- 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 03:25:35
|
顯示全部樓層
Sexual Precocity in a 16-Month-Old
( L- O5 ]# i, gBoy Induced by Indirect Topical; R4 G: s: d/ J
Exposure to Testosterone9 h0 u' y( S" R1 D6 H) F" T" b
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2; W* e8 {: J- j! N5 w
and Kenneth R. Rettig, MD1) t& A4 f2 L( V- p. p
Clinical Pediatrics0 e, X x( ~5 c+ h7 T
Volume 46 Number 6
7 Y& m, R/ G) m6 U2 vJuly 2007 540-5435 d6 ~6 w5 x2 u8 n J5 M
© 2007 Sage Publications7 |1 _5 B! J6 z' N
10.1177/0009922806296651
1 ?; V, | q% [ N. Shttp://clp.sagepub.com
& o3 q0 b% j) zhosted at
8 @6 z$ Q3 x& y: z! ], G+ L" I4 Vhttp://online.sagepub.com" x& q6 b# a! Y
Precocious puberty in boys, central or peripheral,
2 A: @* o9 I9 t! g9 l0 j& ~ d/ t, mis a significant concern for physicians. Central
% [ Q. i, d6 wprecocious puberty (CPP), which is mediated
$ v( ]$ O$ _- x4 c6 N4 Athrough the hypothalamic pituitary gonadal axis, has
0 q* x5 q1 V4 p, ea higher incidence of organic central nervous system
' c4 f' Q7 A" I; C, b3 x- flesions in boys.1,2 Virilization in boys, as manifested
0 q y! @/ p6 W- {by enlargement of the penis, development of pubic% b# A4 l/ f. H* u. S$ n
hair, and facial acne without enlargement of testi-
0 g6 |, }9 s0 q* y% I" Scles, suggests peripheral or pseudopuberty.1-3 We
6 D8 F( b& O5 b3 U0 c0 ^* X9 {$ Ureport a 16-month-old boy who presented with the5 W: ]: s2 G6 ?0 U& k! Z
enlargement of the phallus and pubic hair develop-/ u* D6 J! M+ I! R7 p5 F( @
ment without testicular enlargement, which was due
& _8 d! A" O. F8 T1 b1 J; cto the unintentional exposure to androgen gel used by
' W5 h& Q6 F, R" Vthe father. The family initially concealed this infor-
; f# x2 Z ~9 |) C+ a8 M+ R# [mation, resulting in an extensive work-up for this9 k1 k3 _; {8 b6 ?8 w* O
child. Given the widespread and easy availability of
) j& R i8 v' m5 ~9 V* itestosterone gel and cream, we believe this is proba-
( S0 k- P4 y* Y2 Z" t" Sbly more common than the rare case report in the) N- ^* E: }7 D% [
literature.49 E- v- J7 a% P8 a/ R6 f; A
Patient Report6 o% l U: E; p" Z! ?+ {" ?
A 16-month-old white child was referred to the1 r7 m2 F1 [' b! k; P I7 f E
endocrine clinic by his pediatrician with the concern
9 a T, b* r2 `9 e3 Nof early sexual development. His mother noticed
* Q) P6 P! [ I! q% _$ Glight colored pubic hair development when he was
) M& v7 K) g! k+ s) k5 ~4 J5 ~. m2 Y- |From the 1Division of Pediatric Endocrinology, 2University of8 D4 _* ]) C) d! ?& j
South Alabama Medical Center, Mobile, Alabama.0 W. U6 z! J. W& M
Address correspondence to: Samar K. Bhowmick, MD, FACE,1 w; y" b6 U" r$ i, K- o* U
Professor of Pediatrics, University of South Alabama, College of% }; N# Q0 e8 T/ l4 \" ?! V: z* I
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;4 E! y; t7 T& ?' H: F
e-mail: [email protected].
" E5 U7 O7 z5 D0 aabout 6 to 7 months old, which progressively became
7 |7 i2 M2 }& }darker. She was also concerned about the enlarge-
$ Q: P* x# p- j- o2 J) I% i/ Oment of his penis and frequent erections. The child
* d8 f6 _5 K8 \- K% k9 vwas the product of a full-term normal delivery, with
6 w) v; z. x6 J& k' na birth weight of 7 lb 14 oz, and birth length of7 O: ^* l4 b) W
20 inches. He was breast-fed throughout the first year
# f! \$ H' F1 k& b* q0 l iof life and was still receiving breast milk along with7 T; F5 O z" K) n
solid food. He had no hospitalizations or surgery,' {; z& Y- l0 c# x
and his psychosocial and psychomotor development8 V! ~% N2 w5 m8 F+ i
was age appropriate.
