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Sexual Precocity in a 16-Month-Old. b3 P% D/ f; g1 h, v+ O
Boy Induced by Indirect Topical
4 r, K* x* C# v% G2 w- B; j% xExposure to Testosterone
9 e8 |6 x( E& L; @. R4 {Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
' `$ Z3 ?' G. U: Rand Kenneth R. Rettig, MD19 v8 V. i$ `% ~+ z2 K3 I# O, M% q: W
Clinical Pediatrics
4 h$ h9 |: w/ B( ~! @6 tVolume 46 Number 6
. j& `% _9 h7 u8 u: S+ @July 2007 540-543
# P: w9 J' U$ S7 H& A, v! M© 2007 Sage Publications
* j- E" \7 B r10.1177/0009922806296651
9 [- X& d S m) n; z# C& M' zhttp://clp.sagepub.com3 {. r$ m4 a* _' {/ _2 u- a5 B
hosted at/ }" @7 w8 f( t# I6 }
http://online.sagepub.com& F3 m# ^4 Y) m/ [+ z5 `
Precocious puberty in boys, central or peripheral,
" z& j# l6 A2 { Yis a significant concern for physicians. Central2 [; y, s5 s$ T7 y# q9 m
precocious puberty (CPP), which is mediated6 I- M7 z2 B; r0 Z0 X+ G
through the hypothalamic pituitary gonadal axis, has; V5 h9 R8 R* Q- H5 t" T
a higher incidence of organic central nervous system
; `) @6 ]7 Q0 `lesions in boys.1,2 Virilization in boys, as manifested
e& R" w/ z2 e( }- O# gby enlargement of the penis, development of pubic2 s" v' L4 h" T2 N1 L
hair, and facial acne without enlargement of testi-
! A$ f ] O5 z+ Ecles, suggests peripheral or pseudopuberty.1-3 We
* Q* G* {$ m. z( L; _3 y8 rreport a 16-month-old boy who presented with the
9 S. d5 D4 n* I# \3 ~& ^3 {enlargement of the phallus and pubic hair develop-" x c) o g) @$ {
ment without testicular enlargement, which was due
' m' N3 M2 v% j7 xto the unintentional exposure to androgen gel used by
i3 h4 M B/ e- K: qthe father. The family initially concealed this infor-
+ a$ [9 a+ J0 V# emation, resulting in an extensive work-up for this
2 J( c6 f7 L* E: U! `, k* Gchild. Given the widespread and easy availability of" r0 `1 T. z0 L2 c
testosterone gel and cream, we believe this is proba-5 P, A% {" Z+ ?1 l3 o2 K
bly more common than the rare case report in the2 x- A8 p6 O' T
literature.4
; a1 U# [1 P( dPatient Report! ~3 j7 W" `4 }$ q ~
A 16-month-old white child was referred to the
8 N( I) ^) l3 p1 b' Kendocrine clinic by his pediatrician with the concern
9 @% o& ?% O. Tof early sexual development. His mother noticed, W; P5 z. E0 m* J
light colored pubic hair development when he was
- S w5 U& ]3 G$ W, u6 w+ `7 zFrom the 1Division of Pediatric Endocrinology, 2University of
9 m; C) U5 [- o5 o' s8 P( ?5 bSouth Alabama Medical Center, Mobile, Alabama.
x0 y" J" I2 v' S, B; S5 tAddress correspondence to: Samar K. Bhowmick, MD, FACE,, F1 ]; V D: |- ~- I1 Q
Professor of Pediatrics, University of South Alabama, College of
9 p3 O. X; [* qMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
* D# v4 o; z. m% }' A* ]+ ie-mail: [email protected].
" @) |& r! ?5 a9 K/ Y. e7 r; qabout 6 to 7 months old, which progressively became
, _1 n3 K. g( _" G5 q F3 fdarker. She was also concerned about the enlarge-
r3 [/ E) p+ z8 }) k) iment of his penis and frequent erections. The child
( {7 i/ j5 w; t& b1 Rwas the product of a full-term normal delivery, with
2 a+ ^2 V7 Y6 ]. K- Ia birth weight of 7 lb 14 oz, and birth length of* y& j- v( y$ a, q, p" A
20 inches. He was breast-fed throughout the first year5 j6 O, A/ F" k! `) @! G1 |/ Z
of life and was still receiving breast milk along with, {- h8 N& M# O6 m# o9 c% t: h
solid food. He had no hospitalizations or surgery,
( k, F/ W8 v# O L3 m+ `; land his psychosocial and psychomotor development
/ i+ {3 q9 L, zwas age appropriate.
