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Sexual Precocity in a 16-Month-Old  P7 A8 P3 p, d$ l+ ^
Boy Induced by Indirect Topical
4 L: V5 k  Y1 MExposure to Testosterone
+ h0 Q" o- D9 j9 p. DSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
1 L( S8 w$ I) \! D- J/ W0 dand Kenneth R. Rettig, MD1
5 H. S. f, n7 ]  C+ oClinical Pediatrics
. H* y* X2 z9 x0 o1 a) ZVolume 46 Number 6' c, [1 v' o# n! d, A- B
July 2007 540-543
9 N  v. b4 r& T& C5 Z: D$ J  L© 2007 Sage Publications2 R$ G7 `6 P1 |! e2 \8 [
10.1177/0009922806296651
1 s9 v; ?+ F! _  rhttp://clp.sagepub.com
' R! a3 x) e8 X" m; x6 m- Khosted at
. ^, Q2 o' x' \9 Whttp://online.sagepub.com7 N" l& b$ T0 X7 a- s
Precocious puberty in boys, central or peripheral,
3 D$ o# U( Q9 h8 t* Xis a significant concern for physicians. Central7 a& q( W2 I- J% n
precocious puberty (CPP), which is mediated
1 _/ |+ H9 E9 U; ^0 \through the hypothalamic pituitary gonadal axis, has
9 h# f- S  l. D8 O' x" ^+ Na higher incidence of organic central nervous system3 N; z# j4 N! Z
lesions in boys.1,2 Virilization in boys, as manifested/ F: t# `0 x) n( {
by enlargement of the penis, development of pubic
: j+ z$ }( j8 M+ i( E0 I% |hair, and facial acne without enlargement of testi-
7 O; Q. ]$ h& X) M2 scles, suggests peripheral or pseudopuberty.1-3 We
) l  p4 P* Z8 Zreport a 16-month-old boy who presented with the
( V% i" Q0 y1 U8 @( genlargement of the phallus and pubic hair develop-/ z3 ]1 ~7 T- U! C# n
ment without testicular enlargement, which was due
% Q3 _6 o2 W: ]' u0 P9 Eto the unintentional exposure to androgen gel used by
8 s5 B: C4 B, u% |9 Athe father. The family initially concealed this infor-* n7 t, h7 O4 L. @1 t
mation, resulting in an extensive work-up for this; W1 S1 N) K1 K0 y$ c. a8 }% L
child. Given the widespread and easy availability of
# B6 f" ?' s* t( Y- vtestosterone gel and cream, we believe this is proba-
+ `) J5 q0 s& ?, nbly more common than the rare case report in the' J' R+ S- B0 u, O% d/ m
literature.4
& C% ?; {* e/ D# m7 KPatient Report9 F& ]: @) p& K3 r0 o# i7 |2 }
A 16-month-old white child was referred to the
  @' m4 L; V) I7 ]! Cendocrine clinic by his pediatrician with the concern
! h" l/ m2 f6 b  w1 Eof early sexual development. His mother noticed+ ]. J) X7 j8 L( D; O5 {( q3 S' \
light colored pubic hair development when he was+ u) c8 v' f* w3 W8 @
From the 1Division of Pediatric Endocrinology, 2University of
7 o; n* _8 l; B# M$ ~/ v, U- NSouth Alabama Medical Center, Mobile, Alabama.& |% f# d9 x5 j, f. P9 \4 C  B! J
Address correspondence to: Samar K. Bhowmick, MD, FACE,
4 Q$ o7 H, s; h2 N* v$ pProfessor of Pediatrics, University of South Alabama, College of  t: w2 h  p; M- K
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;4 \* H2 a7 v8 c
e-mail: [email protected].& a5 G( O& S/ i- X
about 6 to 7 months old, which progressively became
. v5 q* e5 f: j% d9 u* h4 K/ kdarker. She was also concerned about the enlarge-8 P* |6 u+ L; f# f( M; X  Z
ment of his penis and frequent erections. The child) h" I& n& Z* ^
was the product of a full-term normal delivery, with* L: d% t" n" K# X( t- m8 E/ t
a birth weight of 7 lb 14 oz, and birth length of
3 y: i' H* \6 Z. d& t; @  ^20 inches. He was breast-fed throughout the first year: D9 y/ z: D$ ?8 m  _
of life and was still receiving breast milk along with
0 q! ?; b" F8 r; wsolid food. He had no hospitalizations or surgery,% ~% r' U& V' k$ i
and his psychosocial and psychomotor development
1 R- w3 Q# i5 T/ M$ b) Swas age appropriate.
2 g9 M2 m0 j" A# I& _9 ZThe family history was remarkable for the father,4 ]/ F) A7 n8 C( T  N: L
who was diagnosed with hypothyroidism at age 16,
* o  `! s8 j5 ~! nwhich was treated with thyroxine. The father’s  a. g* y+ i" ]4 n2 o9 S
height was 6 feet, and he went through a somewhat& ]- f* X3 r! o; T2 {! t' }& i) u
early puberty and had stopped growing by age 14.
