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Sexual Precocity in a 16-Month-Old7 J2 F/ t! |) r1 G; d
Boy Induced by Indirect Topical# v+ c, p8 V! }( y6 m; w$ c! O
Exposure to Testosterone
! ^3 j8 @7 @, C1 D/ KSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
% @& Z9 F+ c. B5 i" aand Kenneth R. Rettig, MD1
) g( }# q7 b: V+ D' G2 v& NClinical Pediatrics# l) B' n, I4 N. x% B B
Volume 46 Number 6- ~4 G1 I# ` V6 q4 k
July 2007 540-5431 n' \: r% R! e/ r8 o3 x, H' a* m
© 2007 Sage Publications
. Y# j9 x# y1 v10.1177/0009922806296651
+ x: _8 H" t' t, ehttp://clp.sagepub.com
! b9 x. _/ E+ H! Mhosted at4 }( t# {# U+ d
http://online.sagepub.com
i/ w- ^# I1 U: R; u) r' M$ ePrecocious puberty in boys, central or peripheral,' n2 A3 I' [: `- Y- l( I j) K0 J
is a significant concern for physicians. Central
7 y g- C7 q" Fprecocious puberty (CPP), which is mediated
1 J% B1 f" P+ x4 {5 [6 Uthrough the hypothalamic pituitary gonadal axis, has3 Q }# Q2 w" L8 q. w
a higher incidence of organic central nervous system
) m# o/ Y+ o) ~6 J7 `3 o7 ^$ O# Vlesions in boys.1,2 Virilization in boys, as manifested4 {) F! ^' j; t9 F+ \
by enlargement of the penis, development of pubic
4 k0 _% T$ E# u/ _hair, and facial acne without enlargement of testi-
7 |. \$ O |1 ~/ @cles, suggests peripheral or pseudopuberty.1-3 We3 u4 N, s: |- H4 X" x
report a 16-month-old boy who presented with the
: `& W* U1 d- k Genlargement of the phallus and pubic hair develop-( ^6 _: L3 j6 a( I9 P7 T: N
ment without testicular enlargement, which was due
- {. B4 D" }( T, b$ b+ oto the unintentional exposure to androgen gel used by
; X. c3 Q2 o$ ?, R9 C9 s3 Rthe father. The family initially concealed this infor-
" W! F$ t+ l, M- n( Nmation, resulting in an extensive work-up for this
) c. I% R2 D2 o+ v3 ^1 Xchild. Given the widespread and easy availability of
+ w4 Z$ }# a5 I1 v5 a: etestosterone gel and cream, we believe this is proba-
i" c$ k( Y' ]" t9 B) `bly more common than the rare case report in the. }2 f% p8 v; m) G0 `- y# B
literature.4
% |, K6 X2 w7 m% _* [# QPatient Report
4 b C; F- S# B* sA 16-month-old white child was referred to the
2 A9 ]! D! q0 Mendocrine clinic by his pediatrician with the concern
- X) I- d- g' ]0 c- gof early sexual development. His mother noticed6 Q v/ J" E5 S* a/ K, V5 Y
light colored pubic hair development when he was
7 |) Q+ S; d e" [/ S3 \7 zFrom the 1Division of Pediatric Endocrinology, 2University of: W8 {4 o: E2 W/ e0 |; T
South Alabama Medical Center, Mobile, Alabama.
: _" T- X# v) j, |. j$ MAddress correspondence to: Samar K. Bhowmick, MD, FACE,
4 p" e9 F/ u4 O L1 f/ Q, y2 Y: _3 wProfessor of Pediatrics, University of South Alabama, College of
9 |4 l! f$ ?4 o' H( D9 Z ?5 W& ]Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
, W" W) a% T6 x/ b1 He-mail: [email protected].8 e) Q; M Z$ a8 [+ m, @6 \! A% T
about 6 to 7 months old, which progressively became
2 P/ ^6 E3 z) [7 \darker. She was also concerned about the enlarge-2 y2 N; H3 G8 w3 [
ment of his penis and frequent erections. The child
. Z$ | I& F) R I' rwas the product of a full-term normal delivery, with. h% {( l$ B# I
a birth weight of 7 lb 14 oz, and birth length of
7 i7 Q( r. J! j& i3 l* P20 inches. He was breast-fed throughout the first year2 r" X5 }5 I3 S! K, U
of life and was still receiving breast milk along with
- f( E1 L& [2 q Lsolid food. He had no hospitalizations or surgery,, r+ |8 a- H: n
