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Sexual Precocity in a 16-Month-Old
% k7 v1 f/ U4 t7 R/ e  W4 B! ABoy Induced by Indirect Topical: _4 R' k6 t8 i$ l( E3 A
Exposure to Testosterone
5 R9 A6 ~' ^! B" @- Q0 @Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,21 v, f- ]6 C) `0 O3 C( y
and Kenneth R. Rettig, MD1
( E7 k+ G& j8 ?: \Clinical Pediatrics
  a: H3 e8 c% |/ lVolume 46 Number 6
) w1 j8 C, t+ R' e- K% K3 T8 GJuly 2007 540-543; D. d" t6 j& N: g+ j
© 2007 Sage Publications
5 K1 T8 A  S6 R. T4 W10.1177/00099228062966517 ?5 ^- x! `3 f' @$ f" ?: b
http://clp.sagepub.com8 N0 e8 ]8 G: F
hosted at& E& y1 y7 g  d# E8 e
http://online.sagepub.com
$ p+ C$ `# @8 S5 fPrecocious puberty in boys, central or peripheral,. D( @: I0 F/ R: n' P
is a significant concern for physicians. Central$ x& `2 B% N" }: A' k
precocious puberty (CPP), which is mediated& h6 [3 @0 C0 e3 Z6 d" j# a: P& S
through the hypothalamic pituitary gonadal axis, has
4 b4 k: f1 c: d& Q% Ha higher incidence of organic central nervous system7 x& E( I- f6 `2 T2 J2 z
lesions in boys.1,2 Virilization in boys, as manifested
5 N9 c2 g0 {, L' }by enlargement of the penis, development of pubic4 @( J2 Z" G$ ~8 _. I$ F
hair, and facial acne without enlargement of testi-
- X7 I) B7 X3 |: L; _cles, suggests peripheral or pseudopuberty.1-3 We
/ C2 t6 j1 z8 @7 @+ i! l) Preport a 16-month-old boy who presented with the4 P$ a# i; C9 U+ p% z4 o% ]
enlargement of the phallus and pubic hair develop-1 }" R. ]4 I. z, e
ment without testicular enlargement, which was due2 j1 G4 R7 j1 i
to the unintentional exposure to androgen gel used by
; c7 m) c3 K' `7 s4 Zthe father. The family initially concealed this infor-
6 G0 B! H% x" D2 J1 Wmation, resulting in an extensive work-up for this
+ u7 B2 q8 X; Y* y: l' t" ochild. Given the widespread and easy availability of
* u( `! w  E7 A; f# Ztestosterone gel and cream, we believe this is proba-
8 h) H' c& X$ `3 nbly more common than the rare case report in the
8 r" H; i" E, L' X  S9 s7 jliterature.49 U$ S9 J( o+ @9 Z1 h& L
Patient Report. Y) }6 [! e+ Z7 {9 E6 N. a
A 16-month-old white child was referred to the
  T6 o. y9 Q( ?, d( K+ v2 ]  y) f7 r2 |endocrine clinic by his pediatrician with the concern  T8 k1 b  _. r3 ?7 V- ^
of early sexual development. His mother noticed
) w( n' |' x  {1 U. Nlight colored pubic hair development when he was
% L% j& D; [, Y1 z) Q0 rFrom the 1Division of Pediatric Endocrinology, 2University of
9 S: _! }# w7 u$ k. g! M+ MSouth Alabama Medical Center, Mobile, Alabama.
' p7 ]" \& ?% B9 U" V' S# zAddress correspondence to: Samar K. Bhowmick, MD, FACE,8 Z  ?6 H7 O3 g& d/ I" u
Professor of Pediatrics, University of South Alabama, College of5 A+ B" |' |8 ^5 ?5 ^
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;8 c0 ]1 m  X( Y: O  q4 |
e-mail: [email protected].
- U. k7 B* X/ L. Z$ U+ F3 uabout 6 to 7 months old, which progressively became; f" O2 t* I6 W! P5 u/ W) |
darker. She was also concerned about the enlarge-
1 n- x) J' ]7 [( r& V2 S6 Cment of his penis and frequent erections. The child+ Y2 `& Z. t0 e- y% R6 H# [, k7 C
was the product of a full-term normal delivery, with% l7 h$ j! r' p' x' {8 U9 a
a birth weight of 7 lb 14 oz, and birth length of
, |" t( C* l1 m1 H$ ~# J3 x! _20 inches. He was breast-fed throughout the first year
+ F: T0 z0 B1 M) pof life and was still receiving breast milk along with: r, w- c/ [3 I# r6 X* B
solid food. He had no hospitalizations or surgery,2 F% r8 V+ R# Q# N
and his psychosocial and psychomotor development
2 a$ n2 _* E, C% A# {9 B9 zwas age appropriate.9 s- b- a, E+ K5 m! ~: b1 Q; I; W
The family history was remarkable for the father,* s7 Q6 @+ c' t2 x
who was diagnosed with hypothyroidism at age 16,
9 Q- S# G# F, @! F2 f- c6 dwhich was treated with thyroxine. The father’s
0 d& p! e) n3 J& zheight was 6 feet, and he went through a somewhat
) u5 g* i$ y8 @+ M8 aearly puberty and had stopped growing by age 14.
