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
1 Z: n  d% [3 n) b' l. p! IBoy Induced by Indirect Topical! X4 \" c: c/ L) c5 k: v# {
Exposure to Testosterone
) E& s( d( D- I5 u. V5 HSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2: m  U: e! Q0 V1 \( K/ ]
and Kenneth R. Rettig, MD1' U3 Y0 n! }' W* b, j
Clinical Pediatrics  \0 J* ?5 h: E- ?# r/ Z
Volume 46 Number 6
& I) V1 G/ D% a7 ?) c2 a! eJuly 2007 540-543
& C4 A" g7 {% _8 t  k/ z5 m, [© 2007 Sage Publications
- O2 f* X' C# y6 b9 f10.1177/0009922806296651
2 r7 x2 j  x1 Shttp://clp.sagepub.com
& D4 S% V5 U: ?$ Ahosted at
8 r6 P/ B/ p9 t2 q, t8 j) ^" }/ g. B/ ?( Uhttp://online.sagepub.com
, S* y+ k. c$ X8 Y" N" K# p  qPrecocious puberty in boys, central or peripheral,
1 ]. ^: g! o; mis a significant concern for physicians. Central
$ Y, m0 n2 p# c9 a% C. z5 Aprecocious puberty (CPP), which is mediated
0 c; }* E* a% `" U; K. jthrough the hypothalamic pituitary gonadal axis, has" g8 E& X8 ~- a; p: A: Y% L- q
a higher incidence of organic central nervous system
3 |# v  @2 c8 z, U- f/ h2 glesions in boys.1,2 Virilization in boys, as manifested8 f! t" Z1 |1 G8 f8 _
by enlargement of the penis, development of pubic$ T; Y6 E: f, }: Q. h8 Z; ~
hair, and facial acne without enlargement of testi-
: X; U" W7 Y7 Tcles, suggests peripheral or pseudopuberty.1-3 We7 I! a: e' ~4 I
report a 16-month-old boy who presented with the
* s0 M/ T# r- p0 N9 g' H' Venlargement of the phallus and pubic hair develop-
& q. H! P! T  s8 j7 p- {9 zment without testicular enlargement, which was due: f& j2 w4 w2 W+ g" H: s+ B5 U. A
to the unintentional exposure to androgen gel used by, C& B- ~4 L0 J% z4 V7 Q
the father. The family initially concealed this infor-
/ d, `7 R! ?% D, E& X0 Tmation, resulting in an extensive work-up for this
+ k- X' \7 f7 Ychild. Given the widespread and easy availability of
' B( H/ S! r5 j6 q" Y/ g0 ?testosterone gel and cream, we believe this is proba-2 h4 J5 D# C* C9 q' D' I; \
bly more common than the rare case report in the: y" w: {/ }' Q/ @* {1 a0 i
literature.4
! ]$ V, b. }. KPatient Report+ X) g0 ]) m0 m+ L( j' d. }
A 16-month-old white child was referred to the+ O& q2 a. w) S
endocrine clinic by his pediatrician with the concern! _+ M" N, ^  L# a; O
of early sexual development. His mother noticed
8 s) ^, E# l5 Zlight colored pubic hair development when he was
2 N1 L  W) U) ^+ U0 q% `From the 1Division of Pediatric Endocrinology, 2University of
2 V& Z  [+ l: x7 x2 qSouth Alabama Medical Center, Mobile, Alabama./ t  i3 {- V8 X
Address correspondence to: Samar K. Bhowmick, MD, FACE,
3 f7 N$ @! W( o5 HProfessor of Pediatrics, University of South Alabama, College of
( F4 [, T/ q: w* NMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
! N( O( R7 {" K5 o+ p  H6 Te-mail: [email protected].) M7 |; r7 `- G5 ?
about 6 to 7 months old, which progressively became0 x5 p# H3 O' \/ ^; v5 y8 J
darker. She was also concerned about the enlarge-+ U) ^: l: G  p' d
ment of his penis and frequent erections. The child
% L5 e6 W, w* {0 Vwas the product of a full-term normal delivery, with$ @8 l; \0 M! g
a birth weight of 7 lb 14 oz, and birth length of
0 [* Y! A6 Q7 K# d20 inches. He was breast-fed throughout the first year
( g. G( {9 }: hof life and was still receiving breast milk along with# i( x0 z- t$ R& r
solid food. He had no hospitalizations or surgery,8 ~$ v- D' L2 M. A& [7 V- D' K
and his psychosocial and psychomotor development
6 @  m1 o' @6 N& O3 }* A# q/ nwas age appropriate.
* e) d5 D6 g- T+ mThe family history was remarkable for the father,0 r3 ]' d! O3 j: W8 i/ s
who was diagnosed with hypothyroidism at age 16," y! E  ~4 S% P/ S+ m( G
which was treated with thyroxine. The father’s
  d: V3 p/ l3 R" k& v# v% P; lheight was 6 feet, and he went through a somewhat, Q' x' D" ~9 v+ g
early puberty and had stopped growing by age 14.
6 J6 p8 E# i& R# V3 YThe father denied taking any other medication. The
: e" g+ I0 u& p5 I/ Y( Gchild’s mother was in good health. Her menarche% T- p8 x; D% c6 ?
was at 11 years of age, and her height was at 5 feet1 Z( C  Q" c' c5 U" F7 h! P
5 inches. There was no other family history of pre-
  l7 N& q1 S7 N: m' H1 A) N  ]! t' ococious sexual development in the first-degree rela-
5 u) @( N$ J5 D8 D7 r' a7 B/ Z; _tives. There were no siblings.9 J1 o' j' x# N" k* y# j- o
Physical Examination2 H. `6 i, ?. u% l. b0 {
The physical examination revealed a very active,. H5 a- ?( }9 |7 ?8 w
playful, and healthy boy. The vital signs documented
$ |" b$ W' o4 h- Ca blood pressure of 85/50 mm Hg, his length was
( F& G  G, }+ Q  `9 s90 cm (>97th percentile), and his weight was 14.4 kg$ c3 p) M( O+ Q$ c% c+ ]
(also >97th percentile). The observed yearly growth
8 i1 U, [! T6 J+ ^9 J* Gvelocity was 30 cm (12 inches). The examination of; k8 g, B) A3 Z9 I
the neck revealed no thyroid enlargement.7 x2 k: Y  t: V! H! F& l
The genitourinary examination was remarkable for
3 e4 u/ l1 n! E7 s7 @! W6 penlargement of the penis, with a stretched length of
( t  I- E8 r$ K! [' b8 cm and a width of 2 cm. The glans penis was very well6 H& t, @% z3 p/ I
developed. The pubic hair was Tanner II, mostly around
/ j* f2 ?; M/ T% }. r5405 |5 a& T* F* T
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from& G& C7 Q8 E0 Z( ]
the base of the phallus and was dark and curled. The+ r8 ^" n4 ~- ]: [6 o
testicular volume was prepubertal at 2 mL each.
