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Sexual Precocity in a 16-Month-Old
. G, h* c# T, _' h' s: e7 oBoy Induced by Indirect Topical
1 B) N' b' N2 h* oExposure to Testosterone* l" Y7 r% t- m( c: x: X$ @9 }! @: e
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
8 m& L* v) [( f& [- V4 s( }$ Kand Kenneth R. Rettig, MD1
* u) n" {7 T0 ~# Y# pClinical Pediatrics* i% B4 M" S* |% y
Volume 46 Number 6
9 M9 b( {) o d0 c9 ^0 ^2 ]1 \9 XJuly 2007 540-543: q: v b! t4 F# H
© 2007 Sage Publications, F1 d' B2 Y9 m* E3 c! ~
10.1177/0009922806296651+ E5 f- ^! \9 v
http://clp.sagepub.com
/ V# t" o1 { X% Whosted at
0 a) k. ^! ?, Z- G8 s4 T: b5 ahttp://online.sagepub.com
" ]# j! }; ^% J qPrecocious puberty in boys, central or peripheral,
# g3 S$ k7 Z. D0 F. S* x9 Kis a significant concern for physicians. Central
; a4 |+ j( }: f; K2 e# X! L0 Zprecocious puberty (CPP), which is mediated
% b' Z0 h: w& M& K2 K$ B# Pthrough the hypothalamic pituitary gonadal axis, has
! R9 y$ i+ J# ]2 R! Oa higher incidence of organic central nervous system, | k4 i; j ^
lesions in boys.1,2 Virilization in boys, as manifested0 t# j( }5 C, A) U! a9 |" Q
by enlargement of the penis, development of pubic: [( q0 {/ Y7 U) V/ Q3 O; L
hair, and facial acne without enlargement of testi-
* H0 ~' C$ B- H! Wcles, suggests peripheral or pseudopuberty.1-3 We9 l9 b3 T, P2 O$ Y; M) h7 n
report a 16-month-old boy who presented with the( E3 D; {8 g# d G& }% Y
enlargement of the phallus and pubic hair develop-7 H, G$ Y) k1 ?% s
ment without testicular enlargement, which was due
1 Q1 c! b' @4 [! Mto the unintentional exposure to androgen gel used by
: G; F2 V6 ~$ _/ I- d1 Ethe father. The family initially concealed this infor-
, Q: b0 e3 h0 h8 X: z! smation, resulting in an extensive work-up for this
' l0 R/ u! T! _4 K- U: bchild. Given the widespread and easy availability of
- T2 g, u7 W6 [1 Atestosterone gel and cream, we believe this is proba-3 ~# Z4 m* v' t7 r; Z6 ` K
bly more common than the rare case report in the
* z- U2 h8 ]9 u7 o2 Y6 r: u* J. _literature.4# d* |# ?& r" f }8 S A/ p
Patient Report N# n/ E3 s9 G3 P
A 16-month-old white child was referred to the' W7 L6 N; M/ B6 w7 E
endocrine clinic by his pediatrician with the concern
0 f5 i, \- C% o Fof early sexual development. His mother noticed
, t1 m+ e- h! X2 P3 S; E! s, Clight colored pubic hair development when he was
% X8 x+ r, T) e0 v, u2 XFrom the 1Division of Pediatric Endocrinology, 2University of1 w$ p- @4 Q q
South Alabama Medical Center, Mobile, Alabama." T" J5 k2 [1 L" {1 Q
Address correspondence to: Samar K. Bhowmick, MD, FACE,# y3 p: z n4 c9 _2 ]) p' O/ |8 f2 q
Professor of Pediatrics, University of South Alabama, College of
+ [3 v# r2 x; MMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;% t! Q7 J% o% `% y' L; ]
e-mail: [email protected].) u, V) {! x* i8 B
about 6 to 7 months old, which progressively became j4 Q; _( N* C
darker. She was also concerned about the enlarge-4 X. m9 [5 M* ]3 F$ h' T
ment of his penis and frequent erections. The child
8 f0 t6 i/ R4 {9 m6 C6 T/ Mwas the product of a full-term normal delivery, with
, l1 J: M- m G5 Oa birth weight of 7 lb 14 oz, and birth length of
* ^( H) ]. K4 v4 {; Y20 inches. He was breast-fed throughout the first year
) b6 I; Z0 g% |' Lof life and was still receiving breast milk along with2 j8 H* t/ X* d- O1 F
solid food. He had no hospitalizations or surgery,. K5 E! X6 l' [3 Z" G; v
and his psychosocial and psychomotor development9 P, F- i B6 N+ |, i
was age appropriate.0 ~* K2 m4 M8 ]
The family history was remarkable for the father,
- Q: j. ?. z2 ?4 P1 fwho was diagnosed with hypothyroidism at age 16,. S: D+ S' E* c
