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Sexual Precocity in a 16-Month-Old
" g% l% O0 h; z- H0 aBoy Induced by Indirect Topical
1 u3 [0 _3 Q# M4 z sExposure to Testosterone. b* k# M- b1 c+ D
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
. w) @! r# a' a3 z: A/ ~and Kenneth R. Rettig, MD1+ ~. @6 Z1 l4 A
Clinical Pediatrics
+ b' b, V$ n% `$ O+ q' ~+ K9 ?Volume 46 Number 60 m7 X% [, _; J$ E
July 2007 540-5434 s. o- B/ _# K' T& W$ G& v) D
© 2007 Sage Publications
# n$ P& d* S8 N. p9 v# A/ N10.1177/0009922806296651
' z! @) s) U; Z$ D0 Y: f+ o- C* Thttp://clp.sagepub.com z! C" @) _8 o" ]/ X
hosted at
* J. `" E& R5 u, Z5 x) Bhttp://online.sagepub.com8 G! t8 N3 O! v# g @
Precocious puberty in boys, central or peripheral,
' z1 C: p: N! ~7 Lis a significant concern for physicians. Central
3 @& O/ I0 m$ z2 N5 W, I0 t6 Qprecocious puberty (CPP), which is mediated
5 Y. h* F( \$ e2 mthrough the hypothalamic pituitary gonadal axis, has: v- i3 J- L1 `0 }; v/ I% e9 o' d
a higher incidence of organic central nervous system7 s" \, _" e0 I, K
lesions in boys.1,2 Virilization in boys, as manifested0 I+ w7 X8 D6 o% @* p
by enlargement of the penis, development of pubic: q4 p c/ k- W; R. K: ^
hair, and facial acne without enlargement of testi-
! D1 w% C$ Y9 ^cles, suggests peripheral or pseudopuberty.1-3 We
) o9 J5 t( [8 }% lreport a 16-month-old boy who presented with the3 K* p. `0 ^& @7 d% Z0 R+ R% I
enlargement of the phallus and pubic hair develop-' K% |' ?) n1 L& q. b3 w3 |
ment without testicular enlargement, which was due# _' ~ p6 O; C4 ^( x {
to the unintentional exposure to androgen gel used by
& ~: {8 \8 ?! i: l6 Othe father. The family initially concealed this infor-
* g! D1 }3 f5 p, j4 v7 j) @6 x/ hmation, resulting in an extensive work-up for this
( b0 w' \- \, d7 E' f# t6 M wchild. Given the widespread and easy availability of2 w) d, u6 w! i
testosterone gel and cream, we believe this is proba-3 h8 h. g! \% P: I, v/ Q# o
bly more common than the rare case report in the0 |$ m9 y' E U8 h' S8 ]
literature.4
6 T" v& h0 z$ IPatient Report) F9 e2 \- J9 Q3 x1 p5 \
A 16-month-old white child was referred to the; k K6 [5 r8 @* g$ A
endocrine clinic by his pediatrician with the concern
( R5 j! d( W1 F; b9 Sof early sexual development. His mother noticed) _) j; o2 x" V
light colored pubic hair development when he was( G! M4 A! o* I9 f5 \( K c7 F1 C
From the 1Division of Pediatric Endocrinology, 2University of; k, ]; w0 ]5 f
South Alabama Medical Center, Mobile, Alabama.% f6 O, f3 g# }0 E; {5 Q
Address correspondence to: Samar K. Bhowmick, MD, FACE,8 K; q6 B' t0 u0 [( n/ K
Professor of Pediatrics, University of South Alabama, College of. m5 H. L4 Z: V3 Y8 {
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
3 z- H% q! @! @5 b. |e-mail: [email protected].
/ s$ e' Q! ^0 d# l6 E+ babout 6 to 7 months old, which progressively became
) o: @" K. h, ^4 K& Qdarker. She was also concerned about the enlarge-/ @4 L) B4 I& v: f. J: f
ment of his penis and frequent erections. The child# x, D. p( G0 D. p0 ~. ~& o8 l
was the product of a full-term normal delivery, with
* o* I) C! o( N; ^# Xa birth weight of 7 lb 14 oz, and birth length of
6 a; Q; q" `2 G! y20 inches. He was breast-fed throughout the first year
0 |% @' {; x; ]; Z" U# C$ q5 uof life and was still receiving breast milk along with
# T; S2 g/ @) y1 V) b \solid food. He had no hospitalizations or surgery,
$ g. B' Y& d" @( Eand his psychosocial and psychomotor development
" r) p' e2 ?( e8 r& g0 owas age appropriate.
