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Sexual Precocity in a 16-Month-Old
8 y6 o$ `* f, M! {' N9 uBoy Induced by Indirect Topical V* C; x4 C- Q: I3 y/ q2 r3 q
Exposure to Testosterone6 W& d! r3 ]9 q* f) {1 L0 s$ i
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2/ o5 S+ ^" {$ I S2 n; w; b) H
and Kenneth R. Rettig, MD1
3 ? ~. ?5 l" Y- T; HClinical Pediatrics; U' F% W" u% m C: c
Volume 46 Number 6
2 J: V, r# Y2 o% F0 K! ^July 2007 540-543' H# @8 ?1 G+ [! H! Y' {& T/ A
© 2007 Sage Publications' e8 S# Z6 x0 `: j5 F" U+ J e
10.1177/0009922806296651
$ G+ F" T! R' O5 Ohttp://clp.sagepub.com5 T* S& ^( A; ^6 m9 X6 M
hosted at
, E/ q9 S5 E; i; Vhttp://online.sagepub.com
0 x- J) j# ? [* h& yPrecocious puberty in boys, central or peripheral,
9 ]& E0 I+ ?% \/ v, w! Zis a significant concern for physicians. Central
% n6 R8 v8 j ~# p3 Qprecocious puberty (CPP), which is mediated! a- ~; D: n5 D* O5 t( k
through the hypothalamic pituitary gonadal axis, has
R" _& Z; L U) n7 s0 {" Za higher incidence of organic central nervous system
1 y6 s7 d6 }* e) r- H5 klesions in boys.1,2 Virilization in boys, as manifested
: U6 f- l% F8 ~+ s$ yby enlargement of the penis, development of pubic" A1 b. F9 q8 h4 i
hair, and facial acne without enlargement of testi-
+ X0 _0 i7 P( Z9 ycles, suggests peripheral or pseudopuberty.1-3 We
* }% D4 a+ z2 m/ `& ~% treport a 16-month-old boy who presented with the, t5 w! N$ Y" B* e% N8 N
enlargement of the phallus and pubic hair develop-
0 b+ c9 m* Z. E: t: H6 Qment without testicular enlargement, which was due
. N6 [- D: ^8 I% u' s$ o" I8 |to the unintentional exposure to androgen gel used by% D1 u$ ]' v3 w+ a2 x4 B
the father. The family initially concealed this infor-
% M1 { G2 v1 b# l emation, resulting in an extensive work-up for this
. v9 T* c0 \" y1 }: p/ f' Dchild. Given the widespread and easy availability of
7 _* N ~* T j/ b1 f! J2 q" z Ttestosterone gel and cream, we believe this is proba-; W, ?; M s9 b$ B# X- e I8 m
bly more common than the rare case report in the
. L) R2 G/ g3 C* Y+ lliterature.4
% q$ ~% P" a' c# [9 W/ \0 GPatient Report# a: m# l4 ^ T7 q( w" E/ J; k
A 16-month-old white child was referred to the; u, }' J& v! L, o' K. d% Z
endocrine clinic by his pediatrician with the concern
$ `& S% C# P8 O0 b# pof early sexual development. His mother noticed
) w2 Z# l; m7 i* z6 h$ Jlight colored pubic hair development when he was3 u6 M. m4 {, w; u' t
From the 1Division of Pediatric Endocrinology, 2University of1 V+ S E, s) }- C4 s% {% u
South Alabama Medical Center, Mobile, Alabama.
