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Sexual Precocity in a 16-Month-Old
8 z1 C2 t4 _2 n( Y( U0 U, \Boy Induced by Indirect Topical; L7 I- u) D: u# C
Exposure to Testosterone' ?3 H3 \2 k! \9 ?$ W
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2; m" W. V3 @ a( ?; P
and Kenneth R. Rettig, MD1
; b$ t6 B8 I6 z h. \" TClinical Pediatrics
$ r: v- U+ S' UVolume 46 Number 6% o$ F3 K Y$ {1 D% |! ?4 B* Z8 O
July 2007 540-543
. K; [3 r1 F4 Y+ c# F© 2007 Sage Publications+ ]8 o. |6 w: r/ a. r4 [/ s
10.1177/0009922806296651
3 Q* I( K4 U7 D4 n4 c0 G6 ]http://clp.sagepub.com
& `$ g& J- M% `* Q/ W) D; Z y. phosted at$ O0 g! x; }. D! e9 M# n
http://online.sagepub.com
8 ~! b- H8 W9 X6 MPrecocious puberty in boys, central or peripheral,6 S Y/ P/ G" O' |' j3 Z% M
is a significant concern for physicians. Central" K6 ]" {5 V3 d" [4 t" ` u2 N: _
precocious puberty (CPP), which is mediated
& U) ^) Q8 b2 n' cthrough the hypothalamic pituitary gonadal axis, has/ c3 [! I% F$ U& H4 l
a higher incidence of organic central nervous system7 a' L$ N" X0 A/ A; K: l
lesions in boys.1,2 Virilization in boys, as manifested7 w# F/ \. L, H9 i K& C8 h; ?
by enlargement of the penis, development of pubic
7 ^0 K5 A4 P" p& H7 K: v8 ]% whair, and facial acne without enlargement of testi-
$ k% P$ t2 I2 j: gcles, suggests peripheral or pseudopuberty.1-3 We. B% `0 a7 v; S6 F. W
report a 16-month-old boy who presented with the
, E' _5 I+ w2 L2 _" P( senlargement of the phallus and pubic hair develop-
5 N1 v- v/ D7 l# n$ O$ \- tment without testicular enlargement, which was due
$ @+ N, A, Q* Y7 H/ J; j6 Y" Fto the unintentional exposure to androgen gel used by v/ p' z, F9 }& c! Q- p3 {- s
the father. The family initially concealed this infor-5 {0 R& G/ j' B3 ~/ Y! x6 v
mation, resulting in an extensive work-up for this( |* G% c0 J# T% I% n) N
child. Given the widespread and easy availability of; r; ~' a) F. M2 W9 w/ _
testosterone gel and cream, we believe this is proba-
/ w3 s; Z$ \/ e0 @bly more common than the rare case report in the
( w: y/ R+ p9 x7 e1 Lliterature.45 F+ _" x/ \/ O5 K. V
Patient Report9 u% h) s6 V: ? O
A 16-month-old white child was referred to the
; r4 Z& _ I& i7 i2 f+ T- G9 jendocrine clinic by his pediatrician with the concern
4 G) @9 n. p& ` R2 Z0 s; n/ oof early sexual development. His mother noticed
0 U: B; q! [; U4 e2 E8 H- ~& j1 Vlight colored pubic hair development when he was% R% W) H$ V1 n/ X. P/ \
From the 1Division of Pediatric Endocrinology, 2University of
6 k [0 \# P4 f+ w1 f0 vSouth Alabama Medical Center, Mobile, Alabama.# s4 h5 D: y4 @( D, j1 U
Address correspondence to: Samar K. Bhowmick, MD, FACE,7 U" K0 K% @7 ? K3 X) Y7 F
Professor of Pediatrics, University of South Alabama, College of
4 s, C7 e: ~, p6 l5 ?. Y- k' kMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;3 A% g2 G4 _8 [. R+ s
e-mail: [email protected].9 C* D ~0 C0 ~
about 6 to 7 months old, which progressively became' V9 b, o ?+ {* D/ s4 u& U! W
darker. She was also concerned about the enlarge- ~. z- }+ k' W& _
ment of his penis and frequent erections. The child% r t9 ]9 q2 Z6 l: {- D: G
was the product of a full-term normal delivery, with3 I9 ?" x3 i3 B; m7 `
a birth weight of 7 lb 14 oz, and birth length of: w% R/ p# }& M- a& S; p& h
20 inches. He was breast-fed throughout the first year
, h1 n, ]1 L0 K: gof life and was still receiving breast milk along with
3 F8 O1 i7 Y8 e9 |solid food. He had no hospitalizations or surgery,7 r0 }0 l5 x6 O. | L# t, [
and his psychosocial and psychomotor development
0 @) i4 q' ]* P" pwas age appropriate.
