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Sexual Precocity in a 16-Month-Old
: Q1 h1 i, U: iBoy Induced by Indirect Topical' \* H! Z/ S3 F/ C7 u1 w# t
Exposure to Testosterone B' ?* E' Q2 B9 D% v9 k6 ]
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
: r) ?; V" \" _0 e! ?7 Band Kenneth R. Rettig, MD1
$ z! Y0 z8 L% r% O) U4 u- ?Clinical Pediatrics
) p/ y$ ^2 x& |3 EVolume 46 Number 6
6 {$ t# [7 _7 B2 J, g; H; bJuly 2007 540-543% d/ d5 o8 T4 ~8 t. E
© 2007 Sage Publications
+ _1 W4 D( C1 l10.1177/0009922806296651
I& r" N- s0 Q; I' y4 r chttp://clp.sagepub.com9 Q( }4 X c( S5 Z
hosted at: h( O2 G+ {. e2 K5 E
http://online.sagepub.com
2 |6 d( G- w' D3 n8 K, VPrecocious puberty in boys, central or peripheral,
8 \' i5 Y) @0 `$ h9 ~is a significant concern for physicians. Central, Q/ }- H' H; Q/ p
precocious puberty (CPP), which is mediated+ Y$ p" R! T% h8 z9 }1 q4 U% P
through the hypothalamic pituitary gonadal axis, has: @$ b6 c$ p. E3 @
a higher incidence of organic central nervous system; J8 d: ]2 [8 h% _) m" \2 t! Z
lesions in boys.1,2 Virilization in boys, as manifested
+ {: X! f8 T& Fby enlargement of the penis, development of pubic
- ~, ^( h4 g4 Nhair, and facial acne without enlargement of testi-/ N3 X/ M2 c3 E, J: f
cles, suggests peripheral or pseudopuberty.1-3 We
! o4 i$ N Z8 @7 ureport a 16-month-old boy who presented with the
6 R) O5 p, r s/ o& e$ Denlargement of the phallus and pubic hair develop-
; _9 w9 l7 \( s% q- c+ @ment without testicular enlargement, which was due
( V% p% |2 o6 W) C$ E) S3 q' kto the unintentional exposure to androgen gel used by
0 Q$ S( x; q; |the father. The family initially concealed this infor-/ e, P5 o! C6 A
mation, resulting in an extensive work-up for this
; f. {( L; d+ achild. Given the widespread and easy availability of& A9 W- L' V* f1 \
testosterone gel and cream, we believe this is proba-& Q7 i/ V2 r" A0 R! P
bly more common than the rare case report in the0 A1 Z# t( I. @+ ?" h
literature.48 B, L0 Z7 B9 W: b+ \8 P, |
Patient Report
4 N5 {+ e* C+ {' [( GA 16-month-old white child was referred to the" e- A4 I2 O* w# F/ P
endocrine clinic by his pediatrician with the concern
+ H4 E/ B& w! p6 pof early sexual development. His mother noticed' @4 ?3 W9 _) L; l
light colored pubic hair development when he was
+ F* P5 Y9 Z- y0 }; X8 b$ c% }From the 1Division of Pediatric Endocrinology, 2University of- ^; Q) H0 b" q; J3 _: Q) |
South Alabama Medical Center, Mobile, Alabama.
3 w {( q7 ^8 v' iAddress correspondence to: Samar K. Bhowmick, MD, FACE,
5 o! H8 ~: p m' U' uProfessor of Pediatrics, University of South Alabama, College of% Q, w# O( e4 u% y7 g8 R, a/ c
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
7 Z: n/ l: c- t5 C" }7 n* \e-mail: [email protected].
d& m& L- y2 @about 6 to 7 months old, which progressively became/ V! D M! c2 I f+ V6 H j! t
darker. She was also concerned about the enlarge-% t: X7 o9 _! M5 R
ment of his penis and frequent erections. The child# y9 n. L1 }2 r* {! u2 q" X
was the product of a full-term normal delivery, with
: y, b! o+ M+ T( I/ m8 W' xa birth weight of 7 lb 14 oz, and birth length of8 a4 t0 M8 |) A! f% F
20 inches. He was breast-fed throughout the first year: K$ X2 B/ b( F* G/ j
of life and was still receiving breast milk along with
0 ]; A4 x$ i. k9 u5 k. O) Wsolid food. He had no hospitalizations or surgery,7 k' o N. A' B+ f ^5 {6 `
and his psychosocial and psychomotor development
3 { ~7 f9 Y0 r' A @7 }was age appropriate.
