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Sexual Precocity in a 16-Month-Old# _8 s0 U  @4 K
Boy Induced by Indirect Topical
( ]1 r5 L# I3 ?Exposure to Testosterone1 V& H. C7 W% _& R
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
) B/ S: [- C6 T: k/ Band Kenneth R. Rettig, MD1- ?# t: P: |5 a0 [' w- s
Clinical Pediatrics6 w) P$ T9 y) r6 r
Volume 46 Number 6
- k/ F+ D& `7 N* @4 Y% ?$ aJuly 2007 540-543
; B* l2 }" V4 }* u2 b, m© 2007 Sage Publications8 V/ E/ k" m% C+ g  s) m. A: a
10.1177/00099228062966515 }2 F3 K- j* k* S, g0 r
http://clp.sagepub.com7 B  w4 @& P" \0 ]* x& J
hosted at
; f/ U% x- J- T4 B9 ahttp://online.sagepub.com
) W, `6 b# y) }% @. E4 `. g+ r/ WPrecocious puberty in boys, central or peripheral,+ [: |: G" f) x  ^' D* A- G/ y0 w
is a significant concern for physicians. Central" H, E& M$ Q4 d. ~* y0 U
precocious puberty (CPP), which is mediated; {4 F3 r/ z+ R' a; o  @4 e
through the hypothalamic pituitary gonadal axis, has: s$ D/ n$ u1 g# [- }" J5 o
a higher incidence of organic central nervous system5 W( Y: n5 Y+ r
lesions in boys.1,2 Virilization in boys, as manifested, M6 o! }  j7 n! P. Q! w2 i. \
by enlargement of the penis, development of pubic
8 u+ C) @' x+ I. R  e& ^- C& t1 `hair, and facial acne without enlargement of testi-+ n2 d& y) l- g6 A4 {, R
cles, suggests peripheral or pseudopuberty.1-3 We2 n/ y3 n$ ]! F8 [# m
report a 16-month-old boy who presented with the5 N5 s& Q5 X" B) q) Y/ X/ y3 y
enlargement of the phallus and pubic hair develop-
5 R& E7 m" m- U) L8 yment without testicular enlargement, which was due2 |' M7 d8 V: N3 u: M5 S
to the unintentional exposure to androgen gel used by6 R/ ]8 U; `' o" q2 J" C
the father. The family initially concealed this infor-+ J' v* z. P6 |
mation, resulting in an extensive work-up for this
1 w0 s- h* A8 s/ Uchild. Given the widespread and easy availability of
9 m3 @: ]5 @4 ^" [3 g' {testosterone gel and cream, we believe this is proba-
; }7 Q% x0 |& @' [! F6 |4 r  ybly more common than the rare case report in the
6 h$ E5 f& Z  N7 {. i9 b: ]9 G9 ?literature.4
# i- g* Z  V- X  z" UPatient Report
+ i  R' E' Q( C1 G5 ~A 16-month-old white child was referred to the
! n# V! ?( j- q4 y- |endocrine clinic by his pediatrician with the concern
9 z( O2 c  s. Y, N" o5 Mof early sexual development. His mother noticed9 A) H3 k' }9 E' O4 o
light colored pubic hair development when he was3 M* ~4 M# Y8 Y* c2 p: c
From the 1Division of Pediatric Endocrinology, 2University of& v" B8 q6 R2 V( b. p9 X- [
South Alabama Medical Center, Mobile, Alabama.7 C' G5 b, y( g0 v. a
Address correspondence to: Samar K. Bhowmick, MD, FACE,
# l* u* ^3 q" ^- o) U5 aProfessor of Pediatrics, University of South Alabama, College of6 d) D$ p9 G( c. x# ~
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
  f# `8 M$ c8 D# _e-mail: [email protected].
2 J- a$ j" p  ]8 m& Dabout 6 to 7 months old, which progressively became1 R5 k3 x& K! n- q
darker. She was also concerned about the enlarge-" q- T# B8 |- L& a$ [' R
ment of his penis and frequent erections. The child  y" S- ^) X1 e  s0 p
was the product of a full-term normal delivery, with( \) s9 D6 k4 t. [, ~& l
a birth weight of 7 lb 14 oz, and birth length of
5 x) s1 F* y- W7 B/ e* E2 Y2 k20 inches. He was breast-fed throughout the first year$ m9 s9 |. z' x
of life and was still receiving breast milk along with
9 t1 H7 h9 E' q; o1 |' b6 M+ wsolid food. He had no hospitalizations or surgery,6 U6 g% N/ x5 K6 G3 m
and his psychosocial and psychomotor development* X2 l# [; H# s3 }7 j7 }3 N) s
was age appropriate.7 K8 e0 |$ S$ [. }- Y# u) Q
The family history was remarkable for the father," ~4 B8 P" F2 z, a
who was diagnosed with hypothyroidism at age 16," i8 W8 M+ ]' x2 y9 d
which was treated with thyroxine. The father’s
- U; C0 K' \: ~. V! u2 @2 i0 I& A9 dheight was 6 feet, and he went through a somewhat
- F  S' J: U1 Oearly puberty and had stopped growing by age 14." y% f6 a1 k& s- E
The father denied taking any other medication. The* x5 E. ^" I! X. |+ i2 s
child’s mother was in good health. Her menarche" p1 {8 t9 _% Z8 H9 n/ {
was at 11 years of age, and her height was at 5 feet. p8 Y8 [# C- p
5 inches. There was no other family history of pre-
) b9 ]+ [, A" B. hcocious sexual development in the first-degree rela-
" z5 P& V( j. etives. There were no siblings.3 ?6 z9 v" `# |9 b/ ^% h& N8 M0 n9 n
Physical Examination
" S, [- G$ T; A  x. ~The physical examination revealed a very active,
/ r4 T2 ?& `& uplayful, and healthy boy. The vital signs documented: J) A4 n; r( y2 S
a blood pressure of 85/50 mm Hg, his length was
: d7 `* i8 u* d2 z90 cm (>97th percentile), and his weight was 14.4 kg
7 Y' ~/ n; Z$ b0 s(also >97th percentile). The observed yearly growth
  h) T( {& f, s$ _# q! G' L2 b3 N" q. wvelocity was 30 cm (12 inches). The examination of
# I4 e: g, V) L" d+ W7 P7 Wthe neck revealed no thyroid enlargement.  w" A! f5 u- ~: S, n: r; z
The genitourinary examination was remarkable for* i, u- S( i3 X4 I
enlargement of the penis, with a stretched length of0 p1 [# ^; G9 v3 _" ?