- U; K$ c, n; y* d5 E4 r7 T1 mThe skin was moist and smooth and somewhat
& K  _1 A1 k4 joily. No axillary hair was noted. There were no: i1 b) V" z7 V8 J3 @
abnormal skin pigmentations or café-au-lait spots.
% h; C# f  N1 X2 A7 I' cNeurologic evaluation showed deep tendon reflex 2+
" m$ ^3 a+ J4 z/ Abilateral and symmetrical. There was no suggestion
6 h  c" [9 a7 h# A5 bof papilledema." e1 E+ J! a9 j* \9 r& d
Laboratory Evaluation
- A* f  B$ J6 o" w5 A+ hThe bone age was consistent with 28 months by* D6 m% }6 C4 k- Y9 B  B! _; X8 _5 w
using the standard of Greulich and Pyle at a chrono-
; T& v" u' K% z& p: L+ }) ]logic age of 16 months (advanced).5 Chromosomal( e9 }1 u; z7 l! b, g' g
karyotype was 46XY. The thyroid function test( {/ q0 E. u2 M' S' T  L% H
showed a free T4 of 1.69 ng/dL, and thyroid stimu-4 L& m- O3 {- [% j6 h9 z* z$ j
lating hormone level was 1.3 µIU/mL (both normal).. w( T, R) c! _, f: C5 X3 n
The concentrations of serum electrolytes, blood
/ u% w4 X# C% d4 t; Zurea nitrogen, creatinine, and calcium all were$ l0 P; G+ m) n7 g8 Q
within normal range for his age. The concentration4 P/ A3 f8 k# T2 v6 T" W5 @& u! ]# Y% S
of serum 17-hydroxyprogesterone was 16 ng/dL
6 X, W" P8 f; m# t(normal, 3 to 90 ng/dL), androstenedione was 20
5 E0 f' @, q( x, V( ?ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
8 l- K9 K* O2 L! B0 bterone was 38 ng/dL (normal, 50 to 760 ng/dL),
8 c6 x$ j& g2 N2 K/ p/ jdesoxycorticosterone was 4.3 ng/dL (normal, 7 to
7 y: x8 B* R/ M$ K: D49ng/dL), 11-desoxycortisol (specific compound S)
2 e" F; Q! N$ h6 V8 q* ]was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-' L$ ]) o. @4 Y) a5 D. q7 C- E6 ~
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total& t+ f# u, X! `8 d. H
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
3 J) W2 k" ]/ e. vand β-human chorionic gonadotropin was less than4 A5 G" d+ \5 B7 f5 J, [
5 mIU/mL (normal <5 mIU/mL). Serum follicular  }4 P) \! M( W. p2 N1 }6 ^
stimulating hormone and leuteinizing hormone' w1 S  `/ y2 z+ U% Q! _" w5 V
concentrations were less than 0.05 mIU/mL
! V6 K0 Z7 a) r5 _/ x& e; y2 l(prepubertal).9 Q7 q3 w$ [/ d1 S- E) e( C( w
The parents were notified about the laboratory+ ?: Z- |' k: @; |" Y4 p3 g
results and were informed that all of the tests were
# R1 \; A7 u. Q. k5 [normal except the testosterone level was high. The
! u- |8 f7 u; s+ l, w! \follow-up visit was arranged within a few weeks to
% K4 _, l) E5 L: y* h8 b( F, }obtain testicular and abdominal sonograms; how-
: E: j# d8 ^5 {. L5 \ever, the family did not return for 4 months.( w0 ^0 {) r/ _$ y& C0 @
Physical examination at this time revealed that the
) P8 S8 z" E* Wchild had grown 2.5 cm in 4 months and had gained, s3 Z  T3 ]; W. _& k- ~
2 kg of weight. Physical examination remained
4 z8 z$ A2 i- _; |unchanged. Surprisingly, the pubic hair almost com-8 \( |! N' R% e) |+ x. c' x
pletely disappeared except for a few vellous hairs at
( \8 x% b$ V% B# \the base of the phallus. Testicular volume was still 2+ `, ~1 F1 }. @* t' ?$ j
mL, and the size of the penis remained unchanged.
: {4 [3 c/ Q  B. ]4 kThe mother also said that the boy was no longer hav-
1 [1 {+ `( p6 n' [8 ning frequent erections.
( @- t' V8 K- r& `  ZBoth parents were again questioned about use of
' E; d, P/ `- D: W+ {* N0 Yany ointment/creams that they may have applied to+ b5 @6 ]8 }  _, q- ^, B1 S
the child’s skin. This time the father admitted the
& V; t; o. L5 h2 OTopical Testosterone Exposure / Bhowmick et al 541: Q3 f# Y) V* z+ x: E, F
use of testosterone gel twice daily that he was apply-, g- N9 {" R7 Y& K
ing over his own shoulders, chest, and back area for
; H7 Y: T& X  W. ?& f% @+ Z3 Z7 ua year. The father also revealed he was embarrassed. q, }. P/ U* @& _/ Z/ H( X- `
to disclose that he was using a testosterone gel pre-) F; O$ h( d- i% c
scribed by his family physician for decreased libido) ~- K8 T8 |! u. I" ]) r- x( m
secondary to depression.9 I* m- t+ H2 V1 w$ ?' k0 C) [3 u
The child slept in the same bed with parents.- j1 I. d4 a$ N
The father would hug the baby and hold him on his
/ H' n# ~7 r0 E( ?3 P( [6 S- xchest for a considerable period of time, causing sig-  l, h/ d- W: v( I( ^5 Z% ?
nificant bare skin contact between baby and father.
