- 註冊時間
- 2023-5-6
- 精華
- 在線時間
- 小時
- 米币
-
- 最後登錄
- 1970-1-1
|
發表於 2025-1-4 03:27:02
|
顯示全部樓層
Sexual Precocity in a 16-Month-Old
3 B. H7 b. A( T; e( b/ \2 Q2 gBoy Induced by Indirect Topical, k& A$ e+ L0 S1 h# i# W
Exposure to Testosterone
1 s8 U. O/ ~) O, X n W" Z9 m& mSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,24 s: q4 }5 r" A. \
and Kenneth R. Rettig, MD1
; O1 ~/ H8 i+ O7 d, L1 iClinical Pediatrics& C+ n* O/ x5 \! o- J
Volume 46 Number 6. L6 Z) n* _$ u N- ]) ]! U' V
July 2007 540-543
3 \3 W' R) [$ k9 S4 T* s© 2007 Sage Publications
( j, G) W! ^7 Y: b0 q10.1177/0009922806296651
: P$ e' n- i9 \, J. m* uhttp://clp.sagepub.com
5 G, a/ [( l6 Y1 y9 {& N. [, O% xhosted at
5 k; i7 Y' M" d% i6 i! [- \http://online.sagepub.com3 g" I. j' B" \( d: i, k% |. @
Precocious puberty in boys, central or peripheral,. f/ T& J$ E, y/ {6 ]1 N" `, h
is a significant concern for physicians. Central
. c$ a9 z. B7 D3 M, qprecocious puberty (CPP), which is mediated9 V( x4 G( x9 }, x3 F4 x
through the hypothalamic pituitary gonadal axis, has
/ @9 ?8 d9 @: N/ b: z/ {a higher incidence of organic central nervous system
2 k q' `% [+ | k* mlesions in boys.1,2 Virilization in boys, as manifested
6 l0 @5 k7 b* D$ U0 mby enlargement of the penis, development of pubic
, X2 R% f" t+ ^/ k/ yhair, and facial acne without enlargement of testi-2 R9 r% `; _- D# ~8 F/ ^
cles, suggests peripheral or pseudopuberty.1-3 We2 |. t9 P) y! \# w$ g' Y
report a 16-month-old boy who presented with the
; n+ b0 J, z! K. l [0 l3 Renlargement of the phallus and pubic hair develop-0 g# N; B/ ~* s
ment without testicular enlargement, which was due
. x& m% k3 G/ f$ ?% P2 {) j+ Kto the unintentional exposure to androgen gel used by
$ s. e9 L+ t! _+ h1 hthe father. The family initially concealed this infor-! `( X( B9 M+ m& X& j7 o2 E& }6 l( m# c
mation, resulting in an extensive work-up for this7 s8 C2 _- Q/ ^& c7 M2 s$ E
child. Given the widespread and easy availability of; l. z. y/ z }6 m+ _' T6 o8 I
testosterone gel and cream, we believe this is proba-! w" e* \6 r# V9 R8 b( L: g$ y
bly more common than the rare case report in the
* ]: Z$ j# C' m: Tliterature.4
8 v* `2 S& w; N& u( D/ f3 _! }Patient Report
0 \, Q5 o R7 } j3 T( ]0 WA 16-month-old white child was referred to the
9 F# H& a- J0 k- n$ Bendocrine clinic by his pediatrician with the concern
& o$ {" w- s/ C6 _of early sexual development. His mother noticed3 m9 o) J+ T* m. k% \
light colored pubic hair development when he was
. i3 `6 I# Y: T. u, G( R1 [From the 1Division of Pediatric Endocrinology, 2University of
& n: ]2 E9 w6 p3 i9 U6 R9 wSouth Alabama Medical Center, Mobile, Alabama.3 k9 v& V$ F* u, g0 b) F
Address correspondence to: Samar K. Bhowmick, MD, FACE,
' v2 i* J% v) m% TProfessor of Pediatrics, University of South Alabama, College of, \% X3 P( I: m
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
" M# Z" U! a" d# c- f; m, ie-mail: [email protected].2 V' K2 B7 G9 C1 y
about 6 to 7 months old, which progressively became# a- h% c, S9 Q
darker. She was also concerned about the enlarge-$ c1 [# ~7 c6 @$ {9 h
ment of his penis and frequent erections. The child
) l5 H# N6 [+ Q( t! P7 n' W. D0 _was the product of a full-term normal delivery, with3 G( D6 n* }, r/ d: M
a birth weight of 7 lb 14 oz, and birth length of9 T9 [. {2 C$ @: c
20 inches. He was breast-fed throughout the first year
" Q6 ]8 W) A6 o i! \of life and was still receiving breast milk along with
) F. {; i& G! _8 u- F+ f- j7 y1 @) d6 ]solid food. He had no hospitalizations or surgery,2 f: P6 k* l3 P! E+ X2 m
and his psychosocial and psychomotor development* U. [4 ` w% U+ D, c B/ n/ A
was age appropriate.
