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Sexual Precocity in a 16-Month-Old1 p/ u8 ^: i2 e& _
Boy Induced by Indirect Topical
: x) C2 \/ {1 s5 G$ q! wExposure to Testosterone
. h' P0 z' }* E- V9 e: B% e8 ^Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
! K' ^9 r9 T q' q eand Kenneth R. Rettig, MD1# N$ }' C7 k* ~& H9 T/ x7 @) ?
Clinical Pediatrics
" t7 |0 `4 B& Y% D- mVolume 46 Number 6( R3 p5 p) C1 a) f% s" w
July 2007 540-5431 @ S& D1 G9 p" n7 x
© 2007 Sage Publications+ p5 A7 I$ v: M4 m, c3 D9 ]. H0 S1 Y
10.1177/0009922806296651
: p- [# d: [; W& A8 Z% L' x8 t9 Whttp://clp.sagepub.com- d$ o" e4 v$ ?7 ^
hosted at
2 a' h+ o% \: l4 F2 uhttp://online.sagepub.com& m2 S, ?. D. N I/ K- {/ l
Precocious puberty in boys, central or peripheral,% I- m" c4 j# B" @( f5 w
is a significant concern for physicians. Central
& J( Q5 C. M, p& y s% n% X5 zprecocious puberty (CPP), which is mediated9 G" L+ W7 N' f4 T. N; k
through the hypothalamic pituitary gonadal axis, has2 f7 k; `( S" f: T8 p5 i1 Y9 T5 j
a higher incidence of organic central nervous system
' J* }: N9 |5 y2 alesions in boys.1,2 Virilization in boys, as manifested
- B& `5 X. W% _% Z: H2 aby enlargement of the penis, development of pubic
/ L) I$ `" ?% t O% ghair, and facial acne without enlargement of testi-
- I$ a7 o2 Q; q2 dcles, suggests peripheral or pseudopuberty.1-3 We% J+ y' Q% q( i) }3 V
report a 16-month-old boy who presented with the
! {# @! S d& \9 J6 F/ \, F6 jenlargement of the phallus and pubic hair develop-$ r( H% o5 g$ I9 ]
ment without testicular enlargement, which was due& N B. b) D1 [- R# P9 j
to the unintentional exposure to androgen gel used by$ n" l9 {6 F5 X: {3 z: X3 L
the father. The family initially concealed this infor-
4 C* \- \1 G" j \8 Pmation, resulting in an extensive work-up for this
5 l/ H, a5 h! s& Jchild. Given the widespread and easy availability of
. i5 o$ V7 a4 I" Xtestosterone gel and cream, we believe this is proba-5 \8 ?* O/ g# ~$ V7 w1 o' y! {5 ~
bly more common than the rare case report in the" b8 r D3 e# n) z
literature.4, b5 j0 R: T t& K X4 n
Patient Report
; g; M/ \9 m6 R2 `5 h7 v+ mA 16-month-old white child was referred to the
N, z# h# ?# e; |% t+ ~endocrine clinic by his pediatrician with the concern
% }0 ^5 J) N: k& K/ L S# \of early sexual development. His mother noticed# x, k5 I* }, b7 q' ~: a" E
light colored pubic hair development when he was
* y' O! G, _! I s5 lFrom the 1Division of Pediatric Endocrinology, 2University of; N |3 H- O Y1 I* b& b4 O
South Alabama Medical Center, Mobile, Alabama.' X3 [; ?! V1 d0 [0 u
Address correspondence to: Samar K. Bhowmick, MD, FACE,
* X: Q) r z. a# sProfessor of Pediatrics, University of South Alabama, College of
( `3 K) d: F: m- E% k& oMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;" u! ~, g- y8 e8 u: ~
e-mail: [email protected].) _- I: t. r/ i
about 6 to 7 months old, which progressively became- R3 x! z/ {# F( e7 U* e& s
darker. She was also concerned about the enlarge-
0 W% B5 M9 t, `" I) o Pment of his penis and frequent erections. The child
6 y7 F; J# ^3 b* l W5 zwas the product of a full-term normal delivery, with
& J* B- g' R( j( ]+ E) }a birth weight of 7 lb 14 oz, and birth length of
4 t& d- C, Z' W' h20 inches. He was breast-fed throughout the first year# `; {. z. j# y& _. J( p9 q/ {
of life and was still receiving breast milk along with$ n0 g s1 q) W8 M7 F4 g6 O9 \
solid food. He had no hospitalizations or surgery,
/ ~1 r& S) C( F: fand his psychosocial and psychomotor development' r, B0 W/ H+ P0 S8 E
was age appropriate.