' Z# C9 o( m! L* A* rThe family history was remarkable for the father,, g' w5 H4 Q, T% D
who was diagnosed with hypothyroidism at age 16,2 J: i$ O* R* _* M7 d, K6 _3 R. U
which was treated with thyroxine. The father’s7 \8 J$ M& f1 P9 i; V5 T
height was 6 feet, and he went through a somewhat! T; N" C0 V4 B& v- ^+ }9 P
early puberty and had stopped growing by age 14.
8 { O! }5 w9 D, VThe father denied taking any other medication. The
* {& I( c7 V. N7 t s; \4 u. |5 qchild’s mother was in good health. Her menarche2 _0 `# u5 P& n: Y
was at 11 years of age, and her height was at 5 feet
5 a5 h) r2 R2 V4 D5 inches. There was no other family history of pre-
( Z: T0 L. f5 q* {/ J9 J% _cocious sexual development in the first-degree rela-
) {) d" @" b& Qtives. There were no siblings.
2 ~ F) Q4 w; d4 T L/ pPhysical Examination- Y, `4 F! x4 K& A h5 K
The physical examination revealed a very active,9 W2 L% C X: |
playful, and healthy boy. The vital signs documented$ X" P. J+ Q) T8 |; F. O& e+ t
a blood pressure of 85/50 mm Hg, his length was
, G9 B2 a) G) ^# K5 K$ ~90 cm (>97th percentile), and his weight was 14.4 kg. Q1 G* c' M+ @
(also >97th percentile). The observed yearly growth; u( o! W% [+ r" X3 k# q7 n$ }
velocity was 30 cm (12 inches). The examination of
& A) ^5 O w5 T8 w8 Uthe neck revealed no thyroid enlargement.6 D- t; j/ Q8 E4 T, Q
The genitourinary examination was remarkable for* q/ Q, j) t2 c" z; C x. S! f
enlargement of the penis, with a stretched length of% E* n7 T1 y; K! F- d& Q2 n2 k4 r
8 cm and a width of 2 cm. The glans penis was very well% Y* O) M+ S+ R* k
developed. The pubic hair was Tanner II, mostly around! q* n) K+ w8 N# f! u5 |' V4 k
540
$ m2 j/ f1 W8 B% m2 ?' kat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
6 o1 M: t" x- i5 q' rthe base of the phallus and was dark and curled. The3 k& p( \. B' Z
testicular volume was prepubertal at 2 mL each.
$ V" t" q* a$ EThe skin was moist and smooth and somewhat
7 K5 _% e( q) ]5 K9 ooily. No axillary hair was noted. There were no% K* ^! E3 O1 i+ M% Z Q$ |
abnormal skin pigmentations or café-au-lait spots.
3 H; v$ }6 C F7 s z+ TNeurologic evaluation showed deep tendon reflex 2+
! {% T3 S$ j# \: qbilateral and symmetrical. There was no suggestion+ G5 J' J8 G2 j: [( m
of papilledema.. ~$ A' Q j' M; A- {/ e7 F9 O
Laboratory Evaluation: b; ?; j y( A- y, [3 t
The bone age was consistent with 28 months by( \' ~: e& Z- B& f/ B" I6 K
using the standard of Greulich and Pyle at a chrono-5 Z. J" R8 w* O0 {/ p" q
logic age of 16 months (advanced).5 Chromosomal
6 f i& B# _9 L2 N# V5 F0 i9 ~karyotype was 46XY. The thyroid function test _0 C/ ]. b5 ] \- H4 ~
showed a free T4 of 1.69 ng/dL, and thyroid stimu-1 X; y/ W$ Y9 G' n/ F' L1 ?3 R
lating hormone level was 1.3 µIU/mL (both normal).