and his psychosocial and psychomotor development
# x2 W! D+ s8 |was age appropriate.
$ `7 \- Y/ S. C3 D# cThe family history was remarkable for the father,
! Z6 _8 m: w' }' o4 n2 o' Mwho was diagnosed with hypothyroidism at age 16,
2 y; ~% F+ ^5 `7 r% r. jwhich was treated with thyroxine. The father’s
- B3 u% \) m$ r4 {& @height was 6 feet, and he went through a somewhat2 B- D d/ N1 M0 C# {$ d& }+ c
early puberty and had stopped growing by age 14.4 N/ c( w. |0 s
The father denied taking any other medication. The
0 J, Y& x; H) w9 S& V( }4 O% ~child’s mother was in good health. Her menarche
2 i. K7 e _' ?, l! q5 k0 qwas at 11 years of age, and her height was at 5 feet2 l+ B& W# F* ]6 N
5 inches. There was no other family history of pre-2 D; i6 v6 U* e& t+ R
cocious sexual development in the first-degree rela-* C* B6 z" }9 C% O# A
tives. There were no siblings.
; |% }* j; E/ C: d a5 D! SPhysical Examination" p# \ Y0 Z$ ^5 [7 j1 M" ?. |* B
The physical examination revealed a very active,
+ I/ m/ R0 H; }7 a8 q, A' g H- V1 j8 Lplayful, and healthy boy. The vital signs documented
6 h) c" l, L' da blood pressure of 85/50 mm Hg, his length was
2 p/ G% V, V/ h. \7 i90 cm (>97th percentile), and his weight was 14.4 kg
7 Z0 N. `* W$ o$ k9 e1 e(also >97th percentile). The observed yearly growth
8 b! g H( _5 Vvelocity was 30 cm (12 inches). The examination of" t6 ~8 i& ^% r( r$ K
the neck revealed no thyroid enlargement.# ]$ F' P* t4 u( B8 _
The genitourinary examination was remarkable for7 l+ \( J* z0 m4 H9 ^4 g! W
enlargement of the penis, with a stretched length of' h* ?; _3 R3 X9 O, f w* H
8 cm and a width of 2 cm. The glans penis was very well
/ _0 V+ g" Q3 `' X* Gdeveloped. The pubic hair was Tanner II, mostly around
% F# O: _ Y9 W3 ]6 d; a m540) n4 j# k/ ~ D4 D0 U5 W
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
" [( S; A+ N) D& othe base of the phallus and was dark and curled. The
/ R8 ^1 k' ~: ]( a, C9 jtesticular volume was prepubertal at 2 mL each.' y: B- k: _% g9 T8 V8 J
The skin was moist and smooth and somewhat5 d, D8 J- ]5 b1 _$ u: D
oily. No axillary hair was noted. There were no
. n' T* V$ C4 u3 h) D! v' V) xabnormal skin pigmentations or café-au-lait spots.' w3 m( `( S2 {" X* M7 e
Neurologic evaluation showed deep tendon reflex 2+& d" n3 O3 s- n- N5 {
bilateral and symmetrical. There was no suggestion& L, O+ K; {$ T* l
of papilledema.
' z- Y C/ G4 GLaboratory Evaluation# r6 e# N" }8 ?3 F) T8 V& F f, l* Y
The bone age was consistent with 28 months by8 F& M5 n# q3 K+ g5 S5 \) }
using the standard of Greulich and Pyle at a chrono-$ a) {. C+ `1 W
logic age of 16 months (advanced).5 Chromosomal
! U f1 u. N! _! R* K: R5 {2 kkaryotype was 46XY. The thyroid function test. p* O: R: o4 Q4 i5 V
showed a free T4 of 1.69 ng/dL, and thyroid stimu-+ p G# o- u& ~
lating hormone level was 1.3 µIU/mL (both normal).