* N/ D1 ~0 g' LThe father denied taking any other medication. The! E5 q' L# y* W. e3 q
child’s mother was in good health. Her menarche
5 r5 X9 m5 B! O& e: M2 Ewas at 11 years of age, and her height was at 5 feet* X, R* g8 h' F4 t
5 inches. There was no other family history of pre-
2 h# c, e: }: N4 `9 r7 }& R6 Fcocious sexual development in the first-degree rela-
# y! W0 ^' U1 Ttives. There were no siblings.$ d2 I" j' e4 _! v8 z
Physical Examination
4 a; x+ T, t7 S  H. AThe physical examination revealed a very active,
7 V1 l8 a% L9 wplayful, and healthy boy. The vital signs documented) W2 g+ G% ^+ G9 \$ ^- h
a blood pressure of 85/50 mm Hg, his length was# n3 w4 f% R, }
90 cm (>97th percentile), and his weight was 14.4 kg, m' r' J. w. B) _- r
(also >97th percentile). The observed yearly growth
  V: V3 e, s  ~$ g( G* k1 qvelocity was 30 cm (12 inches). The examination of/ a& l0 I2 l0 x  h) B4 z
the neck revealed no thyroid enlargement.: r" y& ?6 j: D' k; |- i9 g
The genitourinary examination was remarkable for
  v. |; z- Z6 U+ h. q- Denlargement of the penis, with a stretched length of
, f5 ^# y4 B+ G$ x+ }% R8 cm and a width of 2 cm. The glans penis was very well( ^$ o2 N0 s8 g- l
developed. The pubic hair was Tanner II, mostly around# ?/ ?2 P: U( a8 x" x8 T% Q6 d
5409 b! @0 k3 q  D: j( \
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from2 M& W$ m  m5 r. Z
the base of the phallus and was dark and curled. The
) ]0 t1 [6 x- |$ h8 C, Etesticular volume was prepubertal at 2 mL each.$ ~: l' _* R2 T; ?  I9 b) @
The skin was moist and smooth and somewhat
2 V* P$ }' J9 noily. No axillary hair was noted. There were no& m5 c& m: V1 i/ U. D% x
abnormal skin pigmentations or café-au-lait spots.' s( [& Z& l. p. @
Neurologic evaluation showed deep tendon reflex 2+
8 u$ w$ b3 {# Y& K- b! e8 ^bilateral and symmetrical. There was no suggestion
& r0 @) Y6 A. O5 N0 N! Dof papilledema.  C7 \; s6 Z& u( T( I
Laboratory Evaluation
& E5 ?  V" ^' O7 F2 _The bone age was consistent with 28 months by9 Z9 J" W. A# n& n% s0 j6 E% J
using the standard of Greulich and Pyle at a chrono-
# C/ B8 l4 C7 L* O. wlogic age of 16 months (advanced).5 Chromosomal
- v. V( }" J. k- w, z& zkaryotype was 46XY. The thyroid function test9 U7 Q: Q6 X. e) d3 P$ A# V9 t
showed a free T4 of 1.69 ng/dL, and thyroid stimu-1 z; o" ?; I) {( M
lating hormone level was 1.3 µIU/mL (both normal).
3 c2 K" _0 {6 _) P& aThe concentrations of serum electrolytes, blood, h4 [/ K) b6 G5 ]; c- x
urea nitrogen, creatinine, and calcium all were1 g& {! V6 j+ G& m8 H
within normal range for his age. The concentration5 Z6 e% T6 o7 f3 s) \
of serum 17-hydroxyprogesterone was 16 ng/dL
5 X* d8 {( d7 w2 o  c(normal, 3 to 90 ng/dL), androstenedione was 20
/ f( P6 P# s& e: m$ ~ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
+ l+ |4 j, B: c8 G: |9 pterone was 38 ng/dL (normal, 50 to 760 ng/dL),
% j6 R/ T/ @7 B, t' K9 x0 h% j( ^desoxycorticosterone was 4.3 ng/dL (normal, 7 to
3 o+ q, C% g8 ?$ w' O49ng/dL), 11-desoxycortisol (specific compound S)( ~9 i4 Q9 I# }; ^
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-( a& Y& {2 w+ Q; P; ?
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total) L7 ]9 u# T/ z0 o. |% y6 r
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
1 ?6 s$ q# ]) _" _$ @. a3 P4 sand β-human chorionic gonadotropin was less than, O9 G" W9 N( l% h) N& L7 a! j
5 mIU/mL (normal <5 mIU/mL). Serum follicular
5 ^% G5 ?3 D8 A; D4 `( [stimulating hormone and leuteinizing hormone! P8 ~" f9 s, z- i
concentrations were less than 0.05 mIU/mL
2 W4 B0 O) h5 N4 I* A9 E(prepubertal).9 G3 Z) o- U. l/ }
The parents were notified about the laboratory* H6 K6 e+ z6 |+ e
results and were informed that all of the tests were
- X: M$ o0 R3 G% Lnormal except the testosterone level was high. The
/ a; _# f, P6 N  b# z$ s  Dfollow-up visit was arranged within a few weeks to( u) D& J5 K& d; d7 Y8 u1 {
obtain testicular and abdominal sonograms; how-' C3 k9 b# ~2 C' {/ \) i
ever, the family did not return for 4 months.
, z$ U7 o$ Z( N: rPhysical examination at this time revealed that the
$ S  W: c5 v- X, u3 m5 Achild had grown 2.5 cm in 4 months and had gained
, R7 s* M3 \( Q2 kg of weight. Physical examination remained. w9 s! o' Q0 D
unchanged. Surprisingly, the pubic hair almost com-! m6 p3 v9 ?4 A; O0 n
pletely disappeared except for a few vellous hairs at. l# A+ Z; K* J
the base of the phallus. Testicular volume was still 2
* C1 A; @7 V9 }2 T( {& [- qmL, and the size of the penis remained unchanged.
! Q( s# V- P1 t0 b' Y% d( iThe mother also said that the boy was no longer hav-
: w, S& W9 P4 J# o8 {& ^- ^8 K. O0 Eing frequent erections.
3 z" n3 M5 {6 B2 |5 ~+ l: bBoth parents were again questioned about use of9 z3 L, F5 `0 Z6 N" F  b5 X
any ointment/creams that they may have applied to' O" V! ~1 F4 [  ?% l. ]
the child’s skin. This time the father admitted the5 e: l  @! _* `3 A- h1 l6 n
Topical Testosterone Exposure / Bhowmick et al 541
9 k. Q$ {1 D) _" Euse of testosterone gel twice daily that he was apply-
$ q- A8 J5 g3 o1 s6 N. eing over his own shoulders, chest, and back area for
7 ^) U2 q$ U6 a, b& e4 T/ t- Ja year. The father also revealed he was embarrassed
0 D3 l; z  T1 ^2 N1 g0 C  C% @. `1 X/ M4 Ato disclose that he was using a testosterone gel pre-
& ~% l; j' J* U$ o  @+ Uscribed by his family physician for decreased libido, D4 w$ ]% f: I4 x* M, {; |- G; ]
secondary to depression.( g/ b1 ?% P, |1 q4 {1 s
The child slept in the same bed with parents.; `) [7 V3 X, N
The father would hug the baby and hold him on his2 k0 [' ~& K3 }- O5 z" y
chest for a considerable period of time, causing sig-
5 q: D2 Z& F: ~4 `: b6 Lnificant bare skin contact between baby and father.0 N8 q- s5 f& J
The father also admitted that after the phone call," m: E" [7 A( f3 L9 V6 w  F! V
when he learned the testosterone level in the baby' t# h3 j/ P! a: C
was high, he then read the product information
# L$ k% ]) ]& L7 K( zpacket and concluded that it was most likely the rea-
) r& I& G  x& R* |# V. t- c7 A4 nson for the child’s virilization. At that time, they
3 z9 B- a/ a" t% w8 M7 q8 Jdecided to put the baby in a separate bed, and the) x# a4 e# c" ~* Z. u
father was not hugging him with bare skin and had0 z  \# ?" i5 P' w& v5 a
been using protective clothing. A repeat testosterone
6 u! G  t9 \/ ]+ Q% r- }: `# [test was ordered, but the family did not go to the
" b9 y( C6 m2 A" g$ A$ p% I* l* Glaboratory to obtain the test.
