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Sexual Precocity in a 16-Month-Old
2 w9 e! e7 H+ RBoy Induced by Indirect Topical N Y ^5 v; D+ e1 l
Exposure to Testosterone
" U# N% E6 k h) {Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2 h$ x- {, W6 N1 Q& h
and Kenneth R. Rettig, MD1
3 P0 c- i, D) i5 P4 X& U, O4 |- ~Clinical Pediatrics; }6 n, n4 X$ L& A4 K! P
Volume 46 Number 6) A: N" D' g1 M* @
July 2007 540-543) K1 W# r4 f- n& x( \: q1 b" V
© 2007 Sage Publications9 {$ b+ I) l$ O1 Y' U
10.1177/0009922806296651% n' b% |3 g- {5 {3 w( o
http://clp.sagepub.com
" W9 b8 s: v( l5 `hosted at
7 f! z1 t: a" W+ W4 Y; \http://online.sagepub.com
; S) F5 I3 [0 J7 JPrecocious puberty in boys, central or peripheral," b9 E8 m7 j# D, k, ^$ ~+ j# P
is a significant concern for physicians. Central |6 {6 q0 u3 L) M, s, e
precocious puberty (CPP), which is mediated/ p/ i$ ?8 Z$ N/ A. n; S i
through the hypothalamic pituitary gonadal axis, has& c! F/ g8 |6 H9 p3 o3 P" b8 l, D
a higher incidence of organic central nervous system; t- n$ Y! K/ M. a; ^
lesions in boys.1,2 Virilization in boys, as manifested' I$ ]' W- j. J3 c
by enlargement of the penis, development of pubic# z8 L* a' s6 Y8 c: s+ N: n* t
hair, and facial acne without enlargement of testi-+ y. `8 } O0 |& {
cles, suggests peripheral or pseudopuberty.1-3 We
3 ^. L" Z, w f4 b0 p, X- Ureport a 16-month-old boy who presented with the
2 {2 z- l7 ^0 x' Senlargement of the phallus and pubic hair develop-4 A8 r( F9 g5 t( e
ment without testicular enlargement, which was due; f% W" k5 I+ d/ I
to the unintentional exposure to androgen gel used by5 p: E% \8 ~1 w1 w
the father. The family initially concealed this infor-
# Y$ Q' a) g, B4 q. Bmation, resulting in an extensive work-up for this
; Z$ R) m# n0 _child. Given the widespread and easy availability of
8 @1 ~4 j6 h& J# q% Dtestosterone gel and cream, we believe this is proba-
a0 I! |' r5 Ubly more common than the rare case report in the ~" e: [1 D$ e/ \5 a" u
literature.4" R5 G& e R: y B5 I/ _
Patient Report' f% u% X6 Z r* z( e* t$ a( V
A 16-month-old white child was referred to the
; ]7 @. c! m" j* `( k6 \' J0 j0 Zendocrine clinic by his pediatrician with the concern2 \* e3 D4 b; d$ m9 d
of early sexual development. His mother noticed
2 P8 A1 L7 P2 Jlight colored pubic hair development when he was! J9 \0 t: X& M
From the 1Division of Pediatric Endocrinology, 2University of
' i8 G. p* J6 [3 Y6 g% W( R2 SSouth Alabama Medical Center, Mobile, Alabama.
0 j/ J+ w- ^3 \; ] r0 b/ eAddress correspondence to: Samar K. Bhowmick, MD, FACE,; X* W( o2 w% r/ C* p. u4 ?7 z
Professor of Pediatrics, University of South Alabama, College of' t, C" w: g9 \' V/ T- h% S) Y
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;" H* F* A' V- }( V$ O9 @& L2 K
e-mail: [email protected].: p N* g6 X8 \; V* L
about 6 to 7 months old, which progressively became2 z) f8 e2 A, n" c- e- S
darker. She was also concerned about the enlarge-6 d% z' ]- p5 \7 E
ment of his penis and frequent erections. The child
) e! h/ @0 H2 M) i. [was the product of a full-term normal delivery, with
u2 u' x; j& R" l3 q; [! N, |a birth weight of 7 lb 14 oz, and birth length of
4 I' ?: k' ?* g+ w8 ^20 inches. He was breast-fed throughout the first year
# q3 W/ ]. N6 y2 Fof life and was still receiving breast milk along with
, S* |- v4 u5 b& F5 o% V; zsolid food. He had no hospitalizations or surgery,
4 H1 z; |2 [( dand his psychosocial and psychomotor development
8 x9 M! Q$ E5 Y! Vwas age appropriate.* ~2 y5 H( L$ E1 N# J
The family history was remarkable for the father,0 ~, L3 i9 `4 ~% i. B6 ?6 r8 O3 n U
who was diagnosed with hypothyroidism at age 16,
$ Y5 F2 \" ^/ Q/ S3 Q0 Owhich was treated with thyroxine. The father’s
o w+ G1 n! M0 oheight was 6 feet, and he went through a somewhat
% a: @% ?: W7 Iearly puberty and had stopped growing by age 14.