- B6 y4 Q6 v4 Q5 E' R. P9 tThe father denied taking any other medication. The" x# V, f, k) Z0 |/ N1 E
child’s mother was in good health. Her menarche, i+ w: ?( P1 w9 |
was at 11 years of age, and her height was at 5 feet1 S" n+ d. |# R1 Y$ B! R/ B- s. Z  y
5 inches. There was no other family history of pre-
# c$ a( Z5 @" W: M2 r4 V+ Bcocious sexual development in the first-degree rela-
& P! C: v$ ~0 p# z8 e7 t3 G+ Mtives. There were no siblings.. y1 B; J4 N1 z' e4 y$ q
Physical Examination4 W- Y! h/ @& n! D6 j3 j7 [  r
The physical examination revealed a very active,9 K, g- P# A3 h+ e9 z) J& d6 [) c# [
playful, and healthy boy. The vital signs documented
4 F2 e# l" @) E0 h9 k& }4 Z% b$ ~, }a blood pressure of 85/50 mm Hg, his length was
1 u- p0 J2 W* [& b+ W90 cm (>97th percentile), and his weight was 14.4 kg* S) `" e& j" y  c0 ]$ ~" `
(also >97th percentile). The observed yearly growth& g$ U9 q/ Z# O! ?7 B. x
velocity was 30 cm (12 inches). The examination of7 k' X8 h$ {9 Z1 b1 U% O
the neck revealed no thyroid enlargement.- O& A8 ^* o9 x) k
The genitourinary examination was remarkable for
( ]& U: g/ ?# o; E3 g! H8 Nenlargement of the penis, with a stretched length of
6 |  m2 c& a0 U8 I( D0 B8 cm and a width of 2 cm. The glans penis was very well
. e; o. Y4 F6 {- o  f3 v3 gdeveloped. The pubic hair was Tanner II, mostly around# @" N& M9 |% |7 j: U$ {3 E) f
5404 S; B: T: S, I
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from" x6 ?3 @. m/ @7 \
the base of the phallus and was dark and curled. The
. K, {# e. _6 m0 Utesticular volume was prepubertal at 2 mL each.  J4 ~& g5 a/ t4 u7 f! z) j
The skin was moist and smooth and somewhat
: l( Y( D9 D/ aoily. No axillary hair was noted. There were no
  {: [- a* t8 O; y& I) Mabnormal skin pigmentations or café-au-lait spots.
& }6 V6 p: X" X5 QNeurologic evaluation showed deep tendon reflex 2+
6 B  r# \* B% x- \3 B) Kbilateral and symmetrical. There was no suggestion
1 J  w+ `5 a1 o+ M7 Y& Dof papilledema.
! s7 i2 p7 m- g* k$ C3 KLaboratory Evaluation
, W' z- J; ^% G: D. ?The bone age was consistent with 28 months by
! [# D# e9 d) ]' ]4 vusing the standard of Greulich and Pyle at a chrono-0 D7 K% h/ d4 L
logic age of 16 months (advanced).5 Chromosomal
. i' F+ ?5 T+ h' jkaryotype was 46XY. The thyroid function test, Q3 F  u5 D% w
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
5 m" y$ I$ U5 d* A, Y& b( P8 Zlating hormone level was 1.3 µIU/mL (both normal).+ d; u" M7 o% t! `* S/ s  ]" }  D6 D& ~
The concentrations of serum electrolytes, blood: x, w! v7 a1 B
urea nitrogen, creatinine, and calcium all were* Q+ }+ J. l% ~/ n* W5 `5 F' ^& c. y
within normal range for his age. The concentration  G) n' ?, S9 u) k
of serum 17-hydroxyprogesterone was 16 ng/dL
( O! L8 c, l  F0 a" @7 v3 ~(normal, 3 to 90 ng/dL), androstenedione was 20
8 K4 b  Q0 \* ~) tng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
& u& @3 k0 X( L* ?9 e$ lterone was 38 ng/dL (normal, 50 to 760 ng/dL),
; E( H; ^5 B4 M4 Zdesoxycorticosterone was 4.3 ng/dL (normal, 7 to$ d) {0 ~& Y' |
49ng/dL), 11-desoxycortisol (specific compound S)
2 e  N$ M! a! {3 B* Bwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
. I1 x7 Z# v, Htisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total; s7 ?9 e  ~, A
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),& c7 h2 [9 ~# b! L& e& X
and β-human chorionic gonadotropin was less than% d. l" U0 L. |+ R* U* |
5 mIU/mL (normal <5 mIU/mL). Serum follicular; n: l6 [) j) A( {& M& ~
stimulating hormone and leuteinizing hormone
9 G/ f+ T1 i  _6 e8 k7 mconcentrations were less than 0.05 mIU/mL; q4 ^4 I0 J" V, O) p  \
(prepubertal).2 \. [" R; {* U4 G. Z
The parents were notified about the laboratory/ g, W8 }- ]5 I$ ?) S: Z
results and were informed that all of the tests were
! q4 ]# X  |1 g3 Xnormal except the testosterone level was high. The9 E: ]2 W5 f% b
follow-up visit was arranged within a few weeks to
7 ~. J/ G4 u6 V0 C3 [/ U! Nobtain testicular and abdominal sonograms; how-  f! y& E6 o9 T6 w% ^8 ?1 o' j2 s* I) S
ever, the family did not return for 4 months.% A* @) I1 H0 h- k
Physical examination at this time revealed that the
0 z. Q* n6 x) w/ {child had grown 2.5 cm in 4 months and had gained+ x  q5 V" @& d. _6 [/ B( ~
2 kg of weight. Physical examination remained# a* @# x7 d  t: R  a( A6 ]
unchanged. Surprisingly, the pubic hair almost com-7 c4 _# c4 R) H) \( l3 m
pletely disappeared except for a few vellous hairs at) D5 n' D9 b; t; Y. a# s4 }
the base of the phallus. Testicular volume was still 2' s$ S  L, X/ ?  e
mL, and the size of the penis remained unchanged.
0 Z- ]% f& c0 i' q6 AThe mother also said that the boy was no longer hav-
4 B9 ]2 d# w" n$ o' o* K3 t3 S! ming frequent erections.
9 @3 T* @, T* O5 PBoth parents were again questioned about use of
/ y5 _7 w9 Y6 ?- Y4 cany ointment/creams that they may have applied to0 ^. z% i) t8 X+ I* V0 J. g: Z4 a2 _
the child’s skin. This time the father admitted the9 U4 e4 l' z& f1 Z
Topical Testosterone Exposure / Bhowmick et al 541
2 U+ @/ w8 H2 e! z! Q& tuse of testosterone gel twice daily that he was apply-8 H/ d5 s4 M5 b
ing over his own shoulders, chest, and back area for! a" Y; W* n0 j6 Z
a year. The father also revealed he was embarrassed5 U, w8 X* z) T" `) |6 k2 O
to disclose that he was using a testosterone gel pre-
7 j6 H9 ^' _5 y  P1 q6 ?, A9 ]scribed by his family physician for decreased libido. `) F4 \0 I7 c& M) x
secondary to depression.7 n0 ]- x9 m' Y8 x6 q3 X$ z+ d
The child slept in the same bed with parents.. q+ I5 Z8 n+ X
The father would hug the baby and hold him on his
7 A  P6 j9 d  _2 T* G. hchest for a considerable period of time, causing sig-
2 P) b6 ^( @" Gnificant bare skin contact between baby and father.# F# e2 n& g+ y2 V: F: G1 a  U1 _
The father also admitted that after the phone call,
, G5 F4 ?5 ~" X% jwhen he learned the testosterone level in the baby
, E# I) H5 v9 b7 Qwas high, he then read the product information
$ T9 T/ c- e3 Hpacket and concluded that it was most likely the rea-- |5 L; z- C$ {' ?/ J
son for the child’s virilization. At that time, they
: Y) A! G: Y; |. U6 `  |' Vdecided to put the baby in a separate bed, and the+ \% i4 [4 W) g# f7 r' a
father was not hugging him with bare skin and had0 ?- \9 f+ M% y
been using protective clothing. A repeat testosterone
9 ]! _! ?8 X$ p& j& i/ otest was ordered, but the family did not go to the' s. e* _2 c/ o6 k0 p1 j6 j
laboratory to obtain the test.
