- 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
w. n" T [! B1 ?Boy Induced by Indirect Topical
i& @) y2 E5 b: F2 yExposure to Testosterone5 O- D/ o1 j7 Z, W* K0 g7 L
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2, ]6 t! {/ ~6 ~. E* Q, f P) T/ {% _3 B
and Kenneth R. Rettig, MD1
$ b( Z8 m; ^- Y0 |* n+ KClinical Pediatrics
+ a9 a q6 D2 |4 P: JVolume 46 Number 6
8 y+ t* P }: `% RJuly 2007 540-5439 W( Q2 H% m' z" K
© 2007 Sage Publications# A7 f! w9 g* W6 v! {5 B3 k
10.1177/0009922806296651
/ l7 f' R) A, hhttp://clp.sagepub.com
, f0 s% d3 Z4 [" j2 ~6 L) K' |hosted at
* W8 e" a9 u* y' w# b: l( q" K1 zhttp://online.sagepub.com
1 r7 s0 e7 I( ]. L/ m& yPrecocious puberty in boys, central or peripheral,/ q( i7 A; s! l3 k; n
is a significant concern for physicians. Central( ^7 b" X( l1 M) Q5 `1 H7 [2 U+ N
precocious puberty (CPP), which is mediated
0 v' t# l% h$ z& @; w7 o% ethrough the hypothalamic pituitary gonadal axis, has
; {9 s# x+ W2 m. f3 l( e" X# |; H, ]9 Pa higher incidence of organic central nervous system$ j$ A+ I( J0 X# q; K1 I4 {
lesions in boys.1,2 Virilization in boys, as manifested' c$ U* t( [4 m2 E; g
by enlargement of the penis, development of pubic
: f) b! \" W7 ~- a# i4 G, uhair, and facial acne without enlargement of testi-; E& {% V& h" D% {7 a0 i' |: a' r
cles, suggests peripheral or pseudopuberty.1-3 We
4 r/ O9 R2 q) T" a: |. [# `report a 16-month-old boy who presented with the
9 n7 i2 U4 z! X g5 l( N. Zenlargement of the phallus and pubic hair develop-5 w" Y7 x5 J6 ^2 [
ment without testicular enlargement, which was due! F% F( W; N; l) f7 D
to the unintentional exposure to androgen gel used by3 H% E! W$ i8 I* U J
the father. The family initially concealed this infor-# r! y/ l9 `) ^- x9 r. B
mation, resulting in an extensive work-up for this
0 J' [/ B, W$ n2 j0 k. }1 O# Wchild. Given the widespread and easy availability of
9 s, \! J+ J+ I# F1 n) [, ktestosterone gel and cream, we believe this is proba-; w- V* e& z c; B# h8 U% U
bly more common than the rare case report in the
, r9 {7 u- y- D0 j; Wliterature.4
+ N3 W1 Z7 M/ B! ~0 f. ZPatient Report' d. s6 m. P$ L5 [) j$ ^" T/ F
A 16-month-old white child was referred to the0 o U. C: \9 k$ M* g
endocrine clinic by his pediatrician with the concern9 c% q. G5 J" C/ M; A
of early sexual development. His mother noticed" f4 ~( q7 X# G6 Y' h
light colored pubic hair development when he was; C! e) ~9 g/ Z) ?2 d) s# e
From the 1Division of Pediatric Endocrinology, 2University of7 }7 u+ m7 S- K
South Alabama Medical Center, Mobile, Alabama.
# l2 W6 m2 d1 ]9 \" S* n% zAddress correspondence to: Samar K. Bhowmick, MD, FACE,5 h8 w9 g$ u- j
Professor of Pediatrics, University of South Alabama, College of" S1 R1 f( z. F! W& W* W( b
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
- l, N1 }7 Q; q) ?( pe-mail: [email protected].) M2 e) e1 F2 y9 R$ U* S
about 6 to 7 months old, which progressively became
9 W) `, n( l! \9 v4 ~( ~' Udarker. She was also concerned about the enlarge-) K: R3 f$ V H8 s
ment of his penis and frequent erections. The child
+ e- \# G6 U" R. H4 C. ^was the product of a full-term normal delivery, with
- |6 @9 x3 B- A2 i2 _a birth weight of 7 lb 14 oz, and birth length of* ]# x% ?* X% [' s! \2 {
20 inches. He was breast-fed throughout the first year6 N+ [% h% t+ ]6 x$ q9 m
of life and was still receiving breast milk along with
! G, ?: b" U. G6 e. p' |$ Isolid food. He had no hospitalizations or surgery,7 J( O' [4 W t6 Z7 M9 Y0 _
and his psychosocial and psychomotor development9 s& g+ S( X0 K# d2 P
was age appropriate.
