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Sexual Precocity in a 16-Month-Old
8 ^, `4 u% D3 `' gBoy Induced by Indirect Topical
7 }8 W) [) e% G9 L5 e; Z1 L5 P9 G. ?Exposure to Testosterone% V! M9 }: t1 F5 u+ o0 _
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,20 ?5 X* K$ u* c) K
and Kenneth R. Rettig, MD11 q0 F& |0 V d. u& ]# Y
Clinical Pediatrics
" ~; z$ j" ]3 M, W6 D; y$ NVolume 46 Number 6
2 T3 D" a+ d& q3 f$ o) tJuly 2007 540-543
0 _$ } _; |4 _- r; R) g© 2007 Sage Publications) C+ k- V' [# _8 S. L
10.1177/0009922806296651
/ S5 F2 l, n9 J- g0 rhttp://clp.sagepub.com8 s4 X& y! V* i/ a
hosted at" |% w+ N6 D2 f
http://online.sagepub.com M2 S% ]+ t! t6 F, C) p
Precocious puberty in boys, central or peripheral,7 x0 v8 K" ~6 Y! T3 _7 z2 x
is a significant concern for physicians. Central3 \5 N6 Q6 G! A" f7 l
precocious puberty (CPP), which is mediated) z3 Z! Y9 }4 L, P6 j) {& N
through the hypothalamic pituitary gonadal axis, has
0 D* t- f! X; Y3 ~0 i8 Ja higher incidence of organic central nervous system
; p# ^* h. M' |0 F' { Elesions in boys.1,2 Virilization in boys, as manifested
1 b" J$ B3 B% o+ \7 F2 zby enlargement of the penis, development of pubic
# @4 g8 S: F" s" P% Nhair, and facial acne without enlargement of testi-+ F+ p8 i- D, e& x4 b6 l5 p- |
cles, suggests peripheral or pseudopuberty.1-3 We; y9 z+ o3 J: e; K; v6 r: K
report a 16-month-old boy who presented with the
# P' p- f& p! u7 i. I! ~enlargement of the phallus and pubic hair develop-; Q B( T& l3 x! l) g4 F0 {, y
ment without testicular enlargement, which was due- C/ G# |' B9 c0 V7 h
to the unintentional exposure to androgen gel used by, z4 W g8 f2 z+ B8 Z
the father. The family initially concealed this infor-
4 h- s/ T* J& o# Omation, resulting in an extensive work-up for this. e8 Q& U; d8 F3 m- e
child. Given the widespread and easy availability of& v. e" R% h; i5 j. O
testosterone gel and cream, we believe this is proba-
% z2 o- _) U7 G% n. W- vbly more common than the rare case report in the
8 N( ?0 | a% ^# w# G. ?literature.4
* O: \6 z; s; a9 w9 l6 LPatient Report
. J6 h: L; i! i8 A0 lA 16-month-old white child was referred to the
; w3 m! a' _! nendocrine clinic by his pediatrician with the concern m5 o- G$ B) S3 _. i! e" p& G; H
of early sexual development. His mother noticed& c" m, d. v5 @
light colored pubic hair development when he was
# e* Z, ]6 ?% j! _8 M7 S- nFrom the 1Division of Pediatric Endocrinology, 2University of1 W5 r+ [; K2 z+ a" g1 H
South Alabama Medical Center, Mobile, Alabama.
& N# |6 z3 x. N- o' ~) { p+ TAddress correspondence to: Samar K. Bhowmick, MD, FACE,
6 L4 G N$ j( b; ^Professor of Pediatrics, University of South Alabama, College of
9 j# Y9 A( ]0 e# b' y: RMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;: N* A) \8 ]9 k! f
e-mail: [email protected].- X# J0 D- x: s5 {8 ]+ h4 u1 v
about 6 to 7 months old, which progressively became7 R# l0 Z9 n5 Q# m: n9 I& P* T& V5 S0 }
darker. She was also concerned about the enlarge-; K- Q, R/ b, k2 G+ p- A3 C
ment of his penis and frequent erections. The child
$ e6 e) C" O P0 gwas the product of a full-term normal delivery, with
S! z! c, S6 u' j. ~4 D! Ja birth weight of 7 lb 14 oz, and birth length of! i% d8 |) B0 H9 o0 Z$ y
20 inches. He was breast-fed throughout the first year
" e4 y+ }) B8 S6 `. Eof life and was still receiving breast milk along with
/ X1 q/ N3 V- P- Q' \8 t2 R$ \8 k& ~solid food. He had no hospitalizations or surgery,
# R2 ?8 c3 _: S% B. N3 r" j) T2 _and his psychosocial and psychomotor development, N; A7 ^! n& A( R4 c! U8 I3 v) d
was age appropriate.
