- 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-Old6 H. \- i4 H# E) i
Boy Induced by Indirect Topical0 F3 ]. H6 G6 J; ~" x
Exposure to Testosterone( _6 @. }5 H" `' p( z
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
3 m( s( y( }; `+ [$ v# F& N0 ]and Kenneth R. Rettig, MD1
) z+ ^+ Y6 @* R- K! G3 }Clinical Pediatrics
: E% Q) I/ Q# ]: z/ Y0 ?9 ]Volume 46 Number 6; z; K% v6 Z; I9 a5 m
July 2007 540-543: W- K5 o: S1 K. V
© 2007 Sage Publications1 {! b* w, g" X0 T% Y5 U
10.1177/00099228062966511 X4 O/ C* \) b9 x
http://clp.sagepub.com
6 \- i" z( |9 K X+ M2 P% U. ^hosted at
, f" o' q$ P8 B6 }3 d4 mhttp://online.sagepub.com- E4 U! c( f3 S# Z
Precocious puberty in boys, central or peripheral,6 G6 S: J0 B' i; M* U. M( n2 r
is a significant concern for physicians. Central% g! H4 O1 K0 I( P: c* Y* ?6 n
precocious puberty (CPP), which is mediated4 [- z/ [; I: I% O( T5 q
through the hypothalamic pituitary gonadal axis, has0 m# e! g# L) Z5 N
a higher incidence of organic central nervous system7 s4 ~( F* a+ O0 b
lesions in boys.1,2 Virilization in boys, as manifested
0 |/ z3 ]0 |) p* o2 ^: W0 v% f& Pby enlargement of the penis, development of pubic6 q, X* t4 `8 e& C, F
hair, and facial acne without enlargement of testi-0 P& C8 T' A3 M' D- _, b
cles, suggests peripheral or pseudopuberty.1-3 We) }4 W& M6 Q# _4 r- g
report a 16-month-old boy who presented with the8 p! r' m$ s, t" X" n( }1 s4 X
enlargement of the phallus and pubic hair develop-2 m. q& E2 q. A' C
ment without testicular enlargement, which was due
& {# g3 a1 u- v! ^! g! v% |- vto the unintentional exposure to androgen gel used by: X* m1 w! X( @, \& i! R- a
the father. The family initially concealed this infor- O2 x. I9 A4 h+ M
mation, resulting in an extensive work-up for this' p( m( ~% N: @& w, Y! ? O
child. Given the widespread and easy availability of+ `! B2 O, l; f$ u& F1 \4 y k
testosterone gel and cream, we believe this is proba-
4 v5 i) p! w) U/ d# J0 qbly more common than the rare case report in the
4 E3 p2 x: I: n* bliterature.4# X P% t7 h5 [2 l7 I7 ]
Patient Report$ J/ N: o" H+ b+ M$ o9 h" g
A 16-month-old white child was referred to the" G& K& l; Z3 H( {9 l, V: {
endocrine clinic by his pediatrician with the concern" d5 G( }6 }1 P& q3 u
of early sexual development. His mother noticed, h2 f. g) H" X' q' j) g% u, {
light colored pubic hair development when he was
`& Z# i4 y0 ^" R. WFrom the 1Division of Pediatric Endocrinology, 2University of
9 N% h X+ k6 s- V |South Alabama Medical Center, Mobile, Alabama.6 h' Q7 x; ?; X& K0 x! t
Address correspondence to: Samar K. Bhowmick, MD, FACE,
M0 q" {7 G. \7 s! t2 MProfessor of Pediatrics, University of South Alabama, College of
: l9 a! g- q* E; i) z, K# b wMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;! I% M! F; w! H; K( U% q% o
e-mail: [email protected].