3 h! J7 h- S/ CThe concentrations of serum electrolytes, blood* u2 P" t, L; L+ Q2 r. P+ l G+ f
urea nitrogen, creatinine, and calcium all were
2 V0 x- }) @7 b/ O& qwithin normal range for his age. The concentration j# O3 t. c$ l4 p) d! |- V, i
of serum 17-hydroxyprogesterone was 16 ng/dL4 o" e( B8 v N+ @4 `
(normal, 3 to 90 ng/dL), androstenedione was 20
. h0 o9 ?8 U9 | lng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
: }2 [8 e& s" qterone was 38 ng/dL (normal, 50 to 760 ng/dL),
+ \# ?; R, s- Wdesoxycorticosterone was 4.3 ng/dL (normal, 7 to3 b& s9 i/ q$ }% ?, p1 A" ]
49ng/dL), 11-desoxycortisol (specific compound S)
9 H( E" \6 N0 C6 S: qwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-$ M9 u9 j/ g9 y+ @: s& Z& P
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
* T. b+ a! U# N7 i6 Ytestosterone was 60 ng/dL (normal <3 to 10 ng/dL),& [9 y! K& T. R+ ]
and β-human chorionic gonadotropin was less than: B. A0 @/ {5 J9 X; `, h8 z
5 mIU/mL (normal <5 mIU/mL). Serum follicular
9 Z# ]5 U* |& N5 }9 `. Jstimulating hormone and leuteinizing hormone2 |- ]% }; c8 w" m$ V5 P. E
concentrations were less than 0.05 mIU/mL
7 Y* u$ j' S1 t0 |* }) `, L(prepubertal).
6 G( n4 p0 N _% ~9 _The parents were notified about the laboratory6 f6 ?. q. ]4 D. S& A) r7 w- U u
results and were informed that all of the tests were
3 E. J( @ L5 Hnormal except the testosterone level was high. The: ^ k! o# v$ H" R/ |+ g3 v
follow-up visit was arranged within a few weeks to* D% Z: C- c2 n; c- A, \
obtain testicular and abdominal sonograms; how-
2 J* y* M, J6 @# q1 h* d4 Aever, the family did not return for 4 months.
& i( Z/ d% ~3 J7 T ^9 @ `Physical examination at this time revealed that the
; V$ \; s1 v0 E- v, nchild had grown 2.5 cm in 4 months and had gained/ N" e6 v5 Q7 y& z, S
2 kg of weight. Physical examination remained, d3 u3 M: H( e
unchanged. Surprisingly, the pubic hair almost com-
2 U% Q; l$ j3 k2 z# N2 z, Dpletely disappeared except for a few vellous hairs at4 R. \, u, |& _3 B
the base of the phallus. Testicular volume was still 2
" q- J( o8 U5 Q" K8 P+ fmL, and the size of the penis remained unchanged.
# d5 \1 G7 X7 P; x; q qThe mother also said that the boy was no longer hav-8 D- M- \7 |4 R: V( m" w2 K* D
ing frequent erections./ B5 n2 O- p( T) r% k
Both parents were again questioned about use of0 u; T' y. o# c
any ointment/creams that they may have applied to2 _+ w6 m( [; m4 u
the child’s skin. This time the father admitted the& j0 |# Y+ i" m7 D( Q1 j+ n
Topical Testosterone Exposure / Bhowmick et al 541
7 u- s# [4 _ {. V' \/ J tuse of testosterone gel twice daily that he was apply-% ^9 `. _+ Z8 g( T# t; s. f3 o; }& h
ing over his own shoulders, chest, and back area for$ P* O5 h* }" S
a year. The father also revealed he was embarrassed
8 f. X5 I4 \2 E. Y+ H1 Bto disclose that he was using a testosterone gel pre-
$ q/ U& ~/ F& `scribed by his family physician for decreased libido
+ j: o6 J2 i4 w8 X; v5 Dsecondary to depression.6 u7 G) S& c( O
The child slept in the same bed with parents.
