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Sexual Precocity in a 16-Month-Old
" ] E, x; @# m) m3 ~Boy Induced by Indirect Topical
* ~: R* D9 N' P+ b6 ?- n2 X) H) z! qExposure to Testosterone
' o6 ^' u! O& Y3 M) J" v6 LSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2/ ^6 I& f& P3 k% C1 \3 W
and Kenneth R. Rettig, MD1
$ m9 V1 ?" ~% BClinical Pediatrics
( e3 J f$ g+ [$ M& gVolume 46 Number 6/ }& ?% Q5 @) T2 v
July 2007 540-5433 M% _& l) q2 U
© 2007 Sage Publications% e3 n) r/ w2 J" d6 [$ W8 n
10.1177/0009922806296651
7 i7 p+ w6 n B {% l) zhttp://clp.sagepub.com% A( Y) \9 J. k! s8 X+ D: [4 L+ l
hosted at
; Y4 {: g2 H: y8 L' g% K3 y& khttp://online.sagepub.com. i* O' R" h$ @
Precocious puberty in boys, central or peripheral,
& Q9 K8 o* M4 ~ a1 h1 V5 q( I) Xis a significant concern for physicians. Central
7 V6 M* [2 s# H F; k$ {precocious puberty (CPP), which is mediated
# R4 e) K9 Q! F4 ~2 Xthrough the hypothalamic pituitary gonadal axis, has
2 ~% `" c2 h, ^; W# Aa higher incidence of organic central nervous system, z. i. Q. l5 U3 p( s+ f
lesions in boys.1,2 Virilization in boys, as manifested
9 K. x$ F7 _# J: {* q) ~by enlargement of the penis, development of pubic
6 T3 g, _1 Z n2 Q6 \0 \. y9 Y6 Ahair, and facial acne without enlargement of testi-
/ P% ~8 j- T* V1 v- n# |. Jcles, suggests peripheral or pseudopuberty.1-3 We* N4 R( d% x" Z3 H1 B6 `7 T
report a 16-month-old boy who presented with the1 |) N [# N% Z8 @
enlargement of the phallus and pubic hair develop-
W& F1 G f6 ^- X$ y, F% h& ^ment without testicular enlargement, which was due: C% R% F5 s3 W) w
to the unintentional exposure to androgen gel used by+ x. k6 m! G/ x3 H" @6 R
the father. The family initially concealed this infor-
' t. X1 U9 q" Z5 e! h& o3 omation, resulting in an extensive work-up for this/ K" t3 X. E% x& z% t
child. Given the widespread and easy availability of
2 I+ @+ k) }( gtestosterone gel and cream, we believe this is proba-
& S3 F9 y* J/ Ubly more common than the rare case report in the
# c" i. d9 q z5 T. nliterature.4
8 b( V L: T! k1 N4 DPatient Report! q. M- z% i+ e2 a
A 16-month-old white child was referred to the
: [3 F) Y! e) q( b: Aendocrine clinic by his pediatrician with the concern) g* b4 c6 ]5 T% u ~! Z7 j# u+ l0 x
of early sexual development. His mother noticed( U4 l* l* T Z' L1 Y- j: x" N
light colored pubic hair development when he was7 K& z+ ]8 P5 Q' h
From the 1Division of Pediatric Endocrinology, 2University of5 k! k7 D4 K! o1 h- Y7 ]
South Alabama Medical Center, Mobile, Alabama.- r# C& ]7 D9 I3 V4 W$ ]5 A
Address correspondence to: Samar K. Bhowmick, MD, FACE,. C, `, i! W. v1 v/ h
Professor of Pediatrics, University of South Alabama, College of
; }+ m5 ~7 V9 \3 h; k5 U. LMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;* R& h3 u9 U2 c# p6 B* S
e-mail: [email protected].8 g, e7 S. m% v+ i5 t+ n7 [
about 6 to 7 months old, which progressively became: c/ O5 w j; g
darker. She was also concerned about the enlarge-
1 N+ s( z, _, N4 ]* `# e5 Cment of his penis and frequent erections. The child3 B+ r& [2 t R( q
was the product of a full-term normal delivery, with, l4 ~; @+ y! c7 `- I+ Y: l* [/ p
a birth weight of 7 lb 14 oz, and birth length of
1 L" Z# A& Q8 G6 n/ ?! d20 inches. He was breast-fed throughout the first year) ^6 P9 a. \: t; R5 T* u J* c
of life and was still receiving breast milk along with
l: ~' ]3 `8 \, Y% E1 x; lsolid food. He had no hospitalizations or surgery,
1 t2 K. f0 K0 N' Iand his psychosocial and psychomotor development
) R" k' U# z- ^0 ~: Y/ [" Kwas age appropriate.8 Q! e0 E9 S2 T `2 a4 N3 x
The family history was remarkable for the father,
! q' l* q, P0 `' p) d b$ p! e1 rwho was diagnosed with hypothyroidism at age 16,
/ h8 y. U( P3 _' ewhich was treated with thyroxine. The father’s3 c; f3 U& ?- q+ j
height was 6 feet, and he went through a somewhat5 ~! U4 {$ z. A( j
early puberty and had stopped growing by age 14.