) J* P$ J) Y, N" K1 `% ]Address correspondence to: Samar K. Bhowmick, MD, FACE,7 Q C. L/ H/ M `! U* K2 `
Professor of Pediatrics, University of South Alabama, College of
4 C# c- s& n* Q# }2 aMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
" ]# M( n+ z" ~ d' \% k; X- P M- Ve-mail: [email protected]. j7 S; L( @4 o) S3 d. W
about 6 to 7 months old, which progressively became; B. Z5 K5 K' Q4 @% g7 P# n
darker. She was also concerned about the enlarge-# A* s* S! @- w& H
ment of his penis and frequent erections. The child
# \3 \' w) e8 n- ?# s2 @ N4 s: Nwas the product of a full-term normal delivery, with; w" z0 {" Y7 a' P
a birth weight of 7 lb 14 oz, and birth length of
6 k1 E" A: `4 ?" a7 U$ I20 inches. He was breast-fed throughout the first year, r$ P7 J4 p/ K' O! d
of life and was still receiving breast milk along with
5 I+ Q6 J6 O, ]3 w" psolid food. He had no hospitalizations or surgery,
( Q9 ~! u$ ` V6 t- A: r! Tand his psychosocial and psychomotor development
! \8 T- H* [* }was age appropriate.1 O" C/ \% }" j2 Z
The family history was remarkable for the father,& O2 Y- g! W! z+ K; P1 V
who was diagnosed with hypothyroidism at age 16,
# q: T! h8 p! @which was treated with thyroxine. The father’s
# _2 ~; K8 a& p \; Eheight was 6 feet, and he went through a somewhat
9 B' c+ B' ^ G& A# s* `% [early puberty and had stopped growing by age 14.
A* v% ~7 _# lThe father denied taking any other medication. The
& Q# X. Z% W. L3 r- ~9 Mchild’s mother was in good health. Her menarche% D, m& P- j) C7 } G( s5 O
was at 11 years of age, and her height was at 5 feet, _5 o7 G; r) h8 ]+ P; B
5 inches. There was no other family history of pre-* n) C4 U: n7 _' u. s, Z, k {
cocious sexual development in the first-degree rela-
8 I: I% w1 e' N/ J0 A: dtives. There were no siblings.: _- E$ a. e) k% B s4 w
Physical Examination' G3 k7 ?2 ?, w% ]3 J
The physical examination revealed a very active,
( f' P0 k0 J. u/ W4 Gplayful, and healthy boy. The vital signs documented# f- O) u- z2 Y8 w/ k
a blood pressure of 85/50 mm Hg, his length was/ b {" j0 X1 m& L) j* {7 B
90 cm (>97th percentile), and his weight was 14.4 kg
T% |; g# b8 ^7 X(also >97th percentile). The observed yearly growth9 A3 k5 ^. e$ W0 Y' z: a$ l
velocity was 30 cm (12 inches). The examination of
m8 |4 A5 ~4 y* qthe neck revealed no thyroid enlargement.$ u7 f' a h4 y% {$ Q& ?
The genitourinary examination was remarkable for* I$ T: q+ k( ~6 @
enlargement of the penis, with a stretched length of
# t, i. e7 P$ u( o8 cm and a width of 2 cm. The glans penis was very well2 c! t$ M% O' I- ~& r
developed. The pubic hair was Tanner II, mostly around# Q8 B# Y! U# B7 D2 T! j) Y9 b* U9 H
540
8 i6 F! y* J3 z! q- e* ]at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from, G$ D9 U6 b. ?6 M$ `
the base of the phallus and was dark and curled. The
5 D3 j1 x- y6 L; p6 Itesticular volume was prepubertal at 2 mL each.9 s8 v2 _% M. k6 i. ^% S% @$ ?; Q
The skin was moist and smooth and somewhat
3 ^% ~- h8 `0 ?- noily. No axillary hair was noted. There were no
! }0 {2 V+ V/ [0 H8 D1 f: Mabnormal skin pigmentations or café-au-lait spots.: f0 r$ I% _0 e1 R5 P
Neurologic evaluation showed deep tendon reflex 2+' g5 n$ K" R2 F0 w- `
bilateral and symmetrical. There was no suggestion8 p* L! ]; ~( D( v$ O2 S0 d
of papilledema.
$ _' ^( N$ w- b) b6 r8 k/ A9 TLaboratory Evaluation+ @0 z7 L- y8 O+ L' A& ^( h
The bone age was consistent with 28 months by
6 b- G$ B \* m& W' Lusing the standard of Greulich and Pyle at a chrono-
) w% e1 Z1 {/ c f4 A( t/ llogic age of 16 months (advanced).5 Chromosomal* X7 ^5 M \4 { g, V# c
karyotype was 46XY. The thyroid function test
, h8 |5 H1 c6 `showed a free T4 of 1.69 ng/dL, and thyroid stimu-0 L. a( p" Y0 T* \
lating hormone level was 1.3 µIU/mL (both normal).& h8 S# J& @4 }0 w* K
The concentrations of serum electrolytes, blood8 f( z9 X( F$ n
urea nitrogen, creatinine, and calcium all were8 o: n8 Z6 W3 I/ ?
