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Sexual Precocity in a 16-Month-Old
/ @1 S$ h. z/ {# @- \5 C" i2 ]Boy Induced by Indirect Topical
9 ]; w1 V x& ~% ~# W. PExposure to Testosterone: w5 D1 |! ~8 X9 H+ J/ }
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
5 P/ q% J1 h% Y; V& r5 F" t1 d6 |and Kenneth R. Rettig, MD1
7 H$ j Z8 P5 v, VClinical Pediatrics
' }) y- E+ S' p9 M! M# `7 d1 _Volume 46 Number 6! V% ]+ J( k* y1 H; h3 E
July 2007 540-543! h& K/ ^% f' J! e
© 2007 Sage Publications
2 v. N6 w: G. S; ]5 B z) T10.1177/0009922806296651
7 ~+ I- Q5 ]3 q5 u* thttp://clp.sagepub.com$ `2 n& z6 b x5 g
hosted at
+ T0 E4 A& O7 A* y- C% O5 A3 Ehttp://online.sagepub.com% u3 f9 q6 A9 M [" s$ {
Precocious puberty in boys, central or peripheral,
3 z9 y: u3 }) F5 ]6 ^( Lis a significant concern for physicians. Central
; ?5 v: t0 C" W% i3 Jprecocious puberty (CPP), which is mediated
' ^4 Z; Q- X) n# m/ o/ Hthrough the hypothalamic pituitary gonadal axis, has
" Z( T) j/ u& L! F6 Ga higher incidence of organic central nervous system, [7 s1 j2 ^9 W9 d4 I+ F% l: N1 R
lesions in boys.1,2 Virilization in boys, as manifested
( Q5 n9 Q' {5 e7 vby enlargement of the penis, development of pubic
& ]/ C u: p- xhair, and facial acne without enlargement of testi-9 [; q" i0 a* |
cles, suggests peripheral or pseudopuberty.1-3 We) I7 d# ~5 z' ~3 V! N* p8 ]6 r
report a 16-month-old boy who presented with the
/ ?0 O. I# \% w6 G, L+ |. L6 jenlargement of the phallus and pubic hair develop-
$ X+ l+ m" Z1 j K& Tment without testicular enlargement, which was due5 h( E9 F S8 U7 \
to the unintentional exposure to androgen gel used by* V: H* U2 b( V4 b0 T" W
the father. The family initially concealed this infor-
# N% t1 v% E! jmation, resulting in an extensive work-up for this
/ ?' `/ e5 R( s6 V8 Ichild. Given the widespread and easy availability of
9 U5 J; {5 A. m4 w% q, V/ I% C' l3 Vtestosterone gel and cream, we believe this is proba-; } t' t: c9 w2 y0 C
bly more common than the rare case report in the0 G5 v+ l$ w! ^9 U, F" @* }
literature.4
* x" D! `3 r) s; E. p3 nPatient Report
1 z T& ~7 B0 U! l' P( lA 16-month-old white child was referred to the
' P% e$ ~* a3 R; j n) Oendocrine clinic by his pediatrician with the concern
F" f& S" ~1 [; R5 m: z. Dof early sexual development. His mother noticed. @+ r5 E( q* e& B/ k
light colored pubic hair development when he was
2 U, W0 N1 C# f' s% ~/ m5 |From the 1Division of Pediatric Endocrinology, 2University of
6 Q n5 u5 z& a* v6 s' F) f% pSouth Alabama Medical Center, Mobile, Alabama.( I) l9 ^( p7 _1 `7 l& X8 {! Q
Address correspondence to: Samar K. Bhowmick, MD, FACE,
8 u8 {$ t$ n" v, MProfessor of Pediatrics, University of South Alabama, College of! C8 v2 a: N8 z" W: D) a
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;* z6 Y, w; b3 j! N, j) ^
e-mail: [email protected].: A! j6 ]6 u& ]9 v a" @2 O
about 6 to 7 months old, which progressively became
1 `8 m1 s ?2 e# i( pdarker. She was also concerned about the enlarge-
+ {2 W% @4 W9 c& Lment of his penis and frequent erections. The child
F( C* o: O t0 ^was the product of a full-term normal delivery, with9 \5 D. f# g: m2 u. f
a birth weight of 7 lb 14 oz, and birth length of
) _+ ^8 C- s, L: E5 E; L20 inches. He was breast-fed throughout the first year2 y; t5 t* D0 [7 n
of life and was still receiving breast milk along with
9 J+ p( L( l# d9 u4 `solid food. He had no hospitalizations or surgery,
* x* H6 n- { S0 p! b- F. k" b iand his psychosocial and psychomotor development# d0 f! ^! C3 L6 _8 Y0 w0 _; L
was age appropriate.
