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發表於 2025-1-4 03:25:35 | 顯示全部樓層
Sexual Precocity in a 16-Month-Old
& u3 q+ s- X* N% a+ YBoy Induced by Indirect Topical
+ ?2 X: ]% E5 z, g* z: \Exposure to Testosterone6 ~8 u$ d9 Y; e) I: v: |
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
' x  R9 i0 i; I3 c5 ~* Xand Kenneth R. Rettig, MD10 }, }( e. O# G" z
Clinical Pediatrics  y& s- v% F8 J. t" [- n
Volume 46 Number 6' L  k! n3 M! G, i+ I
July 2007 540-5436 h/ x' b. d8 C8 x1 l, F
© 2007 Sage Publications( a7 w* S  W; K8 O
10.1177/0009922806296651
. v) r7 a& X  [8 zhttp://clp.sagepub.com
. c. M% ~6 n+ V# @' r, uhosted at
1 Q+ x0 J: W, G" q$ zhttp://online.sagepub.com
; H% x# W# F/ e( G4 {Precocious puberty in boys, central or peripheral,9 w8 `- b' {; s: y) L/ N: O
is a significant concern for physicians. Central8 @: K% b7 T# A9 F4 S; V) x9 Z
precocious puberty (CPP), which is mediated# ?& K! V1 q4 i+ a1 A4 n, l
through the hypothalamic pituitary gonadal axis, has) H7 B: j* [' T9 Z) X' I
a higher incidence of organic central nervous system
6 D5 v! @% T" `: d+ s! B; d" qlesions in boys.1,2 Virilization in boys, as manifested0 D7 m- b$ X0 n: h3 m2 O8 D
by enlargement of the penis, development of pubic1 e: H  _) @  V: o8 l+ |) ~- n
hair, and facial acne without enlargement of testi-9 ]' M1 V- M( w
cles, suggests peripheral or pseudopuberty.1-3 We% X$ }4 ~0 l9 t: F
report a 16-month-old boy who presented with the  r' ?6 g; q( O4 K- `5 ~, n
enlargement of the phallus and pubic hair develop-0 T  C- s8 x$ n# @2 x
ment without testicular enlargement, which was due5 a" ?/ U3 Z+ l1 ?# R- }
to the unintentional exposure to androgen gel used by
" `9 }( O. n+ `the father. The family initially concealed this infor-
: K- O* m+ m; i7 Mmation, resulting in an extensive work-up for this
8 ]2 P0 `2 D0 ~+ X2 R' r/ O( b8 Cchild. Given the widespread and easy availability of
: w3 P" ^8 K5 w9 k+ X2 C$ @testosterone gel and cream, we believe this is proba-
' L" R2 m4 _" h' o% wbly more common than the rare case report in the
3 Z- h6 k# A. A6 @  x# D4 Z  Bliterature.4* P+ a( g& m" u: S" t
Patient Report7 s( L8 s4 V5 d0 H. V
A 16-month-old white child was referred to the
$ Z+ `5 {3 @& m- @endocrine clinic by his pediatrician with the concern) Q4 F, @/ l' {, W
of early sexual development. His mother noticed
* l8 G5 I* i% B/ j: p& X- m7 w" y1 wlight colored pubic hair development when he was
6 z& I$ q" K1 E$ TFrom the 1Division of Pediatric Endocrinology, 2University of
" u& `' `+ k. }6 Q0 C1 qSouth Alabama Medical Center, Mobile, Alabama.. e$ s% Z3 s, S" N/ q/ V
Address correspondence to: Samar K. Bhowmick, MD, FACE,2 M5 R+ G1 X5 G7 @9 y4 [
Professor of Pediatrics, University of South Alabama, College of$ @% C  q/ F* R+ k! S9 d) [. w
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
" G: `3 A3 r9 ?$ K& M9 Q) he-mail: [email protected]./ a3 H, N; r* q4 \- ~
about 6 to 7 months old, which progressively became
" N1 F2 @& E. r0 L4 H! Odarker. She was also concerned about the enlarge-# {  C" O0 N1 x) A
ment of his penis and frequent erections. The child* g, [) R& d5 \
was the product of a full-term normal delivery, with2 T. J1 Y; V* z* Y1 n. A( m, p- b  P
a birth weight of 7 lb 14 oz, and birth length of; S0 `5 ^5 j0 |$ f* h
20 inches. He was breast-fed throughout the first year# n! I- L7 _& `8 G/ y
of life and was still receiving breast milk along with
/ z* R. i5 ]) Ssolid food. He had no hospitalizations or surgery,& W6 @- ~- l# n
and his psychosocial and psychomotor development0 }& l1 ]$ t+ i
was age appropriate.; `6 Z' j" F  d. K) ]$ I
The family history was remarkable for the father,
1 C) V0 r- j( f- O# J! M8 p- `who was diagnosed with hypothyroidism at age 16,, k0 l; S; r8 D4 @" `/ M
which was treated with thyroxine. The father’s
/ Q' Q) P1 S" H( Xheight was 6 feet, and he went through a somewhat
& D; ?! ]4 r* S( U; m: eearly puberty and had stopped growing by age 14.
: p6 y$ n8 e  v2 k; M% L$ r. J% wThe father denied taking any other medication. The
2 d" t5 C/ g$ s  t1 W: t+ w6 {child’s mother was in good health. Her menarche
; U% K( J- l7 ]- f% @was at 11 years of age, and her height was at 5 feet
" s9 y; C' z$ m( l4 y5 inches. There was no other family history of pre-8 c2 ~1 o% n& ?, S; H6 H/ J5 j! s7 R
cocious sexual development in the first-degree rela-
. K" ^( W2 f5 j. X% {. ?. Y4 Qtives. There were no siblings.% a! `( n3 V; A' j7 w* l
Physical Examination
1 g8 V7 K& b0 h, T: A- sThe physical examination revealed a very active,
0 w% u2 w$ h; ~- ~  p: Splayful, and healthy boy. The vital signs documented( a. Z- k  }6 r( \; b
a blood pressure of 85/50 mm Hg, his length was1 T8 H( ?/ P; E7 \! ~. @
90 cm (>97th percentile), and his weight was 14.4 kg
3 g+ v" Z, V$ e+ B% a(also >97th percentile). The observed yearly growth  h# V2 Q5 J$ e8 }8 N! T( s
velocity was 30 cm (12 inches). The examination of
8 `# Z+ T, }5 p9 h6 H- Z) athe neck revealed no thyroid enlargement.+ P3 u) I7 i2 ]/ ^! m  ?
