m0 o4 P0 G; j
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
. Q% z* c9 ]9 Q' L2 A# v8 j' dlating hormone level was 1.3 µIU/mL (both normal).9 V, D. ?2 [' B6 y# M; X( g# n4 M
The concentrations of serum electrolytes, blood
- u6 o; l1 a. y% I/ h0 Yurea nitrogen, creatinine, and calcium all were
: ?, d% q2 N9 N% {6 a0 b# ywithin normal range for his age. The concentration8 C4 V6 N8 c- c2 G
of serum 17-hydroxyprogesterone was 16 ng/dL
3 s! i% @) o  g+ z(normal, 3 to 90 ng/dL), androstenedione was 20/ ^8 ~) C. i/ w0 v% D# |' U# G, O
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
) W1 t/ [! ^# w' Z% L/ \& kterone was 38 ng/dL (normal, 50 to 760 ng/dL),
3 b1 V+ u. K1 g  I1 R7 S7 U9 d$ idesoxycorticosterone was 4.3 ng/dL (normal, 7 to
1 Z/ v* o% O" V1 o! h5 k9 h49ng/dL), 11-desoxycortisol (specific compound S)
7 Y) B, i( C* cwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
" N% |) ]0 s' G$ s  S% ntisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
3 s+ [( H# t. R! htestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
/ }7 g2 _+ n# g& g0 Z* z: p+ c7 gand β-human chorionic gonadotropin was less than
- N( \; r% v+ c3 }5 mIU/mL (normal <5 mIU/mL). Serum follicular6 u5 |: g: T' {8 s" ^
stimulating hormone and leuteinizing hormone3 z* z( H# H/ Y
concentrations were less than 0.05 mIU/mL
4 B$ n5 q; l7 l- N(prepubertal).# @( L" v+ s7 n' j; |
The parents were notified about the laboratory( J' J) b+ |* M, @' |
results and were informed that all of the tests were# c7 {" z3 K; V
normal except the testosterone level was high. The: W# V6 r- H' y" x$ e) o6 O5 Q- W
follow-up visit was arranged within a few weeks to# O+ R4 R6 e. _
obtain testicular and abdominal sonograms; how-: f# A7 a7 Y( |8 ?7 I
ever, the family did not return for 4 months." N3 d' {9 E/ H
Physical examination at this time revealed that the
" s/ D! ?& o/ p. m# Hchild had grown 2.5 cm in 4 months and had gained! W. ^5 V% b( g) P3 Z
2 kg of weight. Physical examination remained+ n% P! E0 r1 O% h$ O
unchanged. Surprisingly, the pubic hair almost com-- f5 o: S3 A7 ~5 a
pletely disappeared except for a few vellous hairs at( d# A8 ~7 r+ i
the base of the phallus. Testicular volume was still 20 U  ^( E( i, S
mL, and the size of the penis remained unchanged.( T% J6 q2 s8 l+ T
The mother also said that the boy was no longer hav-
. h8 U$ E% B& i( D2 D( x% fing frequent erections.- ]; _: w# p2 K
Both parents were again questioned about use of
& Z; U1 r8 ~9 d; O  cany ointment/creams that they may have applied to# F) X% [9 [2 i2 J) U
the child’s skin. This time the father admitted the- F3 p7 J9 b$ m( V
Topical Testosterone Exposure / Bhowmick et al 541
$ z9 j8 f+ n# ?; xuse of testosterone gel twice daily that he was apply-
9 P6 a' {! I, xing over his own shoulders, chest, and back area for
! s8 Y" K! b7 n( W/ ^: ka year. The father also revealed he was embarrassed
: \- n/ G% b  l; y) Fto disclose that he was using a testosterone gel pre-8 v; b- ^$ R8 K" c
scribed by his family physician for decreased libido
2 h9 ~  Y! m' K4 |- [% vsecondary to depression.
; G# G. Y% N5 J3 [6 @* n7 |2 ^* {The child slept in the same bed with parents.
. j: ~5 _& s4 d3 \The father would hug the baby and hold him on his
# p' v0 l6 n" e7 j: V# B0 Mchest for a considerable period of time, causing sig-. o& |1 U/ g% \% K) S, j0 j
nificant bare skin contact between baby and father.
