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Sexual Precocity in a 16-Month-Old+ j% o7 [; |9 y B1 d; ~" i
Boy Induced by Indirect Topical
7 I. x" Y2 Z% dExposure to Testosterone
7 Q, U% m9 c$ s4 E, @% ySamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2& s9 }8 N3 A A" q8 V
and Kenneth R. Rettig, MD1
! p- k0 Z# y! zClinical Pediatrics
! @$ L r* Q( @. I) VVolume 46 Number 6
2 M! b r5 J" G) E8 NJuly 2007 540-543
% Y7 q8 s1 F' m© 2007 Sage Publications
* J! F! D% r: s10.1177/0009922806296651( @2 `, r: k& A: i3 k
http://clp.sagepub.com
0 A0 R* e" ~- {hosted at
" X* O& ` X! k; `http://online.sagepub.com
" R4 Y, `- c6 q8 C! DPrecocious puberty in boys, central or peripheral,, a) c, y k# m0 \- l
is a significant concern for physicians. Central
8 T' g# R6 b ~7 ^4 Yprecocious puberty (CPP), which is mediated, k9 G6 c3 s: I+ K5 \! C4 o
through the hypothalamic pituitary gonadal axis, has0 Y v& Q1 v' F; V5 W" C& \
a higher incidence of organic central nervous system) {* x% P- z! V" n) @% S' @
lesions in boys.1,2 Virilization in boys, as manifested
5 Z5 K9 ~ z5 S& Gby enlargement of the penis, development of pubic, _4 _( D* c+ U' d
hair, and facial acne without enlargement of testi-3 G! y. m" {4 Y/ l- u
cles, suggests peripheral or pseudopuberty.1-3 We
$ u% \# P4 J. C) Yreport a 16-month-old boy who presented with the! l! h) o4 O: v" r+ |! b
enlargement of the phallus and pubic hair develop-3 N9 E- b" G6 l
ment without testicular enlargement, which was due
: u& c5 J/ m* u' z% |to the unintentional exposure to androgen gel used by
! |( b7 L9 o3 v8 o$ f+ C9 S, Q0 dthe father. The family initially concealed this infor-" \3 @7 G- u v. r" Z% r9 ]7 X0 y
mation, resulting in an extensive work-up for this | Q! [' e! a8 \! k* }* Y0 |5 L
child. Given the widespread and easy availability of1 ]0 S% r8 ^1 n d/ g* }( M- \
testosterone gel and cream, we believe this is proba-
8 m9 E& P/ X. K. F* e0 M4 vbly more common than the rare case report in the
0 e5 a/ |# E/ w% P0 j3 eliterature.4
$ I, n1 [6 e! ?, I. EPatient Report5 I9 @ l- ~: H- P+ M9 z/ G6 D/ O
A 16-month-old white child was referred to the9 D \( U/ l* N( K1 |# R
endocrine clinic by his pediatrician with the concern
8 w( S3 N, A' C Eof early sexual development. His mother noticed( [+ l7 G# c1 \' l
light colored pubic hair development when he was5 `- A9 Y+ ]' B( O& G+ k# M
From the 1Division of Pediatric Endocrinology, 2University of P" m4 x3 p. U& R: |
South Alabama Medical Center, Mobile, Alabama.
! _# L' g) d, S5 g6 ^0 lAddress correspondence to: Samar K. Bhowmick, MD, FACE,: _8 q; |( A/ {: x
Professor of Pediatrics, University of South Alabama, College of; Y3 C; f4 L3 I( T. n5 \
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
" @) J( j" j1 Y) fe-mail: [email protected].
' {, v0 g3 h8 Kabout 6 to 7 months old, which progressively became; W! Z4 W2 l `
darker. She was also concerned about the enlarge-
8 p" x0 J* r2 K& `" Bment of his penis and frequent erections. The child0 h: Y/ d# o$ \
was the product of a full-term normal delivery, with
8 |" y4 a6 f9 u6 g% k1 Qa birth weight of 7 lb 14 oz, and birth length of
: p+ v, K+ @$ S6 K20 inches. He was breast-fed throughout the first year
; o. [. `5 ?* J0 f3 v0 ?: rof life and was still receiving breast milk along with: x, L- ]* i7 w, Y
solid food. He had no hospitalizations or surgery,& v, z& D5 Z1 r! ?