J: j$ W" U- X, m; T5 O# m5 n* GThe family history was remarkable for the father,
/ ~5 w ~) O X( X* q* @% Ewho was diagnosed with hypothyroidism at age 16,
2 v$ {) I# S* j. ]) Owhich was treated with thyroxine. The father’s% O% y9 N& b. Y+ R! T4 y
height was 6 feet, and he went through a somewhat- B6 f; ~% y/ B% H
early puberty and had stopped growing by age 14.% E9 d4 d) ?" Y$ {
The father denied taking any other medication. The1 [3 m( ~9 d, y$ P
child’s mother was in good health. Her menarche
4 S+ C1 W/ [: y o/ _was at 11 years of age, and her height was at 5 feet
; F: K1 k7 N' k5 inches. There was no other family history of pre-: R2 N f! `/ {3 m6 s9 Z/ i# V
cocious sexual development in the first-degree rela-
! P7 X: h6 c$ D# u" A! d8 P5 S/ htives. There were no siblings.4 R _* ~) c, ^+ ^
Physical Examination2 t* F M- v% w3 `0 j
The physical examination revealed a very active,
% u$ D1 G, d( f+ x& l& {playful, and healthy boy. The vital signs documented
. U0 E1 A K' g* i' ^- Za blood pressure of 85/50 mm Hg, his length was0 X1 [9 Z2 Z6 x8 H
90 cm (>97th percentile), and his weight was 14.4 kg
+ n# G* s* T% w(also >97th percentile). The observed yearly growth- D9 E+ n. ]1 P' y# O
velocity was 30 cm (12 inches). The examination of
/ W) ]& z& o8 bthe neck revealed no thyroid enlargement.
. r, U6 t, v3 \' `* F2 HThe genitourinary examination was remarkable for
9 b% F; s5 ^; M: `- oenlargement of the penis, with a stretched length of
# C, t0 {) M9 j2 ]3 y! i8 cm and a width of 2 cm. The glans penis was very well( L# l' g6 V) I4 J
developed. The pubic hair was Tanner II, mostly around/ `: n2 \: z# K
540
- y3 e. Z8 k. \9 [at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
! y$ N* b: s/ x& n |/ Sthe base of the phallus and was dark and curled. The
! {$ l/ D1 {0 Q! \testicular volume was prepubertal at 2 mL each.
# l$ P; \4 L* E, T% D- _: dThe skin was moist and smooth and somewhat
8 h$ P" ?& s' F% S) F( xoily. No axillary hair was noted. There were no' i* {/ G4 @# Q: ]! I2 n# Q
abnormal skin pigmentations or café-au-lait spots.# @ Z- ]) G& u4 G! n; F' b
Neurologic evaluation showed deep tendon reflex 2+
6 J! T+ o0 ^7 h) Abilateral and symmetrical. There was no suggestion4 H4 n9 N6 B* S4 [3 `
of papilledema.
8 j$ n9 f- j7 u8 s) k+ LLaboratory Evaluation+ Z2 T. }3 S2 o/ a4 u0 q' }7 h
The bone age was consistent with 28 months by' u3 n2 L6 W. X* l% h, A& [
using the standard of Greulich and Pyle at a chrono-3 L* b, g, m+ `: K, v
logic age of 16 months (advanced).5 Chromosomal( m' @! @' B% k. M
karyotype was 46XY. The thyroid function test, s/ T- n- N7 Q# J' W% W
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
$ r1 Z: t* @3 p: blating hormone level was 1.3 µIU/mL (both normal).