8 cm and a width of 2 cm. The glans penis was very well
. I/ A0 ~. H3 \% O( ~developed. The pubic hair was Tanner II, mostly around1 `& I; X/ M2 Y" [  r& ?* ~
540
% }3 A7 v6 G  [* F5 J, y' g" aat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
8 ~" J  l; P# J. V0 f5 F/ Lthe base of the phallus and was dark and curled. The3 Q7 Q) F0 v  U4 i9 U0 v% Q$ E# Z
testicular volume was prepubertal at 2 mL each.
# O& X: L' P# ]  mThe skin was moist and smooth and somewhat" N$ W1 H4 U- _0 X5 H& Z
oily. No axillary hair was noted. There were no
. O8 f) K# U5 `7 L- }5 _abnormal skin pigmentations or café-au-lait spots.
7 t3 j2 [* F; n- V7 l4 o$ FNeurologic evaluation showed deep tendon reflex 2+% X2 w2 f6 a$ e! \( y5 ^; t: j
bilateral and symmetrical. There was no suggestion
0 j2 R+ L" r+ h3 ^2 mof papilledema.5 h0 N* g+ t+ d/ c. e' @! }5 |$ ?
Laboratory Evaluation
9 U! ], L6 S) I) \- QThe bone age was consistent with 28 months by2 \% G7 \8 Y( q
using the standard of Greulich and Pyle at a chrono-
6 \" R$ ~4 X+ W" Y/ |logic age of 16 months (advanced).5 Chromosomal- I( U" W" Z4 W' X
karyotype was 46XY. The thyroid function test, {, l8 e  n; }+ W. u# Q1 [8 Y
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
* Y) z  X( E  ^  B2 M, ~1 dlating hormone level was 1.3 µIU/mL (both normal).
! R# i0 f, r9 c% Z: J! X# _The concentrations of serum electrolytes, blood9 d9 D# b: \3 m; e, Q8 S
urea nitrogen, creatinine, and calcium all were" y8 k5 M$ x: }" L1 w# [4 o# a% H1 B
within normal range for his age. The concentration, B6 C* L9 m6 X. O: Q
of serum 17-hydroxyprogesterone was 16 ng/dL
  P1 x. ^& F; w(normal, 3 to 90 ng/dL), androstenedione was 202 F# Y5 _# E% D; B
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-5 ~- W2 R/ g, d) T7 g# w
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
/ P! Q$ K: Y2 M. F! t) Jdesoxycorticosterone was 4.3 ng/dL (normal, 7 to( x' p5 c" H8 I
49ng/dL), 11-desoxycortisol (specific compound S)1 }, t4 `& g1 S+ U- n# K& E6 L' S* ]) @
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
) R. \: j% G5 F: N$ ctisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total5 x  v5 Q$ T+ Q
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
4 Q. U; G! k5 n) }4 ?) dand β-human chorionic gonadotropin was less than
$ L5 I/ ~& t! O4 f( J2 c& w5 mIU/mL (normal <5 mIU/mL). Serum follicular
: s2 N2 K6 [. D' ?stimulating hormone and leuteinizing hormone
0 }: o9 F5 A# Xconcentrations were less than 0.05 mIU/mL* {4 z, W: X. ?" d1 d. D( ~2 z
(prepubertal).
7 Y6 ]! q/ |7 s2 a. M( V: c  sThe parents were notified about the laboratory* @1 y) `. z0 h, \# B
results and were informed that all of the tests were; N2 ?- z+ c/ r5 b) {+ o
normal except the testosterone level was high. The8 w" k! M1 h$ T. t) x
follow-up visit was arranged within a few weeks to
; g# e( \. r7 u! A( `* r8 Iobtain testicular and abdominal sonograms; how-
3 v1 s( N% @* ~$ qever, the family did not return for 4 months.
% p! \1 F  S" x  ~( d- ]) hPhysical examination at this time revealed that the9 m! i' |' w$ t& `1 Q
child had grown 2.5 cm in 4 months and had gained
: [& N9 S% l8 }/ Z. |2 kg of weight. Physical examination remained
" B: _4 E1 W# W, X& X% {: Lunchanged. Surprisingly, the pubic hair almost com-1 B0 b; B7 O5 {
pletely disappeared except for a few vellous hairs at1 j$ n# _. t; v4 a$ z8 B
the base of the phallus. Testicular volume was still 23 Y9 D; e. n# L( ]- k+ F
mL, and the size of the penis remained unchanged.  ^' F) L5 d" {
The mother also said that the boy was no longer hav-9 D6 e1 T) W& G' B
ing frequent erections.
1 r5 ^3 b; N1 t, I* S6 EBoth parents were again questioned about use of
, \& h! F# |1 y9 Oany ointment/creams that they may have applied to+ e, G0 {4 r0 M4 _7 s; ^3 J
the child’s skin. This time the father admitted the
- I# G* P# X$ i9 ~: PTopical Testosterone Exposure / Bhowmick et al 5416 I, n& a! \/ p+ _& c  B: K% o
use of testosterone gel twice daily that he was apply-: i# I5 O- p- w$ T+ [+ `! S
ing over his own shoulders, chest, and back area for( a' J8 B! T# C" d+ V
a year. The father also revealed he was embarrassed
( J5 e2 B+ }& Fto disclose that he was using a testosterone gel pre-
' y" D, C4 }! M- wscribed by his family physician for decreased libido2 [2 ]  X( m  D
secondary to depression.
* x8 o2 r9 K: ~- g% y2 vThe child slept in the same bed with parents.
