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Sexual Precocity in a 16-Month-Old
) z3 p8 X9 }. n! W a; VBoy Induced by Indirect Topical. r& J1 k+ k! u) a- t% g& `
Exposure to Testosterone
! ?5 ]+ U2 O/ Y- c& iSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2/ }8 ^; ^; e0 h r7 C1 w+ u- \
and Kenneth R. Rettig, MD1
8 L7 n1 d- C- p* s$ TClinical Pediatrics
7 N. J/ j4 m& B9 z+ t$ J- Q0 A GVolume 46 Number 6
' O N: Y: Z. FJuly 2007 540-5436 O6 W& @6 F4 a% K4 W" u
© 2007 Sage Publications
6 ?: W8 u& i; ?9 y( s10.1177/0009922806296651
* T& Y. `2 c0 W; u1 ]* ]http://clp.sagepub.com T9 V( i' I; a
hosted at
, \9 p# R8 z6 ahttp://online.sagepub.com8 n3 X, u5 ^0 N& {0 W
Precocious puberty in boys, central or peripheral,' d5 O/ }/ H6 `9 u/ i% j
is a significant concern for physicians. Central
1 V9 W; P" B' ], T* Z6 cprecocious puberty (CPP), which is mediated2 _7 B2 B7 y9 H. G8 e
through the hypothalamic pituitary gonadal axis, has2 n p! X4 K9 ^6 J2 Y* R& m
a higher incidence of organic central nervous system; w1 V& h* p0 e5 M: e0 d
lesions in boys.1,2 Virilization in boys, as manifested; K3 S: U) t% Q& }9 W1 `
by enlargement of the penis, development of pubic
( l3 P6 x5 M {2 O9 l0 ]hair, and facial acne without enlargement of testi-9 v0 t& P" f% k. V
cles, suggests peripheral or pseudopuberty.1-3 We* G% H4 p9 a/ |
report a 16-month-old boy who presented with the: Y( j( h: h' O
enlargement of the phallus and pubic hair develop-0 D4 |1 [9 a; I; S! F
ment without testicular enlargement, which was due- a; L% _' d, V( C
to the unintentional exposure to androgen gel used by
1 x( `2 Q9 \6 R2 Dthe father. The family initially concealed this infor-
/ w) m& v$ l1 q3 Y; b& Q% Pmation, resulting in an extensive work-up for this6 c5 R/ L6 R3 G; g
child. Given the widespread and easy availability of# ]: q2 F' m, Y! P& u# j4 o6 u
testosterone gel and cream, we believe this is proba-& A! i: S, t' K, a0 Y/ h" C) s4 p3 I
bly more common than the rare case report in the% X. L7 I% N2 x) c% c4 O3 {- y- \
literature.4& K, d* E/ ]" f
Patient Report7 u3 n: |+ L0 S: I6 |
A 16-month-old white child was referred to the
0 [' o7 X$ L9 }: v( tendocrine clinic by his pediatrician with the concern
7 d6 G- t$ e" z- X. C* xof early sexual development. His mother noticed
' Z$ C) Y9 r( c0 m, Klight colored pubic hair development when he was
3 e6 N1 D$ E( U; U9 P- h$ cFrom the 1Division of Pediatric Endocrinology, 2University of0 o# \# L. h# f1 K6 z$ s3 l
South Alabama Medical Center, Mobile, Alabama.9 U8 i0 j4 L* k, ?# G$ Z- N; X
Address correspondence to: Samar K. Bhowmick, MD, FACE,7 z# k$ b$ c$ Y( t
Professor of Pediatrics, University of South Alabama, College of
1 t Z; M& o: J( f4 JMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
% e1 Q0 j1 Q# _e-mail: [email protected].
3 H( B/ F5 w+ b% d2 S, Dabout 6 to 7 months old, which progressively became
6 T1 x6 `3 |/ H7 V5 G5 Zdarker. She was also concerned about the enlarge- ]9 c, `9 m8 g
ment of his penis and frequent erections. The child
9 b/ A3 l( o3 \2 Cwas the product of a full-term normal delivery, with
+ H, r/ M% [8 [; _( c4 U1 H" l2 Ja birth weight of 7 lb 14 oz, and birth length of
0 x. U2 R& u1 Q$ f1 |* S20 inches. He was breast-fed throughout the first year
# p0 T: b1 P, h8 J" T% m5 Rof life and was still receiving breast milk along with; W3 t) i/ L% p0 q
solid food. He had no hospitalizations or surgery,
% F0 k2 @. `* c6 k8 M' X, Wand his psychosocial and psychomotor development$ a0 s8 c7 N! w$ {! a
was age appropriate.
