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Sexual Precocity in a 16-Month-Old" g4 Q* V; P- [* \' k3 u
Boy Induced by Indirect Topical
& M8 a+ M5 i. `  i0 G) UExposure to Testosterone9 W7 p' b" s: k$ @) ^3 M
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
& V4 Y: T$ l/ j$ E9 Y" L  I5 G" `and Kenneth R. Rettig, MD1
: v+ z' J) d6 I5 o# _2 ?( YClinical Pediatrics
+ g! B7 T' o" ^3 |$ K( TVolume 46 Number 67 y& M1 Q" Y! D7 y* |
July 2007 540-543
- {  I4 b' {3 s) V. o8 v© 2007 Sage Publications
3 d* z6 j- k4 p3 ~2 M10.1177/0009922806296651
+ s) f. y- e; b& O& m; phttp://clp.sagepub.com
" @/ k& y; l/ ?, lhosted at% D- P4 m* r+ ?+ d4 g
http://online.sagepub.com
# ]1 U" B8 @2 D/ u* U8 X+ D5 KPrecocious puberty in boys, central or peripheral,+ C8 Z/ L% }: V5 D; A
is a significant concern for physicians. Central' v$ p% j% g9 m8 A0 c
precocious puberty (CPP), which is mediated1 W2 k# S% c4 P2 m
through the hypothalamic pituitary gonadal axis, has
5 v. p. {7 \; O  Aa higher incidence of organic central nervous system; g! U; U6 r! q# p. E
lesions in boys.1,2 Virilization in boys, as manifested- B1 l2 B2 X+ i, \. F! i: W$ z
by enlargement of the penis, development of pubic5 I! Z% z) c' z( o, M: _
hair, and facial acne without enlargement of testi-. N* W5 d, _: S2 C$ A
cles, suggests peripheral or pseudopuberty.1-3 We
2 M  `$ Q8 K5 Q1 e: Breport a 16-month-old boy who presented with the
) Z$ s4 Z: J& W* p( M. kenlargement of the phallus and pubic hair develop-
9 \/ y# i8 G+ o! }ment without testicular enlargement, which was due
9 d. M! }2 }; e- U# a& I4 T2 oto the unintentional exposure to androgen gel used by' g' x% r/ O4 y# f+ X" H9 z5 Q: n( u
the father. The family initially concealed this infor-
, \2 C- E6 l/ N1 V7 A; qmation, resulting in an extensive work-up for this
, e$ [9 A0 c+ S, Z8 q! R4 Cchild. Given the widespread and easy availability of! c* w1 o9 m$ M2 a- Z% Z. n3 X
testosterone gel and cream, we believe this is proba-9 M) h, K9 E2 d1 v& D9 _/ V
bly more common than the rare case report in the5 x' \4 m9 W$ O9 E- T% w4 i' W, j
literature.44 @- Z( l- ^0 n% |2 M& O& n! }3 S
Patient Report
; a. w/ `( e) j& y9 R# G# m2 [A 16-month-old white child was referred to the
0 C6 ?! I. l) P& J" O* Nendocrine clinic by his pediatrician with the concern
- I3 M/ D: U. E8 bof early sexual development. His mother noticed
0 C: u/ C1 r, U2 P8 olight colored pubic hair development when he was4 N! ^1 e* s+ y! X
From the 1Division of Pediatric Endocrinology, 2University of% i% j% O, }) F
South Alabama Medical Center, Mobile, Alabama.
/ V$ z0 |0 @  k- T& n* {Address correspondence to: Samar K. Bhowmick, MD, FACE,
6 I6 `$ g* M& b4 O& J9 Z% TProfessor of Pediatrics, University of South Alabama, College of1 Z9 y8 G, }. B( c) r) C+ A! o
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
% x( d: [& Y; \  l% `/ He-mail: [email protected].
/ V. V( w2 R5 }; X. h5 k" yabout 6 to 7 months old, which progressively became
$ ]# r1 O& E  B5 Qdarker. She was also concerned about the enlarge-8 Y& Q. P2 J7 V: }) ~
ment of his penis and frequent erections. The child" c0 Z. u# C, y$ w3 _4 x! ]! R
was the product of a full-term normal delivery, with
" J5 S2 {4 H4 M9 A. d+ xa birth weight of 7 lb 14 oz, and birth length of
3 q) r% E' F( Z. ^5 z" s20 inches. He was breast-fed throughout the first year" e0 b. a- C: b: T
of life and was still receiving breast milk along with8 s. V. r+ t- T9 @
solid food. He had no hospitalizations or surgery,5 @0 k5 R' U/ }. _
and his psychosocial and psychomotor development
8 ?, ]- _9 n+ h. F+ M. Zwas age appropriate.; e$ V0 D% \, N# D6 Z: g
The family history was remarkable for the father,
% [- e0 y( W% R: v1 {who was diagnosed with hypothyroidism at age 16,
9 o! o7 i1 E' \which was treated with thyroxine. The father’s3 f* i8 w/ d* H  f
height was 6 feet, and he went through a somewhat& k- {1 T& Z2 }- Y& \8 k
early puberty and had stopped growing by age 14.
* Y; w6 W- U4 p1 DThe father denied taking any other medication. The
3 o. \) d2 Z% s5 v, u& zchild’s mother was in good health. Her menarche
) b& c1 z: f8 S" xwas at 11 years of age, and her height was at 5 feet( ]! Y* y" Q. X. D( Z, g
5 inches. There was no other family history of pre-
  q' A% L. D2 ]4 w5 T2 h& Bcocious sexual development in the first-degree rela-
- w3 f3 Y. I5 i3 O' ctives. There were no siblings.% B5 a0 ~/ f, m. P" G
Physical Examination5 k) P, T8 I  T* I- n( J
The physical examination revealed a very active,( j6 t2 w; X$ Z6 W6 g- U$ }( r
playful, and healthy boy. The vital signs documented
# D8 m2 T" h. ~. na blood pressure of 85/50 mm Hg, his length was
5 t. w! v. m' D4 C90 cm (>97th percentile), and his weight was 14.4 kg' l9 c5 X1 p0 n" @$ f
(also >97th percentile). The observed yearly growth
7 ]" U5 I- {1 ?+ O: E' b% ivelocity was 30 cm (12 inches). The examination of
+ k. C' L$ d5 N1 F6 F& @+ fthe neck revealed no thyroid enlargement.