" L* w0 { x' o4 R$ E" M+ Q+ gThe family history was remarkable for the father,, l! D/ H: t' L
who was diagnosed with hypothyroidism at age 16,6 j! P8 N0 m0 R
which was treated with thyroxine. The father’s
( u6 r9 ~ Z' K7 d- ]. K+ P6 ~+ Pheight was 6 feet, and he went through a somewhat8 k8 u: v. u2 q1 |2 y
early puberty and had stopped growing by age 14., U0 Z* i' k7 t* N( [8 S
The father denied taking any other medication. The- ^2 Z+ |# u* C( M$ s: H" `( n
child’s mother was in good health. Her menarche7 H# o1 Y: b- z! j# W! |9 e& j
was at 11 years of age, and her height was at 5 feet
+ K$ R7 E7 ^ [1 G5 inches. There was no other family history of pre-" Q" w" g1 t/ r/ R7 _& ~1 W6 x
cocious sexual development in the first-degree rela-) \' D8 J1 u1 M& B! {" X% v
tives. There were no siblings.
6 w+ y& { j& cPhysical Examination
/ ?0 ?' q( e4 A% o$ SThe physical examination revealed a very active,) \8 W$ i5 f- r' P7 D" ]3 ^5 f
playful, and healthy boy. The vital signs documented7 ?9 p% ]- X& k! |9 l
a blood pressure of 85/50 mm Hg, his length was, l( U) g& g! M+ d5 T1 P
90 cm (>97th percentile), and his weight was 14.4 kg/ d. O* m/ X7 a) i
(also >97th percentile). The observed yearly growth9 j2 b$ e, a* e$ Y
velocity was 30 cm (12 inches). The examination of
# R" m/ u# G+ C% r/ ^the neck revealed no thyroid enlargement.. @# r* X# s Q" a4 f9 b6 q
The genitourinary examination was remarkable for
( `8 C! |- G) B* ~1 S0 Q9 denlargement of the penis, with a stretched length of
3 k& b* f, Q/ W* Z' _8 cm and a width of 2 cm. The glans penis was very well
1 D6 h% j4 K6 G C) Hdeveloped. The pubic hair was Tanner II, mostly around* _/ I( Q _( ^
540% z# G6 e. ?* f" C
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
+ ]' s4 I. @/ e( |% R8 q' Othe base of the phallus and was dark and curled. The
p; d9 X! o9 b1 A: v" ytesticular volume was prepubertal at 2 mL each.* Y5 @7 l1 w8 A! P
The skin was moist and smooth and somewhat' O {+ a- Z- N6 A
oily. No axillary hair was noted. There were no" r6 x, [# `' {5 H! D! s P; l. j/ t
abnormal skin pigmentations or café-au-lait spots.
% k1 F+ {2 U4 x% @Neurologic evaluation showed deep tendon reflex 2+$ r. h" |$ Z* o, t, x; ]% X4 N: y. h
bilateral and symmetrical. There was no suggestion
8 V: `0 f! J% b; I) d- J. o& xof papilledema.
! A( S& [9 @' n" bLaboratory Evaluation8 P0 p* X2 s% ?' Q6 u) u
The bone age was consistent with 28 months by* I: @7 x4 }6 O1 F0 Q
using the standard of Greulich and Pyle at a chrono-" Z+ ]- x% m% @# L- w
logic age of 16 months (advanced).5 Chromosomal
! `% r. c+ v$ N$ n+ J' w" X- _4 }karyotype was 46XY. The thyroid function test
7 T! w; C5 Y6 f; F1 J5 S" mshowed a free T4 of 1.69 ng/dL, and thyroid stimu-, [; ?) `1 H$ ~' G5 `
lating hormone level was 1.3 µIU/mL (both normal).