* z1 D4 ~! d8 P- I; b% S; SThe family history was remarkable for the father,
( P4 }2 _& h6 l0 @+ m$ n9 ~who was diagnosed with hypothyroidism at age 16,( D3 e+ V2 n: n3 n
which was treated with thyroxine. The father’s
3 u8 v* Q% n) U. z' i: L _5 Bheight was 6 feet, and he went through a somewhat) x2 y m. |$ R6 z' ^) M
early puberty and had stopped growing by age 14.
& d2 ?: q7 e* @- M! _The father denied taking any other medication. The
6 c3 K4 _0 E3 r4 Q! Tchild’s mother was in good health. Her menarche4 f% e+ L$ u7 r/ N, f; C {
was at 11 years of age, and her height was at 5 feet
5 h$ U0 l7 \3 p8 E* Q/ D5 inches. There was no other family history of pre-
1 V- P9 \7 H( L7 d: a+ fcocious sexual development in the first-degree rela-
- i& J+ M8 p# j3 E- z, d2 ntives. There were no siblings.
a. n- t* a3 Z8 P; zPhysical Examination
( V; c: Z: s6 G4 x qThe physical examination revealed a very active,5 w. [* C: d6 ~) @( }
playful, and healthy boy. The vital signs documented
( m. s5 p* E2 X* b8 U9 i, T, [% O; za blood pressure of 85/50 mm Hg, his length was
% X }! m; _/ y90 cm (>97th percentile), and his weight was 14.4 kg0 J/ o d6 v3 z* `6 G; r9 |
(also >97th percentile). The observed yearly growth
& N4 u2 T* _9 R% d7 Ovelocity was 30 cm (12 inches). The examination of7 Q% X# U. h9 B5 K
the neck revealed no thyroid enlargement.
! L, @/ m. R8 T3 l& o! V& S4 I4 yThe genitourinary examination was remarkable for
- R. J! ~+ h. \! s2 _6 D% |8 ^enlargement of the penis, with a stretched length of6 r9 X2 X/ Z% ~8 t/ q5 R+ w; ]
8 cm and a width of 2 cm. The glans penis was very well6 l9 C, F6 J7 \2 ^, w4 k
developed. The pubic hair was Tanner II, mostly around
, B/ ~3 V: X$ |3 D- Y$ g5407 I- Z+ O# T! ~/ }& [# y- [
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
" H9 s( [$ s4 E8 l- ?the base of the phallus and was dark and curled. The
+ P) s) y" P9 Ftesticular volume was prepubertal at 2 mL each.
" \2 H! @, y4 d+ CThe skin was moist and smooth and somewhat
0 \0 ~% _; K9 F4 ?% Goily. No axillary hair was noted. There were no3 W6 Q! H! e. Y- ~# b7 c
abnormal skin pigmentations or café-au-lait spots.. e' W- t1 J' w7 o* P' b6 ~
Neurologic evaluation showed deep tendon reflex 2+
+ z( p8 G; d! A1 j# Q0 mbilateral and symmetrical. There was no suggestion) {: n" O5 O1 a5 x( t0 V+ h
of papilledema.