. J# F1 B/ U; U+ ^The family history was remarkable for the father,8 H# D+ C; l v* e, \. ?) i
who was diagnosed with hypothyroidism at age 16,+ W- T; \ [, _' f
which was treated with thyroxine. The father’s) `+ k. }/ t* w/ ~) |! u! X
height was 6 feet, and he went through a somewhat
& v: A! ]) \% }/ X5 H6 d- Gearly puberty and had stopped growing by age 14.
% S& {9 M' F. t" s; g; o0 W$ YThe father denied taking any other medication. The
" X& k9 h/ B/ ~& Schild’s mother was in good health. Her menarche
( X0 Y1 W8 c; W7 `/ q2 P$ ]9 ?3 Zwas at 11 years of age, and her height was at 5 feet
9 p* y6 O8 s7 S$ j6 Y' _5 inches. There was no other family history of pre-
3 |) J/ Z1 T, k$ s/ Qcocious sexual development in the first-degree rela-
4 T2 z [% r6 y* |7 E) r; }tives. There were no siblings.4 A e- ?7 n! o% K6 }! \/ t( v
Physical Examination0 w+ G: _& `; w$ K. h
The physical examination revealed a very active,& K- C& q$ w+ Y+ b- k P
playful, and healthy boy. The vital signs documented; I1 g6 }% ]! _- ~% c, V ^/ I
a blood pressure of 85/50 mm Hg, his length was6 x ], w+ s. W/ y. d9 w
90 cm (>97th percentile), and his weight was 14.4 kg+ f4 e9 a, j: `. m, W. [
(also >97th percentile). The observed yearly growth
6 r0 j4 D7 ~) u4 q2 ^velocity was 30 cm (12 inches). The examination of4 L& h0 W1 ^% e) `$ v- Z2 x( n
the neck revealed no thyroid enlargement., {' w" m o4 I
The genitourinary examination was remarkable for
7 O; V, B- ~# }& kenlargement of the penis, with a stretched length of! x- j" g/ p: W( | }9 J
8 cm and a width of 2 cm. The glans penis was very well& i. y9 P, }% h5 y9 j% j
developed. The pubic hair was Tanner II, mostly around0 P) g% s- s( F8 C" V
5406 y+ e4 k0 y f6 B4 U" H% v7 s2 z' q
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
& @) K k% R3 x2 ?the base of the phallus and was dark and curled. The# Z+ M; L3 q+ F, @. b
testicular volume was prepubertal at 2 mL each.
: E. i3 n; r7 T5 x& j/ G9 yThe skin was moist and smooth and somewhat7 b8 Z( M6 G5 `# y6 T7 i/ f
oily. No axillary hair was noted. There were no/ j! m! o& [6 [1 T* \ C
abnormal skin pigmentations or café-au-lait spots., r3 i: h' F7 a% A- p
Neurologic evaluation showed deep tendon reflex 2+( ]/ b- u; w" g4 w' p
bilateral and symmetrical. There was no suggestion1 ?* [* p$ j' f! |# b' o
of papilledema.0 ?! Z5 H1 g; K5 B8 H, H
Laboratory Evaluation
9 i* q9 j" o4 e3 Y! j, ~; w2 U, cThe bone age was consistent with 28 months by6 O! n8 s" \8 w
using the standard of Greulich and Pyle at a chrono-9 i9 Y" }) h5 }; G! H- u
logic age of 16 months (advanced).5 Chromosomal3 ]9 o( Y. j/ V2 B5 A
karyotype was 46XY. The thyroid function test2 y P0 ^/ i# p7 S2 L
showed a free T4 of 1.69 ng/dL, and thyroid stimu-( K. p1 Q: o$ x' T" p
lating hormone level was 1.3 µIU/mL (both normal).. s; D( g3 q c
The concentrations of serum electrolytes, blood
0 `0 ^" U& ]* a/ O9 q- Nurea nitrogen, creatinine, and calcium all were
* ]/ ^$ E* s- Qwithin normal range for his age. The concentration# l" B- ^1 O9 }
of serum 17-hydroxyprogesterone was 16 ng/dL2 M B) r, x& w2 y; U) M