" f4 i; v3 u" v- Q& Q& zThe father denied taking any other medication. The
& g" W* x* N0 Achild’s mother was in good health. Her menarche9 C% t$ y& D8 j, Z1 v/ p% O4 \
was at 11 years of age, and her height was at 5 feet9 \ w3 i: E# ?0 z1 ?7 F
5 inches. There was no other family history of pre-
" y6 L8 c8 h1 l4 J1 ncocious sexual development in the first-degree rela-& K% j x0 b; s$ M C
tives. There were no siblings.
$ b7 t R! @1 r5 [! }' e! yPhysical Examination
* U i+ J5 X2 g1 ~6 Z, [The physical examination revealed a very active,9 n- X* `% g( i8 N+ T
playful, and healthy boy. The vital signs documented
0 M( P. V' v1 a* G1 v( d3 y5 q# [a blood pressure of 85/50 mm Hg, his length was4 {. P# z5 F& L% H
90 cm (>97th percentile), and his weight was 14.4 kg7 q! x( Z- G2 e, L
(also >97th percentile). The observed yearly growth
4 m! Z4 |, ^: X# A0 mvelocity was 30 cm (12 inches). The examination of3 M$ u! K7 t& l6 J* W# Y1 q8 I4 j
the neck revealed no thyroid enlargement.4 T9 |* w9 v) I' R5 l' M5 t5 c
The genitourinary examination was remarkable for$ s H. ?. p- x+ ~( ?2 E
enlargement of the penis, with a stretched length of
" K% @$ t: f% k# w" w8 cm and a width of 2 cm. The glans penis was very well
( E4 V1 Z$ X) Hdeveloped. The pubic hair was Tanner II, mostly around N4 L9 T: ]' C! S1 Y
540
2 C4 M/ N* l) v) z9 Uat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
5 _$ \. U4 p3 P; |1 P4 Gthe base of the phallus and was dark and curled. The
0 ~* s0 y h. f8 Stesticular volume was prepubertal at 2 mL each.
* e) l4 P0 k% d2 W5 a: E6 yThe skin was moist and smooth and somewhat
+ G5 H' [" O" D5 n, N# G* ]oily. No axillary hair was noted. There were no. w: b. O7 V9 {+ N& H+ Y
abnormal skin pigmentations or café-au-lait spots.5 H# g+ y; I! M
Neurologic evaluation showed deep tendon reflex 2+% m* a4 _$ E3 u, v6 C& j
bilateral and symmetrical. There was no suggestion/ z y9 y! L' C0 ]2 ]6 u1 A9 }
of papilledema.
& D9 s- N# y5 Z$ r. ]Laboratory Evaluation% v) U8 u! {* S! s9 ?