  P% d% L: s$ o' x8 ?! }Discussion
3 u7 B5 H5 D/ i; x$ zPrecocious puberty in boys is defined as secondary# Y8 e0 \: }7 e4 Y: a. N
sexual development before 9 years of age.1,4
) `; A% u+ U) P: W- F4 n. NPrecocious puberty is termed as central (true) when3 {* `5 {. _- ~7 K
it is caused by the premature activation of hypo-' p3 b0 l" |6 ]0 M
thalamic pituitary gonadal axis. CPP is more com-6 Z8 ?! F9 X6 w& f3 o
mon in girls than in boys.1,3 Most boys with CPP
. s9 h; v! ]; Bmay have a central nervous system lesion that is
8 y* c/ A) X$ h% H4 [responsible for the early activation of the hypothal-
8 n& z# z. {8 `6 X1 ~2 K6 Gamic pituitary gonadal axis.1-3 Thus, greater empha-
8 g" p+ |0 `! Y( e( qsis has been given to neuroradiologic imaging in+ ~' T8 w: k9 {
boys with precocious puberty. In addition to viril-
4 n; }/ v: Y* }! A  B5 r: l5 {ization, the clinical hallmark of CPP is the symmet-2 ^8 }' p$ o8 Y0 A' ~) X
rical testicular growth secondary to stimulation by5 H, r3 B8 u1 i
gonadotropins.1,3
) c5 ?7 D; b4 C% CGonadotropin-independent peripheral preco-
6 w% N8 X* |: I) ocious puberty in boys also results from inappropriate- `! t6 J$ t: j9 W: n6 ^" _4 X9 ^
androgenic stimulation from either endogenous or& t8 N% W# \  R) S* e+ s
exogenous sources, nonpituitary gonadotropin stim-
' n3 g4 V$ b! }. D  Culation, and rare activating mutations.3 Virilizing8 P; }/ N1 [  H, Q1 i7 o
congenital adrenal hyperplasia producing excessive
* l3 _# t. q  Wadrenal androgens is a common cause of precocious
3 O& y$ x; p6 {( Xpuberty in boys.3,4& D) k" c0 p* r! K, r% y" Q2 O
The most common form of congenital adrenal: |( L! B( V/ \: ^+ F/ j  s& X  |
hyperplasia is the 21-hydroxylase enzyme deficiency.
: q! A  w- u9 t/ iThe 11-β hydroxylase deficiency may also result in" T! I6 G$ V' F" L6 y4 u1 L
excessive adrenal androgen production, and rarely,
: n; {( j/ H0 T5 A( [an adrenal tumor may also cause adrenal androgen
4 o4 L6 I8 C3 e- G" jexcess.1,38 A  Q+ _5 w- K9 v' D
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from, c9 T& m% n+ x6 y. L* {
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
3 h' u3 x- Z$ E' ?# IA unique entity of male-limited gonadotropin-* Q0 ]1 i' i: F0 U0 x
independent precocious puberty, which is also known  G8 k) |+ R- D) }& ?" G8 ]
as testotoxicosis, may cause precocious puberty at a4 s$ C4 N& @8 E; c9 p0 }
very young age. The physical findings in these boys
% b* b1 H8 a. b+ i2 Hwith this disorder are full pubertal development,
6 @. D) X1 H+ V4 \4 D3 O% k* B0 Aincluding bilateral testicular growth, similar to boys% x9 c; N$ M' D- e  F1 g
with CPP. The gonadotropin levels in this disorder
! u6 m+ I4 ]4 Y0 i2 K9 {3 Eare suppressed to prepubertal levels and do not show
8 o! ^0 n2 ?7 tpubertal response of gonadotropin after gonadotropin-
5 u" i5 c9 u* P9 zreleasing hormone stimulation. This is a sex-linked
0 p. y! p+ T% H" f# k2 pautosomal dominant disorder that affects only
/ h! t% K3 M# J- nmales; therefore, other male members of the family. ^. d; u: a2 I
may have similar precocious puberty.3  j% v5 a6 l! I! c
In our patient, physical examination was incon-  B8 p, Y" Q" z
sistent with true precocious puberty since his testi-% O5 t3 `6 B8 s- r1 S
cles were prepubertal in size. However, testotoxicosis
( w  p" D) Y5 bwas in the differential diagnosis because his father
( M1 a; |( Y, `started puberty somewhat early, and occasionally,
* E7 ]# ?# l. F1 q0 N# g2 Ftesticular enlargement is not that evident in the
9 z5 D. x5 B& M" R  l+ {beginning of this process.1 In the absence of a neg-
" _* I: Q$ a  n8 A& a; U3 Z# |ative initial history of androgen exposure, our
4 Y: E# p5 p# W4 J7 R  w6 _biggest concern was virilizing adrenal hyperplasia," J% D! ]* C+ p( a1 l- N# j7 M4 w% W
either 21-hydroxylase deficiency or 11-β hydroxylase; k' P- x1 R( b* O/ O% `1 N
deficiency. Those diagnoses were excluded by find-
  A7 c& `$ S2 X$ M" j3 D$ o6 `ing the normal level of adrenal steroids.
* }4 {& q: ~7 r0 m' PThe diagnosis of exogenous androgens was strongly
2 K- x2 s: f/ Tsuspected in a follow-up visit after 4 months because
! a& e7 @# w' [) ithe physical examination revealed the complete disap-
. o2 x0 |; F# F6 v3 Upearance of pubic hair, normal growth velocity, and( F# ?0 w! M# L9 f; M* L% A) H
decreased erections. The father admitted using a testos-
/ Y4 K" O, {! V9 Tterone gel, which he concealed at first visit. He was) g) Z5 Q9 `" I! i5 c! C
using it rather frequently, twice a day. The Physicians’
5 c) y" f4 w) ~9 Y4 c* MDesk Reference, or package insert of this product, gel or
! y+ P# {+ x% D' @/ ucream, cautions about dermal testosterone transfer to6 X0 b) Y. b, L; ?- @5 w3 o
unprotected females through direct skin exposure.