! x- d. u% Y) n/ R9 ZThe concentrations of serum electrolytes, blood
& w' Q% q* c: j E! Purea nitrogen, creatinine, and calcium all were
2 m2 B/ k1 a3 w* [8 g5 zwithin normal range for his age. The concentration0 L9 I% g- k7 B: o4 K1 E2 C4 t2 {
of serum 17-hydroxyprogesterone was 16 ng/dL
1 v. s# ^" @2 [& b1 Z1 q$ Y(normal, 3 to 90 ng/dL), androstenedione was 20
/ ?0 M) J) t# s+ R0 d4 cng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
7 C: J) G! `0 ~" d5 O, pterone was 38 ng/dL (normal, 50 to 760 ng/dL),
+ F0 M+ t7 G3 `) E0 k4 Q' }desoxycorticosterone was 4.3 ng/dL (normal, 7 to8 i% }- W% |4 R+ ~( }" A- x
49ng/dL), 11-desoxycortisol (specific compound S)* a4 h6 w7 n2 d0 S
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-( K7 R7 Q% @1 i3 _# e/ s' A
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total& n4 d2 w' q2 v2 A
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),, A$ Y3 Q1 g: o1 {
and β-human chorionic gonadotropin was less than
( w$ P! H- m4 \5 W, d% \& y5 mIU/mL (normal <5 mIU/mL). Serum follicular
2 l. I5 O0 j6 _8 z! A6 Q# V( Cstimulating hormone and leuteinizing hormone' b2 ]* b% P- K: q
concentrations were less than 0.05 mIU/mL
$ T5 ~! Y3 H0 y6 G f+ m(prepubertal).8 S+ t( k. |, t; k. v. Y
The parents were notified about the laboratory
! R# i# F/ @; a4 P' I5 Y- Wresults and were informed that all of the tests were% q/ B5 A6 d% p1 R" H8 O7 U' |( u
normal except the testosterone level was high. The
5 T k* Y. q/ I6 U: L& Rfollow-up visit was arranged within a few weeks to
% [1 N, n* { m- A1 Jobtain testicular and abdominal sonograms; how-! E9 m4 K6 t" H3 t3 {. u# i
ever, the family did not return for 4 months.
# M6 L5 h% L0 b7 r1 S) }# I' c- ~Physical examination at this time revealed that the! D& j! ]! {. K
child had grown 2.5 cm in 4 months and had gained
8 s$ R7 B% d6 |8 z% {' a. h) E2 kg of weight. Physical examination remained
! t6 ]" H9 ~2 i a/ Bunchanged. Surprisingly, the pubic hair almost com-) J' V! j& ~2 l+ q
pletely disappeared except for a few vellous hairs at3 c* I3 t3 `3 F ?$ O& ~# j
the base of the phallus. Testicular volume was still 2( `; T' Z+ z# N
mL, and the size of the penis remained unchanged.
( u( T X1 I8 \1 s6 |* PThe mother also said that the boy was no longer hav-! @" F& @& U" n9 E
ing frequent erections.% g) u8 Y/ Z' s y8 T+ U
Both parents were again questioned about use of
s- f* q8 O: `) Z. {! U* _" yany ointment/creams that they may have applied to
8 m, Z. }$ A, ethe child’s skin. This time the father admitted the \; s8 m4 Z) |; O
Topical Testosterone Exposure / Bhowmick et al 541
- u+ L% s3 o% F4 ~! fuse of testosterone gel twice daily that he was apply-0 D9 }; Y/ P; g8 L# Q( w7 E& R
ing over his own shoulders, chest, and back area for
5 r8 g1 l. V% b* aa year. The father also revealed he was embarrassed
1 s* l- E* O- N( J- _6 A% b% _" W* F. D# ito disclose that he was using a testosterone gel pre-4 |/ z; L1 r/ O/ w0 ?
scribed by his family physician for decreased libido
, H* T) c3 H" v& M- Osecondary to depression.# E, [3 |6 R* u5 m& F
The child slept in the same bed with parents.% K/ |$ V" b. s' x1 o' e) L$ \
The father would hug the baby and hold him on his
' W" K3 y {7 Cchest for a considerable period of time, causing sig-( j Z9 @$ U2 C4 v @0 K' J
nificant bare skin contact between baby and father.
