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Sexual Precocity in a 16-Month-Old
( l. h* L( h7 P" D8 O9 O& YBoy Induced by Indirect Topical
) L& ?- |* J7 ^& l# p3 cExposure to Testosterone
# O* D; |! i& t* |7 Q0 E2 aSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2' D i2 `8 t2 m, \" a
and Kenneth R. Rettig, MD1
$ Y9 A3 S7 H3 y3 {) k. j, HClinical Pediatrics" M, `+ N0 {! X
Volume 46 Number 69 c4 ` a e9 h% Y* R
July 2007 540-543* N$ {6 m: }3 @! V1 \$ M
© 2007 Sage Publications
2 L/ c% w: S& y8 o10.1177/0009922806296651/ |+ i( t+ J) W; X
http://clp.sagepub.com) N7 k! d: m' v! p3 y
hosted at
4 h) M& O1 P3 }2 x8 J# m: Dhttp://online.sagepub.com
* r' @+ b( q' z/ o; E9 I2 @0 K' w0 QPrecocious puberty in boys, central or peripheral,
# M' k, x1 `- c% P5 i" O4 v; w& Ais a significant concern for physicians. Central; V& V0 U4 @$ C8 p N& e* N
precocious puberty (CPP), which is mediated- `/ X- W5 r1 W9 D' Y
through the hypothalamic pituitary gonadal axis, has
# T3 D2 n: N! H6 Va higher incidence of organic central nervous system5 X& z1 k- g% }6 d: j) x4 s+ V
lesions in boys.1,2 Virilization in boys, as manifested; \! k" d! U# s' m0 x' N: a
by enlargement of the penis, development of pubic( Z) ~+ Y M! S# b
hair, and facial acne without enlargement of testi-& |4 B- h" Y+ @6 P
cles, suggests peripheral or pseudopuberty.1-3 We" L+ E8 D7 G4 t: y7 ~
report a 16-month-old boy who presented with the4 T. z) C" U f& }6 d- f
enlargement of the phallus and pubic hair develop-
: J2 l; o; ~: xment without testicular enlargement, which was due; R* Q2 @* R# f) Y& I7 C; e" J
to the unintentional exposure to androgen gel used by5 P% t& O. P) ~* `& ] _$ v
the father. The family initially concealed this infor-, V @ w% X# k: V6 D0 y a& J
mation, resulting in an extensive work-up for this
5 ?% P# C& n4 R7 mchild. Given the widespread and easy availability of
+ M4 Q4 l2 v: N' I: ~! y& l5 a" ftestosterone gel and cream, we believe this is proba-9 F- t/ `: Q5 W) w& [: p
bly more common than the rare case report in the
8 g3 v5 b* @, O& j" |5 M/ Sliterature.4
! b3 m( ~* m5 s* E. VPatient Report0 G6 {8 [2 ^! y7 Q
A 16-month-old white child was referred to the8 v4 }0 C8 N$ I' q% X
endocrine clinic by his pediatrician with the concern
7 I1 G2 o1 Q4 C$ j( M+ Nof early sexual development. His mother noticed! b" C U1 t9 ^1 C7 c
light colored pubic hair development when he was+ F# u( {; T. f" O# F
From the 1Division of Pediatric Endocrinology, 2University of9 c7 H& ]2 ?+ _
South Alabama Medical Center, Mobile, Alabama.7 r* M1 R; S5 t8 }' e& R
Address correspondence to: Samar K. Bhowmick, MD, FACE,
0 `6 e- |5 N+ mProfessor of Pediatrics, University of South Alabama, College of
8 x: k9 l/ `3 E. O5 W* U3 ?+ SMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
- Q& |9 ]' k, b3 V: k& O' Oe-mail: [email protected].2 g' c( I3 _1 F/ {
about 6 to 7 months old, which progressively became