. k& _& n! f' Y0 C2 K7 U" BSerum testosterone level was found to be 2 times the# S8 y1 ~% _# L! k/ A
baseline value in those females who were exposed to+ b$ _$ {, q  t
even 15 minutes of direct skin contact with their male
# e) T6 {3 E4 F4 _% Qpartners.6 However, when a shirt covered the applica-& ]6 M! w) X! s& ]
tion site, this testosterone transfer was prevented.
! Y7 g* J$ b7 u! P# x' IOur patient’s testosterone level was 60 ng/mL,
6 q. }9 E  E* B: I: |which was clearly high. Some studies suggest that3 o" I: a4 L3 [0 T+ r, m9 x' s
dermal conversion of testosterone to dihydrotestos-8 g+ l1 l7 O( P3 P- z
terone, which is a more potent metabolite, is more: O5 c& C, m: a! Y* W* m3 A
active in young children exposed to testosterone
/ {! O1 w+ U6 K1 |0 X! {8 X  y8 Gexogenously7; however, we did not measure a dihy-
+ w9 y( [6 P, @+ F) R% W1 @  ^: T* k% sdrotestosterone level in our patient. In addition to
8 r. |( O4 X3 m6 b/ z# h$ ?virilization, exposure to exogenous testosterone in
/ z& o0 `9 I' d: H. n' j0 I- o: rchildren results in an increase in growth velocity and
! q- B* @( R/ f( {* C( Eadvanced bone age, as seen in our patient.# |4 F* e0 M' m3 X2 \1 I6 F
The long-term effect of androgen exposure during
/ s+ N, s( p: I: t$ G2 m4 cearly childhood on pubertal development and final
0 h/ k0 D/ v0 J6 x+ Gadult height are not fully known and always remain
$ Z, e. @* n. G4 ^6 y! Ta concern. Children treated with short-term testos-
1 V/ Q8 j% S' [' j' C. ?1 k% Pterone injection or topical androgen may exhibit some
( v6 l4 E) }6 P$ U, ^. B# |: K0 |/ j! cacceleration of the skeletal maturation; however, after
+ j- U2 y7 ?* P9 Ycessation of treatment, the rate of bone maturation9 [; Q8 r7 Z  j' W6 P8 b
decelerates and gradually returns to normal.8,9
6 O0 n- K# l% T5 D( m/ Z. oThere are conflicting reports and controversy
# n5 m7 e  X8 S" r- zover the effect of early androgen exposure on adult
# J  T6 V0 T; ]- Epenile length.10,11 Some reports suggest subnormal
5 p& R$ l1 W9 S5 r2 fadult penile length, apparently because of downreg-# P+ j& D% T0 e4 J/ O& b' @7 A
ulation of androgen receptor number.10,12 However,
' f$ Z8 P8 t5 E' F* u# x1 NSutherland et al13 did not find a correlation between
4 m: u' |4 C/ `$ N; _$ i) p0 Dchildhood testosterone exposure and reduced adult% {/ Y. z' c# m: M
penile length in clinical studies.- q) B; ~+ M% S" W6 B6 d& C
Nonetheless, we do not believe our patient is
( s! d( _3 Y2 R! zgoing to experience any of the untoward effects from; M& R# o0 q2 ]0 U6 p$ d
testosterone exposure as mentioned earlier because4 b. Q4 D* }: P* {  [
the exposure was not for a prolonged period of time.# r: G' C/ ]5 r( F) x3 u; F6 h* g/ F
Although the bone age was advanced at the time of
" ?7 u, Q4 E. I. l9 {0 b  ^' C; cdiagnosis, the child had a normal growth velocity at9 T7 L% R; \/ ^: ^# u
the follow-up visit. It is hoped that his final adult4 G6 o( E8 E2 ^2 ^- Q# s# ~
height will not be affected.
  N) k! I+ a  z3 F8 j0 O- \3 YAlthough rarely reported, the widespread avail-/ p; l, z7 d3 w, N7 F: w
ability of androgen products in our society may
$ s; d5 K/ u5 P3 zindeed cause more virilization in male or female# U1 x% g/ V( h; E' [5 F
children than one would realize. Exposure to andro-3 v: B4 J. L+ k8 k2 t
gen products must be considered and specific ques-$ W7 G9 j, V. Y" a$ v( B! E
tioning about the use of a testosterone product or
  d# [* `9 L1 Z4 l& Mgel should be asked of the family members during
- z/ l, g7 |, Y! J/ Tthe evaluation of any children who present with vir-
. z# H4 g! Q3 R1 dilization or peripheral precocious puberty. The diag-
9 A! G* F4 r2 q! N9 Enosis can be established by just a few tests and by
" q: V3 c& A& Cappropriate history. The inability to obtain such a( q' e% ]6 d2 c! B, W2 \8 |' g9 E
history, or failure to ask the specific questions, may
) v+ J9 I4 L* @& b- ~: rresult in extensive, unnecessary, and expensive1 L7 m8 h# H. A4 o+ n, z
investigation. The primary care physician should be& P4 S  [+ G" y" b  D1 E* ~
aware of this fact, because most of these children
2 H- v! w* ^  t* G1 L. wmay initially present in their practice. The Physicians’
- H3 K- L' m$ @- `9 A, {Desk Reference and package insert should also put a
0 C7 `* F5 I( t, i5 F) j  kwarning about the virilizing effect on a male or
- W0 ^0 {+ }) A# hfemale child who might come in contact with some-# X, }* n9 n3 Z! M' C- t  O
one using any of these products.) o2 w  J, y; A- J2 l
References; H. I- y$ `* C9 r6 }/ _
1. Styne DM. The testes: disorder of sexual differentiation
: p, v/ ~: o+ t" _1 C- Eand puberty in the male. In: Sperling MA, ed. Pediatric/ n: c- R4 C3 S9 Y) y- e# r
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;# h5 N, z# `4 N
2002: 565-628.