The genitourinary examination was remarkable for
1 ]1 K# @* b6 J. _& B8 Cenlargement of the penis, with a stretched length of9 j0 e& m+ ^2 ]( |* y+ c
8 cm and a width of 2 cm. The glans penis was very well4 E" X% z+ \" G  [! a
developed. The pubic hair was Tanner II, mostly around
1 b/ s$ k4 J+ V; j8 x9 Q540
# p# m$ v/ Q; ^) O) O0 r/ _at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
7 B- P, l: U" V- p7 |the base of the phallus and was dark and curled. The( }$ q3 @3 N: z
testicular volume was prepubertal at 2 mL each.
: w' S# \. s. Y; O3 U1 j2 f8 [The skin was moist and smooth and somewhat" F5 ?$ u4 Z2 z) D2 s1 C
oily. No axillary hair was noted. There were no! Q0 R! |) }0 x3 y
abnormal skin pigmentations or café-au-lait spots.
7 I: F0 b5 Q. T5 l5 xNeurologic evaluation showed deep tendon reflex 2+
$ l2 Z8 E' X0 [6 r+ e; Dbilateral and symmetrical. There was no suggestion2 h3 Q% F% K* V+ X, e3 R
of papilledema.6 ~; _* e: Y  b4 \: W9 |
Laboratory Evaluation
7 k( u3 d" ^& Y+ b0 C& |The bone age was consistent with 28 months by: L1 K- Z* k8 n: B+ K
using the standard of Greulich and Pyle at a chrono-) U  T& k9 k6 b0 ]/ \0 x
logic age of 16 months (advanced).5 Chromosomal
. y* }: S& [/ F7 jkaryotype was 46XY. The thyroid function test
/ `* P8 H& G5 t6 }5 I! G& ]" K; tshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
5 U; |" T0 g) D3 ylating hormone level was 1.3 µIU/mL (both normal).
- S% }  V8 e/ i: c5 vThe concentrations of serum electrolytes, blood2 `. ~* r9 Z0 ^' i4 H, k0 C1 `) Y
urea nitrogen, creatinine, and calcium all were
- x. Z* @4 Q- q/ S$ Iwithin normal range for his age. The concentration' B1 ]; \9 p1 u
of serum 17-hydroxyprogesterone was 16 ng/dL
2 _' Q6 l4 Q2 {6 U(normal, 3 to 90 ng/dL), androstenedione was 20# J5 Z5 Z' \7 G, N/ f6 |" Y$ }; T
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
* A* z. z6 N6 }9 Gterone was 38 ng/dL (normal, 50 to 760 ng/dL),
& }# _" v( O4 {7 M4 ?$ w8 kdesoxycorticosterone was 4.3 ng/dL (normal, 7 to
" X& D2 U) `1 {3 h49ng/dL), 11-desoxycortisol (specific compound S)
+ [# t  s: n# D2 Q. V+ R, bwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
9 }/ p  ]1 `1 m; m/ ~. m$ Xtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total5 b% _, B; O; u( h* @- V9 C4 f
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
+ _" K4 G, K+ c2 |( L5 p* M' Hand β-human chorionic gonadotropin was less than2 d6 t# C# j0 u9 y
5 mIU/mL (normal <5 mIU/mL). Serum follicular
2 m1 f# X" {4 b# N, jstimulating hormone and leuteinizing hormone: F. O! U% J% l0 z, Z" n
concentrations were less than 0.05 mIU/mL
8 m* g% R9 H  i! n$ f0 s$ y- E(prepubertal)., B& N, G  r* j& P' x
The parents were notified about the laboratory- e  U( \1 y4 l' h+ S  }+ B
results and were informed that all of the tests were
5 w( j. g$ K; |# G1 ]3 Q! q9 U7 p1 ]normal except the testosterone level was high. The5 v" u& [" B0 x* c, u' _5 m! w  G
follow-up visit was arranged within a few weeks to7 f. V2 u+ z; b, g) b. Z/ {; }
obtain testicular and abdominal sonograms; how-
1 r6 R7 T  A' I" tever, the family did not return for 4 months.4 f, B, [# a  f) Q& |3 _
Physical examination at this time revealed that the. G( }% k# V& k' E( x
child had grown 2.5 cm in 4 months and had gained% y) i+ |4 e4 W% I! g* V5 z5 i8 B
2 kg of weight. Physical examination remained
$ |- V* Y* o2 }$ }& i$ d+ gunchanged. Surprisingly, the pubic hair almost com-
# l) B% _! j0 epletely disappeared except for a few vellous hairs at
/ Y& @  f- a9 b7 ithe base of the phallus. Testicular volume was still 2* C8 f4 @, j# E  d, M* w
mL, and the size of the penis remained unchanged.
4 o, {; @) }2 V) E' O( wThe mother also said that the boy was no longer hav-# \) l8 r0 F0 `/ f
ing frequent erections.
' ~  Q3 v! S8 ~8 q$ b: CBoth parents were again questioned about use of
  h4 J- O& O! p1 v( i# r5 r  C& l) Zany ointment/creams that they may have applied to
# x/ F- D, _2 }! I8 j% }the child’s skin. This time the father admitted the4 N3 p8 W$ f& K0 ]
Topical Testosterone Exposure / Bhowmick et al 541
+ ]3 ^5 R) \0 z/ ?9 Zuse of testosterone gel twice daily that he was apply-
, [4 }( E. U* |' s% O; J9 Hing over his own shoulders, chest, and back area for( \' @0 s" Q( I* G/ H
a year. The father also revealed he was embarrassed
0 n" P( ^* n; T4 t4 `$ Pto disclose that he was using a testosterone gel pre-
3 U/ t  w6 K; g3 o/ v' z9 Fscribed by his family physician for decreased libido* K$ A+ n4 Z: p1 k+ m
secondary to depression.; t9 T) `) E" ~3 n- U1 R  C6 Q
The child slept in the same bed with parents.) G% i4 t* l7 `- b
The father would hug the baby and hold him on his
( F4 J2 P$ @# b9 y; `9 Fchest for a considerable period of time, causing sig-
) z' C4 \; p' q7 [/ T5 gnificant bare skin contact between baby and father.