% b; ~0 U3 V, @- B2 g" c0 I3 GThe family history was remarkable for the father,9 e5 H. m# e& q& T& U
who was diagnosed with hypothyroidism at age 16,
' O% c3 I" Y `; x& \which was treated with thyroxine. The father’s/ {6 O, a- R# ^: P& C4 I
height was 6 feet, and he went through a somewhat+ F( h$ _5 c9 t. z; G/ l' T
early puberty and had stopped growing by age 14.( |$ @( k2 ^2 ^0 R
The father denied taking any other medication. The5 A" U# C# o8 @3 {7 E
child’s mother was in good health. Her menarche
5 G7 O# e1 R. ], v, Kwas at 11 years of age, and her height was at 5 feet
; X* f, B- q; a* K" g5 inches. There was no other family history of pre-
9 _: Y8 M& ^6 a! M, }% K8 U4 ccocious sexual development in the first-degree rela-0 p1 e; b: E e5 Q' I" B
tives. There were no siblings.2 Z( z4 m% T$ {6 c$ Z0 H+ F) n$ w
Physical Examination
3 `/ ^( v- W0 @* ?& kThe physical examination revealed a very active,
9 d% P8 {" f3 H. N4 m4 kplayful, and healthy boy. The vital signs documented, [" H& `8 a$ o' a( L X, W
a blood pressure of 85/50 mm Hg, his length was
; J# \# e& D! a: r' |90 cm (>97th percentile), and his weight was 14.4 kg
! X5 X4 t& f; J* \' E9 v(also >97th percentile). The observed yearly growth
. ]% {8 U1 R, k6 I5 y5 |6 w9 Avelocity was 30 cm (12 inches). The examination of! G' a/ D6 K& r, w6 V$ l
the neck revealed no thyroid enlargement.
/ @9 A1 w, W- `The genitourinary examination was remarkable for
, g8 X2 ]( O+ p0 ^enlargement of the penis, with a stretched length of4 x3 T+ B2 }, Y( q
8 cm and a width of 2 cm. The glans penis was very well! o1 e6 z- n+ q% p3 B
developed. The pubic hair was Tanner II, mostly around+ X* T. h" b, T4 e- ^
540! a% u# z5 ^+ c+ N
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
0 v" H% h" N# S5 Sthe base of the phallus and was dark and curled. The, a: m# q* {, _
testicular volume was prepubertal at 2 mL each.7 U5 Q Z* w# o( g: l+ J
The skin was moist and smooth and somewhat1 s, a& i8 q4 N" q# q
oily. No axillary hair was noted. There were no! \! l s4 K! X5 ^; y5 q! D9 q5 O/ I
abnormal skin pigmentations or café-au-lait spots.* x0 r2 [3 j# W: `$ y1 s
Neurologic evaluation showed deep tendon reflex 2+3 i4 G! L( ?! d+ X- `
bilateral and symmetrical. There was no suggestion6 J% g7 S) i" `, v
of papilledema.. Y. }8 f, F4 p- p
Laboratory Evaluation/ B v& u$ Q4 ?4 C. z& X
The bone age was consistent with 28 months by5 [8 ?$ e0 M k
using the standard of Greulich and Pyle at a chrono-" B: P: M! |* o$ g$ }) K k# a
logic age of 16 months (advanced).5 Chromosomal
8 Q' }# T D, T, G+ nkaryotype was 46XY. The thyroid function test$ H- H4 t7 [* @6 s! f3 S$ {( }% _, n
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
! [; Q- X# a. x2 r3 s; u8 rlating hormone level was 1.3 µIU/mL (both normal).