! l' G2 w  j. s  d2 v6 C  nDiscussion
7 t2 V, ^2 M+ G( o& _7 j4 T6 s1 oPrecocious puberty in boys is defined as secondary* b- ]: c. ^# H$ w. N
sexual development before 9 years of age.1,42 l" {1 B# ?2 T/ D8 s8 _
Precocious puberty is termed as central (true) when( A; ?. v- S8 o2 E& r
it is caused by the premature activation of hypo-
# D5 k7 D9 Q8 @. }/ Nthalamic pituitary gonadal axis. CPP is more com-3 _6 ]/ m/ Z1 G& [
mon in girls than in boys.1,3 Most boys with CPP; v4 z/ }( W2 K4 h0 P
may have a central nervous system lesion that is
/ W$ O4 U, J8 G. S' _  Nresponsible for the early activation of the hypothal-( g6 [7 t& @; O/ D
amic pituitary gonadal axis.1-3 Thus, greater empha-# u' b( r  F( N
sis has been given to neuroradiologic imaging in
" O' e; `" L7 k( ^8 Mboys with precocious puberty. In addition to viril-
/ L8 u1 O6 _5 I# K# U& t# Nization, the clinical hallmark of CPP is the symmet-
  N4 {! w: p4 i8 P3 drical testicular growth secondary to stimulation by$ F; l0 ~7 I3 F- l) z
gonadotropins.1,3; m9 t! k8 \, c0 l; c
Gonadotropin-independent peripheral preco-' D+ K, n% R% q9 d8 v
cious puberty in boys also results from inappropriate
' _0 R. ~, _) F; P" A) mandrogenic stimulation from either endogenous or# K2 e; @8 V8 ^( S6 t) k! O: y
exogenous sources, nonpituitary gonadotropin stim-; L8 K: v- i0 c, _' X3 B% y3 P
ulation, and rare activating mutations.3 Virilizing
: j# Q8 u# x9 p  Hcongenital adrenal hyperplasia producing excessive$ A# Z3 h5 s" \6 E, l. ~
adrenal androgens is a common cause of precocious
5 ~) C8 P. J2 fpuberty in boys.3,4
6 Y* x6 J6 }7 F3 F% wThe most common form of congenital adrenal
' Q+ d! N+ ?% }- G) W- s$ g6 Fhyperplasia is the 21-hydroxylase enzyme deficiency.
9 Y: ~! m! d' `( t% l4 QThe 11-β hydroxylase deficiency may also result in) y9 N, ]/ H4 r4 P1 ?
excessive adrenal androgen production, and rarely,9 [& i& M$ h- |- b
an adrenal tumor may also cause adrenal androgen6 p, [+ Z# [6 x6 ?( I" I
excess.1,3
( ?+ k* d7 G5 H. q* tat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
6 g9 S' o5 k6 {3 P8 B4 z542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
2 W, u0 G( U" z/ fA unique entity of male-limited gonadotropin-
: ^5 w5 @& h' A. z- o& a- Nindependent precocious puberty, which is also known. r) q; h& n3 m" }
as testotoxicosis, may cause precocious puberty at a2 o) K& K8 p. `" D
very young age. The physical findings in these boys
$ _9 u3 k" y" Kwith this disorder are full pubertal development,  }4 e# ~  {' v3 U  k
including bilateral testicular growth, similar to boys
0 ?$ R5 ]/ y6 I7 ~with CPP. The gonadotropin levels in this disorder
! P. _  F% M; R" ~are suppressed to prepubertal levels and do not show
& P( A4 @( x8 J; D; t" Upubertal response of gonadotropin after gonadotropin-
5 T& C; V1 G& c/ ^7 |& q, v. rreleasing hormone stimulation. This is a sex-linked
/ {9 @8 q) M8 w9 M$ hautosomal dominant disorder that affects only
) M# Z5 w+ z  Z/ G# bmales; therefore, other male members of the family
; X- U0 [) Y1 S# ]% `may have similar precocious puberty.3
9 ?, c; ?% w; n2 B- T9 N) [In our patient, physical examination was incon-' E0 O  m1 \' {, K+ `2 L! v
sistent with true precocious puberty since his testi-
9 B5 G6 Y/ N/ P4 i7 m$ Pcles were prepubertal in size. However, testotoxicosis
8 ~" F0 D2 I7 u& Q/ N) U+ mwas in the differential diagnosis because his father
2 Z+ S% P! ^1 s7 _! k, nstarted puberty somewhat early, and occasionally,
* D% U/ \# O0 _! y; |) etesticular enlargement is not that evident in the
4 N( ?  J2 Q. E# }# R% Abeginning of this process.1 In the absence of a neg-
8 R* }& a  E  ?( o3 F( _. Dative initial history of androgen exposure, our
! M. Z$ }# [* \+ t) n% x2 Y) u1 Fbiggest concern was virilizing adrenal hyperplasia,
  s5 [4 U- {% \8 beither 21-hydroxylase deficiency or 11-β hydroxylase# L% C; ?- ~- ]/ S& [
deficiency. Those diagnoses were excluded by find-
6 @1 p! v/ d7 u% H; ding the normal level of adrenal steroids., G/ O, S8 P  B* ?1 G7 v# F! o
The diagnosis of exogenous androgens was strongly
  \8 L" Z  e5 e% O5 }suspected in a follow-up visit after 4 months because4 d! C' P" `* N' l, M
the physical examination revealed the complete disap-
1 U) Q: g  \  mpearance of pubic hair, normal growth velocity, and2 z, @& Y' l9 u
decreased erections. The father admitted using a testos-
: s( I4 k! ]" Y+ f, _7 P; B/ p9 p4 Bterone gel, which he concealed at first visit. He was3 W! `; ?' J" a. Q0 f" Q) w" e
using it rather frequently, twice a day. The Physicians’1 E1 c' @6 ^. g7 l2 P+ N$ P
Desk Reference, or package insert of this product, gel or1 J) j2 b8 b! g
cream, cautions about dermal testosterone transfer to