& Y# ]( Y, b8 o6 labout 6 to 7 months old, which progressively became4 C6 B3 s; Q5 M4 y6 w" M% H) `* Q
darker. She was also concerned about the enlarge-
' T' c/ [1 a. L& ~ment of his penis and frequent erections. The child
8 z( G+ [$ R7 r- uwas the product of a full-term normal delivery, with
2 X, [* g$ f- V* b" c: |+ g) Y/ aa birth weight of 7 lb 14 oz, and birth length of
8 K! l* o @0 V# _% ~! j7 _20 inches. He was breast-fed throughout the first year
5 r! p: F m4 O0 M1 P/ {. `of life and was still receiving breast milk along with8 b8 Q% G' u6 `& t# x
solid food. He had no hospitalizations or surgery,# O/ ]4 ?: w4 q7 G
and his psychosocial and psychomotor development5 k& }7 k: V8 b4 B4 P1 N/ T/ G4 X
was age appropriate.7 c( u6 f5 C! [ ]3 |
The family history was remarkable for the father,
6 N0 s# U1 f1 T rwho was diagnosed with hypothyroidism at age 16,
( {6 d: m) t/ [8 k3 swhich was treated with thyroxine. The father’s1 O6 Q2 C6 z8 K9 O& D8 T9 I) M0 Y
height was 6 feet, and he went through a somewhat
4 V" b: E$ v" U& t; Q- ^& H1 E: }$ b2 |early puberty and had stopped growing by age 14.0 b6 [! G# l6 D# R2 s; t( Q
The father denied taking any other medication. The
6 O+ P7 A S" B! r% ?# qchild’s mother was in good health. Her menarche
@3 {6 ]: ?( t) f3 q9 F- Q5 jwas at 11 years of age, and her height was at 5 feet
: F, M' O# S, R: n/ o5 inches. There was no other family history of pre-9 C/ h) z: V8 ] |- N
cocious sexual development in the first-degree rela-8 g8 G6 A/ d5 z7 n
tives. There were no siblings.
; { L8 j w, }2 CPhysical Examination
1 a4 K, ?6 |, W7 u1 M* j% tThe physical examination revealed a very active,
1 J6 ]) R) y' x/ z0 `, qplayful, and healthy boy. The vital signs documented
! E4 F' Q' j; T. Z3 R+ Ca blood pressure of 85/50 mm Hg, his length was
) X/ v; w& |/ h1 r1 _% j. [8 q90 cm (>97th percentile), and his weight was 14.4 kg3 O/ g: W1 M7 N! I! T( w( I0 h' y
(also >97th percentile). The observed yearly growth
. @) `' V# j( B! Dvelocity was 30 cm (12 inches). The examination of1 Q: }' S9 x/ i4 I
the neck revealed no thyroid enlargement.( Y' }3 Z) q+ n* m$ C/ x* C% i
The genitourinary examination was remarkable for" U8 ]; A, H4 H& |5 o/ q) t; X
enlargement of the penis, with a stretched length of
! U$ w: `, l$ s0 P j4 X. c8 cm and a width of 2 cm. The glans penis was very well
* d8 a, h. }& Y: Q! f$ U' q3 `) ^% c9 Sdeveloped. The pubic hair was Tanner II, mostly around
: r* g$ [% O4 g! v, M5 _540- ]% s6 L% k: F; e, ]$ f
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
. D3 g7 [6 y3 G; ~+ ithe base of the phallus and was dark and curled. The
`7 \8 [7 p/ [+ }+ utesticular volume was prepubertal at 2 mL each.0 Y# n' ?- X; Z2 L% K) D, z0 ?0 z
The skin was moist and smooth and somewhat
; v' U$ t( ^+ G4 v6 U# O' xoily. No axillary hair was noted. There were no
5 b; m1 E( N8 L' sabnormal skin pigmentations or café-au-lait spots.5 q6 c$ A+ v6 h1 q
Neurologic evaluation showed deep tendon reflex 2+
9 g% [3 c# L$ {bilateral and symmetrical. There was no suggestion8 h: e+ C4 c% G9 I. f$ R5 K, u
of papilledema.