. L8 j, `4 o& g- f. OThe family history was remarkable for the father,3 A5 T5 P b$ f; a2 x+ _
who was diagnosed with hypothyroidism at age 16,
) `+ X w( q0 C3 z, }which was treated with thyroxine. The father’s
9 W3 y" o, s2 B0 z% a0 C5 W, mheight was 6 feet, and he went through a somewhat
$ H# U9 H1 g' e: k1 a: i, Xearly puberty and had stopped growing by age 14.
; I% a s, J) i5 ?( s1 Q* C" SThe father denied taking any other medication. The: f: G( q3 c' c0 o( m; ~4 u
child’s mother was in good health. Her menarche
$ n( k5 ?) k/ A/ i7 ~4 Pwas at 11 years of age, and her height was at 5 feet8 A/ s5 F0 k. J r
5 inches. There was no other family history of pre- D. R9 K" Q8 Y
cocious sexual development in the first-degree rela-( i% V% p: f1 g! v7 v* v; p8 A
tives. There were no siblings.* e. k4 C) D+ O; c5 r
Physical Examination
5 c/ \$ r, \- ]9 k3 J ^The physical examination revealed a very active,! j; X1 F6 k. f9 m, M
playful, and healthy boy. The vital signs documented H5 E. d# [( ]! ?
a blood pressure of 85/50 mm Hg, his length was+ U/ E7 E$ _, Z, X7 [
90 cm (>97th percentile), and his weight was 14.4 kg3 o/ L7 f0 U0 g6 }$ T
(also >97th percentile). The observed yearly growth
# x0 I3 |1 b* l7 B7 ^4 R( r! kvelocity was 30 cm (12 inches). The examination of
+ ^3 X0 j2 g: P& othe neck revealed no thyroid enlargement.
) `$ `7 b5 [& `) H% |The genitourinary examination was remarkable for
* o" Y! J. E- Qenlargement of the penis, with a stretched length of m! { T+ {: \" T
8 cm and a width of 2 cm. The glans penis was very well
; @3 x$ f; I# L) Adeveloped. The pubic hair was Tanner II, mostly around X0 C/ X/ n ^- v ?
540
, B: s; S5 z# d8 T2 ?. T$ uat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
! G" K: ]% |8 l( L2 e/ j8 qthe base of the phallus and was dark and curled. The& N, n; f b, y, y/ A, _% o$ V
testicular volume was prepubertal at 2 mL each.4 A, \ a/ k: [* i. ?( l
The skin was moist and smooth and somewhat% a2 K) w* z& d& _" l2 E
oily. No axillary hair was noted. There were no: `3 A0 n# t" a, I& t+ Y
abnormal skin pigmentations or café-au-lait spots.: w4 n" {" a. a; e# Z! U: r2 |
Neurologic evaluation showed deep tendon reflex 2++ o) S8 F( J0 h. @
bilateral and symmetrical. There was no suggestion
+ K) Q' `$ G% e. k6 ^$ `- v+ w$ `of papilledema.# Q$ C' Z9 X* W) i, C4 j& M' x
Laboratory Evaluation
" R1 z( J1 F$ }The bone age was consistent with 28 months by5 z ?2 ]( O* [) `: E; e
using the standard of Greulich and Pyle at a chrono-: b7 M K: S5 e0 Y
logic age of 16 months (advanced).5 Chromosomal
$ k! U* y/ v9 v& T/ i5 Ukaryotype was 46XY. The thyroid function test
i: k j+ Q# d; S* @showed a free T4 of 1.69 ng/dL, and thyroid stimu-9 Y- A* q" L7 n
lating hormone level was 1.3 µIU/mL (both normal).
