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Sexual Precocity in a 16-Month-Old
' K8 G Y8 k B6 ~Boy Induced by Indirect Topical
- \5 b, e: B8 T: M! sExposure to Testosterone; _+ a9 C+ f1 u
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
" S. ?' H2 o @% k! l: r3 Iand Kenneth R. Rettig, MD1' G) F. J1 E; W) \: ]
Clinical Pediatrics
. I. w; M2 i9 n# DVolume 46 Number 67 M* H1 F# a8 C& |' O
July 2007 540-543; o( S# o$ z9 v0 {' Y' t1 q7 q/ T: p7 \
© 2007 Sage Publications" i1 v8 O0 ^/ f5 X6 d
10.1177/0009922806296651
( i, i M! {6 G7 Z5 `; N( f3 bhttp://clp.sagepub.com
, o" z( V8 H7 W* `/ ahosted at9 c% g, J* }: D6 A, j0 G
http://online.sagepub.com2 L* A( I, n5 s4 O' Q5 n4 T
Precocious puberty in boys, central or peripheral,
" ~- N. H( ?/ ~is a significant concern for physicians. Central
2 W& _+ Q; J% j. P8 y, ^precocious puberty (CPP), which is mediated
* ^ x: j3 l: Q& `# {through the hypothalamic pituitary gonadal axis, has, b4 S4 C0 L3 o, {+ G8 n
a higher incidence of organic central nervous system( s6 E8 a* x s% y/ c
lesions in boys.1,2 Virilization in boys, as manifested
! A) J K3 c: Oby enlargement of the penis, development of pubic
9 d2 P1 W) `: Q4 r1 [" chair, and facial acne without enlargement of testi-
3 w: k0 v, B& y+ F& H& ~; S2 Jcles, suggests peripheral or pseudopuberty.1-3 We8 X' z4 ]1 i# L9 M$ G& ]
report a 16-month-old boy who presented with the
X) r( d$ j/ G' r) }2 |enlargement of the phallus and pubic hair develop-
2 T% p# ~7 E0 v6 C( l0 Tment without testicular enlargement, which was due" y9 V% w1 o# \
to the unintentional exposure to androgen gel used by& R3 R/ K6 a$ ^1 E( Y* u6 P
the father. The family initially concealed this infor-
7 a8 U) l0 G0 a' ?5 X& N) wmation, resulting in an extensive work-up for this
1 o- E: }7 k; ?& G3 z. s4 rchild. Given the widespread and easy availability of( F. y- \4 J1 R; P5 H# J
testosterone gel and cream, we believe this is proba-
$ L9 C/ Z* }0 y1 u5 x) {. Wbly more common than the rare case report in the$ V, H: y7 L; ]$ k) Z6 i6 s# M
literature.43 v6 a5 i# A- |/ D4 g' \
Patient Report7 ~* F' r* [' u
A 16-month-old white child was referred to the
4 [6 \1 A ]( n0 p eendocrine clinic by his pediatrician with the concern. ?9 [# ]4 i3 U" Q. k1 u
of early sexual development. His mother noticed
5 s' w2 t# z% W" Y$ H, f5 a+ c# x+ Rlight colored pubic hair development when he was
& B* c) m3 Y) x9 s4 A, ]% w* TFrom the 1Division of Pediatric Endocrinology, 2University of6 A+ p" i% r( O; l: M7 y
South Alabama Medical Center, Mobile, Alabama., Z( j7 s+ _9 O, d3 _
Address correspondence to: Samar K. Bhowmick, MD, FACE,# n3 O( l. ?& u; V# G* T- L
Professor of Pediatrics, University of South Alabama, College of
0 H$ K" L% H% K) fMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;2 R3 q' D r8 \* Z7 W9 R
e-mail: [email protected].1 p+ ?" P) e0 W
about 6 to 7 months old, which progressively became7 B# J. z" ^0 t3 q8 s
darker. She was also concerned about the enlarge-! Y# |1 i8 w$ C7 E3 S
ment of his penis and frequent erections. The child, e+ @3 E/ I# @: d9 i4 |2 L# q
was the product of a full-term normal delivery, with
$ W- x/ r0 K/ H8 Ma birth weight of 7 lb 14 oz, and birth length of
8 u- V2 }9 L* k: v/ i20 inches. He was breast-fed throughout the first year! I5 W6 Y& I8 r% h) \3 o4 ^
of life and was still receiving breast milk along with" {2 S; t$ d+ ]
solid food. He had no hospitalizations or surgery,
0 G: b9 e+ h3 ]$ sand his psychosocial and psychomotor development0 l+ |2 n1 Z" r* O9 [, W& ^- g
was age appropriate.6 ~$ ?' q* z4 }5 u2 z9 Y+ `: L
The family history was remarkable for the father,
7 X# C; z$ G: h0 j) p! G" l% c7 \who was diagnosed with hypothyroidism at age 16,
