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Sexual Precocity in a 16-Month-Old0 T+ O2 m1 ~" G2 c+ R2 L
Boy Induced by Indirect Topical
3 k# A+ R U' S/ LExposure to Testosterone+ V. T- O, n: E" Z' o( E
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,28 B. p' k X+ t( k9 Q- v [
and Kenneth R. Rettig, MD17 O# F0 a w2 f2 G( X
Clinical Pediatrics
( m- n; u, D- s+ `Volume 46 Number 6
9 `/ |; f4 \- Q( p. l- D( }July 2007 540-543/ J! @1 R. y; L8 K
© 2007 Sage Publications
; s/ s# w8 n8 ?) r+ X10.1177/00099228062966510 O2 B5 W2 T5 u) t2 F) ]
http://clp.sagepub.com
$ H B: M9 L1 r- K; G7 V2 Whosted at
( t# Q: P" w5 R7 D0 r- ghttp://online.sagepub.com6 H* V8 y+ U7 @# o) D ~* [
Precocious puberty in boys, central or peripheral,0 {: k" p) S, ]7 a% G
is a significant concern for physicians. Central, \0 \, Q+ k- y
precocious puberty (CPP), which is mediated% I# s$ V8 ?1 P* B9 \5 Q0 a/ `
through the hypothalamic pituitary gonadal axis, has% N& x- [. Q s- Y. M
a higher incidence of organic central nervous system; o% M: V" k1 y9 H
lesions in boys.1,2 Virilization in boys, as manifested
) Z* o" r% i) f$ ~. o7 }; V/ gby enlargement of the penis, development of pubic! ^& z, U1 O9 ?1 n
hair, and facial acne without enlargement of testi-7 o) h- N' H }' @
cles, suggests peripheral or pseudopuberty.1-3 We
; F8 C6 o2 L, h2 p' treport a 16-month-old boy who presented with the, K @3 v1 F3 {4 p0 P( H' `
enlargement of the phallus and pubic hair develop-" a7 F, |+ G% u& L3 q7 M
ment without testicular enlargement, which was due7 S; t5 N$ j5 I+ L' p, v
to the unintentional exposure to androgen gel used by
& s/ g& ^( L$ D" kthe father. The family initially concealed this infor-
+ h4 D; ?4 T! s, omation, resulting in an extensive work-up for this# f2 I. H: p5 V4 [8 ^, O
child. Given the widespread and easy availability of
4 ~5 i; A2 X7 q; f5 htestosterone gel and cream, we believe this is proba-
$ G" H# s3 e v, f [' }( Fbly more common than the rare case report in the" K0 Y' \* F7 a9 h( ]% L
literature.4
9 ~( u7 a; z' R& H$ B4 pPatient Report, Y3 ?; g9 J6 Z7 ^/ B. `
A 16-month-old white child was referred to the
. T8 C& o, H" K' c8 Xendocrine clinic by his pediatrician with the concern
4 ?9 L' `$ [( d2 g; a% T$ G7 Bof early sexual development. His mother noticed4 L5 G- P" N% ~8 O4 R) ~- D! Y# O
light colored pubic hair development when he was+ S. I' k# T5 R/ }. h% f8 D+ C y5 k
From the 1Division of Pediatric Endocrinology, 2University of0 s, G; |# \. Y
South Alabama Medical Center, Mobile, Alabama.
" Z7 t# D8 K$ J% v# ?. LAddress correspondence to: Samar K. Bhowmick, MD, FACE,2 n8 i6 i1 H; G$ p& t3 `* {
Professor of Pediatrics, University of South Alabama, College of
7 Q+ k$ N! Y% w( `; D) s2 p6 UMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;$ n0 J6 l$ c* y' l& _
e-mail: [email protected].6 U! A8 Q" a% u/ l
about 6 to 7 months old, which progressively became n! J. y O8 T
darker. She was also concerned about the enlarge-+ Z9 ^1 m/ u& ^
ment of his penis and frequent erections. The child
) } |0 O5 n# C6 U& B! rwas the product of a full-term normal delivery, with1 p& _& s6 ?/ _' \: b( {, s6 u
a birth weight of 7 lb 14 oz, and birth length of
$ X: Y: ~* M) H% ?( ~20 inches. He was breast-fed throughout the first year3 d) B& K; v' a2 g5 B+ n
of life and was still receiving breast milk along with! p5 T7 k( j- Z) g( s9 H6 o
solid food. He had no hospitalizations or surgery,3 _2 Z* i2 f8 D6 O9 k1 G# F
and his psychosocial and psychomotor development
& P; u, q9 A5 j! k0 w& \was age appropriate.