) j5 |* {5 K3 ^: K5 s2 uThe family history was remarkable for the father,
- A$ Z* J$ x0 W: N/ O- rwho was diagnosed with hypothyroidism at age 16,
! k- G+ s# o& b6 v9 ywhich was treated with thyroxine. The father’s
5 g# }+ q- f- @4 K3 j- \height was 6 feet, and he went through a somewhat
E3 h% P& y) u! Aearly puberty and had stopped growing by age 14.
0 | J; c+ a+ v+ g2 qThe father denied taking any other medication. The' i! _1 ~$ Q ^0 i; ^3 ?
child’s mother was in good health. Her menarche2 v2 M3 ]! L1 d$ x
was at 11 years of age, and her height was at 5 feet5 O1 }! ?/ ~$ ]" R9 M2 ?) N: M0 y
5 inches. There was no other family history of pre-) B# }2 z" H& A
cocious sexual development in the first-degree rela-1 j+ ~/ E, d1 v; l* }# T7 Z: K$ n5 T
tives. There were no siblings.: ^/ n# y; O' p# d" {/ E# |; Z
Physical Examination
+ g7 \9 Y" y7 J3 _' eThe physical examination revealed a very active,
' z# x2 i2 g$ p0 B' R. rplayful, and healthy boy. The vital signs documented
' I8 @4 A, R; D/ |+ A/ M" o& ba blood pressure of 85/50 mm Hg, his length was. o. U' A* q9 x; J& J0 I
90 cm (>97th percentile), and his weight was 14.4 kg# T: ^; p+ O1 V6 E3 d1 {" |
(also >97th percentile). The observed yearly growth
" ]# N8 X1 o* I! gvelocity was 30 cm (12 inches). The examination of
1 [' P% c b/ A4 J; L; Dthe neck revealed no thyroid enlargement.
Q9 {# P" u! d% s6 RThe genitourinary examination was remarkable for
6 X) D3 B$ a" y6 J! i, z8 \enlargement of the penis, with a stretched length of. q4 U6 V3 f/ B v
8 cm and a width of 2 cm. The glans penis was very well3 J. ?7 u& `9 T* [9 N2 y! ?
developed. The pubic hair was Tanner II, mostly around6 N# }; X8 l# H0 ^; Q$ L) P9 e
540/ K) a7 M. T: O
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
3 {! m$ i v& _, |the base of the phallus and was dark and curled. The
H0 p# p# @; y# f: atesticular volume was prepubertal at 2 mL each.. Y9 g$ _* f" A+ k9 q& r
The skin was moist and smooth and somewhat* e" ~5 {0 G7 G9 {: @, g) t; N# E
oily. No axillary hair was noted. There were no9 c- ?5 f5 |) ]) ^. f
abnormal skin pigmentations or café-au-lait spots.1 c. I& G9 o7 g. v# n* h2 A& Z
Neurologic evaluation showed deep tendon reflex 2+
, j% r* Z' E+ N- Obilateral and symmetrical. There was no suggestion+ ]" ~. p# H8 g9 l$ F5 P
of papilledema.
+ T, r9 Y3 ]6 P) T- d3 E6 tLaboratory Evaluation/ D. S# J! p% b+ q; p" O' ]
The bone age was consistent with 28 months by" Z; c# X$ s$ ~) X
using the standard of Greulich and Pyle at a chrono-# j$ ?" V; N* Q$ i! ~. a( I" S
logic age of 16 months (advanced).5 Chromosomal
/ A: Y7 c, \2 ?3 u) tkaryotype was 46XY. The thyroid function test
& Q# k7 ^( s0 j' n: ~8 gshowed a free T4 of 1.69 ng/dL, and thyroid stimu-7 T8 }( o: l* T' w( i& h0 K
lating hormone level was 1.3 µIU/mL (both normal).
