- 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-Old" a- T2 a5 x; F: G7 \
Boy Induced by Indirect Topical) G; S6 _+ e0 b8 g$ T' j: x
Exposure to Testosterone
9 c( j3 L0 H4 v( s' X" ySamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2- ?9 Q7 v7 ]4 E, q
and Kenneth R. Rettig, MD1
/ B% {; A" T- K% HClinical Pediatrics
1 \4 V* h% z8 N* D( B/ ~8 k0 t; U3 |Volume 46 Number 6
0 m% T; H4 U4 X; ~2 o! {July 2007 540-5433 \/ |% F S4 ~0 D3 k
© 2007 Sage Publications* @: Y% G+ C" F4 J) {$ v D
10.1177/0009922806296651/ @. b0 f7 G+ K; q, N
http://clp.sagepub.com
" a9 L ?5 h+ Ihosted at
/ D/ n3 |0 p3 E: uhttp://online.sagepub.com) v2 n5 b) Q' P9 t3 H5 P! h
Precocious puberty in boys, central or peripheral,; }+ J0 b+ R3 o" Q( {* d/ u
is a significant concern for physicians. Central
4 q# G+ D0 o( ], b! c0 @precocious puberty (CPP), which is mediated
! p2 k, Y) @( s. R2 bthrough the hypothalamic pituitary gonadal axis, has1 Q3 S3 ?1 H0 U3 ]
a higher incidence of organic central nervous system3 }* S: y4 u% v
lesions in boys.1,2 Virilization in boys, as manifested
" N3 m8 ?/ e# h, M8 |by enlargement of the penis, development of pubic
/ y) @" P- a% m _7 [hair, and facial acne without enlargement of testi-* L) Z9 t e% [( E
cles, suggests peripheral or pseudopuberty.1-3 We
$ o. [' Y* }3 Z) areport a 16-month-old boy who presented with the
9 P. l- X: M6 R3 J Benlargement of the phallus and pubic hair develop-
8 Y6 W( F% e; n( v+ }) W9 ]' e7 cment without testicular enlargement, which was due( J, J6 v. H4 E& F$ ~2 B- L1 l
to the unintentional exposure to androgen gel used by
# a! R& L6 E4 b/ j! G, {; Kthe father. The family initially concealed this infor-' e4 e( G1 C2 V/ r* ^* G
mation, resulting in an extensive work-up for this; Q) ^' z+ o# F+ [" X
child. Given the widespread and easy availability of, A% j# X0 F" D4 l0 M% Y. ?
testosterone gel and cream, we believe this is proba-
Q( O5 w3 {$ M9 ybly more common than the rare case report in the7 F7 [. c, Z2 u |
literature.4
4 c5 q% a a: f5 GPatient Report2 O! B) A2 h8 O; u+ q) Z
A 16-month-old white child was referred to the
) U! ]- A* s$ ^7 e$ J& k* n3 Gendocrine clinic by his pediatrician with the concern7 O. W( d5 q6 m# h a% A
of early sexual development. His mother noticed! ?0 R4 H8 A, F+ U$ C
light colored pubic hair development when he was }0 G" b5 T m
From the 1Division of Pediatric Endocrinology, 2University of
$ h/ v- t2 a' G1 W z8 QSouth Alabama Medical Center, Mobile, Alabama.
: ^" w6 P/ Y" B$ u( G0 MAddress correspondence to: Samar K. Bhowmick, MD, FACE,
2 W e$ |6 [4 L. d5 JProfessor of Pediatrics, University of South Alabama, College of
8 Z2 R7 g6 ~0 A0 f+ B* ]6 pMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;& M) w4 W. y1 Z8 N4 c$ _
e-mail: [email protected].7 j* ^2 R- K2 {, r6 R% |
about 6 to 7 months old, which progressively became
9 l/ H) K8 C) L9 C( { y4 wdarker. She was also concerned about the enlarge-
! p+ @6 c: O: I1 ~3 \* bment of his penis and frequent erections. The child% `$ k# w! ^- N3 L; z, {
was the product of a full-term normal delivery, with- i5 \1 T7 D6 r; A; k
a birth weight of 7 lb 14 oz, and birth length of/ ^+ G7 A" D6 s% j
20 inches. He was breast-fed throughout the first year
7 K- b: H8 x% }2 ^of life and was still receiving breast milk along with
. ?6 o3 r7 s; d6 P( y- |% fsolid food. He had no hospitalizations or surgery,
* B( k4 J, o9 I1 |and his psychosocial and psychomotor development# [7 w' L) y4 x5 a5 x3 w
was age appropriate.