+ m4 b- E! {2 g& xThe family history was remarkable for the father,
9 Y& g, u3 K7 Y. q$ fwho was diagnosed with hypothyroidism at age 16,4 C1 E: M* |7 w$ Z* U3 J" O2 K
which was treated with thyroxine. The father’s
6 C7 I' a) ~- wheight was 6 feet, and he went through a somewhat) \. z2 G: J* f9 V) Q8 V, G$ t, R$ c
early puberty and had stopped growing by age 14.$ Z/ U& f! h; v7 {. x
The father denied taking any other medication. The' _. H' D3 ~* p# F
child’s mother was in good health. Her menarche
- Y4 X4 X1 D2 N+ [8 vwas at 11 years of age, and her height was at 5 feet
# u. |9 B" X2 i! `; u- x+ A5 inches. There was no other family history of pre-% c1 n3 h5 E T4 u X$ A
cocious sexual development in the first-degree rela-' H" {) U: ~5 r3 V' _& x# o
tives. There were no siblings.- K- w2 j& N8 Y l, X1 L
Physical Examination( ~) f+ J3 d7 T, K
The physical examination revealed a very active,
( ]! @. k; e2 M: [# uplayful, and healthy boy. The vital signs documented3 x. I1 \% r3 U% B, h6 w6 o
a blood pressure of 85/50 mm Hg, his length was
/ r" V+ u5 _9 W90 cm (>97th percentile), and his weight was 14.4 kg
% Z$ a( [5 a. p2 o/ d0 c(also >97th percentile). The observed yearly growth5 W# b' f8 R+ Y) |
velocity was 30 cm (12 inches). The examination of
* B. }4 v ~- x# c% f5 xthe neck revealed no thyroid enlargement.
/ ^. L: R. _+ dThe genitourinary examination was remarkable for2 p2 o U6 ^' X m* H( X5 ?0 i
enlargement of the penis, with a stretched length of7 |7 a" G; ?0 C* r
8 cm and a width of 2 cm. The glans penis was very well
) X( F& R$ |- Udeveloped. The pubic hair was Tanner II, mostly around
1 E9 m0 Y* [$ c7 B540
' S; k7 T' [# F! q/ Bat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
: R8 @+ F6 t6 G8 f% q' sthe base of the phallus and was dark and curled. The q5 s7 x, }# M: E0 U& n5 y W
testicular volume was prepubertal at 2 mL each.& \+ x2 H' A2 n9 T1 X" ]+ m, n
The skin was moist and smooth and somewhat" v9 w+ \; [# t2 P' G0 q& Y; d
oily. No axillary hair was noted. There were no# f l: ^; b0 ]9 w* Y% D* _
abnormal skin pigmentations or café-au-lait spots.
5 G: K% r. v+ Q) c5 JNeurologic evaluation showed deep tendon reflex 2+
7 S3 U# k, p7 [2 `bilateral and symmetrical. There was no suggestion
( O1 U$ ]0 P5 Kof papilledema.; P7 o: B; {# D6 D
Laboratory Evaluation
" F" ~8 n3 h8 J7 zThe bone age was consistent with 28 months by! J8 ]) X0 ]7 S
using the standard of Greulich and Pyle at a chrono-
' y6 o2 V4 N0 u5 n* Ologic age of 16 months (advanced).5 Chromosomal
9 `! Z5 E* p9 X4 ?' m* bkaryotype was 46XY. The thyroid function test! q9 M0 f7 [- Y: W
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
& u v% K5 L9 ~$ F8 Mlating hormone level was 1.3 µIU/mL (both normal).