/ p- d+ ^* X* w! O0 D7 M+ uThe family history was remarkable for the father,$ b& P* }% i' o
who was diagnosed with hypothyroidism at age 16,
* R5 ?" K M% U! Bwhich was treated with thyroxine. The father’s
0 o5 p1 O9 ~2 y- H( N3 A- @height was 6 feet, and he went through a somewhat3 ~, l2 u' m- k T
early puberty and had stopped growing by age 14.
3 z$ U2 E8 P: X/ x9 ]. ~( IThe father denied taking any other medication. The
) ]2 y8 ], o2 ^child’s mother was in good health. Her menarche7 m( `6 o' x7 x3 Y" ~) T( H/ [
was at 11 years of age, and her height was at 5 feet
) y! ]& c- ?; b) P- ~/ U5 [5 inches. There was no other family history of pre-
: u7 B: i* b% X- h/ Wcocious sexual development in the first-degree rela-
# r. h s) C& h& Btives. There were no siblings., W- ?8 J( B: G5 `
Physical Examination
i" \" A7 |& x, fThe physical examination revealed a very active,
% p) m; o8 S) u% u; t* e. wplayful, and healthy boy. The vital signs documented
[; U {5 ?; g" wa blood pressure of 85/50 mm Hg, his length was
1 W3 ^1 J% A# X# x" W; I90 cm (>97th percentile), and his weight was 14.4 kg
2 e. V/ C8 j$ d(also >97th percentile). The observed yearly growth; u5 z2 {7 J; n% Q8 I/ T
velocity was 30 cm (12 inches). The examination of! j/ |( K8 i3 t; c
the neck revealed no thyroid enlargement.+ x8 F% S# |, p2 c* M) |/ o
The genitourinary examination was remarkable for
: e3 k: s! O' P% F& i- Nenlargement of the penis, with a stretched length of( c D8 c, K" Q" V1 I
8 cm and a width of 2 cm. The glans penis was very well4 m" x+ T% j! L' [# x1 V. @! v6 y. c
developed. The pubic hair was Tanner II, mostly around* }; U2 T4 j3 A
540% W0 ^/ |1 G* b% n/ P
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
; i, q( V: ?5 l5 |the base of the phallus and was dark and curled. The
; A8 ?# Z" M q3 g# z) Btesticular volume was prepubertal at 2 mL each.
, ?! L* D: D# V$ L7 aThe skin was moist and smooth and somewhat. ]2 T1 Q5 `; |0 G# u! m" P
oily. No axillary hair was noted. There were no9 M: c; K3 j; J! J: O
abnormal skin pigmentations or café-au-lait spots.* ]( Z4 Q% Y7 n x% P% _; n
Neurologic evaluation showed deep tendon reflex 2+4 |9 ~+ P: d. `8 I
bilateral and symmetrical. There was no suggestion
% x5 ?8 W+ I# Mof papilledema.
3 f$ }" a; H5 Y9 n; v% sLaboratory Evaluation
' P6 j7 q$ M, A* |1 [7 f9 a; PThe bone age was consistent with 28 months by
. r( B4 N" }3 `+ V7 _: b! Qusing the standard of Greulich and Pyle at a chrono-
# d' @4 J* z4 c* J: H: ylogic age of 16 months (advanced).5 Chromosomal5 g3 X% T5 U9 @% |2 [7 N5 j# J8 K
karyotype was 46XY. The thyroid function test2 w9 B* m8 M( L9 m5 c/ |
showed a free T4 of 1.69 ng/dL, and thyroid stimu-8 r# i3 j. |3 |9 c
lating hormone level was 1.3 µIU/mL (both normal).