n/ q' E/ |) y$ A& I$ l+ P' l: h! Udarker. She was also concerned about the enlarge-) ?' E& p! r! A1 n2 {: e
ment of his penis and frequent erections. The child
0 a. N1 C* r' {2 t" I! Ywas the product of a full-term normal delivery, with
- ^9 k! c+ m" k$ i4 d4 d* C0 w- sa birth weight of 7 lb 14 oz, and birth length of8 _- V1 M5 n0 X8 l* c G
20 inches. He was breast-fed throughout the first year9 h! w" _4 A! D: s0 Y4 k
of life and was still receiving breast milk along with
. t, S7 B$ {# u& `, Z" v; W* gsolid food. He had no hospitalizations or surgery,1 g2 F" |% x, D4 o( E
and his psychosocial and psychomotor development) i# P1 T! H. `" v
was age appropriate.2 u+ P" l$ p6 s5 C7 s6 u5 {
The family history was remarkable for the father,) Y7 @; j( _9 ]4 |) v! R0 `
who was diagnosed with hypothyroidism at age 16,
) Y/ m! a# x7 R; zwhich was treated with thyroxine. The father’s
# I$ r+ }+ @7 K: h4 `height was 6 feet, and he went through a somewhat
( x, \0 a2 `; searly puberty and had stopped growing by age 14.# G# U+ y) P( t0 X! Q" X2 e0 f
The father denied taking any other medication. The6 O, l v6 [! ^- [# s) p
child’s mother was in good health. Her menarche+ ~5 }! o0 `: n) ^( E* G: ~% t# n
was at 11 years of age, and her height was at 5 feet
* h( |1 F$ Q1 r( e+ a5 inches. There was no other family history of pre-
% _! F( R {9 u/ _cocious sexual development in the first-degree rela-0 ~& X9 c p: F" X
tives. There were no siblings.
0 @0 C5 Q/ Y& i, RPhysical Examination8 l7 F& ~9 ^6 O' i7 F# X U
The physical examination revealed a very active,
, r3 F6 a4 d) [- v+ s- J- N( Gplayful, and healthy boy. The vital signs documented
' Y- T; l; }6 l3 ^! M3 k# ^a blood pressure of 85/50 mm Hg, his length was
0 T) d+ u$ B3 h. z90 cm (>97th percentile), and his weight was 14.4 kg
7 \9 y4 H( H4 b6 n: a6 {3 `( n2 h(also >97th percentile). The observed yearly growth
6 n4 K# c; J, t: @0 r uvelocity was 30 cm (12 inches). The examination of1 Y3 t2 |9 J2 ?& ?
the neck revealed no thyroid enlargement.
7 U6 ^7 I' b, U! ?The genitourinary examination was remarkable for
+ T( e) X; ?5 u7 H. Tenlargement of the penis, with a stretched length of, D3 q% u" ~& e2 e% J
8 cm and a width of 2 cm. The glans penis was very well
, d; C/ j2 m, B) E9 _$ q5 @$ `developed. The pubic hair was Tanner II, mostly around
! m- F* j* L* D540
8 q& W) ]; k: o+ O% Q2 J; lat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from* k$ M) v* q+ }. R% h7 Z( ]
the base of the phallus and was dark and curled. The
8 o9 Y! I, [) U" N" qtesticular volume was prepubertal at 2 mL each.
0 D1 F4 m+ N( _+ n8 P: GThe skin was moist and smooth and somewhat9 D8 k8 q+ V( w3 j5 ~' v
oily. No axillary hair was noted. There were no& B% D$ H. u0 d! N0 m' k
abnormal skin pigmentations or café-au-lait spots.
( J5 l1 Y$ e, w' T; x ?Neurologic evaluation showed deep tendon reflex 2++ t; |4 v1 E8 P) i; O4 b' U# n! }1 V
bilateral and symmetrical. There was no suggestion S2 N% I u" U( T; A
of papilledema.