H7 A4 `. { i# j% D2 fThe family history was remarkable for the father,# v n& d6 i! f. D/ g
who was diagnosed with hypothyroidism at age 16,/ ` d4 h1 l( Z2 T/ M) `
which was treated with thyroxine. The father’s8 F/ G: H( Y% L" Y7 t
height was 6 feet, and he went through a somewhat
. z2 N3 ?9 t j; P: E/ \$ D( d# qearly puberty and had stopped growing by age 14.5 x7 f+ q2 w0 s( s& U: c; t R
The father denied taking any other medication. The
. y1 q- s1 x% ^ c# Bchild’s mother was in good health. Her menarche
, H8 y5 I0 c5 T( g- c/ ]3 ewas at 11 years of age, and her height was at 5 feet
9 ]& V& Z! k+ b+ ~5 inches. There was no other family history of pre-* w' I/ J$ d3 l! g% `
cocious sexual development in the first-degree rela-
- e; O$ T6 J ~( O* Mtives. There were no siblings.% _* z; f3 \2 e3 r; {+ @, `0 F
Physical Examination
: r; [5 R- w( G; ~: Z, MThe physical examination revealed a very active," O* k8 s3 F+ ]9 q1 {" w1 Y1 p
playful, and healthy boy. The vital signs documented1 b, k; v8 P: c
a blood pressure of 85/50 mm Hg, his length was$ K0 h- Z+ R5 ?3 u
90 cm (>97th percentile), and his weight was 14.4 kg3 r8 _0 A1 q6 j( H
(also >97th percentile). The observed yearly growth! z, g N4 C9 R& {, l! j# t
velocity was 30 cm (12 inches). The examination of: D H" o5 ?) e9 Z2 j) W& }* q
the neck revealed no thyroid enlargement.
9 r* j, e/ [5 mThe genitourinary examination was remarkable for
9 n5 W, X7 s# N* Eenlargement of the penis, with a stretched length of
2 t6 d, r a6 j. o( U: R8 cm and a width of 2 cm. The glans penis was very well
8 d! L4 j7 y1 ?# s5 n6 L6 f3 j/ a& `* `0 rdeveloped. The pubic hair was Tanner II, mostly around
, d( O0 ]* D) L) p2 @2 Q \540$ s% L* R4 e' l4 t
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from2 t: T" w+ R0 A# t
the base of the phallus and was dark and curled. The# M$ k K# H3 t( N
testicular volume was prepubertal at 2 mL each.
9 Y9 _+ Y1 C3 u8 ?9 @The skin was moist and smooth and somewhat
% O& O1 A3 U, q1 q! s: O; ^oily. No axillary hair was noted. There were no
3 V! u" s6 s4 J0 G! aabnormal skin pigmentations or café-au-lait spots.
7 E* i Z v! H! }+ ZNeurologic evaluation showed deep tendon reflex 2+6 q7 d& v; F1 W: ]7 l
bilateral and symmetrical. There was no suggestion6 i% Q, _/ v* V! t
of papilledema." |- }8 `4 Q+ S4 ~
Laboratory Evaluation! I% v# z6 r; C. g$ M% s
The bone age was consistent with 28 months by
u6 h) b; z9 ~: `' i1 Zusing the standard of Greulich and Pyle at a chrono-5 p2 u2 M3 U/ N- V- U$ t K
logic age of 16 months (advanced).5 Chromosomal5 J3 n4 y |2 X7 A) X$ `$ ~6 }
karyotype was 46XY. The thyroid function test) R9 _0 x3 i( K: {% N' _: v
showed a free T4 of 1.69 ng/dL, and thyroid stimu-; n b- j1 \5 d" Y- A7 |% s, `
lating hormone level was 1.3 µIU/mL (both normal).