within normal range for his age. The concentration% v. _- x% v4 i2 T$ l1 O; t: r
of serum 17-hydroxyprogesterone was 16 ng/dL, k2 x z: ~$ ]" s8 y
(normal, 3 to 90 ng/dL), androstenedione was 20* c( W# Z y: ]( u3 T! H
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
/ D; J5 g- q8 l7 T' [. Oterone was 38 ng/dL (normal, 50 to 760 ng/dL),
& z/ C0 |, \: xdesoxycorticosterone was 4.3 ng/dL (normal, 7 to
4 \* Z/ C6 i1 X+ ^8 d# e49ng/dL), 11-desoxycortisol (specific compound S). R4 F; r; A0 b7 G" @" t* L) q
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-. u0 Z; f) b+ c2 K
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
( N5 q* s( [, L4 Y, P! E2 ~testosterone was 60 ng/dL (normal <3 to 10 ng/dL),; _/ S2 |& ]1 b& O
and β-human chorionic gonadotropin was less than' n0 V: h6 U5 p( S& ?6 u! B1 ^% U; h
5 mIU/mL (normal <5 mIU/mL). Serum follicular8 K2 _& p4 @$ ^% U! F' U& X
stimulating hormone and leuteinizing hormone. d( C/ U! n6 Z4 ]
concentrations were less than 0.05 mIU/mL0 ?% D4 c3 l* O; u9 B
(prepubertal).% s8 G& W$ g7 v4 i/ n7 q0 P- H
The parents were notified about the laboratory
& W$ O5 z% ?5 ^' H7 m7 Aresults and were informed that all of the tests were
8 e9 }$ b. Y. G: M: \6 vnormal except the testosterone level was high. The
+ J+ \" I3 u4 }" s9 I$ ?: ]7 Jfollow-up visit was arranged within a few weeks to
- Y3 j2 r$ o/ a% I2 bobtain testicular and abdominal sonograms; how-/ b: k0 x6 \0 r! K( ~9 R
ever, the family did not return for 4 months.
?: m$ r. t5 k, V4 N" @ @Physical examination at this time revealed that the1 i) F$ R% |- |: w z( Y
child had grown 2.5 cm in 4 months and had gained6 e9 y+ W% h$ ]
2 kg of weight. Physical examination remained1 o2 K0 f5 m# u$ A: \1 u8 ^
unchanged. Surprisingly, the pubic hair almost com-
m) v8 J3 p+ Q8 B8 z; [ Dpletely disappeared except for a few vellous hairs at
- Q7 o6 G+ E- {$ Q+ u7 l6 cthe base of the phallus. Testicular volume was still 21 i6 C/ r5 h) a5 k$ @
mL, and the size of the penis remained unchanged.
- C0 K6 L: ^! A. S( r( JThe mother also said that the boy was no longer hav-0 _0 ]! F6 a, i6 W" M% [7 K7 n
ing frequent erections.2 ^) P5 Z3 p% f+ c8 m
Both parents were again questioned about use of
, t; ~; x3 y+ Cany ointment/creams that they may have applied to
; {; ?/ b" W2 I9 L1 p0 M% lthe child’s skin. This time the father admitted the
6 q6 d: K) [2 h1 {Topical Testosterone Exposure / Bhowmick et al 5415 c) t) E, o0 H! s2 |5 V
use of testosterone gel twice daily that he was apply-
+ k( D1 e& H- P+ L3 ning over his own shoulders, chest, and back area for
0 ]! x, d6 N( F o) b: J$ Ca year. The father also revealed he was embarrassed
+ f$ T* R0 y" C+ n/ Lto disclose that he was using a testosterone gel pre-
( G" N5 e* K% e( P. p7 F& ?/ |scribed by his family physician for decreased libido
& W8 i l4 S: G, n2 Y5 F6 y D2 }secondary to depression.# I' r' i4 S) F) {
The child slept in the same bed with parents.; c: b: B U0 B/ k' Y
The father would hug the baby and hold him on his7 @& ^0 N) g' m$ w' d( w0 i
chest for a considerable period of time, causing sig-- Q5 N, c, V: |% p8 _
nificant bare skin contact between baby and father., R9 c& g$ h6 ^ R: e) M# n; E
The father also admitted that after the phone call,
2 I9 K3 ^( w2 ]# V! Swhen he learned the testosterone level in the baby9 n, Z5 p1 B1 y" ?/ K- ?6 E2 C
was high, he then read the product information- F7 j$ h$ b& ~/ H# d, `0 j
packet and concluded that it was most likely the rea-
9 T* x2 f" L [' w" Yson for the child’s virilization. At that time, they
0 q: c) d$ p, \: u/ Idecided to put the baby in a separate bed, and the; s( x7 w$ \ S- P# k) j$ t! B c
father was not hugging him with bare skin and had
* m3 ?8 e1 w# c0 S7 mbeen using protective clothing. A repeat testosterone! } l5 z+ H, a; n2 Z
test was ordered, but the family did not go to the) W# m, A' q: w
laboratory to obtain the test.
