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Sexual Precocity in a 16-Month-Old
5 q1 r3 C _* v' _: B! GBoy Induced by Indirect Topical* U+ S% [+ z4 S! C% q+ n
Exposure to Testosterone
! |3 R) H+ s2 ^1 {1 U% ~Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
- n7 Z1 ]; X- }, O/ k+ Iand Kenneth R. Rettig, MD1
' q; I6 w; L* L7 mClinical Pediatrics! z. U2 q1 Q0 k; j! k
Volume 46 Number 6
8 ?% H* S0 `) d4 JJuly 2007 540-5434 U. D7 u/ \! \3 o
© 2007 Sage Publications" }! b* E% C; |$ d/ l
10.1177/0009922806296651
/ N+ G6 Q: i O1 C% P" u% O5 |http://clp.sagepub.com7 d5 {" k7 \7 w: n" Y' `& L1 G
hosted at
4 [: ]4 ?7 F, k( u5 Uhttp://online.sagepub.com+ M* c# C$ a. w1 f% ^
Precocious puberty in boys, central or peripheral,4 h& |; [# i+ k. P& I- ^6 M
is a significant concern for physicians. Central
" v! z& A1 D) O4 B& zprecocious puberty (CPP), which is mediated2 @! C- I# Y) @' Q! ~5 T
through the hypothalamic pituitary gonadal axis, has6 G& {4 J* V: p v4 \
a higher incidence of organic central nervous system7 ?: h: I5 m: ?- y/ m# U
lesions in boys.1,2 Virilization in boys, as manifested
0 I5 H+ d" o" y* Iby enlargement of the penis, development of pubic# X7 q2 i/ `* L7 O T
hair, and facial acne without enlargement of testi-
. f o5 l- B) G H) Ccles, suggests peripheral or pseudopuberty.1-3 We; E/ g! d/ d J$ i$ W( A
report a 16-month-old boy who presented with the' j: l, u( i5 f3 _
enlargement of the phallus and pubic hair develop-& ?7 ?; n9 }8 U
ment without testicular enlargement, which was due/ d+ Y4 U- j; k, Q) h% z/ z
to the unintentional exposure to androgen gel used by
0 ?* n* D0 s7 L( T/ y! [5 o5 L( zthe father. The family initially concealed this infor-
' @( L+ F; }$ j, f* v6 wmation, resulting in an extensive work-up for this
) o# ~/ \9 \+ ochild. Given the widespread and easy availability of
7 M1 R3 f5 _3 N$ r5 m6 u) ctestosterone gel and cream, we believe this is proba-
: e9 R8 g9 l( v+ S5 W; B& |bly more common than the rare case report in the
$ m; b' }8 E; @ r$ h* p3 o3 u5 oliterature.4
7 d! R1 W- Y& ]3 d. Q3 PPatient Report
7 p% E. M. k6 R5 x% ~6 C5 cA 16-month-old white child was referred to the
8 X" Z7 B) ~7 g: E( ^endocrine clinic by his pediatrician with the concern$ c( z" O: Q5 J6 J
of early sexual development. His mother noticed
# v1 t: ?& _8 t+ d# l, W- Dlight colored pubic hair development when he was4 l9 A3 @3 j1 P! |; b7 ]
From the 1Division of Pediatric Endocrinology, 2University of# }6 R8 G. [: {; _' C# G
South Alabama Medical Center, Mobile, Alabama.
: f0 v: X5 {1 I! T3 BAddress correspondence to: Samar K. Bhowmick, MD, FACE,
: ~+ j3 z% X# k/ z& J: RProfessor of Pediatrics, University of South Alabama, College of% ?& B# R u: P
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
# Z+ J* }" f" p5 V" ge-mail: [email protected].; c5 N, H, c( v& |9 J' L/ r/ E
about 6 to 7 months old, which progressively became
3 R* o" i- k+ e# s& R3 H4 Cdarker. She was also concerned about the enlarge-5 Z# g+ H& h+ V
ment of his penis and frequent erections. The child+ Q5 f5 v& C. X
was the product of a full-term normal delivery, with
/ l! R! |) i8 z; H4 s7 ~a birth weight of 7 lb 14 oz, and birth length of
, b: ^8 z5 B3 ]0 K& D3 w20 inches. He was breast-fed throughout the first year
$ V; Y+ `. ]) c$ ? \ P; K1 Yof life and was still receiving breast milk along with* y. K6 a. W+ n3 u% V4 \
solid food. He had no hospitalizations or surgery,
* R/ i& q5 C! s- S0 z6 T# jand his psychosocial and psychomotor development- [* \) r P n1 c# O/ l
was age appropriate.