which was treated with thyroxine. The father’s
, F: J. K0 F6 I2 H* \7 Sheight was 6 feet, and he went through a somewhat
# L- M& |; L1 R P5 iearly puberty and had stopped growing by age 14.
9 S0 [1 S2 ?4 L# U1 jThe father denied taking any other medication. The
5 h. _ T9 U7 a3 s( O( k. V \child’s mother was in good health. Her menarche7 ~ [( J! _: c: L
was at 11 years of age, and her height was at 5 feet- K7 [2 u. N/ u& `
5 inches. There was no other family history of pre-
$ d* F) @ Z. U. I$ f& K Jcocious sexual development in the first-degree rela-
6 i1 j- }' n- b% \- Q% a6 Atives. There were no siblings. Y4 c, y2 Y3 v* o% w
Physical Examination; H0 b9 t5 J, `, z8 a
The physical examination revealed a very active,! m/ D9 N: d$ H! }7 D
playful, and healthy boy. The vital signs documented! K% z8 D: m J! S, P) ]
a blood pressure of 85/50 mm Hg, his length was/ @, v7 X) E% ]8 a( Y$ S1 h/ h
90 cm (>97th percentile), and his weight was 14.4 kg
( i# X6 N$ j! v/ w0 B5 \(also >97th percentile). The observed yearly growth
+ S0 X1 h9 e0 K* f, nvelocity was 30 cm (12 inches). The examination of: S/ L! u9 i/ [
the neck revealed no thyroid enlargement.
5 D3 w9 R: P% B, G7 F$ a+ A; IThe genitourinary examination was remarkable for
4 W& j5 h3 y* Uenlargement of the penis, with a stretched length of( {! M7 ]$ `' ^" u6 [1 D- _+ ?2 l3 M
8 cm and a width of 2 cm. The glans penis was very well1 h! F, s/ _" _9 B. D R/ p3 E. f
developed. The pubic hair was Tanner II, mostly around
" v# I6 W' g/ `. h) O540
" p. @$ ?% L4 k7 [7 w* Sat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from' }; u: P$ U+ Y# L: J5 j0 l
the base of the phallus and was dark and curled. The
0 i N. S/ ^% ?( D! f% dtesticular volume was prepubertal at 2 mL each.& l5 C$ m6 l& _% o I$ L) v
The skin was moist and smooth and somewhat
2 Q' C5 _: L* ooily. No axillary hair was noted. There were no
/ ~- G( F3 O/ G) [/ Q% iabnormal skin pigmentations or café-au-lait spots.! ^% J8 M$ I2 C
Neurologic evaluation showed deep tendon reflex 2+. X: F- @$ z9 `2 Z G
bilateral and symmetrical. There was no suggestion
- s6 ?1 B& Q5 [3 ^# {; pof papilledema.# l) Z; P; }& F8 K% p8 s
Laboratory Evaluation
! \: Y. S3 I* KThe bone age was consistent with 28 months by
- P6 P" z# ]9 D1 \2 ~" r" zusing the standard of Greulich and Pyle at a chrono-
! D5 k8 S6 B/ E, f% @9 Elogic age of 16 months (advanced).5 Chromosomal
6 A5 }- D, \/ d1 z; _8 `* n. S; xkaryotype was 46XY. The thyroid function test
, ~* \( @, d9 F9 lshowed a free T4 of 1.69 ng/dL, and thyroid stimu-3 C, ~" E5 T2 J- g' e* w+ F
lating hormone level was 1.3 µIU/mL (both normal).* i X4 \9 h8 V3 o* f1 Y
The concentrations of serum electrolytes, blood6 }& |$ O) {( c j0 v; Z
urea nitrogen, creatinine, and calcium all were