: C% T$ x' V$ `/ V+ q8 ?0 V2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
- t5 {- F7 }! O9 z6 U+ C* ~( Upuberty 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) Z4 c; I/ i8 j1 q& K
Boy Induced by Indirect Topical
# {* B& v4 Z! a! ^3 Q5 b1 s' qExposure to Testosterone
9 X2 W- t4 P. U5 ?  jSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
$ f1 l6 x+ m' A. w3 Aand Kenneth R. Rettig, MD1- o. r7 z: M, \, A! ~9 h
Clinical Pediatrics
! D$ Z& i+ O2 j, t8 {/ D( DVolume 46 Number 67 ]6 _" h. Z1 V( |! Y& _
July 2007 540-543
. |3 [6 T3 m' D# x: F" z- T© 2007 Sage Publications- W  K0 J  p3 @2 g
10.1177/0009922806296651: a1 C3 ^0 O" F' m0 \( j( Q7 E
http://clp.sagepub.com) x( T) K( S% ]) K6 c
hosted at! ^- R0 `# Y' u+ X
http://online.sagepub.com
% ?- b( n7 L" y' y! d* sPrecocious puberty in boys, central or peripheral,
5 Y: ]6 Y! f" h* @, wis a significant concern for physicians. Central
% _  E# Q3 f- N/ O( o" Nprecocious puberty (CPP), which is mediated: f% S- H1 U; ^9 ^1 t8 q' f" T
through the hypothalamic pituitary gonadal axis, has+ f+ a2 a1 o0 `: F9 G# a& @2 G
a higher incidence of organic central nervous system: [7 @0 C* C6 N4 S- c7 b
lesions in boys.1,2 Virilization in boys, as manifested- N8 M! p& e! m- P  B& @1 l+ j
by enlargement of the penis, development of pubic
. Z5 f0 I% u3 Y# n! C# U7 thair, and facial acne without enlargement of testi-
4 g  u0 p6 L! }7 _4 f' }cles, suggests peripheral or pseudopuberty.1-3 We
+ U+ _5 }4 b( e# d8 \5 N+ dreport a 16-month-old boy who presented with the
+ g, x$ @1 I& Q/ x# W7 p8 Denlargement of the phallus and pubic hair develop-) A& E0 X5 p, c" e  P4 Y
ment without testicular enlargement, which was due
+ a8 Y6 r2 C: S/ Yto the unintentional exposure to androgen gel used by: p) x4 }5 g* E5 b
the father. The family initially concealed this infor-7 d' C; b+ B( q
mation, resulting in an extensive work-up for this
8 E% x9 n$ ?& a" bchild. Given the widespread and easy availability of
6 R7 R5 ?0 i* X9 c) h# {3 Ktestosterone gel and cream, we believe this is proba-/ |3 F/ |! u3 Z9 Q! G5 R! W$ Y
bly more common than the rare case report in the
8 R3 l2 j8 s7 l$ }literature.40 z, P8 M  C' G6 }" e' _- {
Patient Report% b" B7 ?# P# l' _6 {, @
A 16-month-old white child was referred to the8 Y- v8 R. f6 W9 E9 D6 |' H% l' M
endocrine clinic by his pediatrician with the concern
7 x& J7 Z  y$ _  ]of early sexual development. His mother noticed
0 T; Y8 |2 {9 r. j! I3 ulight colored pubic hair development when he was
- ]# C, O, H8 {+ M6 W# y6 LFrom the 1Division of Pediatric Endocrinology, 2University of
2 f/ r  W7 u" p4 t3 ESouth Alabama Medical Center, Mobile, Alabama.8 O! u: X$ n1 e& I' L7 X
Address correspondence to: Samar K. Bhowmick, MD, FACE,
/ _" o- X5 q9 c8 u% D$ j# }Professor of Pediatrics, University of South Alabama, College of
2 J, q; ?# c" aMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;5 s8 y2 F1 h0 E& }7 v; m( t
e-mail: [email protected].
# x7 ?+ ?+ R  vabout 6 to 7 months old, which progressively became
2 u; E# [4 w+ S7 W8 }darker. She was also concerned about the enlarge-5 C" l' ]0 t  e1 O( E, x; A
ment of his penis and frequent erections. The child
$ x) r7 E/ Z' \) {9 v* w- Swas the product of a full-term normal delivery, with$ t% E3 r. V8 \: K
a birth weight of 7 lb 14 oz, and birth length of
2 C; s# o8 S2 I- k20 inches. He was breast-fed throughout the first year( n9 C  r* ?  |" U) `
of life and was still receiving breast milk along with
/ l! d6 o8 d0 u4 u" }$ M- m- Nsolid food. He had no hospitalizations or surgery,
# B9 K  [1 t* @5 {( _" a( iand his psychosocial and psychomotor development
% U2 b/ z( P2 owas age appropriate." z+ H' G% ~  z! x
The family history was remarkable for the father,4 X: l; K; _! }' O6 t1 d4 {
who was diagnosed with hypothyroidism at age 16,
6 C/ J9 I2 l9 z# cwhich was treated with thyroxine. The father’s
. o: A; B; V/ ?height was 6 feet, and he went through a somewhat" V' E, h$ K$ Z! B9 u3 r, h* `7 ^
early puberty and had stopped growing by age 14.
" y  I+ R4 ^! D. ^7 X: y, zThe father denied taking any other medication. The2 a: ~1 B; ]! p+ C
child’s mother was in good health. Her menarche
0 k: }% I1 m; n5 s6 C7 fwas at 11 years of age, and her height was at 5 feet' x- K3 S. F1 p7 V- h
5 inches. There was no other family history of pre-
/ s3 N. h. `6 Q: B  j  B  ncocious sexual development in the first-degree rela-6 r$ q0 B9 L! n- S9 V
tives. There were no siblings.& q$ V- p6 `% x/ [9 `
Physical Examination$ Q& {7 J  ~& H3 u0 W
The physical examination revealed a very active,( g% v3 L2 j1 Z" ^5 w# O  f3 j
playful, and healthy boy. The vital signs documented
0 K% g2 Q8 j7 u" s# Ra blood pressure of 85/50 mm Hg, his length was
3 M: T- ?' Z) G1 m90 cm (>97th percentile), and his weight was 14.4 kg" g* O0 y9 _7 ]  {! A
(also >97th percentile). The observed yearly growth: h( Q! y" B5 |1 Z0 T, W/ l+ |+ o
velocity was 30 cm (12 inches). The examination of
/ Q; s& p* j6 O. Bthe neck revealed no thyroid enlargement.: f3 L/ v) P* i
The genitourinary examination was remarkable for& Q" U- x3 _9 l, L1 |# c  ~
enlargement of the penis, with a stretched length of
* ]% L) _$ J2 G& D8 cm and a width of 2 cm. The glans penis was very well
1 d1 {3 y5 J" r( p2 f% G0 Tdeveloped. The pubic hair was Tanner II, mostly around
% |- K& k+ _6 @5407 w: R( ?: z( D. Q& P) V- K
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
! P( C8 f, G" ~the base of the phallus and was dark and curled. The5 S  i7 e6 {7 c5 d* v1 v" q9 p1 y
testicular volume was prepubertal at 2 mL each.