. F$ N3 { R; q5 @$ PThe father denied taking any other medication. The3 Q; T/ z* N; @5 s7 ~
child’s mother was in good health. Her menarche- a" X. J1 W8 o# j
was at 11 years of age, and her height was at 5 feet
$ ?, D' ?2 b' N$ u5 inches. There was no other family history of pre-4 O& A, h& R: C' b
cocious sexual development in the first-degree rela-& b7 L! ?' `5 [7 [+ j
tives. There were no siblings.
1 x- t' S5 Y! WPhysical Examination: o! v Z( b+ ~- A
The physical examination revealed a very active,! _# X; A {$ F' c8 J: X" V. R
playful, and healthy boy. The vital signs documented
. E7 n& h# x/ la blood pressure of 85/50 mm Hg, his length was' g& j, j' U* s5 z$ X, H
90 cm (>97th percentile), and his weight was 14.4 kg
) r- ~: Q3 E) y; F( m9 R(also >97th percentile). The observed yearly growth1 c) }+ Q) C. X, [$ _- c
velocity was 30 cm (12 inches). The examination of
1 X, K6 Y1 \/ X* p) v. s c* }- O2 kthe neck revealed no thyroid enlargement.
& v+ C! R7 _7 YThe genitourinary examination was remarkable for$ z/ |' m: Q1 ~6 w5 U/ M
enlargement of the penis, with a stretched length of' L4 x9 K3 c- h1 P! s2 L) {) x# L6 ^
8 cm and a width of 2 cm. The glans penis was very well
0 A2 V9 A& ]2 k# T3 K5 h9 Q) d! bdeveloped. The pubic hair was Tanner II, mostly around
& n2 W1 E. v' E, ?0 m540
1 i5 _% ]2 B: Qat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
( q+ T' s8 X' I8 ]0 H5 N) m7 E( I. fthe base of the phallus and was dark and curled. The4 h1 d5 w; ]3 Z! \2 v
testicular volume was prepubertal at 2 mL each.
! n1 N9 T0 y9 ^The skin was moist and smooth and somewhat
, V& R3 L5 S+ soily. No axillary hair was noted. There were no4 L* |+ G" n+ t$ M& E$ ]) Q
abnormal skin pigmentations or café-au-lait spots." q- S! G+ R3 @
Neurologic evaluation showed deep tendon reflex 2+5 T, d$ f! z, e( B( L2 Z; x
bilateral and symmetrical. There was no suggestion8 L0 B4 v- ?. R: w$ y# a5 ~3 g
of papilledema.
% t+ O' S$ C5 l( _4 _ q2 VLaboratory Evaluation
5 g4 n; T0 w! q8 t) x& ]. C1 b$ g6 NThe bone age was consistent with 28 months by
4 `# R6 O: P5 X6 b3 o0 Yusing the standard of Greulich and Pyle at a chrono-
4 e' p2 ^: Y1 z7 nlogic age of 16 months (advanced).5 Chromosomal
" J1 U+ D* ]5 Y# t+ y8 f. n- {6 vkaryotype was 46XY. The thyroid function test
9 C e. k5 ~ Q5 F7 Jshowed a free T4 of 1.69 ng/dL, and thyroid stimu-; R4 @! `( U9 X3 N/ ~: ^
lating hormone level was 1.3 µIU/mL (both normal).