and his psychosocial and psychomotor development8 k. k" a! b) G' {' Z
was age appropriate.* O2 g( X9 d2 ?7 n4 P; C
The family history was remarkable for the father,
3 k% x7 T" R7 T2 k: G) J9 o- n. x2 Lwho was diagnosed with hypothyroidism at age 16,
7 J( F& W( F0 p E+ W" }# U+ s; V9 xwhich was treated with thyroxine. The father’s) F9 \4 a1 P# M
height was 6 feet, and he went through a somewhat \/ g+ G t/ m+ G2 |
early puberty and had stopped growing by age 14.$ C$ X. z+ a! s. O6 p* r
The father denied taking any other medication. The! ^0 Q4 z/ M6 K) C: y7 k. i M
child’s mother was in good health. Her menarche0 F' g2 K! ]0 Q& a" z
was at 11 years of age, and her height was at 5 feet% r7 m9 X! T' c' T! _
5 inches. There was no other family history of pre-, y* r# i- Y5 X
cocious sexual development in the first-degree rela-
1 C5 \) C- P/ x/ M8 \5 @! ~9 Dtives. There were no siblings.
. a1 u3 a9 ]" O% rPhysical Examination F$ T8 a& E2 S4 N% }& \4 R. _
The physical examination revealed a very active,
( ^- r8 r. o( S6 ?' ?playful, and healthy boy. The vital signs documented! G3 \/ J J4 i0 l, M0 ] H5 F, n' Q; _; u
a blood pressure of 85/50 mm Hg, his length was
* M+ I6 n) F9 g0 M8 K _$ |5 I90 cm (>97th percentile), and his weight was 14.4 kg p* s* q# Y. I
(also >97th percentile). The observed yearly growth g. b- t- Z& W
velocity was 30 cm (12 inches). The examination of0 ~) j, m6 B; ] R
the neck revealed no thyroid enlargement.
- _% [3 \: M) f( C& q E2 C6 GThe genitourinary examination was remarkable for
4 M' W* o$ n! J) ?5 yenlargement of the penis, with a stretched length of
4 ` P; m& h, v8 cm and a width of 2 cm. The glans penis was very well: Y' Q0 }; p# r; B
developed. The pubic hair was Tanner II, mostly around# t+ s" C* l* ]/ d
540# T4 u0 s- i: }: }* a4 ]
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
- d" e/ P8 N' w- j- [. {* ]# Hthe base of the phallus and was dark and curled. The- Y- q) P' D% D; r, Y
testicular volume was prepubertal at 2 mL each., F3 p" z6 }+ L* w, A
The skin was moist and smooth and somewhat1 T. o& m+ b1 H$ c4 L
oily. No axillary hair was noted. There were no @" p, U5 ]+ x$ z* E: |+ ?
abnormal skin pigmentations or café-au-lait spots.
. I4 d# b9 b6 W% L7 `( K kNeurologic evaluation showed deep tendon reflex 2+' p0 h) Z' T0 @' B
bilateral and symmetrical. There was no suggestion* C% J3 \; |$ v$ a4 H, M4 x
of papilledema.$ [$ |) u3 i" a' s
Laboratory Evaluation
- Z& i: y3 @) Q4 LThe bone age was consistent with 28 months by# ?! C$ r5 D4 C
using the standard of Greulich and Pyle at a chrono-
, e# K3 E) R7 c* c7 N0 Clogic age of 16 months (advanced).5 Chromosomal
& m* K* I# d6 Xkaryotype was 46XY. The thyroid function test" Z ^, G* E0 t8 l3 W) a
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
. B" E' s7 J$ z2 n- r) }; t! Zlating hormone level was 1.3 µIU/mL (both normal).
