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Sexual Precocity in a 16-Month-Old
$ E% H5 k. F& Y3 s: f" i2 \* D% ?Boy Induced by Indirect Topical
( o% L& ]: {8 o9 aExposure to Testosterone
. t1 h& q( U M# sSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
, v, k' @# ^, E$ i2 O5 k9 f, Y( `, Oand Kenneth R. Rettig, MD1
3 q- F! C' x+ H# j! u2 }8 sClinical Pediatrics! W/ p7 X. }* C8 X1 u% m, ^/ [1 q
Volume 46 Number 6" v( C: }7 J; F0 H8 M% L3 x
July 2007 540-543, j p T7 Y5 Q. G
© 2007 Sage Publications
# b: `8 Q" g, ], S1 ~10.1177/0009922806296651 p) I# ~( Y9 l$ K% G+ {5 `. F
http://clp.sagepub.com2 v5 k* w- k: |; G- W3 t% f- ]
hosted at7 E, z6 W# A# k9 U$ r+ b
http://online.sagepub.com
9 w; P2 Y8 L* R; nPrecocious puberty in boys, central or peripheral,
8 P' k5 I' C2 dis a significant concern for physicians. Central
; X) a% N! p7 i: vprecocious puberty (CPP), which is mediated
- k- | p6 U8 [' [$ s1 a( ?through the hypothalamic pituitary gonadal axis, has e) G5 ?/ |) C
a higher incidence of organic central nervous system- d6 @4 f c6 e, ~5 v
lesions in boys.1,2 Virilization in boys, as manifested; P5 M* w& V! Y4 i6 p1 q ]
by enlargement of the penis, development of pubic& t0 e3 f/ _6 Q% Z
hair, and facial acne without enlargement of testi-! }$ A# R2 B) C2 \, \% \
cles, suggests peripheral or pseudopuberty.1-3 We0 ]' C( M) R; ]+ g7 G
report a 16-month-old boy who presented with the3 Q) [5 [0 [: d/ p0 L
enlargement of the phallus and pubic hair develop-
* K- c$ {# N% a$ v* g# b1 mment without testicular enlargement, which was due
( W' D+ I/ f3 {2 m) @to the unintentional exposure to androgen gel used by3 x, T- _- U* r, j" @
the father. The family initially concealed this infor-% _+ Z! x1 G+ m2 ~' G6 F) O
mation, resulting in an extensive work-up for this
) p- u7 j, a5 V; Schild. Given the widespread and easy availability of
4 m1 c: B3 {/ @6 ~; _testosterone gel and cream, we believe this is proba-, V2 X: A* q: }% i. |5 `# \
bly more common than the rare case report in the6 K% H7 Y& b3 K5 j! H% s
literature.49 X. v6 W/ C, ^
Patient Report: A- M+ c; ^0 ^( G+ ?% I! l0 p
A 16-month-old white child was referred to the& l# S# t+ l& X' L% b- ~, Q
endocrine clinic by his pediatrician with the concern
7 s: P' F8 F# u' u7 M9 s! Zof early sexual development. His mother noticed
% ]5 j1 O3 p8 N+ \light colored pubic hair development when he was
; h1 r. O9 Q2 t9 Z: {9 a tFrom the 1Division of Pediatric Endocrinology, 2University of$ A6 o( V! q# f6 K
South Alabama Medical Center, Mobile, Alabama.& T) ]3 l% Z2 M
Address correspondence to: Samar K. Bhowmick, MD, FACE,
- ?, U! I, o) o3 t( E0 uProfessor of Pediatrics, University of South Alabama, College of' j0 g& V2 k- p+ X, w$ d
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;: h; t) ^4 p. |3 m% T, v
e-mail: [email protected].$ p4 Q: h: G- r
about 6 to 7 months old, which progressively became2 x" o; M) l' Q0 ^6 @; N( Z/ t
darker. She was also concerned about the enlarge-& W( O5 f" u$ L
ment of his penis and frequent erections. The child I9 p0 U1 t3 h: p. E
was the product of a full-term normal delivery, with/ z6 P% o1 `5 K1 Y
a birth weight of 7 lb 14 oz, and birth length of
+ N5 s/ D `, `3 u1 w4 ~0 [: n20 inches. He was breast-fed throughout the first year9 x- a5 w/ V; A% U) W1 b: b
of life and was still receiving breast milk along with
. H" b( U) _& t3 z: `solid food. He had no hospitalizations or surgery,* `8 Q; a. I B0 l
and his psychosocial and psychomotor development
$ F6 v% W2 h1 n/ s) n' Wwas age appropriate.