0 a& c- `0 J3 e1 Q% t( OThe father also admitted that after the phone call,; i8 T6 j7 x, ]( U2 j- Z
when he learned the testosterone level in the baby
( ~& q4 p1 @" Jwas high, he then read the product information! a: g; O% b H, o6 c( } i
packet and concluded that it was most likely the rea-0 O8 R- l- I0 _* B
son for the child’s virilization. At that time, they9 i+ ^3 {# U9 H/ t/ V! P: Z1 ]
decided to put the baby in a separate bed, and the
# \, ?4 \ F' u2 G2 x6 n1 Gfather was not hugging him with bare skin and had. D* I; o; P' l3 ~5 \) c: Q1 R# s
been using protective clothing. A repeat testosterone9 J+ {$ w- P* q% F& Z9 A
test was ordered, but the family did not go to the
/ a$ |( p- N, B% |- m2 @4 A0 P0 dlaboratory to obtain the test.
0 S$ G; B# z3 ?( n1 rDiscussion
% J/ t, q7 `5 h) f- y7 {Precocious puberty in boys is defined as secondary9 F2 e9 n( |7 {/ v' l+ O k' i1 X: k
sexual development before 9 years of age.1,4
; P$ I0 E2 v2 _1 XPrecocious puberty is termed as central (true) when
) @" A3 v: |/ ]* f: A% a1 Oit is caused by the premature activation of hypo-
! S O" H; y/ P8 ]! ^thalamic pituitary gonadal axis. CPP is more com-4 G4 s( {" G' B
mon in girls than in boys.1,3 Most boys with CPP: q1 J. q, s3 E/ L6 T
may have a central nervous system lesion that is
1 o& E1 C$ L/ \# [) E& a2 F5 X" cresponsible for the early activation of the hypothal-3 K! r9 L2 Z4 }# r0 N& M Z
amic pituitary gonadal axis.1-3 Thus, greater empha-
7 v G$ v( A7 ~9 o, dsis has been given to neuroradiologic imaging in
6 C/ m! l1 F( g% m; T4 n3 K' ^4 Rboys with precocious puberty. In addition to viril-
# \( n5 ~' l7 c- Sization, the clinical hallmark of CPP is the symmet-" X, }# C; r$ [0 j4 t5 \
rical testicular growth secondary to stimulation by, p9 W2 ]1 \" f
gonadotropins.1,3
0 u$ A6 v( M3 N* K! `& F2 _Gonadotropin-independent peripheral preco-+ s8 K$ n+ R- d# t& S& H6 o, M. O- @& o
cious puberty in boys also results from inappropriate5 w) b- v: E; t* e5 m
androgenic stimulation from either endogenous or
' E3 Q9 z" h, K9 ], eexogenous sources, nonpituitary gonadotropin stim- B _- m% `- U0 q
ulation, and rare activating mutations.3 Virilizing
+ `) ^+ g$ ~7 v8 c0 a: @1 jcongenital adrenal hyperplasia producing excessive% V: G+ e! W" a U9 F& P
adrenal androgens is a common cause of precocious3 y8 Q% ]7 A2 o
puberty in boys.3,4
) m5 E8 K& a$ g( M. J) u6 tThe most common form of congenital adrenal: M0 m* x( X. V, Q( W
hyperplasia is the 21-hydroxylase enzyme deficiency.0 f7 X+ U9 I; X9 `8 R
The 11-β hydroxylase deficiency may also result in7 d) \/ G2 \5 Z; S/ {+ ], t" e
excessive adrenal androgen production, and rarely,
7 M+ K: ]! o/ x' Yan adrenal tumor may also cause adrenal androgen1 O/ v2 h$ o8 Z+ |) L
excess.1,3
& A4 m* t/ y, m2 `' ~1 tat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from7 \6 s! s! ]; Z! ?, S5 _0 Z5 `
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
, h) x5 I/ y% o; r! vA unique entity of male-limited gonadotropin-) I( J. Q( m1 L! W! \4 P
independent precocious puberty, which is also known. Y9 U* ]& @9 Q( v+ `. w
as testotoxicosis, may cause precocious puberty at a1 Z+ ~* p, z& J* ^0 b3 ^) Q; f: y
very young age. The physical findings in these boys
2 O: F- N/ ^4 I0 x9 H, l" \with this disorder are full pubertal development,
5 I: B( Y+ z; m2 E- q, h3 Aincluding bilateral testicular growth, similar to boys
6 L' p) k z, a# |4 R0 }; }with CPP. The gonadotropin levels in this disorder