! O: x7 E' p4 e+ fLaboratory Evaluation
8 n, @+ b" t" e4 }" X: o9 xThe bone age was consistent with 28 months by
6 }8 C/ |9 w9 n$ Pusing the standard of Greulich and Pyle at a chrono-4 K& h" K( f+ y0 c( Q1 w3 c0 ]$ y/ |
logic age of 16 months (advanced).5 Chromosomal
: @( H- ?) g6 Akaryotype was 46XY. The thyroid function test
: t/ h/ X. }, ]& Z' h) ishowed a free T4 of 1.69 ng/dL, and thyroid stimu-
$ }+ {4 j. y+ q4 Mlating hormone level was 1.3 µIU/mL (both normal).3 X) I: U; ^ ]% B
The concentrations of serum electrolytes, blood& X' r1 t9 L+ c; Z& a# C
urea nitrogen, creatinine, and calcium all were8 O. {' K4 K4 S5 _8 o
within normal range for his age. The concentration
4 H8 W1 O4 ]& ]/ N+ mof serum 17-hydroxyprogesterone was 16 ng/dL" U0 E% \# ]) s9 H
(normal, 3 to 90 ng/dL), androstenedione was 20
7 p) o. g# k. B+ F) bng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-2 P* m) T1 |4 m' N: E9 l
terone was 38 ng/dL (normal, 50 to 760 ng/dL),. @6 Q/ c" j7 C# Y; u5 H
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
* v q, w4 U1 v! h5 A1 q49ng/dL), 11-desoxycortisol (specific compound S)7 A# ~: s, h9 ]7 F. I+ \! A
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
& W; u' x2 @5 A& Y! rtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
% `) g- s& ^, ~; Ttestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
5 p5 ~' S% L; D4 d0 r3 Cand β-human chorionic gonadotropin was less than
+ m7 z! e" y* m7 }& c# R: ` w% C! I5 mIU/mL (normal <5 mIU/mL). Serum follicular9 |% _+ F6 T& B+ z- E
stimulating hormone and leuteinizing hormone
! J) E( P) M/ t, s* q+ tconcentrations were less than 0.05 mIU/mL
G' _# B! M/ d2 f3 e3 T( d5 Y(prepubertal).
! n1 r! u+ K S- {- F' mThe parents were notified about the laboratory2 Y: W. Z5 U" s; l6 a. \
results and were informed that all of the tests were
8 R& z! L% G& w# K0 r6 p7 `1 pnormal except the testosterone level was high. The9 E6 l1 G6 T0 Q/ y* A- w
follow-up visit was arranged within a few weeks to$ J% t j3 r3 z2 ^3 C
obtain testicular and abdominal sonograms; how-7 N" J) P8 \# @; i& Q
ever, the family did not return for 4 months.9 D& M. C- E2 |' m
Physical examination at this time revealed that the' A! a: ^5 V# |# v7 M( p, b
child had grown 2.5 cm in 4 months and had gained* H6 s3 ]- a* u+ U9 U& u% G8 {
2 kg of weight. Physical examination remained
, c% K0 h3 O! S: s3 f. ^" S. ounchanged. Surprisingly, the pubic hair almost com-
8 A0 V/ `9 N% Xpletely disappeared except for a few vellous hairs at, S6 V+ |0 P& L
the base of the phallus. Testicular volume was still 2
- X: c2 w; {3 l, ^$ YmL, and the size of the penis remained unchanged.( ~, W8 F8 W& H1 u6 P
The mother also said that the boy was no longer hav-
9 C: D- x4 i: J2 {ing frequent erections.1 B# e8 g6 g0 @- |4 c' e
Both parents were again questioned about use of7 v% m1 i6 {9 m# G2 p3 i/ q+ ^
any ointment/creams that they may have applied to
6 ? O) f% L T5 Qthe child’s skin. This time the father admitted the
- B( F" S( b0 j7 x, xTopical Testosterone Exposure / Bhowmick et al 541
+ d) w7 E, z$ ?' `) Suse of testosterone gel twice daily that he was apply-
1 O6 B/ d. K4 `5 \4 Ming over his own shoulders, chest, and back area for# p& f0 i S; R$ F1 M: B2 y
a year. The father also revealed he was embarrassed( y1 q$ \3 J( z
to disclose that he was using a testosterone gel pre-
! s/ Y4 V& t" I: [- x% sscribed by his family physician for decreased libido2 p% E9 b+ g% f, Z
secondary to depression., b& v& c* l) _' H; \1 \ g; R