6 w, I* N, @1 p# @; Z5 h( Lwhich was treated with thyroxine. The father’s8 ]1 m$ p% v1 x4 j2 l* x) D6 A, B3 ^
height was 6 feet, and he went through a somewhat2 o4 Y+ z9 c& _, m, e$ ~
early puberty and had stopped growing by age 14.( H7 n8 s4 t7 [3 |( y
The father denied taking any other medication. The: s9 N2 R; i4 c8 m$ e! I
child’s mother was in good health. Her menarche
@' I+ ?9 [0 Dwas at 11 years of age, and her height was at 5 feet6 T% z( Q% C$ u6 @* K
5 inches. There was no other family history of pre-
1 L% z/ T# @ z8 `, d5 f3 Ecocious sexual development in the first-degree rela-( s( R+ P: ^' p
tives. There were no siblings.! [ B0 Z6 a+ m# B. u5 |
Physical Examination6 E6 i' `3 f8 S; L: l& ~* `6 w
The physical examination revealed a very active,: v9 ^% d2 P$ d( t" i
playful, and healthy boy. The vital signs documented8 f+ c* L M3 D* H* t: K
a blood pressure of 85/50 mm Hg, his length was) S4 c1 R% \5 q0 M6 u- @' q: a4 R
90 cm (>97th percentile), and his weight was 14.4 kg
, x1 v! }' K: G9 W(also >97th percentile). The observed yearly growth
) K- N2 K! F' c' Ivelocity was 30 cm (12 inches). The examination of$ n% d! g/ d' `% ]: q
the neck revealed no thyroid enlargement.
: P' r) y7 J4 y3 R! qThe genitourinary examination was remarkable for: e% I: a+ |5 {, ~$ w
enlargement of the penis, with a stretched length of; |: W4 A+ `2 T7 y; G( [# E& y
8 cm and a width of 2 cm. The glans penis was very well6 a# a1 b* C' t; I) s- L# a
developed. The pubic hair was Tanner II, mostly around
# S! M6 c1 c! O4 Y/ L5408 p6 O- l( l$ ?& B3 Q: z9 K! ?" y
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from8 ]# O" {1 f. K# t
the base of the phallus and was dark and curled. The
' u0 {- D: _% I" j; E# ]/ jtesticular volume was prepubertal at 2 mL each.' y6 L# c3 D: M! |+ ^) i
The skin was moist and smooth and somewhat
; p2 o6 t6 }7 koily. No axillary hair was noted. There were no
6 Z' l- ^" S/ [# ]) Habnormal skin pigmentations or café-au-lait spots." Y+ @9 T9 C' _" K; W
Neurologic evaluation showed deep tendon reflex 2+
) t* F6 i% R+ m7 o, abilateral and symmetrical. There was no suggestion& J3 V& g' y8 t
of papilledema., H3 N H; t7 m* N3 f
Laboratory Evaluation( u& j5 o- d# `1 U0 Z. o# q! G
The bone age was consistent with 28 months by5 p n+ R9 g |, |: H0 i( ? Z
using the standard of Greulich and Pyle at a chrono-% d0 T8 n) O1 L. }3 D: m
logic age of 16 months (advanced).5 Chromosomal
3 T+ I0 V/ w, g1 Q5 k' }0 kkaryotype was 46XY. The thyroid function test) N3 t) ]0 X/ t/ W6 E$ G8 @! I) G! M5 N
showed a free T4 of 1.69 ng/dL, and thyroid stimu-' K! F3 y; p1 M5 x6 ^
lating hormone level was 1.3 µIU/mL (both normal).8 c8 H# W" J& I; n
The concentrations of serum electrolytes, blood
: Q5 [ i) j" {) }! P! @' turea nitrogen, creatinine, and calcium all were
9 e; a7 ^7 ]: W& A8 V2 A) I$ ^+ g4 ^( Gwithin normal range for his age. The concentration
3 Q# j! D0 ~% ^# s$ K# Y4 g- Aof serum 17-hydroxyprogesterone was 16 ng/dL
5 N% g: Z- S, l: [& g6 b$ S) Y( R(normal, 3 to 90 ng/dL), androstenedione was 20
; T `! u& L- u% k% j- rng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-+ x( u. \8 R0 S8 `
terone was 38 ng/dL (normal, 50 to 760 ng/dL),$ ? C) B$ A+ P
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
7 S9 c0 W/ c6 x/ U49ng/dL), 11-desoxycortisol (specific compound S)
& h. J$ ]% T" N$ F9 Iwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-8 R* w* q* x6 \- s3 J
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
c$ |' H: {3 O8 l% S% H+ {' F; Ctestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
, b7 C1 j @# S2 s! S |% iand β-human chorionic gonadotropin was less than; s" N$ c8 S. m N' j! u- ?