* V" S* z: ]% ~+ C; c3 EThe genitourinary examination was remarkable for
# E& ^' I, v3 F9 ], Z7 L& ~$ f8 M: i$ F' Eenlargement of the penis, with a stretched length of) l  p1 z  Q) T7 L
8 cm and a width of 2 cm. The glans penis was very well5 g! W$ {; i, z9 G8 _
developed. The pubic hair was Tanner II, mostly around
  S2 }' B6 E) r, f* k' Z9 Q540: Z) ^0 b4 H7 Z" }# u) b; O5 @: p
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from% ?0 ?$ a, G2 \5 U- }: n
the base of the phallus and was dark and curled. The  ]( `; J* R. n0 u1 \; ?
testicular volume was prepubertal at 2 mL each.
- F; S4 j1 G2 J6 f* @1 M8 CThe skin was moist and smooth and somewhat
8 s9 L' d" {7 C+ f* B- ]oily. No axillary hair was noted. There were no+ h  j/ s- D9 \8 Y3 `" @
abnormal skin pigmentations or café-au-lait spots.* G7 N1 q2 x1 c% B1 g- q) Z& L+ q, ^
Neurologic evaluation showed deep tendon reflex 2+
6 E* u% t2 F- W: e  cbilateral and symmetrical. There was no suggestion
0 v9 t1 m9 H+ g& z& Vof papilledema.
6 v3 d3 V0 g- ~6 m! ]4 [6 B8 eLaboratory Evaluation
. t2 b7 P3 _6 G0 N1 lThe bone age was consistent with 28 months by6 d) s" K- L% r
using the standard of Greulich and Pyle at a chrono-
4 I% r, {- L# o; ^. }3 Flogic age of 16 months (advanced).5 Chromosomal  r- @1 S4 f4 N+ L
karyotype was 46XY. The thyroid function test& u5 R/ B1 Y* Y- t/ @6 G
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
# P. |+ W# U* |4 F/ J) _! p: N# @  Qlating hormone level was 1.3 µIU/mL (both normal)., P, B6 K% i! B* K' k1 _8 c2 O
The concentrations of serum electrolytes, blood' |, K( L0 F, J: N& m% s
urea nitrogen, creatinine, and calcium all were- M; t& P0 @+ _
within normal range for his age. The concentration
, A" z# c! N" H# b# C( k5 Yof serum 17-hydroxyprogesterone was 16 ng/dL
7 Z/ u$ B  g" e* m) x+ v& c( C, D(normal, 3 to 90 ng/dL), androstenedione was 20
, U0 \* }! Y# s  U( qng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
0 F: D3 T/ L' V7 D# }; s+ pterone was 38 ng/dL (normal, 50 to 760 ng/dL),
- T! o% v4 o, k4 X( B+ y) @desoxycorticosterone was 4.3 ng/dL (normal, 7 to
( d  ]) h& q  h8 I49ng/dL), 11-desoxycortisol (specific compound S)3 l7 G+ s* m6 X% |1 `4 r( T
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
! K) J' d0 e! a) O4 m- j! u7 Itisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total; f; P% T- n0 Z# U
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),$ B) F: Q+ M5 F$ {% V
and β-human chorionic gonadotropin was less than
' G- r6 ~1 L% s. g) A7 a5 mIU/mL (normal <5 mIU/mL). Serum follicular
2 {* q/ f' o3 Q2 ?* c! u/ f- ostimulating hormone and leuteinizing hormone
7 ~, z" p0 |6 R1 A4 @concentrations were less than 0.05 mIU/mL
+ v" c# D" v; I  |(prepubertal).6 O) E  j8 w) ]0 B4 l
The parents were notified about the laboratory
( [& O7 ~+ Y" [" Nresults and were informed that all of the tests were
! s9 b) W; Z" h& P. g3 d: Enormal except the testosterone level was high. The
2 d$ t7 Z2 `3 s4 E6 j" I" d- ufollow-up visit was arranged within a few weeks to
4 O7 v1 v: y7 n7 W' L! }9 Gobtain testicular and abdominal sonograms; how-
$ D; z( j" R  oever, the family did not return for 4 months.7 m9 x/ e/ G0 ^6 }9 ^; ?
Physical examination at this time revealed that the) c: H; E8 ?: f
child had grown 2.5 cm in 4 months and had gained9 ^9 [) H; B) l, c2 g
2 kg of weight. Physical examination remained
/ Z, D; b# v: i0 L3 Q6 n* `6 x6 G2 ]unchanged. Surprisingly, the pubic hair almost com-" F! T& D9 E$ z. }% y3 ~; d5 b- z
pletely disappeared except for a few vellous hairs at/ ~7 S" s9 H7 ?! Y+ F6 {
the base of the phallus. Testicular volume was still 2
- ~' ]5 F, P# I$ G) tmL, and the size of the penis remained unchanged.0 U* b6 |! ]* v' }! I; J: x: l- r
The mother also said that the boy was no longer hav-9 N4 |! E* n5 B. j* g/ F2 R1 A
ing frequent erections.
: G/ `* K, [6 q& O1 J& eBoth parents were again questioned about use of# n- L1 u) e1 [. u! b2 K6 b
any ointment/creams that they may have applied to. w7 i) [8 o. V, m; O
the child’s skin. This time the father admitted the
. S% [: Z: j, [  kTopical Testosterone Exposure / Bhowmick et al 541; _7 P) r6 g2 f& r
use of testosterone gel twice daily that he was apply-
' U/ _) q' Z3 w# ~2 _+ Ving over his own shoulders, chest, and back area for
, _+ }/ D6 _* Ua year. The father also revealed he was embarrassed
; ^4 t) @: _. {/ Z$ uto disclose that he was using a testosterone gel pre-
* M5 f: z; ~% Bscribed by his family physician for decreased libido2 @! E, i7 K2 {$ ?- e$ a5 Z
secondary to depression.