3 C/ Q9 w6 J" V. |. ?The concentrations of serum electrolytes, blood/ t+ g: r" ?$ m3 S
urea nitrogen, creatinine, and calcium all were
5 F" ]( ~- g3 O, a; vwithin normal range for his age. The concentration. v& _0 Q- G, d1 j+ e
of serum 17-hydroxyprogesterone was 16 ng/dL
0 p, t# b1 E* U! O7 f: t(normal, 3 to 90 ng/dL), androstenedione was 20
4 y$ p0 @ U& V/ Z' y/ Q4 T3 Cng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
* [: g: j) I; {1 b4 zterone was 38 ng/dL (normal, 50 to 760 ng/dL),' T3 y, Q. M$ Q' z: v7 }6 D
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
/ e- g" F% d5 v. M49ng/dL), 11-desoxycortisol (specific compound S); d, u1 v8 e; i. F, _8 t9 t
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
( ~' E, z( V. {tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
}2 J; X U$ W! ?( x, V' }testosterone was 60 ng/dL (normal <3 to 10 ng/dL),8 X% R5 s, ^- j" l- i2 V {) D! b
and β-human chorionic gonadotropin was less than" F. }2 K6 H8 R+ u- g' Q" ?
5 mIU/mL (normal <5 mIU/mL). Serum follicular4 z; W; G0 o' L1 C' p
stimulating hormone and leuteinizing hormone
, ?+ M" V; _3 v( O' e( Tconcentrations were less than 0.05 mIU/mL
0 M2 Q9 s1 g5 S' U(prepubertal).
; j7 w7 G" |. b) QThe parents were notified about the laboratory
4 R( I1 k6 ~. u+ Z3 d- x1 i) tresults and were informed that all of the tests were% R" Z& G% o. Z
normal except the testosterone level was high. The: x) F! \; g9 n1 O# h8 l
follow-up visit was arranged within a few weeks to# K! [- e' _# _. K) f0 Y6 f$ m$ e
obtain testicular and abdominal sonograms; how-7 U( V- d8 T) @" j/ M% R
ever, the family did not return for 4 months.) E* ~/ O. t1 y. W1 ~
Physical examination at this time revealed that the
% w" {- c7 k1 M/ }1 u" h. Hchild had grown 2.5 cm in 4 months and had gained
! F$ G% o: e8 p t( L# B5 x" J2 kg of weight. Physical examination remained
% X4 f( L9 j9 x( Munchanged. Surprisingly, the pubic hair almost com-) h: z7 p) _4 `
pletely disappeared except for a few vellous hairs at8 J$ [! Z) ^ Q. D
the base of the phallus. Testicular volume was still 2% K: i/ B$ U5 i3 ~" S2 j. u
mL, and the size of the penis remained unchanged.- g; v ?0 q, M) }
The mother also said that the boy was no longer hav-
8 V. B' d: T/ [3 ?, Wing frequent erections.
# U) s( D$ g" ^" v0 E$ QBoth parents were again questioned about use of1 P) m, x8 ]4 Z8 t/ p. b
any ointment/creams that they may have applied to
5 i! Y: @$ q/ s; q4 [. _3 i1 Ethe child’s skin. This time the father admitted the
! C$ Q6 f, [: O2 ~Topical Testosterone Exposure / Bhowmick et al 541+ w0 H0 |+ l2 H
use of testosterone gel twice daily that he was apply-2 F) }# z5 [7 K4 B. h, y, G1 ?# {
ing over his own shoulders, chest, and back area for9 h( D0 Z! P7 G( d+ n) f/ i
a year. The father also revealed he was embarrassed! c2 z2 n6 z$ i/ s
to disclose that he was using a testosterone gel pre-1 \2 j5 Q; o, k# M
scribed by his family physician for decreased libido
3 @9 Y$ X* m, Y6 c6 b9 gsecondary to depression.
! z, [- `+ K% N" a& P4 @The child slept in the same bed with parents.
6 l* J0 _$ V+ x l9 d: ^The father would hug the baby and hold him on his# X3 K% k# |+ q# I3 `* L$ [1 o
chest for a considerable period of time, causing sig-
$ d& p; a. I, c+ Knificant bare skin contact between baby and father.