) Y$ f( f4 `" n6 d- K- V. TThe concentrations of serum electrolytes, blood
1 u j- A/ }3 }% F5 Nurea nitrogen, creatinine, and calcium all were
$ w8 k$ `* b$ s* G* Z4 r" I9 nwithin normal range for his age. The concentration
' e/ ~' W4 j1 K: g) Iof serum 17-hydroxyprogesterone was 16 ng/dL/ D V7 l" T1 P% k0 q* o" k
(normal, 3 to 90 ng/dL), androstenedione was 20$ N. P b" g3 P! Q8 ?- P* _
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-. m! {* n; c5 R; {/ N9 V
terone was 38 ng/dL (normal, 50 to 760 ng/dL),0 e0 w& ^( e' Y" e% t, N* r
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
0 f1 ~4 s$ {8 k% E49ng/dL), 11-desoxycortisol (specific compound S)
7 c5 ^; L4 L0 R8 {! Lwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
( F+ k9 T% d5 ^/ \8 Ftisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
( x: F$ ?+ _8 E8 h; T) Vtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
' ^# Z4 B8 }6 Y1 f9 d0 I# \and β-human chorionic gonadotropin was less than
$ Q% ]2 s) U1 @2 ~5 mIU/mL (normal <5 mIU/mL). Serum follicular5 K$ n- ~2 t' a
stimulating hormone and leuteinizing hormone
- }0 s( B3 H/ }" B$ Bconcentrations were less than 0.05 mIU/mL' i0 R- f2 [1 S! l( U6 v+ N
(prepubertal).6 o8 s8 c( Y0 F- @6 N2 ^3 s1 M
The parents were notified about the laboratory* v- p& U/ B2 K9 J
results and were informed that all of the tests were7 e5 J$ g# Y8 N+ L% ^
normal except the testosterone level was high. The: b$ k* u7 B9 Q9 a' h# }
follow-up visit was arranged within a few weeks to( O! P+ F7 o* I: f% Z7 n* F: @
obtain testicular and abdominal sonograms; how-9 M% i! z' y1 X2 k& g* h
ever, the family did not return for 4 months./ R! N6 x, x+ S6 L0 g& j5 B
Physical examination at this time revealed that the# U1 x7 V; \4 H
child had grown 2.5 cm in 4 months and had gained+ j, k( J+ F: M; \3 Y4 ^
2 kg of weight. Physical examination remained
s$ [* e0 I( }4 ^$ f0 e0 @unchanged. Surprisingly, the pubic hair almost com-! N' f) U3 C& ^% Y+ [
pletely disappeared except for a few vellous hairs at
$ O- {) Z( Q& M0 m# ?# U3 k, Sthe base of the phallus. Testicular volume was still 2) Q$ T' C- l8 v0 \5 }' q+ _6 T
mL, and the size of the penis remained unchanged.$ Q. {; ~) Q0 D- {" P) k& w
The mother also said that the boy was no longer hav-
) l" ` @9 \9 j( E: ]. Wing frequent erections.( f( s9 f) E: @5 T
Both parents were again questioned about use of
2 \4 Z! W: E/ Z% Many ointment/creams that they may have applied to/ Z0 h( ]4 C4 j
the child’s skin. This time the father admitted the+ O1 f4 n6 F5 k$ R
Topical Testosterone Exposure / Bhowmick et al 541 ^% [4 W) r" y
use of testosterone gel twice daily that he was apply-# Q ?, ?/ D, [: u: h$ }! N
ing over his own shoulders, chest, and back area for$ [# U9 \& g& E: x1 p4 |" W
a year. The father also revealed he was embarrassed: A3 X) S' ^1 f) m @8 a
to disclose that he was using a testosterone gel pre-
0 y1 K' p q. T Mscribed by his family physician for decreased libido
" J) {0 X% m( ~1 Y+ M: {secondary to depression.
|' z) }/ ]: e$ P$ cThe child slept in the same bed with parents.
4 x! {8 @8 u' G3 m- {The father would hug the baby and hold him on his
- d- [) A7 @# p3 [8 uchest for a considerable period of time, causing sig-
' e* G) T9 m- Y( q4 Cnificant bare skin contact between baby and father.
