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Sexual Precocity in a 16-Month-Old$ C3 v8 x' e* L" ^- _
Boy Induced by Indirect Topical Q1 t; M- v, v& n( N! I4 _3 V" n
Exposure to Testosterone
. y2 L$ J. y/ xSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
/ l% U/ f: L5 R% r- Z: Rand Kenneth R. Rettig, MD1
0 G; t; U7 S# Q zClinical Pediatrics
% d9 f1 d: ]( M4 rVolume 46 Number 6 Q# g1 c& }8 o" G" i
July 2007 540-543
k. g2 U1 A) \% x+ {$ y0 ^© 2007 Sage Publications1 Q2 w6 m/ I6 j. g
10.1177/0009922806296651- v# | K" \. i6 P' v9 R
http://clp.sagepub.com
/ ?* R/ t% E, h& y# U; p, G( Ihosted at, l- O1 j% s9 d! w1 d" L; N
http://online.sagepub.com% f$ f; O4 h2 l; h0 i2 x, g
Precocious puberty in boys, central or peripheral,
5 W2 |9 e# X( G0 G. G$ {- w+ Yis a significant concern for physicians. Central: G3 ]0 G0 [4 b
precocious puberty (CPP), which is mediated- B8 a9 m+ W& \" O
through the hypothalamic pituitary gonadal axis, has0 c( s% a- Y/ j3 |* i. H( X
a higher incidence of organic central nervous system8 x# u5 ]6 I! W* k
lesions in boys.1,2 Virilization in boys, as manifested
, g; O- S. z0 ^0 N9 p% bby enlargement of the penis, development of pubic" l: w. K! i1 v- r& `7 z+ |, z
hair, and facial acne without enlargement of testi-
# x& n5 D! |2 x, Z O* dcles, suggests peripheral or pseudopuberty.1-3 We: C' j" j& s& f, O- ^2 V# D
report a 16-month-old boy who presented with the
- Y( z' [1 G v: O- oenlargement of the phallus and pubic hair develop-; d" F7 x) Z6 R
ment without testicular enlargement, which was due) S% B. a h1 s4 R3 }
to the unintentional exposure to androgen gel used by4 ^( e4 z+ x2 b2 P1 |9 ^
the father. The family initially concealed this infor-
9 o; [; G) ]6 Wmation, resulting in an extensive work-up for this0 B) U) k: w7 f5 `! ~
child. Given the widespread and easy availability of# K8 u. A! ^8 f
testosterone gel and cream, we believe this is proba-1 O5 L: @2 B1 p/ `
bly more common than the rare case report in the* M- v- \0 b6 J! O9 S9 T9 x
literature.4; {- _8 ~& N: }
Patient Report
+ e0 K6 w# r; ^- IA 16-month-old white child was referred to the+ Z7 f3 l+ [ ?0 N4 f# B& m
endocrine clinic by his pediatrician with the concern
5 Q0 _- u- `4 ~" P3 o6 Aof early sexual development. His mother noticed
6 N% V, A2 w& y; x/ ilight colored pubic hair development when he was# l5 X/ L3 E, I! k
From the 1Division of Pediatric Endocrinology, 2University of ^- H/ v5 R! D) t
South Alabama Medical Center, Mobile, Alabama.5 b5 ^/ C: o* I
Address correspondence to: Samar K. Bhowmick, MD, FACE,
+ w5 u+ @$ u4 {: `( @& }Professor of Pediatrics, University of South Alabama, College of
+ F) \/ m% L7 Y: I( T' o& BMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
% \: \, v9 ?: P9 i7 F, A: Fe-mail: [email protected].
/ s& p! {" J0 B0 s; u f0 R8 Z3 N. _about 6 to 7 months old, which progressively became# I% E9 N, o* g3 [2 _5 g4 q
darker. She was also concerned about the enlarge-/ n8 D% {! L' G/ k2 j2 G* M7 b
ment of his penis and frequent erections. The child, ]. m+ Y) c* J: o; {9 L0 i+ V
was the product of a full-term normal delivery, with s+ O1 a# I. D) `4 ^# U) F. h
a birth weight of 7 lb 14 oz, and birth length of# J7 [6 n" F4 a) A+ Z
20 inches. He was breast-fed throughout the first year
1 f2 {7 o. h/ y3 @9 ?of life and was still receiving breast milk along with
8 q+ I9 D! d0 b. k/ n# ]/ ~solid food. He had no hospitalizations or surgery,! V; L* @# X2 l/ b. [3 \
and his psychosocial and psychomotor development1 D) \, B# i' g9 V/ e
was age appropriate.