$ r- v% l" ?% h% k( H7 P: zThe family history was remarkable for the father,0 E* D# @: a9 ?. }& q, s* \
who was diagnosed with hypothyroidism at age 16,
" g$ {& B4 _+ F q8 j8 |which was treated with thyroxine. The father’s
! v: L9 A, ~ w/ I# `! Kheight was 6 feet, and he went through a somewhat
+ U7 Y/ ?, g) A' I3 T/ _early puberty and had stopped growing by age 14./ A' C( j7 H% n
The father denied taking any other medication. The% L( `' t" w8 V8 ^ h# P
child’s mother was in good health. Her menarche
& T) b% ~. M5 g4 o: fwas at 11 years of age, and her height was at 5 feet0 c }* s9 h: G" G' L
5 inches. There was no other family history of pre-
9 I: f# {% O1 |6 gcocious sexual development in the first-degree rela-
/ {) ~+ b* w, R" B2 ytives. There were no siblings.
9 _; g5 y1 O3 x. BPhysical Examination
, s( ~" _3 b- Q- tThe physical examination revealed a very active,
6 ^! R! U ?0 ^ g) W8 _6 n, _playful, and healthy boy. The vital signs documented6 U c. i! b8 ?% T, _
a blood pressure of 85/50 mm Hg, his length was
) @, O* }! j" p( i90 cm (>97th percentile), and his weight was 14.4 kg9 _5 p- B/ Y- `
(also >97th percentile). The observed yearly growth
; h% b1 k% h! L" z3 x, Mvelocity was 30 cm (12 inches). The examination of8 E4 H" ?8 z- s5 l' a& d
the neck revealed no thyroid enlargement.
5 l% Z; s& W% R: g* ~/ V: i" K- n) xThe genitourinary examination was remarkable for$ i/ k. Y; D. R$ o: ~7 l
enlargement of the penis, with a stretched length of+ r% q- [% Y0 M }( A2 G' ?
8 cm and a width of 2 cm. The glans penis was very well
M# W, e+ ?* c8 v; j- O. j' Ndeveloped. The pubic hair was Tanner II, mostly around% p) j1 U; Z; S7 L' K
540
# F! D& ^/ E+ J+ P8 P/ Lat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
6 g2 [/ }5 b- g$ }! [the base of the phallus and was dark and curled. The
# K; h* Q! l0 `: ^9 O4 B; o4 k# ltesticular volume was prepubertal at 2 mL each./ t' o, E! X' ?5 T% Y8 h2 o# q
The skin was moist and smooth and somewhat
( {/ \0 H( E' k' @0 O) poily. No axillary hair was noted. There were no
# `- k2 X% d2 O1 `2 V! \abnormal skin pigmentations or café-au-lait spots.) Q+ v1 [4 o1 b6 |$ K$ K! _/ I
Neurologic evaluation showed deep tendon reflex 2+
# X0 O- n0 k- T7 I2 n/ O' ^bilateral and symmetrical. There was no suggestion- W- I- x9 W) P6 r3 C$ j, q
of papilledema.