% z: c7 F( m2 M3 ~7 ?5 g. a* `5 vThe father also admitted that after the phone call,
5 {" ^% U2 I0 ~7 n/ K) wwhen he learned the testosterone level in the baby4 u( `6 x8 B" v8 b# V) S0 u- V# ?
was high, he then read the product information
& h: _2 J" |5 d+ z0 u+ s6 Ipacket and concluded that it was most likely the rea-5 j6 X. L1 W* ?$ b y4 i
son for the child’s virilization. At that time, they9 f9 A0 I" j. ^1 P$ s
decided to put the baby in a separate bed, and the4 Q# h0 V& X$ E! m( z
father was not hugging him with bare skin and had2 ?7 T! l: P. b( `% h/ V
been using protective clothing. A repeat testosterone( T" p' P3 Y% e5 ~' o V$ Y
test was ordered, but the family did not go to the
& d& w7 d8 }) [, w$ W$ Blaboratory to obtain the test.! [( n2 n+ g4 g: I! Z9 E6 f/ R; F
Discussion
! G" C# D& i) c2 }Precocious puberty in boys is defined as secondary
' ?! n1 F% k ?# R: V9 A1 `4 m& D0 v7 Ysexual development before 9 years of age.1,4
, B' I" q. Z# D( k9 N2 YPrecocious puberty is termed as central (true) when/ u, R- b8 n9 ]8 H7 h8 b, ~
it is caused by the premature activation of hypo-
- {' v. J3 q' S) J' F6 G% Athalamic pituitary gonadal axis. CPP is more com-5 z6 K. @: z1 b0 ~
mon in girls than in boys.1,3 Most boys with CPP
2 C$ j( n4 X; D y+ _) E. {! x) `may have a central nervous system lesion that is- V3 W# w2 d0 b& @( Z0 G
responsible for the early activation of the hypothal-0 j* z/ S7 d& \& O I0 g2 R
amic pituitary gonadal axis.1-3 Thus, greater empha-
1 [! n+ h3 I5 N, Psis has been given to neuroradiologic imaging in6 A+ |0 g+ g3 }& a, Z6 g$ }
boys with precocious puberty. In addition to viril-
' n2 u. G1 k: E2 A' w7 n9 V$ Kization, the clinical hallmark of CPP is the symmet-6 }1 ^; e ]+ M; |2 Q
rical testicular growth secondary to stimulation by# P( p7 X5 n/ P: f
gonadotropins.1,3+ o7 Z, z6 u5 R
Gonadotropin-independent peripheral preco-& I- J3 I3 U5 X# W
cious puberty in boys also results from inappropriate7 J- ]( n5 @) q! P% X3 y" ?
androgenic stimulation from either endogenous or3 X) L5 c6 K" f8 Z: V
exogenous sources, nonpituitary gonadotropin stim-
: s/ d& z3 |5 `4 fulation, and rare activating mutations.3 Virilizing
! ^8 A9 `" U" {* N* o) y4 V/ Xcongenital adrenal hyperplasia producing excessive
; K* G) i( r/ P+ w# X; Xadrenal androgens is a common cause of precocious
) Q8 I" n( B+ E, Mpuberty in boys.3,4
4 i5 f9 x" X' D- n! Q1 E# R4 T# hThe most common form of congenital adrenal3 ]1 y0 j* T b3 N" l
hyperplasia is the 21-hydroxylase enzyme deficiency.- C) ?1 b: s; D8 A. x
The 11-β hydroxylase deficiency may also result in. r) R' k; ~5 \1 p0 o- \
excessive adrenal androgen production, and rarely,
9 h0 P) [# E/ Q0 `$ ~an adrenal tumor may also cause adrenal androgen6 G. K6 v/ a7 s$ n/ V# s
excess.1,3" F, M& t: E/ z" }
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
2 P: i- Z( }" t0 L- y) {5 D9 z0 c542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
- n! W! Y. k+ I4 b' @0 TA unique entity of male-limited gonadotropin-
) k4 x6 H. W* N7 i3 Q$ O! ]. Pindependent precocious puberty, which is also known
0 n. @) s6 V s4 o) h; p# a, tas testotoxicosis, may cause precocious puberty at a- g! `$ q1 ]( R( v' D
very young age. The physical findings in these boys8 r& X$ v% _8 F$ N- g% f
with this disorder are full pubertal development,9 D7 F1 c4 V4 j