- r5 F# @9 F* {. lThe father also admitted that after the phone call,& t9 z8 ~0 ]1 q7 w: x
when he learned the testosterone level in the baby) H. L. A0 G1 U
was high, he then read the product information
/ Y' s0 {( t+ Q, o( t+ J# z3 Mpacket and concluded that it was most likely the rea-6 P$ b6 H' n% T$ P; K6 L: R
son for the child’s virilization. At that time, they
8 t$ q/ E; x3 m2 @1 o. J# ^4 N" }decided to put the baby in a separate bed, and the/ ^  n. f, N& w% G! g$ u
father was not hugging him with bare skin and had" h. _) D! u8 u8 A- B# k
been using protective clothing. A repeat testosterone, s- I% D& y# z- H
test was ordered, but the family did not go to the" r" H3 I4 w: G% ~$ e0 ?" ~- b+ p
laboratory to obtain the test." u; N7 c0 S$ p" Q
Discussion
4 X; L: p% e3 h/ t1 `" sPrecocious puberty in boys is defined as secondary3 a# [; i- q- _) L  C2 L9 F
sexual development before 9 years of age.1,4: y" `  q; {- q8 z4 O, o
Precocious puberty is termed as central (true) when$ p( o5 F" l6 s& g% I! ^: f9 k6 K
it is caused by the premature activation of hypo-9 O* }" Q: y: ^
thalamic pituitary gonadal axis. CPP is more com-3 w7 S# K( X; y  i. |9 l
mon in girls than in boys.1,3 Most boys with CPP
( m/ r" Q( Q( a) b" M& G: imay have a central nervous system lesion that is8 a* f3 k6 U4 [3 z& U% D
responsible for the early activation of the hypothal-
$ C$ n4 C3 {" T: f  jamic pituitary gonadal axis.1-3 Thus, greater empha-  Y6 c8 P' k' p. u3 s& t& c; T
sis has been given to neuroradiologic imaging in4 ~' B! S- ^' f+ t; Q: R" A  z7 [
boys with precocious puberty. In addition to viril-' m8 p0 ~6 ?- D$ a
ization, the clinical hallmark of CPP is the symmet-
& ^+ G# _  M; v4 Xrical testicular growth secondary to stimulation by
! p2 \3 Z; T$ E( F; Y# b4 M) M# @5 Cgonadotropins.1,3
* G6 \) @) v& f% W+ VGonadotropin-independent peripheral preco-
; r" i3 R4 |7 m! o) dcious puberty in boys also results from inappropriate6 r+ [: T( ^" O
androgenic stimulation from either endogenous or
# k2 R# o+ {" k2 ]8 L# p3 h" R/ |exogenous sources, nonpituitary gonadotropin stim-
7 \8 y$ v" q  }6 Tulation, and rare activating mutations.3 Virilizing
3 |1 o* S- K! L3 s0 C7 c" ~- |congenital adrenal hyperplasia producing excessive5 U0 d/ l  B4 n% L( d, {; \0 I
adrenal androgens is a common cause of precocious" o; A4 G6 A6 a- i
puberty in boys.3,4  o1 Y. r  ]. r
The most common form of congenital adrenal  r8 S9 K  T1 z+ M) X/ `
hyperplasia is the 21-hydroxylase enzyme deficiency.% A. ~7 R2 X- b9 o, V: y
The 11-β hydroxylase deficiency may also result in
6 y7 r6 ^% M& [& z0 j- E1 Kexcessive adrenal androgen production, and rarely,# ^, a2 {- N- P
an adrenal tumor may also cause adrenal androgen) H# O! L8 w; O( B0 k; h" x
excess.1,3' i7 h+ F) `2 ?" F8 V# V8 j
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
) T# x) q5 |4 X7 x$ \+ E542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
. @5 P' f. `# ]: A* uA unique entity of male-limited gonadotropin-
! _& N3 i) m: l! j4 hindependent precocious puberty, which is also known7 d* c1 o3 `# s3 F8 U
as testotoxicosis, may cause precocious puberty at a
! L% _! ]9 _$ l/ |7 R# X( q3 _very young age. The physical findings in these boys
) h- r% D% @& Y3 ?with this disorder are full pubertal development,' h* O* o0 Z7 S& i. X2 m# z' W( Q
including bilateral testicular growth, similar to boys5 Q. n9 L1 h2 a/ f
with CPP. The gonadotropin levels in this disorder6 E: m! y3 C1 t2 J  A' ?4 }3 |
are suppressed to prepubertal levels and do not show
7 x9 O( `& Z2 z" |5 ^* U4 v0 ypubertal response of gonadotropin after gonadotropin-
  c  R/ `  j& Creleasing hormone stimulation. This is a sex-linked
% l9 b! z& Q7 u. pautosomal dominant disorder that affects only, M% L7 j- }& H. W( M) a
males; therefore, other male members of the family
! y4 [5 g. D8 p8 T! A  zmay have similar precocious puberty.3
' [1 Q- t( z8 bIn our patient, physical examination was incon-
1 y" x4 R1 t8 psistent with true precocious puberty since his testi-, j1 w5 E% W6 [
cles were prepubertal in size. However, testotoxicosis' E. k8 O/ p& w4 h) n
was in the differential diagnosis because his father
7 X* U( q, Z7 V' k5 x0 Ostarted puberty somewhat early, and occasionally,/ f$ i% X0 U2 y6 A( Q
testicular enlargement is not that evident in the$ P+ s$ W! l) W6 E
beginning of this process.1 In the absence of a neg-$ n0 p3 I, I) ~6 O
ative initial history of androgen exposure, our
; Y4 j* P/ x& R: u$ H- Bbiggest concern was virilizing adrenal hyperplasia,2 Z5 p) u. A7 f
either 21-hydroxylase deficiency or 11-β hydroxylase1 j& }6 v  k3 s8 }, \4 x. v
deficiency. Those diagnoses were excluded by find-) J: N/ H" g5 O' B
ing the normal level of adrenal steroids.. W+ Y# r) k) k9 m9 g
The diagnosis of exogenous androgens was strongly
9 u1 E! q- L' U  L* I( W; }suspected in a follow-up visit after 4 months because1 k, k" y2 ?+ q) y3 r
the physical examination revealed the complete disap-2 t+ @9 C4 ^: _" R) d0 Y2 k4 R3 _
pearance of pubic hair, normal growth velocity, and
" B  I8 C, e) y  s8 l9 c  hdecreased erections. The father admitted using a testos-
. F7 r* d5 \& c1 e. t1 ~  I/ O/ ]; bterone gel, which he concealed at first visit. He was
2 p2 {; |/ `: a( m# musing it rather frequently, twice a day. The Physicians’1 `% h2 U  W$ ?