& ~' w/ ?% P. b7 G! wThe concentrations of serum electrolytes, blood
! U g( a" l+ M9 Qurea nitrogen, creatinine, and calcium all were3 X$ J* z' i! F* x6 Y. R% s
within normal range for his age. The concentration1 h e7 }7 R% n- y+ ?, V. U; T& T y
of serum 17-hydroxyprogesterone was 16 ng/dL% x- H2 ^) \9 {: `" {2 w: W
(normal, 3 to 90 ng/dL), androstenedione was 20* \1 [/ D: U( O% Y4 w" G2 |
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
- z3 J( i1 L4 g: B0 I& V1 gterone was 38 ng/dL (normal, 50 to 760 ng/dL),
" k) }4 {& k+ q3 `desoxycorticosterone was 4.3 ng/dL (normal, 7 to7 p% k# t+ Z3 w0 O2 n2 I
49ng/dL), 11-desoxycortisol (specific compound S)
) n, s" s- I, i4 x+ M3 T2 g- _was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
& o( H$ n) g, }/ vtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
( A+ |$ W" G) r# w" q* ftestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
& P( D: K8 ^1 \4 vand β-human chorionic gonadotropin was less than
! u- |& I v2 g9 @0 ~- Z5 mIU/mL (normal <5 mIU/mL). Serum follicular
0 ^6 v- t6 E3 \, @$ K$ wstimulating hormone and leuteinizing hormone% R' f& L' _, e# }! V$ I
concentrations were less than 0.05 mIU/mL L( V* j, s1 t5 T9 }
(prepubertal).8 H5 m5 x1 G# v. `0 }, n
The parents were notified about the laboratory
% ^. s) {. t& q. n- B3 [/ Hresults and were informed that all of the tests were
2 X- u* `8 [& e1 c" X7 _normal except the testosterone level was high. The7 S2 X8 K5 k8 q2 U
follow-up visit was arranged within a few weeks to% @% H6 w1 }: j! V, g. z' c: s1 ?1 @
obtain testicular and abdominal sonograms; how-- b* g/ G, z! t7 E9 X6 o( ~
ever, the family did not return for 4 months.
# R: `4 M$ q- E$ `0 j" w V2 _Physical examination at this time revealed that the
' k2 y8 [. n0 N2 M" [/ |! ^) lchild had grown 2.5 cm in 4 months and had gained& _" m# r) d( I' L! C& K
2 kg of weight. Physical examination remained# e, W, d8 Q# P8 a4 p, Y9 u) K$ B
unchanged. Surprisingly, the pubic hair almost com-
( `/ R9 M( ^/ U1 _* n, f& Q: wpletely disappeared except for a few vellous hairs at
1 [' _4 o$ x" Q! u" o1 U1 xthe base of the phallus. Testicular volume was still 2
( @, y! N- y( X4 m' I0 d& fmL, and the size of the penis remained unchanged.
/ {* b( k- v rThe mother also said that the boy was no longer hav-
8 q, Q. Z, ^9 I. P4 t+ Fing frequent erections.4 G/ w6 I+ K0 ?" C
Both parents were again questioned about use of* B0 Z7 j3 ~8 T; ^
any ointment/creams that they may have applied to
1 ]) |- c9 L. v6 mthe child’s skin. This time the father admitted the5 d: ]/ Q$ Q2 D4 ]) C) V- a
Topical Testosterone Exposure / Bhowmick et al 541% f% g+ n5 C5 E
use of testosterone gel twice daily that he was apply-$ d. ^" M7 j, i6 o& O. n
ing over his own shoulders, chest, and back area for/ Y/ J( a3 I7 V# @) }
a year. The father also revealed he was embarrassed
0 _# B$ @! n7 f6 pto disclose that he was using a testosterone gel pre-
4 V2 g5 V& u) L# C ?8 x( hscribed by his family physician for decreased libido
, R$ D" c6 C! t2 A& n% ~secondary to depression.
! m* A+ S6 b: T0 K$ LThe child slept in the same bed with parents.! Q9 P& b# S* c0 k, x2 v
The father would hug the baby and hold him on his1 _( d/ M$ u; v% z! }# D4 Q/ C
chest for a considerable period of time, causing sig-/ H. w1 W( j' k- E7 i/ x9 O
nificant bare skin contact between baby and father.