~: t; s- l1 W5 ^& U/ Ewithin normal range for his age. The concentration3 m1 |9 F' ^4 P4 O
of serum 17-hydroxyprogesterone was 16 ng/dL {" R7 ?" H! T; A6 X1 t
(normal, 3 to 90 ng/dL), androstenedione was 20
" E5 d1 J9 n" L. l8 L# V! d" ~. Ing/dL (normal, 18 to 80 ng/dL), dehydroepiandros-! S6 i0 z, L- _# g$ C
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
( {( G8 \8 m4 x1 M* m& edesoxycorticosterone was 4.3 ng/dL (normal, 7 to
h; m! P% `! y1 C) L49ng/dL), 11-desoxycortisol (specific compound S)
* Y5 w6 u) D6 [1 H4 j3 ~& iwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
7 J4 q j* N1 I9 u" x( ktisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
! f2 ]' B1 b- n2 z Y/ [' [' Mtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),: r& H! k7 y* ?7 k8 n' k
and β-human chorionic gonadotropin was less than/ O& _5 R1 P6 v* N" J' M! r
5 mIU/mL (normal <5 mIU/mL). Serum follicular/ K- t/ Y- v) E
stimulating hormone and leuteinizing hormone
+ Q" `6 c. [! yconcentrations were less than 0.05 mIU/mL
1 F4 U3 R3 r( X" i# ]0 O% f(prepubertal).+ `7 s# c3 S% Y" E6 e# o z
The parents were notified about the laboratory" ?/ m. {+ y& p# j* a- M
results and were informed that all of the tests were" ^# H. H3 L' W g
normal except the testosterone level was high. The
/ O) d& t2 j2 D6 ?( p" ifollow-up visit was arranged within a few weeks to- R2 L" D3 O2 l) m! \4 u+ `
obtain testicular and abdominal sonograms; how-
! V& y9 O5 Q1 D0 N7 a: vever, the family did not return for 4 months.9 f6 C$ P( b5 g9 V6 l
Physical examination at this time revealed that the+ X. d+ c; \# h& h6 x, g+ C
child had grown 2.5 cm in 4 months and had gained: l* r: k) d# T
2 kg of weight. Physical examination remained
: x6 y! |: D& S- Y, nunchanged. Surprisingly, the pubic hair almost com-
* T2 B) [8 `4 n% _7 \ Kpletely disappeared except for a few vellous hairs at; h! G7 [" R% S) L, b
the base of the phallus. Testicular volume was still 2
1 M8 B/ M$ G) u# J# \mL, and the size of the penis remained unchanged.8 q( T/ j+ v3 E0 t/ g3 x1 K
The mother also said that the boy was no longer hav-
. S: c. `$ Y+ h. cing frequent erections.
$ h M9 x7 [& dBoth parents were again questioned about use of
3 \" m6 }' ?( J# Sany ointment/creams that they may have applied to9 i! k7 M; }) t' x
the child’s skin. This time the father admitted the
' E! `' [/ l0 h2 a/ c KTopical Testosterone Exposure / Bhowmick et al 541
7 G, X; {; I% m: Uuse of testosterone gel twice daily that he was apply-
4 N" a. T; u. {4 U8 ping over his own shoulders, chest, and back area for
& g) W: t1 {( m2 ?6 L4 ca year. The father also revealed he was embarrassed
F$ c! r4 j+ o, }2 _' P! A( bto disclose that he was using a testosterone gel pre-" v' C x+ \% P8 {
scribed by his family physician for decreased libido& @4 I6 r+ f! z/ M
secondary to depression.
