- 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 03:25:35
|
顯示全部樓層
Sexual Precocity in a 16-Month-Old% d! [; |. E# B& l& W2 ~
Boy Induced by Indirect Topical
: T f; y# W' {Exposure to Testosterone7 D# W+ T; v9 G4 j
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2/ t! n# l/ j9 L1 O. L
and Kenneth R. Rettig, MD12 a0 O% I7 V' o# I! J6 V& Y; y
Clinical Pediatrics# {% ~7 D4 X0 l" I
Volume 46 Number 6
- ^. ~+ S. z7 [# c: A* NJuly 2007 540-543
8 x/ Z9 o9 J* W© 2007 Sage Publications
1 H& }( o7 a5 r10.1177/0009922806296651
/ j0 g+ H% b! ~, e/ S! Mhttp://clp.sagepub.com, R! r& S& c2 M8 q' I/ w2 ]
hosted at
6 t7 A% ~' ]- ]* u( [1 Hhttp://online.sagepub.com6 N- K: E9 l4 O6 M# T: v
Precocious puberty in boys, central or peripheral,8 B9 }% z) a' e6 b( J
is a significant concern for physicians. Central
& O. _- c- P+ E1 \4 ?precocious puberty (CPP), which is mediated
( T+ ^$ E% B3 G: `- ?through the hypothalamic pituitary gonadal axis, has) x8 p/ \4 v8 R" I2 l, P4 K! e. u
a higher incidence of organic central nervous system' {5 c3 X2 ~/ l& A, X6 W; ~
lesions in boys.1,2 Virilization in boys, as manifested# _; @" O- j( a- ?$ O
by enlargement of the penis, development of pubic
# S* U) G0 C% y' U Ahair, and facial acne without enlargement of testi-
% j+ b# x$ b, M' j/ D: Icles, suggests peripheral or pseudopuberty.1-3 We! [$ B6 ]' q0 V, {+ X5 @
report a 16-month-old boy who presented with the
* v2 K7 g6 ]: r& kenlargement of the phallus and pubic hair develop-7 L* o1 ?; M( [% N( z& i; b
ment without testicular enlargement, which was due
9 m3 `. h) ]) h3 [to the unintentional exposure to androgen gel used by
7 b1 j0 L6 f, V6 h2 M# Vthe father. The family initially concealed this infor-. M3 n7 ?4 b R# U
mation, resulting in an extensive work-up for this, s4 K0 v8 W2 Y( e$ x, x
child. Given the widespread and easy availability of
' R" c) l# v; }: }testosterone gel and cream, we believe this is proba-' ?% c0 L6 I9 g" Q. b
bly more common than the rare case report in the( v4 {+ ]( n. O( k$ q
literature.4
- V: a# n5 s% c0 h* EPatient Report
) {0 R+ ^" H+ R, _A 16-month-old white child was referred to the( z& t. ^3 ?) A! i# n
endocrine clinic by his pediatrician with the concern
( B9 I, V/ P/ e8 x" T* s$ Eof early sexual development. His mother noticed
* t% U3 U! j$ {3 |light colored pubic hair development when he was0 X$ I4 U! e2 K+ m
From the 1Division of Pediatric Endocrinology, 2University of
1 r$ K$ i0 e1 |/ ESouth Alabama Medical Center, Mobile, Alabama." C- i7 b* Z7 B5 {
Address correspondence to: Samar K. Bhowmick, MD, FACE,. o+ j4 d6 J6 F! B2 @6 g
Professor of Pediatrics, University of South Alabama, College of
" a1 O4 M; O1 I, |( G- r5 D" hMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;8 r8 l. N" f4 W. {3 Q3 P: ]
e-mail: [email protected].
