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Sexual Precocity in a 16-Month-Old
+ x7 S' ]$ Z* i* XBoy Induced by Indirect Topical
0 U4 i. }& d" v P% fExposure to Testosterone- \( |+ N0 _. P" r5 q5 _
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2) p3 G ^: p h7 z
and Kenneth R. Rettig, MD1; p$ O- c2 X- K0 v" ?8 y- e: z" w
Clinical Pediatrics
( P; A( c3 e: y! C- c. rVolume 46 Number 6
2 W, p0 d* D' o; o" ?- h/ s: [July 2007 540-5434 T8 e ]4 _. u: Z2 o5 Q
© 2007 Sage Publications
y: e+ F. H% A! m1 y10.1177/0009922806296651
" x1 w+ Q6 f4 mhttp://clp.sagepub.com
7 V( M, ?5 C" u3 Mhosted at2 G |9 E- P0 n/ q) [0 b4 v* t
http://online.sagepub.com8 f4 l( L2 ^% ~. v; V
Precocious puberty in boys, central or peripheral," h% X+ H+ t+ i* }$ g
is a significant concern for physicians. Central
) w6 e- n- B$ U! T9 R- }precocious puberty (CPP), which is mediated* c9 h; H" d. J6 n
through the hypothalamic pituitary gonadal axis, has
9 b' }+ A- a# Ha higher incidence of organic central nervous system
3 R7 ?4 e- E2 O3 \( Y# y- xlesions in boys.1,2 Virilization in boys, as manifested
+ m8 H- h/ `! D7 T, ~by enlargement of the penis, development of pubic
8 [' G% u, A, T A% f' xhair, and facial acne without enlargement of testi-
, d8 @/ ]. q6 ~0 P/ |cles, suggests peripheral or pseudopuberty.1-3 We3 _, B% b Y( h9 F9 R; ~0 J' p& L( Y2 B
report a 16-month-old boy who presented with the2 p8 d) w* ?/ U4 c
enlargement of the phallus and pubic hair develop-/ T' n$ V% I$ O9 o
ment without testicular enlargement, which was due
6 n4 R9 \. ]; D `4 R+ C4 p/ Rto the unintentional exposure to androgen gel used by. O9 w2 G- p5 s6 D4 ~
the father. The family initially concealed this infor-
8 ?+ H% _# d8 P( }mation, resulting in an extensive work-up for this% Q5 P( W3 P. x) C( T7 h# B/ N% T
child. Given the widespread and easy availability of
. t1 a% r4 S E5 ^testosterone gel and cream, we believe this is proba-
! R) V* e; ?# @4 lbly more common than the rare case report in the Q4 F; T; _" L4 h9 v* |, |
literature.4
( A/ o+ Y: s' b6 d- BPatient Report
. J* b- R1 A; s N' I: ^A 16-month-old white child was referred to the
7 X( P* n8 A9 r1 u5 Xendocrine clinic by his pediatrician with the concern
- O2 j, v+ X2 s3 v& Z* vof early sexual development. His mother noticed2 X2 p; @! B4 p
light colored pubic hair development when he was
: R+ w: G+ o) a4 B5 g2 H1 W# VFrom the 1Division of Pediatric Endocrinology, 2University of
/ K% N( ~; q; D6 u, b' ] PSouth Alabama Medical Center, Mobile, Alabama.
