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

WK綜合論壇, WK综合论坛

 找回密碼
 立即注册
樓主: wk007

鄉下的妹子太便宜,一次四個都要了[12P]

[複製鏈接]
發表於 2025-1-4 03:25:35 | 顯示全部樓層
Sexual Precocity in a 16-Month-Old
" ]  E, x; @# m) m3 ~Boy Induced by Indirect Topical
* ~: R* D9 N' P+ b6 ?- n2 X) H) z! qExposure to Testosterone
' o6 ^' u! O& Y3 M) J" v6 LSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2/ ^6 I& f& P3 k% C1 \3 W
and Kenneth R. Rettig, MD1
$ m9 V1 ?" ~% BClinical Pediatrics
( e3 J  f$ g+ [$ M& gVolume 46 Number 6/ }& ?% Q5 @) T2 v
July 2007 540-5433 M% _& l) q2 U
© 2007 Sage Publications% e3 n) r/ w2 J" d6 [$ W8 n
10.1177/0009922806296651
7 i7 p+ w6 n  B  {% l) zhttp://clp.sagepub.com% A( Y) \9 J. k! s8 X+ D: [4 L+ l
hosted at
; Y4 {: g2 H: y8 L' g% K3 y& khttp://online.sagepub.com. i* O' R" h$ @
Precocious puberty in boys, central or peripheral,
& Q9 K8 o* M4 ~  a1 h1 V5 q( I) Xis a significant concern for physicians. Central
7 V6 M* [2 s# H  F; k$ {precocious puberty (CPP), which is mediated
# R4 e) K9 Q! F4 ~2 Xthrough the hypothalamic pituitary gonadal axis, has
2 ~% `" c2 h, ^; W# Aa higher incidence of organic central nervous system, z. i. Q. l5 U3 p( s+ f
lesions in boys.1,2 Virilization in boys, as manifested
9 K. x$ F7 _# J: {* q) ~by enlargement of the penis, development of pubic
6 T3 g, _1 Z  n2 Q6 \0 \. y9 Y6 Ahair, and facial acne without enlargement of testi-
/ P% ~8 j- T* V1 v- n# |. Jcles, suggests peripheral or pseudopuberty.1-3 We* N4 R( d% x" Z3 H1 B6 `7 T
report a 16-month-old boy who presented with the1 |) N  [# N% Z8 @
enlargement of the phallus and pubic hair develop-
  W& F1 G  f6 ^- X$ y, F% h& ^ment without testicular enlargement, which was due: C% R% F5 s3 W) w
to the unintentional exposure to androgen gel used by+ x. k6 m! G/ x3 H" @6 R
the father. The family initially concealed this infor-
' t. X1 U9 q" Z5 e! h& o3 omation, resulting in an extensive work-up for this/ K" t3 X. E% x& z% t
child. Given the widespread and easy availability of
2 I+ @+ k) }( gtestosterone gel and cream, we believe this is proba-
& S3 F9 y* J/ Ubly more common than the rare case report in the
# c" i. d9 q  z5 T. nliterature.4
8 b( V  L: T! k1 N4 DPatient Report! q. M- z% i+ e2 a
A 16-month-old white child was referred to the
: [3 F) Y! e) q( b: Aendocrine clinic by his pediatrician with the concern) g* b4 c6 ]5 T% u  ~! Z7 j# u+ l0 x
of early sexual development. His mother noticed( U4 l* l* T  Z' L1 Y- j: x" N
light colored pubic hair development when he was7 K& z+ ]8 P5 Q' h
From the 1Division of Pediatric Endocrinology, 2University of5 k! k7 D4 K! o1 h- Y7 ]
South Alabama Medical Center, Mobile, Alabama.- r# C& ]7 D9 I3 V4 W$ ]5 A
Address correspondence to: Samar K. Bhowmick, MD, FACE,. C, `, i! W. v1 v/ h
Professor of Pediatrics, University of South Alabama, College of
; }+ m5 ~7 V9 \3 h; k5 U. LMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;* R& h3 u9 U2 c# p6 B* S
e-mail: [email protected].8 g, e7 S. m% v+ i5 t+ n7 [
about 6 to 7 months old, which progressively became: c/ O5 w  j; g
darker. She was also concerned about the enlarge-
1 N+ s( z, _, N4 ]* `# e5 Cment of his penis and frequent erections. The child3 B+ r& [2 t  R( q
was the product of a full-term normal delivery, with, l4 ~; @+ y! c7 `- I+ Y: l* [/ p
a birth weight of 7 lb 14 oz, and birth length of
1 L" Z# A& Q8 G6 n/ ?! d20 inches. He was breast-fed throughout the first year) ^6 P9 a. \: t; R5 T* u  J* c
of life and was still receiving breast milk along with
  l: ~' ]3 `8 \, Y% E1 x; lsolid food. He had no hospitalizations or surgery,
1 t2 K. f0 K0 N' Iand his psychosocial and psychomotor development
) R" k' U# z- ^0 ~: Y/ [" Kwas age appropriate.8 Q! e0 E9 S2 T  `2 a4 N3 x
The family history was remarkable for the father,
! q' l* q, P0 `' p) d  b$ p! e1 rwho was diagnosed with hypothyroidism at age 16,
/ h8 y. U( P3 _' ewhich was treated with thyroxine. The father’s3 c; f3 U& ?- q+ j
height was 6 feet, and he went through a somewhat5 ~! U4 {$ z. A( j
early puberty and had stopped growing by age 14.
" f4 i; v3 u" v- Q& Q& zThe father denied taking any other medication. The
& g" W* x* N0 Achild’s mother was in good health. Her menarche9 C% t$ y& D8 j, Z1 v/ p% O4 \
was at 11 years of age, and her height was at 5 feet9 \  w3 i: E# ?0 z1 ?7 F
5 inches. There was no other family history of pre-
" y6 L8 c8 h1 l4 J1 ncocious sexual development in the first-degree rela-& K% j  x0 b; s$ M  C
tives. There were no siblings.