The child slept in the same bed with parents.. T: s# w* V) Z
The father would hug the baby and hold him on his& F8 m2 x7 w1 T6 S# r
chest for a considerable period of time, causing sig-
) A3 l \' V. |4 R) m5 ]! anificant bare skin contact between baby and father.4 P) n) k6 \7 @4 c
The father also admitted that after the phone call,
9 D" f' \6 P ]5 }1 Q, R4 kwhen he learned the testosterone level in the baby) e; V. _- f7 ~3 i- Q4 w" F
was high, he then read the product information. s9 y% K8 _( r" W) d
packet and concluded that it was most likely the rea-7 S" n0 k E9 F/ u1 P$ N- I
son for the child’s virilization. At that time, they
2 B1 Q9 `# _1 z/ cdecided to put the baby in a separate bed, and the/ }8 q5 f' j0 ], ?) @9 }
father was not hugging him with bare skin and had
. A( y/ Y4 i! P1 v/ E# L6 W" Mbeen using protective clothing. A repeat testosterone
' `! Z) ], ~5 x8 @- F4 Etest was ordered, but the family did not go to the* s4 _ n9 M/ d3 Q* j$ d
laboratory to obtain the test.# ?& f- {* p; k( s
Discussion
% |* a% Q7 |$ {) K$ l( {Precocious puberty in boys is defined as secondary; w" Y2 e, u+ _* b/ n
sexual development before 9 years of age.1,4
- O0 o, |% W/ S) P* c! b ]" ~Precocious puberty is termed as central (true) when! u5 _! m7 A5 N; x
it is caused by the premature activation of hypo-0 N( C, r7 L# b; f9 s- n
thalamic pituitary gonadal axis. CPP is more com-
; [; v4 n1 m$ ~' m( k4 M5 Ymon in girls than in boys.1,3 Most boys with CPP
# W* M1 b! H2 V8 D) Umay have a central nervous system lesion that is' r3 ? S0 f ~' z9 n$ g
responsible for the early activation of the hypothal-
1 n% }+ d& c) m5 b5 _amic pituitary gonadal axis.1-3 Thus, greater empha-/ _7 z" ]( M M) r! Y
sis has been given to neuroradiologic imaging in
( t) N. i4 [+ r& M' J: jboys with precocious puberty. In addition to viril-( C. [1 R' R, v! V
ization, the clinical hallmark of CPP is the symmet-
; ]2 Y! H M; k. Mrical testicular growth secondary to stimulation by
/ ~- `7 {; n8 ?. u& }/ s7 x8 b7 g3 b' T Kgonadotropins.1,3% i; X2 s* Z1 }2 W
Gonadotropin-independent peripheral preco-
& T; z' m0 T0 d9 Q1 Ycious puberty in boys also results from inappropriate2 H9 M1 Y, V7 M Y
androgenic stimulation from either endogenous or
; j; Y9 P3 k1 Iexogenous sources, nonpituitary gonadotropin stim-
) K1 C2 a$ U& c1 l" {# z- r0 Tulation, and rare activating mutations.3 Virilizing9 Z- Z3 s( l) b' M# n
congenital adrenal hyperplasia producing excessive
' G7 o% w" \/ h( J7 J: g$ y4 ]" [: Gadrenal androgens is a common cause of precocious
7 C! N, c+ \; w8 q" F5 Z0 Npuberty in boys.3,4
: F* ?- A* Q5 i* @+ IThe most common form of congenital adrenal
! t1 u i/ S: j; bhyperplasia is the 21-hydroxylase enzyme deficiency.
( M D1 R3 B i0 u: T3 W: ^, CThe 11-β hydroxylase deficiency may also result in
+ a# x+ ^5 h3 g9 q% D4 v% x, cexcessive adrenal androgen production, and rarely,9 i3 t6 M; {1 P5 ] e' k
an adrenal tumor may also cause adrenal androgen1 T9 _2 k5 `! u/ M6 m0 M8 N
excess.1,3
. K- V# B" o: X4 x1 |. ~1 }at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
2 D% v |+ j" R1 d542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
9 q4 v T9 R- I0 N; gA unique entity of male-limited gonadotropin-
& F$ E3 {; ?" P3 G9 k, g' b0 dindependent precocious puberty, which is also known
& ~& ?+ A! ]. x$ f1 }, d" Sas testotoxicosis, may cause precocious puberty at a# G2 j4 v, @4 {2 S1 F9 V3 _/ U
very young age. The physical findings in these boys