: W. D0 ^+ ~2 u1 rThe concentrations of serum electrolytes, blood8 N. `& o/ h3 r
urea nitrogen, creatinine, and calcium all were! v0 ~0 _1 d% B* \6 `. D; j) S
within normal range for his age. The concentration
( Y) \& j E( l5 Q" Jof serum 17-hydroxyprogesterone was 16 ng/dL) J; M4 h$ ]& P6 m; z
(normal, 3 to 90 ng/dL), androstenedione was 20
, t6 c; x2 X" W6 t" }ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
# v$ f# f+ ~5 \- nterone was 38 ng/dL (normal, 50 to 760 ng/dL),
+ @+ k5 _ r9 q' i5 rdesoxycorticosterone was 4.3 ng/dL (normal, 7 to1 v) Z. S; l, b
49ng/dL), 11-desoxycortisol (specific compound S)& m# G4 W3 T# ]
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-1 i( S. e ?! c- ~7 k) i( L
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total1 N, ]3 o) g+ e3 w$ m V; E
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),5 K) c0 t7 m) z+ w, R
and β-human chorionic gonadotropin was less than) y7 ]0 R6 F' j1 f6 U
5 mIU/mL (normal <5 mIU/mL). Serum follicular, D; _+ r. ?: s$ q$ Z" i
stimulating hormone and leuteinizing hormone9 O* v* A6 p/ I# H) j4 F. |" t7 N6 }% j
concentrations were less than 0.05 mIU/mL
. _% Q9 q, [4 b9 F5 O(prepubertal).
" v& r0 L! b- h3 a6 a7 t" DThe parents were notified about the laboratory. Q. i3 B# Z Q
results and were informed that all of the tests were
! X2 z: u+ C4 `5 l" i: D4 Y+ ~normal except the testosterone level was high. The
# K, i# V4 B% d! j! d8 H) gfollow-up visit was arranged within a few weeks to5 n0 Q9 Y4 |1 D- z q
obtain testicular and abdominal sonograms; how-
) i" E1 ?+ F/ K% p. J' Uever, the family did not return for 4 months.1 u% v2 ^' F6 _$ t& O l
Physical examination at this time revealed that the
3 P+ v# \( C7 i' v& A; ichild had grown 2.5 cm in 4 months and had gained
. s8 n8 }' Z! @; L8 S2 V. `$ u1 S2 kg of weight. Physical examination remained
- ]' E6 x* v+ O* [! [unchanged. Surprisingly, the pubic hair almost com-
: E# T' @$ \6 Upletely disappeared except for a few vellous hairs at
/ l3 W/ B0 E! C2 W- bthe base of the phallus. Testicular volume was still 2
; G; `7 t) H% B6 ~6 _* BmL, and the size of the penis remained unchanged.- l( p$ p5 z4 C3 i
The mother also said that the boy was no longer hav-
( ~: j: Y1 y4 T- T# s/ w2 r) Wing frequent erections.4 b* c& L3 C" @6 u
Both parents were again questioned about use of: x9 j! y5 j9 h1 `; V
any ointment/creams that they may have applied to
0 W, ?5 N) _* S* [the child’s skin. This time the father admitted the
$ @/ F- _4 t( A; d0 H0 FTopical Testosterone Exposure / Bhowmick et al 541
' H/ E: G* s, R) l; xuse of testosterone gel twice daily that he was apply-# _4 l( m/ \' z* A
ing over his own shoulders, chest, and back area for
& m4 }- B1 G8 Ga year. The father also revealed he was embarrassed
" x. I( Y6 J2 D1 j# v1 L. R8 zto disclose that he was using a testosterone gel pre-
9 P8 c7 u/ z5 Q' s0 o( h6 s6 R( m: O" Pscribed by his family physician for decreased libido1 j: W) f; O$ h/ ^6 J A; ]9 i
secondary to depression.
" j) S9 ?; S$ ~* }3 t# UThe child slept in the same bed with parents.( B1 V7 _( P. C: Q$ M7 z8 z! J
The father would hug the baby and hold him on his
' E! f+ o* S' ]7 c6 \- L: J, Vchest for a considerable period of time, causing sig-
! }+ a" c2 c5 U9 s$ i/ }0 Vnificant bare skin contact between baby and father.