5 I, S3 [# W- y+ ?) M, m" E  qThe child slept in the same bed with parents.+ {( b0 H# ]& l% A8 Q
The father would hug the baby and hold him on his
5 [- m" x2 H0 f( K3 }  ^8 Kchest for a considerable period of time, causing sig-) x5 v1 u) Y7 _* Z5 \
nificant bare skin contact between baby and father.; G$ M+ I' J7 C+ M9 |  `
The father also admitted that after the phone call," D: U' Y' j9 \9 H# G" N2 D
when he learned the testosterone level in the baby9 y9 ~  Z: y2 _/ t7 s, O) L/ V5 a6 Y' _
was high, he then read the product information# i% j3 W& n3 V; G9 T$ n+ ]% n- U
packet and concluded that it was most likely the rea-: {- ?) [3 f  W' s9 F
son for the child’s virilization. At that time, they* g' q1 x" H. J* Q0 z6 J
decided to put the baby in a separate bed, and the
: f% m% S6 |+ B8 W$ y$ gfather was not hugging him with bare skin and had
! D7 M/ r* o8 S% v5 l) Wbeen using protective clothing. A repeat testosterone
' t* V/ l& K; }6 Htest was ordered, but the family did not go to the8 |/ p( f: s* v7 c; x) I9 h
laboratory to obtain the test.; r1 [5 K# P+ ~+ m3 z- G( c
Discussion) B! [5 A7 }) o  O" D( k
Precocious puberty in boys is defined as secondary5 c: q) w% u3 u  e7 F
sexual development before 9 years of age.1,4
9 m* I" c& h! M7 RPrecocious puberty is termed as central (true) when, R# y7 w9 _8 P; a' c: y- y# W
it is caused by the premature activation of hypo-
0 f' Z$ k" ?2 I9 wthalamic pituitary gonadal axis. CPP is more com-
4 K/ J* L* b- W7 ~1 j' F' Umon in girls than in boys.1,3 Most boys with CPP7 k# e: G) h/ J1 `( w1 F0 J
may have a central nervous system lesion that is# f, V- K* X+ N+ R0 {9 m8 h$ e% d
responsible for the early activation of the hypothal-# G7 N; p8 x0 U
amic pituitary gonadal axis.1-3 Thus, greater empha-
. T6 m/ }2 H/ C: x) [, O$ Jsis has been given to neuroradiologic imaging in& v8 J; |" _! s4 |- ]% |& ^
boys with precocious puberty. In addition to viril-; w7 z& e3 j1 L/ W- A
ization, the clinical hallmark of CPP is the symmet-, x  h5 ]& \  @6 l8 G# j* d" S
rical testicular growth secondary to stimulation by
: H! s- T$ L  U4 H. fgonadotropins.1,36 P; y- P9 W) X5 k
Gonadotropin-independent peripheral preco-
: e9 R- o/ v, Jcious puberty in boys also results from inappropriate" a. n0 p6 ?" ?0 y0 N
androgenic stimulation from either endogenous or: j. L* G" G* x: M
exogenous sources, nonpituitary gonadotropin stim-
- @4 W$ l0 x* \ulation, and rare activating mutations.3 Virilizing/ d. M- X: E/ N" Q. P, {
congenital adrenal hyperplasia producing excessive# k+ _2 L" w; N% G
adrenal androgens is a common cause of precocious$ V- _2 x* w- `$ t9 r2 M" z
puberty in boys.3,4! ~9 }; F1 z6 l3 H2 g3 ]
The most common form of congenital adrenal' S) s6 c/ M4 z# l+ {& L: g
hyperplasia is the 21-hydroxylase enzyme deficiency.  u1 g" X! C9 F+ B9 V
The 11-β hydroxylase deficiency may also result in( V, |" k* A( d0 j0 |$ j
excessive adrenal androgen production, and rarely,
% [: H) F9 |1 m3 a" Z4 G; Fan adrenal tumor may also cause adrenal androgen
: h6 s9 \0 p! Z3 R! V* s9 ~- @excess.1,30 U2 M% T( @( S) M* U' C1 `
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from; H7 i+ H' l6 D( n3 Q4 K
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
6 X4 b$ f. |- O) gA unique entity of male-limited gonadotropin-$ q3 @7 i, R2 K; b6 d
independent precocious puberty, which is also known
; o  u: f6 ?1 T1 g- Bas testotoxicosis, may cause precocious puberty at a. o+ _7 I  }6 W+ P  m. P9 S
very young age. The physical findings in these boys
. D2 \; X/ V% e' x  j; iwith this disorder are full pubertal development,, _( k3 ^- Z0 \3 ]+ K! I
including bilateral testicular growth, similar to boys
: n& S8 z( G2 qwith CPP. The gonadotropin levels in this disorder
. N" \5 X0 Z+ R1 F7 Y7 Xare suppressed to prepubertal levels and do not show
" D2 t; F( m+ P7 N5 ?, Fpubertal response of gonadotropin after gonadotropin-
# S' V2 R0 t6 v. F/ I$ Lreleasing hormone stimulation. This is a sex-linked: E% Y9 |# h6 D3 {( [
autosomal dominant disorder that affects only" d0 K6 I- S; M, O4 r# O
males; therefore, other male members of the family7 V( ?3 H4 D' `& Q5 l
may have similar precocious puberty.3
* L3 l$ k1 h* H4 dIn our patient, physical examination was incon-
: N, C' ?; G8 q3 H, [8 \sistent with true precocious puberty since his testi-! l$ G5 F$ Q3 T4 z
cles were prepubertal in size. However, testotoxicosis4 W( L; {+ S4 c$ l2 ^& t: M' ?) V
was in the differential diagnosis because his father
% [; B$ K( {: y- _1 N. r% K0 Gstarted puberty somewhat early, and occasionally,
- M+ L% G) `, M8 z+ {5 ]4 Wtesticular enlargement is not that evident in the  L3 i; [# a" H1 z, V4 ~- b6 |; |
beginning of this process.1 In the absence of a neg-$ o! A: M, v9 ~) a- F4 _( w
ative initial history of androgen exposure, our
# V, e: b& @2 n3 F3 J/ mbiggest concern was virilizing adrenal hyperplasia,3 ]1 @% Z& _+ Z0 E; ?( k; ^
either 21-hydroxylase deficiency or 11-β hydroxylase
( E6 @4 J. }- O: s( q& s/ }, M- u0 ]deficiency. Those diagnoses were excluded by find-
+ I& J2 @+ w9 T2 n" Aing the normal level of adrenal steroids.2 j. ?" N1 t# y% Q! j$ ?) t5 A: J
The diagnosis of exogenous androgens was strongly
: }! b/ _: n' a$ U* o$ Psuspected in a follow-up visit after 4 months because
- Z* K. N- Z" o8 O! T4 K  Ethe physical examination revealed the complete disap-
1 r7 M# W2 c& z$ Wpearance of pubic hair, normal growth velocity, and/ e' a+ ~( B% ]3 J6 |
decreased erections. The father admitted using a testos-0 m- L8 k7 x# K+ K
terone gel, which he concealed at first visit. He was  D' N" z; s6 j: O' X3 J
using it rather frequently, twice a day. The Physicians’
$ S& q3 z: x6 x+ e# n) EDesk Reference, or package insert of this product, gel or' Z  [  b2 L( V6 l
cream, cautions about dermal testosterone transfer to& R* Q% P" ^% Z* f+ a
unprotected females through direct skin exposure.1 @% s$ P  L" R5 t+ L
Serum testosterone level was found to be 2 times the
, W8 \. c7 `/ O. K: Z7 {8 p" h4 dbaseline value in those females who were exposed to
9 h, u4 O) H' J& q9 xeven 15 minutes of direct skin contact with their male( U1 {9 W* Q5 z! M# k: [
partners.6 However, when a shirt covered the applica-2 [! I3 o! N0 T
tion site, this testosterone transfer was prevented.
