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Sexual Precocity in a 16-Month-Old0 t. d8 z/ }& s z" }
Boy Induced by Indirect Topical
$ s1 r2 D+ G+ R7 h0 BExposure to Testosterone
4 z% ~. D% U& m) \" b2 I! N1 G0 @ vSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2 d+ W4 X, ]- h6 u5 J4 h
and Kenneth R. Rettig, MD1
9 |+ E8 `8 j. f, XClinical Pediatrics* O$ p, B& m+ F% E* J. q0 v5 o) [& t
Volume 46 Number 6( i |4 P' [ m( S9 Q. ?9 o. o
July 2007 540-543
1 w" K3 ~+ w2 f& `© 2007 Sage Publications- y) T M9 y' I/ z( \, b3 L4 C( M
10.1177/0009922806296651/ A6 j5 b9 o4 y, B
http://clp.sagepub.com$ u/ H+ L- ~% u* [
hosted at
) F5 M y& h2 z# q5 c! P( ahttp://online.sagepub.com3 g( ]5 Q+ S7 U" ]) t3 ^5 U
Precocious puberty in boys, central or peripheral,9 Y0 D8 d, Q, L5 e9 @5 C
is a significant concern for physicians. Central
. x2 l6 {- t: B; L5 w: o" vprecocious puberty (CPP), which is mediated
( H/ X3 h: {6 s5 K: T( u$ ?through the hypothalamic pituitary gonadal axis, has
# G. \" S/ [; }$ w r4 |' P" ~a higher incidence of organic central nervous system
' K9 U# H) t3 x9 ]lesions in boys.1,2 Virilization in boys, as manifested% m( Q) O) V, W' j" U
by enlargement of the penis, development of pubic
5 k1 e0 j7 ~: Y; Thair, and facial acne without enlargement of testi-
& |5 \+ ?4 I$ L- q. xcles, suggests peripheral or pseudopuberty.1-3 We8 Q: e2 F4 l' s3 J
report a 16-month-old boy who presented with the! T# m2 H* X4 J7 s8 T% M
enlargement of the phallus and pubic hair develop-
" `% B- L. }# S' l: hment without testicular enlargement, which was due: e* ~% B' Q4 k' C" R9 n
to the unintentional exposure to androgen gel used by
: }; T& X. h( k3 s2 y8 |* ]; wthe father. The family initially concealed this infor-3 a: Y- y5 ?% U4 Q) c1 i3 i
mation, resulting in an extensive work-up for this7 A' n9 R: x8 F
child. Given the widespread and easy availability of9 _* @$ t% c9 K4 [, ?
testosterone gel and cream, we believe this is proba-
. C: i. C- ]; @" D3 i% g+ Ably more common than the rare case report in the! K7 ^1 s S, ~2 Y: i; v
literature.48 R/ G! ^7 U: w9 X$ _
Patient Report+ L- K$ l0 x/ I% `' n. ^% i
A 16-month-old white child was referred to the8 c4 s. D: k7 f" d
endocrine clinic by his pediatrician with the concern
. T+ |8 }6 r8 ^+ q$ b. [. Uof early sexual development. His mother noticed
! @8 d( ~' z( Tlight colored pubic hair development when he was3 R' u/ p. @$ o
From the 1Division of Pediatric Endocrinology, 2University of
! T+ J3 i) ?1 i# }South Alabama Medical Center, Mobile, Alabama.
: e: _$ t! G( T6 Z0 Y8 cAddress correspondence to: Samar K. Bhowmick, MD, FACE,! Q' g" S0 ]6 d3 V% n, E8 b
Professor of Pediatrics, University of South Alabama, College of& s- w m$ @3 g4 z1 s9 T
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;9 j) S! [7 B" _6 U/ j0 {
e-mail: [email protected].# Z; i9 w+ G2 c7 @- L
about 6 to 7 months old, which progressively became
: v1 U& z ?8 r$ `: W" pdarker. She was also concerned about the enlarge-) r) y7 |: m" l G. I; b
ment of his penis and frequent erections. The child
- \: v: b! d, [" Twas the product of a full-term normal delivery, with6 Y0 I2 n7 z$ r; @, h( ^' e# d! L9 P
a birth weight of 7 lb 14 oz, and birth length of
6 @6 J% }# p3 q; g20 inches. He was breast-fed throughout the first year
8 E: p2 k8 s) _: ~' T; y6 c; Wof life and was still receiving breast milk along with& W' s/ c4 S8 o2 R2 T
solid food. He had no hospitalizations or surgery,; Q+ F- r" h7 E
and his psychosocial and psychomotor development/ j4 X' F2 c0 q! r6 R6 D; g
was age appropriate.1 |; q! v' }% X$ J1 U, u
The family history was remarkable for the father,
4 F3 |" \/ P |9 cwho was diagnosed with hypothyroidism at age 16,
2 K% h3 D1 k' Fwhich was treated with thyroxine. The father’s
! `* t8 _1 `, { X0 zheight was 6 feet, and he went through a somewhat: \0 x3 d- {& H) w
early puberty and had stopped growing by age 14.