(normal, 3 to 90 ng/dL), androstenedione was 20
7 y0 |) j8 b$ ~+ z, [ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
" {. |8 A4 V- z4 Tterone was 38 ng/dL (normal, 50 to 760 ng/dL),
) u9 o& q! N) y' |1 q* vdesoxycorticosterone was 4.3 ng/dL (normal, 7 to2 f( ], _1 t3 L: Y6 {% M; O, T: A
49ng/dL), 11-desoxycortisol (specific compound S)
- H8 a! \6 `. s9 b" ywas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-0 e/ {" M+ C$ Q! t1 _& l6 p/ q* S
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
# g% K ^* e" K( \testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
d$ i8 T7 _$ F/ X0 hand β-human chorionic gonadotropin was less than! b5 o8 F( f+ R8 H) B4 \) u
5 mIU/mL (normal <5 mIU/mL). Serum follicular4 U4 Q' R" i# d3 v+ ?' s1 c/ I
stimulating hormone and leuteinizing hormone# p! i) z4 U0 |3 o+ O* o
concentrations were less than 0.05 mIU/mL
! b; Z+ b1 z( X/ Y0 x: E8 y! {$ u(prepubertal).5 i5 {, Z: G/ @9 t: l1 ~
The parents were notified about the laboratory
- P- W7 j6 K( Vresults and were informed that all of the tests were
: X7 @4 b" X8 i9 ~$ gnormal except the testosterone level was high. The0 [ R1 U5 @9 C$ e
follow-up visit was arranged within a few weeks to
* {0 X! ^3 {6 m* ~$ h/ r6 oobtain testicular and abdominal sonograms; how-
, r, A: Q3 r. M0 ^- V# @* jever, the family did not return for 4 months.* R& `, }* U6 J6 s: B! M+ N
Physical examination at this time revealed that the2 h" A( O! `- u$ [8 ~4 s5 A; O) o
child had grown 2.5 cm in 4 months and had gained4 u- u0 z$ n+ o/ g
2 kg of weight. Physical examination remained9 y' i% |, v0 f" [7 w
unchanged. Surprisingly, the pubic hair almost com-, C0 R- c' B# I5 x! A0 @
pletely disappeared except for a few vellous hairs at: T% L/ F+ R. d+ Y
the base of the phallus. Testicular volume was still 2
. p6 h0 l% x9 ^* y# v5 BmL, and the size of the penis remained unchanged.
* E# ?" K! {; E1 NThe mother also said that the boy was no longer hav-
2 Z/ p( S" c& c+ I" Ging frequent erections.
! _! c' y7 v9 fBoth parents were again questioned about use of
2 h' p/ U5 [, \3 {$ c1 R- Kany ointment/creams that they may have applied to
& w- t5 q3 k- I5 w, P" t* n4 |& |the child’s skin. This time the father admitted the
; D" S. A4 D5 WTopical Testosterone Exposure / Bhowmick et al 541
3 i q. d+ Q' ~& ~* }0 Zuse of testosterone gel twice daily that he was apply-
, i3 k3 c5 X; g* D; Fing over his own shoulders, chest, and back area for" k; x% ?" m# j3 T9 ~ f) D
a year. The father also revealed he was embarrassed( S* k7 a* {& C0 P; K% c- _9 k4 p
to disclose that he was using a testosterone gel pre-$ W) [" ~# e" }" P/ t: ~% K+ d
scribed by his family physician for decreased libido
" h( f! r& y1 x) o2 d S/ {secondary to depression.
1 \ n( V$ g' a0 z$ @The child slept in the same bed with parents.
6 I* r) z$ I- t6 v# y2 m- A$ g+ e5 [. `The father would hug the baby and hold him on his
" R5 v. G* \( M" Mchest for a considerable period of time, causing sig-% S3 {$ S% ]4 E% N. P% a
nificant bare skin contact between baby and father.