The bone age was consistent with 28 months by
2 B. \2 {" |$ X% M) Jusing the standard of Greulich and Pyle at a chrono-
9 p) D1 p- C' r, N5 Blogic age of 16 months (advanced).5 Chromosomal5 N# k. g$ U# u3 z) a7 D8 g
karyotype was 46XY. The thyroid function test1 O. D2 B: u! S2 R& z: z$ |. c- F" O
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
) [2 T4 n: r* hlating hormone level was 1.3 µIU/mL (both normal).3 R- |6 \6 j2 C c
The concentrations of serum electrolytes, blood0 v/ s `6 H. K; X8 n
urea nitrogen, creatinine, and calcium all were
: q2 G4 X% y3 m. I1 [( D$ I0 nwithin normal range for his age. The concentration% ^$ W7 ?& U5 e6 w$ H
of serum 17-hydroxyprogesterone was 16 ng/dL7 C' J' Z5 O- z
(normal, 3 to 90 ng/dL), androstenedione was 20
' p+ \4 w# w& j% C3 {ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-" F: b6 I- |/ l9 X! ?+ q
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
8 Y( W+ p. e" A' N/ o/ ddesoxycorticosterone was 4.3 ng/dL (normal, 7 to
1 x4 K+ R9 G0 }5 _49ng/dL), 11-desoxycortisol (specific compound S)
& T k U V0 r+ h, Xwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
+ R/ y* t+ p, w$ o2 F6 vtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
' B/ k+ _# l/ O/ [testosterone was 60 ng/dL (normal <3 to 10 ng/dL),' w, F. O3 w) D/ k' C) v, T
and β-human chorionic gonadotropin was less than
- Y2 e; z3 U( [: ~5 mIU/mL (normal <5 mIU/mL). Serum follicular; e% c# w" l6 d% L6 l0 s
stimulating hormone and leuteinizing hormone# H5 }3 h' u9 }" a& ^) S0 e; b& s
concentrations were less than 0.05 mIU/mL" m; K; K) T$ J! X S/ J
(prepubertal).: E" F5 T! z( Q$ H
The parents were notified about the laboratory
/ c& `6 v( Z' V! xresults and were informed that all of the tests were
7 q) n1 g0 j% J4 Z# {normal except the testosterone level was high. The* j8 v' j- V" C# B$ W
follow-up visit was arranged within a few weeks to+ e# S3 u6 r: M6 n, Z. Y$ q
obtain testicular and abdominal sonograms; how-8 q0 e, ^- p* D4 O- L2 p' V
ever, the family did not return for 4 months.
, Z+ E! s* I' g9 X+ r* XPhysical examination at this time revealed that the' r/ A; Q5 c, T- h R
child had grown 2.5 cm in 4 months and had gained
5 q$ Y; o) y8 @6 r2 S. L2 kg of weight. Physical examination remained4 p2 j3 a8 V, Y7 A9 y! `1 g
unchanged. Surprisingly, the pubic hair almost com-
1 V$ [- j0 P' ~% T8 K& j! Jpletely disappeared except for a few vellous hairs at" ~3 R/ U/ q* h# E5 ~: n# V. w" h
the base of the phallus. Testicular volume was still 2
! _1 [7 l3 L1 BmL, and the size of the penis remained unchanged.& {9 b: y, i4 R3 H
The mother also said that the boy was no longer hav-9 h u4 ]! x8 b3 F& q& v9 L
ing frequent erections.
# N4 N3 I+ g { f0 ~" b0 G7 wBoth parents were again questioned about use of
, F Y! d7 c9 |6 f" Q; I5 Sany ointment/creams that they may have applied to7 B4 U+ B7 V$ e% N! q2 F0 H
the child’s skin. This time the father admitted the
" k4 `! ]3 H0 R w! ITopical Testosterone Exposure / Bhowmick et al 541
+ A1 g& T, }; e, Muse of testosterone gel twice daily that he was apply-8 w* n0 M( @2 E
ing over his own shoulders, chest, and back area for
' Z7 D' t$ }5 h' @7 q/ ca year. The father also revealed he was embarrassed* X+ M& e9 R* x8 E
to disclose that he was using a testosterone gel pre-4 v* \& m8 b1 ?' O
scribed by his family physician for decreased libido
9 J. T% U9 p( }4 I3 f/ `3 ssecondary to depression.
$ }6 i) P9 d6 `7 _# q) LThe child slept in the same bed with parents. E# \+ s% {* ^) i0 C+ ]3 M6 [
The father would hug the baby and hold him on his6 ~; j" d7 \0 _$ V ?5 D0 f
chest for a considerable period of time, causing sig-
) `; H8 L% g/ P" S6 E/ _nificant bare skin contact between baby and father.* g0 R2 D0 d1 x' K* |
The father also admitted that after the phone call,
9 R6 e. t* [! T1 ]when he learned the testosterone level in the baby& h* r. w5 M( G
was high, he then read the product information
+ B. g( }& W( f$ ~5 \packet and concluded that it was most likely the rea-* w% R' T. r; `1 h5 s9 Q/ I5 d
son for the child’s virilization. At that time, they
& g. |& [# c, l, ]( t B% Odecided to put the baby in a separate bed, and the! x5 x- b2 Y. n3 F# V; Y; }# i
father was not hugging him with bare skin and had/ b5 R2 R" ^7 x$ A# B6 y$ Q
been using protective clothing. A repeat testosterone3 p& T" e% ^: U6 g4 K
test was ordered, but the family did not go to the4 h- \" O0 W; e) T
laboratory to obtain the test.
