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Sexual Precocity in a 16-Month-Old% I- B# c( O( z2 n. I6 y$ O
Boy Induced by Indirect Topical0 O. @% ^8 p3 D1 Y& V) }$ a5 `
Exposure to Testosterone7 G* a( ]9 `/ S
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,28 ~( t% V7 i: W" ~* u% a0 Y8 G
and Kenneth R. Rettig, MD1( Q8 @! Y5 |. L! F7 ~6 G
Clinical Pediatrics5 `6 l/ }) k, }8 |
Volume 46 Number 6
5 P, n+ T4 H& Q+ GJuly 2007 540-543
0 c) n/ k1 G( T9 u& I5 d- j© 2007 Sage Publications
4 S/ M6 W" ?( o {) j10.1177/0009922806296651' p6 @* F' ^% I# ^% S4 e1 U
http://clp.sagepub.com
6 \$ S& C& y9 G) k/ x- D) Ohosted at
! r6 c8 d5 ~ D) L( j& a: ]http://online.sagepub.com
% K* \0 p7 `/ H- T* bPrecocious puberty in boys, central or peripheral,1 {& T1 a0 f' k
is a significant concern for physicians. Central
, S0 Z+ _& Y* ], J" _- C3 Jprecocious puberty (CPP), which is mediated8 _4 y) s8 M3 G( U3 K& Q) E
through the hypothalamic pituitary gonadal axis, has
2 X3 `/ y5 c4 D0 `# R( Ra higher incidence of organic central nervous system
7 [8 ?5 g8 X u3 _& o' r- U# Y3 xlesions in boys.1,2 Virilization in boys, as manifested e, w2 _: H) G$ Q( V' W
by enlargement of the penis, development of pubic# M( q0 `1 j! s5 A+ e( }9 j) B, l. w
hair, and facial acne without enlargement of testi-
( G5 P& H# G1 S. v; f2 Kcles, suggests peripheral or pseudopuberty.1-3 We
8 }4 ~1 i/ w; Wreport a 16-month-old boy who presented with the( P6 I+ v8 `& ]5 F2 Z7 J0 N* A
enlargement of the phallus and pubic hair develop-
( X, a% G/ L% M u$ vment without testicular enlargement, which was due
. V1 W; v- G$ A2 C) j' j# E. Qto the unintentional exposure to androgen gel used by
8 P5 }; y2 @) L( P* B# Cthe father. The family initially concealed this infor-% @: K. b8 K! Q$ Q& z' r- `
mation, resulting in an extensive work-up for this6 _6 V4 S' O- |) L
child. Given the widespread and easy availability of
" `) I3 e+ p u& w, ]/ dtestosterone gel and cream, we believe this is proba-
; ^; C9 E e7 u' @( Fbly more common than the rare case report in the* R2 m _3 ` H$ R. L
literature.40 M9 F8 D& ?0 x7 a! {
Patient Report5 U8 W Q$ ?3 n" J1 m
A 16-month-old white child was referred to the
4 }+ B; I: ~& i( n Fendocrine clinic by his pediatrician with the concern+ o) M# G1 g6 H# w) ~" a ~$ d9 w( P
of early sexual development. His mother noticed r- m4 A& k$ L$ K* A# Y3 B
light colored pubic hair development when he was% I) M9 _0 \* C0 K2 Y( I
From the 1Division of Pediatric Endocrinology, 2University of
" u2 c% Q4 S, j; |/ SSouth Alabama Medical Center, Mobile, Alabama.
# h& x6 D. M# g" U) {% ]Address correspondence to: Samar K. Bhowmick, MD, FACE,
6 i. g& l/ L; m8 }" B/ iProfessor of Pediatrics, University of South Alabama, College of
. V3 b% s5 T( K; G/ gMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;- s! Y+ e+ F& q7 r6 O6 V4 K
e-mail: [email protected].