' J7 [/ I/ k3 n( [9 I+ q7 VThe father also admitted that after the phone call,
. }% w: ]$ Z# _4 r. kwhen he learned the testosterone level in the baby
5 K1 x, Z: ^3 f* a8 }( E+ \+ K4 [3 hwas high, he then read the product information
5 m9 L" u6 F; T+ r: a8 Apacket and concluded that it was most likely the rea-
: w" W: r/ V$ J3 n" f8 h' i4 Fson for the child’s virilization. At that time, they
1 j; f8 S0 o6 v4 i4 v0 a; edecided to put the baby in a separate bed, and the
1 V  D1 k5 d' m) j4 O( o7 [father was not hugging him with bare skin and had
/ T" i: F( G" g/ ~3 x# K8 \been using protective clothing. A repeat testosterone
- N) u4 J  a/ [6 I: Htest was ordered, but the family did not go to the3 Y, p; `2 B3 i+ d: j$ Y& ^% q, `
laboratory to obtain the test.( N3 H# q* l3 \5 y- C9 X
Discussion
& y6 w( ]5 o7 i! N: fPrecocious puberty in boys is defined as secondary
" O% O) z. T; c( q$ {2 i9 \sexual development before 9 years of age.1,4+ @7 P5 k) f( v) o4 \
Precocious puberty is termed as central (true) when
+ S  K9 U# |2 L/ _+ x3 v' pit is caused by the premature activation of hypo-) h  h. n* {9 s6 e, s
thalamic pituitary gonadal axis. CPP is more com-
/ Y" t! N4 q% g9 l+ y- @: wmon in girls than in boys.1,3 Most boys with CPP+ x+ C! }1 E: v. ^) g1 r0 g* ^
may have a central nervous system lesion that is
6 J1 `8 s- X: aresponsible for the early activation of the hypothal-
. a! x& \6 k$ J7 xamic pituitary gonadal axis.1-3 Thus, greater empha-. E, d* h3 w% W( {% p9 |+ o
sis has been given to neuroradiologic imaging in  d1 d, n  A/ i% d) ?+ h$ ^. Z
boys with precocious puberty. In addition to viril-
5 _, q* b# o. C, {ization, the clinical hallmark of CPP is the symmet-
2 g% y1 f- T' }& J* K3 irical testicular growth secondary to stimulation by+ ^' k5 r2 N9 H7 [$ |3 B
gonadotropins.1,3
4 l$ w: V4 y5 J/ X4 ?- U7 CGonadotropin-independent peripheral preco-
6 Z& D5 Q+ N" \  V5 d1 N# H- W/ mcious puberty in boys also results from inappropriate
/ I' G( N8 e/ B; B2 dandrogenic stimulation from either endogenous or& F6 w9 {' i9 m4 U* x6 H
exogenous sources, nonpituitary gonadotropin stim-' d- m, {" R/ {* j
ulation, and rare activating mutations.3 Virilizing
% E6 R0 T1 a- {  B5 }$ e0 Icongenital adrenal hyperplasia producing excessive
0 A1 A/ s# T7 d8 R' G# a# X+ F7 iadrenal androgens is a common cause of precocious5 p  S& h3 `! Z  }8 C- D
puberty in boys.3,46 S8 H* c1 a; d3 C( ^2 J+ c8 M: I" U0 [3 k
The most common form of congenital adrenal
& ]! _" P1 c4 T# I) a! t# \hyperplasia is the 21-hydroxylase enzyme deficiency.. h0 z7 v+ u' e* u3 j
The 11-β hydroxylase deficiency may also result in( Q! [$ Y- A. D% G4 K/ g1 s) O
excessive adrenal androgen production, and rarely,
4 Y( s: X& F( z3 p, a2 U, [2 R3 u; |an adrenal tumor may also cause adrenal androgen
6 ^8 ~1 J5 E& S" t* y" `excess.1,3
4 j" U3 g0 f' Q% f* }at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
0 H5 ^0 q  }- P. x% Y542 Clinical Pediatrics / Vol. 46, No. 6, July 20077 ~: L& V) J& ~7 |( s2 a
A unique entity of male-limited gonadotropin-
6 d+ Z  G, D5 x8 Q+ Y7 tindependent precocious puberty, which is also known; W" b4 i0 q" q/ y5 z/ M
as testotoxicosis, may cause precocious puberty at a
  z6 l* T$ ~% y. M% M% w0 q+ Dvery young age. The physical findings in these boys& a/ q  p) C$ ]3 B" [6 z, Z
with this disorder are full pubertal development,
( ?3 {- D* L9 \including bilateral testicular growth, similar to boys
4 B6 P3 K  O3 P3 Owith CPP. The gonadotropin levels in this disorder- i$ u6 E* |* C$ J! s8 }
are suppressed to prepubertal levels and do not show
5 i9 }2 @! m4 Bpubertal response of gonadotropin after gonadotropin-
) u7 }( j5 Y6 R& _3 Freleasing hormone stimulation. This is a sex-linked
$ V& V& v0 _3 c0 R  dautosomal dominant disorder that affects only
& X7 ]* m$ a# ?/ u: \3 Cmales; therefore, other male members of the family* s" y- y" E" D$ V+ _3 f, u) r
may have similar precocious puberty.3& ^. k/ N) ]5 j) h; U9 o+ j
In our patient, physical examination was incon-
  ]5 C) s+ @& a3 _: _5 Y0 zsistent with true precocious puberty since his testi-' ^4 C: J, i  a/ O
cles were prepubertal in size. However, testotoxicosis
8 g$ e; i8 S4 B& F: lwas in the differential diagnosis because his father6 ]6 ^; ^; p: D# Y; v
started puberty somewhat early, and occasionally,
% Z8 X9 D! d' {6 Z( m' Z' dtesticular enlargement is not that evident in the
4 M! ?& ]6 E, U# f  Ybeginning of this process.1 In the absence of a neg-
1 C$ J$ ]: Q! E% V# P# K6 B, Vative initial history of androgen exposure, our# ?* W) u0 [4 P; j" \
biggest concern was virilizing adrenal hyperplasia,
# D( x. ?# E+ Z: e4 zeither 21-hydroxylase deficiency or 11-β hydroxylase0 r& p. j! T* X. l- ?& i, M
deficiency. Those diagnoses were excluded by find-8 w: j+ B% \6 M* a! ~5 C. T
ing the normal level of adrenal steroids.2 h% Y3 e5 F( a7 C3 _" x
The diagnosis of exogenous androgens was strongly
2 c; N6 l  {/ f, q4 t' msuspected in a follow-up visit after 4 months because& x( O  ?- e9 ]3 i+ K0 y" Z
the physical examination revealed the complete disap-4 M5 I* p, \0 w4 ^. g7 R1 D) B
pearance of pubic hair, normal growth velocity, and9 K& f# @3 x8 w% f
decreased erections. The father admitted using a testos-
. M/ p% f6 q1 m  Xterone gel, which he concealed at first visit. He was
6 b, I/ M/ `( b) @using it rather frequently, twice a day. The Physicians’
- x9 ~! K  x8 ?# u( _. s8 bDesk Reference, or package insert of this product, gel or
5 G6 p" b7 R  ncream, cautions about dermal testosterone transfer to5 d. k% H% d* o1 ?/ U( p  N: x0 o- N
unprotected females through direct skin exposure.