6 I; B# Q. v) _: i& F5 n0 X( H9 p7 Xabout 6 to 7 months old, which progressively became$ H o( L3 w( U& n9 u
darker. She was also concerned about the enlarge-
+ }8 S O5 B" X T q+ Sment of his penis and frequent erections. The child* I- k: b& c- O# l+ c0 t
was the product of a full-term normal delivery, with
1 ?6 `% i& h5 Z, l. [6 za birth weight of 7 lb 14 oz, and birth length of$ g$ p4 Y- P, C4 o2 k1 ?% _
20 inches. He was breast-fed throughout the first year* [+ ]0 a% ~7 `+ h
of life and was still receiving breast milk along with
7 E& m1 L9 m- g3 @" hsolid food. He had no hospitalizations or surgery,
$ w; M1 I0 V6 { uand his psychosocial and psychomotor development& T' J- I9 s( P" F0 C% E
was age appropriate.1 u+ |! W: v- b
The family history was remarkable for the father,6 D/ q( H i4 Z$ Y
who was diagnosed with hypothyroidism at age 16,
% Y+ F9 a0 p$ ^3 Awhich was treated with thyroxine. The father’s7 B/ J8 { s$ y% L2 K/ P; E
height was 6 feet, and he went through a somewhat- Z+ a, {' R$ O4 J1 [) w7 d
early puberty and had stopped growing by age 14.: t6 K& d/ D' k
The father denied taking any other medication. The
3 ^4 w9 v: p: I8 g7 x m0 Cchild’s mother was in good health. Her menarche& x7 t7 s/ u! e0 u$ j9 ^
was at 11 years of age, and her height was at 5 feet: q# ~5 [8 z# j- o2 K% C) w
5 inches. There was no other family history of pre-
& G- N# a$ j3 a$ S5 kcocious sexual development in the first-degree rela-
$ N7 y" Q) k5 ]* g9 Ttives. There were no siblings. w+ ~" ^3 R* j! H! A
Physical Examination7 b; Q9 |) m0 @# B' {
The physical examination revealed a very active,
" X' [$ ~% R- O6 \5 C9 pplayful, and healthy boy. The vital signs documented
; ~ H1 k6 m1 f3 z7 c/ T G% Ba blood pressure of 85/50 mm Hg, his length was
3 m' M+ H* K( e6 J" @7 e7 B90 cm (>97th percentile), and his weight was 14.4 kg8 V' ^2 M" J- f9 f0 h) z
(also >97th percentile). The observed yearly growth
! C; Q! c, `0 A' R# i5 Avelocity was 30 cm (12 inches). The examination of
* S! I# B3 T$ G- }9 ?3 |% B+ xthe neck revealed no thyroid enlargement.
. u* C4 y% C! [2 @9 P- HThe genitourinary examination was remarkable for3 M+ O9 ^! }/ R. }7 |' s/ v8 ~
enlargement of the penis, with a stretched length of
& x9 I* d- Z0 p$ n2 Y. S/ ]( X% g8 cm and a width of 2 cm. The glans penis was very well) c! N* i9 @8 M, G
developed. The pubic hair was Tanner II, mostly around' e( D% ?- D1 y. l
540
+ H* }- ~) Q. J8 y* Bat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from: `. K6 _; r& `; X% b0 ~' g
the base of the phallus and was dark and curled. The
& \4 g0 c/ q/ d5 ]$ Htesticular volume was prepubertal at 2 mL each.8 r2 R) |9 Z' i
The skin was moist and smooth and somewhat
P4 }% d, E& H$ p4 `" N$ m+ Hoily. No axillary hair was noted. There were no
2 n3 C* D1 @0 B# p. f" Jabnormal skin pigmentations or café-au-lait spots.
. _$ M% w/ l" K2 S! M" s8 uNeurologic evaluation showed deep tendon reflex 2+
+ _) w6 H5 a& [! b; Lbilateral and symmetrical. There was no suggestion& K# k, Q, w) D T
of papilledema.2 `+ M" K$ Q1 o/ a- V
Laboratory Evaluation
' |& _! ?$ s3 L( R/ o7 s% CThe bone age was consistent with 28 months by {( r( F- m( ~! |' z. h" x
using the standard of Greulich and Pyle at a chrono-
3 p- |' F& X" _logic age of 16 months (advanced).5 Chromosomal$ `% ^; r2 _0 L$ w) O5 n8 e2 Y
karyotype was 46XY. The thyroid function test
# L' F9 D5 l# x6 Nshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
' L+ J2 a' q) ?% \/ ~lating hormone level was 1.3 µIU/mL (both normal).