4 a% k3 J7 U6 j" ]/ HThe family history was remarkable for the father,
- K) c# W( M2 D5 [5 j& xwho was diagnosed with hypothyroidism at age 16,
: r- c/ ?; z8 U- M6 Qwhich was treated with thyroxine. The father’s
% N" f& K& h( r7 r- T6 F$ ^height was 6 feet, and he went through a somewhat) l9 [5 k: h6 C4 F( A' D' a
early puberty and had stopped growing by age 14.
, Q( Q" G* L4 ~# F! M/ x, bThe father denied taking any other medication. The
4 M) R2 {4 _' z( H+ }! Y! Vchild’s mother was in good health. Her menarche) K |% |, M: X
was at 11 years of age, and her height was at 5 feet
0 Z0 ]7 r' [! p- Q% l. F# c/ \3 Y5 inches. There was no other family history of pre-
; w! O1 T' ~/ g7 l# T) wcocious sexual development in the first-degree rela-
& }' ~" A' ~5 J& I: btives. There were no siblings.
8 D5 n) `5 j) l( k3 ~$ W/ {4 A3 ZPhysical Examination
0 x; K8 t# P" B0 jThe physical examination revealed a very active,
/ L$ u9 f% ~0 B( Lplayful, and healthy boy. The vital signs documented
1 a9 M! Y6 A1 U( q; M Ja blood pressure of 85/50 mm Hg, his length was
7 T" T" _1 F2 u, F$ y; M& t2 r90 cm (>97th percentile), and his weight was 14.4 kg
1 M7 N8 O; R/ J' i* n3 @(also >97th percentile). The observed yearly growth( u( b9 d) K' f/ {
velocity was 30 cm (12 inches). The examination of- r; k1 U* w% H+ n7 \
the neck revealed no thyroid enlargement.
w0 J6 R' F O0 A4 b3 fThe genitourinary examination was remarkable for; u0 s" r, x$ ?) s3 Z
enlargement of the penis, with a stretched length of
0 N) y. `/ v7 G6 T8 e0 U0 ~8 cm and a width of 2 cm. The glans penis was very well- f, Q& d( {9 _& Z/ J
developed. The pubic hair was Tanner II, mostly around3 m0 K5 F, O% v/ G" y
540" J& h, S+ @) B: W3 ~: _6 d$ Y2 e
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from) U0 W6 q3 n1 A/ \" G
the base of the phallus and was dark and curled. The
' o" J" C% N4 Stesticular volume was prepubertal at 2 mL each.; g& Z8 C2 K, P4 Z, H4 Y" B/ _7 ~
The skin was moist and smooth and somewhat& ^, u/ O) m e
oily. No axillary hair was noted. There were no( w+ d2 \" J' P( K" \0 K' w" h' [2 F
abnormal skin pigmentations or café-au-lait spots.
# M! b4 |$ N3 e* r1 j% u+ J) RNeurologic evaluation showed deep tendon reflex 2+5 Y5 h, A, U, R4 g
bilateral and symmetrical. There was no suggestion; @5 N* H2 |7 p" w, p5 N2 N9 d% l
of papilledema.
" h) F% t% ~ _) Y) n8 YLaboratory Evaluation
3 E/ o# F# r, }: qThe bone age was consistent with 28 months by
" o6 |; @) Z! o8 Kusing the standard of Greulich and Pyle at a chrono-
% b6 h2 Y/ Q" ]logic age of 16 months (advanced).5 Chromosomal
- D) {7 D3 C; k; T/ @karyotype was 46XY. The thyroid function test9 t4 }# s1 i/ v' L$ b+ K0 B% Z9 t! e
showed a free T4 of 1.69 ng/dL, and thyroid stimu-" z4 C, f* k5 s7 W V4 G* f
lating hormone level was 1.3 µIU/mL (both normal).