7 X8 e. k2 D# j. ZThe family history was remarkable for the father,% U+ G% [- [5 R
who was diagnosed with hypothyroidism at age 16,; S: S* i- i2 ~6 J, L# g7 I U5 p* f
which was treated with thyroxine. The father’s
3 e( p6 M6 o* `3 j/ r. b1 i0 ?/ Bheight was 6 feet, and he went through a somewhat
9 `, T2 @4 @, m0 T- v0 B3 eearly puberty and had stopped growing by age 14.3 Y# y: d' P2 e2 p5 m8 p
The father denied taking any other medication. The" w' W) H/ |6 w. l
child’s mother was in good health. Her menarche+ ^5 e7 @: `! M& n+ [
was at 11 years of age, and her height was at 5 feet
0 o( J8 V2 y6 G' C5 inches. There was no other family history of pre-% P& y* l% L0 a* q; S- l
cocious sexual development in the first-degree rela-
7 y7 k2 W( g' ]4 p8 _- ]& S2 ltives. There were no siblings.
) ^2 m# v( n' d( r0 @6 a% K( DPhysical Examination
+ \; n6 g" a$ y9 I. @( g# oThe physical examination revealed a very active,
/ Y, m8 }0 J6 Splayful, and healthy boy. The vital signs documented, m0 D0 P D* X. b; {1 X; r% W- i2 x7 Y
a blood pressure of 85/50 mm Hg, his length was, }1 S6 P" t7 I# q
90 cm (>97th percentile), and his weight was 14.4 kg- N* h+ X. v$ U6 a- R) `
(also >97th percentile). The observed yearly growth7 a9 o! M" d( `" j3 F
velocity was 30 cm (12 inches). The examination of
5 _1 A9 |! Q+ A( Bthe neck revealed no thyroid enlargement.
+ }6 x5 H! L T5 K9 |, QThe genitourinary examination was remarkable for+ C0 |& _. l: _5 `; P
enlargement of the penis, with a stretched length of& S2 r5 @: L5 g, O/ K' p$ Q% U2 X* K
8 cm and a width of 2 cm. The glans penis was very well
2 b0 X& ^+ ]) |6 w3 y- x+ N& l. z, fdeveloped. The pubic hair was Tanner II, mostly around" N; _! i9 N. s# F
540
( r1 k5 Q3 p1 f6 I' w [at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
! \: f" J3 y! g8 ^- ~$ }) [the base of the phallus and was dark and curled. The
?6 j1 D" D+ l5 K2 [& E9 u5 Ftesticular volume was prepubertal at 2 mL each.
9 [' r4 l; p+ H8 N" @& r' IThe skin was moist and smooth and somewhat0 I: x* j* ?( G, {- i
oily. No axillary hair was noted. There were no
2 y) `& C: B$ O: u/ C3 g7 U" cabnormal skin pigmentations or café-au-lait spots.
9 O/ A7 t6 v, C& M* lNeurologic evaluation showed deep tendon reflex 2+
1 k- r& k1 ]* M7 x) Jbilateral and symmetrical. There was no suggestion
* K6 B, o# u8 {$ L& T1 vof papilledema.