' E* L$ J, l9 s/ J/ w1 M/ m, tThe father would hug the baby and hold him on his, ]% y0 W/ F, M8 O2 b: ]
chest for a considerable period of time, causing sig-, c& N# \1 i& D. m4 Q) I
nificant bare skin contact between baby and father.8 u% k) {" Q  |: |  t# r8 `" E# h
The father also admitted that after the phone call,/ V! I. r! x3 B) ^  E
when he learned the testosterone level in the baby3 n* R  h7 O# |# q$ o; d
was high, he then read the product information
' N0 g. L4 [. O( D" b6 Cpacket and concluded that it was most likely the rea-
9 ]9 N0 y% t& W* r  t- y* ison for the child’s virilization. At that time, they) |; a6 N+ t3 P/ L- g
decided to put the baby in a separate bed, and the
' v  s7 {+ r# C2 Vfather was not hugging him with bare skin and had2 C/ K0 L: X0 U$ i5 G+ V& h
been using protective clothing. A repeat testosterone. d! x+ G1 d- n$ [. W
test was ordered, but the family did not go to the9 L$ K; V2 ?# o9 r$ D; f* i
laboratory to obtain the test., F+ l: S! k! c* B) F; {. K1 [
Discussion
  U" I6 p' T% ]% {+ p) ~$ \Precocious puberty in boys is defined as secondary
6 a8 t, H) C2 zsexual development before 9 years of age.1,4
- [2 C( F' J1 e+ w+ Z' N( y  y+ dPrecocious puberty is termed as central (true) when
) j  V: v1 [9 V+ Z, x' {it is caused by the premature activation of hypo-1 m, c6 A+ j4 M- w: B
thalamic pituitary gonadal axis. CPP is more com-
( A: n% F8 L6 L- f* }& b9 l, dmon in girls than in boys.1,3 Most boys with CPP- F( \; J3 r6 a$ g! Q* r; s* I  p
may have a central nervous system lesion that is6 k0 o$ p6 D8 h5 _0 f
responsible for the early activation of the hypothal-) d3 ]. R! m' n6 |
amic pituitary gonadal axis.1-3 Thus, greater empha-8 w. e7 ^( ?$ T: A! e
sis has been given to neuroradiologic imaging in
0 e* {; i! B! o& k* bboys with precocious puberty. In addition to viril-, B+ r) Y1 v' ~/ Y- |
ization, the clinical hallmark of CPP is the symmet-
' j& |  h$ e5 `. erical testicular growth secondary to stimulation by4 A+ v  u% B3 q" T% I; U
gonadotropins.1,3
3 _1 c3 h" x1 z& N! KGonadotropin-independent peripheral preco-9 V1 ^* [5 o! {" P. {$ F: J
cious puberty in boys also results from inappropriate/ p4 C. l& L$ L5 M  q
androgenic stimulation from either endogenous or5 {' r: |! `! F) @4 w3 t
exogenous sources, nonpituitary gonadotropin stim-  _7 b5 q/ J) {- i$ Q4 P, G2 R
ulation, and rare activating mutations.3 Virilizing$ e# O( I, a$ L4 i" ~. i
congenital adrenal hyperplasia producing excessive
+ |/ w6 g. {3 P4 v2 v) q- j1 {- tadrenal androgens is a common cause of precocious
/ S4 R" ^- z; m% i; k8 w: Wpuberty in boys.3,4
. h% f% R/ p( a/ tThe most common form of congenital adrenal- x  c( q9 K/ L! m" U! f; e
hyperplasia is the 21-hydroxylase enzyme deficiency.
+ Q0 T* S+ e/ ~The 11-β hydroxylase deficiency may also result in) Y5 R7 B% N% _; ]
excessive adrenal androgen production, and rarely,# V: f4 {  m3 G0 U% p% W- g3 U
an adrenal tumor may also cause adrenal androgen
0 S  \7 y" n* ~$ ?0 }' aexcess.1,3
* p0 J" `8 ^8 }9 D$ Tat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from3 R* N# _' g) P0 b( Q  t' y
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
. _5 W1 _3 ]1 F( ~$ Z' }A unique entity of male-limited gonadotropin-$ j& }, p$ J4 ^( i5 s) `+ w& W
independent precocious puberty, which is also known4 l. m# z8 f  N
as testotoxicosis, may cause precocious puberty at a
, e, q# ?' l9 X# T' wvery young age. The physical findings in these boys- L$ G; g( K# u* V
with this disorder are full pubertal development,# ]( s/ M% }  }9 E' x
including bilateral testicular growth, similar to boys# f, Q; r/ x; I. O! O$ ~
with CPP. The gonadotropin levels in this disorder8 c" ?7 h# F- ]: G- ^! }9 Z
are suppressed to prepubertal levels and do not show
" ^3 l* }* Q) o# R3 U7 u0 c0 _( dpubertal response of gonadotropin after gonadotropin-
& f3 a4 @4 R0 a) u; ~3 Nreleasing hormone stimulation. This is a sex-linked$ M! L9 a3 m3 y6 E& l7 m  V. d
autosomal dominant disorder that affects only
. M* M% m6 Q8 }8 `# S2 ~males; therefore, other male members of the family
; n4 ~8 k4 F2 E( dmay have similar precocious puberty.3$ J0 Z; B" e9 p- i$ i  K
In our patient, physical examination was incon-3 f. z4 f1 f- N( I% E  ~
sistent with true precocious puberty since his testi-$ _8 e! c0 J4 ]
cles were prepubertal in size. However, testotoxicosis
$ a: _* p. _* ?5 T3 O# Xwas in the differential diagnosis because his father
; z+ q8 j( g4 e6 J! Z4 c( H* jstarted puberty somewhat early, and occasionally,% N' A. t& y. R4 K; u# ]$ G/ R; Q
testicular enlargement is not that evident in the
+ l. C- b' R4 S$ {1 D/ Kbeginning of this process.1 In the absence of a neg-' q1 @5 l8 I# Z2 _
ative initial history of androgen exposure, our
; \1 v: F- Z/ X3 c6 }- _biggest concern was virilizing adrenal hyperplasia,
# C6 [: W& @/ j6 o9 k. Veither 21-hydroxylase deficiency or 11-β hydroxylase
4 y  }: t- D" b/ s" ndeficiency. Those diagnoses were excluded by find-
( R+ |1 F# N4 Ling the normal level of adrenal steroids.+ `  _5 F7 |9 ^& V
The diagnosis of exogenous androgens was strongly
- K6 H! e1 u/ wsuspected in a follow-up visit after 4 months because
! N5 d' P& s+ I& u9 E& qthe physical examination revealed the complete disap-/ o5 w/ l! v9 Z; j
pearance of pubic hair, normal growth velocity, and5 _2 R+ i4 M: B& F' z9 i
decreased erections. The father admitted using a testos-
( e  R1 z/ q% oterone gel, which he concealed at first visit. He was
' J2 O+ R4 t' s# E8 A" vusing it rather frequently, twice a day. The Physicians’& r2 F2 W2 x! E' G: {, L4 z
Desk Reference, or package insert of this product, gel or6 ?3 j5 q. s& H. r
cream, cautions about dermal testosterone transfer to+ q" j6 D/ ~: Z; [7 I
unprotected females through direct skin exposure., b- E7 E1 `( \
Serum testosterone level was found to be 2 times the7 b4 u6 ]  g+ D2 f# y# D
baseline value in those females who were exposed to8 B: h1 p7 d& X9 m1 v0 j2 L
even 15 minutes of direct skin contact with their male& Q. `6 b7 |. Y8 @
partners.6 However, when a shirt covered the applica-) h. B1 u; U. Q* o1 f& i$ W1 H
tion site, this testosterone transfer was prevented.