/ I" ]9 ?% w3 @0 Z; ]/ P) TDiscussion; g, Z! l( S! o6 f
Precocious puberty in boys is defined as secondary9 Y3 D& r \' ^" A4 M
sexual development before 9 years of age.1,4: j$ [7 j' g# a' m5 j
Precocious puberty is termed as central (true) when
" \1 w$ ]7 e- u$ R2 q3 }it is caused by the premature activation of hypo-
( O% f, }7 Z6 {" K5 ithalamic pituitary gonadal axis. CPP is more com-
' [- ?& M# M6 y! U5 zmon in girls than in boys.1,3 Most boys with CPP8 V" Y/ A [; O/ H& b
may have a central nervous system lesion that is/ t9 g6 T8 D* A0 _9 |$ A
responsible for the early activation of the hypothal- Z) g& x$ d1 T
amic pituitary gonadal axis.1-3 Thus, greater empha-7 G! U: u- d p1 N ]
sis has been given to neuroradiologic imaging in
" |' g; D4 B# s2 v; a2 xboys with precocious puberty. In addition to viril-
5 s# @( i/ u) ]- D+ [ization, the clinical hallmark of CPP is the symmet-
& _/ n+ ]& G4 Krical testicular growth secondary to stimulation by0 K9 [3 X8 U, u3 @
gonadotropins.1,3
; D" W" W0 t2 A* ]9 z- iGonadotropin-independent peripheral preco-1 ^7 ^! ~. V: c% ^8 H& U
cious puberty in boys also results from inappropriate" m, n7 h M# D! N3 f3 z% b3 D
androgenic stimulation from either endogenous or7 ^! ^+ N+ _5 [1 R5 `
exogenous sources, nonpituitary gonadotropin stim-/ m( C; {& G' L! A4 w& j
ulation, and rare activating mutations.3 Virilizing0 e# d. r N+ n" H( d/ T, t3 h- A
congenital adrenal hyperplasia producing excessive
) U- X- ~" O) {adrenal androgens is a common cause of precocious
1 {' V0 p- f) b: s- ]3 kpuberty in boys.3,4
- |- E0 ?! Y4 L x" e( JThe most common form of congenital adrenal
' F* o p. U3 R; O h7 j0 Shyperplasia is the 21-hydroxylase enzyme deficiency." T2 ]* }9 p9 r' U' Y, g, U2 B
The 11-β hydroxylase deficiency may also result in! w. ]: v2 c5 `/ g C3 m& N }
excessive adrenal androgen production, and rarely,
3 t" p% I3 H6 wan adrenal tumor may also cause adrenal androgen3 Q& `+ }& P7 |4 K7 j6 D
excess.1,34 ~* M% Y k8 c' ?2 h+ x
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from2 v+ y- ]% e( R+ Y7 \
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007; L8 q, P N- i( R% m4 D, l: C
A unique entity of male-limited gonadotropin-
: v Y4 }1 [' S7 ]0 G" O" O9 O* D4 Kindependent precocious puberty, which is also known
" t/ R; Q2 t" Pas testotoxicosis, may cause precocious puberty at a0 _. w7 Y r. p
very young age. The physical findings in these boys
7 @5 l$ x4 m) d4 b. D. Dwith this disorder are full pubertal development,
5 v" d$ p4 O& F( Y3 D2 k; a) A Wincluding bilateral testicular growth, similar to boys
9 k. z/ U0 T W2 K- g5 ] Fwith CPP. The gonadotropin levels in this disorder7 J% b# H; Z8 M
are suppressed to prepubertal levels and do not show1 j9 t% r) J6 k, M2 G
pubertal response of gonadotropin after gonadotropin-5 K* u5 Z6 x1 f* ]- ~8 a