" w% n# v; a3 ?( y6 [Serum testosterone level was found to be 2 times the
- Z/ ]7 V% F0 O* `0 tbaseline value in those females who were exposed to1 l* k# y: w: R9 m( _. n
even 15 minutes of direct skin contact with their male
7 k! b! |( a7 e, V7 ?" h$ H3 [partners.6 However, when a shirt covered the applica-. N$ n% I" D" ]" w+ @
tion site, this testosterone transfer was prevented.
% Q0 E* q% b2 y' U; {Our patient’s testosterone level was 60 ng/mL,$ Z3 I: G! d8 h. a0 l
which was clearly high. Some studies suggest that
7 g' p9 L, c- `dermal conversion of testosterone to dihydrotestos-2 c1 M* Y' ^2 ?9 m
terone, which is a more potent metabolite, is more/ \- |% y9 r& S9 X5 V
active in young children exposed to testosterone
6 s- y. e& O2 Q$ C( G  ?2 kexogenously7; however, we did not measure a dihy-
4 O: p$ J$ S7 B5 xdrotestosterone level in our patient. In addition to) c: ~1 N. t- d& `" Q: I0 ^
virilization, exposure to exogenous testosterone in
8 _: J" |1 I' Ichildren results in an increase in growth velocity and
" o* M6 j  x% e4 g* `) hadvanced bone age, as seen in our patient.
* e9 U- s4 }( Y$ U* o; c) W" E9 E+ bThe long-term effect of androgen exposure during
$ D6 |7 m- O$ v  Hearly childhood on pubertal development and final
; K! U4 d! c6 u% r# sadult height are not fully known and always remain% N$ X* p8 N% R
a concern. Children treated with short-term testos-6 K- |, t6 c/ ^. t  F  g; O
terone injection or topical androgen may exhibit some
4 }9 R2 v' H% s5 F, k3 t+ ^9 Lacceleration of the skeletal maturation; however, after  q( M$ ?1 _( T9 ?
cessation of treatment, the rate of bone maturation% Y% X+ a' `  n
decelerates and gradually returns to normal.8,9
$ G4 j5 V. X4 p8 uThere are conflicting reports and controversy9 O9 v* Z* O: v8 G
over the effect of early androgen exposure on adult
9 l) t3 p2 k, H3 T. W% B# v9 N6 @penile length.10,11 Some reports suggest subnormal
& U+ a) A1 X& z: h0 {- cadult penile length, apparently because of downreg-
/ D- P) Y  t# M$ e! X/ O8 _ulation of androgen receptor number.10,12 However,2 D* m$ t" T2 i/ {& |/ R2 L
Sutherland et al13 did not find a correlation between9 ~  M1 a  S4 v' y0 i
childhood testosterone exposure and reduced adult
8 u% k& W* Z# ~% ^penile length in clinical studies.3 B/ V4 G, E2 }9 d0 C
Nonetheless, we do not believe our patient is
' I6 `! W! |3 P/ F5 ]going to experience any of the untoward effects from) ]' G1 F3 w- b0 ?7 F
testosterone exposure as mentioned earlier because: `, ^8 w5 E: @+ g
the exposure was not for a prolonged period of time.
: q1 G! O6 V" m2 T. q! oAlthough the bone age was advanced at the time of
; v7 }/ z6 A' F) W0 Wdiagnosis, the child had a normal growth velocity at+ L/ {" V* \$ ~
the follow-up visit. It is hoped that his final adult; ?5 y5 F% @7 |) y2 `9 T. G
height will not be affected.
) B$ \8 {2 J: |" y7 r; KAlthough rarely reported, the widespread avail-5 C" D+ X/ p* l- H; B3 ~: V
ability of androgen products in our society may
7 }& ^- X0 ~1 m2 ~4 {$ yindeed cause more virilization in male or female6 n7 [( K- h  a# }, ?
children than one would realize. Exposure to andro-
/ _) W+ \. T3 u! Ugen products must be considered and specific ques-7 V) o" e' Z  u" o: g( i3 L
tioning about the use of a testosterone product or
9 s, c4 O! {  Q' wgel should be asked of the family members during3 k0 M2 o3 M. a9 |6 p) G) U
the evaluation of any children who present with vir-
- m6 C7 E3 F2 @* nilization or peripheral precocious puberty. The diag-4 D; m" d, M; |9 h. _
nosis can be established by just a few tests and by1 D9 N: o# V* F& O/ m, o
appropriate history. The inability to obtain such a
2 i( c( d0 C; @9 ~6 w2 C$ fhistory, or failure to ask the specific questions, may$ v) E% W" @9 P4 Y# R
result in extensive, unnecessary, and expensive
$ c0 a1 b) G- ?; d! E5 rinvestigation. The primary care physician should be7 C5 d% s0 s9 j! T4 p3 C
aware of this fact, because most of these children
" e7 ]. k: P2 D$ y* L2 A1 ?may initially present in their practice. The Physicians’' s3 ~% h% A* U5 @4 X- c
Desk Reference and package insert should also put a  }) D  I* M5 V3 k7 ^9 a4 g
warning about the virilizing effect on a male or: ^1 j: v6 v6 n! }: e
female child who might come in contact with some-
, o0 r* h# z/ x" y% K+ e4 v7 \one using any of these products.& N, c- g9 V! C0 i4 \! p
References
/ M9 ~$ Y; o4 R1. Styne DM. The testes: disorder of sexual differentiation  n* A5 L2 a8 `( F4 O4 w) v
and puberty in the male. In: Sperling MA, ed. Pediatric
* v0 |  ^  a+ a# W0 W. {, d8 uEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;6 l" i- Z  x2 l5 \
2002: 565-628.