# a: |6 h" w2 H  |  IThe skin was moist and smooth and somewhat; Z( ^  H0 C" N# c) b5 A
oily. No axillary hair was noted. There were no% U: h, @& B4 ]" t- G
abnormal skin pigmentations or café-au-lait spots.
6 d2 A, |; w$ e+ i7 Q% cNeurologic evaluation showed deep tendon reflex 2+
( R% r/ o$ w$ q, N  B& [4 Hbilateral and symmetrical. There was no suggestion
$ T0 j6 I& q* N- ]4 e4 |2 l- c) c( cof papilledema.
5 E( T" u2 j  f( J. iLaboratory Evaluation/ y7 ?+ a6 N9 A
The bone age was consistent with 28 months by+ N& @4 G7 \3 j' q) |/ Z2 i
using the standard of Greulich and Pyle at a chrono-
8 _( B" M' }6 W+ x5 dlogic age of 16 months (advanced).5 Chromosomal
6 v/ U' @( Z7 `/ a5 vkaryotype was 46XY. The thyroid function test
% g. g+ ?9 K/ U; ?" f, Q4 D) l, Nshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
1 P6 [7 U4 y+ n0 P2 J4 Hlating hormone level was 1.3 µIU/mL (both normal).: T7 v$ c; n0 c8 }4 e% k
The concentrations of serum electrolytes, blood
+ |5 s: h; l1 {# h6 j0 aurea nitrogen, creatinine, and calcium all were' R) P' V8 U6 e
within normal range for his age. The concentration+ J" X* `* E# U, u
of serum 17-hydroxyprogesterone was 16 ng/dL
' Y1 n/ ~! ^1 V" L  z- ]+ ?/ d(normal, 3 to 90 ng/dL), androstenedione was 20$ Y+ u! r- w* j
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-5 ?' G+ x  [7 N( K) {+ N) x6 F" [
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
5 G# C% [. B* k" }+ wdesoxycorticosterone was 4.3 ng/dL (normal, 7 to
# M; @2 t5 R9 d49ng/dL), 11-desoxycortisol (specific compound S)
- E% i2 G  Q; l8 f" qwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-0 G5 P( ]3 l: L$ r; n9 g
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total) i* r% X" F( L0 f& ^7 q7 V0 c- j5 Y
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
% E. X! W( |) D3 R0 i) a; _; Dand β-human chorionic gonadotropin was less than; v: b9 l) G8 T
5 mIU/mL (normal <5 mIU/mL). Serum follicular
& Z4 ~5 x* P6 u" [- g9 v$ fstimulating hormone and leuteinizing hormone
# a. s8 T. k: m, T$ Tconcentrations were less than 0.05 mIU/mL
4 s, [$ m; {' G( s. |: ~(prepubertal).1 }& O/ {# s' T& X
The parents were notified about the laboratory2 |8 @0 O# J4 ^0 ?: C8 j2 h
results and were informed that all of the tests were1 O  P1 V2 U* E3 ^
normal except the testosterone level was high. The4 I( Z" h* |  B7 `# {
follow-up visit was arranged within a few weeks to
) }4 ~$ x) C1 |4 D2 d4 J' _obtain testicular and abdominal sonograms; how-
7 q: N3 U- S+ a! d8 f) X% _2 d* u& uever, the family did not return for 4 months.3 n- e8 I* M1 @2 w8 N% `" L
Physical examination at this time revealed that the
$ o2 [2 G+ V1 o. Ychild had grown 2.5 cm in 4 months and had gained
4 ^4 e' U. h2 A; e5 u3 D& x& ?2 G2 kg of weight. Physical examination remained
7 Q6 |( F6 X' Z  G: N6 iunchanged. Surprisingly, the pubic hair almost com-, q  N, R1 t! i- |+ I
pletely disappeared except for a few vellous hairs at
& Z, n5 L8 y/ k8 }9 x0 S1 c+ v9 fthe base of the phallus. Testicular volume was still 2! y1 D! [$ E+ w5 B
mL, and the size of the penis remained unchanged.; W& ^# A' {) @6 }' |2 v
The mother also said that the boy was no longer hav-
1 _5 m) z! W  }6 Z4 Hing frequent erections.' p( B& T2 @' f% Y3 B, K% J! F
Both parents were again questioned about use of  j$ v- I* j' o$ ^
any ointment/creams that they may have applied to
6 D  L3 @4 K: ~9 y0 Wthe child’s skin. This time the father admitted the/ O; j! _% b) V7 O
Topical Testosterone Exposure / Bhowmick et al 541% v* Y9 g! G* {. V# m, m0 f
use of testosterone gel twice daily that he was apply-
4 I  r& H( k6 X5 ying over his own shoulders, chest, and back area for
' g/ p4 n* n/ N7 _2 Va year. The father also revealed he was embarrassed
* U: t$ z* V2 |, D, I5 T2 u& {+ rto disclose that he was using a testosterone gel pre-
, ~6 g( E& ^5 F! i' hscribed by his family physician for decreased libido% K6 w- F! P! w
secondary to depression.) K1 ~; O" \! T
The child slept in the same bed with parents.
+ D; Y# {% S( p0 ]: ]& o' P' LThe father would hug the baby and hold him on his* _6 }. S+ ^7 q0 Z
chest for a considerable period of time, causing sig-" r5 r* p7 M$ q1 [
nificant bare skin contact between baby and father.