, N0 K% C6 |" `/ l% x# u, }Laboratory Evaluation- R* M4 P9 s0 y# Q. U7 d
The bone age was consistent with 28 months by
6 _; |& e* [' G) L/ kusing the standard of Greulich and Pyle at a chrono-1 e# a+ F" \- d8 A. O; V M
logic age of 16 months (advanced).5 Chromosomal- h- P7 I0 B" h: b1 f4 {, }
karyotype was 46XY. The thyroid function test
' }1 Q- l( W- Pshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
0 g. q7 z- ~9 | u# Vlating hormone level was 1.3 µIU/mL (both normal).# l( t8 A7 Q0 i
The concentrations of serum electrolytes, blood
8 w3 @. m* c- l% Nurea nitrogen, creatinine, and calcium all were" Y4 @* m' [9 S" [2 m' j
within normal range for his age. The concentration
$ x9 C9 {" u8 n' T9 P2 n" ?8 b' Wof serum 17-hydroxyprogesterone was 16 ng/dL: A. p) _, M# W0 U; ?5 b
(normal, 3 to 90 ng/dL), androstenedione was 20
5 ?) T/ s! t' Y3 I; Z& ]+ `. Bng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
' L, y4 {* H4 K) O% S0 X( ~. Iterone was 38 ng/dL (normal, 50 to 760 ng/dL),
9 i. i; H! z: F, i4 r5 @6 g# ^9 Sdesoxycorticosterone was 4.3 ng/dL (normal, 7 to$ O) K: A' _2 o" }4 A H+ e/ i
49ng/dL), 11-desoxycortisol (specific compound S)
; Y% f6 F- l, Z4 U- G& f( wwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
: M' ^# G9 l i' E4 X+ `2 ltisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
6 c9 v) p! C; H* E$ htestosterone was 60 ng/dL (normal <3 to 10 ng/dL),) R" V8 J' V( M4 E# |5 ^# E4 r* N
and β-human chorionic gonadotropin was less than, _: e5 [- O/ W& g* s% P
5 mIU/mL (normal <5 mIU/mL). Serum follicular
% @$ S- _ A4 D3 t; s' astimulating hormone and leuteinizing hormone: p$ f" h, u- o
concentrations were less than 0.05 mIU/mL
$ {$ j0 ?$ A' G8 x" ~7 `& \ a- }7 w(prepubertal).6 u/ X& [. r/ `. g- G# V0 M& `& x) m
The parents were notified about the laboratory! _/ [" _6 E$ `
results and were informed that all of the tests were( r" S E4 M" b. {. X
normal except the testosterone level was high. The/ s; s9 R/ w* J
follow-up visit was arranged within a few weeks to- o5 I5 ~) {* J3 T4 B9 \
obtain testicular and abdominal sonograms; how-
, y6 ~# f: D) b5 x; d. k: uever, the family did not return for 4 months.
8 L* Y% f& p9 [0 N: h) {; \, uPhysical examination at this time revealed that the" e* t e F1 L4 E* w
child had grown 2.5 cm in 4 months and had gained
, S' i0 b! c1 X) J2 kg of weight. Physical examination remained
, l1 |3 X, e. U$ }unchanged. Surprisingly, the pubic hair almost com-/ n7 l- G( j; l7 R" M
pletely disappeared except for a few vellous hairs at: r0 N5 m7 T' ?
the base of the phallus. Testicular volume was still 2. F, Q( t& h% H9 f* [, R
mL, and the size of the penis remained unchanged.
5 Q' t- E% m! d% s# q" FThe mother also said that the boy was no longer hav-3 ?3 L3 p5 K1 ^. m1 L
ing frequent erections.
" B$ W, f: u5 [9 A& wBoth parents were again questioned about use of
/ p' _; r; m) t: j% x: i3 F7 }any ointment/creams that they may have applied to
; ]4 l9 v4 [/ P( ~& d) jthe child’s skin. This time the father admitted the
6 A/ r @: x! r( Y& YTopical Testosterone Exposure / Bhowmick et al 541$ _) t1 s1 y5 e% \$ U/ Z+ p3 a
use of testosterone gel twice daily that he was apply-* X# z( |+ J5 F% d/ v) Z% d( w
ing over his own shoulders, chest, and back area for$ q, H% H) g4 B4 O" t( u
a year. The father also revealed he was embarrassed
1 |* k' m$ a( X; E$ wto disclose that he was using a testosterone gel pre-: h9 @9 z7 E' e3 @
scribed by his family physician for decreased libido
- s! O: {; \% r ]+ jsecondary to depression." ^- o' j; Y0 Z2 x6 a6 l* R2 z
The child slept in the same bed with parents.