" {& _, O3 D }9 oThe concentrations of serum electrolytes, blood& J/ z6 r+ f. I1 Q4 j9 [) X& B# V: P
urea nitrogen, creatinine, and calcium all were. Z( F" A- r$ I0 \) o
within normal range for his age. The concentration; \2 }' B0 V/ y5 T8 H" g' s
of serum 17-hydroxyprogesterone was 16 ng/dL" d/ d; B- h4 q$ H8 j1 {
(normal, 3 to 90 ng/dL), androstenedione was 206 Z9 D9 E |) ^2 S, [+ S
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-) L% o! a+ n/ |* Q6 b3 _
terone was 38 ng/dL (normal, 50 to 760 ng/dL),, ~& U8 b2 [- a! C
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
/ q) @: f5 n Q; X5 F49ng/dL), 11-desoxycortisol (specific compound S)
, x- X! j6 {* v) Ewas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
1 N5 k+ c7 D# _: B! ttisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total! D. u$ o" ^! m/ V- X
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),/ k8 @) d- `3 t9 N0 h$ h
and β-human chorionic gonadotropin was less than4 U. z/ w) V5 `( I, B0 {% }
5 mIU/mL (normal <5 mIU/mL). Serum follicular
0 \+ H/ S. B. G4 j" _ zstimulating hormone and leuteinizing hormone
, W2 L3 }/ Z* gconcentrations were less than 0.05 mIU/mL
- t1 z+ r& C L3 x5 N(prepubertal).; M% m: Q- p4 F* y3 f
The parents were notified about the laboratory
3 |- y8 }8 H) gresults and were informed that all of the tests were. Y4 V P) a5 W' U
normal except the testosterone level was high. The
( I P2 l; ]: M& B/ U+ ]follow-up visit was arranged within a few weeks to
6 W+ F% c5 i% \1 b" K/ w. gobtain testicular and abdominal sonograms; how-
5 {3 s0 X* P1 u- P& m% Pever, the family did not return for 4 months.
' z, b) p0 g% m0 j0 p: cPhysical examination at this time revealed that the3 Z, p9 c; L& y' L" h U
child had grown 2.5 cm in 4 months and had gained
5 V) [+ \& `+ Y P5 C9 N2 kg of weight. Physical examination remained
' G5 K0 G, F3 C1 ?unchanged. Surprisingly, the pubic hair almost com-
3 b+ I: z, Y4 `" ]% spletely disappeared except for a few vellous hairs at7 j& y, _8 Y. ]& L2 C3 [- C
the base of the phallus. Testicular volume was still 2! V* o! c8 l# G7 S
mL, and the size of the penis remained unchanged.: \2 o2 n+ ]+ ]/ ^! R
The mother also said that the boy was no longer hav-% |, J! W3 |* ^) o# ^3 v
ing frequent erections.
. c* d! f; {# G* g2 b5 E+ sBoth parents were again questioned about use of, J) g% L: W. u+ x' X# ?
any ointment/creams that they may have applied to: C0 h8 p; A5 k- o% ^3 i0 i
the child’s skin. This time the father admitted the+ c- Y/ H" G; t. p0 Z0 ^
Topical Testosterone Exposure / Bhowmick et al 541
; B/ H) n; W" R! \0 Zuse of testosterone gel twice daily that he was apply-
) K. w4 f4 I9 r3 m Ging over his own shoulders, chest, and back area for: ]3 \$ m! Y. j, H' N
a year. The father also revealed he was embarrassed e3 {3 Z) g6 z
to disclose that he was using a testosterone gel pre-
& ?% o# t) w! d1 {7 A" pscribed by his family physician for decreased libido2 u5 h0 S, G0 I6 z( [$ _
secondary to depression.% |8 ]2 x' H4 c
The child slept in the same bed with parents.7 P0 L1 O$ U( B4 O0 r
The father would hug the baby and hold him on his
) v: @$ Q! K1 R9 Vchest for a considerable period of time, causing sig-
! a9 n# F; d+ U1 Gnificant bare skin contact between baby and father.