releasing hormone stimulation. This is a sex-linked
4 e9 D5 A% ?0 c& e" @autosomal dominant disorder that affects only4 e: \9 M* G- N* V2 |) p
males; therefore, other male members of the family- j6 x6 @1 M+ G! h$ @
may have similar precocious puberty.3
H; y. L+ o7 M$ @0 S4 rIn our patient, physical examination was incon-
7 n( H Z/ O+ \7 F4 Q, Msistent with true precocious puberty since his testi-/ T* y+ k8 v) ?, x& p
cles were prepubertal in size. However, testotoxicosis
. Q0 F7 Y& o% v& a& h, kwas in the differential diagnosis because his father
/ f; }$ J6 ]1 K" e. T) Astarted puberty somewhat early, and occasionally,% @4 K5 f y: P) B9 [; d
testicular enlargement is not that evident in the0 Y, o1 F$ s" z: n* a
beginning of this process.1 In the absence of a neg-
' O2 R3 v# J2 W! d1 j: t! t( \& dative initial history of androgen exposure, our1 ~1 F. t. R0 b) E1 Z
biggest concern was virilizing adrenal hyperplasia,
( m& d! a" }" R; e9 a: k+ U) e- ^1 X: Neither 21-hydroxylase deficiency or 11-β hydroxylase9 x& e3 i, ~" t5 r
deficiency. Those diagnoses were excluded by find- j1 j/ A; O9 e' U b& I) p- p2 @
ing the normal level of adrenal steroids./ Q2 Y N+ ~* z
The diagnosis of exogenous androgens was strongly
# }6 j8 V: |$ \! W7 |suspected in a follow-up visit after 4 months because0 V0 f9 t s( A6 m$ x7 I- A* }
the physical examination revealed the complete disap-
% s% B# T* c4 O0 Zpearance of pubic hair, normal growth velocity, and
3 Q1 W, S0 S) v* W1 Sdecreased erections. The father admitted using a testos-
+ T! G! n$ }7 S7 H4 t2 b6 d9 C# _% xterone gel, which he concealed at first visit. He was% y1 i$ {& e- n1 ?2 o
using it rather frequently, twice a day. The Physicians’
q" B" a" ]& g) JDesk Reference, or package insert of this product, gel or
7 r* b/ ?$ l$ J* l/ E* acream, cautions about dermal testosterone transfer to
0 B* Z3 S Q5 \! @6 h" k- Y% xunprotected females through direct skin exposure.( A3 ` x) r A+ Y& r/ B4 ]' k
Serum testosterone level was found to be 2 times the5 C$ L9 N. a: {4 C( N
baseline value in those females who were exposed to$ f( F' ^* u( `; I
even 15 minutes of direct skin contact with their male6 O% O0 {" D9 r! \
partners.6 However, when a shirt covered the applica-' T7 o' }- L7 `/ C5 M
tion site, this testosterone transfer was prevented., B2 o: Z: C; `" u: r# M; c8 n* x3 n
Our patient’s testosterone level was 60 ng/mL,
7 X t- a- c' s" N# e6 m& g3 ]which was clearly high. Some studies suggest that
2 u3 p% `, g) ~2 ]9 Tdermal conversion of testosterone to dihydrotestos-
+ f2 |5 Y. J3 I$ xterone, which is a more potent metabolite, is more/ K5 d) {3 U& b7 R
active in young children exposed to testosterone
' n$ j8 E' c* E5 Wexogenously7; however, we did not measure a dihy-. ` q; P: L s* L$ a+ l