& q: K" j) H' l8 E6 Z' C  p% hOur patient’s testosterone level was 60 ng/mL,  p1 G, C/ [- i! u4 U( C: v" e
which was clearly high. Some studies suggest that" y& ?( y5 J* p2 ]; Q6 Y+ Q4 a
dermal conversion of testosterone to dihydrotestos-% a1 m! I7 n5 S9 o) D" Z
terone, which is a more potent metabolite, is more3 c0 j2 P) S+ a2 Q
active in young children exposed to testosterone  R2 h! c4 a$ b/ x( o. f
exogenously7; however, we did not measure a dihy-
5 s" T! x* a& n, b( Rdrotestosterone level in our patient. In addition to
  ?1 M# ]' P) R; j! j: p: m9 R1 ~virilization, exposure to exogenous testosterone in
, M9 h5 [+ `$ T. n% {' ichildren results in an increase in growth velocity and
/ p% q+ ^) c" Zadvanced bone age, as seen in our patient.
: z4 R6 u' z0 {. {. W. _7 {8 ^9 nThe long-term effect of androgen exposure during+ p; |% a$ k) j( \/ ?9 `/ ~; M
early childhood on pubertal development and final
# V4 a8 r  k/ m' N% [; hadult height are not fully known and always remain. y' Z" S' l- h; ~* r
a concern. Children treated with short-term testos-
2 Q6 ^3 r7 Q1 u; E) H: rterone injection or topical androgen may exhibit some
, C* b( {: q* N& Jacceleration of the skeletal maturation; however, after; _4 X% o/ {. m1 }% m% t; t6 t* x
cessation of treatment, the rate of bone maturation
7 o3 v& e8 b6 R$ s( L; ]decelerates and gradually returns to normal.8,9
3 N5 ~! B, L* v) nThere are conflicting reports and controversy2 X( D7 J. I6 b
over the effect of early androgen exposure on adult
  u. s$ b7 T  Z' W- v- {  Zpenile length.10,11 Some reports suggest subnormal, y" }) R( B% Q/ m; f+ o* {
adult penile length, apparently because of downreg-1 d1 ?  i, D% U5 R9 e
ulation of androgen receptor number.10,12 However,( e. D& M5 R+ M0 s
Sutherland et al13 did not find a correlation between
  {8 o; f  ~5 J: uchildhood testosterone exposure and reduced adult
; L" I! J& C; g# y' d  Q0 }penile length in clinical studies.
: R/ t* S2 \. f. {" _- pNonetheless, we do not believe our patient is
( R+ y/ Y. e6 N. L! M3 Y7 ugoing to experience any of the untoward effects from' R% n6 o$ u: E7 @  P" e, t+ N
testosterone exposure as mentioned earlier because# }& {2 J; m" ^! I7 @9 I7 F, N7 h
the exposure was not for a prolonged period of time./ B5 y$ ^+ v5 M/ _$ t2 K3 Q
Although the bone age was advanced at the time of
) W- A* J6 ^1 P8 E# C: u8 Ddiagnosis, the child had a normal growth velocity at
  _$ ~1 }4 O, e1 d9 Pthe follow-up visit. It is hoped that his final adult
2 l1 X: |: \; yheight will not be affected.( v/ q( i# M: ^4 M: c- s) p
Although rarely reported, the widespread avail-
9 E" O# G! ~" X6 s; Aability of androgen products in our society may: R. p  {! G- ]- H
indeed cause more virilization in male or female7 u+ a. R6 Q. J( ?) a
children than one would realize. Exposure to andro-
9 O  ?' ^/ J1 igen products must be considered and specific ques-- @: f# ^  t' z5 B  P+ n
tioning about the use of a testosterone product or
. b4 w2 W1 N, y  h+ d0 `gel should be asked of the family members during: z0 [% r, Q2 n) @. e
the evaluation of any children who present with vir-
+ J/ N+ l6 j$ \5 g+ v; q/ Hilization or peripheral precocious puberty. The diag-2 q/ I& o; d% ]
nosis can be established by just a few tests and by
1 a( M  h/ G3 Z. ^. s/ iappropriate history. The inability to obtain such a
" h+ b2 o- s5 @. t/ zhistory, or failure to ask the specific questions, may6 M. V/ \3 X" n5 ]0 f, y
result in extensive, unnecessary, and expensive! T; g* G9 |& b
investigation. The primary care physician should be
' Q' C* O0 ?$ I, p3 {& c# Eaware of this fact, because most of these children. D4 r7 c5 a* t# O; Y
may initially present in their practice. The Physicians’$ v8 B( G% l# X- @% ~/ W
Desk Reference and package insert should also put a$ ^; X8 n4 k- c
warning about the virilizing effect on a male or
+ ~; p3 h* u8 X* Yfemale child who might come in contact with some-9 _+ w8 W9 ~% e4 W+ V! g
one using any of these products.