( P$ B( h8 L4 GLaboratory Evaluation
$ H: C1 X7 H$ \1 m; M* wThe bone age was consistent with 28 months by
0 S6 v4 j f4 j6 v: v$ X1 V9 Wusing the standard of Greulich and Pyle at a chrono-& i' E* \) N$ f, X7 E
logic age of 16 months (advanced).5 Chromosomal' i9 \! H6 O# u" a# K
karyotype was 46XY. The thyroid function test
) {& d. ~2 P; k; E( L" c6 d% T; @showed a free T4 of 1.69 ng/dL, and thyroid stimu-
2 q- i4 F" X/ F, r7 Z' Elating hormone level was 1.3 µIU/mL (both normal).( A' ^% C; b/ U$ g9 ~; A
The concentrations of serum electrolytes, blood; Y# L2 `$ {2 D: U: \
urea nitrogen, creatinine, and calcium all were
2 X" B1 W% `7 A! f) T" l+ Y4 r! Pwithin normal range for his age. The concentration! X* p+ D ?! i
of serum 17-hydroxyprogesterone was 16 ng/dL
7 P% P5 c7 s7 _1 ^# r; L- p(normal, 3 to 90 ng/dL), androstenedione was 200 _, o1 [% @ M/ o8 p. F& x
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-" J+ C8 ?" s2 D: Y7 ?6 C
terone was 38 ng/dL (normal, 50 to 760 ng/dL),0 L) x$ c/ J, P4 n) K& _5 \8 M
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
) {4 S& p0 U! S2 i49ng/dL), 11-desoxycortisol (specific compound S)
/ M& t2 x' g+ e. A9 u' o, swas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-9 K) R$ V3 H( ~# \# r) _
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total6 P" _: c/ z: G
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),4 `' I$ O, K8 S' Z
and β-human chorionic gonadotropin was less than
& g" S k; B3 w# y* E5 mIU/mL (normal <5 mIU/mL). Serum follicular& Z2 A$ F4 i7 O( K& q5 E
stimulating hormone and leuteinizing hormone
{+ b, V. U- [- a# \concentrations were less than 0.05 mIU/mL
! i2 T- D- {" @2 o$ R% e(prepubertal)." Z: V# m+ J* M/ `, m) ?
The parents were notified about the laboratory
2 Z- Z* c" `) x2 `8 `results and were informed that all of the tests were* Y9 N; b9 f( o
normal except the testosterone level was high. The
2 t! z# o: F1 s* Zfollow-up visit was arranged within a few weeks to
: r5 n( y# g2 g. w/ U o. Q- @obtain testicular and abdominal sonograms; how-' d' x6 c E& R5 ~* b" j
ever, the family did not return for 4 months.
, o8 E8 h U% QPhysical examination at this time revealed that the
: v" h7 E' v1 echild had grown 2.5 cm in 4 months and had gained
% D9 i m {/ r) T; X% e9 \9 E0 W2 kg of weight. Physical examination remained8 n4 z6 m2 t( i) D
unchanged. Surprisingly, the pubic hair almost com-" l; y- ]4 ~& W: r, H- f# ?
pletely disappeared except for a few vellous hairs at
, b. L% ^2 [1 \) W L" H" fthe base of the phallus. Testicular volume was still 2
) T% X/ a; i3 d, c/ GmL, and the size of the penis remained unchanged.
8 i G& X- f. T6 F' A. tThe mother also said that the boy was no longer hav-
! u" A' E% L9 b/ L# m: `0 j( R+ Fing frequent erections.! n/ n) a! D) x
Both parents were again questioned about use of
, X9 v) r) M# f, k v2 |any ointment/creams that they may have applied to4 r- R+ g7 o# O* M) [- c
the child’s skin. This time the father admitted the
2 Y# z8 {7 ^4 o! R$ E& q, u9 ETopical Testosterone Exposure / Bhowmick et al 541: R* C d7 a" ?! v% E) R
use of testosterone gel twice daily that he was apply-
) H% T" V4 a1 o4 V4 F7 Xing over his own shoulders, chest, and back area for
/ W& D. h# f- d0 ]: Z6 s; ? A+ Ja year. The father also revealed he was embarrassed
8 h8 L6 B7 h/ l7 W# pto disclose that he was using a testosterone gel pre-, K) E3 M) U; J1 U& P
scribed by his family physician for decreased libido
" O& T' J' t8 w/ f4 I0 ~secondary to depression.% Q* L" ~2 z, D/ C
The child slept in the same bed with parents.