% n4 b+ {5 h4 h% m. Aare suppressed to prepubertal levels and do not show: O9 S/ i# F. b) D
pubertal response of gonadotropin after gonadotropin-
7 Z, E# Q: s: Greleasing hormone stimulation. This is a sex-linked
! h; o4 s, X& Q; R; wautosomal dominant disorder that affects only
8 l% ?( v K! u& s _males; therefore, other male members of the family
# ]. r7 D4 i- r& qmay have similar precocious puberty.3
' y- q! A k% V L* F% P* nIn our patient, physical examination was incon-
( a: _! W, c' }; U2 R. Ysistent with true precocious puberty since his testi-: N$ N/ c& c$ S1 c: ^7 U* w, H' n
cles were prepubertal in size. However, testotoxicosis3 T$ }" Y6 _2 ^! \: ~0 s; b
was in the differential diagnosis because his father p% Y* h/ s# Y5 i
started puberty somewhat early, and occasionally,
; @) d& p7 f' |% r itesticular enlargement is not that evident in the. P9 ]" c! R& k
beginning of this process.1 In the absence of a neg-& F( C6 V! Y1 p G* @) }
ative initial history of androgen exposure, our, f, Q; z! ]+ n- S- T( i
biggest concern was virilizing adrenal hyperplasia,3 }( }2 I( s; G- h
either 21-hydroxylase deficiency or 11-β hydroxylase
7 U7 H/ W, H3 ]$ Q" T: ideficiency. Those diagnoses were excluded by find-
5 H, q. `7 F) g# P3 T0 Ming the normal level of adrenal steroids.% ]( Y: W" x6 N+ U9 m5 x0 Y( v
The diagnosis of exogenous androgens was strongly
, L5 ~3 _0 h3 j3 X3 _suspected in a follow-up visit after 4 months because% s* }7 l! O- @" u* g$ D
the physical examination revealed the complete disap-
8 d8 N H, X' X+ o/ v5 E) L. Fpearance of pubic hair, normal growth velocity, and
0 M7 |. _% A1 ]) D1 c1 D5 _' G- `decreased erections. The father admitted using a testos-
; H' U y$ [# D% F# l. ^) s' mterone gel, which he concealed at first visit. He was" N. e: Y; y$ l0 f" ^
using it rather frequently, twice a day. The Physicians’
. J* u1 o; X+ z1 ]8 a8 vDesk Reference, or package insert of this product, gel or
" f2 k! h5 r/ ycream, cautions about dermal testosterone transfer to
6 `" i, u4 h) L, ^7 y* lunprotected females through direct skin exposure.
8 J5 P; C- @/ ^: U+ F9 ISerum testosterone level was found to be 2 times the2 z. F3 O, i" |1 Q5 t' S
baseline value in those females who were exposed to
" A/ g3 n4 H# Z9 m$ ]& Xeven 15 minutes of direct skin contact with their male* A6 e h" c1 m8 ^0 X5 s! ]5 M3 s" e
partners.6 However, when a shirt covered the applica-3 V3 j; {) V, w
tion site, this testosterone transfer was prevented.2 n0 J' q9 o0 ~; S! N" l# J
Our patient’s testosterone level was 60 ng/mL,
- T% C( _( ^: V5 f/ Swhich was clearly high. Some studies suggest that; B! K$ y5 }3 e! i
dermal conversion of testosterone to dihydrotestos-
2 U* `2 ?1 u4 j! h) x* Aterone, which is a more potent metabolite, is more
. d3 I* H0 n- O! Q2 @active in young children exposed to testosterone
- T2 F' u. a8 x( x6 K# @exogenously7; however, we did not measure a dihy-& O3 n% c, Q4 N' k( u7 K3 Q
drotestosterone level in our patient. In addition to P! ^3 {5 W0 K& B# a' I
virilization, exposure to exogenous testosterone in4 t4 s3 L% I' C6 U
children results in an increase in growth velocity and
" G% k5 o( D0 ]/ v: v3 Fadvanced bone age, as seen in our patient.8 Y$ o; n) n" D! \- a, ]4 G
The long-term effect of androgen exposure during
; e# [# q# T2 T# @" c E W) \early childhood on pubertal development and final
' D Z% a' a' `2 |/ I* r% w+ z' Gadult height are not fully known and always remain1 \2 h+ s0 b3 q( H% i Y9 D