* y/ p# g5 N6 b* u- _1 q4 |Laboratory Evaluation$ D% z1 c* f; F" _8 X
The bone age was consistent with 28 months by9 @* x3 J) U1 @- a0 Q$ c& O3 Y3 A
using the standard of Greulich and Pyle at a chrono-, F: J) T& }& }- a
logic age of 16 months (advanced).5 Chromosomal
# J+ L# Y5 m1 x5 W* [ J% vkaryotype was 46XY. The thyroid function test) O4 a6 ~& e! ?3 B; h
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
# W; ~9 z* M+ K) `' A# K4 hlating hormone level was 1.3 µIU/mL (both normal).) V# f5 P) q! l( w$ g
The concentrations of serum electrolytes, blood! P, w4 ]! c/ v& l: o1 H+ F% Y
urea nitrogen, creatinine, and calcium all were
m# h7 X* g7 W6 i( m9 twithin normal range for his age. The concentration/ B5 H+ H$ Y# l, L P7 d. c
of serum 17-hydroxyprogesterone was 16 ng/dL
9 ]; Y. t# I( a% U D8 k" r(normal, 3 to 90 ng/dL), androstenedione was 20
0 H2 G- ~8 {7 w: t- [: A0 p: G) Tng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
% y H: a. u) ?4 X- F# M4 Cterone was 38 ng/dL (normal, 50 to 760 ng/dL)," S- k7 |% m2 R" p2 M/ t
desoxycorticosterone was 4.3 ng/dL (normal, 7 to. W4 R8 {0 {* P; l# _6 U0 r
49ng/dL), 11-desoxycortisol (specific compound S)8 ?6 s) i; z% W
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-+ v6 |. v y4 S) C* \/ u
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total. O& v7 h- h7 O3 o8 |( U% w
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),( y4 c* g& T4 C" f
and β-human chorionic gonadotropin was less than5 E5 p' d2 I5 t- f
5 mIU/mL (normal <5 mIU/mL). Serum follicular
, M$ x0 A) T gstimulating hormone and leuteinizing hormone0 O/ V7 V" |: W% Y- M; X" u
concentrations were less than 0.05 mIU/mL
9 s+ J! ?: g* T$ I* r* D' r(prepubertal).& r$ C5 X3 R9 v( |3 R- b
The parents were notified about the laboratory" |( e( R. Z% H6 w7 D
results and were informed that all of the tests were
1 J: z# g4 U. @normal except the testosterone level was high. The
2 G- X5 I" u+ A% g( Gfollow-up visit was arranged within a few weeks to
# E' d$ [5 m2 e7 Xobtain testicular and abdominal sonograms; how-3 k+ v) C" P7 b+ W1 x
ever, the family did not return for 4 months.4 k$ G9 ^3 x4 r( `5 s9 h
Physical examination at this time revealed that the
) v. G8 d; v; j9 o# s' a7 zchild had grown 2.5 cm in 4 months and had gained
' A" ]$ n& x, T# I- v5 x/ f2 kg of weight. Physical examination remained$ E: z% z4 y8 v5 \- J$ ^9 }0 V
unchanged. Surprisingly, the pubic hair almost com-
2 p; z; P! O, J( X5 [: F, `2 @pletely disappeared except for a few vellous hairs at2 J# r* y K! D# L2 x, }
the base of the phallus. Testicular volume was still 2
. h; T, u7 _: Z& t" z% fmL, and the size of the penis remained unchanged.; P" M! L% y) D( q8 ~) ~3 ?
The mother also said that the boy was no longer hav-
( n j$ r8 L8 xing frequent erections.2 _( C1 H) j) m/ n- c3 N
Both parents were again questioned about use of
g9 a; F" K2 l( xany ointment/creams that they may have applied to8 w% @8 p3 C+ J5 D4 a4 x6 I( |
the child’s skin. This time the father admitted the
0 ?. a' E$ i- ?7 f& Y9 G( O& d0 WTopical Testosterone Exposure / Bhowmick et al 541, U0 b# Y2 \* e2 a1 p/ ~
use of testosterone gel twice daily that he was apply-
: a" C. T' \+ G4 p4 Ling over his own shoulders, chest, and back area for- y- O6 `, p% k$ |: P2 M
a year. The father also revealed he was embarrassed2 T( M+ G6 c: r+ k U% m+ Y
to disclose that he was using a testosterone gel pre-
3 A: |" s7 n; F/ t* b: e+ \scribed by his family physician for decreased libido& R9 N5 r$ m( u& q
secondary to depression.