: Q5 W2 ]; Y* [/ _" B2 ZDiscussion
3 @# Z: ]7 E, u- S8 E1 YPrecocious puberty in boys is defined as secondary0 x# m# b0 t7 H3 D+ B
sexual development before 9 years of age.1,4
0 N5 \( X5 u% a% r6 j! l0 [% P _2 KPrecocious puberty is termed as central (true) when4 i6 W: m$ l' G4 l* X; B( m
it is caused by the premature activation of hypo-
$ R0 w: V/ m. ~: z) r6 y9 d7 ethalamic pituitary gonadal axis. CPP is more com-
7 Y- s4 g/ q1 g% P, g# Rmon in girls than in boys.1,3 Most boys with CPP# S: s+ G# R9 X1 V Q
may have a central nervous system lesion that is0 }/ r5 _6 i: I7 g: h1 G W, B
responsible for the early activation of the hypothal-1 b1 Z/ \ J7 N9 p; m( \" O3 O
amic pituitary gonadal axis.1-3 Thus, greater empha-
) k8 v, q2 b' Q% R% ^. Ksis has been given to neuroradiologic imaging in0 ]& A0 v- h# c
boys with precocious puberty. In addition to viril-
6 x# e: R. s6 d4 q! Mization, the clinical hallmark of CPP is the symmet-* W3 ?6 J0 p, j _* j# r8 G
rical testicular growth secondary to stimulation by
8 r, c2 [" g8 V" x3 A6 c Xgonadotropins.1,3
) i+ j7 I* ]& k/ H6 p! fGonadotropin-independent peripheral preco-: W1 z5 y) I7 d5 J+ }( V3 [4 d+ u U
cious puberty in boys also results from inappropriate
8 ]- u* r* g1 Pandrogenic stimulation from either endogenous or
3 ], V0 S# c3 w. _exogenous sources, nonpituitary gonadotropin stim-* k' U. \( q, ^+ F
ulation, and rare activating mutations.3 Virilizing
7 E; n9 O% X' G, y) U2 Dcongenital adrenal hyperplasia producing excessive. ^2 @- Q* }' r
adrenal androgens is a common cause of precocious
1 n& ?7 r2 Y8 t8 W$ Qpuberty in boys.3,4
" c: s) v5 ^4 j% g7 r! q: pThe most common form of congenital adrenal
3 |0 o& _7 L+ W% |' Hhyperplasia is the 21-hydroxylase enzyme deficiency.