1 b! ]8 }3 B" @, u$ l& J5 l4 O) DThe family history was remarkable for the father,
: Z3 }+ G6 u* g+ i6 }who was diagnosed with hypothyroidism at age 16,
1 Z. K: h3 M1 c2 U. Dwhich was treated with thyroxine. The father’s* K4 N7 N1 O3 h1 D1 t" v4 b4 Y" Y
height was 6 feet, and he went through a somewhat; J+ A8 D7 J& o1 D) R% c
early puberty and had stopped growing by age 14." Z6 c& M0 Y7 F; {; N- q
The father denied taking any other medication. The0 L3 J* i i) Y; t' ]2 \
child’s mother was in good health. Her menarche
5 |# u; n) r- R' p) Lwas at 11 years of age, and her height was at 5 feet H* ~0 V" z/ m; G( _, B
5 inches. There was no other family history of pre-. c. g& U( k q8 G
cocious sexual development in the first-degree rela-: Q4 \" M+ v9 ?
tives. There were no siblings.# t7 ~& E: {# @
Physical Examination
! U9 ^# b7 ?9 S' m+ Z' n. xThe physical examination revealed a very active,
1 a) T0 s9 Z' P( j* b/ z0 uplayful, and healthy boy. The vital signs documented# k6 r& r: I. q0 V7 W
a blood pressure of 85/50 mm Hg, his length was) y8 t+ ~5 \9 D& }/ r: n% {
90 cm (>97th percentile), and his weight was 14.4 kg
- _% z- P$ ?' z! o1 \& G(also >97th percentile). The observed yearly growth
' P0 C% \; b5 z9 [% @' dvelocity was 30 cm (12 inches). The examination of
8 s" t. |% ]; a8 dthe neck revealed no thyroid enlargement. k# K& c4 ^& I- Q+ N' ?; \2 i* t# V Y, n
The genitourinary examination was remarkable for
3 y, ?0 E) o, q" zenlargement of the penis, with a stretched length of
6 X q+ a9 R1 m/ F. [3 V: O% E/ H8 cm and a width of 2 cm. The glans penis was very well
# {2 C/ ?3 G* |, b. ~developed. The pubic hair was Tanner II, mostly around
% c+ H* } H; }) L L% {, _" @3 Q$ D8 h540* b) c- W: b1 S! j' ^; J
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from" F7 ^! l/ n9 r/ r7 t" l R
the base of the phallus and was dark and curled. The
& \" |" z! v% i/ W( Ytesticular volume was prepubertal at 2 mL each. v4 O, Z# M7 h+ T, x' f
The skin was moist and smooth and somewhat% |6 m1 j/ W9 b& y; L
oily. No axillary hair was noted. There were no
0 `9 l8 ?3 z$ ^) }) Eabnormal skin pigmentations or café-au-lait spots.
) a( c4 s2 i: T0 pNeurologic evaluation showed deep tendon reflex 2+
9 K& M2 M" Y( v a9 h6 S4 a% Dbilateral and symmetrical. There was no suggestion
4 B4 f7 ?+ b) R' X/ z3 Hof papilledema.
# L1 [. S2 i8 }; T% X' F4 rLaboratory Evaluation/ c- w- M$ {. F- p
The bone age was consistent with 28 months by
! h8 G' t$ \6 `$ v, ], b) Nusing the standard of Greulich and Pyle at a chrono-
3 W! q. [5 y, i! u5 W9 f: Slogic age of 16 months (advanced).5 Chromosomal0 V+ _& K+ m& G j5 S& x
karyotype was 46XY. The thyroid function test, O f/ d2 `' P" l/ M
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
; ~, ?5 x" g, ?$ B3 p4 j c' \6 j2 Clating hormone level was 1.3 µIU/mL (both normal).