% N' h' f2 h1 l, P O6 G AThe father denied taking any other medication. The: ]( |( V2 l- V' }- x n9 w
child’s mother was in good health. Her menarche8 b) j* I' X( d/ N
was at 11 years of age, and her height was at 5 feet, ?( S2 m* }8 g
5 inches. There was no other family history of pre-' {: r% \4 ^/ v/ [$ t# b# U
cocious sexual development in the first-degree rela-3 C; b$ H w6 h! C" G
tives. There were no siblings.
. y0 T8 m% `- NPhysical Examination$ z9 z+ W9 w0 H
The physical examination revealed a very active,
" L! V6 Y2 b& yplayful, and healthy boy. The vital signs documented) Y; Z/ z2 N4 y v
a blood pressure of 85/50 mm Hg, his length was
4 N* i, f( C2 u5 R, @90 cm (>97th percentile), and his weight was 14.4 kg
+ ~# J7 r/ j" f3 [: C, T8 m(also >97th percentile). The observed yearly growth
_: N9 u8 m: s! I8 p8 ?. lvelocity was 30 cm (12 inches). The examination of
3 O5 k3 f) e7 `' e0 Ithe neck revealed no thyroid enlargement.
) ?+ `: s& j) g6 kThe genitourinary examination was remarkable for
0 I3 j, J1 H5 i# T, Ienlargement of the penis, with a stretched length of
# s& c: x9 k% A" c3 ~4 u0 K8 cm and a width of 2 cm. The glans penis was very well
" { ^. u' `5 ?) p# z& O2 ydeveloped. The pubic hair was Tanner II, mostly around
' y( F7 g' M# z540
" \3 @0 \' q4 g1 a& u# yat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
# b" L5 p# T& ^0 q3 u8 ]the base of the phallus and was dark and curled. The
' s; e9 T% d! s2 k" E! }* \2 Rtesticular volume was prepubertal at 2 mL each.$ r! H+ C/ M! p: p/ a7 b) i2 `
The skin was moist and smooth and somewhat
8 P' ^$ k+ Y8 i/ w# m& toily. No axillary hair was noted. There were no
* D5 d* s1 u5 n# H Wabnormal skin pigmentations or café-au-lait spots.
+ w) I! m8 L: I6 YNeurologic evaluation showed deep tendon reflex 2+5 \* d! w% X; N3 ^3 s
bilateral and symmetrical. There was no suggestion
* D- i6 b9 \! E* z aof papilledema.