1 m! L ^3 u, d, H) L1 z$ _The father also admitted that after the phone call,
: M# [& G# o! [# x; i( wwhen he learned the testosterone level in the baby5 |7 h* q+ a' V" |5 Z0 j
was high, he then read the product information
/ `4 m7 M; s8 hpacket and concluded that it was most likely the rea-- t7 E& p: t! [7 B5 S, [1 f2 r( d) s9 F
son for the child’s virilization. At that time, they
# s) ]* l/ Q: b9 kdecided to put the baby in a separate bed, and the, E9 X% {" [5 s5 @
father was not hugging him with bare skin and had
- _7 l/ T+ J8 F) X: k. q5 o* Abeen using protective clothing. A repeat testosterone2 o- F: a9 w# p) G0 C4 l
test was ordered, but the family did not go to the) U) {3 g( n/ a9 k! e6 I& P. p, R
laboratory to obtain the test.7 u+ L$ d& [" Z. A2 q5 d3 [2 w0 J
Discussion
# d) U" b: w5 zPrecocious puberty in boys is defined as secondary
+ m- h x3 n3 ?, {sexual development before 9 years of age.1,4
: |: s" F. c; E; I/ l" @Precocious puberty is termed as central (true) when
$ o, p8 U1 z9 N. [6 E: `# ^it is caused by the premature activation of hypo-9 A7 g$ p* B" [# m( j
thalamic pituitary gonadal axis. CPP is more com-
# s0 v* M* R( v+ F9 r) a( R# ]- ^" amon in girls than in boys.1,3 Most boys with CPP
B; M3 V' u8 j# P# L9 Y% d" c# [may have a central nervous system lesion that is) A; m( L+ l7 N! h1 y% l/ X; R6 |
responsible for the early activation of the hypothal-$ c: ]- G* o" J' g" {9 m
amic pituitary gonadal axis.1-3 Thus, greater empha-
/ V( M7 h( X: q& L2 ?, ~( r" gsis has been given to neuroradiologic imaging in" j. ~4 A4 K& c# X0 T
boys with precocious puberty. In addition to viril-
/ {5 x3 ~) n) `. t/ \ization, the clinical hallmark of CPP is the symmet-" g2 S. i; k2 L) q9 |$ }9 I
rical testicular growth secondary to stimulation by
0 `2 b2 Z' M) ~2 g& g% A$ Vgonadotropins.1,38 n5 ~* L* W- v9 J
Gonadotropin-independent peripheral preco-
z5 S, }, M% M0 F4 f6 S. ]cious puberty in boys also results from inappropriate
2 P J7 |1 s7 jandrogenic stimulation from either endogenous or
( z0 ?: e9 K) a+ c7 i! O8 H* c% qexogenous sources, nonpituitary gonadotropin stim-) V6 h. f O$ Q3 z, K5 V
ulation, and rare activating mutations.3 Virilizing, K' t; O+ |8 u# j! a( w, O
congenital adrenal hyperplasia producing excessive
3 I4 x3 U: k2 J2 |adrenal androgens is a common cause of precocious
3 x, C7 O# v: ^: `0 t6 J& h/ hpuberty in boys.3,4$ G8 [- f! j6 {3 z! P: G
The most common form of congenital adrenal& I8 L. @7 o/ l: G7 j6 ?$ t6 j
hyperplasia is the 21-hydroxylase enzyme deficiency.1 P- u" R/ U( F- N. A% ?