& E+ ?6 i8 E! C8 k: KThe concentrations of serum electrolytes, blood! ~4 [) M9 G8 I. w* H
urea nitrogen, creatinine, and calcium all were
. t6 a/ f! ~" J: pwithin normal range for his age. The concentration
3 |- F, C$ A8 f% V2 cof serum 17-hydroxyprogesterone was 16 ng/dL* a3 M' V6 ^! s
(normal, 3 to 90 ng/dL), androstenedione was 201 e/ d5 s5 L" T
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
6 t7 y3 I6 s' {) Mterone was 38 ng/dL (normal, 50 to 760 ng/dL),0 i+ b4 ~. f I9 Q! |6 j
desoxycorticosterone was 4.3 ng/dL (normal, 7 to, E6 N) e) I& f3 w$ @4 ~% f) M
49ng/dL), 11-desoxycortisol (specific compound S)! I! c- N' I5 x: t; _% y! {
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
% O+ j8 D+ V9 g4 V3 t2 J' ptisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
. V& k1 f$ b/ d3 [: H# ]; Q$ j! i! ?testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
9 c3 P6 g& Z) J' D1 w8 a' W! p$ Jand β-human chorionic gonadotropin was less than
, e$ ~2 N' R- [) c5 mIU/mL (normal <5 mIU/mL). Serum follicular
( {3 ~ L# t* J# `, z1 Hstimulating hormone and leuteinizing hormone
+ m, U B- h, xconcentrations were less than 0.05 mIU/mL, O1 l' X% P3 \& t/ s+ x( l
(prepubertal).; F/ t* J. I- U
The parents were notified about the laboratory
- y5 a/ ?8 V1 }results and were informed that all of the tests were$ Z3 e6 w! `. I- H. U) c5 |# I
normal except the testosterone level was high. The
1 G8 Z0 O" p/ h4 Y- nfollow-up visit was arranged within a few weeks to4 V6 R0 L* j- L( C9 A
obtain testicular and abdominal sonograms; how-! t b# E' q& ~
ever, the family did not return for 4 months.
: M7 d- @/ j5 |% T9 K, z u# C) x- |Physical examination at this time revealed that the
6 l9 f! H4 K1 bchild had grown 2.5 cm in 4 months and had gained3 \1 L d/ p C1 B- n
2 kg of weight. Physical examination remained
, ^3 U0 H6 m. g& s3 Punchanged. Surprisingly, the pubic hair almost com-
% L) _. g& ?. [pletely disappeared except for a few vellous hairs at' ^% V: |- i' e& s
the base of the phallus. Testicular volume was still 23 E+ g. j4 B5 I( F, W
mL, and the size of the penis remained unchanged.; ~7 N; j9 B3 U# W6 g1 }
The mother also said that the boy was no longer hav-5 S: P' r4 [& U$ N* T' {) \( u
ing frequent erections.3 a: M1 U$ j7 f$ X& W
Both parents were again questioned about use of4 G ]* J4 L2 t/ v& f
any ointment/creams that they may have applied to
% C8 P+ y( `! r6 u9 K; {0 r4 s5 x9 Nthe child’s skin. This time the father admitted the; e' N: Y" f3 H: g! p, E W
Topical Testosterone Exposure / Bhowmick et al 541. g$ \' a, a3 k6 a. @2 ?1 j
use of testosterone gel twice daily that he was apply-
+ L. t+ L, v3 ?+ X6 ling over his own shoulders, chest, and back area for
7 N) f0 {% ]$ w4 e' u; ?7 sa year. The father also revealed he was embarrassed
) S6 d; E' W$ m( I& p$ Vto disclose that he was using a testosterone gel pre-