1 U7 e: m0 g! |: y0 t( @& d" c/ oThe concentrations of serum electrolytes, blood3 r; o7 q! D* g$ E1 }
urea nitrogen, creatinine, and calcium all were) ?# d8 x0 ~, r! a5 ^( z
within normal range for his age. The concentration5 U5 V3 n G1 r M' `
of serum 17-hydroxyprogesterone was 16 ng/dL. ]2 m; d1 G" O+ J; d6 T+ G) L$ Z: w
(normal, 3 to 90 ng/dL), androstenedione was 20
8 T% M5 n# k. g5 S [% sng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
; T* P+ K2 F0 K! Hterone was 38 ng/dL (normal, 50 to 760 ng/dL),
3 V* i7 z$ c& m5 j. {# @desoxycorticosterone was 4.3 ng/dL (normal, 7 to
- k4 w: C) h6 P3 F8 s49ng/dL), 11-desoxycortisol (specific compound S)1 I& ?9 k, w( F
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
! ]) U5 U1 ?6 r' R$ d9 stisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
3 [" t2 y4 j6 o* ~/ P# ~testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
7 c- N% `2 S% o* Fand β-human chorionic gonadotropin was less than, k- l7 r& f" U/ ~
5 mIU/mL (normal <5 mIU/mL). Serum follicular7 x! z& p* b6 _$ L
stimulating hormone and leuteinizing hormone* W! K4 ~5 `9 ~* a% u
concentrations were less than 0.05 mIU/mL7 E1 e5 k& q& E9 g& a
(prepubertal).1 W% U: A0 _+ ~# ~. x n
The parents were notified about the laboratory4 f# F- H3 n' r
results and were informed that all of the tests were
/ Y9 f) h% Y: | g o, Knormal except the testosterone level was high. The
) k- E: [2 f( r4 kfollow-up visit was arranged within a few weeks to
% x) P! Q9 L- U; X. ~obtain testicular and abdominal sonograms; how-
3 N; }/ I P0 v2 F( c; I- G3 ~ever, the family did not return for 4 months.
$ g6 g9 w3 J- X l. gPhysical examination at this time revealed that the
. t! ?7 C* e+ X' \8 Cchild had grown 2.5 cm in 4 months and had gained
+ {6 M, N" m; G% p2 kg of weight. Physical examination remained
! Q Q: M! l% [' e7 U9 C' aunchanged. Surprisingly, the pubic hair almost com-
8 k" h, q; x; xpletely disappeared except for a few vellous hairs at
' x/ g$ P* y1 R: ethe base of the phallus. Testicular volume was still 28 [ [4 k+ P4 ]# A9 Z, G
mL, and the size of the penis remained unchanged.
+ V9 `& U8 E4 [4 \1 L7 Q( U9 K( CThe mother also said that the boy was no longer hav-
& s6 q8 Q/ }( N! D& X3 Q! ?! R0 S, @ing frequent erections.! {- P- b) D2 o: i
Both parents were again questioned about use of
: S5 v, K# N; u, y8 Cany ointment/creams that they may have applied to) Q% X' Q7 O% H) S1 S6 T
the child’s skin. This time the father admitted the
+ _/ l8 u$ o1 d& u! q$ `Topical Testosterone Exposure / Bhowmick et al 5416 K# m* E6 I. l
use of testosterone gel twice daily that he was apply-7 B+ W, V1 ~2 S
ing over his own shoulders, chest, and back area for
- S Q9 [) E8 @. o% D2 Ta year. The father also revealed he was embarrassed6 V3 e4 b. I; g' k1 l
to disclose that he was using a testosterone gel pre-
8 m4 G: e9 F' ~1 {6 U4 u" w0 r9 }scribed by his family physician for decreased libido x8 O/ `# c$ k
secondary to depression.8 H2 [/ a" v+ k' B. X- ~
The child slept in the same bed with parents.3 v' T1 J! q7 z- \3 E
The father would hug the baby and hold him on his
# _# {" N0 c$ B: s8 Schest for a considerable period of time, causing sig-% {/ c/ X; }5 w
nificant bare skin contact between baby and father.