' l/ k" a0 g0 }The concentrations of serum electrolytes, blood3 E2 F: ] v3 h) \
urea nitrogen, creatinine, and calcium all were
6 F1 k& F& b$ p: uwithin normal range for his age. The concentration9 F6 u! F9 E1 k# \: @
of serum 17-hydroxyprogesterone was 16 ng/dL
8 |- Q4 c1 { o# T5 b! q0 Y(normal, 3 to 90 ng/dL), androstenedione was 20* Z: F0 t* B2 N* {8 Q2 b
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
1 {9 C. V6 P) A+ s/ |! J, i1 Nterone was 38 ng/dL (normal, 50 to 760 ng/dL),
+ Z4 g5 ]4 G& ]1 A9 X8 B0 rdesoxycorticosterone was 4.3 ng/dL (normal, 7 to! s2 t. z; e, K' u
49ng/dL), 11-desoxycortisol (specific compound S)
0 j2 L9 E$ T) {! G5 U! f3 ^+ awas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-( v8 W y. u. P' s- n! X3 n( @
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total5 n, x {" {0 U# O2 C
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
6 B, s. G) [# O6 E1 P8 X6 t7 aand β-human chorionic gonadotropin was less than/ j- D6 M; s* @
5 mIU/mL (normal <5 mIU/mL). Serum follicular
8 B+ E2 m5 M) T/ V' B& xstimulating hormone and leuteinizing hormone
; y# z# Z/ `! hconcentrations were less than 0.05 mIU/mL3 ~+ h; ~$ V" @9 g+ z# F e5 ~5 V
(prepubertal).$ t* G& b, }9 h6 j, k) s! f3 e/ z! q
The parents were notified about the laboratory
; O: d; m7 X" \! T( C1 Eresults and were informed that all of the tests were0 D; d# f3 j. p, U
normal except the testosterone level was high. The; E `2 z: O2 f* ~- t
follow-up visit was arranged within a few weeks to5 [+ f" R: s/ V Q4 N2 l: F
obtain testicular and abdominal sonograms; how-
* ~# x3 e1 E, r9 j7 }" qever, the family did not return for 4 months.
7 K% h( ]) }2 h% R# u: uPhysical examination at this time revealed that the+ ~- ?0 [% [; d9 [- u$ h1 s
child had grown 2.5 cm in 4 months and had gained
/ m$ g$ i# [6 Y( B2 kg of weight. Physical examination remained* w: V. h6 w% h0 n6 q+ t/ l
unchanged. Surprisingly, the pubic hair almost com-/ E0 E# t+ R; P+ B* J0 b
pletely disappeared except for a few vellous hairs at
, v# P& \& c# Y% I1 bthe base of the phallus. Testicular volume was still 2" ]! B& E, U5 g! @
mL, and the size of the penis remained unchanged.- V* {8 Z. b/ z' `
The mother also said that the boy was no longer hav-( W2 ~7 g$ L; k, O& o
ing frequent erections.& y# M [5 F |3 W. Y# c. e
Both parents were again questioned about use of$ [; E/ K8 O$ N$ c6 t0 d% F7 s' z
any ointment/creams that they may have applied to
; S/ h9 k# I. r, U* o' I3 S1 ]the child’s skin. This time the father admitted the9 c3 {- A: P8 v, F$ }/ z
Topical Testosterone Exposure / Bhowmick et al 541. X0 S3 X3 O, Q9 v
use of testosterone gel twice daily that he was apply-2 m) n2 ] E6 _& \: p$ G
ing over his own shoulders, chest, and back area for6 [, n6 U5 p7 c) T- j
a year. The father also revealed he was embarrassed
* F; c0 E( }5 i0 F$ L; Gto disclose that he was using a testosterone gel pre-
0 C0 t5 s' Z; D& [/ Mscribed by his family physician for decreased libido
, Z* D% O; c, q; [secondary to depression.