4 O" q: C' x8 c$ _1 PThe concentrations of serum electrolytes, blood
; P/ S. W) y e6 ~( [( H/ p, hurea nitrogen, creatinine, and calcium all were w1 h, c8 a# X( {
within normal range for his age. The concentration
/ Y2 b; t" e/ Z4 k, A' q8 rof serum 17-hydroxyprogesterone was 16 ng/dL9 M0 w! C4 C5 U+ @; o
(normal, 3 to 90 ng/dL), androstenedione was 20
$ w6 ]4 `# M2 M" kng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-5 T. J" h" f% H& T, [5 Z' J$ r% L! u9 u
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
1 n1 r6 @1 Y: m" T1 Adesoxycorticosterone was 4.3 ng/dL (normal, 7 to' b, C2 g$ o' g. |
49ng/dL), 11-desoxycortisol (specific compound S)
6 H1 D8 m8 R1 E4 S9 Awas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
& n# |* e, q- r' [1 T3 Jtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
3 ]/ j+ M4 q# b( g& Q. Otestosterone was 60 ng/dL (normal <3 to 10 ng/dL),- x; W' N2 v: [. G% r, D6 t5 q
and β-human chorionic gonadotropin was less than k$ f& }% w: V; A
5 mIU/mL (normal <5 mIU/mL). Serum follicular$ R) F( r0 t- h1 I$ `
stimulating hormone and leuteinizing hormone
- P* `$ |. ^: i- kconcentrations were less than 0.05 mIU/mL$ z0 r6 s5 u; C
(prepubertal).
9 _2 ~2 {" y. bThe parents were notified about the laboratory
# r; v/ j$ Y1 L* {/ N8 M9 Z: ]# zresults and were informed that all of the tests were/ m* Z0 ]3 n/ F6 U: x
normal except the testosterone level was high. The) e" A6 E! N; \6 J n. o! |% b
follow-up visit was arranged within a few weeks to% O9 {! n) f4 d3 {7 X6 n6 q
obtain testicular and abdominal sonograms; how-
/ F/ I' t) ~% }. e! \1 v$ L2 f$ Sever, the family did not return for 4 months.; n8 H& ^/ M, r
Physical examination at this time revealed that the
# j K& l+ X* ?/ U; jchild had grown 2.5 cm in 4 months and had gained
. C4 k" n K5 M% D7 Z, I6 m2 kg of weight. Physical examination remained
; u) b+ D* V! Q }9 ^8 J: y( Munchanged. Surprisingly, the pubic hair almost com-- U4 }% j: S3 F2 i! f6 c
pletely disappeared except for a few vellous hairs at
* G& o8 S K+ A+ u# X1 athe base of the phallus. Testicular volume was still 2
H1 k# Q% k. k _" ImL, and the size of the penis remained unchanged.! A2 ]) e3 P# ` T8 t+ p0 l
The mother also said that the boy was no longer hav-- J% l% i. [7 Y) j& e n+ e# N
ing frequent erections.
6 @' K0 U, Y! }4 w5 JBoth parents were again questioned about use of
! Z' _/ X s% O) [any ointment/creams that they may have applied to# g* w6 Q7 R$ g" s9 I
the child’s skin. This time the father admitted the
" R2 o1 X$ B/ t4 v- N+ z- ZTopical Testosterone Exposure / Bhowmick et al 541
3 p" J% a. }8 J0 b& t* V$ Fuse of testosterone gel twice daily that he was apply-% T7 ]) Y) I/ b5 l4 C9 N
ing over his own shoulders, chest, and back area for3 R0 R n; B! D" G
a year. The father also revealed he was embarrassed. r3 e- Y# w( b( @
to disclose that he was using a testosterone gel pre-
5 l$ d. P$ L5 n3 D- fscribed by his family physician for decreased libido
- S( U! w% L9 t7 Q5 w, z' qsecondary to depression.
- Y9 |; q8 P( C2 T; iThe child slept in the same bed with parents.