: v* L1 J8 o8 u- U4 T' Y3 Z5 [( `Laboratory Evaluation$ k. f4 G3 X1 n; i
The bone age was consistent with 28 months by
1 ~# ?$ v; [* h, @ M; musing the standard of Greulich and Pyle at a chrono-; Y% {2 }, i8 {% j7 Q6 v
logic age of 16 months (advanced).5 Chromosomal
! D; m% Y' T8 i4 O0 @( L6 rkaryotype was 46XY. The thyroid function test. Z3 D. o# S, m# d( L9 x
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
' h7 Z* P, X( S; U' [/ q4 Elating hormone level was 1.3 µIU/mL (both normal)., X; z; T. L+ a8 L, h! {
The concentrations of serum electrolytes, blood; q8 D, D3 S0 |9 a
urea nitrogen, creatinine, and calcium all were
! a' u5 c' R9 G3 Zwithin normal range for his age. The concentration
! T" K. f8 M, a/ N& `of serum 17-hydroxyprogesterone was 16 ng/dL
+ _) ~( B3 \& J; l8 Z% M* P8 y(normal, 3 to 90 ng/dL), androstenedione was 20# e, A2 i0 a$ j3 z
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-. z1 j/ z" E( |% c4 W, k
terone was 38 ng/dL (normal, 50 to 760 ng/dL),3 Q0 S; j1 ^$ c/ s
desoxycorticosterone was 4.3 ng/dL (normal, 7 to( }5 b- F2 d) @: Z- e; ^: @
49ng/dL), 11-desoxycortisol (specific compound S)
. X" ~8 H8 z" w) l5 swas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-. Z. ^" N% V0 z7 p2 w
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
( C$ k. [& T; mtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),: D1 J% u; r! F+ {, s6 E
and β-human chorionic gonadotropin was less than3 P7 U ?& N& j& @* L0 ~
5 mIU/mL (normal <5 mIU/mL). Serum follicular _; Y/ s: @, t6 }0 t& o
stimulating hormone and leuteinizing hormone: F% M" T9 Q- {6 N4 }2 `6 M% c
concentrations were less than 0.05 mIU/mL
! p$ K( o: X" s4 w2 d; |(prepubertal).3 F2 [2 j5 g2 ~8 j7 d5 o
The parents were notified about the laboratory. G& _4 M! N2 O) f' _" q/ o
results and were informed that all of the tests were( A8 X% u3 a/ j5 L' K
normal except the testosterone level was high. The- O" H( E1 R7 p
follow-up visit was arranged within a few weeks to
5 d d; z6 }$ o3 F& S, Aobtain testicular and abdominal sonograms; how-' \( U8 t- [- r' T) }& B# R O
ever, the family did not return for 4 months.( |* l' u( q$ [# n2 D
Physical examination at this time revealed that the
, ^6 I9 h+ K" C& Y- ^' }child had grown 2.5 cm in 4 months and had gained
. K0 ]6 }; g" u3 ]2 q" k$ p' p3 ^2 kg of weight. Physical examination remained9 Q. {3 O% l' ~" O; Z
unchanged. Surprisingly, the pubic hair almost com-
3 k1 f8 I. J$ h+ H) t |pletely disappeared except for a few vellous hairs at
! ]2 E5 ^ q% J$ q1 h4 qthe base of the phallus. Testicular volume was still 2
( k/ D" `$ N; p& I4 ^1 W, _& {4 RmL, and the size of the penis remained unchanged.
! h1 G3 J$ }) o2 w6 _The mother also said that the boy was no longer hav-
6 R7 u& o" Y. y2 Q7 i8 Ring frequent erections.5 V, c# A b. q4 w, p# }* n
Both parents were again questioned about use of- @( Y. ]: f; \2 p Q0 W
any ointment/creams that they may have applied to7 X3 t4 g2 ^, x
the child’s skin. This time the father admitted the5 ^- S# C9 m$ A" ]
Topical Testosterone Exposure / Bhowmick et al 5410 m6 `# f. y& j3 d( f: `
use of testosterone gel twice daily that he was apply-, H1 b2 m9 o+ T, x `
ing over his own shoulders, chest, and back area for
, w/ L/ S0 X; Sa year. The father also revealed he was embarrassed g2 r! h4 R. ~$ l7 O
to disclose that he was using a testosterone gel pre-
) U, L* B g4 ]5 c# ]scribed by his family physician for decreased libido+ N" g$ H2 P% i; a0 k# j
secondary to depression.