3 e# x0 O. v; u3 N6 T0 cThe father also admitted that after the phone call,
# t: G( ~/ T0 I! U; ^* Xwhen he learned the testosterone level in the baby0 N" ~ L6 ~2 u; ^% E! m3 x
was high, he then read the product information
" F2 a. R" q$ Z* Rpacket and concluded that it was most likely the rea-- w# a, t- Y5 I/ e+ R
son for the child’s virilization. At that time, they
2 G7 M4 k+ T: cdecided to put the baby in a separate bed, and the% W1 Z# R0 ~) [1 A: e
father was not hugging him with bare skin and had7 A8 ~4 x ^* Q( @: }3 e V
been using protective clothing. A repeat testosterone
3 E2 j2 Y3 D" m+ n" v1 |1 Dtest was ordered, but the family did not go to the
# r! V1 W0 q; B3 U( Llaboratory to obtain the test.
2 w) A3 x$ \7 T1 E1 Y7 ?0 IDiscussion7 {* `0 I6 I- X# P( I0 J2 c
Precocious puberty in boys is defined as secondary
' I; o5 A- O$ |7 K: ssexual development before 9 years of age.1,4
# I. I! x. k+ _/ Q7 v: M- _- HPrecocious puberty is termed as central (true) when
3 H0 ?6 b4 | f% lit is caused by the premature activation of hypo-
) T% M: @, Z+ F9 gthalamic pituitary gonadal axis. CPP is more com-0 A" q: |& v) Z- P
mon in girls than in boys.1,3 Most boys with CPP
' ^5 H5 C9 ?7 ^! G3 p/ w& nmay have a central nervous system lesion that is
# G3 c1 h7 y/ A' Rresponsible for the early activation of the hypothal-$ H! w. H; U" s' ^4 o+ s
amic pituitary gonadal axis.1-3 Thus, greater empha-
# m. K( E+ F' F! r; z6 tsis has been given to neuroradiologic imaging in
. i; L- \$ `2 U _9 N; C2 @boys with precocious puberty. In addition to viril-
( X0 ^( B- M7 C( Rization, the clinical hallmark of CPP is the symmet-- j& b# X* z# H9 t: C
rical testicular growth secondary to stimulation by
+ s. U3 w1 `6 ggonadotropins.1,31 z2 h# j8 F; ]! { k% |
Gonadotropin-independent peripheral preco-
* i7 I* V$ N( ^8 g8 @5 Dcious puberty in boys also results from inappropriate
2 w; t4 l$ f' j* landrogenic stimulation from either endogenous or6 B( O+ s8 ?8 I, V1 Q# a! i1 K$ B
exogenous sources, nonpituitary gonadotropin stim-
( x E5 j' t0 E, b- Fulation, and rare activating mutations.3 Virilizing3 G( _! A! |1 z7 w: `, m