- V" X2 K+ M6 p+ [5 T% PThe father also admitted that after the phone call,
. r5 f4 ^+ ~7 D# O$ j" Nwhen he learned the testosterone level in the baby
% n* T( t/ I" c& X5 W5 n4 pwas high, he then read the product information/ g0 r2 Q1 ~9 l/ F# _0 y- }- R
packet and concluded that it was most likely the rea-
0 S9 P0 p) y6 p+ ?son for the child’s virilization. At that time, they. }3 u# ^) t6 Q3 a% Q- V4 y/ A
decided to put the baby in a separate bed, and the- f; q0 Q* }8 w& R P
father was not hugging him with bare skin and had
3 _9 U3 T! `% G4 ~9 S" z0 }been using protective clothing. A repeat testosterone
6 f: f$ t. v! ptest was ordered, but the family did not go to the3 [) e" b" T3 D: V7 d% f" h
laboratory to obtain the test.4 J! U& {3 {: r! k
Discussion! G7 e8 l$ @1 A, w2 ]5 H, u- b# A
Precocious puberty in boys is defined as secondary" V$ K) o$ w5 k+ u1 d- X
sexual development before 9 years of age.1,4
% u7 d" v& c+ ~9 l: j% Z. qPrecocious puberty is termed as central (true) when
) B h+ O1 R) y+ {$ `5 nit is caused by the premature activation of hypo-
* j' g2 d, D* cthalamic pituitary gonadal axis. CPP is more com-( Z! K; G9 f* _; m/ t
mon in girls than in boys.1,3 Most boys with CPP
+ Z$ R0 H7 X* C+ g( A' kmay have a central nervous system lesion that is
; p: ]1 C1 r, D- tresponsible for the early activation of the hypothal-0 r( V# a) \2 r
amic pituitary gonadal axis.1-3 Thus, greater empha-
! g7 r% U5 Z/ ~4 N! qsis has been given to neuroradiologic imaging in
3 l" R) p' U; k c/ Aboys with precocious puberty. In addition to viril-% {. M* }* i0 o1 b4 G, T
ization, the clinical hallmark of CPP is the symmet-
# v* I, D! f3 b: Lrical testicular growth secondary to stimulation by
/ S! ?3 u8 ` z: U8 |5 u! {# Hgonadotropins.1,3
+ J( j( r$ l8 `4 }7 e" pGonadotropin-independent peripheral preco-
, e9 @" Q- T3 Q. P9 z5 n6 Kcious puberty in boys also results from inappropriate
4 q* k, j4 l. c/ B4 f Mandrogenic stimulation from either endogenous or
8 p8 k$ G' @1 vexogenous sources, nonpituitary gonadotropin stim-, X! o: r% h# C. c4 p- `( v
ulation, and rare activating mutations.3 Virilizing' W. m: a r/ l1 J. T, ~
congenital adrenal hyperplasia producing excessive P. c4 u/ u" N( \ S! p
adrenal androgens is a common cause of precocious
9 S% i0 ~* M6 ppuberty in boys.3,4
E& `# F8 {0 r" r$ v0 Z6 aThe most common form of congenital adrenal
+ R: y% J( B' R3 I7 d& Rhyperplasia is the 21-hydroxylase enzyme deficiency.0 Q6 t, l! i4 c. I+ L; A
The 11-β hydroxylase deficiency may also result in
% u6 o$ n, T, h! q/ @% O9 o# ^. B% Eexcessive adrenal androgen production, and rarely,6 T9 i( C% _& e+ T4 i9 H; ^
an adrenal tumor may also cause adrenal androgen
8 n, w8 j& v" g8 T* p! Y* ?1 G" C L2 Iexcess.1,3) A5 N8 O) V0 e* p7 M# v3 j T+ o* X
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
# ]( r- |- c0 e542 Clinical Pediatrics / Vol. 46, No. 6, July 2007) u7 `6 J( |* T+ ]# J, x
A unique entity of male-limited gonadotropin-
2 X6 K: i& [- |: Dindependent precocious puberty, which is also known( l8 @) R. _+ @4 V
as testotoxicosis, may cause precocious puberty at a
9 L2 x, g- Q* I1 y: Zvery young age. The physical findings in these boys
+ Y! T! n% b) T+ G, }) L) V9 bwith this disorder are full pubertal development,
" t: M2 A: R' q5 a( j% @including bilateral testicular growth, similar to boys4 w) U4 V% L+ r, L3 ?