$ b7 t  R! @1 r5 [! }' e! yPhysical Examination
* U  i+ J5 X2 g1 ~6 Z, [The physical examination revealed a very active,9 n- X* `% g( i8 N+ T
playful, and healthy boy. The vital signs documented
0 M( P. V' v1 a* G1 v( d3 y5 q# [a blood pressure of 85/50 mm Hg, his length was4 {. P# z5 F& L% H
90 cm (>97th percentile), and his weight was 14.4 kg7 q! x( Z- G2 e, L
(also >97th percentile). The observed yearly growth
4 m! Z4 |, ^: X# A0 mvelocity was 30 cm (12 inches). The examination of3 M$ u! K7 t& l6 J* W# Y1 q8 I4 j
the neck revealed no thyroid enlargement.4 T9 |* w9 v) I' R5 l' M5 t5 c
The genitourinary examination was remarkable for$ s  H. ?. p- x+ ~( ?2 E
enlargement of the penis, with a stretched length of
" K% @$ t: f% k# w" w8 cm and a width of 2 cm. The glans penis was very well
( E4 V1 Z$ X) Hdeveloped. The pubic hair was Tanner II, mostly around  N4 L9 T: ]' C! S1 Y
540
2 C4 M/ N* l) v) z9 Uat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
5 _$ \. U4 p3 P; |1 P4 Gthe base of the phallus and was dark and curled. The
0 ~* s0 y  h. f8 Stesticular volume was prepubertal at 2 mL each.
* e) l4 P0 k% d2 W5 a: E6 yThe skin was moist and smooth and somewhat
+ G5 H' [" O" D5 n, N# G* ]oily. No axillary hair was noted. There were no. w: b. O7 V9 {+ N& H+ Y
abnormal skin pigmentations or café-au-lait spots.5 H# g+ y; I! M
Neurologic evaluation showed deep tendon reflex 2+% m* a4 _$ E3 u, v6 C& j
bilateral and symmetrical. There was no suggestion/ z  y9 y! L' C0 ]2 ]6 u1 A9 }
of papilledema.
& D9 s- N# y5 Z$ r. ]Laboratory Evaluation% v) U8 u! {* S! s9 ?
The bone age was consistent with 28 months by
2 B. \2 {" |$ X% M) Jusing the standard of Greulich and Pyle at a chrono-
9 p) D1 p- C' r, N5 Blogic age of 16 months (advanced).5 Chromosomal5 N# k. g$ U# u3 z) a7 D8 g
karyotype was 46XY. The thyroid function test1 O. D2 B: u! S2 R& z: z$ |. c- F" O
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
) [2 T4 n: r* hlating hormone level was 1.3 µIU/mL (both normal).3 R- |6 \6 j2 C  c
The concentrations of serum electrolytes, blood0 v/ s  `6 H. K; X8 n
urea nitrogen, creatinine, and calcium all were
: q2 G4 X% y3 m. I1 [( D$ I0 nwithin normal range for his age. The concentration% ^$ W7 ?& U5 e6 w$ H
of serum 17-hydroxyprogesterone was 16 ng/dL7 C' J' Z5 O- z
(normal, 3 to 90 ng/dL), androstenedione was 20
' p+ \4 w# w& j% C3 {ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-" F: b6 I- |/ l9 X! ?+ q
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
8 Y( W+ p. e" A' N/ o/ ddesoxycorticosterone was 4.3 ng/dL (normal, 7 to
1 x4 K+ R9 G0 }5 _49ng/dL), 11-desoxycortisol (specific compound S)
& T  k  U  V0 r+ h, Xwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
+ R/ y* t+ p, w$ o2 F6 vtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
' B/ k+ _# l/ O/ [testosterone was 60 ng/dL (normal <3 to 10 ng/dL),' w, F. O3 w) D/ k' C) v, T
and β-human chorionic gonadotropin was less than
- Y2 e; z3 U( [: ~5 mIU/mL (normal <5 mIU/mL). Serum follicular; e% c# w" l6 d% L6 l0 s
stimulating hormone and leuteinizing hormone# H5 }3 h' u9 }" a& ^) S0 e; b& s
concentrations were less than 0.05 mIU/mL" m; K; K) T$ J! X  S/ J
(prepubertal).: E" F5 T! z( Q$ H
The parents were notified about the laboratory
/ c& `6 v( Z' V! xresults and were informed that all of the tests were
7 q) n1 g0 j% J4 Z# {normal except the testosterone level was high. The* j8 v' j- V" C# B$ W
follow-up visit was arranged within a few weeks to+ e# S3 u6 r: M6 n, Z. Y$ q
obtain testicular and abdominal sonograms; how-8 q0 e, ^- p* D4 O- L2 p' V
ever, the family did not return for 4 months.
, Z+ E! s* I' g9 X+ r* XPhysical examination at this time revealed that the' r/ A; Q5 c, T- h  R
child had grown 2.5 cm in 4 months and had gained
5 q$ Y; o) y8 @6 r2 S. L2 kg of weight. Physical examination remained4 p2 j3 a8 V, Y7 A9 y! `1 g
unchanged. Surprisingly, the pubic hair almost com-
1 V$ [- j0 P' ~% T8 K& j! Jpletely disappeared except for a few vellous hairs at" ~3 R/ U/ q* h# E5 ~: n# V. w" h
the base of the phallus. Testicular volume was still 2
! _1 [7 l3 L1 BmL, and the size of the penis remained unchanged.& {9 b: y, i4 R3 H
The mother also said that the boy was no longer hav-9 h  u4 ]! x8 b3 F& q& v9 L
ing frequent erections.
# N4 N3 I+ g  {  f0 ~" b0 G7 wBoth parents were again questioned about use of
, F  Y! d7 c9 |6 f" Q; I5 Sany ointment/creams that they may have applied to7 B4 U+ B7 V$ e% N! q2 F0 H
the child’s skin. This time the father admitted the
" k4 `! ]3 H0 R  w! ITopical Testosterone Exposure / Bhowmick et al 541
+ A1 g& T, }; e, Muse of testosterone gel twice daily that he was apply-8 w* n0 M( @2 E
ing over his own shoulders, chest, and back area for
' Z7 D' t$ }5 h' @7 q/ ca year. The father also revealed he was embarrassed* X+ M& e9 R* x8 E
to disclose that he was using a testosterone gel pre-4 v* \& m8 b1 ?' O
scribed by his family physician for decreased libido
9 J. T% U9 p( }4 I3 f/ `3 ssecondary to depression.
$ }6 i) P9 d6 `7 _# q) LThe child slept in the same bed with parents.  E# \+ s% {* ^) i0 C+ ]3 M6 [
The father would hug the baby and hold him on his6 ~; j" d7 \0 _$ V  ?5 D0 f
chest for a considerable period of time, causing sig-
) `; H8 L% g/ P" S6 E/ _nificant bare skin contact between baby and father.* g0 R2 D0 d1 x' K* |
The father also admitted that after the phone call,
9 R6 e. t* [! T1 ]when he learned the testosterone level in the baby& h* r. w5 M( G
was high, he then read the product information
+ B. g( }& W( f$ ~5 \packet and concluded that it was most likely the rea-* w% R' T. r; `1 h5 s9 Q/ I5 d
son for the child’s virilization. At that time, they
& g. |& [# c, l, ]( t  B% Odecided to put the baby in a separate bed, and the! x5 x- b2 Y. n3 F# V; Y; }# i
father was not hugging him with bare skin and had/ b5 R2 R" ^7 x$ A# B6 y$ Q
been using protective clothing. A repeat testosterone3 p& T" e% ^: U6 g4 K
test was ordered, but the family did not go to the4 h- \" O0 W; e) T
laboratory to obtain the test.