! D9 d7 a, J7 S: b( |The child slept in the same bed with parents.# ^1 N, o' g9 O' ]4 H( F
The father would hug the baby and hold him on his
& Z' j+ t. I8 {9 {% s! l" achest for a considerable period of time, causing sig-
' A+ Z; ~# K* V; }nificant bare skin contact between baby and father.9 G+ }' L" t3 q$ S1 V& h% U
The father also admitted that after the phone call,
8 q7 S7 F8 z; `! b/ N# Hwhen he learned the testosterone level in the baby6 K2 ?: ^3 K$ N
was high, he then read the product information
N5 n2 r; s+ K( D3 ^9 [packet and concluded that it was most likely the rea-. G( f) Y' Q7 l
son for the child’s virilization. At that time, they1 k& p' Q* a4 q' h [; B% e2 K
decided to put the baby in a separate bed, and the; x6 P+ ~; G( J. @
father was not hugging him with bare skin and had
9 v2 y# T; b- p. l' X! X' Nbeen using protective clothing. A repeat testosterone1 Z% B8 i' e* I' e0 {0 ?* s5 z; y
test was ordered, but the family did not go to the, R% {" B h8 A1 P' \/ \% i: ]
laboratory to obtain the test.
! Q& ]9 O/ R3 ~" ZDiscussion
' L) |7 _ K7 `0 t' i, s: Y2 C3 zPrecocious puberty in boys is defined as secondary3 j+ [, h: i* k2 n: G$ L
sexual development before 9 years of age.1,4
L/ @) J( V# K4 l0 J, l# \( uPrecocious puberty is termed as central (true) when: y7 O) @. q; W! W
it is caused by the premature activation of hypo-: W+ \. i% _* O$ \" l
thalamic pituitary gonadal axis. CPP is more com-
& P0 w& |# {. @: Vmon in girls than in boys.1,3 Most boys with CPP
1 t4 ?+ \& ^6 l. o- Umay have a central nervous system lesion that is, l5 i% o# H) G' u' ~
responsible for the early activation of the hypothal-
% B2 J. K- v p/ }7 f( oamic pituitary gonadal axis.1-3 Thus, greater empha-
, ]% [8 @' k3 A; |, ^0 rsis has been given to neuroradiologic imaging in5 ?) {: q1 @9 @4 M; N9 `
boys with precocious puberty. In addition to viril-
1 Y+ u4 Z2 [+ M7 Z& A1 Sization, the clinical hallmark of CPP is the symmet-* @% ?. S* {7 o/ b
rical testicular growth secondary to stimulation by
" }4 x* \' K# \) I1 o. Z! hgonadotropins.1,3
% n1 J* Z- `9 _: ^Gonadotropin-independent peripheral preco-
" y$ P- {- R9 d$ G4 F9 T' @cious puberty in boys also results from inappropriate
- S$ u/ H2 N2 [+ N5 T1 Aandrogenic stimulation from either endogenous or
3 @5 n |' |" ^9 eexogenous sources, nonpituitary gonadotropin stim-5 e% G5 b# J0 X$ A
ulation, and rare activating mutations.3 Virilizing) M. y0 @+ q3 F
congenital adrenal hyperplasia producing excessive
& Q/ t5 m# y" ^- ]adrenal androgens is a common cause of precocious+ G2 d$ } M' l
puberty in boys.3,4$ T0 _) ?0 L* i1 I9 x: k
The most common form of congenital adrenal1 P \9 f9 J3 Y1 S/ \% a7 Y
hyperplasia is the 21-hydroxylase enzyme deficiency., j" `5 Z! F x+ }$ q" z/ m
The 11-β hydroxylase deficiency may also result in e% B: g4 J- i1 x0 d2 F, D& ^/ o$ Z
excessive adrenal androgen production, and rarely,7 Z* X. D, y+ |
an adrenal tumor may also cause adrenal androgen H( {/ _% }$ e) n, D
excess.1,3
" L5 O* u' g! _4 H2 ^at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from a2 n. P9 W; V. J7 {2 ~
542 Clinical Pediatrics / Vol. 46, No. 6, July 20073 N- w' I4 s$ J: ^% X5 z8 Y
A unique entity of male-limited gonadotropin-6 Y& v) y; P1 H" C8 U/ z2 u- Y
independent precocious puberty, which is also known
m7 J- j! z4 Q$ A8 Ras testotoxicosis, may cause precocious puberty at a
* y4 m9 P: D( _8 `" D' Overy young age. The physical findings in these boys
* o. U- \1 \3 A0 Ywith this disorder are full pubertal development, ^* }4 _" M1 d( u5 w0 Z$ l
including bilateral testicular growth, similar to boys