6 S: f/ u9 O( v2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious6 e1 q0 Z, _  k5 Y
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
; Y# r# Y, l% I9 }7 rBoy Induced by Indirect Topical9 o$ n1 ?" a6 x0 I
Exposure to Testosterone
2 v5 Q! L: f, H9 }  KSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,29 l1 |+ h% L/ c( l( m
and Kenneth R. Rettig, MD1$ f; L. ~! V" @& n
Clinical Pediatrics" ^6 h# v- K8 ^0 c5 x  r4 S0 X
Volume 46 Number 6
2 `6 G- ^0 d7 K$ t* i9 D' s6 aJuly 2007 540-543$ D0 g# j" {" x6 {
© 2007 Sage Publications
( q8 X: [/ e; B( \7 c5 c" y' C/ N10.1177/0009922806296651+ ^% {7 W7 n6 a, u/ I+ X+ [9 f
http://clp.sagepub.com
1 I$ C" D. g( P. Ohosted at
& m$ p! P7 Q7 `# E2 lhttp://online.sagepub.com
  B* s- i+ t8 x, J+ H7 rPrecocious puberty in boys, central or peripheral,- i. K' U7 M# P& M3 Q( g
is a significant concern for physicians. Central
. e, M. n4 l' sprecocious puberty (CPP), which is mediated
9 m( u8 i0 _5 |3 A1 h  w7 |through the hypothalamic pituitary gonadal axis, has( o8 A" s+ E; ]0 \9 U
a higher incidence of organic central nervous system6 F% a5 S  N" ^
lesions in boys.1,2 Virilization in boys, as manifested
2 t  ]  y( ?; r2 D7 ]3 M* E3 y$ fby enlargement of the penis, development of pubic
& x1 d# ^# D# l& |+ Nhair, and facial acne without enlargement of testi-* F9 M- ]2 q; ]
cles, suggests peripheral or pseudopuberty.1-3 We- I7 U9 C- u9 D
report a 16-month-old boy who presented with the3 n* u; _5 o/ Q6 d$ j# I
enlargement of the phallus and pubic hair develop-
2 x) [3 p0 j) }1 `* Y) gment without testicular enlargement, which was due* f- Q: u) B5 m- l7 q% `. Z  z
to the unintentional exposure to androgen gel used by
( \7 v! E! X6 N9 l4 pthe father. The family initially concealed this infor-
1 e) C4 _4 E8 Q! ^" Rmation, resulting in an extensive work-up for this, V( N1 @; x5 }- v0 D. s" Q5 m
child. Given the widespread and easy availability of3 b8 [! s4 m' A6 `- F7 m/ [$ c
testosterone gel and cream, we believe this is proba-) i) T: p5 {3 n% c8 @" @& l
bly more common than the rare case report in the1 j' l' c5 R: p% u
literature.43 D$ q. u  i* ?$ _2 d/ A; \
Patient Report% [, q/ O% s" o/ t/ v
A 16-month-old white child was referred to the
# {, j3 N3 b* gendocrine clinic by his pediatrician with the concern3 b' g4 q/ [3 H
of early sexual development. His mother noticed, t3 q4 @; j) L- g, }. v
light colored pubic hair development when he was
5 X$ U1 L8 G! FFrom the 1Division of Pediatric Endocrinology, 2University of/ j( z" \7 w6 Q6 y" d6 m
South Alabama Medical Center, Mobile, Alabama.6 o5 k2 q5 I# r/ j1 ?4 R
Address correspondence to: Samar K. Bhowmick, MD, FACE,6 @* J0 _6 A2 |8 ^5 P
Professor of Pediatrics, University of South Alabama, College of- B  V& V8 M4 o& q& D
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;- ?0 z. I. l" ~) l7 g6 u
e-mail: [email protected].
0 f0 z7 ?- j& y( x1 |about 6 to 7 months old, which progressively became8 O9 `3 Y3 T* P2 W
darker. She was also concerned about the enlarge-
/ w/ H' |( {$ S% pment of his penis and frequent erections. The child
3 l* Y7 u& |3 v4 _* d) S. [was the product of a full-term normal delivery, with9 R1 @$ f9 d! K2 c- I5 V
a birth weight of 7 lb 14 oz, and birth length of
0 k* {5 I# [: J9 I. C! [7 j20 inches. He was breast-fed throughout the first year
  Q, n% L" g* U7 w- M* }of life and was still receiving breast milk along with
6 d) w% }  I4 c& N2 Bsolid food. He had no hospitalizations or surgery,
9 e8 t& b5 I& M% Vand his psychosocial and psychomotor development9 a/ ~( r% ?) o# l& `8 Q
was age appropriate.% @/ ~3 b8 ]( R; z
The family history was remarkable for the father,
3 o. i$ P8 G0 hwho was diagnosed with hypothyroidism at age 16,  U% E) ?" n5 r  Z
which was treated with thyroxine. The father’s$ W. D( m: M  V
height was 6 feet, and he went through a somewhat4 ?. k3 o$ b/ x8 T
early puberty and had stopped growing by age 14." F0 S" ~2 Z  p1 X+ r! `' V
The father denied taking any other medication. The
: y  d; O$ ?9 dchild’s mother was in good health. Her menarche
: @; J" ^7 e% W, l  U7 ^was at 11 years of age, and her height was at 5 feet: i* m$ t' }7 J5 g9 j
5 inches. There was no other family history of pre-
. [6 T3 H; j8 a& dcocious sexual development in the first-degree rela-
) ?1 }- E4 O4 D. l5 h+ Z- P2 Q( otives. There were no siblings.
( P* Z/ v' F6 H5 i7 w, @Physical Examination
* g4 O, N4 U  t0 D# ?. U6 }The physical examination revealed a very active,- I# T. a! M. k  X$ g
playful, and healthy boy. The vital signs documented
' ^% u) V' X( J9 [3 pa blood pressure of 85/50 mm Hg, his length was
/ y: ?" c6 n8 s4 d- d( ]  B90 cm (>97th percentile), and his weight was 14.4 kg
! ^9 d7 F) [) _8 o; Y; B* R$ C(also >97th percentile). The observed yearly growth
9 @0 d* _) _+ K5 P$ \( Ivelocity was 30 cm (12 inches). The examination of
& m. l: ], w! ]: W9 jthe neck revealed no thyroid enlargement.