! d+ t) q2 H0 A4 `. SThe family history was remarkable for the father,
! B& n3 y% \* c9 t1 \- C+ k1 K6 Ewho was diagnosed with hypothyroidism at age 16,
' V! O: g# x9 J j% J& K0 K. R- ?which was treated with thyroxine. The father’s
: C4 n) g7 S) x: E& O8 ^height was 6 feet, and he went through a somewhat f' K1 u U6 l; D
early puberty and had stopped growing by age 14.
8 x- s. w2 P/ Q4 i! F1 g; PThe father denied taking any other medication. The. B6 @6 q* e, A( O9 q8 M
child’s mother was in good health. Her menarche: P$ I2 B& Z9 r1 L% \4 |
was at 11 years of age, and her height was at 5 feet& O; N) R1 ?$ ]: m
5 inches. There was no other family history of pre-
/ G0 [! j/ y1 a& G( ?3 Hcocious sexual development in the first-degree rela-: V. l2 T# a$ n1 n# D8 Z M
tives. There were no siblings.' ^, z$ ~+ O! X, u3 e) s: x
Physical Examination/ D/ r0 o ]9 D
The physical examination revealed a very active,
$ ~. P5 ^8 M) z, r% l5 {# @playful, and healthy boy. The vital signs documented. ^! a* C: _ _
a blood pressure of 85/50 mm Hg, his length was
0 Y E# U' }% f B* O: j90 cm (>97th percentile), and his weight was 14.4 kg- J" H$ A8 ~; W' ^
(also >97th percentile). The observed yearly growth" i$ k+ j* c0 Q4 i" i
velocity was 30 cm (12 inches). The examination of
( `- N L# l; I v5 kthe neck revealed no thyroid enlargement.5 @, I) [" m0 W% A& o& b
The genitourinary examination was remarkable for
* q$ B, E) }# @7 v' A0 Genlargement of the penis, with a stretched length of
: Y7 \+ c! [0 c8 cm and a width of 2 cm. The glans penis was very well' N6 X! v& ?/ p8 ^. p
developed. The pubic hair was Tanner II, mostly around
2 H% q/ U4 ^2 a6 M" p) F9 J- P5405 g" q( A7 l/ H) z5 Z
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
' f) l. ^: Q9 J6 X8 {% lthe base of the phallus and was dark and curled. The5 l/ _! \* \" d; ~8 q
testicular volume was prepubertal at 2 mL each.; ?9 }: m! Y; [5 J! C1 m K
The skin was moist and smooth and somewhat
0 Q" e/ t9 ?/ x" ?8 x8 ooily. No axillary hair was noted. There were no
% a# |7 {# H) q7 N3 V+ jabnormal skin pigmentations or café-au-lait spots.
" g- r, }4 ^! d' G5 |# n5 uNeurologic evaluation showed deep tendon reflex 2+% f7 J2 C. C- P
bilateral and symmetrical. There was no suggestion
; `' Q8 q! J6 Y J9 w$ L" qof papilledema.3 T$ D7 H2 d9 f
Laboratory Evaluation! N! M( }* x! u1 ^5 D7 @- `* z
The bone age was consistent with 28 months by
* P/ m7 X; _( N2 W' {/ {" @7 {7 `using the standard of Greulich and Pyle at a chrono-
' f% _* P% Z% S& G. mlogic age of 16 months (advanced).5 Chromosomal( O9 Y/ U/ Z, b" @
karyotype was 46XY. The thyroid function test
7 k# N; B7 Z6 ]. z% @2 @showed a free T4 of 1.69 ng/dL, and thyroid stimu-
! {2 w: p- T9 ]2 @lating hormone level was 1.3 µIU/mL (both normal).