x5 w n4 m8 s* J% J( fAddress correspondence to: Samar K. Bhowmick, MD, FACE,
1 Y6 T, Q6 r& r- qProfessor of Pediatrics, University of South Alabama, College of# A* c" j" h# b2 n5 J
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
- t& g- e& U( \- o# z6 q) {& pe-mail: [email protected]., [2 _, F: d5 V( u
about 6 to 7 months old, which progressively became
" ^9 x* s3 U* ^: Z. hdarker. She was also concerned about the enlarge-( Y$ m( g F4 ^) C
ment of his penis and frequent erections. The child# c. O7 f! I- [( C6 s
was the product of a full-term normal delivery, with
4 _9 \. Q3 e1 L+ T3 d) X9 Ha birth weight of 7 lb 14 oz, and birth length of% X+ u7 ?! V& o% g5 Z. X
20 inches. He was breast-fed throughout the first year
' Z/ Y9 Q/ d# r! e/ H8 ~of life and was still receiving breast milk along with
2 `( Y. }) b. z8 ], h6 f8 t7 {solid food. He had no hospitalizations or surgery,1 V: z5 ^+ R7 k( p5 [
and his psychosocial and psychomotor development$ f8 P" x, a ]' E
was age appropriate." ]2 W" b4 u; a$ {: Y: F
The family history was remarkable for the father," q; M" @. Z% X' i1 v2 Y5 `
who was diagnosed with hypothyroidism at age 16,, U0 F2 K; {; l* W8 L8 T
which was treated with thyroxine. The father’s
( ^" |/ C1 x: M S, d8 e$ E8 eheight was 6 feet, and he went through a somewhat
L o$ p0 @2 c& L2 l# c8 }early puberty and had stopped growing by age 14.8 Y3 R S/ z" j" Z& n" J. S
The father denied taking any other medication. The1 e8 F. l0 l7 k# j6 p4 E
child’s mother was in good health. Her menarche; h# f/ ^1 T) o. x
was at 11 years of age, and her height was at 5 feet
' n0 m0 F, P, h/ d. Z+ j5 inches. There was no other family history of pre-
) ]' T$ S9 Q d5 ^/ z" P, ~' ecocious sexual development in the first-degree rela-# M4 h2 O0 |5 H, O
tives. There were no siblings.7 {3 o' t) ^4 ^) Z. h D% s
Physical Examination
* @4 h7 C" r5 m; o: EThe physical examination revealed a very active,
% x N: m$ R7 oplayful, and healthy boy. The vital signs documented( {0 x; I4 p" P( F
a blood pressure of 85/50 mm Hg, his length was6 w$ `: k$ W2 M% \
90 cm (>97th percentile), and his weight was 14.4 kg
/ s4 h, m+ w1 b' B4 C; x(also >97th percentile). The observed yearly growth
: X t& H3 U ?2 c, F+ N( uvelocity was 30 cm (12 inches). The examination of
% I! r p7 V+ T+ `. r3 \4 cthe neck revealed no thyroid enlargement.! U# P& n; c ^0 Z4 u
The genitourinary examination was remarkable for
, g4 M( X; X% g/ K @) K: c0 Z/ m+ [enlargement of the penis, with a stretched length of
! Z* k E; A( q8 p1 u8 cm and a width of 2 cm. The glans penis was very well1 Z+ Z* L/ B2 O6 W1 m
developed. The pubic hair was Tanner II, mostly around
+ L. p6 `( v5 d, T( y4 C+ i# t, U/ I5404 Z4 J- m& Y! A6 f6 f$ n! z7 L
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from1 B+ H$ w0 q w% ]
the base of the phallus and was dark and curled. The
$ x( [2 I$ A- K- F( Dtesticular volume was prepubertal at 2 mL each.% M: B: \& m2 D, J8 m- c0 f* X Q
The skin was moist and smooth and somewhat2 G7 ?. C0 E! T5 `( P
oily. No axillary hair was noted. There were no
# L$ p* c- e: w$ B3 x5 aabnormal skin pigmentations or café-au-lait spots.# d( Z) i4 R2 ~3 M6 p- H2 A
Neurologic evaluation showed deep tendon reflex 2+
5 R. f$ A5 |& ?bilateral and symmetrical. There was no suggestion
8 V2 ~! z5 u% e" Z* E7 Aof papilledema.
' s! z2 W. K z1 x8 Y/ {: CLaboratory Evaluation: u+ v- `3 ?3 p& t7 h
The bone age was consistent with 28 months by
* G' f! K4 C2 B% M! K1 I1 Q6 L; nusing the standard of Greulich and Pyle at a chrono-
* Q# ?8 Q4 a, Llogic age of 16 months (advanced).5 Chromosomal
5 r+ W+ q9 A t( Ukaryotype was 46XY. The thyroid function test
, _% W7 U2 r# _showed a free T4 of 1.69 ng/dL, and thyroid stimu-
( I) u. C- j3 C8 R; u N) p( o. xlating hormone level was 1.3 µIU/mL (both normal).