- _, X; K5 _: AThe father also admitted that after the phone call,5 B9 @% X. ~+ E) u# h
when he learned the testosterone level in the baby( X' R$ F" h+ j3 b# R5 I$ G
was high, he then read the product information* C. @3 K7 R$ |, a
packet and concluded that it was most likely the rea-+ p) P0 Y) D; c* N
son for the child’s virilization. At that time, they
$ a3 v1 U: o+ n0 \, G, {decided to put the baby in a separate bed, and the
' O6 `% I- m& ^1 s4 z' x. Ffather was not hugging him with bare skin and had
* H) [+ h& @% G2 g- \! s- Dbeen using protective clothing. A repeat testosterone
' T6 b2 U! D# M& I) ?& X# `7 ~7 Y7 S G) Ytest was ordered, but the family did not go to the
& k/ j' O9 {9 zlaboratory to obtain the test.
6 p3 W/ L& t1 u! x% D& D2 YDiscussion
; F$ u! `1 ^2 o; e D9 p0 F* {: ~Precocious puberty in boys is defined as secondary
, O# d% e2 `/ W! f5 f1 j$ |7 i2 R3 ]sexual development before 9 years of age.1,4
4 p! y6 g" ^$ H9 {7 Z$ }9 GPrecocious puberty is termed as central (true) when
( B+ y! p* c5 }" Rit is caused by the premature activation of hypo-
4 s4 _9 L' o; P" @1 h1 [( ethalamic pituitary gonadal axis. CPP is more com-! L) A+ C1 Z: x0 V0 L" n' n( V
mon in girls than in boys.1,3 Most boys with CPP& w) |" U: V1 E
may have a central nervous system lesion that is& ~5 }9 I! A2 l! F% b! m' W4 W
responsible for the early activation of the hypothal-" f3 M# _* W% A' |& t- E* o7 v F4 h% F
amic pituitary gonadal axis.1-3 Thus, greater empha-1 Z* ]- ?, d! E- `3 h1 N, V
sis has been given to neuroradiologic imaging in9 K( C4 l5 E6 p# I# E8 @
boys with precocious puberty. In addition to viril-' e" C1 q9 c& S6 J% a! Q9 ?
ization, the clinical hallmark of CPP is the symmet-
$ `+ d: h8 _$ f/ s6 z/ O; t5 |% ]* jrical testicular growth secondary to stimulation by
: [2 a! L! e- I. @* ]8 H! [. }3 Igonadotropins.1,3
; c; N( G0 n" U; fGonadotropin-independent peripheral preco-
7 ~: _( c+ f B# F1 ? G; H9 mcious puberty in boys also results from inappropriate
4 b) i4 i- J' X& o$ U* yandrogenic stimulation from either endogenous or. b0 d+ {* [ F4 f
exogenous sources, nonpituitary gonadotropin stim-
5 D- l7 D& O5 U" h' A5 I3 Qulation, and rare activating mutations.3 Virilizing7 ]2 b; o2 G% a5 t) K
congenital adrenal hyperplasia producing excessive
; p7 h9 h5 b6 i7 S4 aadrenal androgens is a common cause of precocious4 O. v, L# N! P
puberty in boys.3,4
% c& ]& H& [, E9 Q5 qThe most common form of congenital adrenal" _9 b( s& e/ O1 s
hyperplasia is the 21-hydroxylase enzyme deficiency.! X- @+ P) j$ E6 b* }0 d
The 11-β hydroxylase deficiency may also result in, U6 W* h% l1 Z! S1 t$ {, o7 R% s
excessive adrenal androgen production, and rarely,4 h7 L ]% c8 C/ {% k" B1 I
an adrenal tumor may also cause adrenal androgen
' O7 }' A" e# I6 nexcess.1,3/ i+ E& ^5 T5 y. ~+ _
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
y3 i' L- n4 c: F$ D0 \ Y542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
7 h7 @8 l2 I) C* D7 d, MA unique entity of male-limited gonadotropin-
6 Z; g# b0 I0 E/ q4 H2 I9 {& ?independent precocious puberty, which is also known
4 ~# A) L( O6 {as testotoxicosis, may cause precocious puberty at a% I" c- N9 x5 K! S& o. s
very young age. The physical findings in these boys
) J, l/ Z- C% ?, X$ m0 Bwith this disorder are full pubertal development,