drotestosterone level in our patient. In addition to
' M, r5 T s u' s* n1 O# ovirilization, exposure to exogenous testosterone in
! Y) h% C, k9 e5 I2 e* }children results in an increase in growth velocity and
0 J, G& J4 E1 G; Xadvanced bone age, as seen in our patient.
, C8 X* h- [0 v' S* y7 X" CThe long-term effect of androgen exposure during, C/ ? H# L" |$ v: j
early childhood on pubertal development and final4 c' E" k% E2 Y9 `' k
adult height are not fully known and always remain3 X- e' i2 e4 O. y
a concern. Children treated with short-term testos-) [0 t5 |1 F: E6 ~. N
terone injection or topical androgen may exhibit some
- d" `, M. P# l* }# |5 Kacceleration of the skeletal maturation; however, after6 j: M5 R5 ]' J5 J$ P1 T3 h: S7 i
cessation of treatment, the rate of bone maturation
, K! v5 |7 D( q! m. n" [decelerates and gradually returns to normal.8,9
, i( Q* s7 ]! `; u$ v& qThere are conflicting reports and controversy5 N& O5 d/ n3 L. f b9 K+ ?$ G
over the effect of early androgen exposure on adult
- ~/ Q1 w% Z8 xpenile length.10,11 Some reports suggest subnormal/ t: o, l, w) C/ r
adult penile length, apparently because of downreg- s, ^# f) X3 X! S* P& L
ulation of androgen receptor number.10,12 However,, Q$ X" r0 U* [: m
Sutherland et al13 did not find a correlation between
8 [2 o: l" D8 Y9 s) ~1 ^childhood testosterone exposure and reduced adult9 H+ K& i, F: l( |
penile length in clinical studies.
: x: R. Q- q, D) SNonetheless, we do not believe our patient is# {3 { D/ z1 D; ^. q
going to experience any of the untoward effects from
; S) `5 u0 J9 c- a' ttestosterone exposure as mentioned earlier because9 R: l8 I% K9 O7 ?/ a! f0 t
the exposure was not for a prolonged period of time.* e; Y% |! p% b: c$ C% c
Although the bone age was advanced at the time of: b' c }0 i4 t6 ]5 O
diagnosis, the child had a normal growth velocity at
6 `* }: o) j. p9 U: _# ethe follow-up visit. It is hoped that his final adult* k+ F. B1 T/ ]2 M' ?
height will not be affected.
$ Z$ E- B* }# V$ E2 VAlthough rarely reported, the widespread avail-
1 {( ~- f$ D8 {! E+ fability of androgen products in our society may
% W: v, a/ g* T' n( b1 E2 `, N; Vindeed cause more virilization in male or female9 ]/ H: |+ p2 A3 g, M
children than one would realize. Exposure to andro-, t6 `/ I P# }" ?8 D
gen products must be considered and specific ques-
! j o+ N" W7 t8 g, d! b) Ptioning about the use of a testosterone product or
N- j, m, x) ^4 X9 j8 V! a& T; dgel should be asked of the family members during
1 n: M/ `% f4 H8 d& ]5 K, Dthe evaluation of any children who present with vir- M9 C% ~( r ^/ q
ilization or peripheral precocious puberty. The diag-
" z( |/ @, o9 x, a( a& t. snosis can be established by just a few tests and by
' E0 D' N1 }& ^. Eappropriate history. The inability to obtain such a
$ q/ S3 E4 W( Uhistory, or failure to ask the specific questions, may6 k3 S$ V# F1 J% f: Z0 P- h3 m
result in extensive, unnecessary, and expensive
+ u% H( k6 u2 y" ^investigation. The primary care physician should be
' |% `- o; L+ z2 Saware of this fact, because most of these children
4 W6 n- f1 R Y5 w# ?# C+ rmay initially present in their practice. The Physicians’9 k* ]2 Z4 R" U
Desk Reference and package insert should also put a
2 L! g& x3 h% P( Zwarning about the virilizing effect on a male or0 V a3 [9 n- k
female child who might come in contact with some-+ a! {8 X! T# \" D4 V# @4 i
one using any of these products.1 `( u5 t z J8 r1 M$ A
References: g. ~3 h- y5 e/ C" ~1 f- i7 {
1. Styne DM. The testes: disorder of sexual differentiation* t* U; ]: P v
and puberty in the male. In: Sperling MA, ed. Pediatric
7 k5 ~& s8 A; H. I- L* ^Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
1 c/ {1 `: x D/ Q- R2 T2002: 565-628.. ]( j, d Z/ Y* y' ]! \# x1 \8 D; {
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
. P; v5 W% i( V6 D$ S" Qpuberty in children with tumours of the suprasellar pineal |
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