* f5 [0 h# }- U* p/ z4 A8 @Laboratory Evaluation
, a# {% A/ s8 b& LThe bone age was consistent with 28 months by
% }( t2 E$ l0 o2 fusing the standard of Greulich and Pyle at a chrono-
; l! Y7 s' C; t! v4 Blogic age of 16 months (advanced).5 Chromosomal5 a* s# n& t% n. H" L3 p1 f
karyotype was 46XY. The thyroid function test* ]% X3 I& W U1 G; {: o* D
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
/ f# o5 N: i4 n1 n8 ]lating hormone level was 1.3 µIU/mL (both normal).2 J4 ~% O' m5 p5 s
The concentrations of serum electrolytes, blood. e9 c l# l* ?' h+ H
urea nitrogen, creatinine, and calcium all were
3 |( w7 n- j1 h/ L1 ^within normal range for his age. The concentration* u% v) s! i# M, V6 z
of serum 17-hydroxyprogesterone was 16 ng/dL7 T( t6 y5 t6 |# N# u
(normal, 3 to 90 ng/dL), androstenedione was 203 [, ~: ?% x* D1 H7 e$ C6 J1 [
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
* C* f3 ?/ v& t1 o7 I9 m' Vterone was 38 ng/dL (normal, 50 to 760 ng/dL)," B2 u" S4 P3 y$ }& y* ?$ n- }( z0 C
desoxycorticosterone was 4.3 ng/dL (normal, 7 to" n- Y. y/ \7 s' f: A' S, Q2 J
49ng/dL), 11-desoxycortisol (specific compound S)' f6 W8 J1 P, M2 L* A5 w7 O3 f
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
$ ?- t# T3 g9 o# Rtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
$ f) @( X9 K/ Etestosterone was 60 ng/dL (normal <3 to 10 ng/dL), a1 l+ I9 L+ q& b- b
and β-human chorionic gonadotropin was less than5 o! e2 P( C7 ] t9 Y! B
5 mIU/mL (normal <5 mIU/mL). Serum follicular i6 U0 F) V4 k0 C3 ]
stimulating hormone and leuteinizing hormone! e3 f2 h+ P' n# z5 g0 W z
concentrations were less than 0.05 mIU/mL
% Y' r: H) o# Z(prepubertal).
& U1 X: W8 m0 F' e: L/ O ^& tThe parents were notified about the laboratory" Q, Z# o2 @0 }
results and were informed that all of the tests were- _" N8 ?2 {+ m: Q
normal except the testosterone level was high. The
! W6 i, P2 k$ B! @! xfollow-up visit was arranged within a few weeks to
& ?8 B H q# C/ e' f0 G& Pobtain testicular and abdominal sonograms; how-
: e# B6 `/ u( xever, the family did not return for 4 months.0 \/ H3 V* e2 N& X
Physical examination at this time revealed that the' @3 L1 `: e# U9 e; }& G1 L
child had grown 2.5 cm in 4 months and had gained% h! t- Q7 t' |4 ~* |5 a. ]
2 kg of weight. Physical examination remained5 t9 W3 g, R. R2 @& d
unchanged. Surprisingly, the pubic hair almost com-
8 t$ e c& {3 C% D. n4 ^pletely disappeared except for a few vellous hairs at
" e' ~( K+ a6 w" cthe base of the phallus. Testicular volume was still 2
! T% ?1 l) Q( C9 `mL, and the size of the penis remained unchanged.
( U: _2 g: N! V5 VThe mother also said that the boy was no longer hav-
( }9 ?) y7 e, f- F# \6 Hing frequent erections.3 ?( D, Z* k/ p3 Z+ }( B
Both parents were again questioned about use of
' i1 m1 E1 l5 D: X) A- Pany ointment/creams that they may have applied to: ^: F$ e$ J9 I2 ] X: @0 a
the child’s skin. This time the father admitted the
2 P0 P6 d' d) B1 y2 s+ B7 lTopical Testosterone Exposure / Bhowmick et al 541+ [, D( P7 \* L9 v* i% c" v3 q
use of testosterone gel twice daily that he was apply-; ?' {5 o! D1 j5 U- X6 } j
ing over his own shoulders, chest, and back area for* U# w4 K: R1 H0 F$ [ m c/ |
a year. The father also revealed he was embarrassed
; Q- q' y s# g3 C& xto disclose that he was using a testosterone gel pre-
5 u! ^; v3 t2 r: N5 u' g( m2 wscribed by his family physician for decreased libido
H& E# [% |. }; csecondary to depression.
$ Z* y5 S, v& B. L# h) qThe child slept in the same bed with parents.# `( W( ~6 |5 f. \# L
The father would hug the baby and hold him on his% q" o$ W8 {4 p+ P4 b; W6 g9 p
chest for a considerable period of time, causing sig-
+ @1 }. [. K% R3 q. ]" P. n/ nnificant bare skin contact between baby and father.