. x }* L4 w- @1 i' C2 `The child slept in the same bed with parents.- w# ]- W. M# t W* F& Y9 O K
The father would hug the baby and hold him on his
$ D7 t! V1 M( d9 Q7 }/ ~" Z3 ?chest for a considerable period of time, causing sig-3 S2 M* \. O- @& \8 z" Z
nificant bare skin contact between baby and father.+ Z6 a, I) G2 L# Q8 ~% I
The father also admitted that after the phone call,
, a; i( D6 Z8 Z: F4 t9 S8 e- p& Nwhen he learned the testosterone level in the baby- z9 u) @1 Y) Z; @& S+ x
was high, he then read the product information
. |* n; h E; f/ q% e+ M3 |# rpacket and concluded that it was most likely the rea-
5 v2 u; v1 N( e$ u) Y8 `( ^son for the child’s virilization. At that time, they: D/ `# Q+ a; E3 r! }# U
decided to put the baby in a separate bed, and the8 M/ Q$ `! K6 O2 B0 v8 C
father was not hugging him with bare skin and had
0 ~% A2 ~& n& X: a1 v( z! xbeen using protective clothing. A repeat testosterone- k: O& i4 D/ p+ o' r; Y. o
test was ordered, but the family did not go to the
& L& N5 h( d, D& Glaboratory to obtain the test.
. v5 A. K, p, ~Discussion; B9 N$ i, ^' I7 u- r6 b
Precocious puberty in boys is defined as secondary* M( ^ N* r( C7 C& }: L
sexual development before 9 years of age.1,42 _. n$ l+ ?5 F9 {1 S
Precocious puberty is termed as central (true) when
8 v8 z) K% M" h" _it is caused by the premature activation of hypo-
+ e3 C# K5 ^$ D- Rthalamic pituitary gonadal axis. CPP is more com-
! t: E' U* L8 u1 ^. I& x: kmon in girls than in boys.1,3 Most boys with CPP5 j ~) Q$ z8 |. C. r1 q: V' \: G
may have a central nervous system lesion that is
2 N3 r' x6 ~+ F/ a! ^5 `responsible for the early activation of the hypothal-. C5 W" h5 S; N X2 H- c% V" x
amic pituitary gonadal axis.1-3 Thus, greater empha-; M e, v( M0 {$ ~" t1 I
sis has been given to neuroradiologic imaging in# Z5 u" [0 d# T& g
boys with precocious puberty. In addition to viril-) I5 f p) ?" ~6 B6 t
ization, the clinical hallmark of CPP is the symmet-. @) V, p! j8 i, X s* w; a& n
rical testicular growth secondary to stimulation by6 O# A8 I6 W% r. P9 T* J. p
gonadotropins.1,36 r& ~, Z+ f3 Y4 U: d
Gonadotropin-independent peripheral preco-# o4 { e- b! A [5 [
cious puberty in boys also results from inappropriate
, p9 f, w' w+ r7 H- `; ~+ O, _* @androgenic stimulation from either endogenous or% P0 C+ h$ W7 w6 r# k
exogenous sources, nonpituitary gonadotropin stim-6 v$ ^7 x. U! \$ t# y
ulation, and rare activating mutations.3 Virilizing A- E7 S0 D+ k) {
congenital adrenal hyperplasia producing excessive
8 E% @$ q/ E& z+ u- [- tadrenal androgens is a common cause of precocious
' ^3 |3 B; v: e4 b$ g Epuberty in boys.3,4' F1 s+ i \0 i, ^, L
The most common form of congenital adrenal
2 p6 Y0 ?: g" g! e1 S) H' ehyperplasia is the 21-hydroxylase enzyme deficiency.6 Z( c! e8 ^/ w/ g8 n9 m8 w; X
The 11-β hydroxylase deficiency may also result in
0 M+ ~3 i& A0 m, |7 z) X* \excessive adrenal androgen production, and rarely,' b/ N' q8 n: Z( G, Q
an adrenal tumor may also cause adrenal androgen
$ v7 v, e1 U' P# X8 oexcess.1,3
% k+ R' }" H* E) x0 Eat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from' t- h4 G" d! T7 [& c: J
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
3 x J& S0 \8 j: U# _/ u2 xA unique entity of male-limited gonadotropin-8 G$ [4 R- H2 _
independent precocious puberty, which is also known( ~# O8 V5 F- N5 B. G* @
as testotoxicosis, may cause precocious puberty at a# D7 Z; Y$ a; g1 A& Z. X% _