8 p. s( M8 [4 y' [, C' bOur patient’s testosterone level was 60 ng/mL,5 K1 g% {" o( c$ O
which was clearly high. Some studies suggest that
* c* n) u* g+ w1 o# _5 h+ R: q5 i7 ldermal conversion of testosterone to dihydrotestos-
% S1 g$ l9 v- h. _4 L. q& yterone, which is a more potent metabolite, is more% o9 j5 @( W; M- [; c! x
active in young children exposed to testosterone
- h- ?" s3 ]7 I+ |2 C  sexogenously7; however, we did not measure a dihy-: W& B& M& l7 x+ H
drotestosterone level in our patient. In addition to
: i+ e( D  y8 S! B( T  uvirilization, exposure to exogenous testosterone in
. C; D; A! \+ @6 Cchildren results in an increase in growth velocity and- a3 W) ^: D, d! H5 [
advanced bone age, as seen in our patient.
" C' a2 p" R" a% }% S2 dThe long-term effect of androgen exposure during
" Y2 f- x' q' t  n' c  `early childhood on pubertal development and final4 H# K& s% |. G# R
adult height are not fully known and always remain* r1 `. E/ ~+ p  r7 o# d
a concern. Children treated with short-term testos-
( @8 k" {! T+ @6 _7 {5 Lterone injection or topical androgen may exhibit some- D% K/ O4 z- j3 ?: ~( F, P
acceleration of the skeletal maturation; however, after
, U! p. s' b. N0 L1 w, A# L. bcessation of treatment, the rate of bone maturation5 E. A- r+ c2 d" C; s
decelerates and gradually returns to normal.8,9
. h* C- R: m, M5 k7 U  F3 U! SThere are conflicting reports and controversy$ V6 d7 n* T; X) q# a0 h1 C2 `& n8 f
over the effect of early androgen exposure on adult7 D9 p/ h( k) X2 ?, d1 D% G
penile length.10,11 Some reports suggest subnormal
2 A5 M6 V: |9 badult penile length, apparently because of downreg-8 {8 o3 z2 j7 m/ c9 J+ |6 Z) N
ulation of androgen receptor number.10,12 However,
& H: F1 s% w; H! W5 p  ESutherland et al13 did not find a correlation between$ }! ?3 ~9 p- y( m" W
childhood testosterone exposure and reduced adult% \: G1 v$ v  U. [4 |5 z, D1 P4 b
penile length in clinical studies.
1 E' H& Q8 a3 ?: A2 X  U1 ZNonetheless, we do not believe our patient is
, H3 c$ W- \3 L: \+ ]0 y2 [. x. qgoing to experience any of the untoward effects from
4 p+ P& J5 x, a% J9 `: qtestosterone exposure as mentioned earlier because$ p* I& o2 e0 \
the exposure was not for a prolonged period of time.
: @; ^% o6 k: Q  n4 _; h& lAlthough the bone age was advanced at the time of
% a/ x7 b. r7 p. m# qdiagnosis, the child had a normal growth velocity at$ v6 q4 [* Z$ w. V( u: ]
the follow-up visit. It is hoped that his final adult/ [* r6 v4 G$ \% A
height will not be affected.$ X' q2 F& }6 `) A( t% g7 x7 _
Although rarely reported, the widespread avail-
( z, h& c: _, K8 Oability of androgen products in our society may
: L/ Q9 }2 h* }" A; aindeed cause more virilization in male or female
' B" f* c& I+ g0 }# J1 [2 v  i  Zchildren than one would realize. Exposure to andro-
" s. V7 c) ~1 A( A" K" M" e7 n- Rgen products must be considered and specific ques-
* ?( j4 r9 F$ T1 q1 Ktioning about the use of a testosterone product or0 n5 e  @% y" k* @6 Y: d
gel should be asked of the family members during
6 P4 r# L# Z, }$ Athe evaluation of any children who present with vir-
! B8 k) ^. P( u: R5 t- g4 `! Dilization or peripheral precocious puberty. The diag-
! g5 R/ }5 p* M" fnosis can be established by just a few tests and by! C9 H! E8 X, I! I: N
appropriate history. The inability to obtain such a0 {# x/ `" [. |) U
history, or failure to ask the specific questions, may8 A, w3 c  j1 z* {7 Z0 z
result in extensive, unnecessary, and expensive
/ }; ~& N+ Z* w/ p0 finvestigation. The primary care physician should be, ]% q7 m2 N: s" R. H4 c5 \9 j  }# i
aware of this fact, because most of these children
7 O9 `* ^* \$ T3 @9 |may initially present in their practice. The Physicians’( J. ^! o2 J# W) F# e: q9 H0 w
Desk Reference and package insert should also put a2 _- Y' |/ ~% J! Y2 z
warning about the virilizing effect on a male or
# x% j! W( Y' ~2 f% g+ T5 Hfemale child who might come in contact with some-+ z7 U3 e: ]- S' v2 T" r
one using any of these products.4 O7 |, A7 P- U8 H( @  X
References/ _/ t; ]6 W$ f' ~* c
1. Styne DM. The testes: disorder of sexual differentiation8 f5 x: ^: f+ k
and puberty in the male. In: Sperling MA, ed. Pediatric
7 g8 {% B) t8 t2 P% M1 G, xEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;) _! h- p3 y- b: o: i3 ?7 n
2002: 565-628., Y' H3 x& S2 }4 x; n  k
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious* F/ C5 s5 t% 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
Sexual Precocity in a 16-Month-Old
- M& q3 b* m1 h% [Boy Induced by Indirect Topical# Z1 r- l" H( d: W
Exposure to Testosterone# S% g8 S$ y0 x* f- [$ K# @
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,29 H4 l0 S3 x* D
and Kenneth R. Rettig, MD1# Y' q# C  k0 L6 d& V1 c
Clinical Pediatrics
% D5 `) b/ f! d& z2 |; x$ DVolume 46 Number 6
, v5 h( v$ D  S' c" a' C; K3 GJuly 2007 540-543) O+ d9 r3 j! B! i, v. _
© 2007 Sage Publications6 [. D3 E  O% l6 _+ X5 U( `3 U
10.1177/0009922806296651
5 R' b4 |* E) d1 H+ W3 ghttp://clp.sagepub.com! a8 t$ W2 s& r# I
hosted at0 l) p3 J: v9 F+ n' O" O$ P8 h
http://online.sagepub.com/ ]8 a% i9 [! z% Y* b
Precocious puberty in boys, central or peripheral,/ t- M& G& K1 N5 F8 @8 O% V$ a
is a significant concern for physicians. Central4 N) J. V; s% }
precocious puberty (CPP), which is mediated) X' ~1 r4 v: M( @
through the hypothalamic pituitary gonadal axis, has
2 g4 i1 F% i  C9 y# `a higher incidence of organic central nervous system
1 \( v5 D6 g: O% C) k$ K$ [lesions in boys.1,2 Virilization in boys, as manifested3 z! _2 y) O: h