1 h% R) W& F. i7 Q1 iThe father also admitted that after the phone call,
6 I; q& u. x vwhen he learned the testosterone level in the baby
( ^% l @, d. d2 E* qwas high, he then read the product information, J. h; [4 { Y5 E4 p3 z
packet and concluded that it was most likely the rea-
: T- X' b/ w: d5 z* U' q- M) u* @# Uson for the child’s virilization. At that time, they
& `: w1 C3 y+ T6 B0 F2 E$ sdecided to put the baby in a separate bed, and the/ w2 s8 c9 ]/ b. C) E& a
father was not hugging him with bare skin and had
' p% B. `0 Q( C0 L. k1 ^2 L4 ~been using protective clothing. A repeat testosterone" {+ p3 K/ }7 }3 d# k- t1 y
test was ordered, but the family did not go to the/ A* T+ o- b* A
laboratory to obtain the test.
$ P# Z- @) M3 uDiscussion
1 D# ]/ b! X! m$ O, mPrecocious puberty in boys is defined as secondary; x Q! W7 o* N# Q
sexual development before 9 years of age.1,4( d' w3 ]2 W3 r* W; Z
Precocious puberty is termed as central (true) when8 L& A! C5 }7 C9 L8 T. V
it is caused by the premature activation of hypo-% L$ j. x, b1 |; k6 d7 E2 O: e5 Y
thalamic pituitary gonadal axis. CPP is more com-
9 @* S+ Q. \, vmon in girls than in boys.1,3 Most boys with CPP
3 [0 ?' y; w- ~5 ^1 Z6 p4 tmay have a central nervous system lesion that is
+ |; Y0 l7 l% N2 Aresponsible for the early activation of the hypothal-. s |# Z5 D9 S& _5 r+ \; w
amic pituitary gonadal axis.1-3 Thus, greater empha-* F. P# E* W1 J' p
sis has been given to neuroradiologic imaging in, V$ i, z3 @% J. M
boys with precocious puberty. In addition to viril-/ k5 V- @, U. j
ization, the clinical hallmark of CPP is the symmet-
4 M- h. |, }! s5 \/ Qrical testicular growth secondary to stimulation by
8 M% l+ E4 s8 A7 _gonadotropins.1,3
# I- h; W9 p0 b# kGonadotropin-independent peripheral preco-
( f9 a* r) x0 x5 bcious puberty in boys also results from inappropriate
8 ], h/ g- ~1 @2 h6 {. A, Randrogenic stimulation from either endogenous or8 q: p: Y* U1 i* f* q V2 ~& f* r
exogenous sources, nonpituitary gonadotropin stim-
7 n! m+ [9 w8 A' ~6 L3 h: ]% julation, and rare activating mutations.3 Virilizing3 m. a* _/ n9 J9 i( L* O
congenital adrenal hyperplasia producing excessive
' F Y1 n; Y) b' U, Tadrenal androgens is a common cause of precocious
/ g* j ]: X5 _puberty in boys.3,4
1 p3 C( B7 k- U5 @The most common form of congenital adrenal
6 T4 n" l! B4 G& @% N/ V) p6 Zhyperplasia is the 21-hydroxylase enzyme deficiency.
( I7 Q$ p6 L* C5 y; J+ HThe 11-β hydroxylase deficiency may also result in1 C% T$ e7 `) s1 i2 M. K: s& g [
excessive adrenal androgen production, and rarely," |! B6 D- Y! o, N% c: L
an adrenal tumor may also cause adrenal androgen% W- Z8 x# M- ] W; m! s+ k
excess.1,3
" g$ H1 K0 L0 qat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
( }+ M( G1 ?, O+ x7 H# U5 g542 Clinical Pediatrics / Vol. 46, No. 6, July 2007* d& ]5 S% k% T9 ^8 L0 x0 o
A unique entity of male-limited gonadotropin-
0 D0 ?( G1 ]: p1 d- |$ ]independent precocious puberty, which is also known3 m* ?' ^; X9 z) v+ A6 o% q
as testotoxicosis, may cause precocious puberty at a, R8 `* b) C& b$ G
very young age. The physical findings in these boys5 N+ F2 N' j# O/ [; N5 U* _0 ~! i
with this disorder are full pubertal development,' Z( f4 t, D: f' {* A
including bilateral testicular growth, similar to boys: S7 \: w4 L: D. k