7 o/ P5 [$ d3 t6 V5 ?including bilateral testicular growth, similar to boys. }" V. o; [2 m. {8 {5 k# W5 `
with CPP. The gonadotropin levels in this disorder b( E4 u+ {9 a4 b6 D0 }
are suppressed to prepubertal levels and do not show
+ N" ?9 W( Q8 v0 H* cpubertal response of gonadotropin after gonadotropin-+ ?% k6 ]% P+ ~! H; ~7 [
releasing hormone stimulation. This is a sex-linked
1 X! T$ ^7 l- ~& R; o" j* a2 Uautosomal dominant disorder that affects only, s: h7 \( A. B; B1 T, x
males; therefore, other male members of the family
: E. U4 v$ }" a4 V! f, K" K8 rmay have similar precocious puberty.3
m* B+ f9 p3 [8 M- W% h4 `* M8 r% wIn our patient, physical examination was incon-% ?. F) U! M% Z/ W* R
sistent with true precocious puberty since his testi-
% C2 T5 t! ^+ _ Z; l; ]3 f* ccles were prepubertal in size. However, testotoxicosis
: b, [4 i4 l) W7 O. |was in the differential diagnosis because his father3 H: A9 A8 q) E8 p* |
started puberty somewhat early, and occasionally,0 U9 B" E8 p; P |: G8 p; x
testicular enlargement is not that evident in the
. @8 l5 Y. R- b1 b9 ?$ R0 y4 ?beginning of this process.1 In the absence of a neg-
; b K# Z7 P0 g( k. j5 |6 J% Native initial history of androgen exposure, our! U1 U' d' h' t" I8 ~0 R% D
biggest concern was virilizing adrenal hyperplasia,
: `. l# m$ W6 M5 S6 u/ h* Aeither 21-hydroxylase deficiency or 11-β hydroxylase, `; r7 f# D5 W% Y1 L
deficiency. Those diagnoses were excluded by find-
/ T+ z) P, ^( j, u( B# eing the normal level of adrenal steroids.1 ?. V+ h' |9 P x! d& [
The diagnosis of exogenous androgens was strongly8 ?/ B* u+ B' C
suspected in a follow-up visit after 4 months because5 Y5 i1 E/ k* `( }$ r7 |
the physical examination revealed the complete disap-
j/ X- L4 c. }+ ]# P; spearance of pubic hair, normal growth velocity, and. D |3 ?0 @7 x
decreased erections. The father admitted using a testos-
! V* {; w+ t- y8 G/ Aterone gel, which he concealed at first visit. He was# G0 Y/ v& `/ {& j# { W. y# i5 Q- ]6 C
using it rather frequently, twice a day. The Physicians’& K/ ^ C/ C7 \% b, C. A
Desk Reference, or package insert of this product, gel or
% J' |) c4 W- X9 v' F r5 }4 z$ a" tcream, cautions about dermal testosterone transfer to
3 }9 l4 b; }$ w; R7 w) hunprotected females through direct skin exposure.
" [. N* ~8 i& g [Serum testosterone level was found to be 2 times the
# q9 Q2 B8 ^3 t, w' N5 E4 |baseline value in those females who were exposed to$ J' `7 u9 L# i/ P* {7 j
even 15 minutes of direct skin contact with their male
, r/ b; `8 y! Q/ }: ypartners.6 However, when a shirt covered the applica-# X/ _ Y8 M2 Y& B
tion site, this testosterone transfer was prevented.! O$ t/ X8 x6 O1 n5 A7 W
Our patient’s testosterone level was 60 ng/mL,: q3 o2 l0 h7 B+ C
which was clearly high. Some studies suggest that
7 n( i' G1 h( Q% Z6 Pdermal conversion of testosterone to dihydrotestos-; @) b- d j% E* l% }, T* S
terone, which is a more potent metabolite, is more* x7 L/ j+ k( D: y$ C& ^
active in young children exposed to testosterone' u, k" b$ A- _$ n$ B
exogenously7; however, we did not measure a dihy-
. @6 R, B8 [0 b7 w x) L1 ]drotestosterone level in our patient. In addition to. r) f0 I* W; u; M, p; ]9 N; t
virilization, exposure to exogenous testosterone in
$ t5 i8 b2 N4 S n: ]' t! Gchildren results in an increase in growth velocity and
/ Y# t6 I _0 [advanced bone age, as seen in our patient.