* M1 _/ P( u+ D' c3 S; mThe concentrations of serum electrolytes, blood
- m, R3 C1 R1 J7 W% kurea nitrogen, creatinine, and calcium all were
/ _2 m. A: u9 f- J9 [2 F) a0 swithin normal range for his age. The concentration2 O' L& `3 [, V
of serum 17-hydroxyprogesterone was 16 ng/dL; W; L4 b0 v0 |5 @
(normal, 3 to 90 ng/dL), androstenedione was 20+ {6 E* |) [) v4 `
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-. z8 T: c( G3 G; ? @5 s
terone was 38 ng/dL (normal, 50 to 760 ng/dL),4 z7 i# B& G' z" J4 \; p
desoxycorticosterone was 4.3 ng/dL (normal, 7 to, A- k' {' K- g: N; v% @
49ng/dL), 11-desoxycortisol (specific compound S)
# n# ^" l! ?; `$ F$ k$ swas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-- i2 _ K4 x. T: T1 @( U0 e
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total& }. R# `4 A; Y- u) w; s" @% V
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),# s3 J. Y2 c, l6 {8 K" v* n
and β-human chorionic gonadotropin was less than
) [1 } x. y2 x+ {0 E3 V5 mIU/mL (normal <5 mIU/mL). Serum follicular
: K4 e* \) b9 e! z* f8 ^2 t% _) vstimulating hormone and leuteinizing hormone' M+ E' M. e, q: c) @4 s8 K
concentrations were less than 0.05 mIU/mL
7 r" w+ G; g4 h; u(prepubertal).& J8 j% N% }# b. J4 Z" K7 Q' b6 ~" Q
The parents were notified about the laboratory
2 Z* W4 c* r; p$ B; b) Iresults and were informed that all of the tests were
) c, }0 Q/ ?8 \2 jnormal except the testosterone level was high. The8 K- t3 |; U* m9 }6 T; \- F
follow-up visit was arranged within a few weeks to
. i8 @2 |# X. I, R0 `obtain testicular and abdominal sonograms; how-
]1 Z$ _0 C9 f5 w# m3 Mever, the family did not return for 4 months.
. l% Y+ d o: W. aPhysical examination at this time revealed that the
p6 Q! M' X2 v' \1 X9 \child had grown 2.5 cm in 4 months and had gained
! O, E$ _# C: ~2 kg of weight. Physical examination remained
( d: |% c$ p* q4 ~unchanged. Surprisingly, the pubic hair almost com- m2 j- L& J" m
pletely disappeared except for a few vellous hairs at
% e; I: S1 r4 ~the base of the phallus. Testicular volume was still 2
; y* n! u0 Y4 y$ mmL, and the size of the penis remained unchanged.2 r* `# N' i6 n- p. ^% k6 U# b; L/ B
The mother also said that the boy was no longer hav-
7 B9 x+ ~; d" ^2 ~& p2 j' K. B9 cing frequent erections.4 i& _2 X4 J+ _. N6 C. \* c
Both parents were again questioned about use of
9 n; z% ^7 p; u* D, ~any ointment/creams that they may have applied to( i$ t$ {9 x& _ _) V5 Z) j
the child’s skin. This time the father admitted the- Z- R. |$ F- o& @% \3 X; q! l' G
Topical Testosterone Exposure / Bhowmick et al 541, X) x& U# G, u9 W" Q# P- N3 i. A
use of testosterone gel twice daily that he was apply-) F& [" B% u. ^: A: j
ing over his own shoulders, chest, and back area for
8 Q& t- U( C4 h Q1 }a year. The father also revealed he was embarrassed
! r: J+ O# a/ o- h& pto disclose that he was using a testosterone gel pre-% X. Q8 x' r: o. j# P
scribed by his family physician for decreased libido
6 p& L4 u! k: C# L( ^0 w; Tsecondary to depression.
$ U# t3 K7 _8 x3 LThe child slept in the same bed with parents.