with CPP. The gonadotropin levels in this disorder
! a+ f$ m+ S& J* Y8 U: O1 P5 Nare suppressed to prepubertal levels and do not show
* {5 E0 P8 j7 tpubertal response of gonadotropin after gonadotropin-5 f4 P [2 R7 W u' [8 M2 I! s
releasing hormone stimulation. This is a sex-linked2 q+ P, T, v% B+ o) h9 K( J
autosomal dominant disorder that affects only
3 P! N u0 x( u1 hmales; therefore, other male members of the family) Q; h$ `8 x4 v' E
may have similar precocious puberty.3% `2 S/ [9 q ?, M/ H. N6 l
In our patient, physical examination was incon-
: J' R0 H+ L, x& K( P6 V8 d& D0 Esistent with true precocious puberty since his testi- G. P0 ?! e( I* m7 n% v
cles were prepubertal in size. However, testotoxicosis
+ ~/ N' c2 @ v' cwas in the differential diagnosis because his father
, \2 ^6 e4 u2 ^6 h/ O! @started puberty somewhat early, and occasionally,/ c, f2 B. I- ^- A( G$ @
testicular enlargement is not that evident in the
2 J3 T O& z9 K9 u( @2 q7 {3 N/ Xbeginning of this process.1 In the absence of a neg-
, t) q W1 }8 n/ b$ Jative initial history of androgen exposure, our7 l0 F, l @* I1 e* w2 V
biggest concern was virilizing adrenal hyperplasia,
1 B6 N( l* I, Xeither 21-hydroxylase deficiency or 11-β hydroxylase
' V5 B2 q9 ^" Pdeficiency. Those diagnoses were excluded by find-# b( W8 J. d: U! ~" F, w
ing the normal level of adrenal steroids.( ]. P# I( v7 t8 w; N) x' O
The diagnosis of exogenous androgens was strongly3 g! D+ Q b' X5 B
suspected in a follow-up visit after 4 months because
7 W; `# a8 [4 |4 R$ @the physical examination revealed the complete disap-
{$ [6 g/ f1 h# ]7 {+ }4 Q3 ~pearance of pubic hair, normal growth velocity, and+ K( O2 k/ k5 }# }8 }9 b/ m9 h w
decreased erections. The father admitted using a testos-
7 e% r. l: w2 I: Q |% z" I' Qterone gel, which he concealed at first visit. He was
& g! o8 T, ~0 g6 tusing it rather frequently, twice a day. The Physicians’
: V5 Z# e0 e9 V5 {8 wDesk Reference, or package insert of this product, gel or
+ f# e1 K- E7 v6 B' C9 U. U) [' [cream, cautions about dermal testosterone transfer to. a$ Z0 E! U) Q
unprotected females through direct skin exposure.
/ M1 [, r7 P. D1 x5 s; sSerum testosterone level was found to be 2 times the
, M# |, o& Q0 s: @0 s! J8 B" S4 Zbaseline value in those females who were exposed to
9 ^* O* k4 C, B8 Leven 15 minutes of direct skin contact with their male/ V0 P* b0 U: A* x c& @3 s
partners.6 However, when a shirt covered the applica-
* @8 V$ L- c+ h, e1 c9 J& ^tion site, this testosterone transfer was prevented.2 }5 G8 U* m! w& c P/ T) h( l
Our patient’s testosterone level was 60 ng/mL,
) c( H& t/ ^1 h. o! Rwhich was clearly high. Some studies suggest that
M" m" N9 ^4 A% t Tdermal conversion of testosterone to dihydrotestos-: J' |, G S, ~5 e* L c
terone, which is a more potent metabolite, is more
6 f# X9 N) ]. G, E$ Iactive in young children exposed to testosterone0 m3 v3 `; L0 ?8 g2 |! T
exogenously7; however, we did not measure a dihy-: k4 S& g; m2 g& `2 K' O; L9 Z2 d' l
drotestosterone level in our patient. In addition to7 d* i$ T v9 l N& j8 b
virilization, exposure to exogenous testosterone in! m$ t: B* S' l4 m% P+ y
children results in an increase in growth velocity and
1 ?# q4 f# e* H! o- r4 F4 Fadvanced bone age, as seen in our patient.