6 o: b( F2 d5 \1 T( I Z8 Wscribed by his family physician for decreased libido% d" e7 r. x- g
secondary to depression.0 N' J% X% ~6 x8 ^0 ] L8 c
The child slept in the same bed with parents.$ s: N/ n5 E2 V! [$ v; |; C
The father would hug the baby and hold him on his! P! I. Y; a) L2 w# \
chest for a considerable period of time, causing sig-: \# V! K$ Z" H3 a0 a
nificant bare skin contact between baby and father.6 z4 t1 ^9 x2 L
The father also admitted that after the phone call,5 \7 _7 w0 c h' P& I1 v# a. Z
when he learned the testosterone level in the baby
4 g# B" ^" Y5 `( R4 `$ A2 rwas high, he then read the product information
$ l# w. Z- B' x+ d- X8 T* cpacket and concluded that it was most likely the rea-
- U p# U* {" c$ Eson for the child’s virilization. At that time, they! h3 V( }' g; J( I$ \# o3 m8 p
decided to put the baby in a separate bed, and the% |0 A# Z2 X5 f$ |2 Y- m
father was not hugging him with bare skin and had2 a% ?3 k8 q8 c+ ]1 J) ^
been using protective clothing. A repeat testosterone9 e8 U: k" q6 ?3 y
test was ordered, but the family did not go to the
7 H/ @9 ~5 Q) `, j: `laboratory to obtain the test.) A) R# j; h/ O) ?) d
Discussion+ u9 f$ |* H' O9 S
Precocious puberty in boys is defined as secondary
, a% c" {' D0 |0 Y5 ~sexual development before 9 years of age.1,4
* }1 n; Z+ t) w/ R Q9 m9 w/ L* ^Precocious puberty is termed as central (true) when+ X/ p3 n* ]: R% S: P
it is caused by the premature activation of hypo-
( F1 _+ W' p$ J$ Z, I" M) \2 X+ {thalamic pituitary gonadal axis. CPP is more com-
$ Y# d: P- \7 Mmon in girls than in boys.1,3 Most boys with CPP5 t8 n9 d" t! M3 K% E
may have a central nervous system lesion that is
4 |/ W# U" P# yresponsible for the early activation of the hypothal-* g7 \7 v6 b) G+ L- m
amic pituitary gonadal axis.1-3 Thus, greater empha-5 G8 J4 |2 Z! o. w+ M
sis has been given to neuroradiologic imaging in2 x# v. j7 l9 A
boys with precocious puberty. In addition to viril-5 M+ a- R9 G! Z( K- o9 t$ ~
ization, the clinical hallmark of CPP is the symmet-
, D/ k0 o/ z6 m% S- E2 urical testicular growth secondary to stimulation by
- X' ?5 @+ c, v- D; w0 m P5 E2 U6 @6 egonadotropins.1,3
6 P k& e+ q# x/ L: o) d$ G% A0 FGonadotropin-independent peripheral preco-
* \8 k* C: c2 D, g" Kcious puberty in boys also results from inappropriate+ i/ B' x. N( G% f% M4 _5 N
androgenic stimulation from either endogenous or& E7 ]: v% r4 o* P E2 R
exogenous sources, nonpituitary gonadotropin stim-
" i0 F* l& F8 O& d, T* D' U6 g) mulation, and rare activating mutations.3 Virilizing
. w! Z1 o& @0 @congenital adrenal hyperplasia producing excessive( v! {2 A- x" L5 j2 |$ x
adrenal androgens is a common cause of precocious
$ a8 F; o( |8 s* jpuberty in boys.3,4
7 @: L( m0 F' A5 P3 H* IThe most common form of congenital adrenal# I4 z. X* b Q0 A# p5 {. T0 S
hyperplasia is the 21-hydroxylase enzyme deficiency.