Desk Reference, or package insert of this product, gel or
5 H, f7 ]4 B4 _2 y" @& I$ ]cream, cautions about dermal testosterone transfer to) F9 O- Z+ n/ D3 n
unprotected females through direct skin exposure.
4 M% Z; q  k1 V1 z+ oSerum testosterone level was found to be 2 times the
" L" z% f: T5 n& N# Vbaseline value in those females who were exposed to. H4 }9 }: c  E: h
even 15 minutes of direct skin contact with their male
; D, b- N# e4 j8 xpartners.6 However, when a shirt covered the applica-: B8 M& g' h+ H: Z
tion site, this testosterone transfer was prevented.6 ^* a, H9 |3 d5 `* e( G8 O' Z$ s. [
Our patient’s testosterone level was 60 ng/mL,
2 G$ U6 N/ y# c5 N8 x6 z0 Hwhich was clearly high. Some studies suggest that
% X! k6 c+ M1 z- j& ndermal conversion of testosterone to dihydrotestos-$ W( v; M0 F! f6 P. |; h
terone, which is a more potent metabolite, is more7 U7 m/ y, r$ Y. Y7 J! G4 o
active in young children exposed to testosterone+ k: F4 _! E6 d) G0 x' f" G6 i
exogenously7; however, we did not measure a dihy-
: p  W  W2 j6 O8 M3 d; Kdrotestosterone level in our patient. In addition to- R9 \# s. c! p
virilization, exposure to exogenous testosterone in! H8 V# d. l' f9 K% q: z7 [! \. b
children results in an increase in growth velocity and) X& @+ Y$ a7 m: R
advanced bone age, as seen in our patient.
0 M6 w4 N+ `1 M" pThe long-term effect of androgen exposure during$ s( |' C1 _1 m- Z* I
early childhood on pubertal development and final, q9 Y9 |5 ^7 x
adult height are not fully known and always remain2 E/ B1 D  s$ Q: @1 U- H
a concern. Children treated with short-term testos-
+ R, y0 x# I7 D1 K' Z, A& f% Hterone injection or topical androgen may exhibit some; X; X5 g0 C2 g/ F1 e2 ~- d
acceleration of the skeletal maturation; however, after1 i1 N: W$ N8 K( k
cessation of treatment, the rate of bone maturation
) ^: G) R* K$ y1 ?9 n9 H9 V2 gdecelerates and gradually returns to normal.8,91 J- }' H4 A* c! j  P
There are conflicting reports and controversy
$ c! B: F8 G& l, h4 I' oover the effect of early androgen exposure on adult7 `' j" [' Y3 G" ~; e9 Y$ R
penile length.10,11 Some reports suggest subnormal
% |6 P) u5 \& q/ Badult penile length, apparently because of downreg-7 p% \: p$ B4 _7 ]# e
ulation of androgen receptor number.10,12 However,% m6 G  ]( K' o
Sutherland et al13 did not find a correlation between* w( ^7 O* p- P2 A9 G
childhood testosterone exposure and reduced adult! y# M: d3 ^2 f/ F
penile length in clinical studies.; g) s/ j. p/ A* B+ B
Nonetheless, we do not believe our patient is, m0 h% R" M( ~2 y& q! V" l, [
going to experience any of the untoward effects from$ I/ o! h; R* F1 N3 _7 @' [( J5 H9 b
testosterone exposure as mentioned earlier because+ j2 h! X/ \* W, h, f3 k
the exposure was not for a prolonged period of time.
* X  D1 D& b& b" lAlthough the bone age was advanced at the time of/ ^/ j, R' i" I
diagnosis, the child had a normal growth velocity at
4 _, ~  O  o9 j4 y0 \0 ?8 O2 hthe follow-up visit. It is hoped that his final adult* ]! p3 l/ p4 m  G9 F4 ^
height will not be affected.
% ^' x* o" P" R; m( bAlthough rarely reported, the widespread avail-
' ^  Z# `) d2 \  n8 h. @- Dability of androgen products in our society may& H* N; b0 A* S1 }6 q3 T
indeed cause more virilization in male or female- I6 n" y8 w  Y
children than one would realize. Exposure to andro-
% R8 J% m- d' I( m3 t6 ?+ _; Egen products must be considered and specific ques-+ J' ^; b, t1 }% C$ w
tioning about the use of a testosterone product or
2 I, |. G( P, ~7 K( R! b1 u3 Ngel should be asked of the family members during* }0 A) Y7 t% y5 F" n! x) h% J, i
the evaluation of any children who present with vir-
) K* j* f2 V2 D$ R1 f9 f% vilization or peripheral precocious puberty. The diag-
5 }, {# y, ?( X; H7 i5 ^nosis can be established by just a few tests and by2 Z3 j" G  U. Q, H1 m. l
appropriate history. The inability to obtain such a
5 q3 o+ Z8 O3 ]/ M+ y; R, N3 Whistory, or failure to ask the specific questions, may9 {4 V8 F9 L  B! v9 N$ D& A
result in extensive, unnecessary, and expensive
2 z9 V" h! H8 ]" L1 C3 d! \investigation. The primary care physician should be3 q, K! d7 p! Q4 X+ H# T3 I: R
aware of this fact, because most of these children
' q# s7 i" \0 g- V: `+ m2 Jmay initially present in their practice. The Physicians’& S+ g+ F4 f# S+ k, ]
Desk Reference and package insert should also put a
2 c& J( r+ l; _1 Q! }warning about the virilizing effect on a male or' L" i; [7 T9 k! A, Z4 O" A
female child who might come in contact with some-
3 \- s( p$ h, f$ M. I6 Fone using any of these products.