by enlargement of the penis, development of pubic
5 C6 k+ M8 M  |hair, and facial acne without enlargement of testi-# v5 z, e' w7 a" U5 {% K& z# F' T4 ?
cles, suggests peripheral or pseudopuberty.1-3 We
5 K, g; ?: j' u4 v3 P9 W: l5 vreport a 16-month-old boy who presented with the6 k7 \" z- z. l: I( e8 `1 D0 K# ~
enlargement of the phallus and pubic hair develop-
5 f& b: g9 b4 w5 [$ g5 ]ment without testicular enlargement, which was due2 @; E$ e$ x. A9 C  ?3 o- z+ ^: t+ w& s
to the unintentional exposure to androgen gel used by
4 g! s3 A, k$ \- Z: m. R6 I$ {# zthe father. The family initially concealed this infor-
3 S2 h# _' P( l8 Zmation, resulting in an extensive work-up for this
, r- ?4 P& j; C, Wchild. Given the widespread and easy availability of) |: ]) L) G  x
testosterone gel and cream, we believe this is proba-* U& R! m5 j; l. p% I
bly more common than the rare case report in the3 u  z* L2 u( O1 J. h
literature.4+ i$ [. p( X& M
Patient Report
+ `# ], S' ?% Z) h$ \/ Q% NA 16-month-old white child was referred to the8 w8 q! g7 r+ R; y8 M
endocrine clinic by his pediatrician with the concern7 V* K9 M/ {1 s4 q, S3 i1 W
of early sexual development. His mother noticed
% Z9 t$ X- {! y: G, v3 ~6 r  C" Wlight colored pubic hair development when he was: W* l) b9 F! M% H- M$ `1 j
From the 1Division of Pediatric Endocrinology, 2University of1 b/ W8 |4 [% @7 C- M
South Alabama Medical Center, Mobile, Alabama.
' ^3 t0 _% d- |6 T+ x$ t; JAddress correspondence to: Samar K. Bhowmick, MD, FACE,
' v) A- y0 Z4 N5 O+ n4 W& N  U% mProfessor of Pediatrics, University of South Alabama, College of
- a% ~9 b8 b# A2 E% X7 y/ xMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
: r  _- y- S- E1 I! T# G9 h  ?e-mail: [email protected].4 V% T- [" ]  }2 X4 _/ m  u
about 6 to 7 months old, which progressively became% x0 A/ f/ l8 D1 A/ L
darker. She was also concerned about the enlarge-
4 I& [2 \. v& P2 C% K! L5 Q/ kment of his penis and frequent erections. The child5 M+ Z+ p. |9 n* Q* C5 y+ L1 Q  N
was the product of a full-term normal delivery, with
' K; V! T' H' U  H9 Ha birth weight of 7 lb 14 oz, and birth length of
) }- j% D: |. ~! r5 J; d- b20 inches. He was breast-fed throughout the first year
8 M7 L9 o9 F- o; `' L) C5 [of life and was still receiving breast milk along with4 e. ?3 F5 B" Z$ }; F2 \9 z
solid food. He had no hospitalizations or surgery,
3 x1 E# \1 f9 }0 ~7 {" _and his psychosocial and psychomotor development
2 r! y, `; P/ u& s, G5 s9 p" owas age appropriate.  X, s$ ?% |5 z) C
The family history was remarkable for the father,& @( v' ^/ _& l" s% u
who was diagnosed with hypothyroidism at age 16,
9 R5 j: X5 b$ Ywhich was treated with thyroxine. The father’s
& N& j/ @8 D- ^2 ~( u8 l' D: aheight was 6 feet, and he went through a somewhat
0 }8 g) l, \, v) H( c& N) }early puberty and had stopped growing by age 14.# c# y. i- H, g, w: }
The father denied taking any other medication. The
& @, l9 w5 m/ {6 x0 a* i( u# ^: \( Ichild’s mother was in good health. Her menarche) i4 b- U0 R; b7 v6 Y  W& _2 Z5 q
was at 11 years of age, and her height was at 5 feet
  q2 V9 o9 }* G. s. g- @5 inches. There was no other family history of pre-
; \3 d) P: Y! i$ `cocious sexual development in the first-degree rela-
' _2 K8 ]. ~+ d+ b$ Ntives. There were no siblings.4 t6 ]% N6 _1 ~
Physical Examination
& o; G" C0 r" Y. ]The physical examination revealed a very active,0 L! r6 g" f/ p' d+ t3 z3 T0 n
playful, and healthy boy. The vital signs documented
6 B  F$ K, C$ |0 C2 }a blood pressure of 85/50 mm Hg, his length was
- o$ ]9 p$ x4 p- d& A& z; W+ d90 cm (>97th percentile), and his weight was 14.4 kg
; `9 X2 i8 \- z9 K" o(also >97th percentile). The observed yearly growth
& i0 m8 Y# ?4 O: x& ~9 I0 j& Yvelocity was 30 cm (12 inches). The examination of
, s  _5 E: \- {% {, J# C) i; Xthe neck revealed no thyroid enlargement.