: V; ?. X# h1 f4 z, L% z OThe 11-β hydroxylase deficiency may also result in0 |/ z! j f- L+ q8 e7 A
excessive adrenal androgen production, and rarely,$ X0 @ s9 b( G9 V
an adrenal tumor may also cause adrenal androgen- }# {) A+ W% x! g
excess.1,3
3 {& b, y3 x" d7 j% _at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
$ w( y2 a9 B) j( m0 n N542 Clinical Pediatrics / Vol. 46, No. 6, July 2007- ~( R# ^4 ^0 d9 g' k* f
A unique entity of male-limited gonadotropin-8 A( B' }0 ~; V% b. u; Y7 P) Y
independent precocious puberty, which is also known) h9 R( V1 X. K0 o4 F/ v7 ^
as testotoxicosis, may cause precocious puberty at a
9 n6 F; `( l, T2 K4 Vvery young age. The physical findings in these boys
1 k$ ~ h+ A9 z) a2 T6 `1 x- [( m) R2 cwith this disorder are full pubertal development,
( Q" b, L) x% A) n2 ?including bilateral testicular growth, similar to boys
. [' _% e7 L" t+ I+ hwith CPP. The gonadotropin levels in this disorder, Y7 I! K, a0 T3 U
are suppressed to prepubertal levels and do not show0 i& i& n/ B }
pubertal response of gonadotropin after gonadotropin-* R. E% W% s2 X5 @9 L
releasing hormone stimulation. This is a sex-linked
% V3 ~! q1 R) q% mautosomal dominant disorder that affects only$ Q3 o# z: x; p- K" Z. h
males; therefore, other male members of the family
. [1 u# Y9 S* f rmay have similar precocious puberty.3
# o4 [' Z! F0 H; R3 iIn our patient, physical examination was incon-" J& M) x: d; y4 J+ u P e6 ~( f
sistent with true precocious puberty since his testi-
# p" N/ t% o+ Ecles were prepubertal in size. However, testotoxicosis
g( x! H$ Z# Q" z0 {- Y, zwas in the differential diagnosis because his father
7 G8 c" {& @' ^) H" B- M estarted puberty somewhat early, and occasionally,
0 R+ B6 `% T; S& M8 `testicular enlargement is not that evident in the6 n7 x0 E; j8 n8 D- t
beginning of this process.1 In the absence of a neg-. u4 J3 N9 q2 h* C: ^& F* `8 }
ative initial history of androgen exposure, our
3 N9 G( @) y( i7 f3 jbiggest concern was virilizing adrenal hyperplasia,1 e8 u! E+ ~/ l
either 21-hydroxylase deficiency or 11-β hydroxylase, p; S: Q3 U5 R
deficiency. Those diagnoses were excluded by find-* {$ {7 Q3 ^) L0 _+ g! I: F
ing the normal level of adrenal steroids.* r; q8 H/ F) E( ^. @5 x! L3 R+ N
The diagnosis of exogenous androgens was strongly
; ?9 Q8 g& T5 S$ v6 f- H- ~7 ~& ususpected in a follow-up visit after 4 months because- v. T/ q' y. |/ d, r! I" @
the physical examination revealed the complete disap-* h* n0 `& `/ e
pearance of pubic hair, normal growth velocity, and6 Y" p, }9 ^, Q3 X, Z) D% m1 O
decreased erections. The father admitted using a testos-7 X9 c! o6 h% n# u0 K
terone gel, which he concealed at first visit. He was
5 W6 m& O$ G+ _, L6 f R# jusing it rather frequently, twice a day. The Physicians’
# _' H1 d7 ]' {Desk Reference, or package insert of this product, gel or
T$ K1 d( a' Fcream, cautions about dermal testosterone transfer to
6 R/ [: k: Y" D. H8 ~9 junprotected females through direct skin exposure.
1 Y5 `, j& P/ @! A6 v5 w" ^Serum testosterone level was found to be 2 times the
. I% f8 u( \/ x: Obaseline value in those females who were exposed to" m" ~ D( R' X; e
even 15 minutes of direct skin contact with their male# C7 [" H% n& B( J4 ]
partners.6 However, when a shirt covered the applica-
* `7 P- j* F" y dtion site, this testosterone transfer was prevented.- Z p" i. }" Z" b
Our patient’s testosterone level was 60 ng/mL,
" C4 e" f' Q4 ?: V- T* p7 l; I# Bwhich was clearly high. Some studies suggest that( c" \% |5 k0 ?2 k2 }& l
dermal conversion of testosterone to dihydrotestos-% r' O& H- g0 I- @5 S, u
terone, which is a more potent metabolite, is more2 ~4 s, t6 v8 u& ~" [4 Z
active in young children exposed to testosterone
5 s4 u9 K$ m! Iexogenously7; however, we did not measure a dihy-& {; @2 B8 F. J- D; z; v
drotestosterone level in our patient. In addition to/ z/ }3 j$ T+ f; q- _
virilization, exposure to exogenous testosterone in
% A' c1 a& C7 F4 i+ wchildren results in an increase in growth velocity and
7 U, z( E0 O9 e: q0 x) Y9 V. radvanced bone age, as seen in our patient.% w4 m, G# v' }& M: H# T, y
The long-term effect of androgen exposure during
# T |0 A+ x7 I+ G" Xearly childhood on pubertal development and final2 L& S0 x3 i T/ ^
adult height are not fully known and always remain
. T0 v0 Z* A' s8 _a concern. Children treated with short-term testos-
2 |( V3 n* p; n8 [3 Aterone injection or topical androgen may exhibit some
! P! C7 A8 E1 }- m5 r2 Y& {acceleration of the skeletal maturation; however, after+ Z1 {- r, B l w6 `
cessation of treatment, the rate of bone maturation, C7 o# e( h# f! I& n. b& d) p( j2 ?