9 l* W9 ?5 e- bThe child slept in the same bed with parents.0 T0 N6 J* H m3 G' d
The father would hug the baby and hold him on his6 D2 |, S, ^+ e2 W) |
chest for a considerable period of time, causing sig-$ \! I( E2 b+ r' {& b8 _
nificant bare skin contact between baby and father.3 R( c$ ~; y# x, s; {
The father also admitted that after the phone call,6 W" Z7 N/ q% X* |- y
when he learned the testosterone level in the baby
# ]* F$ M$ I8 S, o5 Y" Jwas high, he then read the product information" V( ^0 Z: O1 T; U* i
packet and concluded that it was most likely the rea-8 d9 z5 V3 o+ t0 V% [! D6 [
son for the child’s virilization. At that time, they% C; h( t( q9 V' F9 \) \1 D
decided to put the baby in a separate bed, and the
" K8 l P9 M+ E8 @9 {# @$ F. ]father was not hugging him with bare skin and had
6 u$ s5 n$ i4 Y# x8 dbeen using protective clothing. A repeat testosterone, ~; ]2 B, h& x# b/ j, {' a
test was ordered, but the family did not go to the9 Z9 ~7 y5 e3 E4 R8 o6 i- `
laboratory to obtain the test." i3 z8 o( t9 _) {5 T
Discussion8 P9 y- o: d5 g, S
Precocious puberty in boys is defined as secondary
/ J7 E; o) @6 u/ Usexual development before 9 years of age.1,41 w+ g3 Y& d* M% }' o
Precocious puberty is termed as central (true) when/ }% t/ ^7 j$ v1 `
it is caused by the premature activation of hypo-* C o W1 F- t1 U+ W
thalamic pituitary gonadal axis. CPP is more com-0 w. [' x2 S; g: ^! O
mon in girls than in boys.1,3 Most boys with CPP9 z7 ^6 [+ H2 y8 O. Y6 I R% O% ^
may have a central nervous system lesion that is! S a: w1 J, |6 d
responsible for the early activation of the hypothal-
* ?' p4 O( c5 Kamic pituitary gonadal axis.1-3 Thus, greater empha-2 _2 n7 Y* o: U0 j! B& J4 y6 C
sis has been given to neuroradiologic imaging in" ?0 V3 } R' V* c f
boys with precocious puberty. In addition to viril-
. k! Y- [% a1 N$ vization, the clinical hallmark of CPP is the symmet-
/ f: @& }9 G- Y3 h1 Erical testicular growth secondary to stimulation by
5 c+ |+ f. J' x8 q2 Egonadotropins.1,3
; @; A4 r# k" o9 wGonadotropin-independent peripheral preco-
" k& J3 X/ A0 L) K* }5 Ccious puberty in boys also results from inappropriate
; H5 ~$ y! M7 L; l* xandrogenic stimulation from either endogenous or+ I z8 } t6 ?
exogenous sources, nonpituitary gonadotropin stim-9 b1 p$ ?$ @# C4 G( }
ulation, and rare activating mutations.3 Virilizing
8 g0 ~, V% m3 r6 O. ^congenital adrenal hyperplasia producing excessive
0 N3 k% }- ]" B& gadrenal androgens is a common cause of precocious
# e9 O' ~; i0 \ q8 d; a3 Ppuberty in boys.3,4 Y& R, k2 `7 j ?9 O
The most common form of congenital adrenal
$ \1 n ?2 `. ]# bhyperplasia is the 21-hydroxylase enzyme deficiency.0 e4 b, b7 O4 [
The 11-β hydroxylase deficiency may also result in
# P% j6 S* r4 u# j/ N: Qexcessive adrenal androgen production, and rarely,+ |7 C$ O+ X; e% k$ _: w) s
an adrenal tumor may also cause adrenal androgen4 E6 v% e% L3 b+ ~* Q1 T
excess.1,3
' r" T3 f& W2 O& h* |# T4 _at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
! z; a$ R% m9 l- }542 Clinical Pediatrics / Vol. 46, No. 6, July 20075 G: T8 y5 c' \+ x
A unique entity of male-limited gonadotropin-, y W; D! X! V7 J5 P
independent precocious puberty, which is also known
; i4 f9 _0 G$ I- @6 b# l9 ~8 X' i1 tas testotoxicosis, may cause precocious puberty at a" r! p+ M% Q2 {/ K7 ^: L
very young age. The physical findings in these boys% x8 Q% Y( C+ |* T N) t