$ J$ }% }. V. M3 s/ B, nThe father also admitted that after the phone call,7 W) i+ A* i7 w7 w; E
when he learned the testosterone level in the baby  ~3 N$ J- w8 j/ ?& O" f
was high, he then read the product information: L" y% i& ~, d; c) @
packet and concluded that it was most likely the rea-
8 D* G, e9 E1 A. }  B  oson for the child’s virilization. At that time, they
, y3 N. B: v, _3 J" u! R( {decided to put the baby in a separate bed, and the
1 L$ U& x4 m/ U- i4 _father was not hugging him with bare skin and had4 L8 U2 v. t& e/ r
been using protective clothing. A repeat testosterone
  |2 `$ q5 {  @+ b3 ?5 \( ]" q# Otest was ordered, but the family did not go to the9 N% O  i; j/ d0 L+ ~0 L! A
laboratory to obtain the test.
" n7 F/ O0 E' H, b1 X  kDiscussion, P" m& b- z4 W
Precocious puberty in boys is defined as secondary
1 Y, j9 \- A: P4 Z0 |( Bsexual development before 9 years of age.1,4
8 g) M, Z; ^* _+ G4 YPrecocious puberty is termed as central (true) when; [1 G# [" K3 q
it is caused by the premature activation of hypo-& T* E0 U( ?4 r0 u! W9 q
thalamic pituitary gonadal axis. CPP is more com-$ E7 N: P, w6 A4 O9 e
mon in girls than in boys.1,3 Most boys with CPP" m/ ?7 j, ~" i* v; {2 W+ m3 l% c8 E
may have a central nervous system lesion that is
8 s& M3 p7 P9 Q- K% f. Yresponsible for the early activation of the hypothal-7 ~, ^- [) ?! K3 b. Q6 ]1 g
amic pituitary gonadal axis.1-3 Thus, greater empha-+ b2 ^9 ?* w" G  a9 a; l: S
sis has been given to neuroradiologic imaging in2 K1 }6 Q' @+ z' z' M- t0 B9 {
boys with precocious puberty. In addition to viril-
8 |7 V$ l9 a$ m. F% v( f9 L+ Dization, the clinical hallmark of CPP is the symmet-, i9 k" J9 @: x
rical testicular growth secondary to stimulation by
1 F9 R# Q1 h3 ]gonadotropins.1,3
" h1 t/ ]- L4 R. mGonadotropin-independent peripheral preco-
$ y/ B8 Q9 ?2 o0 W9 K; p: ]% acious puberty in boys also results from inappropriate* s1 ^# @6 E0 j( `. }' F
androgenic stimulation from either endogenous or* z6 c( R% U5 O7 @
exogenous sources, nonpituitary gonadotropin stim-
; G5 b) j( D- [3 qulation, and rare activating mutations.3 Virilizing
" ~0 r% J4 r8 \, Econgenital adrenal hyperplasia producing excessive
9 \, p2 p/ c: N) N5 V- y$ u3 x0 Aadrenal androgens is a common cause of precocious8 `" J3 ^  V' i4 N9 G
puberty in boys.3,4" U6 q4 Q5 u0 J! }
The most common form of congenital adrenal* o- x; Z( g3 X( |' z
hyperplasia is the 21-hydroxylase enzyme deficiency.+ m) [8 J) j/ t( ]7 B% E+ c
The 11-β hydroxylase deficiency may also result in5 k( B: @; H; u
excessive adrenal androgen production, and rarely,  |0 Y5 x5 E9 p! D
an adrenal tumor may also cause adrenal androgen% ]8 Y! R( ~  `0 q
excess.1,34 r% {% U: l( z- o
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
4 R4 C! [0 `2 V  {7 w542 Clinical Pediatrics / Vol. 46, No. 6, July 20071 P# E) w0 L# b  p" t
A unique entity of male-limited gonadotropin-
; H# n0 ]9 s" A% w8 s5 Q( f! c% ~  Iindependent precocious puberty, which is also known
. o9 B* T. V3 k! j% Oas testotoxicosis, may cause precocious puberty at a
6 T8 [; q% l7 {/ s" Q0 \very young age. The physical findings in these boys
4 u8 @& Q/ B1 S  B2 C" q$ e, wwith this disorder are full pubertal development,; b* p  y$ k8 ~
including bilateral testicular growth, similar to boys
+ t1 ?, ~( R! |( Y) A: swith CPP. The gonadotropin levels in this disorder# u) h2 n- m+ H) Z$ P
are suppressed to prepubertal levels and do not show
) k8 K" l* l# ^pubertal response of gonadotropin after gonadotropin-
+ e+ j; G, M0 U/ ^# Vreleasing hormone stimulation. This is a sex-linked: L6 e7 g  u) N; V
autosomal dominant disorder that affects only: ^4 K- L( ?; U8 y0 S8 P0 T" i2 C4 |
males; therefore, other male members of the family6 f) ~8 B/ O. z: B# r# ^% k
may have similar precocious puberty.3
/ A# ^; n2 }# ?/ Y- {In our patient, physical examination was incon-; P3 I4 [% \/ P. [) r9 z
sistent with true precocious puberty since his testi-
$ s& O9 Z" K: I; O0 G' Ycles were prepubertal in size. However, testotoxicosis7 b& R* {9 @7 G  G
was in the differential diagnosis because his father
. h1 _/ {' d% z( X3 q$ |; @3 I8 f# Mstarted puberty somewhat early, and occasionally,
% `8 J. S8 U6 z4 N6 J* G) y" s- Ftesticular enlargement is not that evident in the
8 q8 Q2 }* W; C/ P8 P9 Y+ Gbeginning of this process.1 In the absence of a neg-
4 F+ M! Y3 h0 h6 jative initial history of androgen exposure, our" n  H1 \7 s+ q: d$ O6 ~
biggest concern was virilizing adrenal hyperplasia," c& R9 q% P, A& P; _  L9 @
either 21-hydroxylase deficiency or 11-β hydroxylase
) V$ m3 z  V# D, Y# gdeficiency. Those diagnoses were excluded by find-# q$ Y6 m2 J" m  @( I$ \2 u& R. h
ing the normal level of adrenal steroids.