4 {; ?" A8 H: eThe concentrations of serum electrolytes, blood6 y: }4 S' i: R, _% ?) G5 U
urea nitrogen, creatinine, and calcium all were% o) t/ S! P# F
within normal range for his age. The concentration _7 [5 | b$ m1 H
of serum 17-hydroxyprogesterone was 16 ng/dL0 ?6 {5 C' Q( m
(normal, 3 to 90 ng/dL), androstenedione was 202 z* c' u o# B0 Z' o9 h8 y8 A
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
' M2 i6 `& o- T. B* A/ fterone was 38 ng/dL (normal, 50 to 760 ng/dL),& B) P) e/ [- K% ]1 X
desoxycorticosterone was 4.3 ng/dL (normal, 7 to/ `8 S2 c7 S) |$ F; k4 ? E
49ng/dL), 11-desoxycortisol (specific compound S)
. R) Z7 l4 v* V& L) t$ r. pwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
5 }! L V2 K9 _; a5 _( ztisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total4 b2 @$ s- d0 W# r: t
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),4 k+ Z8 O1 P* q. Y* x( ~: e- I
and β-human chorionic gonadotropin was less than
, ~8 c s$ Y* p; q: ?+ D2 y5 mIU/mL (normal <5 mIU/mL). Serum follicular
0 o7 G. B$ ]2 D9 J2 [" u) Kstimulating hormone and leuteinizing hormone
; z' X" I6 t9 U% mconcentrations were less than 0.05 mIU/mL- Y f0 T c9 \, A8 c
(prepubertal).
% B8 S! M* @ {+ f6 @The parents were notified about the laboratory
5 N0 l& K& A8 ~$ G ]0 gresults and were informed that all of the tests were# n' \" n+ Y9 P2 n
normal except the testosterone level was high. The
! s* }/ m! U3 ?% `# b0 B8 d& N/ n; tfollow-up visit was arranged within a few weeks to' I* d6 ?, {3 ~# K8 f
obtain testicular and abdominal sonograms; how-9 t f: M: G* `5 M$ i" o5 @5 |
ever, the family did not return for 4 months.3 L! G. |. D% u0 n, W1 V
Physical examination at this time revealed that the& H9 H; F9 P* o' B
child had grown 2.5 cm in 4 months and had gained
6 D4 |/ B0 v y6 y* d2 kg of weight. Physical examination remained( z, d7 C+ |5 R+ t6 D) J
unchanged. Surprisingly, the pubic hair almost com-
; v# A# d, V3 s8 ^4 Apletely disappeared except for a few vellous hairs at( E" k# @9 \7 ^. }; S9 u8 _
the base of the phallus. Testicular volume was still 2
/ _: j" o8 ]& \+ W! y& dmL, and the size of the penis remained unchanged.9 |4 T" a+ N, m, k9 r
The mother also said that the boy was no longer hav-
! \3 [; |! G6 qing frequent erections.
8 a5 x e0 T5 n% W+ FBoth parents were again questioned about use of4 L7 i0 s; f( @' t% |/ i, a
any ointment/creams that they may have applied to4 A0 L- x8 q+ x. \* G+ D0 n) O
the child’s skin. This time the father admitted the
" I5 S3 ?+ E5 }0 E) p' Y, UTopical Testosterone Exposure / Bhowmick et al 541
1 \! G2 z/ D2 _% Guse of testosterone gel twice daily that he was apply-
+ e- u, ?: Z: T0 ding over his own shoulders, chest, and back area for$ v- Z. t' _- p d
a year. The father also revealed he was embarrassed
& ~' O# O5 m" W- Sto disclose that he was using a testosterone gel pre-
/ Y e# D/ d& J& U7 M* ^- x3 bscribed by his family physician for decreased libido9 b* \+ D" m* e2 J: Q$ V
secondary to depression.% P, D0 O" C* h" t: |0 Q3 b- S" h% T
The child slept in the same bed with parents.* h5 ~( G/ l0 m- a5 ?/ }9 q
The father would hug the baby and hold him on his
* k& Q5 I# e5 h2 L( Fchest for a considerable period of time, causing sig-( h# k: \9 D- O6 }
nificant bare skin contact between baby and father.