" R( o+ N& \* M8 h+ YThe father would hug the baby and hold him on his
1 Q4 C! r7 }8 wchest for a considerable period of time, causing sig-1 N" \4 u. |! @. ^
nificant bare skin contact between baby and father.# v1 z2 B0 H8 e K7 l: s- u
The father also admitted that after the phone call,
, i8 a: ^7 W2 I& t- |$ wwhen he learned the testosterone level in the baby
4 l9 g$ }9 ]* v6 ^3 D' Q0 q9 Pwas high, he then read the product information
' [# P* q5 Y9 M: q) U9 S, opacket and concluded that it was most likely the rea-
2 @' C$ I1 o( I, m! Fson for the child’s virilization. At that time, they
- O8 G( l+ t5 z; r; U# cdecided to put the baby in a separate bed, and the
( B+ R9 h# Z" L* K7 I6 M; |father was not hugging him with bare skin and had% m" X: h8 u: `. D0 K5 W/ r6 ~* K
been using protective clothing. A repeat testosterone" F/ Y$ l2 q) q$ ]( b& p
test was ordered, but the family did not go to the8 E' ?) t) d' W- ?' c* ]
laboratory to obtain the test.# k/ n0 X3 G9 c3 Y! M! s9 \
Discussion( H& n+ ^. y# P% o9 y: O+ u
Precocious puberty in boys is defined as secondary
& Z7 g1 G) v* \7 Esexual development before 9 years of age.1,4
8 x( K8 Z0 \+ d; w% K" wPrecocious puberty is termed as central (true) when% J" e7 M8 K7 y" h, p
it is caused by the premature activation of hypo-" [5 u$ l7 _; y" D& ~- F3 |
thalamic pituitary gonadal axis. CPP is more com-
5 U# r; d9 T2 c& ?* Smon in girls than in boys.1,3 Most boys with CPP
( c) W3 b; X1 a( _" ?may have a central nervous system lesion that is
- W5 P0 M' o: V; A. ?0 |1 }: E/ Hresponsible for the early activation of the hypothal-* [9 E. P& t, `0 N
amic pituitary gonadal axis.1-3 Thus, greater empha-
% t) B, |) f0 Zsis has been given to neuroradiologic imaging in: \: @- S9 `, n# l
boys with precocious puberty. In addition to viril-4 }9 p8 q. d2 h# M- D* j0 }9 g
ization, the clinical hallmark of CPP is the symmet-
$ M- z) e- V2 q0 c/ O2 A. Rrical testicular growth secondary to stimulation by
6 y" Z5 v0 X$ T$ xgonadotropins.1,3$ @" K8 [! S4 f7 B
Gonadotropin-independent peripheral preco-
* { Y2 T& M4 U6 L/ bcious puberty in boys also results from inappropriate
( y) t# B/ `2 e+ N$ ?androgenic stimulation from either endogenous or! ^3 C# l5 \& g+ }4 O
exogenous sources, nonpituitary gonadotropin stim- ]. _& @8 j- m
ulation, and rare activating mutations.3 Virilizing7 \( N @5 G! {% u! x7 O
congenital adrenal hyperplasia producing excessive
3 ^5 A e, {5 eadrenal androgens is a common cause of precocious6 j+ K* X3 G( |# @0 T" v3 G4 x2 X5 B
puberty in boys.3,4
9 O, M$ ]+ k( k3 p: w5 KThe most common form of congenital adrenal0 ~( J8 [4 P3 ^+ w/ ?9 |8 F3 t/ v: }
hyperplasia is the 21-hydroxylase enzyme deficiency.* `' l* J# z" }( l
The 11-β hydroxylase deficiency may also result in4 ]* B5 M7 }. i% {7 u" }: f
excessive adrenal androgen production, and rarely,
& Q- X% Y1 A3 M6 X8 q. J2 ]' ]an adrenal tumor may also cause adrenal androgen% l! I/ |9 a& t! j1 X! P; P
excess.1,3
4 G( ^3 B# m" E/ _at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
5 Z7 L0 G. f$ {! F; ]; a# u542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
! T+ K# U/ a# b7 PA unique entity of male-limited gonadotropin-
' z! e- ~7 ~. u9 iindependent precocious puberty, which is also known
; z; P9 g6 V, Zas testotoxicosis, may cause precocious puberty at a _( U5 N6 e. |/ C9 a
very young age. The physical findings in these boys" j3 F. x/ E% q% _( w5 j
with this disorder are full pubertal development,, y- f) A) W% M
including bilateral testicular growth, similar to boys
1 m& c9 o" a6 @4 Y* Zwith CPP. The gonadotropin levels in this disorder
, D3 h, f4 O1 P9 rare suppressed to prepubertal levels and do not show
. a& T. B+ z# o W$ a- K0 Kpubertal response of gonadotropin after gonadotropin-* C0 l+ V7 o! I# v4 m( R1 Y
releasing hormone stimulation. This is a sex-linked
1 { `1 t5 d( Q( v! l8 Y& m8 R) r `autosomal dominant disorder that affects only
! L3 l( v0 C7 `3 G) \males; therefore, other male members of the family2 v7 a1 M4 m" k# L