9 k+ Y* r+ C% f) }The concentrations of serum electrolytes, blood' `4 v" O# Y6 s4 J% ^
urea nitrogen, creatinine, and calcium all were
% Q% q4 I8 ~8 P% Wwithin normal range for his age. The concentration L' q3 V6 B% t$ z
of serum 17-hydroxyprogesterone was 16 ng/dL! D" v1 h2 R3 C" D+ X$ s
(normal, 3 to 90 ng/dL), androstenedione was 20" G0 z/ L7 Q R4 n
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-2 S" s4 {. n9 S! _% h8 P4 N
terone was 38 ng/dL (normal, 50 to 760 ng/dL),# U: U$ M; l6 v" C4 c' |1 C
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
B; h7 `9 o# h! G49ng/dL), 11-desoxycortisol (specific compound S)
4 t2 f( ]9 e) K w) Swas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-5 A1 |' ]5 D: g
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total/ p+ I: C6 N. J5 g# L& a
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),9 a) u- E, }2 g( u
and β-human chorionic gonadotropin was less than
( ]9 o) o5 G+ H! q0 E( g' n5 mIU/mL (normal <5 mIU/mL). Serum follicular
% p( B1 \" \. f' u3 H d5 ]: Pstimulating hormone and leuteinizing hormone1 m2 W3 ]1 B/ I8 [. U0 i! Y
concentrations were less than 0.05 mIU/mL
' O; a, Q9 _1 S(prepubertal).
/ C% y& x( E- C0 N4 ~" q7 mThe parents were notified about the laboratory9 V+ m: L2 C" |$ G
results and were informed that all of the tests were* g: Z* R8 D/ I, M" _2 _3 @
normal except the testosterone level was high. The+ s' Q" l, m2 o" x6 F
follow-up visit was arranged within a few weeks to3 X- S2 ~" u1 d' N
obtain testicular and abdominal sonograms; how-0 \$ r3 V9 r7 p$ u. ~5 y+ H
ever, the family did not return for 4 months.
% M: ~3 H, C. j( t7 r* }8 k8 {Physical examination at this time revealed that the
; ^7 Q- X. W; P3 S6 X2 D; H) P2 Pchild had grown 2.5 cm in 4 months and had gained
* A$ E& ~" A O1 A) a+ O2 kg of weight. Physical examination remained
8 K* _4 w- i3 f) c4 i& Yunchanged. Surprisingly, the pubic hair almost com-) |- _& @4 K5 r& `
pletely disappeared except for a few vellous hairs at6 S. M6 w; y5 U- s& F
the base of the phallus. Testicular volume was still 2* }3 x" M& D2 \
mL, and the size of the penis remained unchanged.: ?' w6 h3 R; z- Q" n: b O* w
The mother also said that the boy was no longer hav-
5 ]3 T6 t; S5 T1 [7 m' V/ ning frequent erections.
. \, d: G1 p, _# \3 P; J7 s5 WBoth parents were again questioned about use of+ `0 X' ]) P& o$ v7 D
any ointment/creams that they may have applied to& |: n# Y6 [; b0 z" |( V9 r
the child’s skin. This time the father admitted the
; V% H3 l1 ~; F0 q0 OTopical Testosterone Exposure / Bhowmick et al 5419 @) s- q" q0 e. _: U' T' _
use of testosterone gel twice daily that he was apply-
! R& g6 B6 y% u! g( [. Z+ }ing over his own shoulders, chest, and back area for
$ O+ ~/ S, S4 w) f0 Ra year. The father also revealed he was embarrassed P$ A N1 Q% a6 Z: ~
to disclose that he was using a testosterone gel pre-' m" D- K; z) y3 P
scribed by his family physician for decreased libido
! L- m, H) `; Z- b8 Wsecondary to depression.