) W$ i" ~5 A  l8 pReferences
# k  k: E( \' _' W1. Styne DM. The testes: disorder of sexual differentiation' D: y2 P2 n" a) q
and puberty in the male. In: Sperling MA, ed. Pediatric3 O0 @  o" ?/ v) I: h+ U
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
  T; Y- P' C7 S% L; O! ~) u2002: 565-628.7 I  r! b/ z  a
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious: g- g* C" t& ]3 f; i9 N
puberty in children with tumours of the suprasellar pineal
發表於 2025-1-4 03:27:02 | 顯示全部樓層
VIP精品區,資源無限好賺金任務區,輕松賺金幣
加入VIP,享受高級特權宣傳賺金又升級,超級棒
Sexual Precocity in a 16-Month-Old/ k: A% u! F6 k' k, t, \& v* ^
Boy Induced by Indirect Topical
- e8 P3 z# U5 O2 ^1 t" K# AExposure to Testosterone; ^  T& r  t; l: T2 ?# B5 \
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,27 A$ R8 f0 r* ~% T; w2 P
and Kenneth R. Rettig, MD1
$ O* O5 _' B$ CClinical Pediatrics9 F2 y4 P+ R; k: O' L& R
Volume 46 Number 6
3 o5 z8 x$ [% o( B6 rJuly 2007 540-5433 }5 L5 O) Q) u4 `& q2 K) k: f& R
© 2007 Sage Publications
" _( `: a4 _; [$ e2 D6 \10.1177/0009922806296651
; b  k* J* l1 Q3 M7 \http://clp.sagepub.com& B* Z5 s1 C7 `4 a
hosted at" l. r% y- \: g9 h$ V
http://online.sagepub.com0 G( c) a) g3 r1 j
Precocious puberty in boys, central or peripheral,6 q5 {/ [! }4 ?, m' M& {' H# O* [
is a significant concern for physicians. Central
1 Z4 N7 d! P: @, t7 c6 mprecocious puberty (CPP), which is mediated9 r+ g8 u, C+ o8 Y4 Z" o$ `
through the hypothalamic pituitary gonadal axis, has+ \: X7 D; \$ @( L* G
a higher incidence of organic central nervous system
- w  h7 ]+ z2 Xlesions in boys.1,2 Virilization in boys, as manifested
1 @& y  @- S! Y5 a; l. Zby enlargement of the penis, development of pubic8 H7 L7 ]! b! g6 n( z$ e; _" x
hair, and facial acne without enlargement of testi-
+ H& x: {- H  h4 c: L9 S+ p# T2 Rcles, suggests peripheral or pseudopuberty.1-3 We
$ T3 H) _  I- s7 |. p  kreport a 16-month-old boy who presented with the# k5 u8 l4 g0 R; A0 L" K" O- F4 a% C" A
enlargement of the phallus and pubic hair develop-
0 {/ D! M4 o+ R9 f* rment without testicular enlargement, which was due% G/ h% A9 B+ O7 x7 K8 Y
to the unintentional exposure to androgen gel used by
% V4 o* x) \% `" W$ ythe father. The family initially concealed this infor-
1 [2 V4 X' f! m5 X9 Y! k" E, xmation, resulting in an extensive work-up for this
9 }+ z! m$ ?& B. [* vchild. Given the widespread and easy availability of
* L3 ?8 w1 V- j& ftestosterone gel and cream, we believe this is proba-9 i  q: J' o$ u8 z/ W( {
bly more common than the rare case report in the' g; _4 E: K. g3 [+ a0 q* P6 N
literature.4. p: X8 |" E, k, X' ?
Patient Report
) a2 l( Q4 X9 q" t. {; F+ {A 16-month-old white child was referred to the- b9 ?, X1 F6 F+ V3 d
endocrine clinic by his pediatrician with the concern
6 e3 R( b' u' d$ D& |$ Yof early sexual development. His mother noticed
; R- G1 x% E5 a  b& ylight colored pubic hair development when he was9 d6 d9 i% I7 k8 a) G
From the 1Division of Pediatric Endocrinology, 2University of7 Z3 @2 y) {+ q1 M+ e
South Alabama Medical Center, Mobile, Alabama.2 e2 c( h% u4 X% W& i/ C. S( T3 u
Address correspondence to: Samar K. Bhowmick, MD, FACE,
7 j5 i% f) ]  q/ h) gProfessor of Pediatrics, University of South Alabama, College of
2 ?' h3 }  `" Q, u0 Y  X7 ~# s( }Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;! m" k/ P; ]. h2 D  ^, ~% R
e-mail: [email protected].$ Y; Q" ?+ Z+ t4 u+ L
about 6 to 7 months old, which progressively became
, g, s4 I6 \# a3 U" |darker. She was also concerned about the enlarge-
$ t* D: x8 J' O" q7 [% Ament of his penis and frequent erections. The child- ~( n7 [) H6 U6 t/ Q  }# k' G+ r
was the product of a full-term normal delivery, with/ S0 h& ?% i. M0 \5 _
a birth weight of 7 lb 14 oz, and birth length of! I7 H; c! o1 X* ]
20 inches. He was breast-fed throughout the first year
; E2 f9 F) O# rof life and was still receiving breast milk along with
7 w8 N/ Q7 U$ ssolid food. He had no hospitalizations or surgery," C8 Z1 j' M" N
and his psychosocial and psychomotor development
  o" D( H, o; Uwas age appropriate.