: Q5 W2 ]; Y* [/ _" B2 ZDiscussion
3 @# Z: ]7 E, u- S8 E1 YPrecocious puberty in boys is defined as secondary0 x# m# b0 t7 H3 D+ B
sexual development before 9 years of age.1,4
0 N5 \( X5 u% a% r6 j! l0 [% P  _2 KPrecocious puberty is termed as central (true) when4 i6 W: m$ l' G4 l* X; B( m
it is caused by the premature activation of hypo-
$ R0 w: V/ m. ~: z) r6 y9 d7 ethalamic pituitary gonadal axis. CPP is more com-
7 Y- s4 g/ q1 g% P, g# Rmon in girls than in boys.1,3 Most boys with CPP# S: s+ G# R9 X1 V  Q
may have a central nervous system lesion that is0 }/ r5 _6 i: I7 g: h1 G  W, B
responsible for the early activation of the hypothal-1 b1 Z/ \  J7 N9 p; m( \" O3 O
amic pituitary gonadal axis.1-3 Thus, greater empha-
) k8 v, q2 b' Q% R% ^. Ksis has been given to neuroradiologic imaging in0 ]& A0 v- h# c
boys with precocious puberty. In addition to viril-
6 x# e: R. s6 d4 q! Mization, the clinical hallmark of CPP is the symmet-* W3 ?6 J0 p, j  _* j# r8 G
rical testicular growth secondary to stimulation by
8 r, c2 [" g8 V" x3 A6 c  Xgonadotropins.1,3
) i+ j7 I* ]& k/ H6 p! fGonadotropin-independent peripheral preco-: W1 z5 y) I7 d5 J+ }( V3 [4 d+ u  U
cious puberty in boys also results from inappropriate
8 ]- u* r* g1 Pandrogenic stimulation from either endogenous or
3 ], V0 S# c3 w. _exogenous sources, nonpituitary gonadotropin stim-* k' U. \( q, ^+ F
ulation, and rare activating mutations.3 Virilizing
7 E; n9 O% X' G, y) U2 Dcongenital adrenal hyperplasia producing excessive. ^2 @- Q* }' r
adrenal androgens is a common cause of precocious
1 n& ?7 r2 Y8 t8 W$ Qpuberty in boys.3,4
" c: s) v5 ^4 j% g7 r! q: pThe most common form of congenital adrenal
3 |0 o& _7 L+ W% |' Hhyperplasia is the 21-hydroxylase enzyme deficiency.
! ?% h& y6 S' L2 R" pThe 11-β hydroxylase deficiency may also result in
' S7 Z( q  D% t  Eexcessive adrenal androgen production, and rarely,2 K1 `8 K. i' o7 q
an adrenal tumor may also cause adrenal androgen& z9 n- i6 F1 U! M0 j
excess.1,3. f. C9 i: ]# `* `8 i
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
$ B2 |7 S$ M6 Y$ N* ?: Y$ A542 Clinical Pediatrics / Vol. 46, No. 6, July 2007# z: ~7 g: d- L: n% ?4 K
A unique entity of male-limited gonadotropin-
0 w' @8 d2 s5 {7 P0 X# n# ]% Xindependent precocious puberty, which is also known
# f2 L2 Y/ n: mas testotoxicosis, may cause precocious puberty at a
7 r" O' ?0 ?- o9 k1 }- cvery young age. The physical findings in these boys$ \% t0 D0 ?- t* j0 ^1 g3 {
with this disorder are full pubertal development,8 C6 E& R: a! \8 {: K$ x: h' r3 m
including bilateral testicular growth, similar to boys
# K, U2 i! \8 x' \1 ]7 u; uwith CPP. The gonadotropin levels in this disorder: S, E/ O; t. @6 {0 I( L2 i
are suppressed to prepubertal levels and do not show
; m% K' n" c) u. n, Rpubertal response of gonadotropin after gonadotropin-
+ Y9 M) B: ~4 z$ k! vreleasing hormone stimulation. This is a sex-linked$ ^9 Z! j4 N0 ~  Z# y- i
autosomal dominant disorder that affects only1 E1 a7 ]7 n- [& u% S. L1 k) b* A% K
males; therefore, other male members of the family
* e" L9 X& t+ t, l! }4 X! c8 G; G9 r9 U# qmay have similar precocious puberty.3* w0 ^% [% n3 u- ]$ t
In our patient, physical examination was incon-
- A' {/ y" n8 t0 ]: {* esistent with true precocious puberty since his testi-% W% d2 Q) W. J- X  n1 y* A3 U4 X8 B
cles were prepubertal in size. However, testotoxicosis
6 t# J0 t( j- A* x: U! c9 Owas in the differential diagnosis because his father: a2 c- r0 f8 Y# ~  L9 n9 r
started puberty somewhat early, and occasionally,
, s8 V) m3 z" V& m7 Vtesticular enlargement is not that evident in the
- C$ |0 j& [4 i( @1 Mbeginning of this process.1 In the absence of a neg-
  M" j7 X. s1 n0 H8 k4 pative initial history of androgen exposure, our8 e. v. c! E0 Q5 y) ~
biggest concern was virilizing adrenal hyperplasia,
- M$ N8 o3 L0 ]( E' T2 Yeither 21-hydroxylase deficiency or 11-β hydroxylase
' j' |! i- f0 {9 A! z7 y) v! M5 ?  ideficiency. Those diagnoses were excluded by find-
, r2 u* M+ a- _) Ving the normal level of adrenal steroids.