+ ?1 S. s# h* }, ~0 I' a0 u# DThe father also admitted that after the phone call,1 q% c& y4 ^! \1 W
when he learned the testosterone level in the baby
' P  l# n; Y& Z& Ewas high, he then read the product information" k3 H0 o& g4 P- r
packet and concluded that it was most likely the rea-
! X* f- |" y- J" d* json for the child’s virilization. At that time, they
4 V, y$ A- |: g. {7 ?# Ydecided to put the baby in a separate bed, and the
! J) P5 k" |9 K! Kfather was not hugging him with bare skin and had8 ]: P( Z+ k2 |4 m& W! x) ~
been using protective clothing. A repeat testosterone1 L: R/ W2 j( h- k0 U3 I
test was ordered, but the family did not go to the( G8 ?- T0 A9 H4 \2 L# {1 f
laboratory to obtain the test.; x7 j/ q9 \5 C& B! d
Discussion: M' N9 i1 M! H8 `6 `2 x' `" F& j
Precocious puberty in boys is defined as secondary, X4 Y$ Z5 ]& E
sexual development before 9 years of age.1,4
8 j5 B/ p$ U9 |Precocious puberty is termed as central (true) when7 Z3 o* H+ K% n. r* `
it is caused by the premature activation of hypo-
9 [" q! [, `/ z0 ]6 Sthalamic pituitary gonadal axis. CPP is more com-9 U) o; C& r$ w! s
mon in girls than in boys.1,3 Most boys with CPP+ B& K3 g! e, I2 H: P
may have a central nervous system lesion that is
" B: O3 Q6 u; |9 T  w- Y# presponsible for the early activation of the hypothal-
0 R4 g# q8 Q  \9 }+ T1 ]' r! Qamic pituitary gonadal axis.1-3 Thus, greater empha-
# B4 x; c. u* Y0 O$ v* @- qsis has been given to neuroradiologic imaging in
) L  N+ _' `/ j0 j6 T2 Z- Lboys with precocious puberty. In addition to viril-
# N2 x8 e1 n  A9 R) bization, the clinical hallmark of CPP is the symmet-& S) c% X( M. |; g* e
rical testicular growth secondary to stimulation by
; m% x) N2 D- |/ Agonadotropins.1,37 R6 c$ T* l4 Q% @3 A. Z1 T
Gonadotropin-independent peripheral preco-$ K. M& k+ o  L4 Y; S2 S
cious puberty in boys also results from inappropriate" X8 ^" W. v) q& \
androgenic stimulation from either endogenous or
( V+ ~  R! J' }* L" N- Lexogenous sources, nonpituitary gonadotropin stim-# p+ D8 e0 H* T% q
ulation, and rare activating mutations.3 Virilizing' Y3 |3 N# h% A3 ]
congenital adrenal hyperplasia producing excessive1 r, W% e3 u6 x' F# i8 r8 {
adrenal androgens is a common cause of precocious
4 ]$ P% ^, K/ j9 A, o5 Ipuberty in boys.3,4
% b4 I1 V5 {+ H1 V9 }The most common form of congenital adrenal
6 [+ g1 A6 T9 H% P; O6 Ohyperplasia is the 21-hydroxylase enzyme deficiency.
) I( U3 x3 i: oThe 11-β hydroxylase deficiency may also result in& x" ~# t4 f( Q. }
excessive adrenal androgen production, and rarely,
$ a6 V7 \1 N; [  X- kan adrenal tumor may also cause adrenal androgen+ e: H8 M7 R% S4 Z, w
excess.1,3
$ U" P, t% W* I" ~at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from+ j$ W: k/ L1 j# t2 C: g# ^- ^
542 Clinical Pediatrics / Vol. 46, No. 6, July 20076 E, Z9 r5 z5 r8 G& I
A unique entity of male-limited gonadotropin-- @, i) m( @2 U/ ?- e" Q
independent precocious puberty, which is also known
+ A. H" S9 B: F, ras testotoxicosis, may cause precocious puberty at a
) a- ~+ @6 i$ `8 m+ N. Ivery young age. The physical findings in these boys: H% w' n. [4 {! ]' C8 o
with this disorder are full pubertal development,
( w: p6 q, Z6 d4 Z3 Cincluding bilateral testicular growth, similar to boys1 F4 f4 X1 x2 L& }
with CPP. The gonadotropin levels in this disorder
( d  S' |5 `3 {/ M$ i0 pare suppressed to prepubertal levels and do not show) H% T& j( T* I, g
pubertal response of gonadotropin after gonadotropin-- D$ K# R* d0 ~# T6 H
releasing hormone stimulation. This is a sex-linked
8 H8 W/ v% U* D4 |' }autosomal dominant disorder that affects only6 H- p+ d6 t) c; K
males; therefore, other male members of the family$ U) l4 ^/ Z$ `
may have similar precocious puberty.3
+ s* {  v/ [- _8 d. `. v2 o+ i" AIn our patient, physical examination was incon-
5 G2 p- U# }! z2 n: M5 q' A9 }sistent with true precocious puberty since his testi-5 K, D9 u" C) `/ z3 I) k: l
cles were prepubertal in size. However, testotoxicosis
- }1 m% p; R) n- q5 Wwas in the differential diagnosis because his father
0 Z: N6 B+ D% L" ?$ k9 qstarted puberty somewhat early, and occasionally,
4 x# [+ o5 _0 n, Ztesticular enlargement is not that evident in the
8 I( @$ [( S( p, _1 d6 Bbeginning of this process.1 In the absence of a neg-
& X9 G# u5 c# D( _/ I/ Pative initial history of androgen exposure, our$ g6 F3 u1 g3 J& C' g6 K3 u4 I
biggest concern was virilizing adrenal hyperplasia,
1 x1 @3 ^( o. s, w1 ?either 21-hydroxylase deficiency or 11-β hydroxylase5 t% x8 f! l4 a3 u1 C
deficiency. Those diagnoses were excluded by find-% ~7 N7 N1 M( I) t8 @
ing the normal level of adrenal steroids.
6 h; y0 L* d! O4 m. x* e% }2 RThe diagnosis of exogenous androgens was strongly; w* e0 Q; i+ }* e! l( K
suspected in a follow-up visit after 4 months because
3 Z* [1 k% T2 z8 D3 c1 V' gthe physical examination revealed the complete disap-
* Z" `0 D' w( B4 `$ Npearance of pubic hair, normal growth velocity, and! ]9 n/ m5 J! X5 I
decreased erections. The father admitted using a testos-
* @' P# s/ z0 Nterone gel, which he concealed at first visit. He was
+ K3 z# T, M2 k( |using it rather frequently, twice a day. The Physicians’
( A  S* Z) S$ a5 g+ P3 {Desk Reference, or package insert of this product, gel or& c: {* P* O# Y# @0 W+ |
cream, cautions about dermal testosterone transfer to( r/ @: Y7 i0 ]/ U% G6 b
unprotected females through direct skin exposure.