; u* l# ]/ p, g" L ^The father would hug the baby and hold him on his
( t+ ]9 ?' P6 Y$ n# ~" Dchest for a considerable period of time, causing sig- S9 R$ T' Q1 A% h8 I' ] Y* j
nificant bare skin contact between baby and father.* Q2 ?) o6 ]. ]% c0 o% F; s
The father also admitted that after the phone call,
& O8 L& k1 @8 `: Rwhen he learned the testosterone level in the baby/ x5 z- x; ~, s1 B! p) L0 P# @
was high, he then read the product information
2 m; i. t2 f: L# G4 s6 ^! Vpacket and concluded that it was most likely the rea-
* A: V1 S* Z0 W* a' Q6 F- E7 Uson for the child’s virilization. At that time, they
* O, n$ l6 ]: T4 W+ Bdecided to put the baby in a separate bed, and the
. C6 x* y* s) q5 x4 ?. `3 v5 s8 j3 _$ |father was not hugging him with bare skin and had7 B* D% N" }( G
been using protective clothing. A repeat testosterone
% ^) Y5 |: `0 K! Vtest was ordered, but the family did not go to the/ K8 f/ [/ r( I
laboratory to obtain the test.
, L+ d+ U0 N( \! B3 ~, ^; }& hDiscussion
8 e2 K. e# ~* pPrecocious puberty in boys is defined as secondary
/ N6 o' L3 w9 S1 q0 \- Q* D: s1 Xsexual development before 9 years of age.1,4
( L$ A, Q" X: @2 n* }' @, j$ aPrecocious puberty is termed as central (true) when
/ f. g# }9 V! y5 _/ t2 y" l7 T* Kit is caused by the premature activation of hypo-
/ s" i" H x; w* u7 o* `% rthalamic pituitary gonadal axis. CPP is more com-
" @" X1 {7 x" q; |mon in girls than in boys.1,3 Most boys with CPP
L7 C) \* k) s4 q' |7 Cmay have a central nervous system lesion that is7 T3 S0 s& ]$ F: u5 K. m. G
responsible for the early activation of the hypothal-
; T1 ~ S. M' E) g$ Lamic pituitary gonadal axis.1-3 Thus, greater empha-+ c$ U1 w8 f% Z
sis has been given to neuroradiologic imaging in U. W6 ~3 K4 T, B
boys with precocious puberty. In addition to viril-$ R3 G$ p- V) t2 H
ization, the clinical hallmark of CPP is the symmet-7 k$ H t8 Q: f
rical testicular growth secondary to stimulation by% |5 x* a( t$ y
gonadotropins.1,3* g( c: P: A" U7 }8 r6 W
Gonadotropin-independent peripheral preco-
( u+ U3 f, ^% s4 ], k H. Jcious puberty in boys also results from inappropriate
& C( S6 ]# B- \7 A$ u3 }" landrogenic stimulation from either endogenous or
( B6 j* l' n" N+ Q5 E; Kexogenous sources, nonpituitary gonadotropin stim-, C; V0 m4 X9 C+ t. |* I, Q! G
ulation, and rare activating mutations.3 Virilizing
3 Q5 q2 B' H* ^: t- Y- p8 ~congenital adrenal hyperplasia producing excessive
1 V; `+ ?% t" f- k0 Y$ eadrenal androgens is a common cause of precocious4 g! F& u7 D, U3 S, C
puberty in boys.3,4
0 F7 m9 k% s, x8 R, NThe most common form of congenital adrenal1 g! `' H4 i7 Z. v
hyperplasia is the 21-hydroxylase enzyme deficiency.' R! F8 _9 S P- W: j- m
The 11-β hydroxylase deficiency may also result in: n& x( o0 t5 t5 r( g
excessive adrenal androgen production, and rarely,% J3 t/ M6 [" E) o
an adrenal tumor may also cause adrenal androgen" d8 A6 _' S, Y, o- x
excess.1,3. ~4 W6 J( V+ D: A' A
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from$ U, T7 e s. y; c: o. x8 c
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007# e1 r/ s7 N! Y, M
A unique entity of male-limited gonadotropin- j& F6 g K: W( r& y! |
independent precocious puberty, which is also known& D) ~4 h4 U+ |2 N
as testotoxicosis, may cause precocious puberty at a' ^! \' @4 j i. K7 s2 s0 P
very young age. The physical findings in these boys