* R8 z* S& u+ K# VThe genitourinary examination was remarkable for2 m& g  _) L  w3 I7 B% t4 f2 ?
enlargement of the penis, with a stretched length of! ^  H# e: x5 \, w, K
8 cm and a width of 2 cm. The glans penis was very well
8 @0 Y+ \7 h  D( adeveloped. The pubic hair was Tanner II, mostly around. c" u/ l! D& R7 C/ d
540
9 R+ ]( S7 H* A* jat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
; Z1 @4 [: @& b/ ~the base of the phallus and was dark and curled. The  L, Y# j9 |6 ^- t
testicular volume was prepubertal at 2 mL each.
& k2 d6 n7 R( F( O! TThe skin was moist and smooth and somewhat' L* C, e2 w3 V- D/ u
oily. No axillary hair was noted. There were no
) [3 h; E" X; J  Uabnormal skin pigmentations or café-au-lait spots.
* z* X8 F8 a6 Z7 g) @3 xNeurologic evaluation showed deep tendon reflex 2+
, L: s# j3 q; R) o( Kbilateral and symmetrical. There was no suggestion
1 j7 z0 t$ C" W" [5 x6 n. E. hof papilledema.: r, m9 H& D  t# t" i
Laboratory Evaluation# P, b$ o/ W6 \  W
The bone age was consistent with 28 months by
6 O5 e$ T* G" s" T6 Pusing the standard of Greulich and Pyle at a chrono-
% I1 ]1 P3 U) h9 h# v5 Elogic age of 16 months (advanced).5 Chromosomal* @+ u, a: K/ {& D7 {1 h- d  Q( N* B7 H
karyotype was 46XY. The thyroid function test! {9 v1 `9 {/ P" w( i
showed a free T4 of 1.69 ng/dL, and thyroid stimu-# R) ^. t8 n3 Q0 C: A  a: P* [
lating hormone level was 1.3 µIU/mL (both normal).' q4 P" }3 Y% P/ b* K, s% h
The concentrations of serum electrolytes, blood" T( q/ R* v2 j! Q
urea nitrogen, creatinine, and calcium all were% V( V0 x" j" X8 D
within normal range for his age. The concentration7 I9 @2 u5 C/ Z) r- D' E
of serum 17-hydroxyprogesterone was 16 ng/dL7 V+ T9 y) H, a8 g
(normal, 3 to 90 ng/dL), androstenedione was 20
8 H; t7 B6 t, Tng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-* s6 {; ^* O% ?+ z% ~3 E: e
terone was 38 ng/dL (normal, 50 to 760 ng/dL),, u  S5 ~9 d1 d9 D
desoxycorticosterone was 4.3 ng/dL (normal, 7 to9 y$ F/ H; L2 k% q$ u
49ng/dL), 11-desoxycortisol (specific compound S)4 k! M" z* Q' ]3 g* p7 ^6 I8 x
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
8 M: G2 L# g3 C4 itisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
% \- Z4 V$ _8 p& G6 `8 Rtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
2 ]& V) i- y2 A# b' x& A7 ^7 Dand β-human chorionic gonadotropin was less than
: _8 W/ i+ [$ e, p+ J' `7 H5 mIU/mL (normal <5 mIU/mL). Serum follicular
% J- s5 o/ ^4 M* q, ^stimulating hormone and leuteinizing hormone
6 l) R1 Y9 E/ s5 C% Bconcentrations were less than 0.05 mIU/mL
% [: F8 x  y: F; @& R(prepubertal).
" X4 y6 o6 }8 I7 }The parents were notified about the laboratory
4 E; L3 H8 A  r5 H' j5 N5 ]& oresults and were informed that all of the tests were
0 T* T) r( D  ^/ w" Q2 h% P, z# Jnormal except the testosterone level was high. The
" K, l0 k( Y( B0 Ffollow-up visit was arranged within a few weeks to
3 [% |' G( i9 l# d. nobtain testicular and abdominal sonograms; how-
2 H" B; s/ q, R% a$ D* Fever, the family did not return for 4 months.9 R& a$ W1 T3 ~  L
Physical examination at this time revealed that the$ f/ w& g" g1 Y5 T* e4 n9 C
child had grown 2.5 cm in 4 months and had gained0 m3 b* e  K- V+ {4 S
2 kg of weight. Physical examination remained4 q+ H* k( I4 L/ ]% _
unchanged. Surprisingly, the pubic hair almost com-
. K4 c9 z# T% m8 _9 gpletely disappeared except for a few vellous hairs at0 \( T3 ^3 `3 l2 p- z5 u/ u1 o
the base of the phallus. Testicular volume was still 2
; U- G8 E) R8 w8 `mL, and the size of the penis remained unchanged.
$ C7 k" M  {, A9 \3 a4 xThe mother also said that the boy was no longer hav-  j5 E# ^$ g( U: {
ing frequent erections.
, P; m  I* Y$ D2 HBoth parents were again questioned about use of5 \  q5 q4 g9 P
any ointment/creams that they may have applied to
% C" T: V) F$ [2 |9 }* t! }8 kthe child’s skin. This time the father admitted the5 q4 _0 t; V# v! O, {. d0 f
Topical Testosterone Exposure / Bhowmick et al 541
+ ^4 n4 G6 }+ Ause of testosterone gel twice daily that he was apply-2 m0 `7 o+ H' G, ~
ing over his own shoulders, chest, and back area for. I* ^( C* w: L& Q9 l5 ~
a year. The father also revealed he was embarrassed
2 a3 H( h  `' y& ?" R6 ]to disclose that he was using a testosterone gel pre-
( ~% M- W1 |; r$ A* }3 D6 qscribed by his family physician for decreased libido
0 X. f6 r" D2 n$ N! j$ Xsecondary to depression.
2 a! E8 n9 r, ^3 LThe child slept in the same bed with parents.; ]& t& m  [5 E- I& I8 j
The father would hug the baby and hold him on his
. h3 k8 b' x0 S) Uchest for a considerable period of time, causing sig-0 }0 E& L4 }/ Z) |$ R
nificant bare skin contact between baby and father.% X9 }7 Z, i! O+ X
The father also admitted that after the phone call,
0 {% E' y5 ]: v) P/ Mwhen he learned the testosterone level in the baby( c, r- j1 l, B( M2 w+ f
was high, he then read the product information
/ w; r) G3 H7 p# k8 s. |/ ~" q# Jpacket and concluded that it was most likely the rea-
; `: i1 G6 n2 @; @7 c& T4 q( zson for the child’s virilization. At that time, they
) o, Y. s! I2 ^3 Y4 F# @3 Ldecided to put the baby in a separate bed, and the
2 ]& ^3 {6 ^: \- yfather was not hugging him with bare skin and had
6 ?8 u+ I1 j  [% h, ubeen using protective clothing. A repeat testosterone+ f+ Q" A& l) x( e, L, V
test was ordered, but the family did not go to the
, J: H. ~7 x- c. x! c, \( M8 R) ilaboratory to obtain the test.