5 mIU/mL (normal <5 mIU/mL). Serum follicular
6 L# g3 x3 \6 [/ T+ v) _ C3 a% Astimulating hormone and leuteinizing hormone
$ H. v! r2 R% \ |' j$ uconcentrations were less than 0.05 mIU/mL; C7 Y! R) K+ D+ L* v' \0 u3 M, U0 @* P! G
(prepubertal)., R6 Q8 R' L6 O' r
The parents were notified about the laboratory
3 i5 @4 g0 K0 Jresults and were informed that all of the tests were
. U# B* ~3 Y/ c; d# Wnormal except the testosterone level was high. The
! }& H! |5 P% K- W6 Lfollow-up visit was arranged within a few weeks to0 G, T+ O9 z8 `* M0 n. o, t
obtain testicular and abdominal sonograms; how-2 C2 M% f2 H5 d* |
ever, the family did not return for 4 months.
8 t; Q1 R) `8 E2 s CPhysical examination at this time revealed that the
Z) h/ K: v2 n1 [. Ochild had grown 2.5 cm in 4 months and had gained" _) o1 b w. \) h
2 kg of weight. Physical examination remained
3 F5 |3 H. J( E. c3 R2 Q0 j7 dunchanged. Surprisingly, the pubic hair almost com-
' _& }, R1 T. D- Q" Y8 @pletely disappeared except for a few vellous hairs at
; b! R. X9 t* ]; R q7 P& pthe base of the phallus. Testicular volume was still 2; q0 X( w6 w5 W/ L
mL, and the size of the penis remained unchanged.
/ g4 _# j5 q: p2 {The mother also said that the boy was no longer hav-$ g+ _1 H* L$ R& Z) b
ing frequent erections.& _# J8 H" q- M! A
Both parents were again questioned about use of
# c" T2 u( A7 e% X5 p+ [any ointment/creams that they may have applied to
/ f/ V1 r1 V3 mthe child’s skin. This time the father admitted the3 K- u5 K- K2 { ~% v$ k: m
Topical Testosterone Exposure / Bhowmick et al 541
% S& ~ R6 h1 z' o2 ?$ ^use of testosterone gel twice daily that he was apply-
+ y0 U, m1 z1 S2 \# J7 d. D' D# \ing over his own shoulders, chest, and back area for
4 X+ x) R% J5 `3 \% W0 p% ua year. The father also revealed he was embarrassed
$ [. r) e( Q$ e+ q9 x/ m2 y5 Nto disclose that he was using a testosterone gel pre-; `% b- E# B& Q$ k
scribed by his family physician for decreased libido/ \& Q3 L. C, J: C
secondary to depression.% {8 b0 b. r& J0 R! {
The child slept in the same bed with parents.- k7 |) z& c1 N
The father would hug the baby and hold him on his
; C+ ^1 e8 j% B3 t' Lchest for a considerable period of time, causing sig-
( b3 p' o0 J# ]1 j( | tnificant bare skin contact between baby and father.9 q# N/ R( _. ~, A% z O
The father also admitted that after the phone call,: t6 m& o& M# r! @
when he learned the testosterone level in the baby
9 g5 w3 }" P; ]7 Y8 awas high, he then read the product information. A8 P/ Y& }/ ?( _
packet and concluded that it was most likely the rea-4 a& a# f& U3 S
son for the child’s virilization. At that time, they, x# m% i( i( _- {; }. O- c
decided to put the baby in a separate bed, and the& D/ d" C) v) p% P
father was not hugging him with bare skin and had
/ ?6 v# }+ o, ybeen using protective clothing. A repeat testosterone
/ b% b0 j# O2 d) X/ C& Utest was ordered, but the family did not go to the
$ T. ^, t: _( plaboratory to obtain the test.