$ h4 b! ~: T( h9 c5 [$ Swith this disorder are full pubertal development,
. i3 [- l1 r& S# W wincluding bilateral testicular growth, similar to boys
1 p% m0 \5 a4 j3 q1 F2 k6 e$ Z' d0 ewith CPP. The gonadotropin levels in this disorder
" w8 s. C# R* y. d% T kare suppressed to prepubertal levels and do not show% P& h# B* D% `% h: n% {
pubertal response of gonadotropin after gonadotropin-9 v6 m: g* c7 n: J) a' q
releasing hormone stimulation. This is a sex-linked
4 F7 u! g5 I' N `" D ` c6 Zautosomal dominant disorder that affects only6 N2 I7 Y) ^' n0 E3 E
males; therefore, other male members of the family
# x2 d0 E3 |5 u" m$ Dmay have similar precocious puberty.3
. M N& u+ }6 b+ F( a5 L# J) cIn our patient, physical examination was incon-& i; f. H* e% f- ]( B: E f# h
sistent with true precocious puberty since his testi-9 L7 }6 r& `" C# J& s0 H
cles were prepubertal in size. However, testotoxicosis6 J' q' y5 t" C. R! K: A ?1 p
was in the differential diagnosis because his father
7 p( {! E9 m: ~+ x; W! Q- pstarted puberty somewhat early, and occasionally,
. z2 x9 x" q; N. ]' Qtesticular enlargement is not that evident in the1 V9 n5 `+ K( Z/ p) l* d
beginning of this process.1 In the absence of a neg-
" k$ ], A7 V/ Aative initial history of androgen exposure, our4 R; F9 E/ h1 ~8 Z+ i
biggest concern was virilizing adrenal hyperplasia, P" L2 B8 \0 D6 R5 W J
either 21-hydroxylase deficiency or 11-β hydroxylase
- V, r8 M; m" Jdeficiency. Those diagnoses were excluded by find-
! h W: h* K( i$ K: xing the normal level of adrenal steroids.5 [1 }2 x! @+ t
The diagnosis of exogenous androgens was strongly* v; M( _% ~: s: }! L2 L
suspected in a follow-up visit after 4 months because9 ^) ?, |8 v. T9 m9 {1 F
the physical examination revealed the complete disap-
2 B0 i$ h* G9 _" R( H" bpearance of pubic hair, normal growth velocity, and) ~) B S! ?% K8 ?5 p
decreased erections. The father admitted using a testos-" N: X/ p; o f1 l5 r- g
terone gel, which he concealed at first visit. He was4 m6 m8 J0 w$ D) s* N$ v
using it rather frequently, twice a day. The Physicians’
# L3 G+ w S0 c+ F$ F; Q8 ~Desk Reference, or package insert of this product, gel or
! K$ Z( T& Z( r0 I1 k6 E3 {& jcream, cautions about dermal testosterone transfer to) h0 K" X1 z4 e4 e# q
unprotected females through direct skin exposure.
9 j7 H M( z- x4 t$ ASerum testosterone level was found to be 2 times the2 ^& g* \, f' Q6 [8 W
baseline value in those females who were exposed to0 @/ W6 Y+ e8 t. n
even 15 minutes of direct skin contact with their male
- u( M9 q4 ~8 ^- ?partners.6 However, when a shirt covered the applica-
8 v" S4 M: ?# y9 ?" e4 Ltion site, this testosterone transfer was prevented.
2 R- z$ \* M$ s9 a7 mOur patient’s testosterone level was 60 ng/mL, ?$ v) ?) o# K
which was clearly high. Some studies suggest that! F- `: v# O4 k4 N) K B( ^) F
dermal conversion of testosterone to dihydrotestos-
3 \" b0 ^1 U: B% w3 F: qterone, which is a more potent metabolite, is more3 J! h( o, O5 o+ G
active in young children exposed to testosterone
. K3 o5 w. X5 ^4 oexogenously7; however, we did not measure a dihy-
1 E" C0 I- o* t3 S9 Y' s( M/ J- Kdrotestosterone level in our patient. In addition to
& {& V* J* E. T) D: p" T6 B6 Yvirilization, exposure to exogenous testosterone in
' u7 L a' T. s3 jchildren results in an increase in growth velocity and. p: c% J+ _! _
advanced bone age, as seen in our patient.