including bilateral testicular growth, similar to boys
, v: R! n: \/ b! q7 Wwith CPP. The gonadotropin levels in this disorder2 p2 w1 d7 r3 u1 v
are suppressed to prepubertal levels and do not show
& w4 W- ?/ l6 N- A# Gpubertal response of gonadotropin after gonadotropin-
6 O5 o. I! P) B" c2 I9 greleasing hormone stimulation. This is a sex-linked
q% S) ^; ^- W8 t4 p. lautosomal dominant disorder that affects only( s9 h$ j3 O q5 ^$ L
males; therefore, other male members of the family3 d; D; [! m0 U% b' T) B
may have similar precocious puberty.3
! c2 y* `- ]- C2 {( ZIn our patient, physical examination was incon-- v- ~$ w) p; Q8 k3 [9 ]
sistent with true precocious puberty since his testi-4 v' s6 V8 k- n4 g& X5 j
cles were prepubertal in size. However, testotoxicosis8 l# D! Z, ^2 k7 } _
was in the differential diagnosis because his father7 {, r! `, j, r- {/ l
started puberty somewhat early, and occasionally,( M9 N1 G K4 Z. ? C7 n* `7 C
testicular enlargement is not that evident in the3 F" Q6 M) G6 j% D" B: [2 f7 E
beginning of this process.1 In the absence of a neg-
7 E& z- G. {& ~& `2 h+ Bative initial history of androgen exposure, our8 l/ ?$ @; i+ Z% i) Y: E
biggest concern was virilizing adrenal hyperplasia,
3 u6 Q, D' ^5 Z0 H" |either 21-hydroxylase deficiency or 11-β hydroxylase
% ?1 j$ r; K! b* ~: Xdeficiency. Those diagnoses were excluded by find-
8 Q( j7 J. z# D, Y. Cing the normal level of adrenal steroids.( H* R* c/ H9 t D& g
The diagnosis of exogenous androgens was strongly
% `$ B' i5 j- m$ Y9 b6 M- F# M" dsuspected in a follow-up visit after 4 months because
% h3 Z4 I1 j- L, P7 ethe physical examination revealed the complete disap-
5 t+ B1 ]* d( G, l4 g/ r# Upearance of pubic hair, normal growth velocity, and F5 t$ X- Z* J- R9 S) d# [. y6 g$ h
decreased erections. The father admitted using a testos-
/ n# ]) f! Y, E; }terone gel, which he concealed at first visit. He was M' a( C/ a5 e* o; {$ a
using it rather frequently, twice a day. The Physicians’
/ b; V- E% l7 g$ A6 N6 k( q, ^Desk Reference, or package insert of this product, gel or
4 ~8 D* i! @! n+ E) X2 D3 ^: kcream, cautions about dermal testosterone transfer to. t, g! S3 T6 G! n4 T0 z' m
unprotected females through direct skin exposure.
0 S/ a9 S. O2 L4 [* C; }) sSerum testosterone level was found to be 2 times the' u- d3 d+ x/ i7 b. ~2 g; U
baseline value in those females who were exposed to% K! _, x( R+ q
even 15 minutes of direct skin contact with their male
' g! }2 ^, ~( W3 z. |* D$ q, E* |partners.6 However, when a shirt covered the applica-
, P/ s6 o( T8 f0 B' i8 y" A: Z; Ption site, this testosterone transfer was prevented.
/ D& N3 d$ g, |' w- ]- jOur patient’s testosterone level was 60 ng/mL,
2 E, D4 N) r. E! A+ N( swhich was clearly high. Some studies suggest that% M2 T3 R1 y6 d; m7 @
dermal conversion of testosterone to dihydrotestos-% N* V( q: G4 `
terone, which is a more potent metabolite, is more
4 `4 j; A N t! Cactive in young children exposed to testosterone
, g3 i Z* b$ u# t- Wexogenously7; however, we did not measure a dihy-# O* O; Z8 M& X4 L2 [7 p7 `
drotestosterone level in our patient. In addition to
: i7 J$ Y5 `: fvirilization, exposure to exogenous testosterone in
$ s* Q9 d! N; {- S( A0 echildren results in an increase in growth velocity and
) c, V/ ~# W g; D% d Eadvanced bone age, as seen in our patient.