9 V9 x) _' d4 l) _0 q/ \, r5 {0 CThe father also admitted that after the phone call,) [4 Q9 s; z; |: G
when he learned the testosterone level in the baby
& U+ b, B- U- Y' h) Pwas high, he then read the product information2 S- I i6 h: H i, l5 `
packet and concluded that it was most likely the rea-
/ E' K# O9 k/ D( K8 Z$ Ison for the child’s virilization. At that time, they
, C5 k8 n _, H' ]' {decided to put the baby in a separate bed, and the
8 d5 `7 k. t/ @& g0 ~2 Sfather was not hugging him with bare skin and had
( @ p$ O: F" E/ S: ebeen using protective clothing. A repeat testosterone
+ y3 i. }6 Z% ^8 O8 utest was ordered, but the family did not go to the
+ \' m4 K8 ^$ |, `/ l$ K Rlaboratory to obtain the test.
1 r$ W$ Q' }) [1 Z6 j1 z9 F8 DDiscussion
0 v3 n4 a7 ]' sPrecocious puberty in boys is defined as secondary
/ W- N0 l" F1 ^sexual development before 9 years of age.1,44 b; M: K3 b5 D C2 s* c* p- {1 m
Precocious puberty is termed as central (true) when7 ?$ X' y7 C8 [7 m; \$ g4 m' j1 r
it is caused by the premature activation of hypo-' e+ k$ o3 y* X& h& N( V
thalamic pituitary gonadal axis. CPP is more com-0 j7 R% v* g! B# Z; T; v; j
mon in girls than in boys.1,3 Most boys with CPP
6 N. U7 l5 Z# ^9 rmay have a central nervous system lesion that is0 B# s1 U+ x! q3 M- [; O
responsible for the early activation of the hypothal-
/ s* H0 Z5 a6 d/ Gamic pituitary gonadal axis.1-3 Thus, greater empha-
* {; I# m3 J" J; @+ P$ csis has been given to neuroradiologic imaging in
, I3 s- o( y" h( E" A; Zboys with precocious puberty. In addition to viril-& B* Y1 Y/ P. F
ization, the clinical hallmark of CPP is the symmet-
1 O; W8 @7 V [" Arical testicular growth secondary to stimulation by; X) k( E, M! q7 ?; g1 i) \7 u
gonadotropins.1,3
# P' a' P `. A5 z4 |, E9 G/ j) WGonadotropin-independent peripheral preco-
2 Y+ U8 a5 q/ M1 X6 qcious puberty in boys also results from inappropriate
/ ?( |( S3 \! C' a5 ]4 ~; Sandrogenic stimulation from either endogenous or
' `, q. J" f; ^' j' C! ^exogenous sources, nonpituitary gonadotropin stim-
; k" X; |3 D6 I' s/ w- Sulation, and rare activating mutations.3 Virilizing
+ l; n$ d% B7 ~, `+ acongenital adrenal hyperplasia producing excessive, C$ M8 g/ J% V7 R8 h
adrenal androgens is a common cause of precocious
7 X* q; R8 m& Apuberty in boys.3,43 J& o# x. i9 k3 G5 `. \) x& [
The most common form of congenital adrenal. u- c4 d, B. c+ F* P9 K7 A9 q
hyperplasia is the 21-hydroxylase enzyme deficiency.