! c+ \) E& I9 f' f0 U. F) {with this disorder are full pubertal development," P% V- Q2 p/ C8 i* c# Y6 C8 b
including bilateral testicular growth, similar to boys
- A, e8 ]" ^! U" K6 g9 B/ hwith CPP. The gonadotropin levels in this disorder
% I7 d2 f7 s9 x6 b7 s0 ?are suppressed to prepubertal levels and do not show) j* D8 H5 _( z, o1 w
pubertal response of gonadotropin after gonadotropin-
6 d$ @6 J0 P( N( c, i3 N% Breleasing hormone stimulation. This is a sex-linked
6 j4 O( P/ V) U e7 vautosomal dominant disorder that affects only
2 N" q. k' G7 ^! j! g* `males; therefore, other male members of the family; F$ _ j$ ` H! l, z: _9 T
may have similar precocious puberty.3
0 h8 ]. u$ O. }* W$ YIn our patient, physical examination was incon-. {4 S( Z/ D4 k( m* x5 U# t: J8 `" u
sistent with true precocious puberty since his testi-
# @7 h* k, Z6 o3 ccles were prepubertal in size. However, testotoxicosis
; w0 H( T, t) V6 D- ?2 ~, fwas in the differential diagnosis because his father
! L( G! \3 r5 K' u2 D2 l: R7 ~started puberty somewhat early, and occasionally,9 o, t4 L: G3 q; N4 D: c- D
testicular enlargement is not that evident in the! W$ v' F9 ^& b
beginning of this process.1 In the absence of a neg-
5 Y1 J$ i& W, ~- m$ Iative initial history of androgen exposure, our8 W) K/ |& V- H. d
biggest concern was virilizing adrenal hyperplasia,+ D& o, G$ X, g
either 21-hydroxylase deficiency or 11-β hydroxylase% o H1 G0 c6 y! n b/ l
deficiency. Those diagnoses were excluded by find-. s8 P: M8 ~9 E
ing the normal level of adrenal steroids.2 n" q5 A ^$ q! u
The diagnosis of exogenous androgens was strongly
4 m. ^- q" A& ssuspected in a follow-up visit after 4 months because: }( k. [& g% F
the physical examination revealed the complete disap-
, m$ g6 X/ I, s- C: j& ~* y E, fpearance of pubic hair, normal growth velocity, and1 F/ i! M! ]4 }7 S( y8 B
decreased erections. The father admitted using a testos-
& D7 c2 J0 z+ f6 k8 F4 {terone gel, which he concealed at first visit. He was
$ I9 y) ?& T1 i/ tusing it rather frequently, twice a day. The Physicians’
4 b7 g! `' o5 i# s& w6 ]. _' }+ bDesk Reference, or package insert of this product, gel or
! z* X: w/ e6 v: F4 u/ i/ Fcream, cautions about dermal testosterone transfer to. v7 K, D5 z+ Y9 l$ B, S
unprotected females through direct skin exposure.9 l$ _8 v& R) L3 |7 J
Serum testosterone level was found to be 2 times the {0 k9 w( Z H5 S) J9 ]
baseline value in those females who were exposed to
4 F: L& z. W' Z' b/ r9 teven 15 minutes of direct skin contact with their male! w4 v3 K X/ t9 y
partners.6 However, when a shirt covered the applica-8 e$ l+ z: L4 G) R5 h2 z2 Y" T; a: ?
tion site, this testosterone transfer was prevented.
5 z% O1 X4 _5 K( lOur patient’s testosterone level was 60 ng/mL,8 o; n9 i# z& ]0 P0 v, t: B
which was clearly high. Some studies suggest that9 ^& k+ C% \) R) k4 u$ h
dermal conversion of testosterone to dihydrotestos-4 ~# O$ j8 j7 n# w( K
terone, which is a more potent metabolite, is more
. ^! B# _, E4 [, Zactive in young children exposed to testosterone& Z d* N4 M' \. \$ Z. `
exogenously7; however, we did not measure a dihy-
0 A; a- }3 K3 s9 i' Udrotestosterone level in our patient. In addition to
% c+ d; U5 t6 ~! B/ [virilization, exposure to exogenous testosterone in
+ v; ?$ M2 {1 R/ C$ w$ Lchildren results in an increase in growth velocity and
/ P! }5 E5 B: \( ]5 B7 Q/ V, yadvanced bone age, as seen in our patient.