! Q# M/ B  L' R, kReferences7 B) F2 H7 x4 T
1. Styne DM. The testes: disorder of sexual differentiation
0 G- q) h# W' \3 M3 \6 Qand puberty in the male. In: Sperling MA, ed. Pediatric! Z; p+ O" A" [, j
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
2 V" G! i0 f, o2002: 565-628.
8 I% Z* T6 y5 i2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious" u* U5 K9 l9 F1 d. I/ I& H
puberty in children with tumours of the suprasellar pineal
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Sexual Precocity in a 16-Month-Old
! v$ l4 O4 F+ IBoy Induced by Indirect Topical+ A( C. C6 T7 \- X5 O
Exposure to Testosterone
# b# C2 |- Q5 A, X+ {6 FSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
5 k2 `* v! Y6 n# o  |; I. l) K( nand Kenneth R. Rettig, MD1* k9 q& a8 f2 h& _: X
Clinical Pediatrics5 Q3 P! ]* j+ z) h3 M2 S( T* C
Volume 46 Number 6
; b3 o0 y% o: V. X  p; G0 fJuly 2007 540-543
, Q7 e; U7 r( W2 F8 W& z© 2007 Sage Publications1 I  w! C2 h8 x9 g9 F+ t$ h, w
10.1177/00099228062966514 w" H; B. `& }% w8 g! ]0 a
http://clp.sagepub.com
& a- \9 v2 _- P% A6 b+ uhosted at
. ^3 h/ c' c3 Jhttp://online.sagepub.com& r, E2 ~* m( \$ G  c
Precocious puberty in boys, central or peripheral,
7 U3 l4 d; s  G! @& v2 L$ zis a significant concern for physicians. Central
5 A9 L1 B1 o5 @- }$ b, Fprecocious puberty (CPP), which is mediated* P$ S! a& y7 s' W% h8 y
through the hypothalamic pituitary gonadal axis, has
5 m6 {) |6 C5 @9 `- F: [5 ia higher incidence of organic central nervous system5 K" J# X$ E* N' t
lesions in boys.1,2 Virilization in boys, as manifested
3 a* |) e( a5 g# L' ]' Jby enlargement of the penis, development of pubic
* w6 b4 w; j' k2 d* Ihair, and facial acne without enlargement of testi-3 ]: A! k! F7 W, ^+ P
cles, suggests peripheral or pseudopuberty.1-3 We- H5 B' y3 a3 v
report a 16-month-old boy who presented with the
  f1 A( s. N( [% qenlargement of the phallus and pubic hair develop-
8 J( u/ E) v5 `- K( j0 [# cment without testicular enlargement, which was due
% Z( H0 j6 l- e6 S' p5 j; pto the unintentional exposure to androgen gel used by1 ^# S; ^# v0 R
the father. The family initially concealed this infor-
2 ~! }6 U* D+ m- n( T, S+ ^mation, resulting in an extensive work-up for this
: `) Q1 [) L% D5 A0 Hchild. Given the widespread and easy availability of
& _8 I4 Q1 f' W( Etestosterone gel and cream, we believe this is proba-
( w. \+ `1 `/ I# E' B0 Cbly more common than the rare case report in the9 z) m7 ?" ^: s3 V6 B0 b
literature.4" X9 m+ V$ S( V2 `
Patient Report! ]' f- \" E* O; \8 F& G, X
A 16-month-old white child was referred to the
, X+ J0 I# T$ S# w: m+ n0 _0 \endocrine clinic by his pediatrician with the concern
2 k8 K- Z6 u2 P0 \. o: pof early sexual development. His mother noticed
6 R) n& ^! Y; `2 Z  @! e' S, elight colored pubic hair development when he was4 T6 w, M8 X. s) K
From the 1Division of Pediatric Endocrinology, 2University of7 F7 O* j! Z8 P: X
South Alabama Medical Center, Mobile, Alabama.3 M, ?) v( O; C: T% l
Address correspondence to: Samar K. Bhowmick, MD, FACE,- Z6 w2 ]. B) v+ \* s7 q& A
Professor of Pediatrics, University of South Alabama, College of
% b. \3 X0 w7 T* t; }7 D# H) yMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
$ o) H  Z8 o+ N. Ze-mail: [email protected].
( Z( \( O8 A4 u4 d; u9 Q8 ]2 {* Kabout 6 to 7 months old, which progressively became
3 U3 f" D9 \  m* O, y& |$ bdarker. She was also concerned about the enlarge-) [) n( o1 `. F- s# L% [
ment of his penis and frequent erections. The child
0 d0 u/ ]* F) N* B; n. ?was the product of a full-term normal delivery, with
- c" Q: r" G9 Y8 ]* b0 Q1 Ea birth weight of 7 lb 14 oz, and birth length of
  x+ j/ H' G2 |2 U' Y! `6 O9 l20 inches. He was breast-fed throughout the first year- l* i: a3 L2 ~) C7 k
of life and was still receiving breast milk along with& R3 c5 M: ~; f. l! f. r3 ]/ M4 u
solid food. He had no hospitalizations or surgery," ~  G% |  S' g2 @1 C$ D* N5 ^
and his psychosocial and psychomotor development5 w2 M% r+ V- w4 X/ g, U2 T8 y" W
was age appropriate.5 X( t. j4 t( x. ~9 L2 n7 @- J5 O6 D
The family history was remarkable for the father,
" S; c( d& n3 q1 T) F9 L* Iwho was diagnosed with hypothyroidism at age 16,
/ S& M: u5 M( ewhich was treated with thyroxine. The father’s$ P- \9 G1 F+ a& [7 Q" c) w; `
height was 6 feet, and he went through a somewhat- g" w+ C  R# }( K: P' O0 \1 e
early puberty and had stopped growing by age 14.- ^; ~8 U, J5 Y
The father denied taking any other medication. The
7 u7 K4 g7 @9 y/ U$ X, J" m0 |child’s mother was in good health. Her menarche2 t5 x1 g' @" c- n
was at 11 years of age, and her height was at 5 feet- w0 o4 e7 p' }1 K: P. Z
5 inches. There was no other family history of pre-, h/ e0 }  a( l9 `9 L' k1 }# k
cocious sexual development in the first-degree rela-2 R( |3 \9 y4 k( i0 h
tives. There were no siblings.5 X% d5 V8 s/ ?2 S* R2 j6 `
Physical Examination
6 ]2 {2 t# p- F' \9 b: d' dThe physical examination revealed a very active,; \3 ^+ \# N1 O/ S- H& e9 k
playful, and healthy boy. The vital signs documented
* a0 p3 y9 V7 O; U2 ha blood pressure of 85/50 mm Hg, his length was  a; @1 n6 s2 t; w
90 cm (>97th percentile), and his weight was 14.4 kg
7 B& o$ r  {" V$ ~5 W* T/ Q. {(also >97th percentile). The observed yearly growth- w/ T& u$ b/ d6 T
velocity was 30 cm (12 inches). The examination of
6 U  ?; Q4 p4 R: Y3 @- k; bthe neck revealed no thyroid enlargement.
+ S" c# O2 @  }8 iThe genitourinary examination was remarkable for
# a; A/ g7 G" D; U, |1 Venlargement of the penis, with a stretched length of' ~7 V2 T5 z7 `( \$ T8 w
8 cm and a width of 2 cm. The glans penis was very well) g( z" S+ O, k. [
developed. The pubic hair was Tanner II, mostly around
* _, C2 b! D# @8 U" k& `) x7 i5404 j/ _. K8 e! B- C" L
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
) W1 |. |# b. O1 }% A& Cthe base of the phallus and was dark and curled. The5 G# a: R' i/ y$ M5 n$ N+ ]5 `1 @# J
testicular volume was prepubertal at 2 mL each.