. ~5 }. v/ {6 B% h; o& tThe father also admitted that after the phone call,1 b) |7 c/ C+ s# s0 h4 I( R% }
when he learned the testosterone level in the baby# I" c% T% c% d$ g+ }
was high, he then read the product information8 g1 |, `" V, e. d
packet and concluded that it was most likely the rea-+ f7 S* P0 N+ K
son for the child’s virilization. At that time, they' f$ L9 K0 R. J
decided to put the baby in a separate bed, and the
0 y- a( y2 ?$ C1 k2 O: Lfather was not hugging him with bare skin and had
' Q9 j/ Y* Z/ ^0 {, R" Lbeen using protective clothing. A repeat testosterone+ i* m6 _/ L( i5 ~
test was ordered, but the family did not go to the+ g7 R" D# ^: C5 s# w
laboratory to obtain the test.- w3 \0 i) ]# B1 m( U
Discussion3 g$ Q3 ?& g6 J4 v( @3 Z
Precocious puberty in boys is defined as secondary
- q8 j+ x2 h1 L! lsexual development before 9 years of age.1,4
- r0 a6 _% Z* ~9 {9 pPrecocious puberty is termed as central (true) when
+ b; r* x' y- v5 o% B) tit is caused by the premature activation of hypo-
" [% q! A% `& s+ Kthalamic pituitary gonadal axis. CPP is more com-: G& h; ^! I8 F) J
mon in girls than in boys.1,3 Most boys with CPP) ]7 _0 H m! D
may have a central nervous system lesion that is
1 ~: U1 a- M- z, V0 ^responsible for the early activation of the hypothal-
& a+ y8 K4 G" L. s% v& {* i1 \amic pituitary gonadal axis.1-3 Thus, greater empha-2 e3 N, s. Q# @6 O# p7 d' Q f
sis has been given to neuroradiologic imaging in
2 l7 u/ o3 p5 b, e( D3 V8 yboys with precocious puberty. In addition to viril-
; z1 A# [- W9 t3 r; xization, the clinical hallmark of CPP is the symmet-
$ S. s$ J: y2 ?% S( I- r3 Hrical testicular growth secondary to stimulation by
' N' U! j" j+ rgonadotropins.1,3
/ @" t# h/ k" y( f6 Q, k, Z' v- TGonadotropin-independent peripheral preco-
3 j0 u# h6 C4 S% o7 }* tcious puberty in boys also results from inappropriate$ c( f; h# [; ?3 Z0 U
androgenic stimulation from either endogenous or
) f! r4 Q6 v9 E% s `& Lexogenous sources, nonpituitary gonadotropin stim-3 {* l# |. l0 K+ C0 M
ulation, and rare activating mutations.3 Virilizing# s$ P6 f: H9 \/ g
congenital adrenal hyperplasia producing excessive- _- p+ h0 y! T' b7 @. r9 j) }
adrenal androgens is a common cause of precocious
8 d( ^6 [8 |1 O* L' ?puberty in boys.3,4
+ E4 b5 A, L1 a* D3 VThe most common form of congenital adrenal" a, O4 G4 _: X
hyperplasia is the 21-hydroxylase enzyme deficiency.