very young age. The physical findings in these boys
+ X5 s. J( B; ~6 gwith this disorder are full pubertal development,4 U: [% W' m% D! S5 @
including bilateral testicular growth, similar to boys
2 D1 D8 Z/ F. q7 O- Bwith CPP. The gonadotropin levels in this disorder4 Y* r" s; ]+ l n* E R; V
are suppressed to prepubertal levels and do not show
+ j$ P+ u/ H& ^pubertal response of gonadotropin after gonadotropin-( I( H) B- w% |; o: Q8 T
releasing hormone stimulation. This is a sex-linked2 K$ M% t' ?- j9 x2 g
autosomal dominant disorder that affects only
: r, a4 N# ~- N( ^6 ?males; therefore, other male members of the family( z/ h$ ?9 j1 h* r v0 c
may have similar precocious puberty.3
8 E) \& ?7 S! x" M( N) nIn our patient, physical examination was incon-8 I. {+ M3 Q3 a- S7 F Y
sistent with true precocious puberty since his testi-
* _, ^4 O9 f" F3 p; [, ]4 \cles were prepubertal in size. However, testotoxicosis5 W# r5 o' W% u, S
was in the differential diagnosis because his father) E& H' p/ Q+ _# c. q
started puberty somewhat early, and occasionally,; l; L: W) a- a: A
testicular enlargement is not that evident in the7 ?2 z) b& R. a# ^- m! ~
beginning of this process.1 In the absence of a neg-
& x8 ?3 H U1 K: pative initial history of androgen exposure, our
) J5 E! U1 m1 s( Ibiggest concern was virilizing adrenal hyperplasia,) I. f; U2 v" ~! Y7 p6 x+ z
either 21-hydroxylase deficiency or 11-β hydroxylase, R: ^/ q& e' ]' x% J: V8 O) B% _' Q
deficiency. Those diagnoses were excluded by find-
- b; t9 C3 u# P( }7 sing the normal level of adrenal steroids.6 i, e9 D' P4 i2 s7 e
The diagnosis of exogenous androgens was strongly
! N* n' I9 a+ V- M; @2 vsuspected in a follow-up visit after 4 months because9 E K* L% p! ?3 j
the physical examination revealed the complete disap-
% x: v$ [& l* S5 K/ k3 tpearance of pubic hair, normal growth velocity, and
, e9 q% x: p9 u! p+ W0 {; gdecreased erections. The father admitted using a testos-
$ ]% N; i- b+ M0 Q7 c2 Lterone gel, which he concealed at first visit. He was# ]! n* J u; Z% b
using it rather frequently, twice a day. The Physicians’
7 j0 S1 l! [; D- d' {6 ]* B1 |4 v) IDesk Reference, or package insert of this product, gel or2 _5 b7 B" t& e" j# U
cream, cautions about dermal testosterone transfer to9 T5 C1 R6 l2 N0 A6 n
unprotected females through direct skin exposure.
N/ h& e6 w5 e, E' H! fSerum testosterone level was found to be 2 times the) K1 r1 ^% F* ^
baseline value in those females who were exposed to4 O" {( e. Y4 c! O
even 15 minutes of direct skin contact with their male6 g% C/ B* ~3 i+ a3 q6 l+ W
partners.6 However, when a shirt covered the applica-0 E" B ^9 ?) p$ ?3 t6 _% Z
tion site, this testosterone transfer was prevented.
# D. b% t8 {) l! v, U! kOur patient’s testosterone level was 60 ng/mL,
% n' G% m5 N+ x {8 ]which was clearly high. Some studies suggest that
, n ?8 u* s) i6 k2 C5 \5 h- X% A. [dermal conversion of testosterone to dihydrotestos-" o- f% X* K% d" x4 J/ D' q
terone, which is a more potent metabolite, is more
1 r: V# }' p; c. `6 h1 Bactive in young children exposed to testosterone
& q7 t2 Q! z3 ~ ], r" W5 Zexogenously7; however, we did not measure a dihy-( Z& A9 ]5 Y* H7 O
drotestosterone level in our patient. In addition to
: G0 r6 z; q+ _% @virilization, exposure to exogenous testosterone in! ~0 y" x6 ]( T
children results in an increase in growth velocity and, Y7 @( c1 v& C+ i+ p
advanced bone age, as seen in our patient.