+ d7 M0 L# d' P' S. e! b5 eThe father would hug the baby and hold him on his
6 E J1 E; ?. D) H9 k# K# Y% ]chest for a considerable period of time, causing sig-
- _0 t2 I- l5 }* Onificant bare skin contact between baby and father.0 g: E; S# }. n! z+ r
The father also admitted that after the phone call," W- \' | o5 N/ I4 B( m
when he learned the testosterone level in the baby
; T2 r' e6 Q$ H5 Dwas high, he then read the product information
! @! H b3 j8 S6 j& R% Fpacket and concluded that it was most likely the rea-
" I' \' S! W% s3 Qson for the child’s virilization. At that time, they0 Z- X7 w6 w( Z
decided to put the baby in a separate bed, and the2 ~4 J) w9 Y2 q* a
father was not hugging him with bare skin and had
+ ~3 X8 y# |" K, G9 U- ^& Ubeen using protective clothing. A repeat testosterone
' Y* S4 u1 D1 V5 |3 g9 atest was ordered, but the family did not go to the
" {! i8 M z/ G4 Nlaboratory to obtain the test.
[# P$ n0 {" Q7 |4 k% d! f ]Discussion$ A. p; t6 T% j/ l9 Y* |
Precocious puberty in boys is defined as secondary
# e+ n& o" e4 w, [/ A4 {0 k4 {2 Wsexual development before 9 years of age.1,4
: I0 h$ k5 T1 i/ |# x5 EPrecocious puberty is termed as central (true) when* X7 Q. A1 a; ]: B1 L+ h! ]+ P
it is caused by the premature activation of hypo-
: c8 d: j2 {0 J7 Z5 {8 _; N4 Pthalamic pituitary gonadal axis. CPP is more com-
2 n* x8 C( A' \5 u6 S9 tmon in girls than in boys.1,3 Most boys with CPP
; ^& S: ?- `8 z$ x+ Y4 smay have a central nervous system lesion that is
& @" k6 e: C/ b: Fresponsible for the early activation of the hypothal-' R* B8 B+ K% q' @; w5 ^
amic pituitary gonadal axis.1-3 Thus, greater empha-# F+ t+ Q |7 T; A* s
sis has been given to neuroradiologic imaging in& v9 Q9 r1 J, x# ~ X! N: P' e2 b
boys with precocious puberty. In addition to viril-
+ F5 K/ ~6 d( a( n1 Q1 ?# z8 c zization, the clinical hallmark of CPP is the symmet-
( Y/ H5 Y. y7 zrical testicular growth secondary to stimulation by
' e& E1 t+ M+ N8 a, X8 Egonadotropins.1,3$ [, H% P6 O+ C5 x6 [) R
Gonadotropin-independent peripheral preco-! J6 O; p- @+ e7 K
cious puberty in boys also results from inappropriate
! _1 E G7 h7 z, N2 Uandrogenic stimulation from either endogenous or! h7 W$ |& j& f+ E# `
exogenous sources, nonpituitary gonadotropin stim-
# k- M. y/ C4 @. dulation, and rare activating mutations.3 Virilizing
( w) C8 a3 K$ tcongenital adrenal hyperplasia producing excessive+ p% j% l3 w- H3 p( o7 q
adrenal androgens is a common cause of precocious% q h0 M' z! ?6 t- {
puberty in boys.3,4: z1 G1 i' B6 M
The most common form of congenital adrenal8 q* c; K) v6 G6 |/ K5 \6 L; Z: L
hyperplasia is the 21-hydroxylase enzyme deficiency.