: Z# Q: O7 E% Z1 T& @, ]The concentrations of serum electrolytes, blood1 {0 g* P) u* B1 l& U9 A3 G
urea nitrogen, creatinine, and calcium all were
! R5 d) `1 x+ a3 B7 n# ~$ Z% Qwithin normal range for his age. The concentration
4 P) E0 Z$ b( ?: W4 Xof serum 17-hydroxyprogesterone was 16 ng/dL) ^" r: _0 y' a% d5 T
(normal, 3 to 90 ng/dL), androstenedione was 20
) P* h; m# K/ @' z `ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros- s( _% H8 {8 s2 o7 V
terone was 38 ng/dL (normal, 50 to 760 ng/dL),3 k% k1 ~4 L( {4 z% \. Y
desoxycorticosterone was 4.3 ng/dL (normal, 7 to6 e6 J8 [; p: F
49ng/dL), 11-desoxycortisol (specific compound S)
. o+ \6 ?7 h2 P+ C- Rwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-! G+ J1 s6 S* F" D ~& i9 h" t; W+ v. b
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
4 F# n7 s+ u7 r$ R" J0 rtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),4 [ p4 Z5 N4 H
and β-human chorionic gonadotropin was less than
7 L$ r) D7 p: i# R4 y* V, v7 @5 mIU/mL (normal <5 mIU/mL). Serum follicular. Y3 m- c, F# n7 h
stimulating hormone and leuteinizing hormone
. E6 F1 Q% Z7 P5 h; Sconcentrations were less than 0.05 mIU/mL" _. E1 `7 M; ^1 H- b0 t. k, T$ Z
(prepubertal).
2 s' Y9 z9 t! G ?The parents were notified about the laboratory
# e1 k* k0 d9 C! X7 a. Fresults and were informed that all of the tests were: N% ^, ^2 w! c5 l
normal except the testosterone level was high. The, t* s1 l, k& }
follow-up visit was arranged within a few weeks to
3 G% e6 ~6 i. ?7 dobtain testicular and abdominal sonograms; how-
" z: b c% l" g! a. never, the family did not return for 4 months.
$ c7 {$ _7 b8 U, _8 dPhysical examination at this time revealed that the
J$ y2 r. k" d8 r3 j+ wchild had grown 2.5 cm in 4 months and had gained# i6 t( h0 x: s8 i }
2 kg of weight. Physical examination remained; ?0 ^/ B' d* P1 W0 V" Y9 c D' d
unchanged. Surprisingly, the pubic hair almost com-; B" H& V" O. k$ A( ~9 }
pletely disappeared except for a few vellous hairs at
- b* }& j* e5 ]+ @- zthe base of the phallus. Testicular volume was still 26 V3 g, p3 x/ G: [$ _
mL, and the size of the penis remained unchanged.
6 u% Q; s* }' K @( HThe mother also said that the boy was no longer hav-6 d% K2 b) s; F( E
ing frequent erections.
( o! v" Z& A: H0 }7 V N( q- Q- {Both parents were again questioned about use of
+ s. D) p+ k: v; J7 nany ointment/creams that they may have applied to
* v; j! J0 }6 ]1 athe child’s skin. This time the father admitted the, ~. p& b$ X/ w" x
Topical Testosterone Exposure / Bhowmick et al 541& s! Z' _+ B; @ _/ y( s% [- e2 i
use of testosterone gel twice daily that he was apply-
7 C( y3 Z5 @0 {3 p1 |1 king over his own shoulders, chest, and back area for' U% w9 X$ g; q6 T6 Y3 X$ T$ @
a year. The father also revealed he was embarrassed F8 U" Q# Q; S: n6 ~) `: n' q
to disclose that he was using a testosterone gel pre-/ [- |9 K6 n' z* E9 `
scribed by his family physician for decreased libido* J, d- U* L$ D# w% P/ `' n# a8 ^
secondary to depression.0 t' S% w+ r: l
The child slept in the same bed with parents.