# x4 k, ^$ [- C% Oabout 6 to 7 months old, which progressively became! t; Q6 H" ]. a# Q3 H' o
darker. She was also concerned about the enlarge-
1 ?1 G/ E, z' E% p6 r1 L+ T: Dment of his penis and frequent erections. The child
: s; }5 t, Q- `was the product of a full-term normal delivery, with) D; |" ~# Z9 A; S6 E
a birth weight of 7 lb 14 oz, and birth length of
' c3 p3 W3 {; e# K$ |: u1 s20 inches. He was breast-fed throughout the first year
3 ]; T- ~- Y7 h% ^of life and was still receiving breast milk along with# q8 C9 f" c6 P. ?# z
solid food. He had no hospitalizations or surgery,, D9 m, ]- a( ~0 e- ~, n
and his psychosocial and psychomotor development$ K& {3 }2 m1 i' ~/ R' }
was age appropriate.3 V! { b! ]$ U' I! @
The family history was remarkable for the father,/ t# B* S, E- B' m8 q n8 m
who was diagnosed with hypothyroidism at age 16,# g4 ~8 A) r, g0 r
which was treated with thyroxine. The father’s
) t9 j1 M4 I2 rheight was 6 feet, and he went through a somewhat
0 w& N4 O m: N0 @" P$ bearly puberty and had stopped growing by age 14.
5 i5 ]1 P% W3 Q2 zThe father denied taking any other medication. The
/ _ n9 H( r' t0 x9 D6 tchild’s mother was in good health. Her menarche
. u( ` G. J7 A& T- dwas at 11 years of age, and her height was at 5 feet$ n$ w6 ~8 k# Q1 r
5 inches. There was no other family history of pre-) Q+ M4 O2 t" d/ O
cocious sexual development in the first-degree rela-) `! y$ G# t/ l/ r( f) {
tives. There were no siblings.
* D; ^: R6 y" _0 ZPhysical Examination, N. ?9 \4 l% a* [
The physical examination revealed a very active,
3 A5 u. G4 Q- Aplayful, and healthy boy. The vital signs documented. s) Z! [; Y f8 c# r% S* D
a blood pressure of 85/50 mm Hg, his length was
( \% {1 u0 Z5 ^0 G90 cm (>97th percentile), and his weight was 14.4 kg
/ N y7 j! H+ X1 y4 O(also >97th percentile). The observed yearly growth) I& @. u! f) R% N# k+ O1 V
velocity was 30 cm (12 inches). The examination of
# o* B) O/ O, Cthe neck revealed no thyroid enlargement.4 ^( u. ^' F9 D' T
The genitourinary examination was remarkable for% V4 `0 H/ E$ w% J
enlargement of the penis, with a stretched length of
: Y/ n/ W( z1 [8 cm and a width of 2 cm. The glans penis was very well
4 j( _6 R* L5 ~7 _8 i( cdeveloped. The pubic hair was Tanner II, mostly around
# x. T/ X3 w8 h540
& @* |, Q8 l1 Q% x. G( K. cat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
- t* _+ z" i# e2 u) _2 O; gthe base of the phallus and was dark and curled. The
% }3 b6 L& \/ a3 S) J. g3 utesticular volume was prepubertal at 2 mL each. f! t! N8 z# [0 f
The skin was moist and smooth and somewhat
6 T% _% H# w; }3 L" G* \' \ {oily. No axillary hair was noted. There were no
7 ?: ]6 P2 u2 v/ Q# Jabnormal skin pigmentations or café-au-lait spots.5 t" x. \; U- r- s# ~# h2 D
Neurologic evaluation showed deep tendon reflex 2+ c0 P0 _' G. A5 |; |
bilateral and symmetrical. There was no suggestion
- g. P- I+ P1 k3 C9 b- ?7 I* bof papilledema., s3 M2 Q# R+ }
Laboratory Evaluation0 _) [& W( m% S: n) X
The bone age was consistent with 28 months by
& e' Q2 }. g0 N9 r5 n6 H! Q8 q( E7 Kusing the standard of Greulich and Pyle at a chrono-( F; L# A6 ~6 U2 y
logic age of 16 months (advanced).5 Chromosomal) X2 E. }) k. L+ n' d
karyotype was 46XY. The thyroid function test& w" o6 w+ Y' }7 x3 }
showed a free T4 of 1.69 ng/dL, and thyroid stimu- y6 w% A' |+ Z3 g# M2 `