4 T* @) Y% h) `. {* N. qwith CPP. The gonadotropin levels in this disorder
+ h$ m+ |% }* k, E8 S/ Hare suppressed to prepubertal levels and do not show
3 }* J ?+ ], t; N( opubertal response of gonadotropin after gonadotropin-
8 Z" E+ L1 L& ]releasing hormone stimulation. This is a sex-linked
3 ?$ F" G( M; Z/ a5 ?% Nautosomal dominant disorder that affects only
5 M7 |1 q, H4 Ymales; therefore, other male members of the family& p) T1 |$ M6 S/ Y# m( G. @
may have similar precocious puberty.3# }. n4 S v7 u' r: v3 Z+ }
In our patient, physical examination was incon-' u0 r; y' a8 H" T# h0 n( f: @
sistent with true precocious puberty since his testi-1 e, v" Y# j2 h! u
cles were prepubertal in size. However, testotoxicosis/ t( p+ N2 U% q! K5 K. k
was in the differential diagnosis because his father
8 z8 N$ S) R6 b! C$ O1 b% Dstarted puberty somewhat early, and occasionally,
4 Q$ S2 K0 j. c3 k* |% Ftesticular enlargement is not that evident in the
% a) t, ^9 g0 B$ {4 J( e/ ?4 k& N( N* dbeginning of this process.1 In the absence of a neg-
3 H6 P0 |. p0 K0 wative initial history of androgen exposure, our
" |" R' p/ k3 x' |biggest concern was virilizing adrenal hyperplasia,
; ]+ y3 [$ p8 heither 21-hydroxylase deficiency or 11-β hydroxylase
. C! ^. C8 n$ J; q) j! Sdeficiency. Those diagnoses were excluded by find- _& ]' t) {+ f) ^1 ^" ?6 k \
ing the normal level of adrenal steroids.
& d4 g5 u( e( p4 K0 A5 G# x# PThe diagnosis of exogenous androgens was strongly, Y1 U& {" i/ P9 \& Q; Y
suspected in a follow-up visit after 4 months because+ Y! i) O/ M* I* y* T, A
the physical examination revealed the complete disap-
% _5 G% |, r1 u) k( ]6 lpearance of pubic hair, normal growth velocity, and
, @& A! e3 ]! F; J: fdecreased erections. The father admitted using a testos-
( Z: ?! Z8 c4 B& o9 `. oterone gel, which he concealed at first visit. He was( u$ t K Q8 N7 c& d
using it rather frequently, twice a day. The Physicians’9 k7 p# m0 J( ]4 k2 f! v
Desk Reference, or package insert of this product, gel or
& w* S) v& v6 |2 Ncream, cautions about dermal testosterone transfer to
* ^- `* F) x! K9 tunprotected females through direct skin exposure.
2 w, W! b8 V/ X. N0 i, V. xSerum testosterone level was found to be 2 times the' M( W+ w/ Y$ V, I3 R; H/ w+ R
baseline value in those females who were exposed to! {, _4 W5 Z9 F C
even 15 minutes of direct skin contact with their male# b: k+ T9 B5 I; j& ?
partners.6 However, when a shirt covered the applica-
5 l" ~4 v8 p, a, Ytion site, this testosterone transfer was prevented.
" N9 i0 H+ b& e( `8 IOur patient’s testosterone level was 60 ng/mL,) g! D+ D5 l$ ^4 C/ x
which was clearly high. Some studies suggest that* y! x7 E. @3 K
dermal conversion of testosterone to dihydrotestos-* l+ U# J0 }/ V& F9 f
terone, which is a more potent metabolite, is more
9 T% Y4 T2 {* f+ i+ k" R' q8 Q7 Wactive in young children exposed to testosterone. M8 d3 Q8 g% n: a
exogenously7; however, we did not measure a dihy- m4 ?# q; H" t
drotestosterone level in our patient. In addition to
* J" N6 `1 s" u( `, Z9 ?, uvirilization, exposure to exogenous testosterone in- u& o; ^' D- v* f4 y: R
children results in an increase in growth velocity and. c8 @6 h0 |2 S& b8 y
advanced bone age, as seen in our patient.' p& [% b- M+ i
The long-term effect of androgen exposure during
2 o q( x7 ?5 q+ _% l) Uearly childhood on pubertal development and final: W0 r5 V3 l1 d+ U
adult height are not fully known and always remain' P6 N; w2 t% m9 l9 J8 T- y- i3 Y+ R
a concern. Children treated with short-term testos-
- ^1 E8 O% a1 cterone injection or topical androgen may exhibit some% V; T9 ?, I4 ?8 g& w+ ?