! ?% h& y6 S' L2 R" pThe 11-β hydroxylase deficiency may also result in
' S7 Z( q D% t Eexcessive adrenal androgen production, and rarely,2 K1 `8 K. i' o7 q
an adrenal tumor may also cause adrenal androgen& z9 n- i6 F1 U! M0 j
excess.1,3. f. C9 i: ]# `* `8 i
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
$ B2 |7 S$ M6 Y$ N* ?: Y$ A542 Clinical Pediatrics / Vol. 46, No. 6, July 2007# z: ~7 g: d- L: n% ?4 K
A unique entity of male-limited gonadotropin-
0 w' @8 d2 s5 {7 P0 X# n# ]% Xindependent precocious puberty, which is also known
# f2 L2 Y/ n: mas testotoxicosis, may cause precocious puberty at a
7 r" O' ?0 ?- o9 k1 }- cvery young age. The physical findings in these boys$ \% t0 D0 ?- t* j0 ^1 g3 {
with this disorder are full pubertal development,8 C6 E& R: a! \8 {: K$ x: h' r3 m
including bilateral testicular growth, similar to boys
# K, U2 i! \8 x' \1 ]7 u; uwith CPP. The gonadotropin levels in this disorder: S, E/ O; t. @6 {0 I( L2 i
are suppressed to prepubertal levels and do not show
; m% K' n" c) u. n, Rpubertal response of gonadotropin after gonadotropin-
+ Y9 M) B: ~4 z$ k! vreleasing hormone stimulation. This is a sex-linked$ ^9 Z! j4 N0 ~ Z# y- i
autosomal dominant disorder that affects only1 E1 a7 ]7 n- [& u% S. L1 k) b* A% K
males; therefore, other male members of the family
* e" L9 X& t+ t, l! }4 X! c8 G; G9 r9 U# qmay have similar precocious puberty.3* w0 ^% [% n3 u- ]$ t
In our patient, physical examination was incon-
- A' {/ y" n8 t0 ]: {* esistent with true precocious puberty since his testi-% W% d2 Q) W. J- X n1 y* A3 U4 X8 B
cles were prepubertal in size. However, testotoxicosis
6 t# J0 t( j- A* x: U! c9 Owas in the differential diagnosis because his father: a2 c- r0 f8 Y# ~ L9 n9 r
started puberty somewhat early, and occasionally,
, s8 V) m3 z" V& m7 Vtesticular enlargement is not that evident in the
- C$ |0 j& [4 i( @1 Mbeginning of this process.1 In the absence of a neg-
M" j7 X. s1 n0 H8 k4 pative initial history of androgen exposure, our8 e. v. c! E0 Q5 y) ~
biggest concern was virilizing adrenal hyperplasia,
- M$ N8 o3 L0 ]( E' T2 Yeither 21-hydroxylase deficiency or 11-β hydroxylase
' j' |! i- f0 {9 A! z7 y) v! M5 ? ideficiency. Those diagnoses were excluded by find-
, r2 u* M+ a- _) Ving the normal level of adrenal steroids.
) K" \* Z5 Y% t8 H$ W5 uThe diagnosis of exogenous androgens was strongly+ [* l3 A; I5 e1 @
suspected in a follow-up visit after 4 months because0 V* X" G) z" e+ R9 f
the physical examination revealed the complete disap-4 L6 x& `8 M/ [( X( m6 m
pearance of pubic hair, normal growth velocity, and
7 {" P0 b# E" z. M9 U- m2 Cdecreased erections. The father admitted using a testos-
2 h4 @& t* Y/ p* `3 {/ t$ \6 W; `( bterone gel, which he concealed at first visit. He was1 ^/ G% A/ P& s! R, R& u
using it rather frequently, twice a day. The Physicians’4 S" ]2 m; ~, _, k& `) x7 S: X5 Q
Desk Reference, or package insert of this product, gel or! j* j @0 o0 X1 d8 w
cream, cautions about dermal testosterone transfer to
8 C9 m+ X2 t4 ` punprotected females through direct skin exposure.8 Q2 J# O" {* @. B3 _
Serum testosterone level was found to be 2 times the
. c+ [! Z4 R+ E6 y a" _4 abaseline value in those females who were exposed to+ Z) l# n0 z/ o9 X- u; Z
even 15 minutes of direct skin contact with their male2 i T2 ]4 z6 z( v6 N0 S
partners.6 However, when a shirt covered the applica-5 J6 M5 Z' y4 ~0 @5 U
tion site, this testosterone transfer was prevented.) |6 K. \ ^! M7 j
Our patient’s testosterone level was 60 ng/mL,% [6 k! w3 Y2 ?( L+ P
which was clearly high. Some studies suggest that
# b# }, X/ ?" O7 ^9 L( Ddermal conversion of testosterone to dihydrotestos-
- \# o+ O, U8 O1 pterone, which is a more potent metabolite, is more- o* ~0 p& e" s# d! q
active in young children exposed to testosterone5 X: j# N% [0 Z; D2 P0 f: Q' t
exogenously7; however, we did not measure a dihy-
" Q: h9 }; [3 V- i: ndrotestosterone level in our patient. In addition to; `/ I6 x. d4 D9 w$ l" T: q