. {: ?, _5 k' YDiscussion2 K+ `  ]$ h9 H4 S
Precocious puberty in boys is defined as secondary
- q5 A+ f8 k) T( F. U" R' F0 }sexual development before 9 years of age.1,4
- e& }% |" P% NPrecocious puberty is termed as central (true) when+ D4 M" t5 R1 d' R, a. Q
it is caused by the premature activation of hypo-4 O8 z3 {: q0 b; M- j7 X( L
thalamic pituitary gonadal axis. CPP is more com-
) N& Z; P* e& fmon in girls than in boys.1,3 Most boys with CPP$ Y( ?5 G* S' X4 b+ u  Y2 R6 n
may have a central nervous system lesion that is
& ^3 M! w( }: W/ D6 N& G6 a/ jresponsible for the early activation of the hypothal-) m, t9 d/ v4 {6 R+ S1 f
amic pituitary gonadal axis.1-3 Thus, greater empha-
9 _. Z. v- c+ _) bsis has been given to neuroradiologic imaging in" ?; K) a: A4 d+ Y: n
boys with precocious puberty. In addition to viril-
, g6 ]4 {( q1 W, |ization, the clinical hallmark of CPP is the symmet-' ^& ~; A9 A$ s  v0 G
rical testicular growth secondary to stimulation by/ A) f! ~0 c$ E
gonadotropins.1,3
: X! A+ x4 D: AGonadotropin-independent peripheral preco-
( Q7 X! x9 E; V: Q7 Bcious puberty in boys also results from inappropriate
0 k: _5 f! O% c- w+ Uandrogenic stimulation from either endogenous or
+ y6 X% e# D5 Q- \exogenous sources, nonpituitary gonadotropin stim-: g5 a( J4 ]' j+ ^( P
ulation, and rare activating mutations.3 Virilizing8 `+ G* }5 E- S
congenital adrenal hyperplasia producing excessive5 g' _9 S3 {. E4 o9 g
adrenal androgens is a common cause of precocious
+ h( X5 K$ G( k  c' g+ opuberty in boys.3,4
: O0 N! c1 v9 b/ ~5 H% qThe most common form of congenital adrenal' C* G! w- D: p
hyperplasia is the 21-hydroxylase enzyme deficiency.
5 X8 K5 V# Q, O) @: H5 cThe 11-β hydroxylase deficiency may also result in- g6 Q7 W( ?: `
excessive adrenal androgen production, and rarely,, ]  ^) v1 N  U- n
an adrenal tumor may also cause adrenal androgen# D+ L9 X/ k; q- |  T
excess.1,3
7 B, d. @0 c( c6 \# Jat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
- x$ d5 S( b1 M& o0 C- v( [542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
5 {* G, t0 g; b( K$ ^5 M5 [A unique entity of male-limited gonadotropin-
2 y. O1 b  s, n3 yindependent precocious puberty, which is also known2 f5 P/ u$ A) \
as testotoxicosis, may cause precocious puberty at a
. X: l  s3 R, V1 G, `) |& J- Kvery young age. The physical findings in these boys
# |1 K8 e7 {& b1 Q! Wwith this disorder are full pubertal development,& t% W4 o8 V# Z
including bilateral testicular growth, similar to boys
5 j7 O# B2 p9 b' R4 n" Wwith CPP. The gonadotropin levels in this disorder3 E( O6 j/ }' T( F5 l& u
are suppressed to prepubertal levels and do not show5 K" ^+ z/ B2 \0 {
pubertal response of gonadotropin after gonadotropin-
8 }7 }" b' f3 r9 r8 l+ Creleasing hormone stimulation. This is a sex-linked
6 ]( K% H8 I* ?0 V5 Dautosomal dominant disorder that affects only
; S9 K8 m2 {. N* wmales; therefore, other male members of the family# k: K' R0 D' W7 O5 Y
may have similar precocious puberty.3' [& T; E9 R+ l- ~% g& @( z; U8 `
In our patient, physical examination was incon-
" {) N# T0 S" }9 D: @' Msistent with true precocious puberty since his testi-
- v  t' _2 q; D& Z: lcles were prepubertal in size. However, testotoxicosis
9 ~6 J8 J; D. _was in the differential diagnosis because his father
; d4 v- [( t* P+ J* l5 e8 ]started puberty somewhat early, and occasionally,' |* O* d& Q: [; i7 w  q  j
testicular enlargement is not that evident in the
  y: T3 A: V4 E+ S# zbeginning of this process.1 In the absence of a neg-
$ s+ N2 ?1 [0 o! j$ f" p3 oative initial history of androgen exposure, our* d9 F7 O! ^7 C3 O+ j
biggest concern was virilizing adrenal hyperplasia,! Y$ G8 n- E, n( j! w
either 21-hydroxylase deficiency or 11-β hydroxylase5 M/ ^! C2 I# P1 B& `9 o
deficiency. Those diagnoses were excluded by find-
$ X$ I7 B1 L' J! }ing the normal level of adrenal steroids.