' @* N& M8 G6 U# c; iThe concentrations of serum electrolytes, blood8 j$ k) I, u9 R! x
urea nitrogen, creatinine, and calcium all were
2 ~. Y- D( [' p4 t7 y, I% _( ^# ywithin normal range for his age. The concentration
8 ?7 V9 S5 ]6 r& Mof serum 17-hydroxyprogesterone was 16 ng/dL
, W$ V9 H0 U) @: J, Y% V(normal, 3 to 90 ng/dL), androstenedione was 20/ q2 z" |8 f0 D7 d! |
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
( O }! K# L& g4 n/ _terone was 38 ng/dL (normal, 50 to 760 ng/dL),# q/ K& A) X r; T
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
: x1 E3 [& X4 X6 g49ng/dL), 11-desoxycortisol (specific compound S)9 D8 g- e' ~0 w, H
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-9 g+ s: s3 `) a4 O
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
0 B7 v' H& t& o$ C0 l# Htestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
8 X1 q( A% ]3 J, ?* land β-human chorionic gonadotropin was less than
/ I4 m6 [* u. A; w! k5 mIU/mL (normal <5 mIU/mL). Serum follicular
+ c5 B5 {4 ]5 astimulating hormone and leuteinizing hormone
0 @; F! k4 q3 Wconcentrations were less than 0.05 mIU/mL, R, O# R; Z/ h
(prepubertal)./ ]4 R% ~2 o/ T4 T1 q. P
The parents were notified about the laboratory
0 T6 Z: N; t) s4 E' presults and were informed that all of the tests were
; ?& c7 W, u* E% Enormal except the testosterone level was high. The
8 W7 x! a5 @4 v8 o p9 S4 {- Yfollow-up visit was arranged within a few weeks to2 O/ ]1 b# C7 n; G- V+ y6 \ T! F
obtain testicular and abdominal sonograms; how-
" v |. n0 F0 k! \ever, the family did not return for 4 months.
# X, W6 ?7 v# e- d- L4 z5 pPhysical examination at this time revealed that the5 e1 [( e6 d7 m
child had grown 2.5 cm in 4 months and had gained: ?# _ e4 n2 W8 ?/ a3 n" [# a
2 kg of weight. Physical examination remained
" X" S3 Y' }& u+ z9 B- {unchanged. Surprisingly, the pubic hair almost com-
2 @3 e! `# y8 H9 S3 @5 k: Cpletely disappeared except for a few vellous hairs at
* g9 V$ S& \0 p1 F: Nthe base of the phallus. Testicular volume was still 2) @2 N- \3 J+ ]/ ^
mL, and the size of the penis remained unchanged.. b3 A/ W% M' Y9 w9 [5 k) K/ Y) a
The mother also said that the boy was no longer hav-
3 [9 k7 p% W* t x9 r aing frequent erections.# g+ j) r4 x4 s' }6 T
Both parents were again questioned about use of
% Y" h" F- f6 U9 X7 P7 qany ointment/creams that they may have applied to6 P0 M+ U, j% \) W* j
the child’s skin. This time the father admitted the
% X6 N. q+ O9 s2 H, h) @: VTopical Testosterone Exposure / Bhowmick et al 541
$ F) f+ w+ N* T2 juse of testosterone gel twice daily that he was apply-
5 N) s1 z$ [3 V$ Eing over his own shoulders, chest, and back area for; G0 P: |9 ~/ Y6 L9 {3 i8 i
a year. The father also revealed he was embarrassed, [# ~; u& g; L! O' n' ]$ F& E0 A
to disclose that he was using a testosterone gel pre-
3 }! V( {$ A- h: V7 ~- F& Kscribed by his family physician for decreased libido
/ y2 J- V& \0 o: Hsecondary to depression.
1 f3 [7 H L$ v0 \The child slept in the same bed with parents.$ Q6 Q# @' [9 I
The father would hug the baby and hold him on his
k# H& F0 e3 k' h8 ~) Q5 B; {8 H4 M' p+ Rchest for a considerable period of time, causing sig-. d6 o# d* t( b/ k6 S$ S
nificant bare skin contact between baby and father.