( Z& n( |4 _' \. r" x4 [. wThe family history was remarkable for the father,
7 D. _( c: f; d: f- _4 b  _: jwho was diagnosed with hypothyroidism at age 16,' Y/ _- V0 C. U6 k' m0 ?' d6 r
which was treated with thyroxine. The father’s, k2 r- h9 o4 D/ o
height was 6 feet, and he went through a somewhat
: ]% `5 U' T5 Qearly puberty and had stopped growing by age 14.
3 L' K: U( Q0 B) O" N& i1 Q- BThe father denied taking any other medication. The" j- O- l, \! t9 L! E' ^& t( N
child’s mother was in good health. Her menarche9 H' U4 q+ q6 L# g' z0 j
was at 11 years of age, and her height was at 5 feet
- |# E0 B( }6 u# X8 b5 inches. There was no other family history of pre-
  U# _$ q* _1 acocious sexual development in the first-degree rela-
8 w# Y9 j1 O( C) _% M, m7 ltives. There were no siblings.
& X: @. H- U3 i) L3 V! GPhysical Examination
' @! ?* j. v& K: fThe physical examination revealed a very active,) @( L' y% M" W8 O5 Y) E+ G
playful, and healthy boy. The vital signs documented
8 {3 z+ v8 ], T: f. J  oa blood pressure of 85/50 mm Hg, his length was+ k9 ~; l5 s5 D; Z/ l, h2 d. U4 X! w8 M
90 cm (>97th percentile), and his weight was 14.4 kg
4 H$ F' Q) V1 _  T& y0 [3 @- z(also >97th percentile). The observed yearly growth" t5 z5 V. v  j# j2 K6 W. [
velocity was 30 cm (12 inches). The examination of
+ h: B, X' S# @7 ]+ P7 T4 qthe neck revealed no thyroid enlargement./ n9 h* x+ |$ i* n- W: W
The genitourinary examination was remarkable for
9 A$ J* v8 P9 P3 ~; O6 nenlargement of the penis, with a stretched length of. c! g: j* D2 i4 ]5 W0 A$ a
8 cm and a width of 2 cm. The glans penis was very well3 x  w% a1 m# p  w- P" M
developed. The pubic hair was Tanner II, mostly around& K4 a7 U3 j/ ^
540
2 n# q- v6 Y5 `6 d: r% {4 ]& ?6 bat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
: D( G; p4 T5 K( Q8 \9 C+ jthe base of the phallus and was dark and curled. The
; Z- ~1 |% N% U4 E+ Atesticular volume was prepubertal at 2 mL each.
' p+ z& ~- u5 V- d% \" [The skin was moist and smooth and somewhat6 w. X* \6 d, }# B+ _
oily. No axillary hair was noted. There were no
: a$ C  f" {( u  k$ g1 n- mabnormal skin pigmentations or café-au-lait spots.. G9 B5 F$ w* h9 A& }
Neurologic evaluation showed deep tendon reflex 2+% q+ k% A. j* i7 C: y% F  Q
bilateral and symmetrical. There was no suggestion
; y0 ~) G* ^1 [of papilledema.
' M/ l# c( i4 i% g( w2 p: m4 |Laboratory Evaluation/ R( k1 `. H1 P4 u+ a
The bone age was consistent with 28 months by9 B  n6 p+ e- y1 I; ^
using the standard of Greulich and Pyle at a chrono-1 r8 _/ ?$ L* M% k, o
logic age of 16 months (advanced).5 Chromosomal
6 R8 H* l7 @5 P4 {* Y7 `karyotype was 46XY. The thyroid function test
  Y, h/ V5 _7 x8 o  e! Hshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
) m) x! |5 Q5 X; A7 W; Q: w0 T# C4 olating hormone level was 1.3 µIU/mL (both normal).