6 P. r; n- c* D5 p& j0 W( Q9 gunprotected females through direct skin exposure.' D9 ]: b9 m) [! R% F( J3 c# A
Serum testosterone level was found to be 2 times the
% j& D* k& ~5 W0 l+ {+ a9 ?baseline value in those females who were exposed to3 ]" i; I& v  j- y+ T+ P9 T9 A( b
even 15 minutes of direct skin contact with their male: @' b  N1 G& Y& s, k' c
partners.6 However, when a shirt covered the applica-
0 @! L+ a( T4 G$ z$ ^3 g; otion site, this testosterone transfer was prevented.! Y, L4 d" M. H3 K
Our patient’s testosterone level was 60 ng/mL,
* |3 C3 z3 k0 j8 {  @5 e5 p$ `6 @% kwhich was clearly high. Some studies suggest that
* u5 R# z2 ]  c' n$ W5 Gdermal conversion of testosterone to dihydrotestos-
8 B' ~! O( e3 n8 ?; e2 ~terone, which is a more potent metabolite, is more
  x( g: o  c2 w6 }# }  q) M' iactive in young children exposed to testosterone
! ]* V! a  y6 U9 d" T8 aexogenously7; however, we did not measure a dihy-
$ m# \5 X. {" S: Q. q! gdrotestosterone level in our patient. In addition to) D% J: q0 |% B9 `
virilization, exposure to exogenous testosterone in4 O' l4 P5 v" b, ]
children results in an increase in growth velocity and
& s; {0 A! s( z2 D7 h) V! cadvanced bone age, as seen in our patient.  F& G9 ]+ k: V, H8 d
The long-term effect of androgen exposure during+ p( v2 \, I. h- K- C4 M: W" s$ S
early childhood on pubertal development and final
3 B1 N4 m. [8 N2 A3 w0 J! V# b/ zadult height are not fully known and always remain
9 {/ b' ?( A7 ~" F- d2 k% A2 qa concern. Children treated with short-term testos-9 `7 l7 B+ [+ F5 h7 Z/ O
terone injection or topical androgen may exhibit some% l# [" Q8 ~: t5 p
acceleration of the skeletal maturation; however, after& |1 ~1 `4 P9 G, [4 V  t# d
cessation of treatment, the rate of bone maturation& C; C) S" {1 G1 @
decelerates and gradually returns to normal.8,93 \' d4 D8 ]3 r
There are conflicting reports and controversy
+ T) D4 X4 a, P; s. J/ I. Gover the effect of early androgen exposure on adult
1 S+ W) L- B; X7 L+ [% X$ jpenile length.10,11 Some reports suggest subnormal' l0 p; {6 X% d
adult penile length, apparently because of downreg-
4 a- Z4 \* m# wulation of androgen receptor number.10,12 However,( u) s/ q4 f& ]( n
Sutherland et al13 did not find a correlation between. q* r/ I: O& ~* E
childhood testosterone exposure and reduced adult  e8 }3 u" J- `, ]& g8 c
penile length in clinical studies.4 ]: q/ O5 ]. m0 Z( X
Nonetheless, we do not believe our patient is, F$ A7 k  f6 d; [8 `& l4 D8 y9 o
going to experience any of the untoward effects from  q& a  M3 \( q  g& W
testosterone exposure as mentioned earlier because; `3 b* [- z% f9 p- G0 c
the exposure was not for a prolonged period of time.
# D; Z# o& F9 E. Q. ]Although the bone age was advanced at the time of) j* `/ `0 P- N' d
diagnosis, the child had a normal growth velocity at  J" z; F& Z" D
the follow-up visit. It is hoped that his final adult9 ?* w1 v. }' ]! k: g! |4 T0 j
height will not be affected.) t' O1 ~  b& i4 k* V5 ?9 j/ ~
Although rarely reported, the widespread avail-! |5 z* T0 ?# \4 G' s4 M4 v
ability of androgen products in our society may
& ^1 N( J0 M: J/ S7 v! s: Cindeed cause more virilization in male or female" u) ^) c: Y1 B+ x) u
children than one would realize. Exposure to andro-0 K: o) y  W/ \+ V# x
gen products must be considered and specific ques-) e% P+ j/ b$ w
tioning about the use of a testosterone product or# p" i, M6 w7 A$ ]3 Y
gel should be asked of the family members during& r, w; q; p7 J' l7 H
the evaluation of any children who present with vir-
8 P3 G/ f3 C8 ~. d; P; n! dilization or peripheral precocious puberty. The diag-
3 G0 w/ a5 `9 m& q$ y/ Knosis can be established by just a few tests and by3 f- V- a( s" }# x/ g8 Q+ _& R: d0 Z
appropriate history. The inability to obtain such a
0 D3 c3 |9 I' q# uhistory, or failure to ask the specific questions, may
! Q. W' J) C6 W+ S0 @result in extensive, unnecessary, and expensive5 t) Q1 h4 V" H( V
investigation. The primary care physician should be, U) Q& x+ v3 G2 _
aware of this fact, because most of these children
) z1 ^8 Y) S2 Fmay initially present in their practice. The Physicians’5 n  A; J0 F! F5 P. p! l' B+ x
Desk Reference and package insert should also put a
# P, l! t. Q* f3 wwarning about the virilizing effect on a male or/ A) X- K- R3 @1 o9 _. G, y. E
female child who might come in contact with some-
- X, l9 }/ s# h; Tone using any of these products.# h6 _5 A& a! m+ ?
References1 t& }% g! X" P; F  W2 S: N
1. Styne DM. The testes: disorder of sexual differentiation9 o$ m0 a* I5 w: v' T
and puberty in the male. In: Sperling MA, ed. Pediatric. F* a5 A8 K; K2 [8 X+ X
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
  Z4 c. F/ u+ h2 @( b3 o3 v$ Z2002: 565-628.