$ X% k3 n7 z1 f- f! u1 c4 x7 qThe child slept in the same bed with parents.1 S' e' o/ ~; [1 N
The father would hug the baby and hold him on his8 i/ `/ b" h' ?
chest for a considerable period of time, causing sig-! i+ K, B6 G8 B! K+ `+ b; B
nificant bare skin contact between baby and father.$ E8 z) j" x5 s$ d: N' l
The father also admitted that after the phone call,
3 C- d* q8 K3 @. M! h6 V! i3 Iwhen he learned the testosterone level in the baby
V: k T- a4 t1 @8 x& }was high, he then read the product information
9 C# `* i7 X; d w/ g4 npacket and concluded that it was most likely the rea-
) ]* Q4 O( [( m" Json for the child’s virilization. At that time, they
: P' J0 ~9 B# e) V5 Adecided to put the baby in a separate bed, and the1 F# I' G; U% r
father was not hugging him with bare skin and had
. w) ]5 i8 W% ~1 T3 |* Q4 X5 \' {been using protective clothing. A repeat testosterone
! n! \( q' \9 stest was ordered, but the family did not go to the! W: s3 k$ \3 V! x
laboratory to obtain the test." {( x; s! [( I- t
Discussion
' v$ `8 d: X {8 j* Y6 Z8 dPrecocious puberty in boys is defined as secondary
) `7 H1 d3 j/ j: ?4 v1 lsexual development before 9 years of age.1,4
/ P6 l) d8 f. D) MPrecocious puberty is termed as central (true) when
1 S* L- E8 n' Y. w; Lit is caused by the premature activation of hypo-
+ a, }' P0 R xthalamic pituitary gonadal axis. CPP is more com-
5 E$ \( B. }+ |$ O7 ~/ kmon in girls than in boys.1,3 Most boys with CPP0 l) s! @2 O7 ^4 |6 @$ B" O
may have a central nervous system lesion that is) m7 Q+ S! a( a( k/ j1 T
responsible for the early activation of the hypothal-& |4 ]+ k# F. [+ t. o
amic pituitary gonadal axis.1-3 Thus, greater empha-) y8 F& h7 |9 m. ^9 c5 x) d
sis has been given to neuroradiologic imaging in
- g/ P {# G5 ~7 Vboys with precocious puberty. In addition to viril-& g' W' _' ]$ v# J* ~
ization, the clinical hallmark of CPP is the symmet-. v- x* V% n& k& t3 \! w( V1 }& T
rical testicular growth secondary to stimulation by9 h: k& a) N* K" A5 F; {& D. m
gonadotropins.1,33 S% } e* W2 |" z! O5 F# T+ U
Gonadotropin-independent peripheral preco-
) r: F7 I+ ^6 a' C5 Z; u/ N# F. [0 ucious puberty in boys also results from inappropriate
: o' t5 D; B( D- l ~8 Candrogenic stimulation from either endogenous or1 k( U3 b; n: m8 O
exogenous sources, nonpituitary gonadotropin stim-! ~6 k% A5 D/ J7 n* l
ulation, and rare activating mutations.3 Virilizing9 F' w, a. Y. x5 t7 n
congenital adrenal hyperplasia producing excessive
! O& }# Q1 w% |adrenal androgens is a common cause of precocious
, t: q9 n5 e# l( o3 Z- xpuberty in boys.3,4
8 `- H* ^. h4 u5 Y; kThe most common form of congenital adrenal
" D) w7 p. }$ I$ d2 ]( q) Z4 Rhyperplasia is the 21-hydroxylase enzyme deficiency.