, E# C: _5 h7 A5 s# L$ |# EThe father also admitted that after the phone call,: h- s+ ]6 {$ q# h/ u5 h: G. u2 F
when he learned the testosterone level in the baby' R; ?- w1 y2 C; l, @7 c
was high, he then read the product information
( w+ |" M2 H+ A" ~4 P1 Lpacket and concluded that it was most likely the rea-
/ I# S- L( e# V$ I" w4 y( Json for the child’s virilization. At that time, they1 E$ c- y r* { I8 }0 H
decided to put the baby in a separate bed, and the H- c6 }# e, s9 C* @8 F
father was not hugging him with bare skin and had, o8 l: I& |8 J: j9 v! {0 e
been using protective clothing. A repeat testosterone
$ ?3 z& s* k- G( q$ A3 \/ ^; dtest was ordered, but the family did not go to the7 h; ]2 z5 S7 ?: Y4 I8 s6 {% d
laboratory to obtain the test.
N. ?9 z1 W$ {; g5 ~Discussion
n: \% m7 {) x) b0 `Precocious puberty in boys is defined as secondary3 [( K* o: M% y2 H7 b. n' v' F. @
sexual development before 9 years of age.1,4
W* k( J: W( @+ \+ C* mPrecocious puberty is termed as central (true) when. i3 B; {1 U5 z
it is caused by the premature activation of hypo-
1 h/ A/ C- v8 }( {4 b* Pthalamic pituitary gonadal axis. CPP is more com-8 b1 y" F' ` R& p: K* @
mon in girls than in boys.1,3 Most boys with CPP
( N2 j, u- S- x$ g( c; Gmay have a central nervous system lesion that is
( B8 C2 A. p! uresponsible for the early activation of the hypothal-
, ?- I, u% ?( ]7 V% Z7 jamic pituitary gonadal axis.1-3 Thus, greater empha-9 \7 q/ k" H S* m7 {- U) R
sis has been given to neuroradiologic imaging in
0 T$ v* ?, [7 i, O% o4 n2 L9 Jboys with precocious puberty. In addition to viril-# {0 G8 S; m1 z x6 g# c
ization, the clinical hallmark of CPP is the symmet-
6 X9 y4 P! N* _4 i/ ^# {$ r5 O% K; ?) Krical testicular growth secondary to stimulation by
# F- p$ O. Q$ E* xgonadotropins.1,3
! R+ G; L; N8 X( T. H& P+ _/ eGonadotropin-independent peripheral preco-. @5 q! l3 \; r- d7 r: u4 k
cious puberty in boys also results from inappropriate
5 H7 {# p+ y! C; ?) C j: Gandrogenic stimulation from either endogenous or
( Q. ^: D6 `1 I4 n" |exogenous sources, nonpituitary gonadotropin stim-
' L. D/ ]- Y, j4 I# L) Yulation, and rare activating mutations.3 Virilizing
. k% Z3 N/ I" w6 ucongenital adrenal hyperplasia producing excessive& Y9 Z0 }' D/ O: D9 |) d X
adrenal androgens is a common cause of precocious6 P8 N C+ @, w& e
puberty in boys.3,4* B- ]7 A+ h0 H( n. ^# D
The most common form of congenital adrenal
( ~1 K1 {4 r9 K4 X3 A% ^hyperplasia is the 21-hydroxylase enzyme deficiency.