) K" \* Z5 Y% t8 H$ W5 uThe diagnosis of exogenous androgens was strongly+ [* l3 A; I5 e1 @
suspected in a follow-up visit after 4 months because0 V* X" G) z" e+ R9 f
the physical examination revealed the complete disap-4 L6 x& `8 M/ [( X( m6 m
pearance of pubic hair, normal growth velocity, and
7 {" P0 b# E" z. M9 U- m2 Cdecreased erections. The father admitted using a testos-
2 h4 @& t* Y/ p* `3 {/ t$ \6 W; `( bterone gel, which he concealed at first visit. He was1 ^/ G% A/ P& s! R, R& u
using it rather frequently, twice a day. The Physicians’4 S" ]2 m; ~, _, k& `) x7 S: X5 Q
Desk Reference, or package insert of this product, gel or! j* j  @0 o0 X1 d8 w
cream, cautions about dermal testosterone transfer to
8 C9 m+ X2 t4 `  punprotected females through direct skin exposure.8 Q2 J# O" {* @. B3 _
Serum testosterone level was found to be 2 times the
. c+ [! Z4 R+ E6 y  a" _4 abaseline value in those females who were exposed to+ Z) l# n0 z/ o9 X- u; Z
even 15 minutes of direct skin contact with their male2 i  T2 ]4 z6 z( v6 N0 S
partners.6 However, when a shirt covered the applica-5 J6 M5 Z' y4 ~0 @5 U
tion site, this testosterone transfer was prevented.) |6 K. \  ^! M7 j
Our patient’s testosterone level was 60 ng/mL,% [6 k! w3 Y2 ?( L+ P
which was clearly high. Some studies suggest that
# b# }, X/ ?" O7 ^9 L( Ddermal conversion of testosterone to dihydrotestos-
- \# o+ O, U8 O1 pterone, which is a more potent metabolite, is more- o* ~0 p& e" s# d! q
active in young children exposed to testosterone5 X: j# N% [0 Z; D2 P0 f: Q' t
exogenously7; however, we did not measure a dihy-
" Q: h9 }; [3 V- i: ndrotestosterone level in our patient. In addition to; `/ I6 x. d4 D9 w$ l" T: q
virilization, exposure to exogenous testosterone in3 e  g: p9 N. @. y" K( j" b' V
children results in an increase in growth velocity and
1 Q  `0 e: [1 X& C4 F, sadvanced bone age, as seen in our patient.
; k* Q3 k$ L, m0 tThe long-term effect of androgen exposure during% S/ s$ T9 \) f8 y4 h& A- S
early childhood on pubertal development and final
" ~2 j) w" U7 z- y  Madult height are not fully known and always remain; s: G" w" F# j4 |" h3 F8 ^  y
a concern. Children treated with short-term testos-
6 O/ K9 Q: R# g& k' Yterone injection or topical androgen may exhibit some
0 p3 q( }7 c6 vacceleration of the skeletal maturation; however, after
! e0 v; M) }  J# t* }0 K* g# b, Ncessation of treatment, the rate of bone maturation
/ s' @5 k' |; O2 x, P1 x& adecelerates and gradually returns to normal.8,9+ U$ `8 y8 V! S6 b
There are conflicting reports and controversy
: ?3 u5 F2 s, D1 Uover the effect of early androgen exposure on adult$ `; e0 q( a$ q& s, U3 s
penile length.10,11 Some reports suggest subnormal/ t+ P! L4 r' T8 X9 ~2 c3 o
adult penile length, apparently because of downreg-
. i+ x8 m1 w2 Vulation of androgen receptor number.10,12 However,
  C! T( g5 L0 z, T4 mSutherland et al13 did not find a correlation between
4 F2 |8 {7 J9 c' Vchildhood testosterone exposure and reduced adult
2 s9 l: k5 P! u- u# l) v- @penile length in clinical studies.
0 M0 h+ K, \4 z% P2 }; x, _Nonetheless, we do not believe our patient is
0 S7 I/ y) R, v2 r7 c- egoing to experience any of the untoward effects from0 a3 Y5 l  |% I5 W8 c
testosterone exposure as mentioned earlier because* w6 p0 p. r9 s9 Q& b
the exposure was not for a prolonged period of time.( _4 ?/ ]+ \. }; H
Although the bone age was advanced at the time of9 ^7 L8 A1 |% A6 }) m
diagnosis, the child had a normal growth velocity at: E3 q9 C7 B3 ^- y/ u4 `# r
the follow-up visit. It is hoped that his final adult
- g& @/ u4 @1 h/ y# lheight will not be affected.
& I' k2 z$ g+ A; {) DAlthough rarely reported, the widespread avail-! q9 Q( z4 M/ B) G8 s' {. O
ability of androgen products in our society may
" Z9 b: g/ d4 q! [+ |1 @( Jindeed cause more virilization in male or female! F2 {7 [8 A! F" ^1 Q4 A( d8 T
children than one would realize. Exposure to andro-
1 Y0 h, o8 V2 l$ Vgen products must be considered and specific ques-
7 |( D# V: O8 [, m, n" X/ mtioning about the use of a testosterone product or$ a- g4 t. s6 h
gel should be asked of the family members during
# U+ c% x) v- n1 T* @! d& u  `the evaluation of any children who present with vir-$ N; W% z  Q+ r2 y
ilization or peripheral precocious puberty. The diag-
4 \2 c5 d5 p: r" nnosis can be established by just a few tests and by$ W5 m3 t' g$ u! x/ [+ s
appropriate history. The inability to obtain such a
: l7 q9 M, J: l' b4 [& bhistory, or failure to ask the specific questions, may! D9 _+ Y4 w+ t8 {# d
result in extensive, unnecessary, and expensive
) H9 j- M9 q; A. Winvestigation. The primary care physician should be1 ]& g: D5 c7 j( T- Y
aware of this fact, because most of these children
' x4 U# h( q/ m7 n2 {% p( omay initially present in their practice. The Physicians’! W1 n& |" m& @' Q8 o, s9 ~
Desk Reference and package insert should also put a
5 s  l0 [) i5 K* q. Awarning about the virilizing effect on a male or2 B: w. i+ f6 v
female child who might come in contact with some-
' \; E1 L! B2 w" q# j! Uone using any of these products.
" O# F+ e* \! ]& tReferences
, t2 m& ~7 h0 E8 ]1. Styne DM. The testes: disorder of sexual differentiation# e2 t& J# u& P0 {0 |. ]! S7 o5 M& V
and puberty in the male. In: Sperling MA, ed. Pediatric* c0 s% f4 b. u9 y+ g
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;( p2 _  ?/ A) L# k
2002: 565-628.