& F$ W1 [. g0 u BThe father also admitted that after the phone call,, n1 F* N" F5 T: ~2 o
when he learned the testosterone level in the baby
5 m5 J+ C7 z, Hwas high, he then read the product information
) a7 z) Z/ a8 Y" Qpacket and concluded that it was most likely the rea-
+ u* V5 n& Y3 q6 dson for the child’s virilization. At that time, they) m0 n- E9 E+ f; _
decided to put the baby in a separate bed, and the# ]7 }+ U. r1 [ u! ]' a
father was not hugging him with bare skin and had
# K' C- f4 m: @4 L* b2 w! sbeen using protective clothing. A repeat testosterone
W% v/ h$ D, t$ l7 P* s* mtest was ordered, but the family did not go to the
/ b! i1 N$ w: x3 J8 c- V2 |laboratory to obtain the test.2 x! D4 ]# c5 K& Z" \
Discussion- @4 z6 ^! n6 u9 T/ n& B
Precocious puberty in boys is defined as secondary
' R) M# ~5 h9 ~; M8 N2 Hsexual development before 9 years of age.1,4
" O- k9 E0 `3 q' ?1 ?Precocious puberty is termed as central (true) when) {% C$ R% M7 V( d* b
it is caused by the premature activation of hypo-2 H$ d F% }0 O! x
thalamic pituitary gonadal axis. CPP is more com-
5 R- W2 O9 d0 bmon in girls than in boys.1,3 Most boys with CPP
9 V* I! S. w. p& [* N$ qmay have a central nervous system lesion that is
Q) M( }. j$ A. f8 rresponsible for the early activation of the hypothal-
: D$ C6 D( F B: [% vamic pituitary gonadal axis.1-3 Thus, greater empha-% h2 v" C/ n9 }( q
sis has been given to neuroradiologic imaging in$ I5 W% h9 D2 ]& J
boys with precocious puberty. In addition to viril-
9 y. `$ \( J( p" r Nization, the clinical hallmark of CPP is the symmet-5 p, |; {" J4 R2 v+ e
rical testicular growth secondary to stimulation by
3 w. D# B0 q1 N" ?' @8 v) J; agonadotropins.1,3
1 F' W \0 y! H: R. l( c2 HGonadotropin-independent peripheral preco-
- x# H- S* A5 S% ^cious puberty in boys also results from inappropriate
) F$ d. y: d; E6 E) D% {androgenic stimulation from either endogenous or, e* q! r- K* q; H5 I
exogenous sources, nonpituitary gonadotropin stim-" w) \2 b; k$ P. R+ V
ulation, and rare activating mutations.3 Virilizing+ f% o2 X0 f$ R
congenital adrenal hyperplasia producing excessive
+ D5 s, L% U4 }/ `+ t2 K' D6 Uadrenal androgens is a common cause of precocious T. B! O6 r' ?: ?6 ]1 |
puberty in boys.3,4+ i* }. w6 z- O. ^2 R
The most common form of congenital adrenal7 c% K5 M: s+ C% t% ?
hyperplasia is the 21-hydroxylase enzyme deficiency.
3 w8 i; ?* m7 z5 Z: x; ?' HThe 11-β hydroxylase deficiency may also result in
0 f' i2 Z* f# ^+ uexcessive adrenal androgen production, and rarely,# d( z/ }: d9 X1 P5 v. C
an adrenal tumor may also cause adrenal androgen- r- O2 S6 z8 x" n: e
excess.1,35 _/ ^2 {2 k* G" g) _3 H
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
5 V7 B$ G1 E7 E3 j3 X5 E, U3 ^542 Clinical Pediatrics / Vol. 46, No. 6, July 2007/ {$ }0 _6 \7 D$ w3 ^: D5 G
A unique entity of male-limited gonadotropin-. |; b- E' N0 o: b9 M& h% F
independent precocious puberty, which is also known
2 G o2 ]0 }! ^as testotoxicosis, may cause precocious puberty at a
: P' {' s% ?2 ]. i' E7 Svery young age. The physical findings in these boys5 o. J0 }& \' ^
with this disorder are full pubertal development,; m( \0 E) A- g& ~
including bilateral testicular growth, similar to boys/ ^0 H7 {9 I) Q7 l T( X