6 B* g R! V/ B' \; ]. fThe concentrations of serum electrolytes, blood
, Y, [; }; f( A4 P, ?urea nitrogen, creatinine, and calcium all were6 t' ~6 b' l* D f' B, R
within normal range for his age. The concentration
1 ?2 x* \( p$ yof serum 17-hydroxyprogesterone was 16 ng/dL' t# S* P8 A: k: k$ ^$ W$ L
(normal, 3 to 90 ng/dL), androstenedione was 205 e* w' G( C8 _- V1 R r
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-) }0 L7 [6 h* h/ d
terone was 38 ng/dL (normal, 50 to 760 ng/dL),, r7 e' E9 L3 q% t7 a. P p) u6 v
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
$ I5 `* _2 g H2 p& F49ng/dL), 11-desoxycortisol (specific compound S)
# f- f8 C, G" T& a0 ?was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor- y L. A+ s i* q9 p$ a
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
4 X0 |6 M. u% h' Otestosterone was 60 ng/dL (normal <3 to 10 ng/dL),: r. \4 {, ^0 x$ P
and β-human chorionic gonadotropin was less than: J9 H- z3 n8 w8 `2 C
5 mIU/mL (normal <5 mIU/mL). Serum follicular
. a5 h* c( \4 M! `' Wstimulating hormone and leuteinizing hormone; x' Y) |5 T8 Z% {7 N% \9 X1 u) l
concentrations were less than 0.05 mIU/mL
# U# T; Y( N0 W ?0 \5 R: h(prepubertal).
) j3 f# G. v# `The parents were notified about the laboratory, o4 S# D6 y5 @! U# x7 L
results and were informed that all of the tests were
: h7 ^0 h' w( S- J* Z0 I0 [normal except the testosterone level was high. The
9 Q+ D% A) `0 N' V% c2 @8 m+ D/ yfollow-up visit was arranged within a few weeks to
- [3 U5 r3 e* t$ k7 _8 K& ~5 t- |* Dobtain testicular and abdominal sonograms; how-' f: x* M, \8 X% D
ever, the family did not return for 4 months.7 m) A( c2 I% T- M& z/ t$ J
Physical examination at this time revealed that the9 t( D U( r- W; B- W) p
child had grown 2.5 cm in 4 months and had gained$ O5 ~( A1 E* l4 ~. F9 q
2 kg of weight. Physical examination remained# Z; O3 ^! E' g: G1 k
unchanged. Surprisingly, the pubic hair almost com-8 _+ }) e! D5 }0 j6 ^9 K
pletely disappeared except for a few vellous hairs at
: Q4 W" ^8 Q1 j! K$ _the base of the phallus. Testicular volume was still 2
! O; ?- K" e: EmL, and the size of the penis remained unchanged.5 h* W% l2 l3 y7 G
The mother also said that the boy was no longer hav-+ |. L' j% x/ y4 i) C
ing frequent erections.
$ N9 }3 `4 a! M+ b1 M4 b/ a- [Both parents were again questioned about use of
& p- T6 M. C0 y1 G: }# D R; I: Q" B7 |3 hany ointment/creams that they may have applied to
" d- A' L4 O% l* ~0 W5 S5 Wthe child’s skin. This time the father admitted the( V) |. w8 c A6 p
Topical Testosterone Exposure / Bhowmick et al 541
. r2 ?" I7 R, i4 n) Guse of testosterone gel twice daily that he was apply-* n- c2 S% B: I O/ r ?- `4 J9 f
ing over his own shoulders, chest, and back area for1 Z2 S X% z2 I* W: |/ P" [
a year. The father also revealed he was embarrassed5 d$ C0 m+ a: Z
to disclose that he was using a testosterone gel pre-9 B$ s1 w5 L; @/ U$ f
scribed by his family physician for decreased libido1 g o; O- F( ~# m* a
secondary to depression.
, _( a/ p. q$ ~2 z5 {The child slept in the same bed with parents.