with CPP. The gonadotropin levels in this disorder v F: f4 n/ \2 Z, T3 e4 l
are suppressed to prepubertal levels and do not show
* Y0 K4 H4 \2 [+ zpubertal response of gonadotropin after gonadotropin-
6 L n+ W- {. f, `% Y* }6 zreleasing hormone stimulation. This is a sex-linked8 } H5 `. v0 q8 u
autosomal dominant disorder that affects only5 y2 M5 v8 w* y# p0 N+ T0 e( _
males; therefore, other male members of the family
4 h% U: i! j4 F) T: Dmay have similar precocious puberty.3
/ k7 a/ }; G# G l/ jIn our patient, physical examination was incon-
$ t9 o; m2 P- \. n( z* M& m# `sistent with true precocious puberty since his testi-
# l$ E/ g8 F, h7 N* Hcles were prepubertal in size. However, testotoxicosis& r. J* K8 d5 n. z9 m; ?3 s
was in the differential diagnosis because his father
2 l) Y6 c! L) g- }$ G( Istarted puberty somewhat early, and occasionally,
9 F; m& U! C- @$ mtesticular enlargement is not that evident in the
; w' `/ Q1 R+ y5 h& t% nbeginning of this process.1 In the absence of a neg-
. B u4 H( C5 Z0 i, r7 sative initial history of androgen exposure, our; q$ D# J4 Z! a/ E, ~' y
biggest concern was virilizing adrenal hyperplasia,
1 V9 H/ L& u) Y& f% b seither 21-hydroxylase deficiency or 11-β hydroxylase
8 u+ B; Q; Q- H- q5 P/ K2 S9 g3 Ideficiency. Those diagnoses were excluded by find-; K7 {% O& q& t+ p; Q
ing the normal level of adrenal steroids.+ q. ?7 d, M7 I2 P9 U7 q* I
The diagnosis of exogenous androgens was strongly1 J8 U& Y! D& Q8 `; m: q: V
suspected in a follow-up visit after 4 months because2 J) D% k z o9 h# c
the physical examination revealed the complete disap-
4 R- }1 Q' L2 ~) R5 X @pearance of pubic hair, normal growth velocity, and% y- S5 H4 T, n5 t
decreased erections. The father admitted using a testos-5 _3 ~* U: x- o. @6 ~' s/ ]. m
terone gel, which he concealed at first visit. He was$ o D( ?$ T6 o& a
using it rather frequently, twice a day. The Physicians’
4 u+ q0 A0 {7 F- E. }! MDesk Reference, or package insert of this product, gel or s5 n5 |: Z5 A" \) @/ t# q* F' x
cream, cautions about dermal testosterone transfer to
$ D8 T* D2 p R8 S/ A" N( Funprotected females through direct skin exposure.
- h+ N7 w, S% l$ Q; d9 ~$ SSerum testosterone level was found to be 2 times the1 h, U" r$ Z8 a0 K& d
baseline value in those females who were exposed to
7 O' s/ d7 j& |0 q# I. feven 15 minutes of direct skin contact with their male5 s+ D* f* z1 {! W; a2 \# ~$ f3 S
partners.6 However, when a shirt covered the applica-* t+ i; N( U" h! @. Z1 o0 Z) p6 S. o
tion site, this testosterone transfer was prevented.
' R; ~4 L) {8 s& mOur patient’s testosterone level was 60 ng/mL,/ I( t7 w7 L( H8 P* _4 F
which was clearly high. Some studies suggest that. I8 `! ? Z v1 y' ~1 @
dermal conversion of testosterone to dihydrotestos-% j0 Y7 O6 o! s& m0 H0 [) \0 x
terone, which is a more potent metabolite, is more" j N: A8 k+ L2 n: ~, u
active in young children exposed to testosterone/ O- E* n9 ~. v- f& S2 q- {
exogenously7; however, we did not measure a dihy-
/ _+ M. U9 q8 f$ Ydrotestosterone level in our patient. In addition to
T; L0 F% N% n3 Nvirilization, exposure to exogenous testosterone in F: x" Z' x1 z7 F6 Q4 @, \
children results in an increase in growth velocity and
( w6 C& m8 r& }" F, ], ~advanced bone age, as seen in our patient.& K% C$ Z. b! e3 [* ?