$ }/ \' O' P& Y. i0 rDiscussion
0 y% r, ?( J' c3 gPrecocious puberty in boys is defined as secondary
; i t, b* A' o* \( p" O' g' M+ k& lsexual development before 9 years of age.1,4
9 A* O$ H* y. x& kPrecocious puberty is termed as central (true) when
$ p' f5 E, l9 k+ I& j3 z% cit is caused by the premature activation of hypo-: M% F: J# s1 A0 Q! n9 Q2 ?) f A3 I
thalamic pituitary gonadal axis. CPP is more com-/ N% c3 B, }& P; \
mon in girls than in boys.1,3 Most boys with CPP1 b: n4 W/ a0 J8 N
may have a central nervous system lesion that is
* p8 U' k3 G2 X: Oresponsible for the early activation of the hypothal-5 r0 l/ n3 o2 t! |( k. {8 ]
amic pituitary gonadal axis.1-3 Thus, greater empha-
" b9 I% |: c$ P4 L; h W9 E Msis has been given to neuroradiologic imaging in
" H @4 `/ T6 pboys with precocious puberty. In addition to viril-) |7 C! ^7 K6 W- p" ?* F# u# o
ization, the clinical hallmark of CPP is the symmet-) u/ c4 |3 L" E8 a. R# x
rical testicular growth secondary to stimulation by! d& f. n, J7 m0 i- B$ x
gonadotropins.1,3
! Y. _& b" K7 {& X1 U4 |Gonadotropin-independent peripheral preco-
+ g+ P# q" W3 qcious puberty in boys also results from inappropriate
" O4 n$ A8 g7 f, \/ F7 w& {% candrogenic stimulation from either endogenous or5 J2 q1 M. c# }8 s( \
exogenous sources, nonpituitary gonadotropin stim-
8 V* L5 ]- n: S: u/ V& k8 D5 bulation, and rare activating mutations.3 Virilizing
- F) f: B; {( U4 \2 g5 d: Jcongenital adrenal hyperplasia producing excessive( f% x$ T9 f; g$ Y I: F. G& m
adrenal androgens is a common cause of precocious, z- f! [7 P! g
puberty in boys.3,47 p0 Z; D2 `2 X
The most common form of congenital adrenal( o$ w0 t, ^8 E# w
hyperplasia is the 21-hydroxylase enzyme deficiency.