acceleration of the skeletal maturation; however, after" X* H g U# o4 f0 o7 Y
cessation of treatment, the rate of bone maturation" `* m# E- b6 ~/ C* k Y
decelerates and gradually returns to normal.8,9( n: L: f$ C3 N7 D
There are conflicting reports and controversy
& p, E& i/ _5 I7 bover the effect of early androgen exposure on adult* U" R3 W8 Y0 E5 N; i" j1 |( T
penile length.10,11 Some reports suggest subnormal
6 N0 y0 D/ N9 I! J G" hadult penile length, apparently because of downreg- W! ~. c. O! l* r" }
ulation of androgen receptor number.10,12 However,
/ o, T i( W: b1 U. Q: `% XSutherland et al13 did not find a correlation between+ s) r4 ~6 L# f& y& U
childhood testosterone exposure and reduced adult
, ^) l3 d. w9 Z8 L- hpenile length in clinical studies.- m" H* r$ F9 i4 N* v4 A
Nonetheless, we do not believe our patient is
" T/ Z0 H# c6 `& u+ A. ]going to experience any of the untoward effects from
. Z/ `) e8 h/ C+ h6 m4 d6 D0 V1 T( X9 Vtestosterone exposure as mentioned earlier because2 A) b: h6 g! ?. A% h0 w. Y6 V
the exposure was not for a prolonged period of time.
7 A3 h2 ?8 G7 Y3 tAlthough the bone age was advanced at the time of& F5 m1 d1 |* w; e+ W/ }
diagnosis, the child had a normal growth velocity at
+ G" r9 f, f: o: }; _: _" W/ Lthe follow-up visit. It is hoped that his final adult# B" g) t0 O( R' s) D3 z4 L6 u0 ^# Z
height will not be affected.
3 k2 X& F5 r5 b4 D6 D1 aAlthough rarely reported, the widespread avail-
i# j4 ?& B3 a8 O% r5 Sability of androgen products in our society may
. R4 Q" E8 J7 P7 z( |- L" uindeed cause more virilization in male or female& d: ^& q: t- [4 ^+ c' @" h
children than one would realize. Exposure to andro-: z) f9 Z4 c% A. D3 Q1 K1 w5 ^
gen products must be considered and specific ques-+ M) F, M4 Q% i* ^4 I! G
tioning about the use of a testosterone product or
. |! K$ j# C9 e! `9 Agel should be asked of the family members during
' \9 G0 e) J4 b5 K z- a& f1 U$ Qthe evaluation of any children who present with vir-
3 ^/ V+ }2 ~! q( W* milization or peripheral precocious puberty. The diag-7 Y7 a2 ]2 k9 ~& M
nosis can be established by just a few tests and by- a+ K. N( _) ^# _
appropriate history. The inability to obtain such a
* h9 l3 H( w' { |' Ehistory, or failure to ask the specific questions, may# v' X. \( [4 Q$ j9 x: s7 ^
result in extensive, unnecessary, and expensive
) K) ^" }! {3 F0 o* V! einvestigation. The primary care physician should be: q: g4 X4 U" j+ n7 y
aware of this fact, because most of these children! M/ ?3 E G, Q7 h ?$ j, r
may initially present in their practice. The Physicians’
) P0 h' R* |' Q6 @( h% nDesk Reference and package insert should also put a
Y5 e- T" P q0 F* \warning about the virilizing effect on a male or
; |. K* v8 X* Q. X$ W; u3 ], Pfemale child who might come in contact with some-
+ O% D2 T8 `: J- l7 `one using any of these products.
9 ^2 x* u! P% E9 ?1 ?References, l9 V( E) q" R7 \! m
1. Styne DM. The testes: disorder of sexual differentiation
* j6 x- n) ]% \, }and puberty in the male. In: Sperling MA, ed. Pediatric3 |5 k4 z) N5 V2 Z* _
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;4 X2 M0 p1 G4 G' o9 E' A; w
2002: 565-628.2 s6 Z) |& }! c" _, s- a1 ~
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious% ]3 l5 h* [/ f6 s* s$ H& U
puberty in children with tumours of the suprasellar pineal |
|