  B! C2 D: M/ f3 B( R4 hThe diagnosis of exogenous androgens was strongly# y! v% C8 r) [
suspected in a follow-up visit after 4 months because+ }$ q9 J% a; c6 T. s, t* E9 r5 H% u
the physical examination revealed the complete disap-6 T+ z8 ], P/ K: c
pearance of pubic hair, normal growth velocity, and
- I2 q$ a0 d5 M3 [4 L: Q; E2 odecreased erections. The father admitted using a testos-
( r* Z9 H) m! M- k1 M7 y8 Lterone gel, which he concealed at first visit. He was
5 ~  b; i. j; busing it rather frequently, twice a day. The Physicians’* N/ P. Z* c* E# ?! T. k
Desk Reference, or package insert of this product, gel or9 _$ x; m1 X0 p6 f
cream, cautions about dermal testosterone transfer to4 ^' Z, W3 d" c& U
unprotected females through direct skin exposure.
# r( N9 d3 T8 @* j  G+ ZSerum testosterone level was found to be 2 times the9 o0 @* w9 w" c2 d8 e' ^* _& \2 D6 }% ]6 v& j
baseline value in those females who were exposed to
5 p9 `& D. \: \, K: p7 m& b: leven 15 minutes of direct skin contact with their male
1 H# K* X4 v: h( A, E5 @partners.6 However, when a shirt covered the applica-) R  [' ?- N( R4 F: ]) _
tion site, this testosterone transfer was prevented.
% j5 G9 P9 G( U: I$ H/ ?: x9 y6 uOur patient’s testosterone level was 60 ng/mL,
( a5 s0 l* r5 Wwhich was clearly high. Some studies suggest that1 H7 Y. D" |5 M' h
dermal conversion of testosterone to dihydrotestos-
# _& l5 X- n! |, E: w% Pterone, which is a more potent metabolite, is more
/ ^. H& `$ @  ^/ e+ e6 ^active in young children exposed to testosterone% h$ K0 H1 ~: l  c0 H
exogenously7; however, we did not measure a dihy-
6 t  ?6 k4 W4 m4 ^! I0 Pdrotestosterone level in our patient. In addition to
/ e; z, ~4 k! i& Vvirilization, exposure to exogenous testosterone in7 I4 ?" A% ?" x: M
children results in an increase in growth velocity and. d  P' x3 m7 M1 g2 D4 P4 q
advanced bone age, as seen in our patient.9 Z4 B3 _  y9 h
The long-term effect of androgen exposure during% ~" E) l" N$ T- I
early childhood on pubertal development and final0 {4 ]- w' {2 `
adult height are not fully known and always remain% R* b( w( y& C" s2 t
a concern. Children treated with short-term testos-
2 [. `1 U/ l: I! Qterone injection or topical androgen may exhibit some8 P9 j2 T9 u& u5 q
acceleration of the skeletal maturation; however, after; g/ e- O; h4 J, G
cessation of treatment, the rate of bone maturation$ J4 @8 c3 m: A/ h# ]$ n1 ]7 w/ a' w
decelerates and gradually returns to normal.8,9' Y, r. Q, [4 w- f
There are conflicting reports and controversy
* m) N+ Y+ D. B+ x0 p& j4 @6 A2 A0 mover the effect of early androgen exposure on adult
  @9 Z/ t+ W/ r- lpenile length.10,11 Some reports suggest subnormal/ z" Y$ l3 Q8 D2 T
adult penile length, apparently because of downreg-
3 l3 p/ d; y2 W) yulation of androgen receptor number.10,12 However,6 P/ c! [) L7 G  ~5 W. q3 j
Sutherland et al13 did not find a correlation between( T: O8 i6 G0 r4 ^6 F4 V; b
childhood testosterone exposure and reduced adult
8 Q6 U6 ?9 l4 G* m/ H# ^penile length in clinical studies.
# A! h& w- a0 X! E2 aNonetheless, we do not believe our patient is
: K. h7 _7 Y9 Zgoing to experience any of the untoward effects from
+ u% l& D1 \4 \7 a: qtestosterone exposure as mentioned earlier because' |2 I- w% K! M, \
the exposure was not for a prolonged period of time.
8 P- C8 P' r/ y2 lAlthough the bone age was advanced at the time of& Y) B* i/ c5 ?) K/ y7 r
diagnosis, the child had a normal growth velocity at
8 S# H7 b& Z2 A: `- ]/ z1 |the follow-up visit. It is hoped that his final adult7 |' B5 E- u8 N5 A
height will not be affected.0 t5 @" d* k5 N1 k! P
Although rarely reported, the widespread avail-9 c0 X+ ]2 F& X
ability of androgen products in our society may
* o  i( R6 g8 s. [" W' oindeed cause more virilization in male or female
$ b9 [& N$ ^2 l. schildren than one would realize. Exposure to andro-
2 s, V* _$ Q6 x0 K+ C5 t4 hgen products must be considered and specific ques-. p) C3 e3 [; L( x, E. I
tioning about the use of a testosterone product or
! X2 U& M" c1 z0 [7 qgel should be asked of the family members during
& v# A1 o/ ]6 e- _) Ythe evaluation of any children who present with vir-- X# N& \! \2 N" L/ b# Y3 n2 U
ilization or peripheral precocious puberty. The diag-4 X; i: s3 }5 g  @& ~
nosis can be established by just a few tests and by
5 Q  J% W. T1 @; G3 H9 oappropriate history. The inability to obtain such a1 o1 |2 k" ^: ?2 r" ]; ~
history, or failure to ask the specific questions, may# `. Y9 f2 u* z, Z1 q1 V
result in extensive, unnecessary, and expensive9 u4 u5 g6 p. R! r
investigation. The primary care physician should be) n/ i9 T* k# h; j
aware of this fact, because most of these children
" I9 u; V9 p2 a" s: f7 dmay initially present in their practice. The Physicians’
  @/ i" }& j, D8 A; }* |! sDesk Reference and package insert should also put a
  k$ i' i- G. R' P9 a$ i& X8 Dwarning about the virilizing effect on a male or9 Z; W7 m7 F; g; R# K