: q: N2 l% Q  ^: ]The concentrations of serum electrolytes, blood
- g* ?  `+ a, J# Yurea nitrogen, creatinine, and calcium all were
5 i/ T- [3 }, b& {within normal range for his age. The concentration
6 K0 P, Q. `- ~$ H' t* N5 wof serum 17-hydroxyprogesterone was 16 ng/dL& ^  E% J. z6 d3 @! J" p6 [
(normal, 3 to 90 ng/dL), androstenedione was 20
6 d1 ^, ~, A( d5 K/ ^ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-9 Y& c$ c% r! Y( L: i
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
5 X- J& |3 _& o. Q, J; o  sdesoxycorticosterone was 4.3 ng/dL (normal, 7 to; D3 K, Z4 Y4 I# y3 w
49ng/dL), 11-desoxycortisol (specific compound S)! u4 P/ {: \6 P- x
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-6 U1 H/ B% h3 ^! F' X8 _
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
3 a1 }" C) i7 ~7 |! {, w# d8 ^testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
* L# z1 w( B& w/ d2 ?and β-human chorionic gonadotropin was less than
+ K" q- r) t; y/ {+ C5 j  V5 mIU/mL (normal <5 mIU/mL). Serum follicular
8 o6 m) O2 n3 Q; L8 |3 ustimulating hormone and leuteinizing hormone) c+ K8 z7 Q2 ~- L. P1 c
concentrations were less than 0.05 mIU/mL
8 S6 s) S1 o& x0 I0 J(prepubertal).: p% D$ X/ x+ n; d# I+ g7 w
The parents were notified about the laboratory  d# ~6 d9 U' F$ \* w. T+ c
results and were informed that all of the tests were
6 s( R! a+ b, Anormal except the testosterone level was high. The
# s, a4 `' l) N8 ~4 Afollow-up visit was arranged within a few weeks to
4 U1 Z  f- X) qobtain testicular and abdominal sonograms; how-9 V8 L# h" v0 R7 R" V( @1 c
ever, the family did not return for 4 months.( Q9 x& I* O& O' j+ x
Physical examination at this time revealed that the5 t" @2 j; w2 d
child had grown 2.5 cm in 4 months and had gained% v, j+ ?" N& j- t/ h/ D
2 kg of weight. Physical examination remained
9 }: M, d; n# u! t/ cunchanged. Surprisingly, the pubic hair almost com-0 r: m$ D" V& e6 j' Q1 l3 v
pletely disappeared except for a few vellous hairs at
. g$ m0 j8 P8 w; C; W, J. U& c* Ethe base of the phallus. Testicular volume was still 29 S+ |1 N3 K, ^' i& z
mL, and the size of the penis remained unchanged.4 W4 n( S+ z7 h- ?$ _3 v/ J% d
The mother also said that the boy was no longer hav-
, t: @0 l& f# ?6 g9 l% p- ding frequent erections.' y. m0 J& C- k1 j/ O
Both parents were again questioned about use of
2 [8 K2 T) N; Y9 d' r4 F6 E2 tany ointment/creams that they may have applied to
% O5 X; H, b( `: z2 Z- v- cthe child’s skin. This time the father admitted the
, x/ s5 O- M& J% s: hTopical Testosterone Exposure / Bhowmick et al 541, e9 r  R4 z+ G+ O+ h
use of testosterone gel twice daily that he was apply-6 [  @3 u8 m" S! f1 a
ing over his own shoulders, chest, and back area for  o$ k' J7 O* ]% {% _  A8 W
a year. The father also revealed he was embarrassed
+ d+ Z5 t; B& T3 a: L! E2 Vto disclose that he was using a testosterone gel pre-- O# j. K7 e8 Y. c
scribed by his family physician for decreased libido- Z  L$ h9 j  w: s0 y: d- S
secondary to depression.) U/ F4 n0 _0 ]' k% P5 N
The child slept in the same bed with parents./ c  p0 E4 h. |- W$ Z
The father would hug the baby and hold him on his
% B" w: k$ G- U# r/ @( ?9 ychest for a considerable period of time, causing sig-
9 \2 `# V1 ^6 Y; }  I: Q  vnificant bare skin contact between baby and father.  b5 J& @' B% q4 v' W: d  h
The father also admitted that after the phone call,
% _9 n! l( Q, i2 d1 d& owhen he learned the testosterone level in the baby9 E) d9 W; ~+ `( L) s- p8 j7 G: @* r8 h
was high, he then read the product information; N* V+ U6 H$ t9 ~4 [$ j
packet and concluded that it was most likely the rea-
) B; I/ i) M) M4 _son for the child’s virilization. At that time, they
7 q% i, X0 M& p- e+ c' Wdecided to put the baby in a separate bed, and the/ e/ j. t+ D, F2 v- w
father was not hugging him with bare skin and had
. R8 e# w1 m4 gbeen using protective clothing. A repeat testosterone
+ g* u( _# K# y% B2 e0 _test was ordered, but the family did not go to the. _. f! c" P. T
laboratory to obtain the test.3 x2 C& c7 ^6 R( A' o# X$ _
Discussion  q# W! ]+ s- G  B/ O& E+ b* K
Precocious puberty in boys is defined as secondary
$ M. n4 f, Y& Xsexual development before 9 years of age.1,4
. }6 O  Q  q; O/ }* U7 B- C( s8 {+ QPrecocious puberty is termed as central (true) when3 \0 L0 J8 \, X' ~  X- e
it is caused by the premature activation of hypo-" I, U* W5 P2 L9 q% i
thalamic pituitary gonadal axis. CPP is more com-; T; d- q3 s: i. _2 W
mon in girls than in boys.1,3 Most boys with CPP
8 m3 e$ \, e. l2 Y6 _! _" H& f( Mmay have a central nervous system lesion that is
6 J8 s3 E+ L6 cresponsible for the early activation of the hypothal-1 q5 R* ^, g/ y, k
amic pituitary gonadal axis.1-3 Thus, greater empha-' o( H/ a$ a. A- @' ?