  O3 {7 ~: {& X& [9 W0 eThe genitourinary examination was remarkable for- {3 Z! m% V: T$ S
enlargement of the penis, with a stretched length of
- K/ W  Q( }$ m; s) u# J8 cm and a width of 2 cm. The glans penis was very well
2 o1 Q1 ]& J, k" |developed. The pubic hair was Tanner II, mostly around& E; l3 y8 I  z5 o, Y0 k$ `
540  B# h. f  ?8 G3 c3 T7 \( A
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from; k- I1 A) z. a$ P" m. {. S
the base of the phallus and was dark and curled. The
2 t$ n! k% K* x. V$ k, itesticular volume was prepubertal at 2 mL each.- s& c: `3 n0 b; ?2 O# `. T
The skin was moist and smooth and somewhat! D( B7 Z! ]# [- _
oily. No axillary hair was noted. There were no2 s; Z4 j3 I/ N( J" Q/ L, h! B% V
abnormal skin pigmentations or café-au-lait spots.
" m  _. Y8 ]$ JNeurologic evaluation showed deep tendon reflex 2+4 }9 z; K& ~" d# {+ W
bilateral and symmetrical. There was no suggestion
0 F9 g+ \  f% T5 t8 V0 Nof papilledema.
" `  }  `2 u# }1 q7 `* g" r4 {Laboratory Evaluation
8 B; Z/ E9 b) l$ l2 j2 t$ L3 d, T- ~  HThe bone age was consistent with 28 months by/ Q' D2 p* x; j0 b/ C; y( J
using the standard of Greulich and Pyle at a chrono-0 h0 i7 @# e- ~' T# @1 H
logic age of 16 months (advanced).5 Chromosomal
8 G7 s1 c! W( Y7 x3 jkaryotype was 46XY. The thyroid function test* t& A9 _2 `+ q# k$ d2 D
showed a free T4 of 1.69 ng/dL, and thyroid stimu-% D# B5 G- [4 \3 ~/ u
lating hormone level was 1.3 µIU/mL (both normal).  e0 Z: Y) w$ A  {- Z' `
The concentrations of serum electrolytes, blood& g. X" k# d; v" a& G9 l: J
urea nitrogen, creatinine, and calcium all were
# c; T+ N# Y& Q, `, Iwithin normal range for his age. The concentration
7 o8 W4 u' ]' m6 d0 lof serum 17-hydroxyprogesterone was 16 ng/dL2 ^: k/ f" n- b
(normal, 3 to 90 ng/dL), androstenedione was 20% @0 u, Q5 R$ [& ]* c5 i
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
5 e8 D1 R( S2 hterone was 38 ng/dL (normal, 50 to 760 ng/dL),% ]: }" Y$ J  b: B2 k3 d
desoxycorticosterone was 4.3 ng/dL (normal, 7 to2 x) Z4 ^6 N" P- e- T
49ng/dL), 11-desoxycortisol (specific compound S)
5 {; h* t5 R( ^4 q) X2 s9 Kwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-- |: }& c  f% I/ l
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total  l  ^1 p. ?& v
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
9 P2 B/ R/ X* x5 }- D; Aand β-human chorionic gonadotropin was less than' J) O; v) S1 W
5 mIU/mL (normal <5 mIU/mL). Serum follicular& S! j/ F, c9 b' n% F
stimulating hormone and leuteinizing hormone3 [' f2 I/ I7 r& l& g9 k9 d' ]' [( P
concentrations were less than 0.05 mIU/mL
0 c+ A7 n* D9 X: ]2 ~& H: G(prepubertal).9 R: H' Z) E" m! t' Y
The parents were notified about the laboratory
- g0 a& C* A4 N2 Dresults and were informed that all of the tests were- l" p9 Y1 a& e2 C+ w. g
normal except the testosterone level was high. The
. c1 J1 v0 n! z  Dfollow-up visit was arranged within a few weeks to' s" P0 p4 T$ Q0 p* @6 D
obtain testicular and abdominal sonograms; how-
. p* ^: P4 g2 B# s5 J! u$ M6 Fever, the family did not return for 4 months.
, P+ W" ]$ ~. w) p' D7 u; PPhysical examination at this time revealed that the
. g3 V, o" A4 x7 o8 d8 J: Pchild had grown 2.5 cm in 4 months and had gained0 G3 _/ T9 S* o/ z( c; n' X
2 kg of weight. Physical examination remained; J5 g, s" }! g& K7 T( v
unchanged. Surprisingly, the pubic hair almost com-
7 d, A% k  X6 [# V2 l, ^; w; fpletely disappeared except for a few vellous hairs at, j7 e8 y% T: s( [. Z5 Q* g0 q
the base of the phallus. Testicular volume was still 2
+ D2 C# e3 [( z# C6 I! g* |mL, and the size of the penis remained unchanged.* `6 J) i+ F: @$ \( |; u" H
The mother also said that the boy was no longer hav-
8 t- v" F& c/ c! Q& h- ?' [; D  S( ding frequent erections.
6 I! L' \4 }. Z2 s6 A& UBoth parents were again questioned about use of  B) f2 Q5 {+ R6 w) R5 x2 k$ Z* Z
any ointment/creams that they may have applied to
7 @" j% S; M! c1 b7 n3 U; @' ~5 n" }the child’s skin. This time the father admitted the
0 a5 a' h8 f- `, S, L% d" F% QTopical Testosterone Exposure / Bhowmick et al 541* ^' x4 g2 \: H8 U& x; S, f" C
use of testosterone gel twice daily that he was apply-
# O# f- z0 d' Q. [/ B8 Aing over his own shoulders, chest, and back area for
$ p: q, L+ r) ]a year. The father also revealed he was embarrassed. H5 z: [* R5 [( P& V) p) k5 D
to disclose that he was using a testosterone gel pre-
( M8 @/ ]& o. |scribed by his family physician for decreased libido+ R4 J, T/ u+ J, p; j
secondary to depression.) ^6 O5 s  g" x( g
The child slept in the same bed with parents., l& y% L4 q) z7 h3 z# A
The father would hug the baby and hold him on his. Q* G9 r) i4 ]
chest for a considerable period of time, causing sig-
0 i/ ?; l/ v8 H+ B$ H1 knificant bare skin contact between baby and father.