The long-term effect of androgen exposure during' s, r% w6 [3 p
early childhood on pubertal development and final( Q' W4 H+ x+ \; l4 u
adult height are not fully known and always remain
i. i* w; ` U# f# W4 J6 Ha concern. Children treated with short-term testos-
4 R7 y. K) e1 Eterone injection or topical androgen may exhibit some
! G) |1 z0 `0 k( o: |, Iacceleration of the skeletal maturation; however, after" R: ?2 I8 G& v6 G6 Z* o. e
cessation of treatment, the rate of bone maturation
5 v3 h. e6 N6 q0 r9 \" Gdecelerates and gradually returns to normal.8,94 n. r5 Y# e- O6 U2 ^% ]! O. ]" o
There are conflicting reports and controversy: y$ I8 K' _ A9 v
over the effect of early androgen exposure on adult* m1 R! w( y+ w7 U
penile length.10,11 Some reports suggest subnormal. ^3 Z' r. b5 G" G1 [
adult penile length, apparently because of downreg-
+ E" K& |/ S* l( f, { L* a2 {ulation of androgen receptor number.10,12 However,
. X- j' |# G! O# iSutherland et al13 did not find a correlation between( O3 w2 K( W2 w7 \+ q6 ^) ^6 H9 |
childhood testosterone exposure and reduced adult
4 O& H" c) \$ [# |penile length in clinical studies.( N- `7 y7 s1 c
Nonetheless, we do not believe our patient is) {, f1 m2 h) o! d1 D
going to experience any of the untoward effects from8 w0 N3 B! J: ], @8 n
testosterone exposure as mentioned earlier because* W+ k0 s# J% `; L
the exposure was not for a prolonged period of time.
) V+ v) d; G! U/ |0 kAlthough the bone age was advanced at the time of
# W$ w, j) X( [ Rdiagnosis, the child had a normal growth velocity at
) t9 }/ Z' O# W, e/ |2 d: Othe follow-up visit. It is hoped that his final adult3 a8 E, e! C+ J7 t8 c
height will not be affected.
- e' f# p; b) U& x( u% OAlthough rarely reported, the widespread avail-; F. J7 ~% m F; K2 m4 y0 a @. V
ability of androgen products in our society may: M3 y2 D$ J+ u% H' d( D, W
indeed cause more virilization in male or female
s9 C. U+ r) Q7 Achildren than one would realize. Exposure to andro-: c1 Z2 D6 w( u7 |# t
gen products must be considered and specific ques-
1 a) F- u1 Y( y# v3 f8 _# |tioning about the use of a testosterone product or9 L$ F) @4 d+ E* @
gel should be asked of the family members during
2 x% R) B |7 ~* t# t# K- Xthe evaluation of any children who present with vir-
8 w7 u, L+ B1 a& {ilization or peripheral precocious puberty. The diag-
# \) x& \+ a& u+ a$ Z' qnosis can be established by just a few tests and by- R3 s/ U7 T! D. W3 U
appropriate history. The inability to obtain such a& `1 b4 i1 k: q6 X |, {
history, or failure to ask the specific questions, may
+ ^! D- s4 m% T0 sresult in extensive, unnecessary, and expensive+ @3 T- H+ ]% k: S" ~
investigation. The primary care physician should be$ C; q, [# U @7 m
aware of this fact, because most of these children
, |8 E+ c' w2 Y5 {" Smay initially present in their practice. The Physicians’+ ~0 @2 L* s1 K* X5 q" [4 y
Desk Reference and package insert should also put a
. X5 H; Z6 M6 p/ X; [warning about the virilizing effect on a male or
3 ?- W# z+ ^) E# h! M% Q- k4 pfemale child who might come in contact with some-$ u+ h" j3 f1 f/ b
one using any of these products.4 P8 g$ W4 V- m2 J1 d' ~( d3 H& ^
References' ?% u' Y! D, i% H$ Q* B% u
1. Styne DM. The testes: disorder of sexual differentiation. E4 ?; C. w$ i1 |1 E
and puberty in the male. In: Sperling MA, ed. Pediatric
/ l* v/ ~: Y' X* K* ^Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;! v) K& o. z4 P8 ]* M7 b
2002: 565-628.
) m/ B$ J, X4 Y) B1 E. G2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
3 g5 ?, A$ z* ?/ Z5 a! apuberty in children with tumours of the suprasellar pineal |
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