, o: l/ v( C6 f+ t) u. eThe father would hug the baby and hold him on his% b3 ~) Y1 h. d6 c* ]
chest for a considerable period of time, causing sig-
0 {6 d8 ]% R* v/ F& _& anificant bare skin contact between baby and father.8 l# x( \; A; k
The father also admitted that after the phone call,) q9 u, j) h1 [
when he learned the testosterone level in the baby
: }- X8 [# Z+ {was high, he then read the product information5 X. k6 B: r/ ]6 ~) @
packet and concluded that it was most likely the rea-
7 u8 ]% @$ c$ x Z8 @! r! `son for the child’s virilization. At that time, they
) j; m+ V- o' Z H# K( Z/ Ddecided to put the baby in a separate bed, and the
; \! n; O- Y, c& _, o/ ]8 g! p% kfather was not hugging him with bare skin and had
' M$ z" P7 a% Zbeen using protective clothing. A repeat testosterone( M3 I* ?; q; ]' ?; M1 c7 ?7 V8 W- X
test was ordered, but the family did not go to the2 ~ S: {6 g- {
laboratory to obtain the test.
. ^. _' J& J: ^( BDiscussion4 S: K" D* k# y% D0 E. U. O
Precocious puberty in boys is defined as secondary7 Q: ?% [! e! Q2 V) h5 b9 f
sexual development before 9 years of age.1,41 f2 A, J# N v9 F0 `* E0 j9 S
Precocious puberty is termed as central (true) when6 s6 A0 e$ F+ @& J$ U& R! Z+ ?: f
it is caused by the premature activation of hypo-! ^; W) {0 d' N' ~
thalamic pituitary gonadal axis. CPP is more com-1 D/ k% l7 b: p' q
mon in girls than in boys.1,3 Most boys with CPP
3 j+ u$ g" O2 z7 ]. o( B5 i/ Gmay have a central nervous system lesion that is c! D; c1 d5 d- Q Q7 @
responsible for the early activation of the hypothal- v8 k. N2 ]: d& Z. I
amic pituitary gonadal axis.1-3 Thus, greater empha-0 s- X& g( _; F! h, E; J
sis has been given to neuroradiologic imaging in3 p1 T0 J% F; A
boys with precocious puberty. In addition to viril-
, l. V2 P4 f+ ]! A7 D! ]. X3 gization, the clinical hallmark of CPP is the symmet-: ~9 J6 n# m. `1 a- {5 M0 D$ \: X
rical testicular growth secondary to stimulation by
) x, d' S$ Z- o) t" ^- Egonadotropins.1,33 d8 I- d* _4 ?9 {
Gonadotropin-independent peripheral preco-
( h {4 U* [" s+ }cious puberty in boys also results from inappropriate! _. k' e6 _8 W! ]. x1 n
androgenic stimulation from either endogenous or& G) x" Z& A" x7 Q1 h8 _
exogenous sources, nonpituitary gonadotropin stim-& I. F' k0 P$ y& [4 s* b7 v
ulation, and rare activating mutations.3 Virilizing6 u! z/ H6 M7 y, g; _! S) K
congenital adrenal hyperplasia producing excessive9 [; s e7 |) F& O& ?) l) K; s6 o
adrenal androgens is a common cause of precocious
" s) z3 R* v6 _% qpuberty in boys.3,4
9 ?; \; o4 [4 \The most common form of congenital adrenal8 B3 W' n3 ?7 S1 L
hyperplasia is the 21-hydroxylase enzyme deficiency.