# |8 k8 q7 n; |) z" y: i- AThe long-term effect of androgen exposure during% c3 n3 m; ], N2 t" T3 ]! b9 J) ^' ~
early childhood on pubertal development and final' n; Q! J5 Z0 s. ]9 d
adult height are not fully known and always remain' {5 M# Y" N! m, X, \) |3 R
a concern. Children treated with short-term testos-
% ~; m$ |9 R' y2 H5 F$ k5 Eterone injection or topical androgen may exhibit some. j" g8 A& y. k& H' [
acceleration of the skeletal maturation; however, after9 L7 i) q6 U Q0 i
cessation of treatment, the rate of bone maturation- m6 T1 D, f! h3 D T
decelerates and gradually returns to normal.8,9
& s: q4 O ]: z& R9 T0 MThere are conflicting reports and controversy
E$ ~# y) h9 e, r9 e, u. ]over the effect of early androgen exposure on adult& d( I+ S& z9 o& q
penile length.10,11 Some reports suggest subnormal+ I& ]: ?, A& I" e" k
adult penile length, apparently because of downreg-& g( T8 q5 `9 }" T4 D ^& G
ulation of androgen receptor number.10,12 However,
+ E( r# J# {* P7 q m8 aSutherland et al13 did not find a correlation between" ?' j* T8 J3 }. J. \6 l
childhood testosterone exposure and reduced adult) P6 L/ `+ w, L& P! Y* o) C8 @
penile length in clinical studies.8 p& H& {4 }% z( N( e( v2 E
Nonetheless, we do not believe our patient is3 y G) G0 |. X& _2 d/ P$ e3 ]
going to experience any of the untoward effects from
5 @3 B4 ]5 h5 S! X- ctestosterone exposure as mentioned earlier because
1 z8 q& t6 V" J/ Mthe exposure was not for a prolonged period of time.3 E) t% L% {5 _" X; m
Although the bone age was advanced at the time of/ \- h% _; J9 a% K" Y" l
diagnosis, the child had a normal growth velocity at
6 H: Y3 m( x% h) R: ]& E0 Fthe follow-up visit. It is hoped that his final adult
+ @% n0 B5 S( G( J {height will not be affected.
t& c4 k3 q9 aAlthough rarely reported, the widespread avail-! u" E# `' r! W3 R: j; \2 E
ability of androgen products in our society may
D; o& ]" ~! kindeed cause more virilization in male or female* S- J+ n# k9 y! t
children than one would realize. Exposure to andro-4 N2 ?" b" a% \/ ]
gen products must be considered and specific ques-# y. I2 n) G9 t) W6 q. j- \2 A
tioning about the use of a testosterone product or& \5 C: q5 K1 J. K P8 f
gel should be asked of the family members during g% @$ A% X) c5 J6 u1 w: }
the evaluation of any children who present with vir-0 f% P6 y0 T. k/ b& t. @
ilization or peripheral precocious puberty. The diag-4 }# I- d9 r: {
nosis can be established by just a few tests and by
$ A N( H( D2 _7 jappropriate history. The inability to obtain such a( d* C9 Z6 S( r \( Z" s
history, or failure to ask the specific questions, may# c) }) M* f4 `5 M( u2 b$ }: d* N2 |
result in extensive, unnecessary, and expensive
( ?( J% a' d7 einvestigation. The primary care physician should be2 M8 p' L6 @: w* P3 J7 l0 L
aware of this fact, because most of these children
x8 h! Q# r }$ ^/ Hmay initially present in their practice. The Physicians’
- ]2 r& [6 `( G9 I" V" qDesk Reference and package insert should also put a
5 s) y) D2 V" F4 A4 P$ X* nwarning about the virilizing effect on a male or# d( `) B2 j8 b. C+ j- t7 a
female child who might come in contact with some-
l V0 M8 I3 _* B! G; l' D8 e2 ` Aone using any of these products.$ e$ ^: ]8 M/ n R
References
t+ D* y6 |% ?- w1. Styne DM. The testes: disorder of sexual differentiation5 t/ G" S h! d& X, e
and puberty in the male. In: Sperling MA, ed. Pediatric
9 J7 }$ E$ X& H9 T& hEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
5 J! K3 u" D$ j4 r0 y! @2002: 565-628.7 t- @8 M, F" b* J! p
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
$ q0 c" l/ f% {6 ^puberty in children with tumours of the suprasellar pineal |
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