lating hormone level was 1.3 µIU/mL (both normal).4 G) \3 A' i G+ z. L4 m9 k( w
The concentrations of serum electrolytes, blood
4 r$ r' d, Y" _urea nitrogen, creatinine, and calcium all were$ J& d0 R+ z! b; j( p2 s
within normal range for his age. The concentration4 m9 z* K$ y' Y1 r7 S) h M
of serum 17-hydroxyprogesterone was 16 ng/dL
3 B0 f% N9 W ]8 I0 ~' H(normal, 3 to 90 ng/dL), androstenedione was 202 S0 m: z4 W! ^ x: t& h
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-1 o: [# q8 p' M- r9 i, `. X
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
0 Y6 z. ~4 h! X& pdesoxycorticosterone was 4.3 ng/dL (normal, 7 to/ J$ x: l& J( o- s; A6 m
49ng/dL), 11-desoxycortisol (specific compound S)4 k- h, F- R4 z8 }, {
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
, H4 C! ?) D$ Ptisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total4 C) o* O! G7 O8 T
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),9 y2 i0 E# P3 l7 g! B* K0 Z
and β-human chorionic gonadotropin was less than# X7 s4 _8 W* z6 s3 d& n4 w4 k/ b
5 mIU/mL (normal <5 mIU/mL). Serum follicular
8 D4 p# x. {6 M0 o1 d7 Estimulating hormone and leuteinizing hormone+ L4 `9 @% N1 F% O. p+ j% f: M
concentrations were less than 0.05 mIU/mL; I% E% D3 c. P0 C
(prepubertal).5 `; U' c* V- G9 c# v1 Q, S
The parents were notified about the laboratory6 t$ a0 c- K! f4 P
results and were informed that all of the tests were+ O5 \( D) I4 o' Y/ F2 J
normal except the testosterone level was high. The
! \" T& J: ]& Dfollow-up visit was arranged within a few weeks to
. L e$ i1 J- |8 V( j3 Y- f4 ~obtain testicular and abdominal sonograms; how-
, q- o {1 w/ s5 N4 gever, the family did not return for 4 months.5 ~+ H Z" Y) ^9 m
Physical examination at this time revealed that the' V7 t: I) z/ ]4 e% s. y
child had grown 2.5 cm in 4 months and had gained
3 n! l: z) J" H2 kg of weight. Physical examination remained
: f& T4 N0 l+ s- o) w2 p3 Iunchanged. Surprisingly, the pubic hair almost com-+ o, ?. y1 N( B$ C/ O
pletely disappeared except for a few vellous hairs at% {) k1 H- d1 y& a! n
the base of the phallus. Testicular volume was still 2
! b& }! Y* c3 y: Z9 S+ D, _mL, and the size of the penis remained unchanged.( B1 e4 c5 o: V$ R/ h
The mother also said that the boy was no longer hav-/ Y- v/ H( v- ~( K5 o4 |
ing frequent erections.
3 l. S# g+ @0 q" `- xBoth parents were again questioned about use of0 K- |9 m1 R$ m m
any ointment/creams that they may have applied to
# ]8 t- _& g/ {the child’s skin. This time the father admitted the
# J2 a1 h; Z1 g& y' CTopical Testosterone Exposure / Bhowmick et al 541# ]- r8 T9 D' f( X( ?% g
use of testosterone gel twice daily that he was apply-3 D6 N2 i( m: ^8 i/ s
ing over his own shoulders, chest, and back area for
8 ]; c) W: @# s% s' R" Na year. The father also revealed he was embarrassed
( l3 |0 c8 ^' _+ U/ e# X4 ?to disclose that he was using a testosterone gel pre-, \) \9 E- Z: C* D U1 u1 i
scribed by his family physician for decreased libido; y! T$ [8 E( ^3 c& t
secondary to depression.
; N4 F8 [- c+ dThe child slept in the same bed with parents.% ~3 R, f% j9 X9 L. [9 m: B
The father would hug the baby and hold him on his; W- b/ S' `) H; \* w
chest for a considerable period of time, causing sig-% l" o. G: l# E( E; i0 { n
nificant bare skin contact between baby and father.