3 m" Z; L1 V' I2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
# k/ T) N! q1 c' _puberty in children with tumours of the suprasellar pineal
發表於 2025-1-4 03:27:02 | 顯示全部樓層
Sexual Precocity in a 16-Month-Old3 O$ E/ S5 Q' l! Y4 O
Boy Induced by Indirect Topical
1 J, g6 ]* K" tExposure to Testosterone& M1 W9 y" r. C: m# D/ Q1 Q
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2% H0 n4 u. e. v; r! f! S" |, v  F
and Kenneth R. Rettig, MD1* @# L* D3 w. O; Q# B
Clinical Pediatrics
, }9 R6 L& W# G" J) IVolume 46 Number 66 k* t$ y$ M! H/ E# H: D, Y/ y
July 2007 540-5432 m  Q% |4 D9 `8 i( h( G! e
© 2007 Sage Publications6 }- e) }: |% a; z
10.1177/00099228062966514 v4 O! B; e/ H5 m4 I& m
http://clp.sagepub.com
$ S" I4 ^3 d& y1 A; m( B$ ahosted at# r" k! F' X  u: a
http://online.sagepub.com, v. n, _- ?/ R% I
Precocious puberty in boys, central or peripheral,
  d: ^) ~8 c" q2 s/ k2 Q( L9 Eis a significant concern for physicians. Central: V% }5 C3 T. t7 _
precocious puberty (CPP), which is mediated3 A. x  ]9 O( `$ F7 c; G/ t
through the hypothalamic pituitary gonadal axis, has
( Y/ {% H2 c1 E' P* k. u1 _  V: va higher incidence of organic central nervous system
, _& _: q/ O- ^( wlesions in boys.1,2 Virilization in boys, as manifested/ p  i3 z9 f! b) J: u
by enlargement of the penis, development of pubic
5 P/ k6 s  K- [5 w  zhair, and facial acne without enlargement of testi-6 G3 q0 V/ f( O# `
cles, suggests peripheral or pseudopuberty.1-3 We
/ [" I7 r- J# X, K; ureport a 16-month-old boy who presented with the
# ?; V  B, U& q& ^7 T; cenlargement of the phallus and pubic hair develop-( ~) J$ a# _8 |9 M
ment without testicular enlargement, which was due3 Y* s+ M" ]1 |, Y5 ~7 D
to the unintentional exposure to androgen gel used by$ ]0 [' c3 p$ }1 l  B* q1 O! E
the father. The family initially concealed this infor-$ D% M/ ]; y3 B& X% v: b- l+ G
mation, resulting in an extensive work-up for this
( S# m! |% Z" nchild. Given the widespread and easy availability of
6 E9 O5 M+ T) k/ j! {8 P6 l1 f7 Qtestosterone gel and cream, we believe this is proba-
) \  o: a' h! j! ibly more common than the rare case report in the
) W9 O9 @- h" g: Fliterature.4
3 Y1 ^9 _& L6 ?9 T/ }( Y! BPatient Report4 D; L/ L5 y# ~" `& R$ O
A 16-month-old white child was referred to the
7 ?' J- s: d. ~* ^/ v. R2 T! Wendocrine clinic by his pediatrician with the concern
; b2 `: M8 R& j. _1 n% d/ C6 s% r  [of early sexual development. His mother noticed* I2 ~- U; x& D: R0 a" L* ?/ x
light colored pubic hair development when he was9 ]' i0 K$ F' u4 M( @' z% ?  A
From the 1Division of Pediatric Endocrinology, 2University of
$ }! e" L! i8 B2 J5 s. j  GSouth Alabama Medical Center, Mobile, Alabama.8 a4 Z* N1 I# b% k3 T) v0 ^
Address correspondence to: Samar K. Bhowmick, MD, FACE,
9 i5 p( x/ D0 r& m' O' {Professor of Pediatrics, University of South Alabama, College of% D: n0 \7 \6 L, c
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;( O/ \% v# v- X
e-mail: [email protected].. q7 j+ _3 V" r+ t0 H
about 6 to 7 months old, which progressively became6 {& ]$ v( d0 A( ^# P  @
darker. She was also concerned about the enlarge-  c# C8 H3 f; {+ U& H
ment of his penis and frequent erections. The child' M3 t6 R* C3 g6 v
was the product of a full-term normal delivery, with
: X! [+ j  ^. A. e* K  \3 Ia birth weight of 7 lb 14 oz, and birth length of4 K/ U4 X" V: S% t% R
20 inches. He was breast-fed throughout the first year1 D! Z) }3 `) M. ~
of life and was still receiving breast milk along with" i0 l' S8 c) l. `. V6 m
solid food. He had no hospitalizations or surgery,
$ D3 R) x2 q4 F% B; v9 F5 [7 J' v9 r5 Dand his psychosocial and psychomotor development
. o$ r# X5 S- }* gwas age appropriate.
' ]2 r: @5 v3 e0 J" G: j9 E$ @The family history was remarkable for the father,3 t7 }( m" J% s" L9 T  u7 S
who was diagnosed with hypothyroidism at age 16,
- h# ~  z/ P0 D2 `& q; D6 Ywhich was treated with thyroxine. The father’s5 T) [) T& w; K0 M! b+ ^3 m3 r: ^# q
height was 6 feet, and he went through a somewhat7 Z$ U- ?$ t8 \
early puberty and had stopped growing by age 14.$ C! @  Q3 w$ `. Z' k3 {
The father denied taking any other medication. The) s* }: h: J; c  L8 H* \
child’s mother was in good health. Her menarche
5 _% K; M0 t/ U! ~1 G  Ywas at 11 years of age, and her height was at 5 feet
2 `  a5 s' ?( j5 inches. There was no other family history of pre-! `5 Q9 z1 X( z
cocious sexual development in the first-degree rela-
4 u7 m- p! U9 c- D; Atives. There were no siblings.# \$ F1 A0 N9 b: P$ _* ^' W% N* M
Physical Examination2 U: N* @, S. z, X7 {+ \2 G
The physical examination revealed a very active,# U6 M& h7 R* c( T5 h
playful, and healthy boy. The vital signs documented  |1 {9 m  t' B/ d
a blood pressure of 85/50 mm Hg, his length was2 }: o3 v/ b* q2 V
90 cm (>97th percentile), and his weight was 14.4 kg1 A4 u/ @8 y2 H9 C/ v5 [
(also >97th percentile). The observed yearly growth
# G9 `* S. g  M* I% @velocity was 30 cm (12 inches). The examination of( x  s, ?/ j7 E$ N
the neck revealed no thyroid enlargement.) P2 O0 }- p8 |
The genitourinary examination was remarkable for4 L1 f9 D1 {, j* [' ?* R6 H1 ]
enlargement of the penis, with a stretched length of) m# N# U6 E  T. G2 p0 K/ I+ [
8 cm and a width of 2 cm. The glans penis was very well7 ~& Q8 H9 |2 c" r" ?0 `( _
developed. The pubic hair was Tanner II, mostly around" k) X  g5 b) G
540
( \, v7 o+ e4 l) C' Y( G4 x9 Sat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from. Z/ z; d/ B% T3 W$ z3 F- E' d7 t
the base of the phallus and was dark and curled. The
" B6 k/ `5 Y8 ?* ~( k  xtesticular volume was prepubertal at 2 mL each.