- `5 v" r- i1 A9 W, |& v3 XThe diagnosis of exogenous androgens was strongly# ]) f6 M' }% l8 A- w
suspected in a follow-up visit after 4 months because: v1 x0 ?+ d, y7 h& k& y
the physical examination revealed the complete disap-+ l! J, C" A: `6 z0 S4 R
pearance of pubic hair, normal growth velocity, and
$ }$ w! Y7 T" J3 P/ b% [decreased erections. The father admitted using a testos-" K2 x6 F( h5 L7 A
terone gel, which he concealed at first visit. He was& G4 m! p! e! U) M; c; C) c" c
using it rather frequently, twice a day. The Physicians’
, q# ^  x% }4 t% l. e2 iDesk Reference, or package insert of this product, gel or$ W7 |% b; [1 Z% D3 q
cream, cautions about dermal testosterone transfer to
8 w8 O7 ~3 F$ p# L: @& f8 c" s1 N" V' wunprotected females through direct skin exposure.& l0 k0 u* E9 f7 w
Serum testosterone level was found to be 2 times the
, Q! r! K& N% i/ i) I# Y, ybaseline value in those females who were exposed to! `! t9 w7 b) t! |
even 15 minutes of direct skin contact with their male
0 i6 c* a+ Z  C. b" Bpartners.6 However, when a shirt covered the applica-
- K( |& ^& {9 b9 L3 Qtion site, this testosterone transfer was prevented.
, J2 V, S' a9 t! ^Our patient’s testosterone level was 60 ng/mL,
5 l/ m- \, l( M1 y$ W0 Q; ]which was clearly high. Some studies suggest that1 M$ R. F6 \/ h( e) I
dermal conversion of testosterone to dihydrotestos-
$ X4 d% ^$ o. y+ U- h5 u% m9 Fterone, which is a more potent metabolite, is more
$ S% H/ Y' h+ b/ P0 }active in young children exposed to testosterone
' J: I) V& F+ f& v; K: Zexogenously7; however, we did not measure a dihy-+ C# K5 W4 a8 K0 I" i& v2 V* s  {
drotestosterone level in our patient. In addition to1 I/ r3 S2 A9 b# W7 o
virilization, exposure to exogenous testosterone in
; }8 Y7 _% r3 Z$ ]/ r! M" k6 @children results in an increase in growth velocity and
) e& X. B( O' Z" m- ^) Hadvanced bone age, as seen in our patient.
) I7 q. w+ y. t+ Z, M8 iThe long-term effect of androgen exposure during
0 z; h$ `0 e3 f5 K4 kearly childhood on pubertal development and final. j; J4 f* O# v& ~! S( U" M
adult height are not fully known and always remain* Y8 E- H0 F3 t7 F% |
a concern. Children treated with short-term testos-
8 K% I% h# `9 ~  ]terone injection or topical androgen may exhibit some
9 g0 R$ t; {' v  j; Y, Q, t4 m2 d" D! ?acceleration of the skeletal maturation; however, after2 U5 E  ?1 B; J3 ~/ R* z
cessation of treatment, the rate of bone maturation- h2 L: x( L/ C; P1 e! k" z3 C
decelerates and gradually returns to normal.8,9* |) E7 Q0 f" X; j0 G
There are conflicting reports and controversy
# n2 A9 C9 A+ M8 B$ ]: T8 T+ {1 \, @over the effect of early androgen exposure on adult% F1 j2 M( ~0 y  M
penile length.10,11 Some reports suggest subnormal8 A, F0 u) l- q' W- c, D
adult penile length, apparently because of downreg-
* l- D1 c5 p. Y) D& g! b: [ulation of androgen receptor number.10,12 However,# e) i# S4 x; t' Z$ ?
Sutherland et al13 did not find a correlation between
) `$ L1 o( k) V1 a) c+ uchildhood testosterone exposure and reduced adult
9 ~: Q1 R& a) w  X& ^penile length in clinical studies.2 }6 z" L" R4 @3 f
Nonetheless, we do not believe our patient is7 i' f8 e5 O, `% |  I/ Y
going to experience any of the untoward effects from) `2 }$ Q' h/ x0 K- f5 ?2 l
testosterone exposure as mentioned earlier because
! @: t* C/ }% a' Bthe exposure was not for a prolonged period of time.
& F5 f5 E; M0 [+ vAlthough the bone age was advanced at the time of
4 `* N1 [- ~8 h, Y+ o! y6 {diagnosis, the child had a normal growth velocity at+ u& ~. ?* A' E* l8 m
the follow-up visit. It is hoped that his final adult/ q, `! h, Q, z& S0 W# Y
height will not be affected.
3 I* m( j; I! w$ a0 u, F+ M- iAlthough rarely reported, the widespread avail-
' r+ U: M3 v, s9 d7 o2 {ability of androgen products in our society may" D4 i8 z; g$ ^3 T
indeed cause more virilization in male or female1 _2 j! T( V7 E9 a- r- h# j- m" ?9 x
children than one would realize. Exposure to andro-  b" P6 f* v7 m3 l+ z! T; b- l
gen products must be considered and specific ques-, f( A) ?# R) I6 W6 T/ _2 f
tioning about the use of a testosterone product or
7 e0 L4 j) H6 b, }( S& j5 ^gel should be asked of the family members during
7 Y! l* B+ A1 s$ x5 fthe evaluation of any children who present with vir-
* G# d* y$ M) filization or peripheral precocious puberty. The diag-
6 S, A5 u" j9 t3 m# o; U  @  u+ dnosis can be established by just a few tests and by
* v5 V* r% e6 Rappropriate history. The inability to obtain such a
  `& I6 `$ n- H6 r  Y* ?# b; ihistory, or failure to ask the specific questions, may  {, b  O0 x- O4 k, l
result in extensive, unnecessary, and expensive7 ~2 S3 l; L' Y4 K  s) {9 l! O" v
investigation. The primary care physician should be( ]( m; {5 `9 Z4 W* F6 Q
aware of this fact, because most of these children
9 |8 A& c6 H. ^6 _- @9 Nmay initially present in their practice. The Physicians’" U, }* K' m# E5 Q$ p4 S$ w7 ?2 V
Desk Reference and package insert should also put a
& g5 \, D* H+ W  ]0 Gwarning about the virilizing effect on a male or& h* E7 L7 |8 N
female child who might come in contact with some-( d, C' Q& m& S9 \; ^
one using any of these products.4 Q. ?: m  d& h5 X
References
2 t& L+ I: P, t& S0 }/ V1. Styne DM. The testes: disorder of sexual differentiation
( A% S5 t% }  c4 c1 f2 fand puberty in the male. In: Sperling MA, ed. Pediatric
/ Y2 C8 _0 E6 uEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
5 k6 U5 e6 h* }1 F* D) V2002: 565-628.1 c% [+ l8 T8 ~0 N  t- z. ]! N5 E+ t; L
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious) ]' v5 M7 i, S7 l% ?3 b/ `3 Y
puberty 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

% {9 g- m* r  f2 N+ Q1 `0 r# b6 s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