0 _: H9 G1 P9 _* A4 N# Y* KThe father would hug the baby and hold him on his
% G4 ?( x5 l' m$ qchest for a considerable period of time, causing sig-, t/ X- H, I( M- j( t
nificant bare skin contact between baby and father.( T- Y3 i% h1 G. h
The father also admitted that after the phone call,
& n4 K6 |0 ^. Z5 A% u1 rwhen he learned the testosterone level in the baby; V9 P9 d3 l7 H, d+ B0 _- U
was high, he then read the product information: D" t2 M1 W: M8 D
packet and concluded that it was most likely the rea-! b7 ?. E" I0 f6 N1 @% D% Q
son for the child’s virilization. At that time, they5 j+ P# l- [6 k- W( D
decided to put the baby in a separate bed, and the
- l7 S' f( t2 |9 Vfather was not hugging him with bare skin and had- @0 e- V8 `5 i
been using protective clothing. A repeat testosterone
9 d+ r! `* ]& `& p, ptest was ordered, but the family did not go to the
8 T4 L/ s1 j$ U" A0 g3 Dlaboratory to obtain the test.9 w/ [! W5 o1 ?
Discussion! g @3 u9 c5 t
Precocious puberty in boys is defined as secondary, Z; C6 A0 X! S7 D% q
sexual development before 9 years of age.1,4! f- J) j: _4 g# ]+ ~+ [4 H
Precocious puberty is termed as central (true) when
} M& P- s- B! H, W( s5 Zit is caused by the premature activation of hypo-
# b* ?/ t5 K; @7 s& L# \thalamic pituitary gonadal axis. CPP is more com-
+ c+ g* c6 E9 L) w) Y6 J; omon in girls than in boys.1,3 Most boys with CPP
4 j, Z L; c( B% c9 kmay have a central nervous system lesion that is& [4 V* ~/ Y; V6 J" d& M( a2 E
responsible for the early activation of the hypothal-: _* I3 B7 ]$ u
amic pituitary gonadal axis.1-3 Thus, greater empha-4 s* c3 X/ V% g/ h. h7 g7 g
sis has been given to neuroradiologic imaging in
6 h, Q# P) z! _5 `2 M# Q6 Lboys with precocious puberty. In addition to viril-- n" l' Z! ]7 b9 ?4 T9 a
ization, the clinical hallmark of CPP is the symmet-( C; N/ m) A/ `8 ]6 d5 g- H. g7 C9 V
rical testicular growth secondary to stimulation by: h! N& K- j8 ^4 G% S1 @- [
gonadotropins.1,3
: `: M* `4 B2 @5 QGonadotropin-independent peripheral preco-4 N% V2 G# A" h6 o5 U! I
cious puberty in boys also results from inappropriate5 _% ?8 i" Y2 A2 p0 z2 Y
androgenic stimulation from either endogenous or K# X# X9 z# [3 D/ c; L
exogenous sources, nonpituitary gonadotropin stim-
3 \& |1 F) Y5 E+ o9 Y& `ulation, and rare activating mutations.3 Virilizing
7 ^4 Y; @. b8 Z# d5 i' Lcongenital adrenal hyperplasia producing excessive2 t/ l" U0 R5 h' P# G/ _- a
adrenal androgens is a common cause of precocious
, U) L) k, Q& jpuberty in boys.3,4* J- a+ m4 Z, i* r4 z0 i2 m9 @% a6 A
The most common form of congenital adrenal
. b! h1 b4 i( |% W+ x% m( Khyperplasia is the 21-hydroxylase enzyme deficiency.