7 j6 e3 v# U7 _The father would hug the baby and hold him on his3 O) e" s+ Y: Q
chest for a considerable period of time, causing sig-
6 U, _1 A; q' U! Bnificant bare skin contact between baby and father.
0 w# G$ ~" I2 HThe father also admitted that after the phone call,
?- t8 d6 `; Z. F7 |when he learned the testosterone level in the baby5 Z4 U7 Q5 T; W
was high, he then read the product information- T, C# G4 y8 R
packet and concluded that it was most likely the rea-
; k, {8 ~+ Z; x( T5 ?son for the child’s virilization. At that time, they
8 O9 t" X1 |* R" J5 v( m) D9 Y! ydecided to put the baby in a separate bed, and the
! _8 r8 v7 d5 W3 j2 K: M0 k: Y% Ffather was not hugging him with bare skin and had9 }# f+ r9 b1 I- m5 @+ F
been using protective clothing. A repeat testosterone
. ~) _4 _# a, h1 Gtest was ordered, but the family did not go to the+ i7 D! O( [, Q. p. q7 k
laboratory to obtain the test.
A: m y) X7 C& }0 [ wDiscussion
, d) t7 C9 g+ m/ BPrecocious puberty in boys is defined as secondary
' q) p+ `! k U+ t2 psexual development before 9 years of age.1,4
9 `& F, p. U0 N# ]' c5 OPrecocious puberty is termed as central (true) when
) A+ q- V. F8 A, Bit is caused by the premature activation of hypo-1 j/ q0 }& _$ R3 s: O, [4 g
thalamic pituitary gonadal axis. CPP is more com-" M K0 z, v1 s) L2 Q7 ~
mon in girls than in boys.1,3 Most boys with CPP
`7 q; R- v: F# U0 K7 R3 gmay have a central nervous system lesion that is9 H4 |# g# F6 h' S/ D" U6 M
responsible for the early activation of the hypothal-
' A, X. D5 i# damic pituitary gonadal axis.1-3 Thus, greater empha-8 L; \$ \" d4 a5 L5 r* F& m$ _
sis has been given to neuroradiologic imaging in1 q) C4 }8 q% h9 R6 t& V
boys with precocious puberty. In addition to viril-
& J" `6 Y J* b5 sization, the clinical hallmark of CPP is the symmet-& i/ u& z' `8 C: Q$ _
rical testicular growth secondary to stimulation by
( f u% V5 d3 J' G! ~0 x9 `' _5 xgonadotropins.1,3
7 n( j6 w. H, ?3 c" MGonadotropin-independent peripheral preco-
8 [* [) K/ E; T u, X5 T) Jcious puberty in boys also results from inappropriate
9 L# p* |0 S( dandrogenic stimulation from either endogenous or4 Z+ d8 E K, d' u. W, X( [- A
exogenous sources, nonpituitary gonadotropin stim-
3 G" P) z- [/ U" F* `+ h/ s- lulation, and rare activating mutations.3 Virilizing
( j+ I, n1 V2 t: w' j$ `- fcongenital adrenal hyperplasia producing excessive
/ J) I. K! M+ t3 M& b2 ^1 dadrenal androgens is a common cause of precocious
+ n" q, d c6 B$ upuberty in boys.3,4" {2 W( a- f1 h/ V4 n9 y Z- C
The most common form of congenital adrenal/ _( m4 ]: Y8 ?2 d. ?* D
hyperplasia is the 21-hydroxylase enzyme deficiency.
, [' f: F- B. \% {- C3 xThe 11-β hydroxylase deficiency may also result in. H& O. n, S. ], T. y) F
excessive adrenal androgen production, and rarely,
( R8 W, @9 k1 E' }an adrenal tumor may also cause adrenal androgen
: Y- a% |4 ?, _: nexcess.1,3* z: [0 l7 X$ B6 v# R; {
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from% ]9 Q( W- e% T0 Z1 h! E5 Q3 I2 _) T
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
2 s; v5 E8 g! ~* n' N# N% @% b1 aA unique entity of male-limited gonadotropin-
- h( r0 t; Q' W0 G1 L/ g5 oindependent precocious puberty, which is also known
" n) j% W+ F2 T% V) R: D& z& yas testotoxicosis, may cause precocious puberty at a
+ n% I$ o& M. {( a Y& C) Rvery young age. The physical findings in these boys
! N; w# e9 _: S5 F5 s4 \with this disorder are full pubertal development,# M+ k5 I/ A6 R" I
including bilateral testicular growth, similar to boys) S- M# E0 ?: p
with CPP. The gonadotropin levels in this disorder
- V; G! A+ L! w& ~are suppressed to prepubertal levels and do not show
5 h' w0 F0 B7 ypubertal response of gonadotropin after gonadotropin-8 |- a' ?- r4 d