a concern. Children treated with short-term testos-- @" m2 X$ o; C2 j! x. o' i
terone injection or topical androgen may exhibit some8 x0 L; m; ?- l+ i
acceleration of the skeletal maturation; however, after
# T) R! V, J6 o' K* a' t, I% Hcessation of treatment, the rate of bone maturation6 j! |; Y% T, B. h. K$ H
decelerates and gradually returns to normal.8,9
% ]" f) k! V2 w# s* l0 u8 p1 U" vThere are conflicting reports and controversy: c5 _4 V3 s" Q5 a' v
over the effect of early androgen exposure on adult
3 ?: O8 ~+ m, C0 E* X8 Vpenile length.10,11 Some reports suggest subnormal, \8 w/ ~$ Y: {
adult penile length, apparently because of downreg-9 i% m6 ^( ]! ]# u7 W
ulation of androgen receptor number.10,12 However,
3 Y8 }4 G* k( a: L: P- H+ `Sutherland et al13 did not find a correlation between4 |$ B0 Y6 ^( ]1 p
childhood testosterone exposure and reduced adult9 P3 I# U; m2 ~
penile length in clinical studies.
- F9 h! r# K; Q5 Z" |Nonetheless, we do not believe our patient is
. q5 `+ T8 j! K4 _going to experience any of the untoward effects from/ C2 t3 ^/ t0 X1 l
testosterone exposure as mentioned earlier because
; T4 L! P( b+ a/ rthe exposure was not for a prolonged period of time.
+ o; Z5 F' [9 [! d4 wAlthough the bone age was advanced at the time of- ?# q/ s, r2 m$ J* R
diagnosis, the child had a normal growth velocity at
7 {( ^' T1 I! r9 nthe follow-up visit. It is hoped that his final adult
! s$ w' W l9 l% I2 E9 W6 O8 b* j _height will not be affected.( @9 ]$ L8 r9 n, V
Although rarely reported, the widespread avail-8 \5 E" t+ \) W/ Q' p$ r
ability of androgen products in our society may
* s5 E4 N0 h, i e- f. j7 m2 R; |5 Pindeed cause more virilization in male or female* O4 n( T! A9 G4 c. z# l
children than one would realize. Exposure to andro-/ G/ s4 F2 y8 r* d$ B
gen products must be considered and specific ques-4 b7 i" }" @4 z- i5 j- I
tioning about the use of a testosterone product or" P+ e7 D0 f% U; K" _$ y
gel should be asked of the family members during( G Q. b2 l) ^4 A/ o W9 U1 `
the evaluation of any children who present with vir-! \0 m- W; i7 o# j0 y# o
ilization or peripheral precocious puberty. The diag-( ~/ s D3 R) @5 i" O; z' t
nosis can be established by just a few tests and by
8 I" s8 u: \5 x" O8 ?appropriate history. The inability to obtain such a3 K$ Q' r( f( a4 U' H
history, or failure to ask the specific questions, may# r/ Y K9 F3 Z8 R K
result in extensive, unnecessary, and expensive- y* ?" w( [: G" d$ N; \( H
investigation. The primary care physician should be
0 r( D: n4 p% H! o5 caware of this fact, because most of these children
2 w9 ]2 w0 ~, u, X- L* Y; G( Imay initially present in their practice. The Physicians’
. y8 M2 h% Y, v1 a. N9 oDesk Reference and package insert should also put a! m) j; V/ O G. o
warning about the virilizing effect on a male or
1 I, G, l, K1 Xfemale child who might come in contact with some-& g/ G9 J7 A/ z% t4 d! X0 r- }, R% B
one using any of these products.
+ K. p0 \6 I* C, a4 h: pReferences5 v- H, w! [8 k
1. Styne DM. The testes: disorder of sexual differentiation: l5 w5 a& u. I% K3 a
and puberty in the male. In: Sperling MA, ed. Pediatric8 l4 a' L( i7 H2 b% c6 Q
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;+ I1 J; b ?& N4 Y; F9 n
2002: 565-628.8 | \- p7 a8 q' u" s
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious' ^# f& e' ]; g$ ^
puberty in children with tumours of the suprasellar pineal |
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