; B" I7 i, m2 MThe 11-β hydroxylase deficiency may also result in
! t# }) x+ o; b7 Sexcessive adrenal androgen production, and rarely,
) H" {6 c5 W- c2 H: Han adrenal tumor may also cause adrenal androgen# A/ i, @7 H* W3 h0 q c
excess.1,3- q, P. ~' i2 j N* J! z+ }9 p
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
* X. d R6 c; i" M$ K$ ?542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
/ v7 M" c, X& B5 }A unique entity of male-limited gonadotropin-# ? t- o8 W8 `3 w* _
independent precocious puberty, which is also known$ u1 D1 W1 y; t$ E2 K- G' p
as testotoxicosis, may cause precocious puberty at a
) ?3 d% q% A% O+ _6 O C: A3 h9 A svery young age. The physical findings in these boys
- Z( T; U; i8 T) y: fwith this disorder are full pubertal development,1 v! E% T, ~5 R A; j
including bilateral testicular growth, similar to boys9 b! U# }! `2 Q# p
with CPP. The gonadotropin levels in this disorder
. v4 Z D, A5 C1 p. p" G! p# Aare suppressed to prepubertal levels and do not show# [8 L( u- ^) W8 t5 y2 g. I
pubertal response of gonadotropin after gonadotropin-
& o) [2 U) h- |' |. ?+ P( Kreleasing hormone stimulation. This is a sex-linked' T& b5 _4 t5 g" D# o8 A3 |
autosomal dominant disorder that affects only
5 W3 D( {! U- @, f& W9 dmales; therefore, other male members of the family
2 V9 l2 ]# f- B9 ?may have similar precocious puberty.3
/ l" r8 l& z. T4 y) Y' _: [ pIn our patient, physical examination was incon-7 d' T1 E( ?2 x# k
sistent with true precocious puberty since his testi-# r! ?/ _; x) z
cles were prepubertal in size. However, testotoxicosis
/ m* H4 \3 V8 V' }! {+ Owas in the differential diagnosis because his father
* F; V$ z+ l$ F0 ^5 w1 Sstarted puberty somewhat early, and occasionally,
3 c, ^2 Z3 N4 h$ u( Ftesticular enlargement is not that evident in the& m$ ?, J1 i6 J* ?3 A& H& ~. t. M. z/ h
beginning of this process.1 In the absence of a neg-
6 P# j3 A! \ J3 t" u) ^ative initial history of androgen exposure, our+ q. m: N$ e4 C. M0 e5 o
biggest concern was virilizing adrenal hyperplasia,
: ]+ D7 N* g& ~" O. s3 keither 21-hydroxylase deficiency or 11-β hydroxylase
) b7 L* H m% {4 i" I# K8 Z# Qdeficiency. Those diagnoses were excluded by find-
' Y! Z) K- }$ xing the normal level of adrenal steroids.
8 @* k" `8 u8 j& |7 E3 ], H/ {1 [" EThe diagnosis of exogenous androgens was strongly
. F7 Z, h5 P# m' V- ~suspected in a follow-up visit after 4 months because; E6 N$ E, p8 E8 u
the physical examination revealed the complete disap-' o8 {) Y% W" G2 [( U3 s D
pearance of pubic hair, normal growth velocity, and9 c; M7 C! c0 U1 a2 y7 E
decreased erections. The father admitted using a testos-( h, a Z5 c+ ^( t1 n
terone gel, which he concealed at first visit. He was+ q3 O- E ]" H. \# m' f1 D' J
using it rather frequently, twice a day. The Physicians’
& S& q5 M3 d+ b$ \# ?Desk Reference, or package insert of this product, gel or$ ^7 g0 O0 O" Q9 W' {' ~% L2 y
cream, cautions about dermal testosterone transfer to3 j( ~/ y1 W) Q
unprotected females through direct skin exposure.
% o7 R, f$ H- ^) \, c: qSerum testosterone level was found to be 2 times the
3 M2 j R4 l: S) q( |baseline value in those females who were exposed to
) L$ W7 g( q, |. i: yeven 15 minutes of direct skin contact with their male
8 i- O: Q2 u# i+ l, u ~partners.6 However, when a shirt covered the applica-
7 \. P" v- B# c6 e8 ~ r5 _tion site, this testosterone transfer was prevented.# P |; S x( T: u d* {
Our patient’s testosterone level was 60 ng/mL,
0 a9 ]6 P# O" x: f( b: ?which was clearly high. Some studies suggest that
+ ?# z3 n$ T8 Q; s: ndermal conversion of testosterone to dihydrotestos-+ _( L" d* P5 P' W- O1 x/ W4 F
terone, which is a more potent metabolite, is more1 h: Q) I2 J& \; D
active in young children exposed to testosterone7 m7 }. `+ R' j( B* B. o
exogenously7; however, we did not measure a dihy-6 D5 e, y! P1 X9 K
drotestosterone level in our patient. In addition to# M) q2 g$ r0 Y. m, ]- o) ?+ L
virilization, exposure to exogenous testosterone in
/ K. [& d* K' \: hchildren results in an increase in growth velocity and
% C: @& _6 I( Q8 x* m5 A+ Zadvanced bone age, as seen in our patient.* q1 Q5 {* E* e* y
The long-term effect of androgen exposure during$ X% [( O% m0 w2 d
early childhood on pubertal development and final
) D# X% I, Q; V0 t# Ladult height are not fully known and always remain
; x/ G" I. M' t5 S& B$ c& w3 n% ]a concern. Children treated with short-term testos-3 v2 j4 | j" r% a) ^
terone injection or topical androgen may exhibit some, G. q: w: A( P
acceleration of the skeletal maturation; however, after# F% y% v, C9 e/ C
cessation of treatment, the rate of bone maturation
0 _" h7 m- G# j2 l& N- V1 wdecelerates and gradually returns to normal.8,9
+ c& T% A1 k( P& h+ R9 }3 gThere are conflicting reports and controversy. C; |' A7 K+ h4 d) n" w* X8 ?6 a
over the effect of early androgen exposure on adult
" ^- s6 v- o* |5 h! D7 Wpenile length.10,11 Some reports suggest subnormal
5 ^5 N. d# B% U7 K5 N! R4 Aadult penile length, apparently because of downreg-
! y c' W$ Q4 ]$ a" z* x f, Pulation of androgen receptor number.10,12 However," ]0 q- w0 e" D! F5 f+ U. Z
Sutherland et al13 did not find a correlation between
0 F) k5 U0 C3 Q. Zchildhood testosterone exposure and reduced adult
- E, N1 e0 w" T. {: c' U: D2 Mpenile length in clinical studies.