! B% R! b6 ?/ {6 P; B9 hThe skin was moist and smooth and somewhat5 w& @' c! S8 E: H+ w
oily. No axillary hair was noted. There were no0 ~& x9 N# \# P' y0 j8 q8 u& @
abnormal skin pigmentations or café-au-lait spots.+ x, Y! t  ^" V* ^
Neurologic evaluation showed deep tendon reflex 2+
" N6 ]$ i( `  A3 n3 ybilateral and symmetrical. There was no suggestion5 e% h/ Z4 l6 H% o/ B$ l2 v+ H
of papilledema.
( @7 r. K- P0 h, Q8 K! G3 Z4 vLaboratory Evaluation% e+ n9 h' e7 J; @- L
The bone age was consistent with 28 months by* p/ _/ a2 C" v. ]' F2 ?0 f
using the standard of Greulich and Pyle at a chrono-
  h, h7 ~  J! N  z# Flogic age of 16 months (advanced).5 Chromosomal
* g' A. p( }. T9 p6 K# U& Qkaryotype was 46XY. The thyroid function test) |! b9 h+ R. B6 V5 h
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
8 {( F4 q3 K7 J; [lating hormone level was 1.3 µIU/mL (both normal).; n2 n) X/ O* t
The concentrations of serum electrolytes, blood" Y' L* R+ m# R! n& a
urea nitrogen, creatinine, and calcium all were  ]. w% E  @7 _5 }
within normal range for his age. The concentration  T" ~# C. D/ P: Y8 S4 E
of serum 17-hydroxyprogesterone was 16 ng/dL
# c; r& L4 q* e. w(normal, 3 to 90 ng/dL), androstenedione was 205 w+ V+ @/ ^9 r; m# L
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
. ^( ], u4 z7 |8 y: X7 `* K5 bterone was 38 ng/dL (normal, 50 to 760 ng/dL),& Q' b! _1 r6 ~
desoxycorticosterone was 4.3 ng/dL (normal, 7 to* d1 A& g- k) p4 Z# K' u; o
49ng/dL), 11-desoxycortisol (specific compound S)5 r& r1 m/ E7 B7 ?
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-: R2 A& Q& r2 Z) r( h
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
# x9 b% }  h4 L. rtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
% S+ o: |3 y2 r& o) B" dand β-human chorionic gonadotropin was less than
& o/ T& k+ K- B! c1 c9 Z5 mIU/mL (normal <5 mIU/mL). Serum follicular
4 [- g0 p6 Z# C: I7 g! R6 e" ^stimulating hormone and leuteinizing hormone
$ m/ ^$ F( ^* _concentrations were less than 0.05 mIU/mL$ o, X9 b/ W$ C
(prepubertal).6 B* U* B) ^* O, [
The parents were notified about the laboratory
6 t+ N% u5 w" n  b/ _results and were informed that all of the tests were
/ ]- S; D' F0 G- enormal except the testosterone level was high. The3 ~+ S- F6 @0 M: `% |
follow-up visit was arranged within a few weeks to
' ?0 v" k' Q9 q6 Pobtain testicular and abdominal sonograms; how-
0 [+ ~5 P. |9 f/ g" Hever, the family did not return for 4 months.6 D2 L8 b; E  c# N
Physical examination at this time revealed that the
2 Q( V0 @$ I; ~' S& j5 c$ ~child had grown 2.5 cm in 4 months and had gained
" k$ {* |: Y, C# t0 u2 kg of weight. Physical examination remained5 ]) i* Q5 k8 H* @$ O  f
unchanged. Surprisingly, the pubic hair almost com-
' Z$ Y3 C6 H0 I8 w% ^pletely disappeared except for a few vellous hairs at7 D+ f8 P8 b" _
the base of the phallus. Testicular volume was still 2
8 h( O: n! j0 J- q* omL, and the size of the penis remained unchanged.5 q/ U4 a2 a- F( }) y& Q
The mother also said that the boy was no longer hav-
, Z* h4 {) l1 Y: W  y" @ing frequent erections.
, M# {) v- t! D4 d# f6 ]0 x9 ^5 FBoth parents were again questioned about use of5 U8 p) S8 m% c9 }% r1 M
any ointment/creams that they may have applied to5 N* l! g+ ~  @2 h! Y" S" q
the child’s skin. This time the father admitted the
+ B! Z' L  k8 ~) Q  U* r- bTopical Testosterone Exposure / Bhowmick et al 541+ g6 T% S7 k' O$ F5 u0 J) o+ a9 _9 X: r( W
use of testosterone gel twice daily that he was apply-" y* i6 }9 V  w4 Y
ing over his own shoulders, chest, and back area for
; o7 v; b# t" o# M- {a year. The father also revealed he was embarrassed+ Z. K1 V4 a. }$ y5 R
to disclose that he was using a testosterone gel pre-
4 f+ f4 h5 n& ^! D; @; a$ B; p9 Zscribed by his family physician for decreased libido9 g7 q. d) {0 z. w
secondary to depression.
3 {0 F2 a$ g0 w* F8 B0 l7 J& [* oThe child slept in the same bed with parents.
! \, t1 t( l* L# MThe father would hug the baby and hold him on his
3 F2 _. F1 P. p/ q$ Y  a& M3 @chest for a considerable period of time, causing sig-
8 s( b/ d1 ~  j2 i/ R! a- pnificant bare skin contact between baby and father.
6 C2 o! N2 u5 `The father also admitted that after the phone call,
1 i0 a0 e* q* V; m9 C0 D: swhen he learned the testosterone level in the baby
4 ^9 f& ^4 b" u! s# F0 ]was high, he then read the product information
: ]* N1 u. M/ o- {- x+ epacket and concluded that it was most likely the rea-
7 A& G# \: s( _- oson for the child’s virilization. At that time, they
: a' ~5 t6 J9 l' E# ndecided to put the baby in a separate bed, and the* t* e) T* P# c6 U# S- A( ~
father was not hugging him with bare skin and had( E) O( T/ h( a; l
been using protective clothing. A repeat testosterone
- l) f9 n& Z0 ptest was ordered, but the family did not go to the+ k6 J0 C* k$ c
laboratory to obtain the test.