! x9 R2 w. T" m/ T: \The father would hug the baby and hold him on his
4 _+ D+ N4 N' D Zchest for a considerable period of time, causing sig-$ D0 P, i5 P2 R, ~& d" I9 T
nificant bare skin contact between baby and father.2 C9 v2 V4 @9 D S
The father also admitted that after the phone call,
9 [% ]' R9 M% H; J4 j. ywhen he learned the testosterone level in the baby
3 S5 p& C2 ]3 jwas high, he then read the product information2 m* j, R" i. l% k+ T7 d, ]0 V/ p
packet and concluded that it was most likely the rea-
% q' F& V2 Q) s4 z3 }5 z. G* ^3 D' |, uson for the child’s virilization. At that time, they8 y# d0 @$ x8 R0 R, N: p
decided to put the baby in a separate bed, and the
& \5 _4 P+ e7 C; Y1 f6 Tfather was not hugging him with bare skin and had8 a$ \' k6 ]" n1 {
been using protective clothing. A repeat testosterone' d) X3 @; i+ ^* Q( j5 ^
test was ordered, but the family did not go to the
% b1 w$ M0 Z' b; a" Zlaboratory to obtain the test.( G+ R3 d- Y- s8 @) B: J8 ~7 m
Discussion; C: g/ \! Y) G! L. V; h
Precocious puberty in boys is defined as secondary
; c- Q: J; n/ l; ^5 T8 ssexual development before 9 years of age.1,4
( N9 \, V4 z u$ g% r0 s+ T" uPrecocious puberty is termed as central (true) when( {' n4 J6 }- |6 |+ B
it is caused by the premature activation of hypo-
3 ^0 [% V5 Q6 p# Rthalamic pituitary gonadal axis. CPP is more com-
% r( C; s$ A( Zmon in girls than in boys.1,3 Most boys with CPP
% X4 L: z3 R% lmay have a central nervous system lesion that is
6 j# O: s8 A1 \( R% ^3 r* gresponsible for the early activation of the hypothal-
; {9 T; V: O3 I4 @amic pituitary gonadal axis.1-3 Thus, greater empha-
- f) ?2 f7 ^$ Gsis has been given to neuroradiologic imaging in' ]- [% `9 F, v& @9 i& m/ C' A% q
boys with precocious puberty. In addition to viril-
7 t" @. B0 m( iization, the clinical hallmark of CPP is the symmet-
/ Z8 s% p- V9 H1 vrical testicular growth secondary to stimulation by
) G1 m9 |+ t" F9 e4 Pgonadotropins.1,3
2 z, W1 p; R( R; d! Y- bGonadotropin-independent peripheral preco-8 l! v. Z n- M9 a8 h7 _
cious puberty in boys also results from inappropriate
" y5 A2 ^* Z7 U+ ]' }* wandrogenic stimulation from either endogenous or i- Z4 V& c0 [: J2 A6 S# r1 R! n: A
exogenous sources, nonpituitary gonadotropin stim-0 i4 F y" @6 {0 z- L: S
ulation, and rare activating mutations.3 Virilizing
& M4 \/ _$ Z, W. Fcongenital adrenal hyperplasia producing excessive
1 i5 P# j6 U$ t* d0 Zadrenal androgens is a common cause of precocious
' a2 ?0 m: L o H7 Q) [: m1 \$ T& {puberty in boys.3,4
' L3 k+ L! I* L5 W5 oThe most common form of congenital adrenal/ W. p" o$ C+ L- y8 \( C
hyperplasia is the 21-hydroxylase enzyme deficiency." e" i$ X: i, m5 a# a
The 11-β hydroxylase deficiency may also result in
) p D1 |* B( j& \3 Bexcessive adrenal androgen production, and rarely,; ]7 c% E3 I. G
an adrenal tumor may also cause adrenal androgen
* E8 @+ Y4 y8 Qexcess.1,3
& k0 r( L8 h0 Z; o( z `+ X+ F; hat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from G" i$ ^# ]# W2 y4 I A
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
1 z& ]* A0 R8 q0 [5 p- c; _, K: r BA unique entity of male-limited gonadotropin-
6 d- D U; Z( V g) P# i; W; v% P+ Mindependent precocious puberty, which is also known
: c( q5 z/ S% B. S6 z1 u7 \as testotoxicosis, may cause precocious puberty at a* h, i; c1 j: U- l, d9 }* m
very young age. The physical findings in these boys& H/ R$ z5 G l+ N. t8 x# k. z
with this disorder are full pubertal development,9 u9 |, X/ E* x7 Z0 k; r( A
including bilateral testicular growth, similar to boys/ k |8 K) \' b1 @) d9 c2 r