; b& b: @: n9 FThe 11-β hydroxylase deficiency may also result in! d4 I; p; m, g d- _8 F7 B! S
excessive adrenal androgen production, and rarely,3 Z. a) h c* k( o
an adrenal tumor may also cause adrenal androgen
% W3 T; h/ J3 V( }excess.1,3" w+ u# H. ]1 }2 p* |6 V
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from' |2 }5 F5 n+ z5 I
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
. i5 h% N+ w/ w* G8 G9 vA unique entity of male-limited gonadotropin-% ?' z( }/ F# E1 Q- P; c' ]3 P1 T
independent precocious puberty, which is also known% Y, f$ G9 v/ y1 Q
as testotoxicosis, may cause precocious puberty at a
* a( W/ e& ?0 C$ Vvery young age. The physical findings in these boys
- X- C; A, e% d* i0 w }0 }$ dwith this disorder are full pubertal development,
5 m6 b+ Y$ z% z$ G7 E. E( e: K% Bincluding bilateral testicular growth, similar to boys+ P7 L3 K9 k6 ?* y
with CPP. The gonadotropin levels in this disorder
( R; L! P D: w! u3 k! f& Qare suppressed to prepubertal levels and do not show( N! O# ` A* o
pubertal response of gonadotropin after gonadotropin-
; v' y- K: V. s [+ breleasing hormone stimulation. This is a sex-linked2 T! y3 B) O* m' }1 R! Y; c
autosomal dominant disorder that affects only
[, ]. f. L3 w5 [5 Fmales; therefore, other male members of the family
6 W5 E( ] ^! h3 {1 q0 A5 Fmay have similar precocious puberty.3. G1 R1 \8 z; a9 K1 v0 i4 n9 `; h
In our patient, physical examination was incon-; Q$ `8 o- t$ q J4 c
sistent with true precocious puberty since his testi-
( P' c: v! e, v% l% p/ r# Ocles were prepubertal in size. However, testotoxicosis3 X( h/ F4 L: j
was in the differential diagnosis because his father# ~; R2 l1 k3 m$ p! e& k6 @
started puberty somewhat early, and occasionally,
" L& l$ }9 K2 ]# f( etesticular enlargement is not that evident in the
8 R/ s- ]' {. abeginning of this process.1 In the absence of a neg-
! W. B5 G6 C8 _1 H$ L9 k3 @9 Qative initial history of androgen exposure, our
2 {* r; J% h# y* t `: ^! J7 v- Abiggest concern was virilizing adrenal hyperplasia,/ O2 o; B0 k, W1 ?3 M
either 21-hydroxylase deficiency or 11-β hydroxylase) I" {. C. S, Z' Z4 q4 i" Q
deficiency. Those diagnoses were excluded by find-8 V l) o" E, }4 c5 v
ing the normal level of adrenal steroids.$ ~3 ^3 u P& b7 f
The diagnosis of exogenous androgens was strongly
5 a* }# V q: Tsuspected in a follow-up visit after 4 months because; w9 ~; i0 e1 w# R% t+ p6 {2 @
the physical examination revealed the complete disap-
- ]! w; ~2 e- w9 D4 j9 _pearance of pubic hair, normal growth velocity, and& I) Y y5 j6 o8 c1 h N7 e# z8 e
decreased erections. The father admitted using a testos-9 J0 N) X6 l# ?3 W) @0 X2 p7 T
terone gel, which he concealed at first visit. He was
/ l% S. [& b0 J. Uusing it rather frequently, twice a day. The Physicians’0 [9 E3 H. c+ w/ r
Desk Reference, or package insert of this product, gel or& Y5 A5 l( b2 r$ s. b* N
cream, cautions about dermal testosterone transfer to
; k3 L4 p- L2 d% bunprotected females through direct skin exposure.
! R1 ]0 z! [. qSerum testosterone level was found to be 2 times the
# {: v( s x8 vbaseline value in those females who were exposed to
7 F0 Y, r! u% ~even 15 minutes of direct skin contact with their male
v8 ?% g m# e- |9 C: Ppartners.6 However, when a shirt covered the applica- q1 I3 O) y3 e, A# }" p) M+ c; s
tion site, this testosterone transfer was prevented.; g$ O! k" W# I& Q1 o2 S
Our patient’s testosterone level was 60 ng/mL,
E, E3 d* [7 i/ \) K$ qwhich was clearly high. Some studies suggest that! d, o) v& p l% v5 [
dermal conversion of testosterone to dihydrotestos-: j# l" K. X7 Y$ K
terone, which is a more potent metabolite, is more. b8 G' W. N2 n/ l3 \
active in young children exposed to testosterone
4 L0 a3 a* T- H, {, E* \7 Jexogenously7; however, we did not measure a dihy-$ J7 \" N, {: F( X" Z8 g
drotestosterone level in our patient. In addition to