1 z! h% C- m/ v! S" r- _The father also admitted that after the phone call,8 E; n; j% ^8 G, M( K, H- J5 e+ s
when he learned the testosterone level in the baby
+ z. J/ E9 v4 |$ Qwas high, he then read the product information
( P) ~7 o: V' u" U3 r; {0 S( R! Mpacket and concluded that it was most likely the rea-! O6 [3 n' `$ S) b  ^
son for the child’s virilization. At that time, they. P. [' \8 `) h! @8 x1 t
decided to put the baby in a separate bed, and the
) x9 _& B) k6 E* m& p% o* ffather was not hugging him with bare skin and had
1 b4 s! y3 y$ Z1 [been using protective clothing. A repeat testosterone
/ G# v; |6 z: Q& ?( h- g/ Otest was ordered, but the family did not go to the
( v3 m. w$ @. i" L. j7 P1 Xlaboratory to obtain the test./ v  D  @. T4 s
Discussion4 `4 |$ B3 C4 G3 S8 H
Precocious puberty in boys is defined as secondary
; Y. a. I* s$ s: [sexual development before 9 years of age.1,4
7 d, ]3 j( ~# c2 lPrecocious puberty is termed as central (true) when$ q$ Q( b, ^- d7 J! L. ~, E$ e
it is caused by the premature activation of hypo-
. L2 I+ u! J( cthalamic pituitary gonadal axis. CPP is more com-6 ]. y$ V8 b9 y3 n/ P: {2 `1 o
mon in girls than in boys.1,3 Most boys with CPP( T  E- D7 |' E! x  o
may have a central nervous system lesion that is
- v4 f! S3 E8 E1 d7 b0 {responsible for the early activation of the hypothal-4 S& C) B2 Y) E1 X8 c: y
amic pituitary gonadal axis.1-3 Thus, greater empha-. N1 v- x3 T3 ?/ y
sis has been given to neuroradiologic imaging in1 X, E9 p  j5 ]# {( i
boys with precocious puberty. In addition to viril-1 T) @/ E  m$ F: T
ization, the clinical hallmark of CPP is the symmet-
/ s) \$ |* d3 Z* K  d/ s( o# srical testicular growth secondary to stimulation by3 [8 j  T0 U4 m! R9 y
gonadotropins.1,3
' f: b* r" N8 P; u; C. AGonadotropin-independent peripheral preco-# x) v% z/ P) Z- Z6 x
cious puberty in boys also results from inappropriate9 O) Y# Y* Q. ^) S& Z) ]
androgenic stimulation from either endogenous or' z3 s- K1 e- k' n3 z1 x* s
exogenous sources, nonpituitary gonadotropin stim-( R1 e' K( h- [- r+ K, X; l* Q
ulation, and rare activating mutations.3 Virilizing; K! ^- `* N; f) `2 {# Z8 e
congenital adrenal hyperplasia producing excessive
" T" Y  |# W& v0 {, T% W( eadrenal androgens is a common cause of precocious
& }3 L9 r2 d7 W: o3 x4 g' x* U& Spuberty in boys.3,4
9 j% x/ J# E. W+ g! P! F9 R( L# YThe most common form of congenital adrenal
& k8 K/ G, V1 a! v8 q2 ]- u! thyperplasia is the 21-hydroxylase enzyme deficiency.4 M5 J+ |" A8 ~! K' O
The 11-β hydroxylase deficiency may also result in
; L) c' N- J1 }4 z) `8 zexcessive adrenal androgen production, and rarely,
2 q! o$ I" r1 H% }& l+ Wan adrenal tumor may also cause adrenal androgen' j( F3 L/ _* n' G: u+ F
excess.1,3
! V% K, z# u! Eat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
" K- e" F8 S$ m* z542 Clinical Pediatrics / Vol. 46, No. 6, July 2007* K9 B2 f! ^! a/ Z# K
A unique entity of male-limited gonadotropin-4 X+ [  F/ H1 Z2 E3 b
independent precocious puberty, which is also known$ n  d  d) M$ I. u
as testotoxicosis, may cause precocious puberty at a
1 |7 a' k9 K4 {3 b* dvery young age. The physical findings in these boys
' z8 X& r" t+ ]: i4 r7 k2 iwith this disorder are full pubertal development,
% V  R2 }, j9 X& jincluding bilateral testicular growth, similar to boys
2 |- Z# O) p! {, \5 Twith CPP. The gonadotropin levels in this disorder& H, h, F! ^, `0 v
are suppressed to prepubertal levels and do not show" w5 u: k! T7 F( _# {$ ?
pubertal response of gonadotropin after gonadotropin-) E& D$ {* d: `8 P" i# g6 y! i0 x
releasing hormone stimulation. This is a sex-linked
' M- C5 V+ {: S, b& kautosomal dominant disorder that affects only
% A4 }! ^) J2 |males; therefore, other male members of the family0 [% D" }" k2 C, @
may have similar precocious puberty.3' @; ~2 X, ]4 K, X0 D; \
In our patient, physical examination was incon-3 a- U# ~  W% k# w1 a3 U5 S
sistent with true precocious puberty since his testi-
# K/ J$ Z6 A( J% h* |: D& Hcles were prepubertal in size. However, testotoxicosis
3 ]! j' X" a5 M) X7 Y. p" z2 Lwas in the differential diagnosis because his father+ P0 V% q& D% U2 @
started puberty somewhat early, and occasionally,
: V$ G# ?: H8 m9 }6 B& Wtesticular enlargement is not that evident in the7 @+ N; g" v5 O, d5 {' G
beginning of this process.1 In the absence of a neg-
& j8 k. x1 x- z5 _+ fative initial history of androgen exposure, our. w0 _4 t4 |. J! C" g1 e  ?
biggest concern was virilizing adrenal hyperplasia,
3 i0 o( }" y1 q5 @) zeither 21-hydroxylase deficiency or 11-β hydroxylase
' o+ r* G, F4 T9 N. U% c: j+ odeficiency. Those diagnoses were excluded by find-: E( R: Q. J" m7 U7 @6 ?
ing the normal level of adrenal steroids.
4 w; P6 b6 |3 [# oThe diagnosis of exogenous androgens was strongly; E" c, j% z/ e$ b
suspected in a follow-up visit after 4 months because& M9 z) h) t- N8 a
the physical examination revealed the complete disap-" K" }8 m) u& J1 U4 S
pearance of pubic hair, normal growth velocity, and
3 O' [8 c9 h) x' \( i+ Fdecreased erections. The father admitted using a testos-
: ?+ z& K) G8 q- e8 l" Oterone gel, which he concealed at first visit. He was% P; e( M* H5 q# ^/ L4 H8 R
using it rather frequently, twice a day. The Physicians’
9 `- v! g$ M( ?6 B. l% CDesk Reference, or package insert of this product, gel or0 `# Z! i! S6 a) S( {
cream, cautions about dermal testosterone transfer to
2 ~7 y; X4 Y! \  _8 Lunprotected females through direct skin exposure.