decelerates and gradually returns to normal.8,9$ p! ~1 M% _& L4 M
There are conflicting reports and controversy5 k& t% l% o7 H: F! ^
over the effect of early androgen exposure on adult& Z7 ^6 e* a. [& H$ g' @
penile length.10,11 Some reports suggest subnormal8 r: y% D+ t: g A& c# M
adult penile length, apparently because of downreg-
( ^2 o) q& U/ H* {9 ~& ^8 {; K0 Aulation of androgen receptor number.10,12 However,7 E, B% d$ { H2 ^- J
Sutherland et al13 did not find a correlation between8 L6 x. n9 m5 y1 v: W2 t- f
childhood testosterone exposure and reduced adult
/ h7 n5 j; A( A) q0 C% lpenile length in clinical studies.6 x$ X( E( G, g7 w8 [
Nonetheless, we do not believe our patient is
; G4 s) W* j/ g4 a+ d# bgoing to experience any of the untoward effects from* h1 C. i6 o+ K$ u0 ?
testosterone exposure as mentioned earlier because
3 A8 f' V. H8 N- pthe exposure was not for a prolonged period of time.
6 Q% t/ B( |; C0 ~0 ]Although the bone age was advanced at the time of$ R# N! Y1 h" e2 S
diagnosis, the child had a normal growth velocity at ?% Z K3 ~7 p, W
the follow-up visit. It is hoped that his final adult% K" r8 ?3 m A, ~) b
height will not be affected.% o% C+ T* Y, D6 r: R
Although rarely reported, the widespread avail-$ J2 C& f; n4 {7 e3 M! ? |
ability of androgen products in our society may6 [6 q- u) {) g& l: }' n$ i) J0 y3 _
indeed cause more virilization in male or female
* w7 S: a4 F. a/ R- o% E* D+ \children than one would realize. Exposure to andro-; h/ x7 k7 j0 Q9 _$ i
gen products must be considered and specific ques-: G/ j0 D7 |8 Q$ A% [+ W5 Z
tioning about the use of a testosterone product or
B8 E0 P2 O3 T4 _2 ?) N" X8 kgel should be asked of the family members during
9 x8 `6 l6 B' e: Y/ a$ p% P6 Bthe evaluation of any children who present with vir-
9 a k, S- M& A1 r, Y% `6 c& Gilization or peripheral precocious puberty. The diag-
1 W0 W" K+ X0 e! S0 B3 Qnosis can be established by just a few tests and by; t% z% u$ y# g' V5 [) Y p
appropriate history. The inability to obtain such a
4 f Y; F o6 g, [history, or failure to ask the specific questions, may2 S7 E4 E9 f5 e C# o
result in extensive, unnecessary, and expensive" f0 S& R$ b+ ?$ V2 y) \
investigation. The primary care physician should be/ K8 ]3 W0 E7 q6 r: A
aware of this fact, because most of these children
) k, b* L% l1 k, {, Nmay initially present in their practice. The Physicians’9 v, T& t- b4 a" G
Desk Reference and package insert should also put a% X& I+ M4 j& D) F% I+ j- O
warning about the virilizing effect on a male or
" T7 c" f" r/ U/ A0 d7 pfemale child who might come in contact with some-& V5 D( x% z9 o: Q
one using any of these products.
- z' B; {* C' Q: sReferences
) D4 c. E& N: V* o* J6 |3 K1. Styne DM. The testes: disorder of sexual differentiation& F: O6 F, J& C9 y- k$ E2 l. B- `
and puberty in the male. In: Sperling MA, ed. Pediatric
+ c( f" o# h( ^; t2 kEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;. }% P# s* B+ H( L: f9 a& d
2002: 565-628.' A: b( V4 t1 e! `3 J. v1 t
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
( P; X: H2 r- b' U1 cpuberty in children with tumours of the suprasellar pineal |
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