with CPP. The gonadotropin levels in this disorder4 j# v9 m2 `' f* n8 ]( h
are suppressed to prepubertal levels and do not show! @) O# M6 n# c/ E
pubertal response of gonadotropin after gonadotropin-1 _7 p6 m4 m6 j
releasing hormone stimulation. This is a sex-linked; y0 |! l7 z7 i7 F
autosomal dominant disorder that affects only
+ t+ V6 i% C a# X9 M6 m8 B/ jmales; therefore, other male members of the family# S1 Q$ j6 K' P, `4 m( S) s/ O
may have similar precocious puberty.3# a6 g. A( `# G# y* A2 B% o5 P" T
In our patient, physical examination was incon-
5 X, k2 c9 ~% f6 xsistent with true precocious puberty since his testi-3 \( K, j0 O; Z: l: j: ~1 Q
cles were prepubertal in size. However, testotoxicosis
$ g+ l* _- f; O& Hwas in the differential diagnosis because his father. l8 s2 b* [$ h- v
started puberty somewhat early, and occasionally,$ O4 b8 Q0 |" G( E; J/ I4 o3 M$ k1 s7 S4 ~
testicular enlargement is not that evident in the
4 \9 R1 @# b: nbeginning of this process.1 In the absence of a neg-
+ V4 w0 ?3 a4 v" }! |- o& Rative initial history of androgen exposure, our
! T- _3 F/ P# o3 r, P$ n" ~biggest concern was virilizing adrenal hyperplasia,
; M" E, h" n' a3 l4 q& `either 21-hydroxylase deficiency or 11-β hydroxylase
# s( l" j' ?, P0 p# Zdeficiency. Those diagnoses were excluded by find-% J& l7 ]+ }0 [2 ~/ X- {* L* X
ing the normal level of adrenal steroids.! Q# D; d, l+ B' V/ J" a7 K. D
The diagnosis of exogenous androgens was strongly/ Y/ v1 B/ ~. ^7 H! [% ^* E
suspected in a follow-up visit after 4 months because2 ]+ y8 |- O8 `9 @ Q
the physical examination revealed the complete disap-" a$ d2 u, E7 c6 i7 P
pearance of pubic hair, normal growth velocity, and
: S& u) \! _+ i4 r- [$ p5 qdecreased erections. The father admitted using a testos-
6 R- B- `; e+ B" j$ Wterone gel, which he concealed at first visit. He was% d: w' o* K: {5 L6 A: r( [0 C
using it rather frequently, twice a day. The Physicians’$ W' }) X B$ s5 b" H! }& U m, Y
Desk Reference, or package insert of this product, gel or
$ R# }( E! z- S8 _cream, cautions about dermal testosterone transfer to0 R( o7 V) N' M, z5 a5 b
unprotected females through direct skin exposure.
" { ?( @$ c. {8 V8 `; Y7 a% S# G$ G+ i! vSerum testosterone level was found to be 2 times the
5 F- M4 Y8 t7 O5 z7 k' Mbaseline value in those females who were exposed to
' G& F i0 G0 M }( _even 15 minutes of direct skin contact with their male
& z7 b5 a7 @. ppartners.6 However, when a shirt covered the applica-
) k# h8 K: M8 V, Q3 v3 Ition site, this testosterone transfer was prevented.
+ L1 ]( n9 U1 I0 j5 }, ~0 sOur patient’s testosterone level was 60 ng/mL,
; m/ r5 U9 i: L) o! l9 Bwhich was clearly high. Some studies suggest that* ~; y9 u- |$ d G
dermal conversion of testosterone to dihydrotestos-
( m; U1 p7 F) D! z& ?: s& yterone, which is a more potent metabolite, is more
2 T' i! k! S. Zactive in young children exposed to testosterone
9 E8 s3 t; a' b# C' ^" E$ ]exogenously7; however, we did not measure a dihy-
6 x/ T; M; m! U: x6 ]7 H+ Ndrotestosterone level in our patient. In addition to
, c, @6 R. p( a) Pvirilization, exposure to exogenous testosterone in
" o* n( \' t$ f6 ~, ~9 u8 L* }children results in an increase in growth velocity and# ?9 a$ H% \* L, k
advanced bone age, as seen in our patient.