) v. Q' F2 ?$ P. T2 wThe 11-β hydroxylase deficiency may also result in* p/ y# J! j+ v; z' F1 a
excessive adrenal androgen production, and rarely,2 ?$ K" [" v. p; _7 ^
an adrenal tumor may also cause adrenal androgen
2 J4 W1 V {0 Eexcess.1,33 A z4 x# Y( z: D
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from+ p0 \8 l1 r4 h% d
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
- o. b& w+ i* a- aA unique entity of male-limited gonadotropin-
2 n' j4 }. M3 y. Aindependent precocious puberty, which is also known* @3 R% F/ \% a+ d
as testotoxicosis, may cause precocious puberty at a
1 ~, f Z$ U: V& p( B4 w+ mvery young age. The physical findings in these boys
+ i* D* s) d( a$ g& T# U Vwith this disorder are full pubertal development,5 |/ g. f4 J0 x, j; I5 k
including bilateral testicular growth, similar to boys
5 c# i: c( k. D% d/ S3 {with CPP. The gonadotropin levels in this disorder9 r3 h# m1 d5 C( F) d
are suppressed to prepubertal levels and do not show
* s) ?+ C( ]6 P+ `pubertal response of gonadotropin after gonadotropin-8 o+ D9 J. {* }, z* E- Z
releasing hormone stimulation. This is a sex-linked
# I4 c( D2 v% |autosomal dominant disorder that affects only
* X4 X9 Z' S7 [males; therefore, other male members of the family
; ~2 Y$ l5 w" H6 k1 w" imay have similar precocious puberty.3! X/ \0 v# R c" X0 M
In our patient, physical examination was incon-
8 m! I3 m" z: c0 Q6 A" rsistent with true precocious puberty since his testi-
9 Z8 {2 u0 y9 n# Vcles were prepubertal in size. However, testotoxicosis# w l% H Z' G9 U" V# B0 u
was in the differential diagnosis because his father
9 T% p: I" P' bstarted puberty somewhat early, and occasionally,& V3 X, B5 Q5 V8 {
testicular enlargement is not that evident in the
0 W7 ?( h/ @1 k$ T; Y3 _beginning of this process.1 In the absence of a neg-
" [ }8 @+ W2 p% X# J4 fative initial history of androgen exposure, our
" b6 D1 I+ R7 D' [+ v Mbiggest concern was virilizing adrenal hyperplasia,& _# A9 A0 Z) m! e
either 21-hydroxylase deficiency or 11-β hydroxylase
9 c' o7 o2 M3 H2 G7 Udeficiency. Those diagnoses were excluded by find-
/ L+ K/ O) ~3 |+ b" Ling the normal level of adrenal steroids.
' m; S. s! x; Z1 S. [ sThe diagnosis of exogenous androgens was strongly
( J1 ~1 Y2 p' i( H0 d, ksuspected in a follow-up visit after 4 months because
' a; c# H+ W% C2 e6 P! w( Dthe physical examination revealed the complete disap-! F1 U3 S, _& W, [7 {
pearance of pubic hair, normal growth velocity, and
4 d% _$ h+ I; j9 e5 odecreased erections. The father admitted using a testos-2 i+ x) o2 |* b
terone gel, which he concealed at first visit. He was
; v: y5 v% ?7 k* Husing it rather frequently, twice a day. The Physicians’
8 P) G N/ [' i) y: F ]Desk Reference, or package insert of this product, gel or
$ Q+ ?3 p7 ^7 E6 N: _% {& ucream, cautions about dermal testosterone transfer to, l4 c. z; Q' ^1 h/ f+ P3 @
unprotected females through direct skin exposure.1 q3 i3 b% J2 L: T0 n$ g
Serum testosterone level was found to be 2 times the
" D, m1 d( K& J% \. j/ B+ pbaseline value in those females who were exposed to
; F1 X% u6 W: c5 o, o% B& E! veven 15 minutes of direct skin contact with their male
' q. V+ {4 l1 ppartners.6 However, when a shirt covered the applica-4 S+ V. N- f7 U6 j% O# l% S2 r/ h* \
tion site, this testosterone transfer was prevented.
5 O- j" v$ H* A7 nOur patient’s testosterone level was 60 ng/mL,9 z1 l% l& x* l4 n3 \" x) W; f& W
which was clearly high. Some studies suggest that' A, y( i0 A7 f" R
dermal conversion of testosterone to dihydrotestos- B- F9 _; L3 S: L. a
terone, which is a more potent metabolite, is more5 q- X' D O. D; d7 C! \; x
active in young children exposed to testosterone
( z: Y8 ~1 X% X6 x0 @% iexogenously7; however, we did not measure a dihy-
" _3 C( v: e. I& K6 idrotestosterone level in our patient. In addition to8 O9 H; Q3 B, [# C& C i5 Y% ?
virilization, exposure to exogenous testosterone in" u( B ^5 E% Z( }7 K; E9 p
children results in an increase in growth velocity and/ U' U+ E+ O) X( B' y, K
advanced bone age, as seen in our patient.