with this disorder are full pubertal development,3 i& x* r; v! J- M
including bilateral testicular growth, similar to boys
" i# j3 c0 _; _with CPP. The gonadotropin levels in this disorder) W7 h& N/ b( f
are suppressed to prepubertal levels and do not show
8 M2 V* k& G) Dpubertal response of gonadotropin after gonadotropin-
3 t* c" b! P7 B1 Rreleasing hormone stimulation. This is a sex-linked
, o( t! B; z3 |" x q* F; xautosomal dominant disorder that affects only! B" N x7 J& o" |
males; therefore, other male members of the family: Y, U1 c1 t' O
may have similar precocious puberty.3' C6 t) [: Q- Q, u& i
In our patient, physical examination was incon-$ c3 L/ V0 f% z6 g' P
sistent with true precocious puberty since his testi-
2 F; `6 y# s1 ^cles were prepubertal in size. However, testotoxicosis8 g: ]- u Q, r+ ~9 c# M
was in the differential diagnosis because his father
0 g; L: E/ B6 {2 xstarted puberty somewhat early, and occasionally,! f$ H4 T9 G& M
testicular enlargement is not that evident in the
" H0 o! y' |8 [( V) K7 \7 _' }. R; Bbeginning of this process.1 In the absence of a neg-
7 ~; A$ q7 I' d3 V4 _ative initial history of androgen exposure, our' I8 |9 M1 u9 D0 k9 T# Z( N$ a
biggest concern was virilizing adrenal hyperplasia,% A6 S: Z$ ?7 P$ P, K
either 21-hydroxylase deficiency or 11-β hydroxylase
N$ t3 P+ M j# X% ideficiency. Those diagnoses were excluded by find-/ N: k. f, @2 d( }/ w% D+ F- Y' }/ L
ing the normal level of adrenal steroids.
3 H6 H: W5 n8 D/ V7 yThe diagnosis of exogenous androgens was strongly; }6 G! x! U* _% _( r
suspected in a follow-up visit after 4 months because
O, Q0 `) ^' ^$ g! Zthe physical examination revealed the complete disap-. n% K, k+ _8 C6 \# L% }& x
pearance of pubic hair, normal growth velocity, and3 d' w$ \" h* G; z+ o
decreased erections. The father admitted using a testos-! c' j3 d* x- E. o/ D
terone gel, which he concealed at first visit. He was
8 z! j- l+ k( V9 _2 X, rusing it rather frequently, twice a day. The Physicians’' u* u; f/ g: U# V9 H9 t
Desk Reference, or package insert of this product, gel or
* X6 ~& Q6 p0 x- r1 n: xcream, cautions about dermal testosterone transfer to
4 X4 I) V4 Q, O, z" r3 Wunprotected females through direct skin exposure.
6 F% ?- F2 a! m, E/ |7 |Serum testosterone level was found to be 2 times the; s3 O7 E5 ^1 R
baseline value in those females who were exposed to
4 M/ |7 P# i: o# A# ^# \. u# keven 15 minutes of direct skin contact with their male. Z' t8 N* y7 P9 X1 ?2 g5 \1 t
partners.6 However, when a shirt covered the applica-3 c: M _8 C" p
tion site, this testosterone transfer was prevented.
* w6 z5 c2 ?9 }) sOur patient’s testosterone level was 60 ng/mL,
$ u2 Z7 e+ s$ v& z7 X _6 Lwhich was clearly high. Some studies suggest that# Y0 [9 M9 o% V% y1 j& e4 {
dermal conversion of testosterone to dihydrotestos-$ D, d6 J& I2 X3 Z F; s/ C
terone, which is a more potent metabolite, is more9 v. x; ^2 u& z* X. @! a* q
active in young children exposed to testosterone( k9 q% P( c. S( f. g% q
exogenously7; however, we did not measure a dihy-
; U2 b/ l' g% Kdrotestosterone level in our patient. In addition to
7 f7 o, C% e' ]* D" vvirilization, exposure to exogenous testosterone in
% o' V6 t* z0 b; E( Uchildren results in an increase in growth velocity and" B& Y0 I6 }' x% B3 L
advanced bone age, as seen in our patient.