& c) N0 j+ {; j7 o2 Bvirilization, exposure to exogenous testosterone in
; Z+ r# ?% K2 l- x R$ Hchildren results in an increase in growth velocity and
9 C- `6 I, y* @4 V; l/ I5 u" Uadvanced bone age, as seen in our patient.2 [; A' z; S2 C: a y1 H
The long-term effect of androgen exposure during
; d) s& \$ Z" I: }! ] H8 wearly childhood on pubertal development and final
2 m7 h2 `0 R& ~9 J+ m0 [adult height are not fully known and always remain
; z& W+ ]) Z0 o5 e' \a concern. Children treated with short-term testos-* Q0 K& X* M3 J8 g
terone injection or topical androgen may exhibit some
/ y0 `; z7 I* W- R7 Pacceleration of the skeletal maturation; however, after0 }& K U3 W$ \' S
cessation of treatment, the rate of bone maturation
0 s# W2 ~# {( m% Udecelerates and gradually returns to normal.8,9
2 ?7 u$ @1 {: mThere are conflicting reports and controversy
; A$ N7 V- X) ?, h1 l& T' xover the effect of early androgen exposure on adult6 y' N2 Y) L5 N0 Y. f
penile length.10,11 Some reports suggest subnormal- l! {& k2 H2 \. j
adult penile length, apparently because of downreg-
. L) a1 t' Q- q2 a: Nulation of androgen receptor number.10,12 However,/ `# F, Z- n0 i, S
Sutherland et al13 did not find a correlation between
; @4 a# a7 Z- M6 Jchildhood testosterone exposure and reduced adult
& S9 }) t, ]% vpenile length in clinical studies.. @. u- A1 y- o0 ?$ O
Nonetheless, we do not believe our patient is, ] b1 \# p8 J) F6 c# W8 y
going to experience any of the untoward effects from6 Q% B2 S6 h+ @% q: _6 m% N
testosterone exposure as mentioned earlier because
5 c0 ^- u/ h0 A: x8 I+ k$ W3 jthe exposure was not for a prolonged period of time.$ H% }: d5 N2 j2 F. ?3 h- Q
Although the bone age was advanced at the time of3 q+ {$ X6 s: h$ |
diagnosis, the child had a normal growth velocity at6 h/ i/ Q) ^) I, a3 K- H" v2 a
the follow-up visit. It is hoped that his final adult. W- B# n/ J r g# h0 t% H
height will not be affected.* V5 j8 H [7 y: k
Although rarely reported, the widespread avail-
~* e }) ]( S# E) ]% z% h. e7 Nability of androgen products in our society may7 a. m6 _' `3 }% d( L2 m
indeed cause more virilization in male or female
, f) ?# H% d, b' @. M) uchildren than one would realize. Exposure to andro-. N5 ^, x2 G. e4 r) |+ J9 z
gen products must be considered and specific ques- [8 u/ f! i. j+ ]
tioning about the use of a testosterone product or
% O8 v, @: K+ Hgel should be asked of the family members during/ Y/ n. T- ~9 Y# S! J- C9 x
the evaluation of any children who present with vir-
9 J* M/ p5 ]; m0 Qilization or peripheral precocious puberty. The diag-
# c: j& v, H5 L/ p$ {nosis can be established by just a few tests and by
* }/ \ M4 Y* O% iappropriate history. The inability to obtain such a
7 w7 y. ?2 F* y" Fhistory, or failure to ask the specific questions, may7 z$ f5 |0 t6 U+ C- E
result in extensive, unnecessary, and expensive
3 P9 W7 Q3 | O, I# Hinvestigation. The primary care physician should be) K" K1 a9 E4 P
aware of this fact, because most of these children
" L% k* r8 W# m5 amay initially present in their practice. The Physicians’
- f& Z0 r# G: P* }3 V1 l1 \$ X/ c4 r5 ZDesk Reference and package insert should also put a
! L9 ]; [, R4 p! w: L" x3 swarning about the virilizing effect on a male or/ N0 L7 I! r8 Q9 `7 `( H
female child who might come in contact with some-/ h& S/ X1 T. `1 F7 r) S
one using any of these products.; _3 P+ i7 `5 X- J
References, @4 K3 U) r# H: {) w
1. Styne DM. The testes: disorder of sexual differentiation
$ e1 S A! i* e6 S) {4 d- oand puberty in the male. In: Sperling MA, ed. Pediatric0 X% n e. X/ {. V9 A
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;3 f+ \: z3 A6 K; ]3 M, J6 G; z
2002: 565-628.2 q* s! t U1 [- y# i% p) Q
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious' h* u7 T# m5 N: j
puberty in children with tumours of the suprasellar pineal |
|