female child who might come in contact with some-- Z0 Z1 ~6 y; c
one using any of these products.$ G7 N% G0 C7 H- K* K& ^8 Y3 _5 b" J
References" z3 K; q, t! ?. T* P6 n
1. Styne DM. The testes: disorder of sexual differentiation% O' H* u/ Q( J; R* ^
and puberty in the male. In: Sperling MA, ed. Pediatric' ]2 f( J9 z) ~+ l
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
1 D0 c$ o- [# O' F/ d2002: 565-628.
9 ^+ \: ?! x* L" t; \1 ?; n1 w2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious4 e2 S4 p- t" M. S/ V$ w
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-Old
! {! S' I- P) P3 p# tBoy Induced by Indirect Topical
$ z/ c! ]9 G( eExposure to Testosterone
1 s. `+ s. M* c: a7 F3 C3 [2 lSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2" m5 U9 T' [6 y
and Kenneth R. Rettig, MD1' d4 O7 C0 c7 {) x0 `
Clinical Pediatrics, T/ k) z' i2 b4 ^  K
Volume 46 Number 6
0 r1 U. c; k" TJuly 2007 540-543  }% M! |& l% h; C5 `
© 2007 Sage Publications- ^) g1 |5 W& P: g+ U5 Q% X
10.1177/0009922806296651
  x7 B9 M) q1 Y, V. \$ L% ]) dhttp://clp.sagepub.com- E0 H; f$ L+ R- b; D
hosted at
' z6 v! s* ]  {$ |+ Dhttp://online.sagepub.com
$ g! t' {* r( RPrecocious puberty in boys, central or peripheral,
* w0 V& E0 x% O- c- J+ W. dis a significant concern for physicians. Central
- n+ u; C* U# D9 C+ W6 E! iprecocious puberty (CPP), which is mediated
+ f1 C8 O: Z+ [: G8 vthrough the hypothalamic pituitary gonadal axis, has( c9 r# E; m6 S% ?) i( J
a higher incidence of organic central nervous system
' y1 F. D6 R4 Rlesions in boys.1,2 Virilization in boys, as manifested
4 J! g# R) h5 b7 {" ~by enlargement of the penis, development of pubic2 o5 V; G5 x  P) A) o. v; y0 F
hair, and facial acne without enlargement of testi-
# M% F$ J" H4 s) Xcles, suggests peripheral or pseudopuberty.1-3 We
  C) ^1 G  ~' l7 F$ {report a 16-month-old boy who presented with the
: J, R2 M  k6 D) N5 R2 benlargement of the phallus and pubic hair develop-# O5 k: V+ |9 h% o2 t' ]% r
ment without testicular enlargement, which was due: k* K) s, b. j# A+ t7 M: M# ]* o
to the unintentional exposure to androgen gel used by* W+ a1 O; X6 z3 x) R) [2 B
the father. The family initially concealed this infor-, c, q+ ~/ y6 o2 P" h7 ?
mation, resulting in an extensive work-up for this. [9 _* L- F9 T1 G' W3 r0 r
child. Given the widespread and easy availability of! G, v$ u( G/ z0 @% `
testosterone gel and cream, we believe this is proba-
& e5 X  @2 N8 o3 z; r6 Jbly more common than the rare case report in the  N4 }6 e! c* T: ^0 D
literature.42 [# _, O5 I& o1 ]
Patient Report
% j+ H; ]  }9 G+ i! R0 bA 16-month-old white child was referred to the
8 O) d" R9 H( H8 {% N( L6 \* bendocrine clinic by his pediatrician with the concern! [9 m+ [" a- F/ b2 J6 Z) |8 O
of early sexual development. His mother noticed. I+ i/ z  s8 N, d
light colored pubic hair development when he was
" Z- E, E; g6 I! G! o2 O8 s+ P+ cFrom the 1Division of Pediatric Endocrinology, 2University of
1 [9 d; t9 i, l* |% g; N2 mSouth Alabama Medical Center, Mobile, Alabama.
( S7 x- X, F/ t0 z" m7 O7 nAddress correspondence to: Samar K. Bhowmick, MD, FACE,
2 c( k6 y$ m5 X: n, B. iProfessor of Pediatrics, University of South Alabama, College of7 r6 R- Z# v3 }3 |- n! x. X
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;: p) a) |" \3 k) }! g
e-mail: [email protected].8 l  ]* [* R# I. v; ~
about 6 to 7 months old, which progressively became
* e6 |5 r. m1 g2 ]. N6 ^4 i0 p/ M' }darker. She was also concerned about the enlarge-
- f+ ^: @4 l, [$ e% t8 `, p5 Zment of his penis and frequent erections. The child
2 u& z/ b' O! F- A4 y0 gwas the product of a full-term normal delivery, with
5 A' z, {/ Y- U+ r8 J. Ma birth weight of 7 lb 14 oz, and birth length of
. K) x6 i0 u4 E& i% j20 inches. He was breast-fed throughout the first year
& y) r5 Z7 |$ c2 dof life and was still receiving breast milk along with
/ ^: @1 Q* h1 [3 h, dsolid food. He had no hospitalizations or surgery,
& z6 d: ~( D5 w' o5 Aand his psychosocial and psychomotor development
2 z* @8 R" Y4 f# Gwas age appropriate.* ^, `2 v2 z. I+ q
The family history was remarkable for the father,6 y( t$ S, K* I4 S) d
who was diagnosed with hypothyroidism at age 16,% v& F+ _2 k5 ~3 N" B& s1 ~
which was treated with thyroxine. The father’s
: G* l7 S6 a1 o5 m- a' O, K3 Rheight was 6 feet, and he went through a somewhat# o' i/ j' V- ~9 o; F
early puberty and had stopped growing by age 14.
% V% ^; T- q* \The father denied taking any other medication. The
* N  G' v8 z1 p) qchild’s mother was in good health. Her menarche
7 Q! E) j$ J4 c) S0 _" {8 s+ wwas at 11 years of age, and her height was at 5 feet% G' B7 ~* J$ I
5 inches. There was no other family history of pre-
6 s1 l) T1 \: o# m0 H8 ^8 X: s7 J. Lcocious sexual development in the first-degree rela-
0 _7 |  C* l0 P# Stives. There were no siblings.
" t6 ]! s0 a% l1 {& tPhysical Examination
$ n3 g6 u$ d- q3 J3 TThe physical examination revealed a very active,
* [9 ?/ j) j# H9 t) J* vplayful, and healthy boy. The vital signs documented: F: C1 i: ^2 T# B; ^
a blood pressure of 85/50 mm Hg, his length was, M) ~7 H0 y# |4 J" {2 g& t
90 cm (>97th percentile), and his weight was 14.4 kg
1 H7 O9 T; \, f; t, i7 n(also >97th percentile). The observed yearly growth
  O. l6 _1 b( b8 [velocity was 30 cm (12 inches). The examination of& R& M" W2 T- @: B+ ]6 u' B8 _
the neck revealed no thyroid enlargement.