) E/ F$ D! q5 P& C4 N' k2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious* _$ I) l3 e" T
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
+ X; I7 \3 f- ^% I$ w. vBoy Induced by Indirect Topical
/ o! b0 Z& @; Y) a. RExposure to Testosterone3 Q! ~! ^3 ?' G7 t
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
3 @. y/ C  s$ S8 S3 F. Wand Kenneth R. Rettig, MD1. g+ ~( _0 v* r6 [6 H3 i
Clinical Pediatrics
! T. d& v" }/ }3 R$ B' MVolume 46 Number 6
- I! r" y' Q4 L& T# ^5 m& IJuly 2007 540-5430 X1 q) L0 e8 I3 c( s! d0 e0 l
© 2007 Sage Publications$ w0 n5 L$ T6 k1 G: h% w* o/ S: `+ p
10.1177/0009922806296651/ x+ U# B, H' y2 L
http://clp.sagepub.com
, _8 P( r( ]1 i( |1 A: z  shosted at& l7 Q: Z; J! l' J+ s1 P) l
http://online.sagepub.com6 s* z: s" d- m0 k3 i
Precocious puberty in boys, central or peripheral,
* K6 `* O) ]+ g+ H3 }2 Z6 F, {is a significant concern for physicians. Central5 A: E9 f0 [! t% O
precocious puberty (CPP), which is mediated% d" f' ~7 B9 m: v; d# o% Y
through the hypothalamic pituitary gonadal axis, has& m# P* j/ |. m# P6 o
a higher incidence of organic central nervous system
- i; e! j; @# F6 O9 o6 Ulesions in boys.1,2 Virilization in boys, as manifested
# E" @$ f# A3 c% U2 x6 e2 wby enlargement of the penis, development of pubic
$ J. T5 Y8 J0 P3 O* ~hair, and facial acne without enlargement of testi-( h/ z* {  Q) S$ B8 g* e5 ]
cles, suggests peripheral or pseudopuberty.1-3 We1 Q0 k8 t8 g# C
report a 16-month-old boy who presented with the: i1 O3 |9 v0 G5 E( ^
enlargement of the phallus and pubic hair develop-# ~6 x7 R4 N" `6 q/ }
ment without testicular enlargement, which was due7 k2 b/ e' e, w3 Q4 e4 P+ {
to the unintentional exposure to androgen gel used by8 u+ ^7 X# @1 h7 q0 X
the father. The family initially concealed this infor-# S3 N  ]( ?- N* Z+ B2 r
mation, resulting in an extensive work-up for this
, W) t' }6 k9 w" y' F; zchild. Given the widespread and easy availability of5 r" W4 b/ Y/ R6 ^' d& C4 U
testosterone gel and cream, we believe this is proba-% U6 L3 l# Y) ]6 x
bly more common than the rare case report in the* |9 _  X& o& [  L
literature.4
7 I( F- P, P5 ^; o4 m- }8 w1 l% E3 oPatient Report
9 w1 `& \5 \9 SA 16-month-old white child was referred to the' A  L+ r: u4 p1 a7 b
endocrine clinic by his pediatrician with the concern" D% }3 X& D0 Y' \8 a: ~4 m$ l
of early sexual development. His mother noticed2 a& T( V0 V4 P% _4 q- b5 M0 x
light colored pubic hair development when he was
) n' F  x  f8 n# |) E6 s6 DFrom the 1Division of Pediatric Endocrinology, 2University of% M! j$ L7 h* V3 }# w9 p
South Alabama Medical Center, Mobile, Alabama.  p" `/ \( q) h, u2 R
Address correspondence to: Samar K. Bhowmick, MD, FACE,
! t) ]$ T- l- g. [Professor of Pediatrics, University of South Alabama, College of
6 T: F6 C- `' R) U& o4 gMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;5 t' D3 Z% F: T
e-mail: [email protected].
. k+ @8 Y+ T" Dabout 6 to 7 months old, which progressively became
. K9 b% G" N" ?+ C4 j$ Gdarker. She was also concerned about the enlarge-' S1 g+ o6 S  }" a/ F; @5 I
ment of his penis and frequent erections. The child
. y, k4 p/ S7 wwas the product of a full-term normal delivery, with3 _- |) y$ }# F$ u2 G- m; c. W
a birth weight of 7 lb 14 oz, and birth length of& V: X  `4 X& }4 p
20 inches. He was breast-fed throughout the first year/ W+ {# Z" \6 j$ }8 B
of life and was still receiving breast milk along with
+ g1 _0 e4 ~1 f8 V3 w% ]% wsolid food. He had no hospitalizations or surgery,
: a% _" t2 u% T% p5 q' iand his psychosocial and psychomotor development
/ t! w; k9 S* m% w. v, Y; gwas age appropriate.! U2 a" F) d" U( T; A, j. o
The family history was remarkable for the father,9 \5 x: _2 G# v. z
who was diagnosed with hypothyroidism at age 16,5 z" ?- w# ^# d( L( A
which was treated with thyroxine. The father’s/ P( d6 _+ N: k
height was 6 feet, and he went through a somewhat  Y* |* S6 n" y! z3 O, s) r
early puberty and had stopped growing by age 14.0 z. B2 j4 |" g
The father denied taking any other medication. The
9 S' t5 i* j) X8 tchild’s mother was in good health. Her menarche, [/ F" q  k2 L( }4 l+ R" \# g1 ]
was at 11 years of age, and her height was at 5 feet7 i; _& W0 d) W. t/ _- N. k# e
5 inches. There was no other family history of pre-
/ f! o3 x/ A2 [, Gcocious sexual development in the first-degree rela-: S/ k2 a+ G  @$ M: m
tives. There were no siblings.9 P, F8 j- G' k8 u  }
Physical Examination0 ], T/ [: ~- A: D; P$ N; W
The physical examination revealed a very active," ~1 T' G4 l: K; g, U; Y7 _0 C6 G
playful, and healthy boy. The vital signs documented
9 ^& N5 B0 c, H" _a blood pressure of 85/50 mm Hg, his length was" ^0 ~% L# p9 u
90 cm (>97th percentile), and his weight was 14.4 kg" a8 Q/ s4 w0 I2 e
(also >97th percentile). The observed yearly growth5 s, _. \+ W3 a! |7 ?- Z
velocity was 30 cm (12 inches). The examination of2 v( F- _2 m  t) @$ b
the neck revealed no thyroid enlargement.7 p+ `% |' @4 G! H* T5 Q
The genitourinary examination was remarkable for8 e8 V2 p" l0 Q* y3 y; k! M  L
enlargement of the penis, with a stretched length of5 I/ |0 A' B: W( {( w
8 cm and a width of 2 cm. The glans penis was very well
6 [; u6 F* D# y" }  u( v3 [1 Udeveloped. The pubic hair was Tanner II, mostly around
1 L  W8 ^+ D- g1 I) n% U0 u540- K: z, D" S. Y4 g) C( M% ]. N
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
5 Z/ V* u; q, }; ~the base of the phallus and was dark and curled. The5 V) z5 _$ L" e+ w
testicular volume was prepubertal at 2 mL each.  c; s2 _( e1 C$ Q
The skin was moist and smooth and somewhat" K. p! G: a7 }+ }
oily. No axillary hair was noted. There were no' l+ I8 v4 C  ^
abnormal skin pigmentations or café-au-lait spots./ H% \" z4 X% X4 b: Y3 S
Neurologic evaluation showed deep tendon reflex 2+
# F2 |3 p  V( @4 Qbilateral and symmetrical. There was no suggestion
& g0 J0 K- g4 e: |9 Eof papilledema.