* L: E% G4 y3 L2 z! _The skin was moist and smooth and somewhat7 q  F/ `4 a  f& ]6 M
oily. No axillary hair was noted. There were no
" ~' N: }5 O9 J8 k# U- t2 aabnormal skin pigmentations or café-au-lait spots.
- E4 s4 z8 a  f2 o, _1 }" wNeurologic evaluation showed deep tendon reflex 2+
* [- N7 ^/ U/ Z7 Q2 t" y* ^bilateral and symmetrical. There was no suggestion
* M# M+ `# T5 m/ _& L; w8 uof papilledema., ?! V0 N8 K2 H1 r, P" V2 g
Laboratory Evaluation
, b: j! E( O2 d9 sThe bone age was consistent with 28 months by+ |, L# ~$ D$ p' L
using the standard of Greulich and Pyle at a chrono-2 d. Y1 |) c0 R1 C& f
logic age of 16 months (advanced).5 Chromosomal/ z6 d- G) v/ r, n+ M7 f
karyotype was 46XY. The thyroid function test
- R8 a2 S8 f- vshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
6 N5 ~% l" O; Qlating hormone level was 1.3 µIU/mL (both normal).
2 n1 q- l6 w: d& Z8 y" DThe concentrations of serum electrolytes, blood
6 r8 V+ n( Q  i; D) S4 Y8 Y0 X2 |urea nitrogen, creatinine, and calcium all were
" b# z/ D; P" g3 p. ]0 Y$ c: Cwithin normal range for his age. The concentration4 `# W1 G* @3 F& A8 S' t3 t
of serum 17-hydroxyprogesterone was 16 ng/dL" ^7 |6 c3 a$ T4 O2 X
(normal, 3 to 90 ng/dL), androstenedione was 20% O) q2 `7 k9 F1 m
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-' m6 I2 V' A8 u3 \4 d
terone was 38 ng/dL (normal, 50 to 760 ng/dL),# |8 P: _0 C7 \: S. s
desoxycorticosterone was 4.3 ng/dL (normal, 7 to$ e& k. ^$ v' V. Q
49ng/dL), 11-desoxycortisol (specific compound S)! e6 Q1 W* f( V! p
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-, Y! m/ s4 q4 n2 g
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total% v! f5 G5 Z- r+ [( Z
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),! c; j  k( I' Z- G" {% Y
and β-human chorionic gonadotropin was less than% l6 d5 J7 ?0 l( ]' A5 D
5 mIU/mL (normal <5 mIU/mL). Serum follicular, A, S$ B' J$ M) p0 u; M4 L
stimulating hormone and leuteinizing hormone* l" l+ ]' c1 A, p0 w5 O
concentrations were less than 0.05 mIU/mL
$ K0 ?: K( G7 X7 ](prepubertal).2 J7 L+ ^2 Y# x8 F
The parents were notified about the laboratory
7 L1 @& C1 z% o" e& bresults and were informed that all of the tests were- I9 u* ]+ K  E7 Q, Y1 [
normal except the testosterone level was high. The
. U$ G, o8 K1 I& ^* ~follow-up visit was arranged within a few weeks to
9 x, ]% \; }) r9 }obtain testicular and abdominal sonograms; how-
, R; m+ V) H  u& z0 X  a, \ever, the family did not return for 4 months.
5 j. e: X# v0 yPhysical examination at this time revealed that the, ?9 |  z4 L  i& D
child had grown 2.5 cm in 4 months and had gained
& {7 v- r' ^% W: g5 Y$ z  n2 kg of weight. Physical examination remained
$ @1 G: ^# T/ C8 Y% a6 Funchanged. Surprisingly, the pubic hair almost com-# y- }& K2 F: c
pletely disappeared except for a few vellous hairs at: o- x; F& i1 J/ Q
the base of the phallus. Testicular volume was still 2
! p( N& n5 c& S; c* j* [) z; PmL, and the size of the penis remained unchanged.  o8 f  e$ o; |9 f9 t  Q* s9 |
The mother also said that the boy was no longer hav-5 c& `; `3 W. F% L8 K
ing frequent erections.
' r& e$ M; r% m: {  `' e# LBoth parents were again questioned about use of
! a) H; K/ G) Oany ointment/creams that they may have applied to# h. r2 N6 R3 S0 d
the child’s skin. This time the father admitted the2 U9 @" F& _3 W1 `
Topical Testosterone Exposure / Bhowmick et al 541
. a3 ?# v2 s) d8 iuse of testosterone gel twice daily that he was apply-! g+ @& v" |- y6 k3 D
ing over his own shoulders, chest, and back area for. A3 u# F1 n3 C" D0 p# H1 B+ B
a year. The father also revealed he was embarrassed
+ Q9 f3 @" b2 f% e* ato disclose that he was using a testosterone gel pre-6 n0 t! Q/ k0 N" W9 V( D+ c6 B
scribed by his family physician for decreased libido; }8 R1 A4 ^' x# s  l6 F, r
secondary to depression.9 `7 n  J  P( S  ]
The child slept in the same bed with parents.
/ V% G" @) ^  M4 y3 X$ hThe father would hug the baby and hold him on his  K! M1 H( \/ P+ P* @" }
chest for a considerable period of time, causing sig-
, w: G- O5 y' O: G, M# Dnificant bare skin contact between baby and father.