0 p% d) ]7 \$ Z. Z: F% V# J3 VThe long-term effect of androgen exposure during. r$ c: ^3 a J5 U& _
early childhood on pubertal development and final3 v h, Y; e0 B' V
adult height are not fully known and always remain. k) k; \" S( `) J
a concern. Children treated with short-term testos-
+ ~5 P. [# w( b* p \; R+ Rterone injection or topical androgen may exhibit some/ \6 M4 G- n2 ]
acceleration of the skeletal maturation; however, after
8 Z. z! _4 {0 v$ }6 I+ @cessation of treatment, the rate of bone maturation; X4 I- ]# p9 |
decelerates and gradually returns to normal.8,9
0 V. m' @7 v% KThere are conflicting reports and controversy
' a9 d) N3 d. k* uover the effect of early androgen exposure on adult- e9 V0 h' s+ W* |2 b
penile length.10,11 Some reports suggest subnormal
' P7 s; \, h6 E, ]adult penile length, apparently because of downreg-" O9 C& v0 {, Q3 R2 N5 J
ulation of androgen receptor number.10,12 However,
: z4 K6 `$ B% _* S3 {( ESutherland et al13 did not find a correlation between) S, ~: X# }& z, K3 D3 E/ g4 t
childhood testosterone exposure and reduced adult$ c" i. }+ U$ x- A% n8 q) w
penile length in clinical studies.1 O; D; s' K4 J k
Nonetheless, we do not believe our patient is
- E9 c1 ~6 G! U" fgoing to experience any of the untoward effects from& \$ o7 t* b6 d$ \' b; C+ c/ f& M: c
testosterone exposure as mentioned earlier because0 w: T' Z0 r$ v; j3 a
the exposure was not for a prolonged period of time.
$ j2 m1 Y8 o A* X' I) X- _Although the bone age was advanced at the time of2 g# ]0 B% @4 A# c
diagnosis, the child had a normal growth velocity at
% x* d. H6 w& D5 Hthe follow-up visit. It is hoped that his final adult
4 X. b& W; z* [height will not be affected.
$ V: L6 {8 m0 Y6 @Although rarely reported, the widespread avail-) c! |4 [2 d+ _
ability of androgen products in our society may" {0 g7 \$ h! E# E& u+ B/ f& J, K
indeed cause more virilization in male or female
9 i* M9 A- V! |children than one would realize. Exposure to andro-$ n' e0 B1 S. k* i- d1 t) p6 v {
gen products must be considered and specific ques-; d) ]9 H9 m3 S3 m% B5 e
tioning about the use of a testosterone product or& r$ `! K4 y+ T: b
gel should be asked of the family members during
" ?9 w& V8 m K% L& P) othe evaluation of any children who present with vir-; M. h- l2 c6 @( l
ilization or peripheral precocious puberty. The diag-
4 [0 j, l! [0 E0 I3 mnosis can be established by just a few tests and by
$ B3 G! _, u- x. t& nappropriate history. The inability to obtain such a
( V4 O. r& R: Thistory, or failure to ask the specific questions, may7 Y z% Y i2 @0 Z, I4 W) ]1 ^( x: p, T
result in extensive, unnecessary, and expensive0 h3 Z' J" B1 o
investigation. The primary care physician should be6 Y0 U4 r5 s! t( ?+ I% m
aware of this fact, because most of these children c' [) `# N9 P$ u+ c6 U/ P
may initially present in their practice. The Physicians’ X' g* E+ D- L3 N1 Q* r
Desk Reference and package insert should also put a5 X% k, Y0 q0 ^: W
warning about the virilizing effect on a male or ?: S0 z' `9 ^8 f8 O( N" n
female child who might come in contact with some-
6 D8 p# p; S4 j( t8 Xone using any of these products.
4 F0 Q6 _' l E X8 {% n4 XReferences
- N# P: g8 r w9 I z6 z3 f3 z: Q1. Styne DM. The testes: disorder of sexual differentiation" w0 G8 U, [+ l
and puberty in the male. In: Sperling MA, ed. Pediatric: U2 L, l2 G( n6 k
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders; l+ J& A$ r" e. l+ x
2002: 565-628.. H d# Q; \0 Y% l! ~
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
: N4 T: [& v. Epuberty in children with tumours of the suprasellar pineal |
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