with CPP. The gonadotropin levels in this disorder: t& S/ d: @2 c9 u
are suppressed to prepubertal levels and do not show
6 A% W5 K/ S# ^1 Mpubertal response of gonadotropin after gonadotropin-7 o% d5 }, b# n& K) [6 U
releasing hormone stimulation. This is a sex-linked
( p1 ]) G: T; rautosomal dominant disorder that affects only
# Y7 q$ i! K' j( fmales; therefore, other male members of the family
- { J( P2 l ? X# j$ M8 d! @may have similar precocious puberty.3
9 l# ~" L$ a, U6 n/ G, GIn our patient, physical examination was incon-% a% J" k4 o& z1 V* ]# u
sistent with true precocious puberty since his testi-
7 ]' o+ y0 v- a8 W( e7 D) ycles were prepubertal in size. However, testotoxicosis
# T; x8 o( N$ m" u. K* |$ jwas in the differential diagnosis because his father
) W* @( l9 ]: f* L5 ustarted puberty somewhat early, and occasionally,
* ? B. f/ b, wtesticular enlargement is not that evident in the
+ d$ O) X; S* w! X: Tbeginning of this process.1 In the absence of a neg-1 a/ h5 p1 w( H5 N, |2 k
ative initial history of androgen exposure, our8 k& u! [4 [/ X" t) C3 E
biggest concern was virilizing adrenal hyperplasia,5 @0 f' o( I$ U' g3 i& z: E
either 21-hydroxylase deficiency or 11-β hydroxylase
! t! f& z8 a2 l. O6 w) hdeficiency. Those diagnoses were excluded by find-
0 f) h3 p* \6 r; L+ Ling the normal level of adrenal steroids. E- [) E- ^7 e+ A$ W3 y8 Y6 I1 t% @
The diagnosis of exogenous androgens was strongly% T1 d; r* M( V: s+ Y% E: H) q3 P
suspected in a follow-up visit after 4 months because
" u6 F$ m- G/ w4 V' m( e6 Sthe physical examination revealed the complete disap-+ @, q: l a1 u, Y$ X
pearance of pubic hair, normal growth velocity, and
1 x1 Z8 w/ o8 a, w- O- J6 Odecreased erections. The father admitted using a testos-/ A# o$ R( C- ?" I/ x+ [0 I; M: [
terone gel, which he concealed at first visit. He was
; ?) `- Q; ^5 Y. I) _& }2 x( Eusing it rather frequently, twice a day. The Physicians’& O. F* k9 g4 R5 K0 H8 L! c" @1 f
Desk Reference, or package insert of this product, gel or
* [! a" e8 ~ m! Pcream, cautions about dermal testosterone transfer to t4 \$ z2 t5 I4 L
unprotected females through direct skin exposure.
+ M7 s r# W* p/ r- X5 h9 J# BSerum testosterone level was found to be 2 times the4 T9 ~* N n( u+ t
baseline value in those females who were exposed to
% A4 F! K' m4 \+ F' K/ G. J+ p2 @even 15 minutes of direct skin contact with their male, K+ q/ w% \# T
partners.6 However, when a shirt covered the applica-
: ?% g1 g" [0 z/ q( |; {tion site, this testosterone transfer was prevented.7 d2 v0 E1 ~: Z
Our patient’s testosterone level was 60 ng/mL,
/ u2 m0 z2 @( q% Lwhich was clearly high. Some studies suggest that7 W7 R1 L' r/ q
dermal conversion of testosterone to dihydrotestos-
# F/ }$ W" V6 Y: S( p; o% q/ hterone, which is a more potent metabolite, is more) Q0 p- P U4 `) S- ^3 B' r. ~2 r
active in young children exposed to testosterone. ?: g! ?7 Z9 q/ i" a5 K
exogenously7; however, we did not measure a dihy-; _ H/ U3 P, a$ L
drotestosterone level in our patient. In addition to
. P8 B/ [: H0 u! f# [6 Avirilization, exposure to exogenous testosterone in8 |+ ~0 T. Y% U/ M `
children results in an increase in growth velocity and
9 B$ `2 p- L# u) b' N6 Yadvanced bone age, as seen in our patient.# x3 N; J$ M4 C+ ~7 W" ]/ S" f9 j
The long-term effect of androgen exposure during
) M- ?2 O6 ~' z2 v* q, wearly childhood on pubertal development and final- Z& c0 S5 |. K9 F
adult height are not fully known and always remain