sis has been given to neuroradiologic imaging in# w& ^9 Q6 V- ~
boys with precocious puberty. In addition to viril-8 {- x2 L3 S, m5 q/ ]; m2 J
ization, the clinical hallmark of CPP is the symmet-' `8 Q: J8 l  I1 t6 W: L! _/ B
rical testicular growth secondary to stimulation by& w" m  P$ \. \
gonadotropins.1,3
, O' I& B- d+ q0 fGonadotropin-independent peripheral preco-
  S; X  Q% e- h; C) C3 K4 xcious puberty in boys also results from inappropriate
5 b: e% d) e6 R: R8 j+ oandrogenic stimulation from either endogenous or' U* `  t1 s+ [+ H* f
exogenous sources, nonpituitary gonadotropin stim-8 Y* B# @0 i* Z5 o
ulation, and rare activating mutations.3 Virilizing
7 u0 \  V4 ^9 w6 Fcongenital adrenal hyperplasia producing excessive" G2 o; T$ O1 A, s& K
adrenal androgens is a common cause of precocious7 T! ]9 O2 P5 @# @
puberty in boys.3,4* I" _, z$ ]# z# g; m- I5 ?3 h
The most common form of congenital adrenal
9 M) B+ s- x( W$ K2 ~hyperplasia is the 21-hydroxylase enzyme deficiency., D; w( f( j5 J$ b3 |* O$ U
The 11-β hydroxylase deficiency may also result in
: W+ D+ u9 z" ?7 U5 g. Zexcessive adrenal androgen production, and rarely,8 V" y7 Y* t- N* |9 Q7 S
an adrenal tumor may also cause adrenal androgen
- W% ^- p* ~8 S' p: v+ Rexcess.1,3* R# {$ U/ g1 \
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from6 l' V& ]* C+ z. e( x+ g6 M
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007! ^5 x" q. R7 _5 [
A unique entity of male-limited gonadotropin-7 G  A/ H$ ]; N% Y$ I6 l& t0 v! K
independent precocious puberty, which is also known
" p+ h: i9 M& ias testotoxicosis, may cause precocious puberty at a% G) H! P7 B2 t+ p$ Q
very young age. The physical findings in these boys# o9 R1 \: x; Z# j  K4 @5 v+ z9 R
with this disorder are full pubertal development,) U+ O4 [& f1 n" d
including bilateral testicular growth, similar to boys
. d  N4 Y) }5 i, n9 `with CPP. The gonadotropin levels in this disorder
: k5 {& A9 x( u" X% care suppressed to prepubertal levels and do not show3 O1 `) {. z: x; A
pubertal response of gonadotropin after gonadotropin-5 Z% j1 t6 h, }) V# y
releasing hormone stimulation. This is a sex-linked
6 Z- W) G# @9 n4 L7 b6 _# |autosomal dominant disorder that affects only& [4 U7 F: [! ^( U, s! L
males; therefore, other male members of the family/ V: t- x6 d0 p9 N; ]
may have similar precocious puberty.36 n. _& b5 F8 x  `
In our patient, physical examination was incon-
" d# b* b1 X; \; lsistent with true precocious puberty since his testi-
+ X/ E# h+ B& f1 M7 {cles were prepubertal in size. However, testotoxicosis
$ e# r. J4 \$ ~' Lwas in the differential diagnosis because his father
4 Y7 n9 b9 L; i. @5 vstarted puberty somewhat early, and occasionally,
$ e1 F6 b% W% e- Utesticular enlargement is not that evident in the
" D$ m  {8 \* T- s( F) @2 r+ ?$ I! Ibeginning of this process.1 In the absence of a neg-
' u' z& o( }, }& r1 ^6 pative initial history of androgen exposure, our
# l/ s, e& K6 Sbiggest concern was virilizing adrenal hyperplasia,
; q( g8 ^% ^5 A. z- \either 21-hydroxylase deficiency or 11-β hydroxylase" }1 ^: w' ?3 O7 t7 o+ m5 y
deficiency. Those diagnoses were excluded by find-
+ r0 }- n1 v  jing the normal level of adrenal steroids.+ d2 i: q. @8 v! g+ L+ h2 Q1 W
The diagnosis of exogenous androgens was strongly
9 W8 D5 {4 C7 R+ y( G( S% Y' {2 fsuspected in a follow-up visit after 4 months because
# B/ ?$ k9 O% w0 lthe physical examination revealed the complete disap-5 i% x2 |6 A8 _6 r9 m' l6 A0 e* [# ]# A
pearance of pubic hair, normal growth velocity, and9 o; G( {1 P; O7 q4 k8 z
decreased erections. The father admitted using a testos-- s1 j) G" |' U
terone gel, which he concealed at first visit. He was4 G. X+ ]7 i( `
using it rather frequently, twice a day. The Physicians’  C; P: {7 N3 l" I9 K8 P
Desk Reference, or package insert of this product, gel or5 x! Y5 T: [5 y' ]+ u8 r+ k$ M! M
cream, cautions about dermal testosterone transfer to; k- k; x$ S, Y( Q" z& g0 r
unprotected females through direct skin exposure.  ~0 S' [5 W4 h* S  S
Serum testosterone level was found to be 2 times the
# O# ^! d% b6 g+ L! Ubaseline value in those females who were exposed to
& [$ R: i  }6 a4 p, l( Veven 15 minutes of direct skin contact with their male/ l" E9 x6 L* @4 b1 D9 L7 }
partners.6 However, when a shirt covered the applica-
$ {( W- }) X! B% ction site, this testosterone transfer was prevented.
" K! j# P# e: G- r1 g1 M0 gOur patient’s testosterone level was 60 ng/mL,
% t: @+ n/ @; m+ N& }5 [7 uwhich was clearly high. Some studies suggest that
2 t- g+ ~. H% @5 Z, ]1 n- Ldermal conversion of testosterone to dihydrotestos-: O0 O2 t7 u+ i+ H
terone, which is a more potent metabolite, is more
- R0 ]. }3 S5 bactive in young children exposed to testosterone) s! B, y* l6 z- i- W& x) @8 G# Z
exogenously7; however, we did not measure a dihy-, {1 p. v6 W  f# j  r2 L: c
drotestosterone level in our patient. In addition to0 n: ]5 N/ l5 R
virilization, exposure to exogenous testosterone in; c) ?6 |6 ~9 M2 k2 W
children results in an increase in growth velocity and9 {0 |$ q4 z+ H  k
advanced bone age, as seen in our patient.