+ W f/ p" l3 A) w+ BThe 11-β hydroxylase deficiency may also result in
% k1 @$ S" L0 `8 k) uexcessive adrenal androgen production, and rarely,
% ^- ^5 G, u$ t3 E" g- Can adrenal tumor may also cause adrenal androgen
& ]) s7 E8 y) eexcess.1,3
5 R6 _# d1 A( O0 O% G4 ~at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
- a# c/ z# f1 m! R. X' b) G542 Clinical Pediatrics / Vol. 46, No. 6, July 2007/ m8 a E3 R+ Z5 g
A unique entity of male-limited gonadotropin-
/ _0 `5 v2 ^% _independent precocious puberty, which is also known6 K: x: m9 O5 Y" ^
as testotoxicosis, may cause precocious puberty at a
1 v2 f J4 e" [" k5 t! _very young age. The physical findings in these boys
, {4 I1 |* C; Z P! b7 t9 Kwith this disorder are full pubertal development,
, U7 T9 S& M! \. e# z7 E" o; Xincluding bilateral testicular growth, similar to boys
5 e# S7 G7 D3 I8 \' hwith CPP. The gonadotropin levels in this disorder' h" D# `! I E0 F- g
are suppressed to prepubertal levels and do not show5 a" W7 B' A2 o, V- V
pubertal response of gonadotropin after gonadotropin-/ P5 h6 y+ a6 ^8 i* b1 W! U: W% k
releasing hormone stimulation. This is a sex-linked
, ]2 Q7 b3 Q- q; ?* j; Pautosomal dominant disorder that affects only
6 {# p9 Y3 P) Q, |$ n5 `* ymales; therefore, other male members of the family& L; k( }: R2 O# m% n. {4 C" e
may have similar precocious puberty.3
. R+ Q1 o5 W3 W3 O* \' h3 bIn our patient, physical examination was incon-& l- E4 J5 J; k% J& ]# r' _- E
sistent with true precocious puberty since his testi-
8 K2 o$ L8 }8 h" l; R. Ocles were prepubertal in size. However, testotoxicosis6 z3 x9 W2 [! [9 O+ d1 @+ A
was in the differential diagnosis because his father: a3 d& K& Q: D7 R
started puberty somewhat early, and occasionally,
. h7 \! y0 Z1 U) @! w, `1 ktesticular enlargement is not that evident in the
H# G( O, ?1 P2 h. ~' Gbeginning of this process.1 In the absence of a neg-# [! L$ O) S9 Q
ative initial history of androgen exposure, our4 b! u8 b' y1 R6 b. V" }
biggest concern was virilizing adrenal hyperplasia,$ {2 @9 w+ S8 d j
either 21-hydroxylase deficiency or 11-β hydroxylase
+ S W6 z- z3 u+ D! R, o! @0 ddeficiency. Those diagnoses were excluded by find-+ m) j" ]' I) ?% x% a
ing the normal level of adrenal steroids.
, P+ k: [( e" ^0 ], q8 K6 b! rThe diagnosis of exogenous androgens was strongly( q3 _6 Z' y* |0 r U+ |
suspected in a follow-up visit after 4 months because. W- s9 R# ?$ W* p
the physical examination revealed the complete disap-
2 w! I# @; d! L2 {$ epearance of pubic hair, normal growth velocity, and
% S0 Y9 j. k/ D" Pdecreased erections. The father admitted using a testos-1 I/ B9 ?6 @2 P5 O: ?
terone gel, which he concealed at first visit. He was
, d0 B/ x) ]2 a W1 Nusing it rather frequently, twice a day. The Physicians’
& p' s) p& o6 b7 m1 _Desk Reference, or package insert of this product, gel or8 V4 t4 U& N; U$ A
cream, cautions about dermal testosterone transfer to
; J: l( n9 P, r6 ?2 Junprotected females through direct skin exposure.
: F! l8 s. j3 N7 D. v' W% uSerum testosterone level was found to be 2 times the1 x! B6 g. F% m$ X# x9 ]
baseline value in those females who were exposed to
2 f$ W3 [& P5 |( x& ]even 15 minutes of direct skin contact with their male% V# r! \0 `% |( ^
partners.6 However, when a shirt covered the applica-* e. G+ x9 G' \9 Q) C6 E( _
tion site, this testosterone transfer was prevented.5 p2 U/ G5 i1 ~
Our patient’s testosterone level was 60 ng/mL,
4 ^0 |0 ^& S! A5 X( zwhich was clearly high. Some studies suggest that9 l9 n r1 A4 z$ z" {0 D+ k; [
dermal conversion of testosterone to dihydrotestos-. G+ R2 F+ v7 _* S" g
terone, which is a more potent metabolite, is more( u0 y! l; {3 o; m
active in young children exposed to testosterone
4 z: O+ |$ m6 ~4 Rexogenously7; however, we did not measure a dihy-' a/ K2 L2 p+ Q: F: t6 S
drotestosterone level in our patient. In addition to
6 r5 V8 m. `# avirilization, exposure to exogenous testosterone in
. O( b- w+ f/ Z& ?( F, Bchildren results in an increase in growth velocity and% b# H/ @( @: K- F0 c
advanced bone age, as seen in our patient.