7 ^0 p; i" T d9 {! eThe long-term effect of androgen exposure during5 H) s: Z, a9 t" G1 q9 ?9 Q1 l
early childhood on pubertal development and final
5 Q# v, |5 {7 V0 T! D: o2 |adult height are not fully known and always remain
' C" o* _3 O1 @' Y% c# va concern. Children treated with short-term testos-+ {4 g. m# D2 L# Q
terone injection or topical androgen may exhibit some
5 e7 L! x+ b( uacceleration of the skeletal maturation; however, after
; d# y+ B3 P+ M( C _/ u/ Gcessation of treatment, the rate of bone maturation
: R& Y! \$ E* U$ c" L! t- |decelerates and gradually returns to normal.8,9
1 K# m7 r6 j6 r9 W% L0 ~There are conflicting reports and controversy
( L; {' m `/ }# @4 r% {* T' {over the effect of early androgen exposure on adult
6 b8 j8 r( n" }: J5 m* J1 M$ S2 C8 ppenile length.10,11 Some reports suggest subnormal
, f5 H! H3 M/ L' nadult penile length, apparently because of downreg-# _2 |5 f$ P# Y; c. W
ulation of androgen receptor number.10,12 However,
/ Y! R7 u" R! a8 M! [1 W+ @/ uSutherland et al13 did not find a correlation between% T& ?" {" a3 @ m& d( X0 s- P: \
childhood testosterone exposure and reduced adult' ?, o5 G9 Y0 B0 V" i: n
penile length in clinical studies.
. G7 U# X' h& l: iNonetheless, we do not believe our patient is8 J) f2 C% Y# p$ S
going to experience any of the untoward effects from3 [4 x3 N4 u' m; u, [9 m! [ b
testosterone exposure as mentioned earlier because, w/ s8 w9 w2 A' t) [1 H
the exposure was not for a prolonged period of time.
- K& P) N2 W9 Z3 F0 a5 S1 H2 `Although the bone age was advanced at the time of
3 e$ v. Q1 Y; l, N+ tdiagnosis, the child had a normal growth velocity at
( y3 x) S" Y; athe follow-up visit. It is hoped that his final adult1 b; K- m0 S- i0 V9 I0 [8 K
height will not be affected.
+ J+ I" c* B% vAlthough rarely reported, the widespread avail-
; K% d* X8 ?2 cability of androgen products in our society may
+ j3 r- [3 \3 y" |indeed cause more virilization in male or female
: x8 }& n. s v$ {children than one would realize. Exposure to andro-. J' y h" i X5 ]
gen products must be considered and specific ques-# D. R5 T6 Q( D/ L/ K
tioning about the use of a testosterone product or$ ^& K3 x) D" C+ ?! o7 Z3 u9 n$ t
gel should be asked of the family members during
7 u+ N8 C6 Y- R9 g* Rthe evaluation of any children who present with vir-7 A$ H8 [" \) b: K5 E
ilization or peripheral precocious puberty. The diag-( k0 I2 R# n0 Q1 R
nosis can be established by just a few tests and by
( l, L, I l) r! happropriate history. The inability to obtain such a+ V6 l& _, J/ k
history, or failure to ask the specific questions, may
3 |* V) K( ]; z/ P' Tresult in extensive, unnecessary, and expensive; H0 [5 p7 R* [+ X9 N' `
investigation. The primary care physician should be
4 V; [: w) D6 {, h) e! R+ Taware of this fact, because most of these children
# r- X+ y5 X. Z( G# R7 }6 B, lmay initially present in their practice. The Physicians’
/ e, F ?7 @6 |* l- a: w. {Desk Reference and package insert should also put a
4 d8 W9 [: q9 Q) p9 ^+ z4 }1 fwarning about the virilizing effect on a male or
8 g. I; `6 E; k; P( Sfemale child who might come in contact with some-
! L2 v" `" V1 C& I& Uone using any of these products.
: M( ]: g/ j6 B6 hReferences
7 |) W1 i) @# X" s3 M1. Styne DM. The testes: disorder of sexual differentiation' j. f5 K, v: t% }8 d4 l; U6 k
and puberty in the male. In: Sperling MA, ed. Pediatric0 Q) S) v" f) g' x1 s) G
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
& m" r- a! K. S2002: 565-628.
. U: G" p2 H. v' P# x: k2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious, M! L9 W5 A6 g4 p! _
puberty in children with tumours of the suprasellar pineal |
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