% i6 m4 y( I, [The 11-β hydroxylase deficiency may also result in
, O" H0 A+ U. @, w$ U) W/ |excessive adrenal androgen production, and rarely,: ?2 _. G5 X! ]8 d
an adrenal tumor may also cause adrenal androgen0 M" D5 i3 C1 Q6 [, r/ A
excess.1,3
0 ]" O, r( P- Q l, U, f* aat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from8 M' [4 ~8 ~6 B
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007; F0 J$ Q. |; M4 Q- k
A unique entity of male-limited gonadotropin-
7 k% ~) {" e- P5 y8 _independent precocious puberty, which is also known! e! P3 G) m+ x" P9 U
as testotoxicosis, may cause precocious puberty at a
9 b5 |7 `7 B# Y6 Lvery young age. The physical findings in these boys8 z% V) |. J' C( n) b- d! }8 |& w
with this disorder are full pubertal development,
8 ^& q8 K: F! A& o) s9 J; Wincluding bilateral testicular growth, similar to boys
" n! l) g# B6 ?with CPP. The gonadotropin levels in this disorder' v6 W( j# U3 a; m d! c3 q7 s
are suppressed to prepubertal levels and do not show
: }: ]; V: u' @( `% I1 z0 |5 I1 V' mpubertal response of gonadotropin after gonadotropin-, w8 p* t8 f7 ]8 a* P
releasing hormone stimulation. This is a sex-linked
% }/ u7 c( G( V& j( Cautosomal dominant disorder that affects only% L3 k: c. J" P8 K
males; therefore, other male members of the family; x' j, [& R; {6 ]0 _) P
may have similar precocious puberty.3
- E1 j4 L( G& {In our patient, physical examination was incon-
* A# g O4 Y' R+ A* ?9 osistent with true precocious puberty since his testi-
0 }( S& }6 ?, Y" u( ocles were prepubertal in size. However, testotoxicosis
8 G5 {3 s: m# F& L ]was in the differential diagnosis because his father
+ `- L, J D2 N0 y, Z# |: l( Bstarted puberty somewhat early, and occasionally,( T, X4 s% l" V3 f* l
testicular enlargement is not that evident in the
0 ]6 j D! }1 q2 i* `beginning of this process.1 In the absence of a neg-3 K: E) u' z3 M
ative initial history of androgen exposure, our7 \( v3 ]; j2 X+ o
biggest concern was virilizing adrenal hyperplasia,
6 K& ^! r! o3 y# y7 J+ t8 Q6 W; h# peither 21-hydroxylase deficiency or 11-β hydroxylase
( b& s; s3 i# K) e8 b2 Fdeficiency. Those diagnoses were excluded by find-
+ D, F! f; o- e; Ging the normal level of adrenal steroids.9 G0 }6 W5 u2 Y# \& K9 Q% @
The diagnosis of exogenous androgens was strongly; ~$ [8 a# M; l9 Z
suspected in a follow-up visit after 4 months because! _7 ~' Y; f1 z0 o1 ^: K+ k1 N& P
the physical examination revealed the complete disap-
2 E$ {. [, u* g" Apearance of pubic hair, normal growth velocity, and I8 @8 ?6 ~$ d. f7 @7 ~
decreased erections. The father admitted using a testos-
0 Z# P, W( B2 X! kterone gel, which he concealed at first visit. He was* {+ j3 r: i+ ^
using it rather frequently, twice a day. The Physicians’: @. ]: R, ]- L2 G* Z
Desk Reference, or package insert of this product, gel or: I7 t. s' `9 f# E d
cream, cautions about dermal testosterone transfer to
: A2 c5 e; L% U1 I/ u3 j, qunprotected females through direct skin exposure.
0 V# K0 a J& u+ \8 p' aSerum testosterone level was found to be 2 times the4 N; @/ S2 w2 w; V
baseline value in those females who were exposed to
6 \1 {0 |, j6 Z0 x& Keven 15 minutes of direct skin contact with their male8 i9 a( M* I; [) h+ r* ~$ Y6 f
partners.6 However, when a shirt covered the applica-) _* G! i* P1 Y2 ]& i0 W: c
tion site, this testosterone transfer was prevented.