- Y$ ^* l5 E; ?# UThe father also admitted that after the phone call,' `8 x9 \8 K/ p& y. @1 |
when he learned the testosterone level in the baby
" J2 ?' H7 K8 t6 k4 o: nwas high, he then read the product information
6 i3 W3 x( V& X+ hpacket and concluded that it was most likely the rea-
6 j; E2 j% e) U* p8 @# Tson for the child’s virilization. At that time, they
0 ]$ \7 Y2 A( U9 I, }6 h6 l; ?% Hdecided to put the baby in a separate bed, and the
' N5 M; T4 A: v- jfather was not hugging him with bare skin and had
7 R: Z+ R; N0 J; Mbeen using protective clothing. A repeat testosterone: s- i5 M8 ^8 {! b6 p& H2 d
test was ordered, but the family did not go to the$ n& A) w6 G$ V3 V# X. P
laboratory to obtain the test.8 _, L4 e8 B3 z* v/ t4 c3 X- j
Discussion
# R: C: P# E3 D6 aPrecocious puberty in boys is defined as secondary5 j& C1 P) H( s* @* @
sexual development before 9 years of age.1,41 o& s/ U3 o# R- B
Precocious puberty is termed as central (true) when
; I. A& _- |' F9 bit is caused by the premature activation of hypo-
. h) A! w4 Z# }( R* Uthalamic pituitary gonadal axis. CPP is more com-
) N9 v- |7 s) h8 l* u9 qmon in girls than in boys.1,3 Most boys with CPP1 ?7 L( d3 z/ q
may have a central nervous system lesion that is2 H, \1 Y( b% @# w5 }! n' y
responsible for the early activation of the hypothal-
* d2 @3 | V4 h/ g0 Y0 c: zamic pituitary gonadal axis.1-3 Thus, greater empha-
# `2 I5 j* w1 Q8 Fsis has been given to neuroradiologic imaging in
) X+ Q* e2 n* ^# {6 sboys with precocious puberty. In addition to viril-5 K* B# k i+ W# ?6 ~
ization, the clinical hallmark of CPP is the symmet-5 ^9 x. c9 c' I9 T) A5 @
rical testicular growth secondary to stimulation by
. l# w4 K6 @1 P! E, D) fgonadotropins.1,3
2 x% n, h3 s) _. X6 ]/ p5 SGonadotropin-independent peripheral preco-4 }/ X/ D! ?. ?# ^6 @- o" e' l
cious puberty in boys also results from inappropriate
& x: B. \5 `7 f: ]& Jandrogenic stimulation from either endogenous or. Y9 Z; D4 r( _
exogenous sources, nonpituitary gonadotropin stim-6 E" Y- k: `- |4 V* p0 N; }, ]/ Q
ulation, and rare activating mutations.3 Virilizing5 I' U. O# I9 V) O" R$ E& s
congenital adrenal hyperplasia producing excessive
: o1 ^9 V/ m( p) _) h1 @8 Z. ?adrenal androgens is a common cause of precocious- m9 C5 z! d6 S
puberty in boys.3,4" m9 w) o8 x3 B( y: k5 K# R: i5 _
The most common form of congenital adrenal
# n' i. u- R P- ?) ^* Zhyperplasia is the 21-hydroxylase enzyme deficiency.3 z2 s, R8 O) x, `* O3 e ~, Y8 O- ]' B" f
The 11-β hydroxylase deficiency may also result in( J; n3 z: x6 j, U% J, r: B( c; @0 I; }8 ?
excessive adrenal androgen production, and rarely,
& ^; P! |7 b# C+ z4 Xan adrenal tumor may also cause adrenal androgen
* r3 `5 X) ^& J0 ?! zexcess.1,3# G" q+ t- h; l9 z8 S2 @+ U
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
% ^5 I# Q }0 ]! z9 x542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
8 S! v2 A( N- N3 {* C0 VA unique entity of male-limited gonadotropin-
& h Q8 j; M/ r0 f( s& M. \# {independent precocious puberty, which is also known
6 l) _4 y$ u! I O4 n% h Xas testotoxicosis, may cause precocious puberty at a
" M1 P, n6 o0 v: B, i2 X; cvery young age. The physical findings in these boys
& F! a! x0 f; G. ~with this disorder are full pubertal development,
( x9 f, m! ]4 O. Z/ e' F0 cincluding bilateral testicular growth, similar to boys! q4 }% L/ N, b5 ?& N
with CPP. The gonadotropin levels in this disorder! a# Y/ i% d _0 t9 p
are suppressed to prepubertal levels and do not show" Q' m3 W. t F( E
pubertal response of gonadotropin after gonadotropin-2 D+ A9 i3 ]; Z6 ?