$ `+ \* C, Z6 m3 ~, R H& b& @The child slept in the same bed with parents.6 V* E) G: J, r1 l
The father would hug the baby and hold him on his1 s7 I8 T5 U R3 ~
chest for a considerable period of time, causing sig-9 n$ L) ], Q7 O9 f
nificant bare skin contact between baby and father.: T, w& q( B: ?8 e
The father also admitted that after the phone call,
/ n' {# a( J! H$ xwhen he learned the testosterone level in the baby a* v3 z! k6 L9 r
was high, he then read the product information
) E2 V5 f8 ]7 Z0 Fpacket and concluded that it was most likely the rea-
- T% {! Z- o& b$ gson for the child’s virilization. At that time, they
n' R" w9 Q. jdecided to put the baby in a separate bed, and the
7 y A) ^2 V1 Y/ O6 C, _) qfather was not hugging him with bare skin and had2 e( ]# p! O8 V) p c C2 f
been using protective clothing. A repeat testosterone
% z0 N' Y4 A$ ^" O& n9 s! W' ~test was ordered, but the family did not go to the
$ r, P0 L9 i3 s0 Plaboratory to obtain the test.1 g/ L1 [ o/ L3 X5 h5 p! ^
Discussion- I4 B8 A+ K* Q4 ^
Precocious puberty in boys is defined as secondary, k- o7 ?$ _: B3 L9 z" q5 O
sexual development before 9 years of age.1,4
, [8 ?- S5 s- d7 Q5 T8 n- c6 \Precocious puberty is termed as central (true) when
3 `- |& g# n0 g+ E3 P. sit is caused by the premature activation of hypo-
# |* n) H8 Z9 `7 Jthalamic pituitary gonadal axis. CPP is more com- l7 ~* h9 i/ z! m" K! H; |0 n
mon in girls than in boys.1,3 Most boys with CPP6 @5 Y" i6 z9 u7 C
may have a central nervous system lesion that is& \; N" z \; p; L; R$ n V' r
responsible for the early activation of the hypothal-
1 u6 {% T6 s0 _amic pituitary gonadal axis.1-3 Thus, greater empha-: ^: l; H2 Y0 v! ]9 f7 w! [
sis has been given to neuroradiologic imaging in
# d- i& b( m! Z' y* @$ Uboys with precocious puberty. In addition to viril-
5 J/ f0 f. R) x# p6 [+ v$ I3 Hization, the clinical hallmark of CPP is the symmet-3 m" ^4 j& _$ O
rical testicular growth secondary to stimulation by" k1 B) x, E4 q# u; k
gonadotropins.1,3# A: E. m/ ?( c% o8 `6 g# |1 X
Gonadotropin-independent peripheral preco-
) _! ?, F* f) B$ b% [cious puberty in boys also results from inappropriate
7 L+ S1 }$ C$ p8 @androgenic stimulation from either endogenous or( J% s5 d2 X: K9 ~
exogenous sources, nonpituitary gonadotropin stim-
: C4 _& e: W" Q" e- hulation, and rare activating mutations.3 Virilizing
/ V, |# j! y% V+ g3 I* \" econgenital adrenal hyperplasia producing excessive- \0 e: T% A/ ^" c4 O
adrenal androgens is a common cause of precocious
. u2 ~- r$ y, U/ m, Kpuberty in boys.3,41 S0 E7 ]5 I8 V( @
The most common form of congenital adrenal4 v- d8 ~) }/ p3 L& Z J: q
hyperplasia is the 21-hydroxylase enzyme deficiency.
) `, `7 h) U" z# d5 DThe 11-β hydroxylase deficiency may also result in
2 o* E$ m. Q8 g# Wexcessive adrenal androgen production, and rarely,
% h' O- [" y$ f& G, w3 S' Qan adrenal tumor may also cause adrenal androgen! V3 g- \; f$ n7 p
excess.1,34 J, h4 S3 M9 {4 X p
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from- H B4 Z7 w5 G% P0 \ _
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
( x* P; P- K0 S2 B$ P0 WA unique entity of male-limited gonadotropin-' [" e8 L9 x& ^9 H5 i) v1 f
independent precocious puberty, which is also known9 U+ _$ V: G% q8 m3 E, y
as testotoxicosis, may cause precocious puberty at a
% k5 f* |) H* ~2 }8 g; o; \very young age. The physical findings in these boys: X! d# W6 z; a, ^3 f U; V/ X5 h