0 D# s" @9 K1 v5 [The father also admitted that after the phone call,
8 t9 R# g; Y' y0 K) E/ a: zwhen he learned the testosterone level in the baby3 r. c( c7 C7 X( d# G
was high, he then read the product information$ b8 q* ?7 T+ k+ N/ z: m
packet and concluded that it was most likely the rea-7 d# j5 V# u, s5 x) D) j3 }
son for the child’s virilization. At that time, they
$ Y6 d; M! f& W+ k' A" [/ ?( u2 Udecided to put the baby in a separate bed, and the8 c- f+ b8 y, F6 L' |. k( P9 ]
father was not hugging him with bare skin and had
; Z/ A, {7 R8 dbeen using protective clothing. A repeat testosterone
+ v; ]. S4 S5 dtest was ordered, but the family did not go to the7 N& o7 E2 K+ b: j' l
laboratory to obtain the test.! t$ R" O/ }' C: n, @& ]; _
Discussion
4 c7 E+ P- h0 q3 o0 p% xPrecocious puberty in boys is defined as secondary- p8 j4 L6 I# f2 A! v. c" \8 y! t
sexual development before 9 years of age.1,4
4 n. H9 y7 l1 l- E: ~Precocious puberty is termed as central (true) when1 ^' w# z6 B5 d" i
it is caused by the premature activation of hypo-& x, w' A; J* h( e
thalamic pituitary gonadal axis. CPP is more com-
* F4 u" ]" |+ ?. |mon in girls than in boys.1,3 Most boys with CPP
, ^& @$ J) L5 Y5 x# W/ xmay have a central nervous system lesion that is
; K3 ]% _/ z/ dresponsible for the early activation of the hypothal-* f- o6 V/ K, m8 u' Y' w
amic pituitary gonadal axis.1-3 Thus, greater empha-  l$ M5 [" Y- H8 S" j
sis has been given to neuroradiologic imaging in! s* g; ~* E' l+ d
boys with precocious puberty. In addition to viril-% O( J: Y9 _& _9 ?
ization, the clinical hallmark of CPP is the symmet-8 b9 u" L& K) p9 F! g( y
rical testicular growth secondary to stimulation by1 P3 f) F1 g3 E  s$ A3 [
gonadotropins.1,3
& l+ Y! x3 C8 V* `7 gGonadotropin-independent peripheral preco-
, L, u0 ?% B1 @3 A2 B# ecious puberty in boys also results from inappropriate
% s) I: G/ k: i! L- D+ _) randrogenic stimulation from either endogenous or) W+ O$ E7 T2 s0 Q
exogenous sources, nonpituitary gonadotropin stim-0 v/ t0 A% @" ]9 T
ulation, and rare activating mutations.3 Virilizing
8 {; f, S7 Y' I$ Ncongenital adrenal hyperplasia producing excessive
/ d. ?% j3 O4 k- Oadrenal androgens is a common cause of precocious
* g* d* I" v4 {% |  @0 Qpuberty in boys.3,4
- t/ t' y/ a; g5 V3 W! M0 d6 HThe most common form of congenital adrenal
- B" u8 w$ _* J3 K" V) {6 chyperplasia is the 21-hydroxylase enzyme deficiency.
8 E- h$ |& M; fThe 11-β hydroxylase deficiency may also result in; ?, @4 @1 @. p0 |: u
excessive adrenal androgen production, and rarely,
$ s7 Y7 y0 _5 b  i' y8 h2 m( van adrenal tumor may also cause adrenal androgen. p. z  z& M0 U/ w6 f9 u
excess.1,3
, A2 c1 M; p4 J3 K0 kat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
9 X5 F7 E* g( O' G" x542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
- r; O# D+ D9 K0 M" ]  ZA unique entity of male-limited gonadotropin-
% H" U/ }# O+ uindependent precocious puberty, which is also known7 z- U. o3 ~( v$ \0 J4 Y! @* ~
as testotoxicosis, may cause precocious puberty at a8 d1 H' c0 U. C/ l" G- R
very young age. The physical findings in these boys9 q/ s7 ?2 ]4 h& ?/ S9 q5 c
with this disorder are full pubertal development,
  ~) f) @) s& n! sincluding bilateral testicular growth, similar to boys0 P6 d- b; t7 b
with CPP. The gonadotropin levels in this disorder
. @2 l5 w3 a  L, T3 `8 Z, X: ware suppressed to prepubertal levels and do not show
/ }1 h% |: B' v6 Y' S, X+ `pubertal response of gonadotropin after gonadotropin-
" k0 i- r/ m. c" L5 X; b8 Creleasing hormone stimulation. This is a sex-linked0 W# o( A& ]: U
autosomal dominant disorder that affects only
% c, @* q7 j7 q6 qmales; therefore, other male members of the family# [0 F9 M: U. r8 w/ C. v
may have similar precocious puberty.3
% f2 h  L- P$ |1 B% [$ A2 Z9 ^In our patient, physical examination was incon-; K0 Y( M& |3 |1 F2 ]2 ?9 t* c
sistent with true precocious puberty since his testi-  g% _, P  t8 \
cles were prepubertal in size. However, testotoxicosis6 Z) J7 H' H" P% K+ p# b1 b# b
was in the differential diagnosis because his father8 Q" @' X9 x) H# d5 h! `
started puberty somewhat early, and occasionally,/ Q5 v! r9 P( `4 V) u% |
testicular enlargement is not that evident in the) F1 n4 P, a9 }# m1 v6 V
beginning of this process.1 In the absence of a neg-& R# V# I( ?7 n
ative initial history of androgen exposure, our
( R6 v7 U7 l- j$ tbiggest concern was virilizing adrenal hyperplasia,
  N5 I6 e. H+ b+ Q& h4 ?/ J) |1 Teither 21-hydroxylase deficiency or 11-β hydroxylase+ F, E# m' i. c' ~
deficiency. Those diagnoses were excluded by find-
3 G1 E, H3 D6 A9 h% b7 D0 R: Aing the normal level of adrenal steroids.' _: `; m, @, Q5 M& A& F
The diagnosis of exogenous androgens was strongly6 N4 f3 K- f4 f( g) i2 b
suspected in a follow-up visit after 4 months because) K  h; K, k9 |" [4 d- K  i
the physical examination revealed the complete disap-
9 G' N& F2 l1 K" h- hpearance of pubic hair, normal growth velocity, and
! L- p4 ^/ O7 y& Qdecreased erections. The father admitted using a testos-0 ]7 }/ ]4 R5 f$ H2 {$ r
terone gel, which he concealed at first visit. He was9 N1 ?7 Y) g( q( h
using it rather frequently, twice a day. The Physicians’+ ]  K) L, e' T
Desk Reference, or package insert of this product, gel or0 \* A: L- Y$ D  b- A2 M
cream, cautions about dermal testosterone transfer to6 ^- K: z6 k' A/ E2 C* ]& d
unprotected females through direct skin exposure.