* T5 H. ]5 k/ m- b+ V0 X9 A3 TThe 11-β hydroxylase deficiency may also result in) `5 M+ d* v% M: t/ |/ ]: T
excessive adrenal androgen production, and rarely, s. Z" p& U5 ~. M# @3 N
an adrenal tumor may also cause adrenal androgen7 w5 y. e. T1 {4 V1 D4 m. {- L
excess.1,31 v: F `* a9 V7 s3 Y
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
1 \ X3 S" ?& e7 Q: X# |542 Clinical Pediatrics / Vol. 46, No. 6, July 20075 O" r. E5 X- o7 y
A unique entity of male-limited gonadotropin-
4 H1 d: u% P( E! |independent precocious puberty, which is also known
i* E$ p2 Q1 F$ j \/ D7 ras testotoxicosis, may cause precocious puberty at a- y" H1 x% O; L0 _# C
very young age. The physical findings in these boys) |3 Z4 K+ F* r
with this disorder are full pubertal development,
- T, s0 R+ D2 n9 E' Pincluding bilateral testicular growth, similar to boys/ o% c6 W |7 j' T5 o; }* C" o0 s
with CPP. The gonadotropin levels in this disorder
( `+ q' `! e( q, S% E' `! {are suppressed to prepubertal levels and do not show
3 S+ t- P0 u3 Tpubertal response of gonadotropin after gonadotropin- Z6 }. U3 }2 P
releasing hormone stimulation. This is a sex-linked
7 ^! Q4 {9 x& q& G1 r6 {: yautosomal dominant disorder that affects only
9 }# ~2 W3 F, S7 N: t, Hmales; therefore, other male members of the family
0 B6 Y; m8 M% S j# X# bmay have similar precocious puberty.3* Q; O3 P! ~. a2 Y. M
In our patient, physical examination was incon-
0 p5 T' V: p( e7 {( l7 ]; Asistent with true precocious puberty since his testi-! j8 S' a. [# j" J
cles were prepubertal in size. However, testotoxicosis
9 l- G9 j+ i5 s+ e$ v6 Wwas in the differential diagnosis because his father
: k4 {. K- P3 Q6 |7 rstarted puberty somewhat early, and occasionally,: H- ~- \$ |& g k4 {% D
testicular enlargement is not that evident in the
( a7 e- C* I' sbeginning of this process.1 In the absence of a neg-0 }2 R* G( @; n0 b9 g
ative initial history of androgen exposure, our
0 t1 ]1 s' Z/ A9 O) p7 Ibiggest concern was virilizing adrenal hyperplasia,
* R/ f, n$ W3 s4 ^either 21-hydroxylase deficiency or 11-β hydroxylase+ @% Q0 m( X- r$ t4 ?; r
deficiency. Those diagnoses were excluded by find-5 _2 B8 J- H H$ w7 p2 z
ing the normal level of adrenal steroids.
# Z4 v) s) Z) u, uThe diagnosis of exogenous androgens was strongly
/ e4 ]" l* Z5 Xsuspected in a follow-up visit after 4 months because
4 ~4 R/ Q; q+ ^4 A( @" b3 \- \the physical examination revealed the complete disap-7 e, s/ o- D1 x) m0 Q* u& s
pearance of pubic hair, normal growth velocity, and3 h* w- h8 C' w- B7 ~
decreased erections. The father admitted using a testos-0 p/ x. |% {# K
terone gel, which he concealed at first visit. He was
6 a+ h( V6 i6 k/ B+ ausing it rather frequently, twice a day. The Physicians’, f# s& l- [) ]- g
Desk Reference, or package insert of this product, gel or0 |1 _4 a! M% b2 Z
cream, cautions about dermal testosterone transfer to7 l* s6 {- j1 e/ L# F
unprotected females through direct skin exposure.
5 p1 W; W* U8 W5 D2 wSerum testosterone level was found to be 2 times the& k) j: l, ^5 `: S) A
baseline value in those females who were exposed to
8 j0 K3 f, i) Y$ [" A- geven 15 minutes of direct skin contact with their male8 L& ]5 q3 _6 C
partners.6 However, when a shirt covered the applica-! D2 P7 X1 g" M l
tion site, this testosterone transfer was prevented.
4 D! y/ t, c- o% v) e0 xOur patient’s testosterone level was 60 ng/mL,
: |1 w' {- E) g" T% X. dwhich was clearly high. Some studies suggest that/ _5 b3 F" j; t/ j7 s7 \
dermal conversion of testosterone to dihydrotestos-# {8 t5 C/ n/ K4 e/ I. T
terone, which is a more potent metabolite, is more
8 _- A; f5 i6 U0 [2 Oactive in young children exposed to testosterone* K" P: K( `+ o& E) D
exogenously7; however, we did not measure a dihy-
0 A8 @8 ?+ }+ I- a% Fdrotestosterone level in our patient. In addition to0 G& m" v/ t' J9 I
virilization, exposure to exogenous testosterone in
( F; ~$ @7 H" Wchildren results in an increase in growth velocity and
/ i2 {& A: x# A1 y4 Aadvanced bone age, as seen in our patient.