& C8 f; J0 O% R0 sThe long-term effect of androgen exposure during& _# [1 \ _" P) d3 K$ {2 A; P
early childhood on pubertal development and final
0 _$ ^7 }) Y! e. ?: Xadult height are not fully known and always remain
! v7 z- l) ]) H$ _+ {a concern. Children treated with short-term testos-
) d8 X: q; o" i1 L0 |1 pterone injection or topical androgen may exhibit some
1 d G0 @9 W: @- _- w5 qacceleration of the skeletal maturation; however, after* K' g. O( f, `7 a! p( N# V
cessation of treatment, the rate of bone maturation) X2 A- w( f( ^ o9 a
decelerates and gradually returns to normal.8,9
6 f9 ]1 ]/ c, M6 J5 EThere are conflicting reports and controversy
( Q2 J* `: s: y$ _' H& N/ cover the effect of early androgen exposure on adult
+ Y, }& M& w0 D8 `! J4 N5 gpenile length.10,11 Some reports suggest subnormal4 x& F7 _" E4 I
adult penile length, apparently because of downreg-$ A& F. n' u" ?9 X+ b9 `5 g' D
ulation of androgen receptor number.10,12 However,# q: I7 N+ L2 Z& m) g
Sutherland et al13 did not find a correlation between( ]1 h6 v( u" a! g$ E- e
childhood testosterone exposure and reduced adult
$ O9 W6 ^' T5 Z6 K$ }* S$ ppenile length in clinical studies." I, i: n& z9 b$ T% ~2 d$ K. g) ^6 ?
Nonetheless, we do not believe our patient is
8 [9 _8 c' r2 r8 D1 Z0 Cgoing to experience any of the untoward effects from
4 N) K" D1 x( }& P; ztestosterone exposure as mentioned earlier because5 f" D# X8 T8 v: c' C! X
the exposure was not for a prolonged period of time.
?2 C" }# T6 y+ |Although the bone age was advanced at the time of
& A8 o* W6 k9 ?4 I, k5 A: _diagnosis, the child had a normal growth velocity at
" N6 ] k- o M9 [: \9 Nthe follow-up visit. It is hoped that his final adult
) K9 H- ]7 s8 a/ G( Dheight will not be affected.. O5 j( L$ ?4 a! I
Although rarely reported, the widespread avail-
2 a3 Q& B4 Q+ b& n7 Zability of androgen products in our society may
# g7 V6 J, q' s) i/ gindeed cause more virilization in male or female1 j* \6 F1 ]8 ^; n
children than one would realize. Exposure to andro-
0 ^: _/ p' B! Agen products must be considered and specific ques-+ x) P$ _% U ? o
tioning about the use of a testosterone product or1 ?6 z* m2 Z5 D" O, G8 \3 H- Y
gel should be asked of the family members during
+ ^% ~/ C$ d# Hthe evaluation of any children who present with vir-# H; Y. c$ X. k; [3 u4 O
ilization or peripheral precocious puberty. The diag-! @2 K8 e( m& s5 c* c" X1 k* B
nosis can be established by just a few tests and by) V) h, C8 B0 l, r: R3 R- t
appropriate history. The inability to obtain such a
+ b, _5 ?$ P. J( s8 `& {8 h/ nhistory, or failure to ask the specific questions, may
) }, A9 }0 Y4 k- U3 b% |* @" h3 qresult in extensive, unnecessary, and expensive
/ u. D. o4 c* x- sinvestigation. The primary care physician should be( \% n+ i& W% H- x( k* N5 w& s
aware of this fact, because most of these children% g/ r& z5 ~; x0 t3 L' T
may initially present in their practice. The Physicians’
7 k3 X+ \" U& T3 ZDesk Reference and package insert should also put a9 c* e* @" l* l! ]
warning about the virilizing effect on a male or
+ ~ @, o) T. Y# Pfemale child who might come in contact with some-9 T( c+ |2 o7 f9 u5 ~
one using any of these products.
: w; H- d" m: @6 T: L5 aReferences2 c0 G/ b/ p1 Z. L* J& b0 ]
1. Styne DM. The testes: disorder of sexual differentiation
- ^ G. R* d- ?! v* T1 }3 d$ k6 mand puberty in the male. In: Sperling MA, ed. Pediatric
, J9 {) z# K! Z, b7 a1 S* JEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
2 f* l; J! f) j9 X( p0 r2002: 565-628.' h9 g9 Z: ^2 |& \2 b
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious: ^. N# F8 ?6 s: j* o" A W" b
puberty in children with tumours of the suprasellar pineal |
|