4 l+ B* a! G& q; Q0 SThe long-term effect of androgen exposure during
( V6 c5 z2 Y: W6 U! e1 H2 n, uearly childhood on pubertal development and final$ [/ ?$ h+ Z3 j% J9 W( {
adult height are not fully known and always remain8 x; } p) |3 \" n" v
a concern. Children treated with short-term testos- G S& b% v5 T6 u- r
terone injection or topical androgen may exhibit some
9 V! J9 [/ ^: G9 C! {! I: ?acceleration of the skeletal maturation; however, after
% f: E$ t" T+ X; ?; D' mcessation of treatment, the rate of bone maturation
8 d, g0 A; K( G0 \+ ?decelerates and gradually returns to normal.8,9% i% p; s+ E; e1 X
There are conflicting reports and controversy0 I3 w# t) b* p
over the effect of early androgen exposure on adult( B3 \. B0 q1 j6 J4 I, A/ r
penile length.10,11 Some reports suggest subnormal7 A- d1 R2 k0 x8 y3 c% E
adult penile length, apparently because of downreg- x* q+ R! [0 [: b/ ^1 {
ulation of androgen receptor number.10,12 However,9 c! n0 a5 L6 v5 W1 G9 ^
Sutherland et al13 did not find a correlation between1 t+ w& [# M8 d7 [9 [7 G
childhood testosterone exposure and reduced adult8 `* I8 z1 z. ^6 L$ P# E
penile length in clinical studies.
! L; S9 r% p2 aNonetheless, we do not believe our patient is v" u+ m7 I8 p$ Z2 s
going to experience any of the untoward effects from- q: A+ t, y6 k
testosterone exposure as mentioned earlier because
1 h( S! A) k+ r) Gthe exposure was not for a prolonged period of time.
/ X+ o' S0 f. {$ CAlthough the bone age was advanced at the time of+ C: f; O( A. I% E0 @
diagnosis, the child had a normal growth velocity at& B$ D/ |7 p, x
the follow-up visit. It is hoped that his final adult( J1 A( U) D8 p' V* ~6 U; `
height will not be affected.
* ^' d9 ]! ~ @! c5 MAlthough rarely reported, the widespread avail-
% o; h R/ M% T' U' C Qability of androgen products in our society may, Y5 E; ]: l4 |
indeed cause more virilization in male or female, B& y% b4 V& q- @
children than one would realize. Exposure to andro-
! V6 E! ?& a$ B) O, G/ ~gen products must be considered and specific ques-- |. o+ A6 i: j% g' H1 _
tioning about the use of a testosterone product or5 @; b2 A( k r* z- V2 ~- _
gel should be asked of the family members during# l1 ^0 O5 ~8 y n; y9 V0 P
the evaluation of any children who present with vir-5 l7 y) c: d" s( y" K; f1 S+ e
ilization or peripheral precocious puberty. The diag-
3 M1 E$ }; k& t7 n) k) n' ]nosis can be established by just a few tests and by( J# b8 t5 }* l" i1 q% S/ V9 }: J0 j
appropriate history. The inability to obtain such a% P3 s7 n3 J4 P8 t; Q
history, or failure to ask the specific questions, may
) V1 e' \$ R/ q q9 c; {" J( k- U$ ?6 D0 Wresult in extensive, unnecessary, and expensive( N8 Y1 \/ A; \7 U1 V1 U9 x4 W- J
investigation. The primary care physician should be
i* y1 B# ~- l; p, L. xaware of this fact, because most of these children
$ ]) h& V# k; v! _, Q+ smay initially present in their practice. The Physicians’6 B2 q3 l8 s+ Q# [3 b# D
Desk Reference and package insert should also put a
, E! @( E0 B m1 twarning about the virilizing effect on a male or
8 F8 W/ ?- b6 K5 `; ~' p9 ffemale child who might come in contact with some-! D& P# R6 G, z3 E8 h
one using any of these products.: ?) l" {6 o+ q) }$ F
References
7 }) Z9 D0 R) K1 O. ^- |6 I( B1. Styne DM. The testes: disorder of sexual differentiation
! l' ]! B) [% [& Uand puberty in the male. In: Sperling MA, ed. Pediatric
+ [& A8 b% j hEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
1 [/ P' M5 h5 \/ i- c G2002: 565-628.- h% _- O/ z/ d) ]) M/ N
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
9 e5 n& N5 `" s4 o" [, F Cpuberty in children with tumours of the suprasellar pineal |
|