may have similar precocious puberty.3
: ` [) C" @) r. L" n6 tIn our patient, physical examination was incon-/ ~, R0 G; Z" F- p1 P" s* l
sistent with true precocious puberty since his testi-
3 V* Z" [- F o- icles were prepubertal in size. However, testotoxicosis
! c |0 z- Y: F- q7 N! Q8 _* lwas in the differential diagnosis because his father' p5 e& c# N' {+ n% f. L
started puberty somewhat early, and occasionally,' y/ Y9 m* I( ^6 ^
testicular enlargement is not that evident in the
# s/ V: s2 @* {! Y7 A: ~1 Ibeginning of this process.1 In the absence of a neg-
6 i6 H- a" F5 R. p! rative initial history of androgen exposure, our( `. @* z4 O$ b. `8 C" v2 |/ w
biggest concern was virilizing adrenal hyperplasia,: p _; @% j; w) K9 n
either 21-hydroxylase deficiency or 11-β hydroxylase7 z4 z: @" S" x, k* o- U$ q) T
deficiency. Those diagnoses were excluded by find-+ F9 C, H, {$ F" L
ing the normal level of adrenal steroids.
0 d. ?8 s! H$ W* I# k2 FThe diagnosis of exogenous androgens was strongly) ]' m, r' {; A
suspected in a follow-up visit after 4 months because
/ h. ~ H) r+ y! C$ A! U' r zthe physical examination revealed the complete disap-0 u1 U/ _6 V8 Z% I3 G/ _2 N3 [% W
pearance of pubic hair, normal growth velocity, and
~) ~) r# t* k2 fdecreased erections. The father admitted using a testos-! G/ v: K* b6 W) C6 Z
terone gel, which he concealed at first visit. He was9 ^4 y6 e- |0 C) [/ w
using it rather frequently, twice a day. The Physicians’; L" w* ?6 o2 O' y# N& W5 K, I( E
Desk Reference, or package insert of this product, gel or
" D- B, U- w! m+ ^cream, cautions about dermal testosterone transfer to
" I3 o) R" S! P' X! G+ xunprotected females through direct skin exposure.
- _) X- z% d- O' sSerum testosterone level was found to be 2 times the
" S7 b7 [, d" fbaseline value in those females who were exposed to: p' d& r h, K" {5 Y! O
even 15 minutes of direct skin contact with their male( b1 j6 B6 X2 X3 O
partners.6 However, when a shirt covered the applica-
$ R- }3 K# ^, j/ Q( n8 btion site, this testosterone transfer was prevented.
1 R d% P5 I! a4 ROur patient’s testosterone level was 60 ng/mL,
0 j. d; L, }" p/ b2 p9 D3 uwhich was clearly high. Some studies suggest that! ~( S/ w0 G: g; U: p
dermal conversion of testosterone to dihydrotestos-' K0 m, m: A8 u9 x' r
terone, which is a more potent metabolite, is more
. m. |+ B y; ]" a# pactive in young children exposed to testosterone+ {& P3 j9 W. ~3 o3 U$ e
exogenously7; however, we did not measure a dihy-
0 }3 x- |& r* R; r& o: r/ F& rdrotestosterone level in our patient. In addition to( \! C" ~) K% h7 k
virilization, exposure to exogenous testosterone in
+ K! e, K' `/ U ichildren results in an increase in growth velocity and) f/ N( [6 c0 ^* S
advanced bone age, as seen in our patient./ T$ V/ m( l! ^2 d1 Z# }! J
The long-term effect of androgen exposure during
6 p8 V) ~# M8 H0 s5 w) [0 nearly childhood on pubertal development and final
( r8 v; ]5 \$ e% aadult height are not fully known and always remain
) I% p0 }7 [+ ~8 S6 g, X: Na concern. Children treated with short-term testos-
# W3 v9 G" d" Y4 @& \terone injection or topical androgen may exhibit some' ]% Q) A: V; t+ E& }4 |
acceleration of the skeletal maturation; however, after9 e0 A1 m0 n1 D$ z, x K' ]
cessation of treatment, the rate of bone maturation
2 d# ]% V1 b3 K8 Pdecelerates and gradually returns to normal.8,96 X' K7 A' w$ Q) Y$ \
There are conflicting reports and controversy" O5 K. y& C: Q4 m) [8 Y
over the effect of early androgen exposure on adult
8 A1 y# B4 ?3 ypenile length.10,11 Some reports suggest subnormal% M2 ?/ K0 @1 y! j. |2 W
adult penile length, apparently because of downreg-
, x8 |6 f$ `$ U" Y4 s7 gulation of androgen receptor number.10,12 However, |" {7 `: X; d9 v. I$ J1 R( n1 M
Sutherland et al13 did not find a correlation between
! d1 I% P+ N! p; Ochildhood testosterone exposure and reduced adult
, f6 P" [* L/ h- d* B- T0 openile length in clinical studies.