6 X1 v* o) X9 m3 K) _The long-term effect of androgen exposure during ~. b4 {4 b4 [% C& y4 [* b4 v
early childhood on pubertal development and final2 D. E- e7 l3 J, \9 C5 \( m0 A
adult height are not fully known and always remain. }" I& h4 Q; c0 M1 ~7 @
a concern. Children treated with short-term testos-
6 [) H& O& K5 ]1 |terone injection or topical androgen may exhibit some
! x: d5 y- K/ Y% M6 `- M: `6 [acceleration of the skeletal maturation; however, after
6 e& V# ?: c: Bcessation of treatment, the rate of bone maturation
' n: g9 ^" ]* ~' @: Z. j, vdecelerates and gradually returns to normal.8,9
& s# C; ?, \, T5 [. q' HThere are conflicting reports and controversy
# W# Q P7 `( Iover the effect of early androgen exposure on adult! n+ C1 t3 H" S8 U ~: k9 A
penile length.10,11 Some reports suggest subnormal" D3 y9 V8 J4 r7 E5 b' E i
adult penile length, apparently because of downreg-) |+ G6 s: I+ f' E) o% T
ulation of androgen receptor number.10,12 However,$ } _8 v% v: u- G( W1 H
Sutherland et al13 did not find a correlation between0 C7 t7 W' c& b8 O
childhood testosterone exposure and reduced adult# [( }# Z$ `; K' W, o4 `! Q" A" E
penile length in clinical studies.
3 p8 X4 b% f7 vNonetheless, we do not believe our patient is
# w9 @7 z6 n p) u! R/ z( y3 mgoing to experience any of the untoward effects from
7 L) `+ ` ]+ c3 h9 ?+ ntestosterone exposure as mentioned earlier because
; ?! @$ M8 {' Y5 k8 Y$ q' g! zthe exposure was not for a prolonged period of time.) i2 Q c1 |/ J- B% H/ J
Although the bone age was advanced at the time of
2 U. Z" P/ W' W0 I; d; b& Z5 m. bdiagnosis, the child had a normal growth velocity at
4 `$ ]7 M" w* N/ q4 v6 F/ P! ?the follow-up visit. It is hoped that his final adult" i A$ ?8 G5 P/ K. C/ u
height will not be affected.
/ u( ]: r4 }( C8 F' UAlthough rarely reported, the widespread avail-
' Q) N+ H4 u0 m5 H) y( ^. L9 z& nability of androgen products in our society may
6 J e8 @# w; ^! z# Oindeed cause more virilization in male or female5 U2 z# |' f# I" |( a% L. t
children than one would realize. Exposure to andro-
+ |/ ? O6 ^% {/ Y) [1 Xgen products must be considered and specific ques-( K% u4 T1 w* L6 V z" L
tioning about the use of a testosterone product or
6 T4 W- I c) n8 H7 O% ]gel should be asked of the family members during: `* K; s4 E! H9 R, X; k* \
the evaluation of any children who present with vir-: p* q! `6 i" P: f
ilization or peripheral precocious puberty. The diag-
1 M; W0 C5 @) b% mnosis can be established by just a few tests and by
7 r2 z5 P5 ~$ y+ G# }" l7 d3 S0 b2 nappropriate history. The inability to obtain such a
- e# a3 X( U! T: ], ~" x0 j2 ^6 dhistory, or failure to ask the specific questions, may: ^- M. M) K5 a% S
result in extensive, unnecessary, and expensive
( |/ ~2 I, e6 g# N1 v: L& Qinvestigation. The primary care physician should be
6 G. a; i4 ]4 Uaware of this fact, because most of these children, Y) b: l J7 O/ j
may initially present in their practice. The Physicians’- X8 z6 D. \/ H/ w; ~1 a) q1 \4 I
Desk Reference and package insert should also put a
4 R0 ^& p! [& c- nwarning about the virilizing effect on a male or
4 W5 W4 C* ]! ofemale child who might come in contact with some-
1 R: o" ]) z. ^! @6 l6 Kone using any of these products.
: T0 e8 B$ B2 i: n qReferences$ R+ r4 ?- o i3 m* Q1 `
1. Styne DM. The testes: disorder of sexual differentiation
" n, l7 \* ~: j0 R: iand puberty in the male. In: Sperling MA, ed. Pediatric
$ `% c7 g( {) j; o, G! WEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
- v% M9 P! j% ~2002: 565-628.5 ]# @* `" L+ _4 M
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
- e; l* S) d' L. Z; n# `puberty in children with tumours of the suprasellar pineal |
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