congenital adrenal hyperplasia producing excessive: v+ R8 r; U& x0 ^4 F
adrenal androgens is a common cause of precocious* p! ]. a) i" x+ R
puberty in boys.3,4) @1 {8 g* p9 }7 s) S/ o9 Y; ]8 H
The most common form of congenital adrenal
# _( z$ ~9 m" r9 Jhyperplasia is the 21-hydroxylase enzyme deficiency.
* {- E7 A' J+ j u9 }5 z$ xThe 11-β hydroxylase deficiency may also result in
* r! ~$ J; _& O3 L1 q, W( wexcessive adrenal androgen production, and rarely,$ s/ Y1 S6 v5 {$ I
an adrenal tumor may also cause adrenal androgen6 J& e& X3 u2 n+ h( S: O
excess.1,3
6 {& \- M7 p# T {8 A4 f. H& Tat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from# N! S$ p8 h. v% p. ]' l; [7 i
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
* {$ m* c' {! x6 KA unique entity of male-limited gonadotropin-
2 c! S' v; m& Y w" B6 Mindependent precocious puberty, which is also known
! X3 k6 e% Z- o, [4 X7 a0 t9 ias testotoxicosis, may cause precocious puberty at a$ o) i7 p* |4 R# q3 V' \ Z. }
very young age. The physical findings in these boys
+ q- F& b) \0 u2 G# @& K. swith this disorder are full pubertal development,/ N* B) a# E- n) g
including bilateral testicular growth, similar to boys$ v; N8 q' l1 c$ j5 f
with CPP. The gonadotropin levels in this disorder
3 ^* n6 Y4 b" ]% e D Yare suppressed to prepubertal levels and do not show
7 Y: `- ^6 M1 d' R" b3 ^pubertal response of gonadotropin after gonadotropin-6 _. T) t# o$ Y7 X
releasing hormone stimulation. This is a sex-linked0 U3 h% U( u) R
autosomal dominant disorder that affects only7 e" Q0 g |8 X, ^# L7 v/ k
males; therefore, other male members of the family: ?9 {6 }1 h; ~$ k
may have similar precocious puberty.3
1 Q$ j4 F" o" q8 hIn our patient, physical examination was incon-" y" M& D( V$ x3 y
sistent with true precocious puberty since his testi-- g" T8 V# H; `( X, V8 h
cles were prepubertal in size. However, testotoxicosis+ ~1 j. r8 }6 [ Y4 b, o
was in the differential diagnosis because his father
% w/ }& C, k7 P+ v5 Q: kstarted puberty somewhat early, and occasionally,
! x5 M: _$ V" [! p: ?; htesticular enlargement is not that evident in the9 _0 o5 S) l O' v
beginning of this process.1 In the absence of a neg-
) m: C* Y: q s: @, @( t" Vative initial history of androgen exposure, our
8 R! G5 `& C6 w; E% X# @biggest concern was virilizing adrenal hyperplasia,3 [, P: b. j% ?! o. N5 d- s2 `
either 21-hydroxylase deficiency or 11-β hydroxylase8 w; o8 R0 R. C( n
deficiency. Those diagnoses were excluded by find-
" o+ b2 u8 H I2 Q! L/ uing the normal level of adrenal steroids.+ d: D. L3 d' G0 X6 J, W
The diagnosis of exogenous androgens was strongly; r! f' L T6 M
suspected in a follow-up visit after 4 months because
9 l, I$ ], F/ p' z5 Vthe physical examination revealed the complete disap-5 `1 K/ [, z7 D% z) T7 l
pearance of pubic hair, normal growth velocity, and) J' L+ b8 B, ~& h! N- ?$ `7 t
decreased erections. The father admitted using a testos-. d( ^ r8 }4 Q$ O7 q0 {0 g+ U. w3 D
terone gel, which he concealed at first visit. He was
6 c% m* S# t; v' z2 B r+ pusing it rather frequently, twice a day. The Physicians’
7 |" r& u0 A- z, [( RDesk Reference, or package insert of this product, gel or
/ X% U! K" b9 x. f z7 Lcream, cautions about dermal testosterone transfer to! N4 Y) `" K2 y! e4 o( N
unprotected females through direct skin exposure.
% ?- ^) g+ |/ \0 b2 ~; tSerum testosterone level was found to be 2 times the
, x/ W d/ v% o7 }9 \baseline value in those females who were exposed to3 H: J1 j& A/ b- L; v
even 15 minutes of direct skin contact with their male7 ~- b# e* m0 p1 h, w# t
partners.6 However, when a shirt covered the applica-. m0 r2 \4 N Y0 z2 g2 ?
tion site, this testosterone transfer was prevented.& j. `7 J* m+ ]+ S
Our patient’s testosterone level was 60 ng/mL,
: P9 g, \: g' t& E) t/ X% dwhich was clearly high. Some studies suggest that
* A$ `3 u3 R1 t, ~" Xdermal conversion of testosterone to dihydrotestos-! S) X2 ], m" [1 j" Z0 D
terone, which is a more potent metabolite, is more
5 ^0 H9 h1 [: H9 U7 W5 C F4 d. Aactive in young children exposed to testosterone
P/ I- U% v0 Q. i1 Y) h6 `3 rexogenously7; however, we did not measure a dihy-6 |: z' x& m' u) j