releasing hormone stimulation. This is a sex-linked9 E' W6 i0 m* m9 @4 V
autosomal dominant disorder that affects only
" u! e8 A7 `* r# Cmales; therefore, other male members of the family
2 l' C0 l z9 Q1 Y% Q2 |, dmay have similar precocious puberty.3
/ G# U% R9 a) e& P9 j/ [! }In our patient, physical examination was incon-
3 Z! W$ `: _4 C qsistent with true precocious puberty since his testi-
) _& p2 `" b- s' m; m7 {8 H Vcles were prepubertal in size. However, testotoxicosis
; F1 Z* S7 P& k: b/ K4 u; Gwas in the differential diagnosis because his father* G0 ]% g0 d. Q1 P7 r2 O9 u
started puberty somewhat early, and occasionally,
7 f8 Z- S5 P/ |testicular enlargement is not that evident in the ~0 [6 d5 h Y4 _# `9 o8 u+ J% I# l
beginning of this process.1 In the absence of a neg-
3 x. K; e+ R$ o/ Z" ]ative initial history of androgen exposure, our; e, B; R" Q* q* m4 ?
biggest concern was virilizing adrenal hyperplasia," f9 \' @0 i1 i% ?4 E* q$ D: W1 Y
either 21-hydroxylase deficiency or 11-β hydroxylase
9 |$ `+ ^1 K4 M; [deficiency. Those diagnoses were excluded by find-
) Q" S3 A) O, a* W' w- xing the normal level of adrenal steroids.
7 f6 | N5 R' w% b) }2 `( vThe diagnosis of exogenous androgens was strongly
/ l7 m6 W* e2 T- f& X* P, r0 Hsuspected in a follow-up visit after 4 months because
" c: Y/ W4 T: t$ t- Hthe physical examination revealed the complete disap-' p( H8 `( P6 `2 k
pearance of pubic hair, normal growth velocity, and0 Y+ r4 i2 m- I/ q& b! v$ _0 ?5 K
decreased erections. The father admitted using a testos-) z# B( a v1 ~/ N- f
terone gel, which he concealed at first visit. He was6 _! r8 W0 ^2 d5 F6 c7 }0 H# Q* x
using it rather frequently, twice a day. The Physicians’( Y0 Z5 F2 a0 f/ h
Desk Reference, or package insert of this product, gel or
, ]* Z, }2 y4 Mcream, cautions about dermal testosterone transfer to
, ~6 T" t/ b8 e# U! R6 Hunprotected females through direct skin exposure.& a/ v `$ Z- }$ V, S5 M
Serum testosterone level was found to be 2 times the
# p% R5 u, ?8 c1 xbaseline value in those females who were exposed to
5 [9 F* p# ^# m# Xeven 15 minutes of direct skin contact with their male
; t' R" U5 N: g$ m7 b5 b. Dpartners.6 However, when a shirt covered the applica-9 J& u8 {+ _1 r3 z
tion site, this testosterone transfer was prevented.) F% H+ H4 H( K. |4 a
Our patient’s testosterone level was 60 ng/mL,
# X* c# @% T# L. Hwhich was clearly high. Some studies suggest that
# O- c7 e: ?3 V h. f r+ s& \dermal conversion of testosterone to dihydrotestos-9 j2 {! B6 A3 t/ R
terone, which is a more potent metabolite, is more% \& V& \* f" q1 V7 A
active in young children exposed to testosterone! r3 [9 K8 }! n! m" q7 U, x
exogenously7; however, we did not measure a dihy-
2 n# ~8 [/ A$ `/ ^drotestosterone level in our patient. In addition to
B9 M* e" m b" B' w Jvirilization, exposure to exogenous testosterone in
9 _; U/ W" }% W! ?children results in an increase in growth velocity and9 j1 i8 F" ~; P; a
advanced bone age, as seen in our patient.