8 `- |" e4 p# t' o' WThe 11-β hydroxylase deficiency may also result in
6 t1 E; o0 e2 [8 ~+ vexcessive adrenal androgen production, and rarely,
$ K7 r" u9 g b' Tan adrenal tumor may also cause adrenal androgen
/ m( _6 f8 K2 texcess.1,3
3 Z* g# v% H3 l! \' c9 Mat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
$ `0 s9 K& y C m- t( O* ^542 Clinical Pediatrics / Vol. 46, No. 6, July 20075 h: A! q4 T7 U3 W2 J
A unique entity of male-limited gonadotropin-# H. J, W' h6 N, e+ H! V( H
independent precocious puberty, which is also known
: f4 s- _( N$ k/ x0 mas testotoxicosis, may cause precocious puberty at a
' t* o# s9 p! ^. t( n5 P0 Z7 ?% y2 nvery young age. The physical findings in these boys
1 i1 ]: Y1 W+ f) \2 P2 V! awith this disorder are full pubertal development,
( w0 G, J S" ~$ @) Hincluding bilateral testicular growth, similar to boys
4 ^( q) ^( Z6 Zwith CPP. The gonadotropin levels in this disorder
; V* f( W- O' rare suppressed to prepubertal levels and do not show0 y2 G; ^: T2 d0 i( }' e
pubertal response of gonadotropin after gonadotropin-
* p8 b& l o/ N* w) b* X6 o7 freleasing hormone stimulation. This is a sex-linked. |2 S0 p& o1 c; v( a
autosomal dominant disorder that affects only; p y& ]7 _4 y& M; |0 _" [8 Z
males; therefore, other male members of the family; r* `' V" C6 [( l9 @$ H5 U9 m
may have similar precocious puberty.3) z" U9 t% |5 J$ A; s9 {
In our patient, physical examination was incon-) x2 J& F6 Q2 l9 B8 g1 f" g) k5 a
sistent with true precocious puberty since his testi-. `7 o1 W; w/ @
cles were prepubertal in size. However, testotoxicosis
# f2 v7 s/ v# s) \! Rwas in the differential diagnosis because his father
5 a* h V1 N' z3 c Q* q; ystarted puberty somewhat early, and occasionally,
' K1 a4 e6 z8 F* v6 L4 Htesticular enlargement is not that evident in the0 p! ?) o; d9 H+ j0 N/ M; i# S
beginning of this process.1 In the absence of a neg-
: A: T/ d$ S5 T0 E$ q1 m, Pative initial history of androgen exposure, our _' e1 O1 e+ g; z, d" S. t
biggest concern was virilizing adrenal hyperplasia, c* R& L8 ~9 x6 \
either 21-hydroxylase deficiency or 11-β hydroxylase$ l9 U. Q# k8 ?6 L3 ~
deficiency. Those diagnoses were excluded by find-! S2 u+ @5 d2 z5 k
ing the normal level of adrenal steroids./ E* W/ r4 A7 C ?
The diagnosis of exogenous androgens was strongly8 u( m9 w% K9 K$ i( g
suspected in a follow-up visit after 4 months because
1 l9 O3 T4 \ }6 s1 B9 v% sthe physical examination revealed the complete disap-
; S2 n0 f+ l$ A1 B" j5 A: M! Y0 z; zpearance of pubic hair, normal growth velocity, and
0 F. ^2 T& O! I$ Sdecreased erections. The father admitted using a testos-
! {" ^+ L B# Bterone gel, which he concealed at first visit. He was$ _: t, `+ @- S
using it rather frequently, twice a day. The Physicians’3 `) H2 K: \4 R" ^
Desk Reference, or package insert of this product, gel or
9 Y3 G2 i/ S7 T; I3 `cream, cautions about dermal testosterone transfer to! p' L8 r2 }3 C7 O& T
unprotected females through direct skin exposure.
4 h8 c) P8 }1 U6 FSerum testosterone level was found to be 2 times the
# ]( C7 D% g1 @: H+ {- v) N2 @8 _baseline value in those females who were exposed to
/ D6 |3 j% j4 [$ Y* i$ D7 `even 15 minutes of direct skin contact with their male* f& K o" D7 h2 ]
partners.6 However, when a shirt covered the applica-
4 O i1 M* g. Wtion site, this testosterone transfer was prevented.
& I# i3 _+ a% X" iOur patient’s testosterone level was 60 ng/mL,
& Z2 Q) {* a/ q+ ^which was clearly high. Some studies suggest that+ g% z! c6 j: n5 l, Q
dermal conversion of testosterone to dihydrotestos-
9 J4 d" ^: F/ I7 a- Y2 fterone, which is a more potent metabolite, is more! [) ^% y6 e9 g
active in young children exposed to testosterone2 D+ H/ s6 ^2 `1 Z4 e* g
exogenously7; however, we did not measure a dihy-
~$ C' b0 A B2 adrotestosterone level in our patient. In addition to
- M% J# S. ^9 B- _- h- f& svirilization, exposure to exogenous testosterone in
; ^ w4 M' f+ U+ R; G+ F% mchildren results in an increase in growth velocity and
0 h4 f& D n x1 H) padvanced bone age, as seen in our patient.