releasing hormone stimulation. This is a sex-linked
0 W7 T/ i' J) x4 x$ h( o; yautosomal dominant disorder that affects only; C( d3 K/ H ?
males; therefore, other male members of the family
A# n, E$ j9 x& O2 R- d; _: |may have similar precocious puberty.3
/ W! \& ]5 E, T) r% R6 k" ~In our patient, physical examination was incon-. H, p) i# I- P& P" F+ Y; m
sistent with true precocious puberty since his testi-& i2 m( |' ]+ u o9 ~6 v1 ] @" H
cles were prepubertal in size. However, testotoxicosis4 q; h, T& j' M7 L
was in the differential diagnosis because his father
9 b8 s, C+ r3 f$ [* b$ Y! Astarted puberty somewhat early, and occasionally," H0 n. o, G! x" Q$ ^6 b
testicular enlargement is not that evident in the
1 o9 {- N( `' }8 G, H% S( wbeginning of this process.1 In the absence of a neg-: u$ y, Y9 K; W$ w: ^
ative initial history of androgen exposure, our
7 y6 d/ B& M0 B6 m2 o Jbiggest concern was virilizing adrenal hyperplasia,7 g8 G1 o8 Y( n% N- w8 Z
either 21-hydroxylase deficiency or 11-β hydroxylase
5 ]2 t: o- s; vdeficiency. Those diagnoses were excluded by find-: E. x; W8 i8 {; n& `
ing the normal level of adrenal steroids.
0 N0 @9 q, L, l, M% r cThe diagnosis of exogenous androgens was strongly
) X7 A: i8 l+ D; Fsuspected in a follow-up visit after 4 months because
1 F, x0 R8 L, s8 [the physical examination revealed the complete disap-: y* F$ d( @/ q0 V; c! H
pearance of pubic hair, normal growth velocity, and; w& j7 g4 ?' B/ \
decreased erections. The father admitted using a testos-- D9 @6 _# s# x( I
terone gel, which he concealed at first visit. He was
, J! F& }2 w- u, ]/ vusing it rather frequently, twice a day. The Physicians’
" V4 }# F1 T- DDesk Reference, or package insert of this product, gel or9 i2 D" V) p( m( M$ Y( Y& Y9 U
cream, cautions about dermal testosterone transfer to
2 ?# O% a1 r* Zunprotected females through direct skin exposure.) m. @7 N# @7 f0 j
Serum testosterone level was found to be 2 times the9 N: J' R# h! s( R& \6 e
baseline value in those females who were exposed to' ]+ T2 [( w; h3 I5 Y8 ]. }
even 15 minutes of direct skin contact with their male
+ _+ w" j4 h/ O; I. _( Wpartners.6 However, when a shirt covered the applica-% X! F0 a \2 Y1 Z9 G/ Z
tion site, this testosterone transfer was prevented.2 `' p4 }8 j9 P4 g
Our patient’s testosterone level was 60 ng/mL,, _( t5 u6 {2 q5 l0 K( e' O I
which was clearly high. Some studies suggest that7 U! K5 m' b# b
dermal conversion of testosterone to dihydrotestos-/ I6 U9 m, v( z0 x6 O& |: a: X
terone, which is a more potent metabolite, is more6 V3 g6 W# Y5 j' g" Y' E
active in young children exposed to testosterone
: J1 l& ?, |7 h9 j9 @& }exogenously7; however, we did not measure a dihy-
9 W% I$ u: @" O$ H' W6 v1 ddrotestosterone level in our patient. In addition to3 j. U! X) W3 X" b/ E
virilization, exposure to exogenous testosterone in
0 J) |6 ]/ ~% z% Y7 |children results in an increase in growth velocity and
2 ^# E% h4 i: Y- b* J3 Vadvanced bone age, as seen in our patient.5 d N6 m" d9 ~8 c+ A
The long-term effect of androgen exposure during, T, L% l b/ R$ P1 _
early childhood on pubertal development and final
! g6 }$ _* O9 aadult height are not fully known and always remain
. |2 G& u4 o. s2 |6 d* R6 {a concern. Children treated with short-term testos-: F$ H4 q) S" l7 @
terone injection or topical androgen may exhibit some w4 z/ ~: c6 f: V/ v