virilization, exposure to exogenous testosterone in3 e g: p9 N. @. y" K( j" b' V
children results in an increase in growth velocity and
1 Q `0 e: [1 X& C4 F, sadvanced bone age, as seen in our patient.
; k* Q3 k$ L, m0 tThe long-term effect of androgen exposure during% S/ s$ T9 \) f8 y4 h& A- S
early childhood on pubertal development and final
" ~2 j) w" U7 z- y Madult height are not fully known and always remain; s: G" w" F# j4 |" h3 F8 ^ y
a concern. Children treated with short-term testos-
6 O/ K9 Q: R# g& k' Yterone injection or topical androgen may exhibit some
0 p3 q( }7 c6 vacceleration of the skeletal maturation; however, after
! e0 v; M) } J# t* }0 K* g# b, Ncessation of treatment, the rate of bone maturation
/ s' @5 k' |; O2 x, P1 x& adecelerates and gradually returns to normal.8,9+ U$ `8 y8 V! S6 b
There are conflicting reports and controversy
: ?3 u5 F2 s, D1 Uover the effect of early androgen exposure on adult$ `; e0 q( a$ q& s, U3 s
penile length.10,11 Some reports suggest subnormal/ t+ P! L4 r' T8 X9 ~2 c3 o
adult penile length, apparently because of downreg-
. i+ x8 m1 w2 Vulation of androgen receptor number.10,12 However,
C! T( g5 L0 z, T4 mSutherland et al13 did not find a correlation between
4 F2 |8 {7 J9 c' Vchildhood testosterone exposure and reduced adult
2 s9 l: k5 P! u- u# l) v- @penile length in clinical studies.
0 M0 h+ K, \4 z% P2 }; x, _Nonetheless, we do not believe our patient is
0 S7 I/ y) R, v2 r7 c- egoing to experience any of the untoward effects from0 a3 Y5 l |% I5 W8 c
testosterone exposure as mentioned earlier because* w6 p0 p. r9 s9 Q& b
the exposure was not for a prolonged period of time.( _4 ?/ ]+ \. }; H
Although the bone age was advanced at the time of9 ^7 L8 A1 |% A6 }) m
diagnosis, the child had a normal growth velocity at: E3 q9 C7 B3 ^- y/ u4 `# r
the follow-up visit. It is hoped that his final adult
- g& @/ u4 @1 h/ y# lheight will not be affected.
& I' k2 z$ g+ A; {) DAlthough rarely reported, the widespread avail-! q9 Q( z4 M/ B) G8 s' {. O
ability of androgen products in our society may
" Z9 b: g/ d4 q! [+ |1 @( Jindeed cause more virilization in male or female! F2 {7 [8 A! F" ^1 Q4 A( d8 T
children than one would realize. Exposure to andro-
1 Y0 h, o8 V2 l$ Vgen products must be considered and specific ques-
7 |( D# V: O8 [, m, n" X/ mtioning about the use of a testosterone product or$ a- g4 t. s6 h
gel should be asked of the family members during
# U+ c% x) v- n1 T* @! d& u `the evaluation of any children who present with vir-$ N; W% z Q+ r2 y
ilization or peripheral precocious puberty. The diag-
4 \2 c5 d5 p: r" nnosis can be established by just a few tests and by$ W5 m3 t' g$ u! x/ [+ s
appropriate history. The inability to obtain such a
: l7 q9 M, J: l' b4 [& bhistory, or failure to ask the specific questions, may! D9 _+ Y4 w+ t8 {# d
result in extensive, unnecessary, and expensive
) H9 j- M9 q; A. Winvestigation. The primary care physician should be1 ]& g: D5 c7 j( T- Y
aware of this fact, because most of these children
' x4 U# h( q/ m7 n2 {% p( omay initially present in their practice. The Physicians’! W1 n& |" m& @' Q8 o, s9 ~
Desk Reference and package insert should also put a
5 s l0 [) i5 K* q. Awarning about the virilizing effect on a male or2 B: w. i+ f6 v
female child who might come in contact with some-
' \; E1 L! B2 w" q# j! Uone using any of these products.
" O# F+ e* \! ]& tReferences
, t2 m& ~7 h0 E8 ]1. Styne DM. The testes: disorder of sexual differentiation# e2 t& J# u& P0 {0 |. ]! S7 o5 M& V
and puberty in the male. In: Sperling MA, ed. Pediatric* c0 s% f4 b. u9 y+ g
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;( p2 _ ?/ A) L# k
2002: 565-628.
3 m" Z; L1 V' I2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
# k/ T) N! q1 c' _puberty in children with tumours of the suprasellar pineal |
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