# E- Z4 e& O% k) Q3 aLaboratory Evaluation6 `/ a! v/ h9 C8 W9 u
The bone age was consistent with 28 months by5 S1 ]9 P! m9 U8 s+ ]
using the standard of Greulich and Pyle at a chrono-
" J; b  T( C) f  Flogic age of 16 months (advanced).5 Chromosomal
; u* n* O- s* `$ Z- mkaryotype was 46XY. The thyroid function test
: h2 r( [$ J8 k1 kshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
% T( C8 C$ R8 b  A7 }1 J! ulating hormone level was 1.3 µIU/mL (both normal).
+ s* v. j: ?3 }, F4 ZThe concentrations of serum electrolytes, blood  Y( I7 t! c( T0 s' E* a1 A
urea nitrogen, creatinine, and calcium all were2 X: \/ {. v: R- |4 Y0 S
within normal range for his age. The concentration
' _+ Q; c: o# D, Pof serum 17-hydroxyprogesterone was 16 ng/dL& J" [# d, K* r  V% M
(normal, 3 to 90 ng/dL), androstenedione was 20* }4 E1 K  @( d6 P5 u
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-" {# N/ q: C3 q  E
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
' `; `( g* l( D; [3 hdesoxycorticosterone was 4.3 ng/dL (normal, 7 to8 m& U& v2 h) m  O
49ng/dL), 11-desoxycortisol (specific compound S)
, G' d0 l! y0 Vwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-* o: d! I1 N- a- [& s2 X0 U& @7 p, U
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
: T% Y1 e' b# _+ d( Qtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
7 o4 E1 n* B8 w1 [4 H" t$ uand β-human chorionic gonadotropin was less than
& K$ w& s( [2 `0 {+ Z9 V5 mIU/mL (normal <5 mIU/mL). Serum follicular
& L: L& r. d. u8 zstimulating hormone and leuteinizing hormone
5 @6 _  ?) L7 F/ D. L7 b9 {4 Dconcentrations were less than 0.05 mIU/mL: N. |  w% }: b; p* [) ~
(prepubertal).2 d9 M/ E$ ^! @
The parents were notified about the laboratory0 \) J& h, M. f& O- Q8 J  i8 k
results and were informed that all of the tests were
2 G& V4 C0 t5 [. t, q; t4 O4 \normal except the testosterone level was high. The9 @( {. T! j( H5 }
follow-up visit was arranged within a few weeks to
0 \$ V+ v) z* ^obtain testicular and abdominal sonograms; how-
4 n$ e0 U; O6 oever, the family did not return for 4 months.$ f; r$ T& C" t  H
Physical examination at this time revealed that the. O" ^# X* Y& X/ a+ u, D
child had grown 2.5 cm in 4 months and had gained
$ x9 }5 r1 a% j2 e4 b' n2 kg of weight. Physical examination remained6 i: L* M3 p- {9 q* K
unchanged. Surprisingly, the pubic hair almost com-, t8 M/ n: g4 }; g; E( b
pletely disappeared except for a few vellous hairs at
2 I' S0 z& `! D) a2 b: Z# O: Qthe base of the phallus. Testicular volume was still 2( D' T$ |% _# q: q
mL, and the size of the penis remained unchanged.# j2 Y& s5 t3 {
The mother also said that the boy was no longer hav-
: o$ {! w# p. G' B3 Y5 Ying frequent erections.
7 Q  }8 L' k' n0 _Both parents were again questioned about use of3 y# }. n0 f" V7 E; ^
any ointment/creams that they may have applied to
: Z0 j* ^% ^+ l( J9 bthe child’s skin. This time the father admitted the. Q# H1 {- q' ~( ?. |. B
Topical Testosterone Exposure / Bhowmick et al 5412 @4 H2 w2 A% H, i) r; z" Q
use of testosterone gel twice daily that he was apply-4 R+ n) i% O6 w
ing over his own shoulders, chest, and back area for
9 u0 G, [" N6 i- f$ u7 va year. The father also revealed he was embarrassed
: e* D: h) e. k7 M" z4 P' hto disclose that he was using a testosterone gel pre-) i0 _" @7 I' I( V9 |5 M, m: C4 i+ W
scribed by his family physician for decreased libido
. @- `% K1 ]3 ^secondary to depression.# n; c0 J4 U6 W/ J# X# d4 ?' ^
The child slept in the same bed with parents.
/ A+ w  F6 c2 c0 m/ D5 G# ^The father would hug the baby and hold him on his4 p2 [  A, o- c1 ~( }" b
chest for a considerable period of time, causing sig-  T3 I6 S: @2 E8 i! U' o
nificant bare skin contact between baby and father.! y) T+ l- l5 @# O
The father also admitted that after the phone call,0 g8 e% E3 k( h! Y# h2 b. ], M
when he learned the testosterone level in the baby+ o3 w) o; K- W5 c: n1 c' \
was high, he then read the product information* j/ o4 Y* r* W3 y+ Y; M
packet and concluded that it was most likely the rea-8 z, c3 y  A9 O9 q
son for the child’s virilization. At that time, they
3 f* L( R3 m, B5 D& n) ^decided to put the baby in a separate bed, and the- W% ?9 H/ w9 V$ h8 G
father was not hugging him with bare skin and had; V8 \( P5 Y" K
been using protective clothing. A repeat testosterone5 U! w9 ?# k9 r1 c6 I
test was ordered, but the family did not go to the, z1 o! _8 w; j; s
laboratory to obtain the test.