1 y. B- @1 O0 O7 mThe genitourinary examination was remarkable for1 @0 G7 T1 `+ K9 L" g
enlargement of the penis, with a stretched length of
; \5 C9 @% k4 l! m+ S- U& z" V8 cm and a width of 2 cm. The glans penis was very well7 l( L1 p8 K  O' y: t
developed. The pubic hair was Tanner II, mostly around' L! L. W) z( ~! t- a' s  B
540/ ?9 S+ q1 g% a; @3 M' i
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from# B8 [1 v9 [* V/ y$ v3 X5 j- O) K
the base of the phallus and was dark and curled. The
: ?8 K- e5 Q1 X% b) L' g# i8 wtesticular volume was prepubertal at 2 mL each.4 h* u2 x# R9 e' k3 I
The skin was moist and smooth and somewhat5 U% m4 N$ G7 m: A* [8 l5 {& `9 A
oily. No axillary hair was noted. There were no
) }) i$ i7 e( m9 t1 Z6 A/ mabnormal skin pigmentations or café-au-lait spots.
  _2 [$ s+ M% P6 q0 @Neurologic evaluation showed deep tendon reflex 2+( \! d; Z: v7 B9 `! {. S, S
bilateral and symmetrical. There was no suggestion/ z1 q$ k8 ^9 V; R2 e
of papilledema.
+ G! I7 g" r* |Laboratory Evaluation
: |- o+ q' {. X$ G) b5 }# CThe bone age was consistent with 28 months by0 S, U, C& t6 [2 ?
using the standard of Greulich and Pyle at a chrono-
8 A$ r; r8 `  i) Q0 Plogic age of 16 months (advanced).5 Chromosomal" S, N* \7 A, C/ S/ g+ A' `
karyotype was 46XY. The thyroid function test+ ]4 Z+ V, V6 M0 Y; t4 h6 |8 w$ ^
showed a free T4 of 1.69 ng/dL, and thyroid stimu-/ Z7 C& D5 E3 @4 F. v3 R5 H" m7 S
lating hormone level was 1.3 µIU/mL (both normal).
& E, P; E6 w7 D" B  O9 I' b8 cThe concentrations of serum electrolytes, blood
) P5 c1 G" b& curea nitrogen, creatinine, and calcium all were
! J) V1 m8 s8 _6 k4 Vwithin normal range for his age. The concentration
2 w! c* g2 s( b3 Tof serum 17-hydroxyprogesterone was 16 ng/dL7 C0 p. S! C$ p6 u
(normal, 3 to 90 ng/dL), androstenedione was 20* c0 j' B  |% ~* a: \
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
7 i" W; T7 y' E: Xterone was 38 ng/dL (normal, 50 to 760 ng/dL),3 G( j, w5 O8 K7 b7 q1 W7 j
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
5 P# |( B2 T3 F' A2 v2 P49ng/dL), 11-desoxycortisol (specific compound S). a) h7 s4 K1 u0 Y
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-4 N7 r" U9 y8 C! c$ o" M
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
4 y/ v6 s! j3 vtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),( K! `, n/ s- m1 x2 M
and β-human chorionic gonadotropin was less than, j& Z. X, q1 s+ u
5 mIU/mL (normal <5 mIU/mL). Serum follicular4 I! _6 m, C( z4 H  i, f7 |
stimulating hormone and leuteinizing hormone  S- C9 B# ^( t( f( k( e4 }% _7 |
concentrations were less than 0.05 mIU/mL6 {& [. }% f# x5 Q; D) A- F+ v& k. l
(prepubertal).4 y6 w" V, h7 m$ D8 i7 I
The parents were notified about the laboratory
1 g/ N# I$ y7 Wresults and were informed that all of the tests were0 u$ B: ]" S* ]6 k9 c
normal except the testosterone level was high. The
7 X/ t+ }+ E& W! T7 ufollow-up visit was arranged within a few weeks to
' I7 |& Y  @( I) ^( mobtain testicular and abdominal sonograms; how-% _8 g3 f- S( d8 l1 a- ], |! }
ever, the family did not return for 4 months./ o# T% U3 g# I$ q
Physical examination at this time revealed that the
; B. }$ [  W% S" Uchild had grown 2.5 cm in 4 months and had gained/ N' N- Y: o! a, T/ C1 V- f; D
2 kg of weight. Physical examination remained
6 }6 O  i  L/ i) `! [- }" h' Tunchanged. Surprisingly, the pubic hair almost com-
- I: Y# @2 o9 K8 O' S/ b4 w0 Opletely disappeared except for a few vellous hairs at
0 z# u$ C: w* M& D! ?! Vthe base of the phallus. Testicular volume was still 2+ V/ N/ Z! ^& r2 v; r( V
mL, and the size of the penis remained unchanged.' D2 j/ M4 n/ S, g
The mother also said that the boy was no longer hav-
: s3 d0 n) T3 ning frequent erections.
" d, n4 S/ R/ H: [" E! H2 |" DBoth parents were again questioned about use of
) q1 }- A/ P0 T- F/ Wany ointment/creams that they may have applied to! N) Z$ ]( N4 O, u
the child’s skin. This time the father admitted the4 H/ V; c/ O/ _: i
Topical Testosterone Exposure / Bhowmick et al 541
* H$ E, K9 f8 e( s  huse of testosterone gel twice daily that he was apply-
" y3 l0 B2 z7 q* ~' f0 t8 e1 O- Wing over his own shoulders, chest, and back area for
' \% a; t; w+ q! F- T# C7 oa year. The father also revealed he was embarrassed5 R( e' V7 h5 Z8 M- d  ?
to disclose that he was using a testosterone gel pre-
; @' c2 Q4 J9 pscribed by his family physician for decreased libido/ V( J/ W! J% G: }6 E( j
secondary to depression.9 y5 ~1 f3 m- O4 A, w$ n7 u/ G! Q
The child slept in the same bed with parents.
9 ?# N! S# E2 v" Y3 ~" i8 LThe father would hug the baby and hold him on his
3 @) [% J8 z& Mchest for a considerable period of time, causing sig-
4 d2 g5 Y$ z' o! a* x. Anificant bare skin contact between baby and father.