: f+ ~" X8 D" b: {# _The long-term effect of androgen exposure during
: U5 `7 A1 e7 M, q. P, G. Hearly childhood on pubertal development and final' q9 j, F. o% W
adult height are not fully known and always remain0 Z( Z7 ^6 N/ q5 N9 l1 l- X# @
a concern. Children treated with short-term testos-9 j% N( t8 a% u+ L8 i ^( j
terone injection or topical androgen may exhibit some! ]- \: ]& t; e7 X( [ `
acceleration of the skeletal maturation; however, after
7 e. H* w1 k% C1 T+ tcessation of treatment, the rate of bone maturation1 r; H) |& D9 I. J
decelerates and gradually returns to normal.8,9
& c' ^5 ?* e. n6 K- Y% _+ D' QThere are conflicting reports and controversy
/ z, C8 d! ^) @: Y; Qover the effect of early androgen exposure on adult
4 f1 ]. V% A- b! Vpenile length.10,11 Some reports suggest subnormal( q) g1 L2 D* n, |
adult penile length, apparently because of downreg-
# n$ E9 K/ a* |) f% K% z: Z7 }% eulation of androgen receptor number.10,12 However,9 j$ ?7 A4 i W3 e/ j4 P
Sutherland et al13 did not find a correlation between
( `) z: ~# t( D3 t' `childhood testosterone exposure and reduced adult
; |2 y- |! X" y4 @0 ?/ fpenile length in clinical studies.
6 B, d& ]1 H' R3 ?% G3 hNonetheless, we do not believe our patient is
# Q+ I% D1 b5 P0 {$ Z4 bgoing to experience any of the untoward effects from/ p& x! _ ^3 ?
testosterone exposure as mentioned earlier because
# Y& x Z' X9 u- Jthe exposure was not for a prolonged period of time.1 I$ w9 ~9 z4 ]8 G/ l7 ]! h
Although the bone age was advanced at the time of
0 i% H, w7 G% ^/ Ydiagnosis, the child had a normal growth velocity at
, ?5 O3 B& {, {9 @5 C* `; xthe follow-up visit. It is hoped that his final adult
) G5 O( w2 l: ?) `3 Xheight will not be affected.
( r6 |; I V9 l( C( ^# x) B2 g5 @- rAlthough rarely reported, the widespread avail-: R( L8 }, x- k5 y, N
ability of androgen products in our society may2 _2 Q1 O( d' _& Y$ h
indeed cause more virilization in male or female
) K& D, l( e' t5 Z- q: Wchildren than one would realize. Exposure to andro-
' W+ W3 J7 X. F5 N/ |! egen products must be considered and specific ques-
- U" d& `) G2 U2 rtioning about the use of a testosterone product or
$ r; w W( @2 K9 P* ]gel should be asked of the family members during
& F3 u1 A( d0 W0 h' r4 }. f3 |6 Sthe evaluation of any children who present with vir-
+ g# L! A- H0 [# a" `ilization or peripheral precocious puberty. The diag-4 _3 T; Q1 h$ D' U! l% W
nosis can be established by just a few tests and by3 g3 Z' o4 S" Z7 O3 u; F
appropriate history. The inability to obtain such a4 M: S5 ?: h$ w3 R& K. V- q" X
history, or failure to ask the specific questions, may
6 q) @. V0 q2 b# ^! U* W0 ?result in extensive, unnecessary, and expensive) ~% f1 ?/ N. y4 t$ C* p
investigation. The primary care physician should be3 N. M1 B* ?: d2 I h' C
aware of this fact, because most of these children3 l# G8 V" i! z1 k
may initially present in their practice. The Physicians’; y& R0 }. A1 X2 f
Desk Reference and package insert should also put a
; E6 l# a& [$ K9 ~2 Owarning about the virilizing effect on a male or
9 f. S" X+ h+ ^: \/ u/ Vfemale child who might come in contact with some-
. G; A7 q8 `$ O$ \7 yone using any of these products.) R0 {4 a% y2 \0 J
References" X/ D }8 g2 S
1. Styne DM. The testes: disorder of sexual differentiation/ ^3 u) }- A9 j9 K
and puberty in the male. In: Sperling MA, ed. Pediatric
/ t( U% L6 y% ~% u+ _Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders; F( [2 n7 m; V W; G
2002: 565-628.' q# X8 I" O* e* P8 R
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious9 v$ M+ ?3 s$ A; z C
puberty in children with tumours of the suprasellar pineal |
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