3 G5 r& p& ^- ]) HThe long-term effect of androgen exposure during
( E0 v" x" j1 m# cearly childhood on pubertal development and final
) F9 J3 s) Q2 _5 y2 [; J W( [adult height are not fully known and always remain
* m4 T' F8 f4 `0 Q) z8 U/ P* H/ Ja concern. Children treated with short-term testos-
% Q% A& C0 w9 E* T7 w3 ?5 qterone injection or topical androgen may exhibit some
- W0 \$ k. o6 m( L; p* Jacceleration of the skeletal maturation; however, after3 h: _) ^4 @* ^& z/ W; g1 p! r% Y% c, g
cessation of treatment, the rate of bone maturation
, y2 ] t d! p/ ~) s& r m: p# adecelerates and gradually returns to normal.8,9
/ z$ I- i2 r* E" H8 |8 |There are conflicting reports and controversy
% P& o7 p1 R/ ?over the effect of early androgen exposure on adult
; j6 S- L8 W: E6 ?* \/ E0 b* spenile length.10,11 Some reports suggest subnormal C4 Q! [4 ]3 c% S Z- }+ \3 @7 Z
adult penile length, apparently because of downreg-
$ n' f% i* s6 L+ n0 lulation of androgen receptor number.10,12 However,
( }& X: z/ J. V: _& _. zSutherland et al13 did not find a correlation between
1 |/ g9 o- u: U5 A* schildhood testosterone exposure and reduced adult
( `4 Z; m s3 R$ T5 V$ fpenile length in clinical studies.
; P' Y* y/ O, z! U) ONonetheless, we do not believe our patient is& _8 `5 m1 N0 @* O1 B
going to experience any of the untoward effects from$ A1 |4 r" Y$ Q/ j* ]7 G7 s
testosterone exposure as mentioned earlier because
% h! ]9 |7 G) v- |# athe exposure was not for a prolonged period of time.$ r' I; W" P' j6 _
Although the bone age was advanced at the time of- t4 Z, V/ N! j
diagnosis, the child had a normal growth velocity at
9 N9 V5 z0 u- {( }+ gthe follow-up visit. It is hoped that his final adult
9 d# \8 A4 F$ ~# o, oheight will not be affected.& _1 H* M9 K4 E, `: a; |2 V, v
Although rarely reported, the widespread avail-
' E3 w+ g* {: y' {) c% D9 Oability of androgen products in our society may
% Y3 W! Z( c7 @9 D3 Iindeed cause more virilization in male or female
3 d( Z2 ^, |! b) v: i; Cchildren than one would realize. Exposure to andro-; Z. Y/ V6 O$ d Q3 d3 V( x
gen products must be considered and specific ques-
+ Q8 `4 F& J% ptioning about the use of a testosterone product or% t" k6 ^+ @; `. y9 M4 V( H0 c
gel should be asked of the family members during6 G; s" T8 |5 v$ e
the evaluation of any children who present with vir-
4 v! @8 J; W7 Q4 j D' K( M2 V' Eilization or peripheral precocious puberty. The diag-
, R7 _( q' r- Hnosis can be established by just a few tests and by1 y) q K; x+ x; D. z
appropriate history. The inability to obtain such a
. I0 Z1 ^: x2 Q' F( I9 shistory, or failure to ask the specific questions, may
4 m) E3 y, g$ J* `: J6 g& C; Xresult in extensive, unnecessary, and expensive
4 u6 |7 r7 Z' p% }- kinvestigation. The primary care physician should be+ @% P4 P5 t8 b: r9 Q+ B" C
aware of this fact, because most of these children' B; b, [9 y' M
may initially present in their practice. The Physicians’" T0 f) e! u4 T; m) L |0 H2 o) o
Desk Reference and package insert should also put a' S& f! @6 s4 I+ \/ N0 m/ @" y
warning about the virilizing effect on a male or
7 n1 P" o7 }9 i8 h1 X" zfemale child who might come in contact with some-
( p* J/ d( Y0 z- `- k5 Z' Kone using any of these products.
1 y, S& W8 E/ d7 r4 W! v, oReferences6 `" I2 S2 i, t2 d
1. Styne DM. The testes: disorder of sexual differentiation$ J* Q( F- e' W8 C" P n
and puberty in the male. In: Sperling MA, ed. Pediatric
6 p4 W3 z7 N" U' ZEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;: V: l- L7 W, M! ]1 j( y0 b; g2 Q
2002: 565-628.
, d5 w! Z- N9 {, U! a2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
% {# |5 w) {, y2 Q6 A( E; ~puberty in children with tumours of the suprasellar pineal |
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