The 11-β hydroxylase deficiency may also result in
1 @: [3 r a* f9 {1 a. W: C& Yexcessive adrenal androgen production, and rarely,( m3 Z6 C0 u' r1 O1 C' `. I
an adrenal tumor may also cause adrenal androgen
" P9 J% D7 b# y: w) G0 @, iexcess.1,3! A- z2 W/ {! | O" I8 l i, f+ q
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from9 q" j- d7 j8 J$ q3 y5 k- L8 D
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
: Q1 l8 c, F t1 T& A; F4 YA unique entity of male-limited gonadotropin-
" o" G8 s; {8 Vindependent precocious puberty, which is also known
9 N1 c! |! b- q' |( y3 Cas testotoxicosis, may cause precocious puberty at a7 L# D; K! `& m
very young age. The physical findings in these boys; e9 X" E* T' U7 g4 d& b
with this disorder are full pubertal development,4 P0 ~2 V" J2 J% v
including bilateral testicular growth, similar to boys
' x& N+ v6 o3 ?with CPP. The gonadotropin levels in this disorder i6 |0 s( ^" |$ w7 x
are suppressed to prepubertal levels and do not show
' W( v# ~0 N( G* @4 ~7 r1 A1 dpubertal response of gonadotropin after gonadotropin-
( Z3 h- {2 R0 t( ~) P: l7 Creleasing hormone stimulation. This is a sex-linked
1 m' ~9 x5 F2 F [# N: Yautosomal dominant disorder that affects only
: Z/ ^4 W" n4 ?: b, r5 imales; therefore, other male members of the family
' w) m0 [& Q2 `1 ] r) c5 Q9 Zmay have similar precocious puberty.3
6 J' p& A( A6 [! `1 aIn our patient, physical examination was incon-% {. a. G w- n/ b
sistent with true precocious puberty since his testi-$ H+ s$ b. S2 \1 p' U9 w
cles were prepubertal in size. However, testotoxicosis, s% y; K/ e2 N5 }' m* [8 @
was in the differential diagnosis because his father1 e9 V+ k4 o9 [* r7 o7 S
started puberty somewhat early, and occasionally,
" r+ e+ S0 k. D* a! etesticular enlargement is not that evident in the
" j4 g! b! Y9 z1 @7 Rbeginning of this process.1 In the absence of a neg-
0 Z! }# {" b3 @/ C7 Qative initial history of androgen exposure, our
1 D- w# w5 e; b" ]) h1 F# Obiggest concern was virilizing adrenal hyperplasia,
' S7 e/ r$ O W, e; v3 L4 y. weither 21-hydroxylase deficiency or 11-β hydroxylase
9 E; Y! S& S* Wdeficiency. Those diagnoses were excluded by find-
- L/ Y0 L1 g: ding the normal level of adrenal steroids.4 z7 H% `. D s6 |* p
The diagnosis of exogenous androgens was strongly
( H8 r0 h* O& o: h2 R9 }suspected in a follow-up visit after 4 months because) C: [' A3 l" h
the physical examination revealed the complete disap-
% u6 S7 Z0 s2 B) tpearance of pubic hair, normal growth velocity, and
; H& e4 O: b' [! [* Rdecreased erections. The father admitted using a testos-
9 V9 j/ N- |4 t! O: {5 Kterone gel, which he concealed at first visit. He was
, K+ ~8 P7 h6 Z' xusing it rather frequently, twice a day. The Physicians’
* t u* ?( z# W3 |" |' iDesk Reference, or package insert of this product, gel or
# b! v4 p: M7 ucream, cautions about dermal testosterone transfer to
2 Y# {3 o) e5 Lunprotected females through direct skin exposure.7 C1 O @0 ^, ?0 j$ b1 n
Serum testosterone level was found to be 2 times the# L& i! `# y+ m
baseline value in those females who were exposed to& Y: ~- D* L2 F+ V" {
even 15 minutes of direct skin contact with their male
# _. E6 ~% z1 Hpartners.6 However, when a shirt covered the applica-9 M( Y- F- s% X9 F) o S4 y' [
tion site, this testosterone transfer was prevented.3 `3 S4 M- Y+ O6 A2 j* ^
Our patient’s testosterone level was 60 ng/mL,
. E; Z* K6 K* @4 swhich was clearly high. Some studies suggest that
: }, o! ~- k5 z/ Z) e% g* vdermal conversion of testosterone to dihydrotestos-, j$ ^+ N( C' k1 i( L% u+ V1 n
terone, which is a more potent metabolite, is more
* V5 @, N6 r9 g- h4 K+ c) W1 D) kactive in young children exposed to testosterone
+ V/ c5 m Z9 l. _/ xexogenously7; however, we did not measure a dihy-
i/ l" u7 u+ e2 ^; Q Adrotestosterone level in our patient. In addition to