+ m# R u8 a! x' R4 sThe long-term effect of androgen exposure during5 o1 K) _1 N% e8 w1 R; a+ f( I
early childhood on pubertal development and final
+ k; Q+ r5 N2 Zadult height are not fully known and always remain
- t' x3 N5 {" X/ m, ua concern. Children treated with short-term testos-
# i5 ~" E8 h* `) `terone injection or topical androgen may exhibit some
0 @% |! H8 X Oacceleration of the skeletal maturation; however, after
3 D; `8 G' O# Jcessation of treatment, the rate of bone maturation
# M+ }& x' I6 a3 I) sdecelerates and gradually returns to normal.8,96 j2 c; N( O, A2 ~5 v; s& H
There are conflicting reports and controversy
" \' o5 p5 T1 P8 S& T% M$ fover the effect of early androgen exposure on adult8 p, {: l- H# r/ p6 u! n
penile length.10,11 Some reports suggest subnormal
+ d5 j l& T1 N# P0 r3 E O' c( Wadult penile length, apparently because of downreg-' g# L( h1 z& g( k5 Y4 Z
ulation of androgen receptor number.10,12 However,' k9 _3 ^, \% j0 u
Sutherland et al13 did not find a correlation between5 @5 J0 E [; c& R8 R7 E4 O
childhood testosterone exposure and reduced adult' n1 v- i8 o8 T% w& X9 e! I$ G
penile length in clinical studies.
- S( z A: W% ^. BNonetheless, we do not believe our patient is
7 P i$ i2 e" l: g( jgoing to experience any of the untoward effects from
! f+ h0 N- W" d1 i9 ?/ _! f6 Btestosterone exposure as mentioned earlier because' K! Y5 h3 w5 a6 x
the exposure was not for a prolonged period of time.; c, Q4 L- C/ a7 b
Although the bone age was advanced at the time of6 b; k& h% O) o7 ?% {
diagnosis, the child had a normal growth velocity at
: f n- b3 ?, f; dthe follow-up visit. It is hoped that his final adult
3 m4 j0 K' X' f- Nheight will not be affected.
5 }7 @ R, v# J8 i" GAlthough rarely reported, the widespread avail-
9 {- z* ?) O9 s$ |ability of androgen products in our society may
4 P8 e" _# e9 N) l8 ~indeed cause more virilization in male or female
: A+ S/ a1 j& O6 H0 V) xchildren than one would realize. Exposure to andro-8 b/ J/ [3 A% d0 m3 w
gen products must be considered and specific ques-8 e6 l3 z; ~# R6 j0 a: M9 `
tioning about the use of a testosterone product or+ F1 S5 J4 r; O
gel should be asked of the family members during' v+ `0 |! m) z9 N
the evaluation of any children who present with vir-6 I# j+ I+ e# L$ p Z
ilization or peripheral precocious puberty. The diag-
; T- n Q8 M1 i/ ?2 z# s, i4 ]nosis can be established by just a few tests and by6 \$ F, }( }6 f- c
appropriate history. The inability to obtain such a
' W/ p, o) L w6 m' C" F/ s- ]history, or failure to ask the specific questions, may
- ]% ^ m; _, a! V4 Sresult in extensive, unnecessary, and expensive2 Q( E. [# @" ?8 b' F5 }2 @
investigation. The primary care physician should be
- M' ^7 n: z Laware of this fact, because most of these children0 C! g" U2 p/ M# ~# {. O
may initially present in their practice. The Physicians’
* N: E0 b0 B1 F3 PDesk Reference and package insert should also put a
" O. z2 i5 C9 [9 m6 B8 _) rwarning about the virilizing effect on a male or
! ~. X, E# p) d2 }1 d5 ~5 {female child who might come in contact with some-1 [2 ]2 P& [: L/ j; a& `8 E% [
one using any of these products.! q! p, F. a9 w% J1 _7 l
References
; l- ^: C2 d* ~3 i; }7 D ? o1. Styne DM. The testes: disorder of sexual differentiation
7 ~% S/ _: ~3 L+ V: Uand puberty in the male. In: Sperling MA, ed. Pediatric
7 a1 u; x& C/ ^. mEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
/ ? `8 x3 ~" U" W2002: 565-628.
1 h8 Y" O# H1 j) L: c+ j" |7 M2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious0 |* r' f) |! }
puberty in children with tumours of the suprasellar pineal |
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