. I% Z8 _& p7 c |* Q& g) xOur patient’s testosterone level was 60 ng/mL,
5 a0 ^# |) m1 Ywhich was clearly high. Some studies suggest that; o9 S- k- U" z
dermal conversion of testosterone to dihydrotestos-
' M; Z2 Z! ~! Dterone, which is a more potent metabolite, is more
4 X7 C' _' o% w; Kactive in young children exposed to testosterone$ G- B- M* T' O" ~$ |
exogenously7; however, we did not measure a dihy-# o/ n6 D+ Q2 v3 L9 ]
drotestosterone level in our patient. In addition to
U$ n+ `$ F0 B0 V% H1 mvirilization, exposure to exogenous testosterone in3 m! @8 d1 ], D0 w% k+ f/ [
children results in an increase in growth velocity and, x# p2 j" b9 Y* V( v1 C5 s2 J
advanced bone age, as seen in our patient., `" W* q9 `# t& C2 _, B( v
The long-term effect of androgen exposure during5 @# M! v/ ~0 O y
early childhood on pubertal development and final
, j1 }7 m8 D- L6 Eadult height are not fully known and always remain
1 U f3 f1 G ka concern. Children treated with short-term testos-; P- y% y, ~( Z8 r, L
terone injection or topical androgen may exhibit some5 X8 r5 F- a) l- w, t, L# o1 @. @/ X3 l
acceleration of the skeletal maturation; however, after; b) T" w- ^6 Q r
cessation of treatment, the rate of bone maturation
5 F. d: L, D3 `% g$ c; o! Q9 l- edecelerates and gradually returns to normal.8,9
: T9 }, c( k3 B7 C! e" a4 {! T- sThere are conflicting reports and controversy
5 }. n) o! T. r# `* c4 F2 Oover the effect of early androgen exposure on adult
5 M5 l- T! K9 x ~penile length.10,11 Some reports suggest subnormal
3 y1 _7 `6 m4 y2 l- `adult penile length, apparently because of downreg-* q( p- l, o5 x# m! U# K
ulation of androgen receptor number.10,12 However,. L% k, s, n/ e. C$ k* H$ f
Sutherland et al13 did not find a correlation between
E1 K6 @( e- v4 ~# n- l0 qchildhood testosterone exposure and reduced adult
" \( ]+ F5 g5 ^; T" l& }penile length in clinical studies.& E! T4 R, ~) z1 P" J# w! p
Nonetheless, we do not believe our patient is5 D" N+ R) z5 g8 \, D
going to experience any of the untoward effects from
! M8 ]2 h/ Q/ L4 b0 T P2 f0 a) G% e1 Otestosterone exposure as mentioned earlier because
# o" v8 _2 i0 n) O' n' z. kthe exposure was not for a prolonged period of time.
3 w4 @+ j9 G3 m" t4 @' V1 N1 x9 UAlthough the bone age was advanced at the time of( n& F2 |9 r# @" K1 y
diagnosis, the child had a normal growth velocity at6 U) W/ J% X0 W8 k9 U! ^3 D
the follow-up visit. It is hoped that his final adult {& }' B& _3 T) `6 H
height will not be affected.+ I+ K+ Z1 U% [' h6 R; G; T
Although rarely reported, the widespread avail-; d' n* k+ F+ G, E$ Z/ \
ability of androgen products in our society may
0 k' N3 t! P/ ]. Cindeed cause more virilization in male or female
& l( s$ [6 W; g C) [0 ^/ qchildren than one would realize. Exposure to andro-* R' }. c9 ]7 K) b
gen products must be considered and specific ques-# t' ~" y9 K% Q r$ [3 h9 ?
tioning about the use of a testosterone product or
" D! g2 f% A% t( Qgel should be asked of the family members during$ f$ {. ~7 p0 K/ I' L7 f! W
the evaluation of any children who present with vir-
' b; [7 Q! B6 g' Qilization or peripheral precocious puberty. The diag-
" ?( `3 g# F4 a/ x) V5 Inosis can be established by just a few tests and by
+ ? x ~2 v- D$ W( L) |4 A; Rappropriate history. The inability to obtain such a: A5 ?# i `& Z2 z
history, or failure to ask the specific questions, may
% k* i+ i" w5 w# bresult in extensive, unnecessary, and expensive6 @% |9 A# c) Q$ u* u, V S
investigation. The primary care physician should be& o; y1 J6 s- F+ j
aware of this fact, because most of these children! d9 L% v. K0 z
may initially present in their practice. The Physicians’
) d ^+ b1 s' \% H5 J( T. }Desk Reference and package insert should also put a
7 r% Q6 M! v) `/ w, i- Q3 }warning about the virilizing effect on a male or
5 Y4 ]; ?5 I. M5 ^female child who might come in contact with some-* z8 x0 E, o- F& x4 N$ T
one using any of these products.
& c0 R! C/ D2 F" jReferences
3 O y% `* R3 m1. Styne DM. The testes: disorder of sexual differentiation* L* N$ m# w! Q; D1 j4 R' ~1 G
and puberty in the male. In: Sperling MA, ed. Pediatric
* k' x- S* { `/ H1 t: n) IEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;9 T3 [. ~0 ^' n2 W, o) z
2002: 565-628.
~! Q4 D& [7 L# S6 \2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious3 R( W6 ]' ?" _6 J$ |2 s
puberty in children with tumours of the suprasellar pineal |
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