/ n9 V6 E8 X7 @; e5 |The long-term effect of androgen exposure during9 e6 u0 U1 P' `8 k3 V) L! r+ m
early childhood on pubertal development and final( Y* r2 S0 I) G& U3 S5 p) f4 j: t
adult height are not fully known and always remain1 W) [6 x% c" j- `( ~
a concern. Children treated with short-term testos-$ z6 h3 ?" M; P/ I/ z( F
terone injection or topical androgen may exhibit some
8 b# f( D9 v+ ?) B7 Gacceleration of the skeletal maturation; however, after
  i0 Y; r4 Y/ ~2 F* N! b. xcessation of treatment, the rate of bone maturation3 W- P! z" q; t' a4 H
decelerates and gradually returns to normal.8,9
% _5 V- B! k. t) Y5 Y$ w1 E7 O7 oThere are conflicting reports and controversy, k- M, }! o5 V9 N% M5 f8 ?
over the effect of early androgen exposure on adult: X8 g) O+ k1 X( N6 J
penile length.10,11 Some reports suggest subnormal0 J- g; A' P* B: l0 {
adult penile length, apparently because of downreg-9 s9 ~2 g0 }) c! f3 ]
ulation of androgen receptor number.10,12 However,
" f5 e" z* j. eSutherland et al13 did not find a correlation between/ o* q) y' G1 _0 b0 l2 S  {2 F( L" C
childhood testosterone exposure and reduced adult
7 c# }/ C# ^9 _) s& a& \penile length in clinical studies.
4 A% ?1 y* k: s/ }- \! `( _* ]Nonetheless, we do not believe our patient is* Q  G+ [, O: A, e: d/ s+ w
going to experience any of the untoward effects from" |! C; i0 R/ G% Q. Y8 T" y0 {
testosterone exposure as mentioned earlier because6 A. \% N- Q! Q, q2 K1 E
the exposure was not for a prolonged period of time.3 M' |$ c! N$ M
Although the bone age was advanced at the time of
6 Z8 i! G! V, M6 W$ ediagnosis, the child had a normal growth velocity at
# R6 V2 p/ c% x1 ~, l: |" \+ l! P* athe follow-up visit. It is hoped that his final adult
* O  N0 G; S* aheight will not be affected.9 H/ j) K" L+ j
Although rarely reported, the widespread avail-
7 y9 v  Y( n. Z; k  K6 b* ]ability of androgen products in our society may0 |$ y& e1 X2 T+ \
indeed cause more virilization in male or female  s8 U3 A# H$ N
children than one would realize. Exposure to andro-
9 _. N. W# a2 \$ v' N0 egen products must be considered and specific ques-
: _. ?! Q& T3 vtioning about the use of a testosterone product or
# k* \$ ~) T. c! Sgel should be asked of the family members during
' f, z$ q/ Z6 V- _) ethe evaluation of any children who present with vir-& N/ _7 E6 M( v) o, m  q. [
ilization or peripheral precocious puberty. The diag-
  h) t9 B+ Y. W. F5 Inosis can be established by just a few tests and by5 d+ e+ I( }% }) C# t! v% V
appropriate history. The inability to obtain such a* g+ @0 h, c4 {" Z
history, or failure to ask the specific questions, may
* L8 E  a! o) U' l4 K4 V2 J$ d& Gresult in extensive, unnecessary, and expensive: Q- D) N' o! m" Y6 G* q$ U
investigation. The primary care physician should be
; s2 f! m4 n' t: aaware of this fact, because most of these children5 d$ O* S( u8 _) Z( u
may initially present in their practice. The Physicians’
: K. A0 q1 i5 y, w, [3 ADesk Reference and package insert should also put a  ]( G0 N- l" Z5 m( F+ _+ g
warning about the virilizing effect on a male or; x$ N0 {4 V; E: d0 C' G
female child who might come in contact with some-8 j: B5 |7 C. N% R2 w# F2 F
one using any of these products.
9 w' |3 i3 Z. ^2 a: r3 V( CReferences
3 \) P' S. Z  l- [1. Styne DM. The testes: disorder of sexual differentiation" x9 s& u9 t/ x) n8 [
and puberty in the male. In: Sperling MA, ed. Pediatric3 Q& O5 e) ~4 I( X
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
9 X; L" A* `( G7 e+ A. m# d0 _  ]2002: 565-628.  G) h/ q1 P- E9 y+ y# [
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
. L: r, F% a- u( Z, g+ mpuberty in children with tumours of the suprasellar pineal
發表於 2025-1-7 21:59:43 | 顯示全部樓層
這個我收藏了!謝謝分享!WK的資源越來越豐富,這少不了大大的辛勞!
發表於 2025-1-10 10:43:39 | 顯示全部樓層
VIP精品區,資源無限好賺金任務區,輕松賺金幣
加入VIP,享受高級特權宣傳賺金又升級,超級棒
感謝大大的辛勞分享!我會繼續在WK關注大大的文章!
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
VIP精品區,資源無限好賺金任務區,輕松賺金幣
加入VIP,享受高級特權宣傳賺金又升級,超級棒
4个什么样的?
發表於 2025-1-19 02:41:05 | 顯示全部樓層

1 {3 M* n0 `" p1 d2 D精妙絕倫的精品,感謝啊!期待你更多更好的創作哦!
發表於 2025-3-8 22:04:50 | 顯示全部樓層
絕對的好貼!謝謝啊!逐字逐圖地看完這個帖子以後,我的心久久不能平靜,感恩啊!
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