) }0 ^1 W1 \6 @) c0 l7 V' D$ i1 yvirilization, exposure to exogenous testosterone in; z7 P: E& D( ^
children results in an increase in growth velocity and
2 |2 N! P) H: o _: uadvanced bone age, as seen in our patient.5 D7 E b$ ?1 a. j J" h7 K
The long-term effect of androgen exposure during
7 U3 _4 L$ }; m/ k, r- Fearly childhood on pubertal development and final
2 l) K5 I6 M. O1 o' w# Q) o1 hadult height are not fully known and always remain, Y6 C" R8 x$ O: S# H0 l
a concern. Children treated with short-term testos-: B* u5 `: h; U/ X7 |
terone injection or topical androgen may exhibit some$ [1 X' Q0 L! F% a, [& b5 E
acceleration of the skeletal maturation; however, after
8 R2 s8 ~6 B4 n8 @cessation of treatment, the rate of bone maturation3 A/ Z% _) A4 ?2 c
decelerates and gradually returns to normal.8,9
7 z% i# S6 i$ [There are conflicting reports and controversy
Z. n9 A- A( a# F mover the effect of early androgen exposure on adult
/ k# ]4 l4 X# ~% v1 K' x9 K) k- Lpenile length.10,11 Some reports suggest subnormal
; V0 e: ~, N @6 ]4 b4 Hadult penile length, apparently because of downreg-( {+ ?1 k6 n$ A% N+ @, \. D
ulation of androgen receptor number.10,12 However,
2 Y$ b: r% x ZSutherland et al13 did not find a correlation between
) W5 T2 ~* j; Y, N% Mchildhood testosterone exposure and reduced adult
9 ^' l& c. f9 ^; _7 k3 upenile length in clinical studies.( C2 w+ X# f7 }# I' S; u
Nonetheless, we do not believe our patient is
# d- }' I' P; ?going to experience any of the untoward effects from
# [1 w, J$ H2 g, ytestosterone exposure as mentioned earlier because, ~; e \- d F% R! w% w$ o
the exposure was not for a prolonged period of time.# c# J3 y4 M J* R3 \6 u
Although the bone age was advanced at the time of
* ^ s5 f/ `0 D7 W# a! wdiagnosis, the child had a normal growth velocity at
9 K! P# S( ^& ?' B2 S, l2 i, Ythe follow-up visit. It is hoped that his final adult1 J d! w" @ {/ m
height will not be affected.% N3 }: h) k$ Q" n
Although rarely reported, the widespread avail-
: _3 B+ w0 O. kability of androgen products in our society may
Y# ^9 w# d4 C; N3 y! w- }indeed cause more virilization in male or female" r9 `; X. T' r" V. l
children than one would realize. Exposure to andro-9 J |3 p1 x2 n/ ]" F0 x7 m7 p
gen products must be considered and specific ques-
" ?8 m$ q8 N. L* jtioning about the use of a testosterone product or
' M1 y! l8 K Z. ~* G1 c4 l/ igel should be asked of the family members during# Z1 W0 J T* X9 E# Z( z7 H0 D
the evaluation of any children who present with vir-$ G: ]& ~) g0 `- b$ x% z( y" d
ilization or peripheral precocious puberty. The diag-# e2 o: V0 x' Y( g2 |" |; u
nosis can be established by just a few tests and by
5 F' e. D) O1 O& {) a3 Wappropriate history. The inability to obtain such a
! }/ `( s, Z7 w: F* ~" ]( r7 f# Chistory, or failure to ask the specific questions, may
4 [6 t C4 t7 h G: Lresult in extensive, unnecessary, and expensive; p# ^" g ]5 i4 `, j
investigation. The primary care physician should be
" z0 c( @, I1 P( Q! s h( Jaware of this fact, because most of these children/ U4 ?, V4 ]4 S8 ?8 y' z
may initially present in their practice. The Physicians’
2 D- J d& L2 A- @: ?Desk Reference and package insert should also put a
/ u8 l! f( K' Iwarning about the virilizing effect on a male or
4 M9 ? u9 \7 ~/ T2 o0 ^. C6 g1 h% s1 Cfemale child who might come in contact with some-$ ^! H0 B" W6 G. d, O- j
one using any of these products.5 @/ F7 J* C) S! Y9 b
References) B1 \; E# m5 j0 A" E% L; [
1. Styne DM. The testes: disorder of sexual differentiation2 ~7 w6 ~; m, T9 e8 p2 n
and puberty in the male. In: Sperling MA, ed. Pediatric
& J; O% j7 i/ F0 n, X. q; u4 ~Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
$ e! K* o; d! m2002: 565-628.$ `. v3 G' r% d
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
/ C/ W6 O K$ O4 Spuberty in children with tumours of the suprasellar pineal |
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