/ q1 B$ P' \: c4 {Nonetheless, we do not believe our patient is
+ n1 H# f* I G2 |) ^+ f7 ggoing to experience any of the untoward effects from
* M% K. X+ |! P; vtestosterone exposure as mentioned earlier because9 `- R6 ~5 z' {: v7 S
the exposure was not for a prolonged period of time.5 j5 c v, k, t! ?
Although the bone age was advanced at the time of
& G% U! U: N' [+ H8 Rdiagnosis, the child had a normal growth velocity at
I( t0 v& E4 _0 C C+ nthe follow-up visit. It is hoped that his final adult d/ k, @5 D* p& Y' X4 G3 f
height will not be affected.5 j6 w4 S( k4 h- z! P, X1 n
Although rarely reported, the widespread avail-
8 h/ P& @; a! iability of androgen products in our society may4 u0 N( Z0 w4 l0 X6 g) k: e. P
indeed cause more virilization in male or female
6 k7 `! i* J$ V6 Gchildren than one would realize. Exposure to andro-5 }" @( d$ O, T# a2 Q& S z
gen products must be considered and specific ques-
! J* I6 }2 s8 y+ Y4 ctioning about the use of a testosterone product or
" J: ^; R" c$ r) s2 U! L+ y6 ]gel should be asked of the family members during
5 _* k' b2 K( S' J" e; P* M0 c% _the evaluation of any children who present with vir-4 J. L8 B _) v2 Z9 ^
ilization or peripheral precocious puberty. The diag-
6 E4 U. z ? Lnosis can be established by just a few tests and by
1 Y# k4 G8 g0 q/ U2 J! Xappropriate history. The inability to obtain such a( ]/ L& X+ ^4 s* q& ^% f) ~
history, or failure to ask the specific questions, may
6 N8 ?' S* l$ X' `+ i. Dresult in extensive, unnecessary, and expensive
9 Y9 `7 I0 `( J( t7 X: U3 t( ^* Qinvestigation. The primary care physician should be
9 `6 D5 u) ?6 J R. T( Aaware of this fact, because most of these children
! h4 F' l6 U$ Q7 X G zmay initially present in their practice. The Physicians’ J6 {( K) J9 @
Desk Reference and package insert should also put a4 H* [) P$ ?1 s2 ~9 `, j
warning about the virilizing effect on a male or
: s" W; X, W2 v$ kfemale child who might come in contact with some-; j$ p; _8 }' @
one using any of these products.: O- b5 d+ c+ e9 p1 _
References9 G6 Y. o% Q2 v9 h8 {4 P
1. Styne DM. The testes: disorder of sexual differentiation9 [9 a# c) ?- Z; Y: ~
and puberty in the male. In: Sperling MA, ed. Pediatric6 z2 c/ ]5 P; j/ S6 h
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
3 X+ G) B; l4 r' b& b2002: 565-628.
: ^0 X/ R9 j3 v$ a- z E: X2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious, f5 x# i8 z- I4 y8 P
puberty in children with tumours of the suprasellar pineal |
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