acceleration of the skeletal maturation; however, after
7 h7 e+ Z1 c7 v8 f7 @. I9 ?cessation of treatment, the rate of bone maturation
/ S! w5 A4 K( z* gdecelerates and gradually returns to normal.8,91 L4 G) G7 u& ]: X7 s: j' r/ I
There are conflicting reports and controversy
; b* J0 P( o/ p! ^ |: Yover the effect of early androgen exposure on adult7 W: w& d2 f% P3 a$ u3 }0 M
penile length.10,11 Some reports suggest subnormal3 K, G0 I+ k8 i- q9 q! k3 |
adult penile length, apparently because of downreg-
: e6 I/ E: Y8 A! b3 @# Q! W& Y1 ?ulation of androgen receptor number.10,12 However,
I! Q" k* } b/ A& ^3 VSutherland et al13 did not find a correlation between
. q6 s. k" m$ H' u/ wchildhood testosterone exposure and reduced adult+ y+ p8 I9 Z3 C/ \9 r
penile length in clinical studies.$ k0 v* b/ n4 r& u4 ~0 J
Nonetheless, we do not believe our patient is
1 A \6 p& c _/ vgoing to experience any of the untoward effects from
- {3 h/ R, Z& B7 F: j$ \' d% y% jtestosterone exposure as mentioned earlier because+ ?2 d1 t N0 R" x0 w$ X& L
the exposure was not for a prolonged period of time.
+ C- m, a5 U9 h& W7 Z( vAlthough the bone age was advanced at the time of
5 W3 |' R0 l. O1 ~8 J0 vdiagnosis, the child had a normal growth velocity at2 \$ B1 |4 e, P2 M; [9 K* j
the follow-up visit. It is hoped that his final adult$ j# Q# h, A0 ~& H, M+ o9 c
height will not be affected." g% t/ h1 \, F6 B
Although rarely reported, the widespread avail-9 v$ Z8 c- G: k1 h U
ability of androgen products in our society may
* s( [4 ^$ u- z2 jindeed cause more virilization in male or female6 ?/ V, [. [) F% F$ G* S! W
children than one would realize. Exposure to andro- q9 g$ X* I* `5 b9 _
gen products must be considered and specific ques-, e' [6 I8 ` O, s, d# j+ g& ^! o
tioning about the use of a testosterone product or
* l: B+ Q. A W* L4 _! \& Jgel should be asked of the family members during6 ]) @ q, x8 _7 F
the evaluation of any children who present with vir-
5 ?. L0 T, u% X0 G4 G/ b7 z+ Kilization or peripheral precocious puberty. The diag-9 n" M& ~: c; z2 j, N
nosis can be established by just a few tests and by
; J' e8 K3 b6 B! `5 r, P kappropriate history. The inability to obtain such a& P- a6 o6 p) M4 t- O8 {. h2 U
history, or failure to ask the specific questions, may
, s7 N: K; R5 G3 oresult in extensive, unnecessary, and expensive
8 t7 @( v& ^# Z! s: ?investigation. The primary care physician should be
3 \& }0 @5 n3 c9 Zaware of this fact, because most of these children
6 `* V- G! ]9 o' t, amay initially present in their practice. The Physicians’
) C# z( V* X6 V$ x+ ~$ v" TDesk Reference and package insert should also put a$ x: I# j% L' X! y1 u+ N
warning about the virilizing effect on a male or; c4 H3 B: p {+ T9 U6 l' A
female child who might come in contact with some-& E8 v$ E1 z( `# l+ ?( L) i4 X7 F
one using any of these products.
' k8 y" o, w( s: N+ }% L' }! cReferences
" |0 D x6 O! u( `% H4 B1. Styne DM. The testes: disorder of sexual differentiation
; U, q: ]3 c- _8 {& r, cand puberty in the male. In: Sperling MA, ed. Pediatric* T u( C. t7 [4 Q! n
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;1 e: H+ I: \ s1 e# G, z- N) o( d8 I
2002: 565-628.
" z: r5 q+ J0 I( `2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
9 |! x- c. ^, Y$ z: {# Apuberty in children with tumours of the suprasellar pineal |
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