( ]7 }, e) G0 L7 {+ f- O% r( r( sThe father also admitted that after the phone call,
- ^2 c9 D3 @2 v6 `when he learned the testosterone level in the baby/ v. p: X. ?2 B5 k; V4 {1 d
was high, he then read the product information# S% h$ f8 a& ]+ ^& W
packet and concluded that it was most likely the rea-# C2 _: _4 X% n) e3 q0 G) g
son for the child’s virilization. At that time, they4 ]8 q1 @) |* N- E! T( [
decided to put the baby in a separate bed, and the0 f' l# a2 F' G
father was not hugging him with bare skin and had
! G/ ?5 P% S" }1 D# N; Abeen using protective clothing. A repeat testosterone4 Q8 f6 c- {: p6 x/ B% O
test was ordered, but the family did not go to the
. |3 g# E1 I* z9 l0 ?laboratory to obtain the test.
% J( t- |; f& JDiscussion
4 v5 ?; z. Y0 W1 y- B9 Q8 }/ ?# bPrecocious puberty in boys is defined as secondary9 J7 E4 f5 ]) C$ K6 O
sexual development before 9 years of age.1,4/ v7 K- i4 d% u4 F
Precocious puberty is termed as central (true) when
/ w! K2 i# ~4 h" `6 [1 ~  yit is caused by the premature activation of hypo-, d. u+ i1 X% p( q
thalamic pituitary gonadal axis. CPP is more com-
, f; ?! X/ l( o& ^6 h. }0 M! ymon in girls than in boys.1,3 Most boys with CPP) b+ b0 h( W$ B9 g/ v/ h
may have a central nervous system lesion that is0 n! D8 z( C/ W  d# y
responsible for the early activation of the hypothal-
" t* E; y: c2 S( |' u' {1 Y* Jamic pituitary gonadal axis.1-3 Thus, greater empha-! l0 q7 J4 ~. l
sis has been given to neuroradiologic imaging in# l% e8 q6 w# o' [# r1 x, y7 Y
boys with precocious puberty. In addition to viril-
9 y6 @' f; b7 q# M$ @6 oization, the clinical hallmark of CPP is the symmet-
) Z0 P6 w* e: D# lrical testicular growth secondary to stimulation by" o' c5 G1 @( r2 J' G
gonadotropins.1,3, p* b9 L1 g3 O
Gonadotropin-independent peripheral preco-( Y0 d" `! w& R( a7 e  L
cious puberty in boys also results from inappropriate3 Q. h- o  D  B
androgenic stimulation from either endogenous or
- x/ |! ]! e; {  s9 C( j( S9 P' a. gexogenous sources, nonpituitary gonadotropin stim-
8 w5 Y5 W; `$ gulation, and rare activating mutations.3 Virilizing* F& {2 r. H7 I
congenital adrenal hyperplasia producing excessive- N5 f; m6 U& d
adrenal androgens is a common cause of precocious
. j2 B: C( F" l9 ?0 l3 M7 mpuberty in boys.3,4$ g. x3 ^4 h! ]- W
The most common form of congenital adrenal/ t5 M" ~+ V& ]2 I! {4 q
hyperplasia is the 21-hydroxylase enzyme deficiency.5 }1 k0 Q) ]0 B: n5 i, B* r  d
The 11-β hydroxylase deficiency may also result in' x: J0 }& \$ d0 t. S% R
excessive adrenal androgen production, and rarely,$ N( {( f- x4 f  ]7 \
an adrenal tumor may also cause adrenal androgen
, G; R) r4 X8 x0 d8 P/ Q& p) ^excess.1,33 v' @1 P; g- q% f* \
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from, W8 m- a& V' G, @0 X
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007% _" f0 o- c0 D2 a4 ]- y
A unique entity of male-limited gonadotropin-; K0 E3 ]; S$ P
independent precocious puberty, which is also known
" Q  y3 T: {! kas testotoxicosis, may cause precocious puberty at a
9 f3 z# Y4 L+ n5 ]* C& Rvery young age. The physical findings in these boys
0 y: {6 {0 ~' }0 t, v) x2 owith this disorder are full pubertal development,) Y% R# x) I1 x6 X
including bilateral testicular growth, similar to boys; T# b  d1 c0 |
with CPP. The gonadotropin levels in this disorder' `: b( ?0 C7 ~) Q
are suppressed to prepubertal levels and do not show7 Y- m/ H1 [( Z- q5 R1 h3 x- q
pubertal response of gonadotropin after gonadotropin-' `3 \% D& @0 h# k. H; k
releasing hormone stimulation. This is a sex-linked- X% Z2 ?5 @0 {) `# w( A
autosomal dominant disorder that affects only, {4 d+ C+ X4 l4 A" Z% G7 a
males; therefore, other male members of the family
2 P$ d. a3 Y. n0 R$ z6 umay have similar precocious puberty.3
% V, S' f7 Z5 G* ^' {; Q7 i- cIn our patient, physical examination was incon-
% y2 \4 p4 x- }. @7 zsistent with true precocious puberty since his testi-
1 g% g6 i; I: i- kcles were prepubertal in size. However, testotoxicosis
2 r; o" k4 h3 l# i) S1 l' Ewas in the differential diagnosis because his father
/ I/ N* I' w" V2 Istarted puberty somewhat early, and occasionally,% F2 {. k7 p3 `) }+ a
testicular enlargement is not that evident in the8 G  n$ k( T" F% X' c. d
beginning of this process.1 In the absence of a neg-
; m2 j7 v2 M1 L9 i) `$ native initial history of androgen exposure, our% e- J4 c- u6 R: W# l) O
biggest concern was virilizing adrenal hyperplasia,/ s6 j: P" Q, }5 I6 O( e" M2 J
either 21-hydroxylase deficiency or 11-β hydroxylase
* i. \! ~7 Z/ P, j; G. E6 Bdeficiency. Those diagnoses were excluded by find-
* b- {1 H$ V0 ^4 Cing the normal level of adrenal steroids.1 t% ?# b2 j! H7 p2 C
The diagnosis of exogenous androgens was strongly
' g1 N7 h2 m' D( n' Jsuspected in a follow-up visit after 4 months because3 s( O7 `2 d1 }& t+ ^. _3 }
the physical examination revealed the complete disap-* O$ B% o* Q1 o0 j6 {; t& ^9 R+ R
pearance of pubic hair, normal growth velocity, and
. k+ _( n( w, L" ?! V: x1 }decreased erections. The father admitted using a testos-
" s1 R2 M: e! E9 @/ oterone gel, which he concealed at first visit. He was
' i* V6 A7 T4 g( O  ausing it rather frequently, twice a day. The Physicians’