drotestosterone level in our patient. In addition to. K7 M2 e. J" T J
virilization, exposure to exogenous testosterone in
. t5 ?" ~' \% U. S J* vchildren results in an increase in growth velocity and
# T- n% h* F4 Q* Badvanced bone age, as seen in our patient.
& s* L8 h4 [3 d2 FThe long-term effect of androgen exposure during; ^3 l% \5 W' o1 F7 K, s
early childhood on pubertal development and final
0 {: W# p. F) l. a7 ?' madult height are not fully known and always remain
( o6 Z+ C" g4 h& J$ Fa concern. Children treated with short-term testos-/ |% v( I9 O: E: Y: V
terone injection or topical androgen may exhibit some2 p: v1 z$ x7 N7 t* h$ G
acceleration of the skeletal maturation; however, after) b; v% }, V* ? I2 Z0 t8 I7 q6 {
cessation of treatment, the rate of bone maturation$ d+ G# S" J/ a9 n; _
decelerates and gradually returns to normal.8,9: L" S' i$ i+ ?4 T4 M8 y
There are conflicting reports and controversy. f# {# o1 k3 n8 G7 A5 D
over the effect of early androgen exposure on adult
5 n" J$ r0 A; I5 S4 Q# F6 r' G. \penile length.10,11 Some reports suggest subnormal
; R. y. o# x6 n: f$ Badult penile length, apparently because of downreg-
& u$ M+ a8 d0 u, B5 L: u" f& aulation of androgen receptor number.10,12 However,- C( G9 E$ e5 ^% a/ v" X* ? p
Sutherland et al13 did not find a correlation between$ s7 s0 Z" T. J% d4 d
childhood testosterone exposure and reduced adult' p4 r5 o4 e/ | E
penile length in clinical studies. r1 _ F/ V2 p' {. U3 `
Nonetheless, we do not believe our patient is+ C- x5 K, m: x6 g# R
going to experience any of the untoward effects from, V) S; H# G% d
testosterone exposure as mentioned earlier because# ` O7 h6 a k# c/ K8 m( Y
the exposure was not for a prolonged period of time.8 G; a+ W' G$ a0 {' Z0 e8 W
Although the bone age was advanced at the time of$ D7 z, ?: g( W+ I3 b2 q7 g
diagnosis, the child had a normal growth velocity at
; ^% x3 v* H! [5 _+ k/ c- Ethe follow-up visit. It is hoped that his final adult
2 i7 M1 @1 C( W Iheight will not be affected.. g5 E# F. E* T) v3 G5 |/ t% ~: P
Although rarely reported, the widespread avail-4 k1 }! l8 F( |% H
ability of androgen products in our society may. @& b3 @: C4 g9 x9 w
indeed cause more virilization in male or female, P; X8 {/ p6 ~# I3 I
children than one would realize. Exposure to andro-$ v @8 o7 t- h5 v! F
gen products must be considered and specific ques-
" j( G( D* b/ t2 Mtioning about the use of a testosterone product or% R+ c" g4 @& s4 Q' T+ T& y
gel should be asked of the family members during: @: l# \9 n* F" X- L+ h" ?# z
the evaluation of any children who present with vir-2 Z! i& L3 {9 M
ilization or peripheral precocious puberty. The diag-# U1 Z" u& k0 i+ {! r- m9 ?
nosis can be established by just a few tests and by1 O; P* D1 u1 d6 v3 I6 o H( Y
appropriate history. The inability to obtain such a6 m; @% J9 D% R" m/ V# \0 c( t
history, or failure to ask the specific questions, may8 ]7 w' d. K+ c$ T* S4 V2 M7 A
result in extensive, unnecessary, and expensive
" H+ E2 r H c/ l5 w) binvestigation. The primary care physician should be/ N% f/ X- X' ]1 ?- Y
aware of this fact, because most of these children
' L, x; K2 t& f( ymay initially present in their practice. The Physicians’
& R7 w6 A9 [4 V; y) RDesk Reference and package insert should also put a
3 Y% y6 Z' }0 u/ q% Iwarning about the virilizing effect on a male or8 H' X- \; U" g* L4 o
female child who might come in contact with some-
- w! b& A8 w% ]1 N% c$ pone using any of these products.2 } T, j# |+ k' u
References
1 b& h3 R5 \8 u# K/ r1. Styne DM. The testes: disorder of sexual differentiation
- ~6 ?' s1 a: Sand puberty in the male. In: Sperling MA, ed. Pediatric
2 W, r" t* [' {% C/ ]Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
# k U/ s) \# p: F$ B4 l0 S6 y, [# }2002: 565-628., H# ~8 ~. ~$ o' w% H7 B6 ^4 x
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
" D( x: l, p: E6 n1 X4 rpuberty in children with tumours of the suprasellar pineal |
|