. [1 ?3 I- }! Q* K8 h9 DThe long-term effect of androgen exposure during
: ]' X$ a0 c2 n3 Nearly childhood on pubertal development and final m* A) Q5 f2 b
adult height are not fully known and always remain, o! B$ K4 i# I/ W" U2 M7 K6 J
a concern. Children treated with short-term testos-! G1 y' a$ c, ]' t7 w. y% s
terone injection or topical androgen may exhibit some1 s0 Q8 v- @ e
acceleration of the skeletal maturation; however, after
6 i2 j' G! m9 K* w, rcessation of treatment, the rate of bone maturation5 z# ? j; g H
decelerates and gradually returns to normal.8,9# _! h1 C/ m+ U0 L H
There are conflicting reports and controversy
4 g1 U" N3 N/ Q7 b0 Hover the effect of early androgen exposure on adult3 g8 L7 m2 R# W, h0 v
penile length.10,11 Some reports suggest subnormal* H+ b6 N0 V3 w9 S9 @ |! ?
adult penile length, apparently because of downreg-
! X9 \& |1 ~* F# \7 O9 U7 m. F; J0 vulation of androgen receptor number.10,12 However,7 g' {# d9 E m$ B5 s, @& ~* D
Sutherland et al13 did not find a correlation between
% x n1 }, ~# dchildhood testosterone exposure and reduced adult
. M) Y T2 Q. E. ]2 ~ Vpenile length in clinical studies.
- ]+ V1 K- ^8 y4 F% oNonetheless, we do not believe our patient is
8 b2 D: K) Z, G) |5 Y; mgoing to experience any of the untoward effects from
/ J( @' ~1 h/ F4 i5 d' @+ ~testosterone exposure as mentioned earlier because- z5 N, c% i( k5 ^" y
the exposure was not for a prolonged period of time.3 s2 i: _3 s9 X8 D( C
Although the bone age was advanced at the time of: _* b9 F2 P5 s7 S1 J$ q
diagnosis, the child had a normal growth velocity at
' E7 ?& y$ V; \5 {) E6 E6 H# fthe follow-up visit. It is hoped that his final adult, h6 h. J! o4 T/ e2 U) z: b3 W% e& e
height will not be affected.
" e8 E1 N; }3 m8 z0 i( `9 PAlthough rarely reported, the widespread avail-7 w$ \# S8 i7 F" L
ability of androgen products in our society may+ S- b$ D5 d& B; t" ?2 r1 N% u
indeed cause more virilization in male or female
$ X; Z& D6 D" Y6 `" a. t& Y9 Gchildren than one would realize. Exposure to andro-
* c2 o! ?' z. m, M+ `- ~; R' [1 ?gen products must be considered and specific ques-8 ^* f; L; P# V, _
tioning about the use of a testosterone product or
! [1 r$ q6 G7 B5 Kgel should be asked of the family members during
y' _/ W1 c. uthe evaluation of any children who present with vir-6 H. n" D# e5 t; g/ }) \& l
ilization or peripheral precocious puberty. The diag-; O( @% e2 q+ D' D7 m6 P( Q3 i" _
nosis can be established by just a few tests and by
/ ^% M) ~$ A; `: fappropriate history. The inability to obtain such a( T) n& f8 p( Z3 u1 Z8 j
history, or failure to ask the specific questions, may
: F0 V$ T/ f: \result in extensive, unnecessary, and expensive5 h. d8 z$ A8 W* Y9 p9 |
investigation. The primary care physician should be9 C) Z) m1 B, ?- X+ j
aware of this fact, because most of these children
( ~* \6 N: G, lmay initially present in their practice. The Physicians’
1 _$ u8 u( W0 W2 B7 ]Desk Reference and package insert should also put a. r& @ t1 O2 p ?& j
warning about the virilizing effect on a male or- s j* r5 `% o/ W$ ^% d8 T
female child who might come in contact with some-
# \- K$ d! |# y0 Sone using any of these products.2 {0 h5 x6 L' \* H9 o0 Y" d
References
) H; I3 A k6 x; }1. Styne DM. The testes: disorder of sexual differentiation
1 N4 U3 m: z8 ^& \! Wand puberty in the male. In: Sperling MA, ed. Pediatric
4 J& o$ c; y/ G% o6 t) z B! M7 GEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;3 _/ h* i% @- @- B* U
2002: 565-628.
" Z5 z6 t8 D, u$ ^& R5 r/ i2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious5 _, r6 k- G+ Y3 F! o9 _
puberty in children with tumours of the suprasellar pineal |
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