2 d# @: |0 e- P) ~) v4 D% P2 @The long-term effect of androgen exposure during
8 A) ]+ V& f4 ?* A) A) k: \early childhood on pubertal development and final5 A' o* [! k) |9 z/ \" }5 J
adult height are not fully known and always remain
% P( ^1 L) c" \4 H8 W) `3 ~a concern. Children treated with short-term testos-! O: W' r; G$ r# U
terone injection or topical androgen may exhibit some
9 i' V8 h% I# p) ]2 V& ?8 V$ }acceleration of the skeletal maturation; however, after& Y* @+ V1 G3 b
cessation of treatment, the rate of bone maturation- N0 h, b! G1 r% h( z+ d( ]5 g/ y
decelerates and gradually returns to normal.8,9
. H& r: W) W" v: D2 n, RThere are conflicting reports and controversy4 p3 K0 v2 G: N G
over the effect of early androgen exposure on adult
6 J4 Q- Z! Y: S8 B2 z: O% Y$ @5 i' ipenile length.10,11 Some reports suggest subnormal( u% H4 S) W. d* [" X( P% D0 r
adult penile length, apparently because of downreg-
" Y% |. u! m3 \ ]7 Yulation of androgen receptor number.10,12 However,* e& Z1 _2 R. l+ j/ f, q
Sutherland et al13 did not find a correlation between5 F' r: @3 }# ?7 T/ P% G
childhood testosterone exposure and reduced adult
2 C5 {% c# z0 W+ R5 Ypenile length in clinical studies.
( _2 h; u0 t& o4 x* bNonetheless, we do not believe our patient is
5 g" n6 s3 U% |- a/ ^going to experience any of the untoward effects from
) q/ }1 Q+ F- L! {testosterone exposure as mentioned earlier because
, S1 u$ P! a1 {! P. sthe exposure was not for a prolonged period of time.3 `/ ?' W7 |8 Q* d, Y, s! f2 C
Although the bone age was advanced at the time of
* e7 B; S. Q( gdiagnosis, the child had a normal growth velocity at
7 O' k# |% S6 j1 O: ^8 \& i- qthe follow-up visit. It is hoped that his final adult1 c( o9 K+ _( P7 w1 B' f* T
height will not be affected.
" p& a( c5 ~& N9 RAlthough rarely reported, the widespread avail-
- U$ b9 B8 G7 g" Q T0 ^* }ability of androgen products in our society may
6 m. z& x2 N8 Z8 _indeed cause more virilization in male or female2 Y* t4 L3 i( c8 m5 i
children than one would realize. Exposure to andro-
+ I: a, t$ q% Z4 o: |5 L5 ggen products must be considered and specific ques-7 O+ v( F+ `; Q7 n( m; [: [
tioning about the use of a testosterone product or
, c* Q9 }; ?, D% d; e3 Bgel should be asked of the family members during
" P+ s0 m" f2 ~& v2 b6 _the evaluation of any children who present with vir-7 E* F! m+ u# t8 m$ k) ^
ilization or peripheral precocious puberty. The diag-' |. G; M6 Z0 N- p: w7 L; K
nosis can be established by just a few tests and by
! I: U/ A) h0 D7 p4 qappropriate history. The inability to obtain such a
' U, B) `2 u- j9 A7 Bhistory, or failure to ask the specific questions, may
1 o/ q0 Y$ O1 |. Eresult in extensive, unnecessary, and expensive
7 O3 r" a6 k6 o' g. ]3 @( g& Finvestigation. The primary care physician should be0 t9 f4 y5 X* `1 R% Y5 I" u
aware of this fact, because most of these children
% d( z, z3 c, \9 K( wmay initially present in their practice. The Physicians’
. W+ J+ G$ K; e8 ADesk Reference and package insert should also put a1 U& [8 a6 k: |
warning about the virilizing effect on a male or0 o+ q6 B+ p: o" h1 V
female child who might come in contact with some-
# T$ s7 M. r3 J2 N/ V" Q# j2 Mone using any of these products.% w! O& s# n5 ^( v- x& A
References0 R. t2 ]$ C5 m# B# }
1. Styne DM. The testes: disorder of sexual differentiation
' z" f. \" D8 Y2 n' C4 Z) A' Kand puberty in the male. In: Sperling MA, ed. Pediatric
- L. ~; {* k% Y n8 @0 s; S! IEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;, l, ^$ l: f' F/ g- ]$ k9 C% `
2002: 565-628.
; j2 b5 [. `9 d! Y8 X5 ^, @$ V2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
( S- y" d4 R) v& e! M6 q" spuberty in children with tumours of the suprasellar pineal |
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