0 C% D' G5 g, R1 u& ?Serum testosterone level was found to be 2 times the4 x% {: |. U6 x: _: A; L
baseline value in those females who were exposed to
; e# \) `( l, f! B% `( h+ l0 M& geven 15 minutes of direct skin contact with their male
5 j+ y3 l2 r1 ?9 ]. {. spartners.6 However, when a shirt covered the applica-. Y. o' T7 w' Y% U- C6 y
tion site, this testosterone transfer was prevented.
0 x) h1 `- K- E% n9 xOur patient’s testosterone level was 60 ng/mL,0 n7 [$ S7 E0 n% g; h. q
which was clearly high. Some studies suggest that% d0 o' }/ R9 N1 X( _3 f* D! V
dermal conversion of testosterone to dihydrotestos-
0 h% d! P. f; {9 Mterone, which is a more potent metabolite, is more
" y) T: D! @3 N9 T! \/ k' Ractive in young children exposed to testosterone
( i  Q. D: r3 A5 }exogenously7; however, we did not measure a dihy-& Q- a6 h3 S* ^8 J! T
drotestosterone level in our patient. In addition to
  k; L' O! g* ?9 t4 c, U! `virilization, exposure to exogenous testosterone in5 q: i4 n4 i* R$ N. b: U: A
children results in an increase in growth velocity and4 P; e( B- l9 T* c$ ?( v
advanced bone age, as seen in our patient.5 u8 |0 j' r% i" @$ @: v1 @
The long-term effect of androgen exposure during
0 ^0 u/ O1 n$ G$ e8 h( G6 B6 i7 Tearly childhood on pubertal development and final
! M. w3 f5 B+ X, [; o! u/ s# sadult height are not fully known and always remain/ @3 ]0 b5 t/ `6 `
a concern. Children treated with short-term testos-
" E0 ]+ L; s* z" nterone injection or topical androgen may exhibit some# q3 c+ l8 n6 @- q4 z5 k; S0 [9 Q' J7 @
acceleration of the skeletal maturation; however, after5 O4 |3 t; @4 ~; O, H& X, ^2 o6 Z5 I
cessation of treatment, the rate of bone maturation
+ K, s$ S# t- f; }, |decelerates and gradually returns to normal.8,9& K* l* `# k# ^$ {9 ~, I
There are conflicting reports and controversy
/ E; m$ @( S" ~& I( }9 Hover the effect of early androgen exposure on adult
' a/ n- [$ i9 Y* l, g$ n6 Hpenile length.10,11 Some reports suggest subnormal# T+ f  g  r! O0 |5 k
adult penile length, apparently because of downreg-: a  S6 ]( j  `, Z4 }- A; d
ulation of androgen receptor number.10,12 However,
: ?: u- M7 P3 q# }Sutherland et al13 did not find a correlation between" X, h) G5 C0 c: w5 W" n4 z
childhood testosterone exposure and reduced adult
5 \6 W5 T9 f' D8 Npenile length in clinical studies.
4 R1 l% t$ g  p* q9 A, g6 vNonetheless, we do not believe our patient is
* u2 o$ f' v$ p4 Ygoing to experience any of the untoward effects from/ v4 m2 f; V$ O' x
testosterone exposure as mentioned earlier because
6 C. y4 M! V' d' ^3 ?4 N' Ithe exposure was not for a prolonged period of time.
# g5 T( A1 h/ _' m; F# x$ nAlthough the bone age was advanced at the time of! F) s  [, X; X, e* }
diagnosis, the child had a normal growth velocity at. Q) A* D% B8 a
the follow-up visit. It is hoped that his final adult
. g$ x1 m/ t  x/ z, C: Cheight will not be affected.$ d: \8 Z* e; b
Although rarely reported, the widespread avail-
0 f8 D$ e+ |) ^3 I  |: O( F% P  V# cability of androgen products in our society may
2 C( u7 j' l& p( a$ Hindeed cause more virilization in male or female
! V& G& b5 M0 o- e' K0 U/ fchildren than one would realize. Exposure to andro-
$ s7 ]" _( `, ]7 [7 o. z! Z6 egen products must be considered and specific ques-
4 W3 k+ I6 ~$ j8 [tioning about the use of a testosterone product or5 _$ r3 [! e5 }
gel should be asked of the family members during! j4 n0 g: j+ [4 |5 }' r; E+ [
the evaluation of any children who present with vir-0 u: p" L5 |/ R: z+ f5 ?9 z* }# }
ilization or peripheral precocious puberty. The diag-) U# [6 y& s; B5 L
nosis can be established by just a few tests and by
8 p5 x* B! K: f2 `6 yappropriate history. The inability to obtain such a: K" h" P# B* c" D' w2 o! s7 j
history, or failure to ask the specific questions, may& j& `' t$ p& u& m
result in extensive, unnecessary, and expensive
! X: c! N6 j2 \3 p. D) N7 Rinvestigation. The primary care physician should be6 G8 h8 E! d2 e. R3 A4 o, |: X
aware of this fact, because most of these children
( E% ?" o) m2 F, R0 tmay initially present in their practice. The Physicians’3 r) j, \; Y5 l3 C; ~6 N; f9 A
Desk Reference and package insert should also put a
, ^1 l; W, d; b1 X( N+ R7 fwarning about the virilizing effect on a male or6 M! w8 J3 }: Z! E; A6 ?& ?
female child who might come in contact with some-
2 Y) S4 C2 R0 E* hone using any of these products.) t# V! {+ c$ p# A" ?. m
References
7 F, [$ K9 c! Y. P( r. ^1. Styne DM. The testes: disorder of sexual differentiation
8 ?" u& V3 t3 Xand puberty in the male. In: Sperling MA, ed. Pediatric
7 ?: \" H) w! u9 U9 q. fEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
1 n+ H: p' S! u' |2002: 565-628.- w7 F/ B8 h8 k' _6 p4 C2 y. H
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious: R1 f# B9 K& z  g! I
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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. @: y. h0 \' A3 A6 ~0 l/ }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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