7 {- J, `6 c$ A; ~& T+ N2 ^% ^Desk Reference, or package insert of this product, gel or) \8 `" _, |" Y, v& L+ |+ m
cream, cautions about dermal testosterone transfer to
6 d3 b5 }* n: G; p( E- vunprotected females through direct skin exposure., o6 v% N7 W! O2 Y& E- F5 {# k
Serum testosterone level was found to be 2 times the
! H7 g0 G9 ^4 F! [baseline value in those females who were exposed to
  L$ ~- |& R! P+ r+ A2 A% `even 15 minutes of direct skin contact with their male  M- L; ]5 _5 g- Y' t, y4 j
partners.6 However, when a shirt covered the applica-) |1 D6 A+ p3 S; }: J
tion site, this testosterone transfer was prevented.4 {9 }8 x4 @) v/ }! m% I
Our patient’s testosterone level was 60 ng/mL,6 [- ^; Z2 ?/ X
which was clearly high. Some studies suggest that4 d7 A. h$ g% q% Z+ L: A5 V  y
dermal conversion of testosterone to dihydrotestos-
. S: A2 B6 K. T, |terone, which is a more potent metabolite, is more
" }: u! j# \; b+ D4 Eactive in young children exposed to testosterone5 {" x  u( Q6 T8 G
exogenously7; however, we did not measure a dihy-0 E; q* R: L7 A3 e+ P) h- Z
drotestosterone level in our patient. In addition to
; \" x* k8 g, ~; R& e; Q7 \virilization, exposure to exogenous testosterone in% T1 q7 @8 m( k$ [5 x- n9 ~
children results in an increase in growth velocity and, g) `( q9 L9 r8 }9 W0 p
advanced bone age, as seen in our patient.% k0 j9 Y2 V, V7 c+ t* P
The long-term effect of androgen exposure during; ]9 j. R( W! [! j: g4 {5 ~
early childhood on pubertal development and final
3 [2 J5 t; k2 H& ^adult height are not fully known and always remain5 i7 |2 C5 [6 k! C
a concern. Children treated with short-term testos-
2 h5 t. C9 _5 ~% R$ T$ Oterone injection or topical androgen may exhibit some7 }: ?+ Z. [7 J3 h0 [& Y4 ]
acceleration of the skeletal maturation; however, after
7 ~; j) T; H& d- H4 k$ [cessation of treatment, the rate of bone maturation; V) n3 r8 ~, q7 y: W* _
decelerates and gradually returns to normal.8,9
. x( g% ?: z! W3 j& l+ FThere are conflicting reports and controversy& B3 w/ _$ h/ j  q1 U" f
over the effect of early androgen exposure on adult
( Z. Y2 |; K$ j8 c5 Npenile length.10,11 Some reports suggest subnormal* g" t+ o7 ^( e- t, |7 B6 s
adult penile length, apparently because of downreg-+ j5 v; t) g" [  v) S
ulation of androgen receptor number.10,12 However,' d7 s4 E3 L6 g, P" U
Sutherland et al13 did not find a correlation between
4 a3 z9 s6 C! O9 C) ?& }5 c( Bchildhood testosterone exposure and reduced adult
# p% H  c1 L! J' b, k( jpenile length in clinical studies.
; r/ H! ?) }* K" lNonetheless, we do not believe our patient is
4 J$ `6 ~* l( L" jgoing to experience any of the untoward effects from; g4 M* ^  {) i, @
testosterone exposure as mentioned earlier because; x9 X, M  ^, W, l. z- {
the exposure was not for a prolonged period of time.
. V$ D0 n$ o3 s8 T% f# |6 E8 JAlthough the bone age was advanced at the time of
% ~5 N! ?7 N; p* V. I" I) Odiagnosis, the child had a normal growth velocity at) u  [' w" K+ J# C1 @4 k1 p, E
the follow-up visit. It is hoped that his final adult: H' e8 C+ \2 u; p
height will not be affected.( d; z# o" h3 `) W! P
Although rarely reported, the widespread avail-8 S4 ~7 P, B8 q7 x: X
ability of androgen products in our society may! o7 I% s) Z; _- Y4 n0 j8 f
indeed cause more virilization in male or female" g: @% ~; c$ ?7 s
children than one would realize. Exposure to andro-! v" X3 @: Q: _( `! E. I
gen products must be considered and specific ques-
7 I7 }2 P: P' U3 d! y: e8 H& Ztioning about the use of a testosterone product or! S# u' `: |; T5 n7 }$ m
gel should be asked of the family members during# L) O, d1 L) U
the evaluation of any children who present with vir-
# y% N) {4 K& O9 D9 rilization or peripheral precocious puberty. The diag-
- z+ A* `8 x! enosis can be established by just a few tests and by* k2 G' p! ?8 ^/ b
appropriate history. The inability to obtain such a
$ G4 Q# b5 Y  F7 r  u; v% {history, or failure to ask the specific questions, may5 N: X" q$ D3 ]% v) {, s* A: B% ?
result in extensive, unnecessary, and expensive
: C" A* v4 r! @, Ainvestigation. The primary care physician should be- ?+ c' V- g, C
aware of this fact, because most of these children
# i( p" V0 l( R* R  N+ Kmay initially present in their practice. The Physicians’8 M1 A. c( h- M8 ~
Desk Reference and package insert should also put a: }  Y1 l$ m' B2 {" c. [
warning about the virilizing effect on a male or9 l) b8 D5 E. l: t+ t$ j0 C8 v
female child who might come in contact with some-& E2 m0 N1 W+ |- k. q' ^5 p+ P
one using any of these products.: `8 Z$ ?) n7 ]- f+ D) N
References
! [9 y" K$ }! N! f6 k2 Z1. Styne DM. The testes: disorder of sexual differentiation
. N( [( a3 i6 K# l: Iand puberty in the male. In: Sperling MA, ed. Pediatric
, ~$ @! R& R. m2 |9 r" h- x( @Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;+ \: l1 c: ~2 I9 W! g, h" B2 Y" _
2002: 565-628.
5 |4 ^  i* R# \9 @& h9 R5 I' g2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
- X* @: N6 \+ H& M2 K3 G7 h, [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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# K4 c, {( ~" T6 d8 ^3 Y
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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