: ]" z/ |/ H) g8 m+ ?Nonetheless, we do not believe our patient is z4 @1 w8 F. {/ m8 W0 t7 `
going to experience any of the untoward effects from8 X+ ~& u Q1 t4 \6 Z
testosterone exposure as mentioned earlier because
" w6 u3 w% y3 X( ~+ |9 @the exposure was not for a prolonged period of time.1 G- z$ P* p& G) S, F; q# ]6 k8 L
Although the bone age was advanced at the time of+ n. A! N% {: U( h, v* q
diagnosis, the child had a normal growth velocity at
7 n- F* p/ y' d% U; Qthe follow-up visit. It is hoped that his final adult4 M( f0 |; A3 N, O. M- t9 h @+ c
height will not be affected.
+ b+ B, o, z% a0 |Although rarely reported, the widespread avail-9 I: o: Y, X& s+ z; f/ ^; p
ability of androgen products in our society may1 ~, W/ [( v2 k0 d3 v
indeed cause more virilization in male or female2 I |( R6 o! B @/ `* ?
children than one would realize. Exposure to andro-3 k2 q9 i7 i' M
gen products must be considered and specific ques-
' S1 Z! n1 X l7 D* m+ A# Ntioning about the use of a testosterone product or
1 G! z5 Q- ~6 w3 Wgel should be asked of the family members during
) D6 E) g# D$ @/ N, h- G1 Tthe evaluation of any children who present with vir-
- m' Z. Z( }1 a) I5 M l1 ailization or peripheral precocious puberty. The diag-9 Q: _9 C7 ]3 o& r
nosis can be established by just a few tests and by: | ~6 |" b; [9 w0 p
appropriate history. The inability to obtain such a3 A6 [/ g) h- I9 ^8 C- n4 W
history, or failure to ask the specific questions, may
+ X% Z4 \( y: Z" Bresult in extensive, unnecessary, and expensive
9 K# R! W6 U( A1 i$ _investigation. The primary care physician should be
" V: r% n$ F% l3 N7 a7 l" A1 m$ Gaware of this fact, because most of these children
2 A/ q7 v) U; ?0 B" S/ nmay initially present in their practice. The Physicians’6 A: C5 i; J, l! l
Desk Reference and package insert should also put a
$ ~ I5 A3 W: a% G6 X+ O Hwarning about the virilizing effect on a male or1 e t, e' l, h9 ]4 W
female child who might come in contact with some-
0 z5 }9 m/ l+ y( c! @% P- done using any of these products.
; q' h! ?3 N* w' _7 S# b# s* jReferences
- E* G- p5 q4 I: C3 ?8 f1. Styne DM. The testes: disorder of sexual differentiation
/ p% e, d' a2 A- Xand puberty in the male. In: Sperling MA, ed. Pediatric
7 F K; ^$ L1 I* Y7 k. IEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;5 |' \( p/ W" T3 f, N, {" J
2002: 565-628. i7 G. ^7 O2 {/ O' K: Y% O5 m
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious$ \6 f- i- N8 P# o/ v
puberty in children with tumours of the suprasellar pineal |
|