* e* z1 d; k# ?/ L9 P2 @Discussion
2 ~8 l8 D4 g% t. }3 S7 ^! HPrecocious puberty in boys is defined as secondary0 |1 f9 X1 j. f; ]9 t
sexual development before 9 years of age.1,4
0 o3 w# M, E  `* y4 {. T% @Precocious puberty is termed as central (true) when
  p: K6 J" t- V0 R& P4 \it is caused by the premature activation of hypo-
8 l: x& w' u$ c6 H' Bthalamic pituitary gonadal axis. CPP is more com-
! w0 F+ \/ t% h& K6 Ymon in girls than in boys.1,3 Most boys with CPP
0 U9 d- g* J  rmay have a central nervous system lesion that is! F4 a' [4 |6 C$ _7 l" a
responsible for the early activation of the hypothal-) m) n6 m+ ]/ q/ x" U& h* {
amic pituitary gonadal axis.1-3 Thus, greater empha-
! l7 b* t% ?8 F" D7 Vsis has been given to neuroradiologic imaging in) W1 q0 h, v) M" d
boys with precocious puberty. In addition to viril-: d; E( |: z* _; L+ g8 a9 s8 |
ization, the clinical hallmark of CPP is the symmet-
7 O9 \7 H$ C0 X4 e' ~: |rical testicular growth secondary to stimulation by" _1 V1 D/ [. F7 ^7 t- K
gonadotropins.1,3
2 C3 U# r2 N# H) I' NGonadotropin-independent peripheral preco-8 j& T  R2 C4 A( N& D9 K
cious puberty in boys also results from inappropriate
1 y. U" [7 v( z0 \androgenic stimulation from either endogenous or$ n& E$ A# O# G- c2 l9 G
exogenous sources, nonpituitary gonadotropin stim-
9 p0 ?4 k8 ?- [5 b0 s! i% eulation, and rare activating mutations.3 Virilizing
; Y, a) s5 D! p& C/ w( Jcongenital adrenal hyperplasia producing excessive; _% ]% k) j! ]/ n
adrenal androgens is a common cause of precocious
3 L( y( D/ s! b' q1 }: wpuberty in boys.3,4
0 p6 |, A5 i. ]( JThe most common form of congenital adrenal# N% l! `0 E$ j0 V4 H& m$ }
hyperplasia is the 21-hydroxylase enzyme deficiency.
3 n# S2 |) H$ O1 R. `9 XThe 11-β hydroxylase deficiency may also result in8 h& o# q/ w9 ]2 I5 r! a! c8 `
excessive adrenal androgen production, and rarely,! |& k- O% u0 `2 D+ E
an adrenal tumor may also cause adrenal androgen. c' u  d7 M% A; q7 }: o& ~# y0 {
excess.1,31 i( K- }: |, G9 j. L
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
* h1 b0 Y  M2 q% ]" p542 Clinical Pediatrics / Vol. 46, No. 6, July 2007, j+ j! `/ T. Q$ p1 l6 M5 K
A unique entity of male-limited gonadotropin-
# F. Q) d% \4 z3 ?$ Y7 rindependent precocious puberty, which is also known; y" X1 u9 L0 h% w
as testotoxicosis, may cause precocious puberty at a
9 p# Y2 z) L# D, q8 U% x( Avery young age. The physical findings in these boys
/ K6 O2 `8 s/ h. W+ o: Q" wwith this disorder are full pubertal development,
' o  z' H7 z6 \6 V" w& G6 K: V" _; Vincluding bilateral testicular growth, similar to boys2 d6 i3 C" h/ K0 G. ^2 T: {2 B; p" q6 @
with CPP. The gonadotropin levels in this disorder
8 [* j+ ~+ j' ?7 `# v# O, lare suppressed to prepubertal levels and do not show
; `5 i6 |( o0 p3 w; a% p: Ypubertal response of gonadotropin after gonadotropin-+ [2 L: F/ F" m! ^! Z( x* C& A
releasing hormone stimulation. This is a sex-linked
% X1 I- P  _) x$ {autosomal dominant disorder that affects only, q% {6 B0 r* ~# m4 Z' U& `
males; therefore, other male members of the family3 i  j1 [7 \( X7 u) o
may have similar precocious puberty.3
) G4 J+ W. m" O5 ~4 `5 yIn our patient, physical examination was incon-  Q# d& V4 l. S7 L/ ]
sistent with true precocious puberty since his testi-
0 d( N& S" c/ R3 Z* E% r" Bcles were prepubertal in size. However, testotoxicosis
7 u! g- O+ ^2 `5 awas in the differential diagnosis because his father
8 `" M8 V" ]  j' {& vstarted puberty somewhat early, and occasionally,$ x5 F0 L! K7 N( A: r* K  ?
testicular enlargement is not that evident in the: R5 T* q  A' N! ^- I/ f
beginning of this process.1 In the absence of a neg-
2 D. r" a% _9 B$ e/ Vative initial history of androgen exposure, our, J' N' z# R$ u1 h0 m! @4 ?
biggest concern was virilizing adrenal hyperplasia,
9 L2 p$ E' _; E6 T6 d" Eeither 21-hydroxylase deficiency or 11-β hydroxylase- j3 V, ]# d) y3 ~2 v
deficiency. Those diagnoses were excluded by find-
" g( f" z! }1 i: bing the normal level of adrenal steroids.5 H) B' {' `9 O* g% n8 a
The diagnosis of exogenous androgens was strongly
/ T/ I  ^8 z& F2 vsuspected in a follow-up visit after 4 months because
# `& d6 A0 b+ f) U* \9 Z7 `the physical examination revealed the complete disap-6 M: r# C( J9 F( N
pearance of pubic hair, normal growth velocity, and
  n* }( @3 t- r, [/ Bdecreased erections. The father admitted using a testos-
( s2 z7 v3 `1 H3 Uterone gel, which he concealed at first visit. He was9 O) V9 Y$ `, s8 E9 E8 o' C
using it rather frequently, twice a day. The Physicians’
; o% `) p2 s' T9 gDesk Reference, or package insert of this product, gel or1 m# U7 M4 k6 I6 I
cream, cautions about dermal testosterone transfer to/ r: v/ Z( G0 y# s! k; E
unprotected females through direct skin exposure.