5 m9 m9 r# t4 q( E+ R- `The long-term effect of androgen exposure during' E8 i3 }0 d3 I2 @) m
early childhood on pubertal development and final: D3 T9 P, w. u7 W
adult height are not fully known and always remain
) L K$ d+ |$ }7 U9 Z- n( {) za concern. Children treated with short-term testos-
8 Z% {# w$ X4 [; Tterone injection or topical androgen may exhibit some
! c' z4 \# D0 Z6 \3 hacceleration of the skeletal maturation; however, after
0 s: U' a8 ?% v. T( B0 F; ncessation of treatment, the rate of bone maturation+ V' ]% u3 L+ s! P
decelerates and gradually returns to normal.8,9
! A: I) P u6 }1 |; GThere are conflicting reports and controversy
J7 y% @- h' h0 mover the effect of early androgen exposure on adult
# W. ^* E+ i4 v% ipenile length.10,11 Some reports suggest subnormal5 g* p' R! D! v# L$ i' I
adult penile length, apparently because of downreg-
/ b$ E- f6 d" L/ Fulation of androgen receptor number.10,12 However,
' _) C7 F( z* g4 r! m& vSutherland et al13 did not find a correlation between
; S; Q- r/ x/ x o/ W! r Ychildhood testosterone exposure and reduced adult
' t: j& c' P- Zpenile length in clinical studies.
9 W4 R' t" @4 X7 ANonetheless, we do not believe our patient is
: z5 @% P) E1 I: L# ~going to experience any of the untoward effects from
& O( F4 e, ?3 v* M6 [! X/ w. ptestosterone exposure as mentioned earlier because2 I0 P2 @) o) F: c9 Z
the exposure was not for a prolonged period of time.
1 _% t7 W) U& ~( I5 X& eAlthough the bone age was advanced at the time of
1 S# Y% ?0 R# J H/ {/ o ~diagnosis, the child had a normal growth velocity at
2 {( N" D+ a8 t6 Rthe follow-up visit. It is hoped that his final adult
6 W, ~4 ^$ a5 o8 F2 J) Q+ b- R9 kheight will not be affected.
3 v4 |! f) e+ Y& v& t) wAlthough rarely reported, the widespread avail-
- v! d, P( k0 v, ^& m0 @- s4 ^ability of androgen products in our society may
# X2 [2 i- H$ q2 J8 _. ~8 Zindeed cause more virilization in male or female" V( C! w7 B2 k5 B3 m- W0 Z* h
children than one would realize. Exposure to andro-
! f+ I5 Q$ Y; X0 ]. wgen products must be considered and specific ques-
3 D% I# x0 {6 i) E7 }- P% Utioning about the use of a testosterone product or
1 R/ ^* }% e% g0 P8 ^gel should be asked of the family members during
$ a# k& ] i# N( \the evaluation of any children who present with vir-
, | `$ R; v% F" b' c+ ?. G. r) }! Pilization or peripheral precocious puberty. The diag-
, Q9 A; v8 O. X% l& p* N; ~nosis can be established by just a few tests and by
4 a8 y g N- ]9 m: Zappropriate history. The inability to obtain such a1 l% X2 H) Q4 M" M
history, or failure to ask the specific questions, may
2 q3 J$ I, Q% h: Presult in extensive, unnecessary, and expensive
: P8 N6 V1 v/ A+ R; |investigation. The primary care physician should be
2 `4 @2 n$ D6 Y# C' `3 xaware of this fact, because most of these children
n+ G0 Q% F" q' U5 kmay initially present in their practice. The Physicians’
1 B1 N8 X6 F3 z+ A; VDesk Reference and package insert should also put a4 e: R3 ^& K5 Q, k
warning about the virilizing effect on a male or
8 U; D4 B1 L8 ]# h) Y3 f0 {; m7 tfemale child who might come in contact with some-
4 s& F, l* r* A( B; W9 x1 O- j: n6 @, uone using any of these products.( q$ Q9 F! j( N, }6 p8 U% k
References
/ Z5 @ ~3 N' `3 z1. Styne DM. The testes: disorder of sexual differentiation
# ~2 A" ?- J1 U! q2 I0 Gand puberty in the male. In: Sperling MA, ed. Pediatric4 R4 j7 P4 O( x) l
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;) O+ A; Y" B% g" i
2002: 565-628.) B3 f* G7 H& f
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious, a- ]: A4 f4 b9 f0 J- ?
puberty in children with tumours of the suprasellar pineal |
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