& s1 {% V1 [8 |Discussion: J. _6 J' U4 h- }: M/ f7 O: |, i1 R
Precocious puberty in boys is defined as secondary
+ P9 P; @1 R+ N& y1 xsexual development before 9 years of age.1,40 T8 }8 Q2 n2 j+ x) @" {& j
Precocious puberty is termed as central (true) when
0 S3 f+ [0 u0 G+ j& t# L. iit is caused by the premature activation of hypo-6 i0 k* _$ y" h3 e" q" H) u
thalamic pituitary gonadal axis. CPP is more com-
2 |% N6 A7 l0 f+ p9 j' I6 J" l% mmon in girls than in boys.1,3 Most boys with CPP% x, o& X* C9 B1 D2 h& T
may have a central nervous system lesion that is8 Y# P- t0 \0 B& V( H( B
responsible for the early activation of the hypothal-
. q! z! X7 p' q+ Iamic pituitary gonadal axis.1-3 Thus, greater empha-
& k: u% q  u  Q; zsis has been given to neuroradiologic imaging in
! e& n6 L$ W3 A2 M* w9 ^& `/ Pboys with precocious puberty. In addition to viril-/ Z6 V5 a, s+ T. T
ization, the clinical hallmark of CPP is the symmet-
' u/ ^7 w5 f+ J; Mrical testicular growth secondary to stimulation by
0 [2 V. s! r) T3 Q( u. ngonadotropins.1,3, [9 f- ^) M/ L
Gonadotropin-independent peripheral preco-2 n) a/ z$ {% Z* F
cious puberty in boys also results from inappropriate+ z/ D% l2 F6 [0 h2 ]
androgenic stimulation from either endogenous or
& B; L: ~# m/ d& [exogenous sources, nonpituitary gonadotropin stim-; c% @' [4 Q4 z! q
ulation, and rare activating mutations.3 Virilizing
8 r$ p8 H' X' T, s' ncongenital adrenal hyperplasia producing excessive
6 s; S+ Q% T8 M# vadrenal androgens is a common cause of precocious% `) d! x1 m4 t* B* C
puberty in boys.3,4- W" P! I# V, Z% K
The most common form of congenital adrenal
% }! A/ H3 T6 b1 c9 Xhyperplasia is the 21-hydroxylase enzyme deficiency.5 T8 }8 K5 K# |5 M
The 11-β hydroxylase deficiency may also result in
6 O+ {0 c2 V/ dexcessive adrenal androgen production, and rarely,- ]+ F: e7 X( y3 a7 S
an adrenal tumor may also cause adrenal androgen
: M! j) R. Y! h# J2 j$ ~excess.1,3
3 M7 [8 H  r) W' xat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from) h' t: u/ X$ a; y0 q9 O2 n
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007* W; R9 [- O$ I8 p  I( M; Y
A unique entity of male-limited gonadotropin-
% Y! w5 V. b8 M4 jindependent precocious puberty, which is also known2 p5 x9 X& Z; U7 s' N% [
as testotoxicosis, may cause precocious puberty at a
8 r  r; R" t6 S, A; R! Jvery young age. The physical findings in these boys$ N. r9 a* H% B0 W  F% v0 @
with this disorder are full pubertal development,
3 m7 r8 }( z7 ~& d4 Fincluding bilateral testicular growth, similar to boys
4 W4 A" Q! a, w. Z5 A6 Rwith CPP. The gonadotropin levels in this disorder; l' a3 q; _3 j; w. n& e
are suppressed to prepubertal levels and do not show
7 F) \& A- _9 h9 Y  Y0 e) v  o+ spubertal response of gonadotropin after gonadotropin-5 P. p* L% z- a& q6 j8 K
releasing hormone stimulation. This is a sex-linked" S8 O, N& ^, ]6 G
autosomal dominant disorder that affects only" V% r; |1 b+ d$ N3 ^' _* Y4 y# R
males; therefore, other male members of the family
" a+ m+ h: |4 Hmay have similar precocious puberty.3
+ D, I  {" R, \* PIn our patient, physical examination was incon-
- n3 @+ r) Z4 B9 M; V& I, Osistent with true precocious puberty since his testi-
! N# G& c( W5 Wcles were prepubertal in size. However, testotoxicosis
+ R8 c: G. O" Iwas in the differential diagnosis because his father- f, E) U% D2 s- K: P1 `4 H
started puberty somewhat early, and occasionally,+ a3 J' }9 v, z+ y
testicular enlargement is not that evident in the' R! x/ Z) o6 a. D5 z; D* v8 Q
beginning of this process.1 In the absence of a neg-
7 N9 g  x5 `! S/ O: M! ^* G0 Oative initial history of androgen exposure, our
2 n7 C1 `& x7 u6 P9 H* \) D' H) h; ^biggest concern was virilizing adrenal hyperplasia,/ _, ^# _- \. ?9 X& x
either 21-hydroxylase deficiency or 11-β hydroxylase
! Z! S3 p: E6 D) x( i$ E3 a( jdeficiency. Those diagnoses were excluded by find-
" o, L$ b0 v( M  |ing the normal level of adrenal steroids.! D9 f. g+ R0 o
The diagnosis of exogenous androgens was strongly9 M  }/ m3 }, B9 C. l$ @4 G
suspected in a follow-up visit after 4 months because5 V- W) S4 B: u, P% J# F- i
the physical examination revealed the complete disap-5 {) Q/ |  l, G, s! K/ G# d
pearance of pubic hair, normal growth velocity, and
; y1 l+ i1 l& n& [6 Z7 @, d' q( mdecreased erections. The father admitted using a testos-4 c* a$ F4 P8 T  G
terone gel, which he concealed at first visit. He was# j# i3 H) X' D; i
using it rather frequently, twice a day. The Physicians’
$ V! ?$ c; i2 s# a( w, N$ iDesk Reference, or package insert of this product, gel or% r& U6 E8 N2 d( u
cream, cautions about dermal testosterone transfer to
# A: J1 I8 j/ N0 s: a1 J! [1 I' Yunprotected females through direct skin exposure.5 j+ }8 U6 D: M. k: w% K$ ]
Serum testosterone level was found to be 2 times the$ }+ \6 a7 T% V- |$ v/ o
baseline value in those females who were exposed to; ?0 N' w; o) R1 Z# o3 l
even 15 minutes of direct skin contact with their male
/ g9 f/ Y) D; E8 j4 ipartners.6 However, when a shirt covered the applica-7 X! J" `* x0 A  T% L+ [0 c
tion site, this testosterone transfer was prevented.  D& K  A+ N0 v0 _/ u+ N: V
Our patient’s testosterone level was 60 ng/mL,
7 G0 N0 @6 z0 Q6 z: H6 twhich was clearly high. Some studies suggest that3 L; d( Z! D3 I0 L6 m
dermal conversion of testosterone to dihydrotestos-5 U1 }% W* m, U$ o; o8 s1 Y  n' @
terone, which is a more potent metabolite, is more
9 h$ O8 a) j: vactive in young children exposed to testosterone) A3 ^5 ~) U) U6 V" U% `
exogenously7; however, we did not measure a dihy-6 Z" [5 p; O' j$ L: ?9 C3 ?