- C9 A* F8 z( l8 V8 F$ ^Serum testosterone level was found to be 2 times the/ a; p) R8 T% L! E, J
baseline value in those females who were exposed to
* V" u/ a! O; T1 ^# E: ]even 15 minutes of direct skin contact with their male1 Y) R  i6 d* @% g4 ]7 K- _0 H) M
partners.6 However, when a shirt covered the applica-
" D! A4 j! _3 d: Y- h) P, w( Ction site, this testosterone transfer was prevented.: O7 M( z' S& J8 h9 a9 I9 w
Our patient’s testosterone level was 60 ng/mL,
! @# t' F4 m0 kwhich was clearly high. Some studies suggest that
7 ~8 i2 c- I7 [- ~dermal conversion of testosterone to dihydrotestos-
4 x# y3 F8 k: ~, O1 Q# \0 z* Vterone, which is a more potent metabolite, is more, p1 A& C6 ?3 Y8 q8 {/ h( M' E3 P' f
active in young children exposed to testosterone
5 s' r$ s. q" n  ?% qexogenously7; however, we did not measure a dihy-  z7 D/ f, e4 W" \# a4 P8 M
drotestosterone level in our patient. In addition to' o) B. b; n: M* ], M$ e
virilization, exposure to exogenous testosterone in) L% X& p& B0 p7 @& d# S+ K
children results in an increase in growth velocity and' w6 N+ J( `! B- M7 n
advanced bone age, as seen in our patient.! ]+ R- l2 N. M* X: r
The long-term effect of androgen exposure during
9 k: \: t* }$ d- [# j! T% searly childhood on pubertal development and final
  ?$ s8 f; u/ v9 Z2 q* zadult height are not fully known and always remain
3 t$ q( }  V3 `- Ga concern. Children treated with short-term testos-
6 t" t% u1 @& [- ]% @/ tterone injection or topical androgen may exhibit some8 H* F$ C/ J& W  k2 f* c; [
acceleration of the skeletal maturation; however, after8 I; G0 Y. `; p& v' }, r: \
cessation of treatment, the rate of bone maturation
( I0 q, f" K, v4 d9 t( Ydecelerates and gradually returns to normal.8,9
5 M- p, _7 @2 a# nThere are conflicting reports and controversy5 X1 s' S# L# Z1 S# y1 \3 }& l
over the effect of early androgen exposure on adult1 U8 Q4 f2 s4 n3 Z
penile length.10,11 Some reports suggest subnormal: O9 `4 W8 F( @" Q7 w
adult penile length, apparently because of downreg-. O3 [4 [* }- P) D- M
ulation of androgen receptor number.10,12 However,
+ b3 h  O# H& C% b6 r: e* e, RSutherland et al13 did not find a correlation between2 `# C/ }0 |2 v. j
childhood testosterone exposure and reduced adult9 o6 C3 k5 l+ m. I. M  j' O
penile length in clinical studies.
$ G0 I8 Z" \, z* w% ]Nonetheless, we do not believe our patient is
* X+ i7 V/ Z! q8 e; X/ u; |going to experience any of the untoward effects from
9 c  l5 O9 _3 a# ~0 Itestosterone exposure as mentioned earlier because
, K0 m" ?4 ^0 Dthe exposure was not for a prolonged period of time.
( P& z, |, D. B8 AAlthough the bone age was advanced at the time of
6 U( C" S( @0 ^1 ?/ d/ i6 idiagnosis, the child had a normal growth velocity at7 e7 u0 i, F# e8 p3 \
the follow-up visit. It is hoped that his final adult
1 w- e. J* N6 V1 O$ o" \  gheight will not be affected.; l, t; o0 q& Z1 Q9 |
Although rarely reported, the widespread avail-
% W8 W0 T$ k& h  l7 a4 f$ l. @ability of androgen products in our society may
  u4 r( P7 |+ O- j2 `2 R- p; ?4 cindeed cause more virilization in male or female3 }! |7 U( G7 F6 F
children than one would realize. Exposure to andro-
' k/ N$ D7 W2 e  O, q8 n$ \+ jgen products must be considered and specific ques-: F+ o; l; L8 M
tioning about the use of a testosterone product or
# L; U- K+ h6 e, |gel should be asked of the family members during
1 K+ p' s, H) X0 |% P2 s; ythe evaluation of any children who present with vir-
( E8 O" E. l! @" n, ailization or peripheral precocious puberty. The diag-* ]) O  g, j& E
nosis can be established by just a few tests and by; y% X$ O3 K% l9 A# G* p2 n# C2 T
appropriate history. The inability to obtain such a4 w5 Q5 [, h* S
history, or failure to ask the specific questions, may3 }5 ]* W' z8 {2 p! K$ G
result in extensive, unnecessary, and expensive) e$ D* g8 z0 _7 `7 c: B$ E1 Y
investigation. The primary care physician should be
* ^* H* ^" J% e& uaware of this fact, because most of these children
4 F" I; o" H* q+ w0 Pmay initially present in their practice. The Physicians’
) l, i; T8 c4 J8 B" ]  _1 `Desk Reference and package insert should also put a4 M8 D" b' S( \1 A/ v5 Q+ U+ T
warning about the virilizing effect on a male or
7 @# D, U4 H: yfemale child who might come in contact with some-
4 v6 z% f3 B" d+ z; o! R2 sone using any of these products.& `) A; b5 y* `3 S4 `
References
$ ]4 R6 M+ b: k; G( V1. Styne DM. The testes: disorder of sexual differentiation
; S" y; c/ u  Z- ~- R, a: i* a" eand puberty in the male. In: Sperling MA, ed. Pediatric5 l4 A) ]$ o% P2 Q
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
7 p) e2 y5 b/ y" r6 X/ U2002: 565-628.% `- }2 V* s& `5 n2 M& y; y
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
% v. J7 Q/ _- M7 W5 vpuberty in children with tumours of the suprasellar pineal
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& h) C, X! q" _* P精妙絕倫的精品,感謝啊!期待你更多更好的創作哦!
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么好吧v进化过程就回国参加发uft成就和;哦i回来就好v科技股份兄弟人的 路由公开vu个v库每年b
發表於 2025-4-8 11:10:25 | 顯示全部樓層
精妙絕倫的精品,感謝啊!期待你更多更好的創作哦!
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