; ~; X$ y7 f& ba concern. Children treated with short-term testos-/ Z! L$ X3 N" {, S
terone injection or topical androgen may exhibit some D. X* @* G8 U
acceleration of the skeletal maturation; however, after
7 W. B1 D0 p5 Q) w8 Rcessation of treatment, the rate of bone maturation1 Q0 F( g Q& N2 k9 x+ t9 q
decelerates and gradually returns to normal.8,9- H/ `/ U5 p/ ~6 o& Z7 X: c% g
There are conflicting reports and controversy
, }9 j, b2 i# V5 D& u6 Iover the effect of early androgen exposure on adult
, q! R5 S% ~3 J7 Q9 tpenile length.10,11 Some reports suggest subnormal
! L2 [1 D" v7 a4 D9 m0 eadult penile length, apparently because of downreg-
% K$ }* q! B0 H8 b* Culation of androgen receptor number.10,12 However,
" G7 `' z" u* jSutherland et al13 did not find a correlation between4 Z1 q2 K: \5 W
childhood testosterone exposure and reduced adult# w$ ]) G" r& f- I9 | f# I) q% m) _7 [1 L
penile length in clinical studies.# r/ d" m7 S3 O5 V" D- [/ _! }
Nonetheless, we do not believe our patient is6 u, w; ^" V& g: E
going to experience any of the untoward effects from# n' K* w. ?8 p% ~( [* S
testosterone exposure as mentioned earlier because
( O* t$ O$ A* Q" n2 H/ Sthe exposure was not for a prolonged period of time.. Y% d- C/ D9 F2 N9 I$ v
Although the bone age was advanced at the time of- Y; P+ S# g& [8 g& m% o
diagnosis, the child had a normal growth velocity at$ b+ ]" x" |: W% A7 F
the follow-up visit. It is hoped that his final adult
5 c2 M0 m3 }+ i* R' p/ X, Hheight will not be affected.
1 ^, {& x7 K5 `: @Although rarely reported, the widespread avail-
5 A% S% e a& |$ ~7 ]0 _) f k8 mability of androgen products in our society may
. r7 Q: o! E' r* V. xindeed cause more virilization in male or female8 p9 C, c+ r8 n4 `1 v$ f
children than one would realize. Exposure to andro-. B: i, F8 {% ^* d
gen products must be considered and specific ques-4 ~, ^" K6 k8 P( T3 z0 ~
tioning about the use of a testosterone product or
8 e- ?- o' U2 V7 j+ [: k: L+ kgel should be asked of the family members during
( U1 O* h6 I6 x; I% lthe evaluation of any children who present with vir-
5 }) W# M: J# X+ Eilization or peripheral precocious puberty. The diag-
/ V* w: q! Y, f; O5 P3 D! K5 [, f: g) l' Anosis can be established by just a few tests and by. V+ r2 L' i1 `0 A" L+ Z1 U
appropriate history. The inability to obtain such a
9 i9 N2 j/ \$ c5 j1 r- \: H3 K( h6 ehistory, or failure to ask the specific questions, may9 P; ^" p- {% }4 R: N8 I2 I, K
result in extensive, unnecessary, and expensive0 R) b" v }5 |" {) u
investigation. The primary care physician should be
& J+ C4 o! K1 x6 S4 B+ Z+ vaware of this fact, because most of these children$ H4 b; J- l+ s1 i2 w, q
may initially present in their practice. The Physicians’' P7 q" G5 M8 u% ` ~" a i
Desk Reference and package insert should also put a
" e! P$ R) E. D" x4 }$ x& Jwarning about the virilizing effect on a male or
9 V0 A1 C& u2 J) }( Ffemale child who might come in contact with some-7 L8 i( Q( T- a2 s" f6 ^ D `" Z- [% F
one using any of these products.
/ S; j" j) Z2 t9 O4 d3 n" DReferences( H6 k5 M: u% \+ F3 ?5 \! J- L
1. Styne DM. The testes: disorder of sexual differentiation
# r5 ?- `8 I2 ]' ~) Rand puberty in the male. In: Sperling MA, ed. Pediatric/ l- e4 E' U7 }4 ~
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
. m" s) O5 }* t. u2002: 565-628.
; ?0 s" Y! a; j8 [ K9 g+ x1 x. s2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious% K, L/ Q4 U3 g
puberty in children with tumours of the suprasellar pineal |
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