with this disorder are full pubertal development,( a' \3 t; q. D4 H V% Z
including bilateral testicular growth, similar to boys
: W9 x1 V7 A& c1 uwith CPP. The gonadotropin levels in this disorder
6 t# S) z+ I5 O0 F7 w7 {are suppressed to prepubertal levels and do not show
4 x* o Z( ^6 l gpubertal response of gonadotropin after gonadotropin-4 E) i$ i/ C$ p8 b! u9 c3 N/ y5 ?+ k
releasing hormone stimulation. This is a sex-linked
& A) h+ `' W4 x' v1 i2 cautosomal dominant disorder that affects only
( j1 l1 L- v; p5 y8 l) |9 u+ d9 nmales; therefore, other male members of the family
, q0 A2 q7 D* W$ P) V7 Fmay have similar precocious puberty.3# i4 \# E. o5 G+ k, I2 `
In our patient, physical examination was incon-
7 k' r/ E! n4 u$ F- w* s6 @' isistent with true precocious puberty since his testi-
' `# b0 t$ F4 B: p; o: Ncles were prepubertal in size. However, testotoxicosis
' T" m3 K$ y: y: E4 lwas in the differential diagnosis because his father+ q! K& l- M; ?. d& Y
started puberty somewhat early, and occasionally,2 c" s; H4 G9 [/ o
testicular enlargement is not that evident in the
9 I5 F2 T- Q# N4 R$ D% Abeginning of this process.1 In the absence of a neg-
( e6 B* u! H6 I/ W' a5 N5 e, y1 lative initial history of androgen exposure, our# y$ S9 c5 ~) |
biggest concern was virilizing adrenal hyperplasia,
1 S+ M6 N+ M$ ]; a6 t- Qeither 21-hydroxylase deficiency or 11-β hydroxylase
4 a# {' ]& m. c Q! l/ `8 p* [: ideficiency. Those diagnoses were excluded by find-5 `+ S3 B/ Z- d- I* Q& V
ing the normal level of adrenal steroids.
1 t1 n" S0 t4 g# M" XThe diagnosis of exogenous androgens was strongly
( h; h7 q$ d; U. m8 d7 O3 nsuspected in a follow-up visit after 4 months because
; m: }$ ^+ q' c; R/ M& zthe physical examination revealed the complete disap-
* \3 }/ ?5 k$ mpearance of pubic hair, normal growth velocity, and4 h% {+ ^* J+ f( }, I4 c
decreased erections. The father admitted using a testos-
! Z( j& y: N& h) D& W3 ]terone gel, which he concealed at first visit. He was
% }" R# s' U% L( b2 j( @, S2 Busing it rather frequently, twice a day. The Physicians’5 I1 Z* h) A6 a& I$ a
Desk Reference, or package insert of this product, gel or/ e5 K- C3 J( u; |% s% E, P; W
cream, cautions about dermal testosterone transfer to% y3 }9 Y) e- {8 e$ i+ V% z1 l
unprotected females through direct skin exposure.- e. e( Q- z! q1 X7 T9 a
Serum testosterone level was found to be 2 times the
" t/ Q' D. U- K7 @$ o) Vbaseline value in those females who were exposed to& t" |/ M3 ~9 x' I
even 15 minutes of direct skin contact with their male
5 V. U. Y7 l( d! U7 n( m$ ppartners.6 However, when a shirt covered the applica-
: J* }# l, m& o, ~tion site, this testosterone transfer was prevented./ Q) c" L. U9 c4 F5 K& c, d9 q- Q
Our patient’s testosterone level was 60 ng/mL,
( B$ C4 u+ g8 o; [1 A/ Jwhich was clearly high. Some studies suggest that
/ e: o7 V3 \0 y" e6 cdermal conversion of testosterone to dihydrotestos-* n; I. m/ |, A% g' ]. I7 _* p' e
terone, which is a more potent metabolite, is more# D" w6 G% x, v+ r
active in young children exposed to testosterone
9 L! ?+ |$ N( ]7 i4 Jexogenously7; however, we did not measure a dihy- j- W5 r& p, l% D+ a; d" B0 z
drotestosterone level in our patient. In addition to
7 ^9 T7 M; p: r: d" L* x% cvirilization, exposure to exogenous testosterone in
/ n* J+ r; w- D8 H; Y9 n/ o$ R1 U% N) echildren results in an increase in growth velocity and( V) @6 \, I- X5 t1 i
advanced bone age, as seen in our patient.