drotestosterone level in our patient. In addition to: l. G9 e: |- Z- L- P: k. b/ p/ b
virilization, exposure to exogenous testosterone in
2 M; {/ A$ a# l; tchildren results in an increase in growth velocity and3 Y3 C8 _2 n3 C) D
advanced bone age, as seen in our patient.0 Y7 j1 U8 q0 M. e6 a; A1 |- `
The long-term effect of androgen exposure during
1 ^5 F+ e: I" t" Xearly childhood on pubertal development and final7 N  E9 Q3 o, F  a3 d2 e+ K1 a
adult height are not fully known and always remain
+ D! Q. N$ r4 l: v2 i3 wa concern. Children treated with short-term testos-
3 y2 C9 T+ V/ g% t3 I+ E+ I  s, Yterone injection or topical androgen may exhibit some$ ^* l7 z, s( [. E% X
acceleration of the skeletal maturation; however, after* h; [, R2 i' x1 N3 t2 C
cessation of treatment, the rate of bone maturation
- }9 U6 D) w* b1 `6 t  Z( Jdecelerates and gradually returns to normal.8,9) ]3 Z8 C' l4 L) m. ?, k) {+ a
There are conflicting reports and controversy
' G( J0 C. W* iover the effect of early androgen exposure on adult- D* v8 I; I" R# a6 g. o; m+ J
penile length.10,11 Some reports suggest subnormal
8 @" V+ R6 G" C) Xadult penile length, apparently because of downreg-
) A( r$ O' ~( w4 R0 [. Lulation of androgen receptor number.10,12 However,
1 E: B5 z) n) u7 BSutherland et al13 did not find a correlation between* o# x: g( N; M' D1 s, v4 G
childhood testosterone exposure and reduced adult
8 o- D3 N, |* c1 e" k2 @penile length in clinical studies.
, |8 x  c/ k- j% Z0 r8 \Nonetheless, we do not believe our patient is
" C0 y# w' _7 d, H; Ngoing to experience any of the untoward effects from0 L, f0 {% y. p2 \  j
testosterone exposure as mentioned earlier because
5 o4 a* c9 A3 U9 Hthe exposure was not for a prolonged period of time.2 w* z: y! }: z1 n1 e
Although the bone age was advanced at the time of7 {) k- Y8 \6 Q4 v9 n) Z+ f" [
diagnosis, the child had a normal growth velocity at
$ Z8 U) z9 M4 ?0 kthe follow-up visit. It is hoped that his final adult( _" s! k; R8 d5 k
height will not be affected.
9 V1 `$ A! a/ P8 _Although rarely reported, the widespread avail-
. Z  j* l$ ?1 P  ]ability of androgen products in our society may- P% r  C7 J2 m1 Y
indeed cause more virilization in male or female
# L4 y& Z" O% w5 |children than one would realize. Exposure to andro-
" `5 q/ p% |/ ggen products must be considered and specific ques-
; j# f& D$ k' M. I8 Y7 M0 U- X4 Ytioning about the use of a testosterone product or6 D+ X0 T$ @4 h4 b2 w% J
gel should be asked of the family members during+ B# B. F# M; m" y
the evaluation of any children who present with vir-
, O) Z+ ~# g% W; G, H) ^ilization or peripheral precocious puberty. The diag-: s+ M; D. L1 @- ]
nosis can be established by just a few tests and by
6 V( E3 `* d  F) }" A6 T  Y" u# bappropriate history. The inability to obtain such a
2 R7 Z- e  [1 Y* _, ihistory, or failure to ask the specific questions, may9 X1 f* b( N& E8 F8 m
result in extensive, unnecessary, and expensive6 |, h$ L: K8 F4 r/ Z' {
investigation. The primary care physician should be
1 z9 P+ c- G3 U/ [- d; m7 f$ U0 Kaware of this fact, because most of these children
& M/ l+ M' A# k3 M; lmay initially present in their practice. The Physicians’4 t3 t" A* B  H1 R
Desk Reference and package insert should also put a
- _$ [# i" Q, Vwarning about the virilizing effect on a male or
7 k8 R, L6 J1 T, Z+ U5 R) ]  {female child who might come in contact with some-
: f; _: n1 Z7 q/ }one using any of these products.
9 c. M* K; y/ VReferences* c  b* e6 ~6 M5 ^( b$ l+ b+ s, t
1. Styne DM. The testes: disorder of sexual differentiation; H2 h/ D0 e9 j8 n! Z+ V
and puberty in the male. In: Sperling MA, ed. Pediatric9 D' I9 w6 D5 F. J4 z# n, k( _! x
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
( M7 e9 ]" n9 H9 P6 U4 A7 [& y2002: 565-628.
6 l  |/ g0 W: a' M- s4 b+ X2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
/ Q+ Y5 i9 F2 i0 _puberty in children with tumours of the suprasellar pineal
發表於 2025-1-11 22:18:01 | 顯示全部樓層
女厕偷拍辅导班主任尿尿老师的逼很嫩还有一点
發表於 2025-1-17 16:31:39 | 顯示全部樓層
4个什么样的?
發表於 2025-1-19 02:41:05 | 顯示全部樓層

: E: h7 T2 ~: _/ [( V1 o精妙絕倫的精品,感謝啊!期待你更多更好的創作哦!
發表於 2025-3-11 12:31:56 | 顯示全部樓層
么好吧v进化过程就回国参加发uft成就和;哦i回来就好v科技股份兄弟人的 路由公开vu个v库每年b
發表於 2025-4-8 11:10:25 | 顯示全部樓層
精妙絕倫的精品,感謝啊!期待你更多更好的創作哦!
您需要登錄後才可以回帖 登錄 | 立即注册

本版積分規則


快速回復 返回頂部 返回列表