$ R/ r  g2 v, T+ }  Z+ e4 Y8 `Serum testosterone level was found to be 2 times the
- {* K2 M; X4 i. K7 b! Rbaseline value in those females who were exposed to
/ u# M, ^+ a5 S' O4 O! V+ g$ Eeven 15 minutes of direct skin contact with their male' r# t  T, K+ F5 Z6 E2 G% i
partners.6 However, when a shirt covered the applica-; ^  h0 h6 f4 ~0 R- I
tion site, this testosterone transfer was prevented.
; _/ T+ n9 |# t( d# P' t: fOur patient’s testosterone level was 60 ng/mL,( r3 f9 K) e3 w; u6 h- }5 c
which was clearly high. Some studies suggest that- P9 F6 P2 E  F1 s
dermal conversion of testosterone to dihydrotestos-6 R( G- z$ c* b' G
terone, which is a more potent metabolite, is more, l; O. l, z  t5 m: T, ]/ j
active in young children exposed to testosterone( x$ W9 U* q) R- i3 D
exogenously7; however, we did not measure a dihy-2 \- M5 G  l8 d7 w* N" m
drotestosterone level in our patient. In addition to0 n$ A5 _: g& d; z1 K  |8 R* R% J
virilization, exposure to exogenous testosterone in0 t1 g6 C- \# m& J7 b) ^
children results in an increase in growth velocity and
% a: F/ ~* s4 [6 N; O; ^; kadvanced bone age, as seen in our patient.  M0 g; z; E! o3 m: G
The long-term effect of androgen exposure during7 C; ]( W& x$ b: {$ {- P) l. n
early childhood on pubertal development and final4 z( }7 j% k# A. }5 i& s
adult height are not fully known and always remain4 P3 P2 z/ Z3 g5 S" y9 D/ O. I
a concern. Children treated with short-term testos-1 S" N+ _+ ^9 `9 l
terone injection or topical androgen may exhibit some$ J" G& y" a/ k4 q$ Q; H" `
acceleration of the skeletal maturation; however, after
8 H8 B: A& A8 m/ w6 h; X+ r; Dcessation of treatment, the rate of bone maturation
  |5 L5 S6 l% R1 ~$ Tdecelerates and gradually returns to normal.8,98 H( l; A3 G+ D0 @+ g. r
There are conflicting reports and controversy+ H8 a1 w, i# ?. ]% k
over the effect of early androgen exposure on adult6 |# v: ?1 U% A
penile length.10,11 Some reports suggest subnormal& a) a& w4 r9 j! D9 e6 c. ~
adult penile length, apparently because of downreg-1 {2 ^: o4 l0 A. Y% P0 J! w
ulation of androgen receptor number.10,12 However,
! \8 A; ]/ i/ N0 y0 k2 k! uSutherland et al13 did not find a correlation between
4 t. o$ A7 t6 s: Q3 l! Nchildhood testosterone exposure and reduced adult
& X8 ]% J, N+ s" Qpenile length in clinical studies.: `/ x/ k( \, \7 K9 G
Nonetheless, we do not believe our patient is
; G4 ?4 e$ Z, {) V' h, J+ r) Vgoing to experience any of the untoward effects from
0 f; F* Y% E1 Z; n7 s+ g" gtestosterone exposure as mentioned earlier because3 l( b( h7 A3 r; O
the exposure was not for a prolonged period of time.) D: f& @! h" X* r6 K$ G4 N
Although the bone age was advanced at the time of3 o: M& G8 e/ B
diagnosis, the child had a normal growth velocity at2 O7 j8 F+ D% q; |9 N! g$ y" N
the follow-up visit. It is hoped that his final adult* O- ^, `" `, E$ Y* l/ k
height will not be affected.
+ C2 e5 u7 T0 ~" O( [3 P, HAlthough rarely reported, the widespread avail-: r  w, {& a2 T& b/ W8 a$ X
ability of androgen products in our society may
+ ]0 K) Q7 `' q4 a% s" B, iindeed cause more virilization in male or female- G/ a# U3 M* C8 c6 F5 {2 S
children than one would realize. Exposure to andro-
$ N3 f1 b: D* x# @gen products must be considered and specific ques-1 R* }0 e: W: P/ x3 L8 ]  `
tioning about the use of a testosterone product or/ A+ J# n) l" R4 v8 X6 l
gel should be asked of the family members during
' O' V4 J  @- U7 Q& _the evaluation of any children who present with vir-
+ P9 L" x; w# lilization or peripheral precocious puberty. The diag-
( E/ ?' R" W2 c3 v& N' k" e" Enosis can be established by just a few tests and by7 X' v- t, y1 U& @' ~: s3 n0 r
appropriate history. The inability to obtain such a& e' M8 l4 s' X$ X# ]3 ]4 I( j9 T
history, or failure to ask the specific questions, may' c2 {9 {: M* x% X( d, n
result in extensive, unnecessary, and expensive
% m. i; u5 b0 U" @- zinvestigation. The primary care physician should be6 T. r) @% Q$ L/ X6 v
aware of this fact, because most of these children
' w/ d  @, c6 {% amay initially present in their practice. The Physicians’7 a' Z% D' [4 H' B
Desk Reference and package insert should also put a
. S! I4 G  F6 p! pwarning about the virilizing effect on a male or, R& p3 k% F- M6 o& W
female child who might come in contact with some-
( z) i) ^$ J4 A* A9 zone using any of these products., o; N' w- J: F' i# s
References
- F2 H/ L9 v$ i$ s: j1. Styne DM. The testes: disorder of sexual differentiation4 g5 ]# Y' X6 \( I( X) E
and puberty in the male. In: Sperling MA, ed. Pediatric
! i/ Y/ r, o0 k; {2 n! f0 sEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;2 d7 |9 I  z! Q/ A' [5 Q# h% ~9 k
2002: 565-628.9 P# y7 Q" {" b" l- s  G4 q
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious/ y) r# ~  l6 u4 e- b& A! z$ s
puberty in children with tumours of the suprasellar pineal
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女厕偷拍辅导班主任尿尿老师的逼很嫩还有一点
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4个什么样的?
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- z7 a- f, B5 P
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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