4 P2 v& U9 z KThe long-term effect of androgen exposure during
; v7 X. L* N4 Bearly childhood on pubertal development and final7 b" g3 V3 s# O8 H X) q. F( ^
adult height are not fully known and always remain
5 p: {$ D7 P4 n5 j' A7 ia concern. Children treated with short-term testos-7 J- j' m' q% s$ M+ n
terone injection or topical androgen may exhibit some
7 l; j+ r' O' h/ nacceleration of the skeletal maturation; however, after
. A" z% v% E* F; F% jcessation of treatment, the rate of bone maturation
7 {% f! p. m$ v b) T0 Vdecelerates and gradually returns to normal.8,9
2 D% A! w8 [$ {0 q T' V. VThere are conflicting reports and controversy5 T* G. @3 _1 M
over the effect of early androgen exposure on adult6 ~& K6 M \' ^7 y/ n
penile length.10,11 Some reports suggest subnormal' B9 K4 q8 ?5 k K+ K
adult penile length, apparently because of downreg-
y4 k$ y, v. |ulation of androgen receptor number.10,12 However,
$ Z5 i7 Z$ J4 u# M3 ^* D+ L8 V2 MSutherland et al13 did not find a correlation between
7 B! U6 y# h7 h& ~) a% Lchildhood testosterone exposure and reduced adult/ T' B! f; Q( V. o" ]; C2 z
penile length in clinical studies.8 Q5 K1 |4 n9 o+ J
Nonetheless, we do not believe our patient is
/ Z- H# ^- P; ?4 t( W9 V7 Egoing to experience any of the untoward effects from
8 h7 a0 z: M& m7 [. e, r/ wtestosterone exposure as mentioned earlier because! Q$ c# Y0 S# Z. u3 g$ z6 j. i
the exposure was not for a prolonged period of time.
/ G' a! ?5 c8 [' g6 O( eAlthough the bone age was advanced at the time of
/ d! R' W" b# r1 H Pdiagnosis, the child had a normal growth velocity at
" [* S( P4 a5 Ythe follow-up visit. It is hoped that his final adult
0 Q) h. H) [; w2 p1 v- ]+ pheight will not be affected.6 X; z3 J7 X+ F) c& D! v
Although rarely reported, the widespread avail-
' s: p& T, o, g# G! l, M, _ability of androgen products in our society may
+ E3 T. g7 J! ~) _- W7 f' Zindeed cause more virilization in male or female5 L5 T. e, O0 L
children than one would realize. Exposure to andro-
% H( o2 |% v8 l: m2 {* ?gen products must be considered and specific ques-& \, d( J ]8 K7 ?
tioning about the use of a testosterone product or2 P1 ^9 ?2 t9 | A
gel should be asked of the family members during7 v& i9 t. w5 A, ~1 \
the evaluation of any children who present with vir-
- [& ~; [! b L. D3 Filization or peripheral precocious puberty. The diag-
% O8 C0 p9 \9 Onosis can be established by just a few tests and by! }* e6 W; d) p
appropriate history. The inability to obtain such a D) c8 E1 G1 l. A' d/ `1 \
history, or failure to ask the specific questions, may1 W) |. F5 t T! Q& E
result in extensive, unnecessary, and expensive
4 C# h6 [* M1 O! [" S* Vinvestigation. The primary care physician should be0 ` w+ z( g4 P& W4 E' i+ J
aware of this fact, because most of these children6 P9 ~* a3 G3 M' T
may initially present in their practice. The Physicians’$ `+ n) j& l }( ~, S* E+ f
Desk Reference and package insert should also put a$ _2 C: s h: \ U; F9 z
warning about the virilizing effect on a male or
9 x% s) ~2 U/ J, n# c; S. n$ T3 ^2 Hfemale child who might come in contact with some-6 p2 J0 K' {& p8 E
one using any of these products.
$ l$ k! x7 `- q2 I N( ZReferences, a4 J7 Q- _4 P" i" W
1. Styne DM. The testes: disorder of sexual differentiation
8 z% q: K, D. J% c! X3 jand puberty in the male. In: Sperling MA, ed. Pediatric
9 J4 M; c5 S# bEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
% U$ K H) Q- C0 w; e1 H! B. ?6 b3 a% S$ \2002: 565-628./ v' p6 d- L: B- |. R
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious( K( T+ A! ~% p8 b
puberty in children with tumours of the suprasellar pineal |
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