}* I6 X3 `5 |" v, ~The long-term effect of androgen exposure during
' {6 V) v6 h* G/ Dearly childhood on pubertal development and final
R' {1 f2 h5 \( \# {( V% ] qadult height are not fully known and always remain
# Z, E% B6 x' r7 z ~# pa concern. Children treated with short-term testos-
! j) ^6 A) y$ Y/ X: ^, h, W$ Aterone injection or topical androgen may exhibit some' K+ a6 C8 h1 ^& J
acceleration of the skeletal maturation; however, after
4 J7 v) p. O/ ncessation of treatment, the rate of bone maturation
4 u* T2 L0 B: R3 b: Vdecelerates and gradually returns to normal.8,9) q7 L! n! M. @0 i' d
There are conflicting reports and controversy
2 J- p7 q$ m+ K2 ~$ aover the effect of early androgen exposure on adult+ b, U3 f$ Q7 {
penile length.10,11 Some reports suggest subnormal5 b. y ~' q) w% m
adult penile length, apparently because of downreg-
4 q& w9 b) a. M3 u$ k- `ulation of androgen receptor number.10,12 However,
1 `% b- {: O7 `" f! }1 USutherland et al13 did not find a correlation between& V9 o9 T5 q. H# K& |6 x
childhood testosterone exposure and reduced adult
) [' z3 X7 N* [' ~penile length in clinical studies.- C- x( J) C, t6 i8 u
Nonetheless, we do not believe our patient is5 Y: D) u9 t! H* B$ i+ z
going to experience any of the untoward effects from; ` v) J5 }$ y0 D7 r
testosterone exposure as mentioned earlier because
( e2 ~$ v3 J6 Xthe exposure was not for a prolonged period of time.
# i0 [6 k0 r% ^) u* `Although the bone age was advanced at the time of) o% C* _, U+ @, A: | V
diagnosis, the child had a normal growth velocity at, x% Z1 S' Z, _
the follow-up visit. It is hoped that his final adult
4 W0 F+ Z# v; b' l0 nheight will not be affected.
3 L* L# ] L% c4 cAlthough rarely reported, the widespread avail-
" ?7 Q, C0 ], ^ability of androgen products in our society may: g7 T4 [& t2 k1 \0 y( D; _
indeed cause more virilization in male or female
2 e% v4 Y+ N6 Y' i" F" uchildren than one would realize. Exposure to andro-. I: h8 ~2 Y, ~$ U5 w
gen products must be considered and specific ques-
, R+ `4 s/ {* q6 |: _' z1 U( rtioning about the use of a testosterone product or
& w5 F0 q+ ^& s8 Y! I. sgel should be asked of the family members during
" i3 T+ r% d, e; {% Jthe evaluation of any children who present with vir-, M& b, j: n7 O" o2 Z4 c
ilization or peripheral precocious puberty. The diag-4 I, k) {+ P6 \( \8 p8 V
nosis can be established by just a few tests and by
^1 p2 ~! k5 |% J4 cappropriate history. The inability to obtain such a8 L0 t- L- O/ v4 n5 ] v: C4 ~% m
history, or failure to ask the specific questions, may$ v& W0 N( {. k% Y
result in extensive, unnecessary, and expensive
- v; m& ~: O2 B& n d3 G$ ?; ~investigation. The primary care physician should be
$ C& U4 C" j. m9 U7 f2 y4 p0 \aware of this fact, because most of these children
! s8 K; @3 ?5 W) \# Lmay initially present in their practice. The Physicians’7 i0 X3 L" y2 G( R
Desk Reference and package insert should also put a
& H* A8 X1 }& E% K6 V, V; ~warning about the virilizing effect on a male or% ?0 q! W2 K) E1 j: r. u. [
female child who might come in contact with some-( L5 ?" r7 U* e
one using any of these products.
6 P3 o7 v% t# _- v; |: YReferences9 X/ B4 W$ E% z. a: \' K
1. Styne DM. The testes: disorder of sexual differentiation' X9 v& }5 b: Q X/ |" g) g6 V
and puberty in the male. In: Sperling MA, ed. Pediatric
8 I+ m9 Y d1 UEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
; }2 Y; j1 u7 t, {0 `, Q" q0 S2002: 565-628.! J P; ~6 v/ o2 L
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
]: \5 ], }& x$ B3 v2 \! Q3 hpuberty in children with tumours of the suprasellar pineal |
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