. y2 M. M/ I) t3 ]& HSerum testosterone level was found to be 2 times the" S4 y. f3 Z: d+ ~  n. `1 T' X" w
baseline value in those females who were exposed to
9 \5 f% B5 ?' w, m% r+ i: q9 {even 15 minutes of direct skin contact with their male' u* v5 Z# }9 w; l
partners.6 However, when a shirt covered the applica-
( o1 O4 T7 u8 p4 Ztion site, this testosterone transfer was prevented.
! y" R- Z' y4 v7 ?  z! LOur patient’s testosterone level was 60 ng/mL,% J, i5 i' p1 z. T# j' C2 c
which was clearly high. Some studies suggest that
* c) b3 m: ~! e: k/ Udermal conversion of testosterone to dihydrotestos-% C6 _7 ]$ ?$ Y- Y1 ]
terone, which is a more potent metabolite, is more# P5 y0 T- f- o9 {, Y3 D" l) D
active in young children exposed to testosterone3 N4 ^7 U4 k/ h
exogenously7; however, we did not measure a dihy-
- L, I: g4 s. _* x. @' \+ \) rdrotestosterone level in our patient. In addition to" b  |. V+ A( i2 C1 ~9 Z. I
virilization, exposure to exogenous testosterone in% W! }$ w2 Z8 A3 \
children results in an increase in growth velocity and
5 P0 T& i: z' T4 k2 wadvanced bone age, as seen in our patient.
! x- `* p/ a1 H1 h7 M. {) HThe long-term effect of androgen exposure during
" a4 Z. |! n* `9 ~- w8 qearly childhood on pubertal development and final
$ R/ R9 @6 K" K4 Q" p8 C  a# D+ Yadult height are not fully known and always remain
7 D, c1 o8 }0 p! N1 ba concern. Children treated with short-term testos-
! l6 |2 q: Y; M; p9 \, Lterone injection or topical androgen may exhibit some# @1 D$ g: {! n4 m8 v' w
acceleration of the skeletal maturation; however, after
! X# B. Z# D5 J6 r$ P, n) d  Lcessation of treatment, the rate of bone maturation. {" k0 g. I& @3 h1 u# P  l0 ~
decelerates and gradually returns to normal.8,99 Z" h* w. p% }1 H
There are conflicting reports and controversy
# r0 D! D- v7 W1 |2 v9 Q8 mover the effect of early androgen exposure on adult3 [' R5 ~/ \* {& o
penile length.10,11 Some reports suggest subnormal/ T5 X, R% ?8 v. o- E! B8 R
adult penile length, apparently because of downreg-
7 u' r2 }: Z8 S* pulation of androgen receptor number.10,12 However,4 `7 k% [, U# x; f" f
Sutherland et al13 did not find a correlation between4 v9 a2 h" U$ E/ G3 m, ?
childhood testosterone exposure and reduced adult
/ Z; e6 T# @  V9 B; X# D1 Fpenile length in clinical studies.  @. R- f' j' U8 J% r
Nonetheless, we do not believe our patient is
0 U) P- x4 N6 l6 H! e  s# ?! V9 ^going to experience any of the untoward effects from
) i  z5 v* }" A: R4 M% {% Itestosterone exposure as mentioned earlier because/ u, @2 |+ G6 Z5 E3 G% C; ~
the exposure was not for a prolonged period of time.  q1 x0 J2 T1 r9 E! V
Although the bone age was advanced at the time of( f. ?6 t% R6 b4 c6 g" J$ |
diagnosis, the child had a normal growth velocity at+ G* E( N, D; Q( y$ f3 d
the follow-up visit. It is hoped that his final adult# V0 \* B, D/ i2 a
height will not be affected.
) h: F1 e# \" F+ v, |Although rarely reported, the widespread avail-  W# r; O9 e. p, E- K/ X* \
ability of androgen products in our society may
  R7 F- g1 q4 e; F' I& z1 rindeed cause more virilization in male or female4 `4 `) w+ e3 K% x9 C8 e+ u$ B
children than one would realize. Exposure to andro-7 q$ {; l' A* H* o& R1 b9 r, j2 o
gen products must be considered and specific ques-
5 N6 T- G# D1 p' E, |4 G: Ltioning about the use of a testosterone product or2 p6 x  B2 j/ ?2 o
gel should be asked of the family members during" j1 [% N. u) v2 A6 A1 ?8 g
the evaluation of any children who present with vir-) ?3 e' m7 i$ t9 U/ o2 e8 q6 `
ilization or peripheral precocious puberty. The diag-* r6 c( p) |, `, r9 A! Y& h2 h
nosis can be established by just a few tests and by
' W% Y$ a; j$ p( h# K. B+ f$ Aappropriate history. The inability to obtain such a, `# f! z: G, \; w( r' H! G
history, or failure to ask the specific questions, may* ]& v0 k# v( f/ P& `) B; o, \1 E
result in extensive, unnecessary, and expensive3 t$ W' i( E. J3 o$ \& u
investigation. The primary care physician should be
5 c# E! X" r. G& I4 waware of this fact, because most of these children
3 M4 k0 ~; L" L; ?7 \2 c! H6 ?may initially present in their practice. The Physicians’/ A( ^' t( b2 `4 s$ z, O( `
Desk Reference and package insert should also put a) B- p) n+ @4 s! q8 k
warning about the virilizing effect on a male or/ `' r. J7 H. _# r  n
female child who might come in contact with some-5 J7 j6 @& P4 x
one using any of these products.) r, }7 [1 g( P
References- f, K  B+ _, a9 s6 ?- G& c, I* e! o2 R2 M
1. Styne DM. The testes: disorder of sexual differentiation
0 i& \. U" g0 b+ ^0 h3 ~and puberty in the male. In: Sperling MA, ed. Pediatric
* [1 r$ Z% ^; o: c- `' REndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
0 }3 j, R. q- [0 K* d2002: 565-628.8 T3 ]. k. {; U+ N5 R* ?3 i) R
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious$ i. f* S. y) o0 k9 O
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
, h0 E7 P2 x2 `/ u1 ?
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!
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