6 k" h& [, ^. O) q' J1 `3 S, XThe 11-β hydroxylase deficiency may also result in9 B8 |* \8 f3 O+ U" m# B# l
excessive adrenal androgen production, and rarely,
" [4 X( O! ?1 [+ p+ g9 yan adrenal tumor may also cause adrenal androgen
6 L0 L1 a+ Q8 L1 g2 Oexcess.1,3% u( F, S1 ` S
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from4 j% B3 u' a `' R
542 Clinical Pediatrics / Vol. 46, No. 6, July 20079 s8 v! O/ P! ]* {. h
A unique entity of male-limited gonadotropin-/ A, D. N z9 @- N2 O$ S' T
independent precocious puberty, which is also known
0 [1 \9 P+ ]; D* k$ x5 w) f5 a" I# Mas testotoxicosis, may cause precocious puberty at a
! O$ b/ ] k V. dvery young age. The physical findings in these boys; ]" z; ^9 y4 _. k6 o" S, d
with this disorder are full pubertal development,1 ~$ v- `8 U5 J2 L6 ~
including bilateral testicular growth, similar to boys
! @ R) X5 w) Ywith CPP. The gonadotropin levels in this disorder
$ H s/ T) O7 k0 A: d6 M% \% Ware suppressed to prepubertal levels and do not show
5 x5 f7 _* W: e; \8 m9 p! jpubertal response of gonadotropin after gonadotropin-
5 ~4 c, J+ Q, h0 b) o) Q i( [releasing hormone stimulation. This is a sex-linked
+ o1 D7 v* F6 M+ l/ }4 b' Eautosomal dominant disorder that affects only3 X0 g' y# |! _" ^. B. _
males; therefore, other male members of the family
+ o# Z- l# R# vmay have similar precocious puberty.33 A3 H# c0 I) L; X! c
In our patient, physical examination was incon-
1 U& `# z( b& v4 R4 U! n8 d3 l* Usistent with true precocious puberty since his testi-
3 F- ]1 @$ E& ?9 [/ M! Icles were prepubertal in size. However, testotoxicosis2 C* E4 a! i7 A" A; t D, P
was in the differential diagnosis because his father6 M) w' X( S- p6 m) _
started puberty somewhat early, and occasionally,5 v/ w: s1 e8 I/ r: A9 M
testicular enlargement is not that evident in the
" |. T3 v3 Y5 Q4 F' }beginning of this process.1 In the absence of a neg-! g+ W% R: K4 h- c2 c+ X# T) E1 h
ative initial history of androgen exposure, our, s) I2 v7 L4 q; K
biggest concern was virilizing adrenal hyperplasia,
?2 L1 |( g' I. H+ f: ^& keither 21-hydroxylase deficiency or 11-β hydroxylase
& N8 x5 O3 n# fdeficiency. Those diagnoses were excluded by find-
& O1 y, ` a. ]1 ~ing the normal level of adrenal steroids.! N7 V9 ~# W# H
The diagnosis of exogenous androgens was strongly; D8 K [- A* c0 {4 `" w; k
suspected in a follow-up visit after 4 months because
8 J4 _$ I5 g* f) B: F7 Xthe physical examination revealed the complete disap-
" [+ b% C4 B7 K/ ]+ |+ A) F8 ipearance of pubic hair, normal growth velocity, and! ^- v' U M: }* n& v# f3 |1 ^
decreased erections. The father admitted using a testos-" O1 u5 }, z4 w# o5 A
terone gel, which he concealed at first visit. He was
^4 ^3 w( c+ a! m5 h5 husing it rather frequently, twice a day. The Physicians’
8 `. i3 ?5 F1 b6 YDesk Reference, or package insert of this product, gel or
3 W+ S5 A/ P% k* d2 q9 Mcream, cautions about dermal testosterone transfer to
( ?) F2 k0 N3 T) P& n% |; {unprotected females through direct skin exposure.
) ]+ O- F1 [; XSerum testosterone level was found to be 2 times the
: P$ v! ^% Y3 }, }6 }baseline value in those females who were exposed to
6 u# P+ A) ]- T+ g" `. b# }even 15 minutes of direct skin contact with their male
! n% \3 w/ V1 r/ h% |2 w+ z2 Ypartners.6 However, when a shirt covered the applica-; O) D7 ^$ W% B, u- o* I
tion site, this testosterone transfer was prevented.0 I- |% P9 D* ?3 }1 K- z) c
Our patient’s testosterone level was 60 ng/mL,% A0 r8 ~9 n6 X8 G
which was clearly high. Some studies suggest that: |" ~# X( I2 z6 R" C! {
dermal conversion of testosterone to dihydrotestos-
& X+ P5 F* u- \terone, which is a more potent metabolite, is more X& H {$ v% ?
active in young children exposed to testosterone
# B$ T8 D/ X* y/ W& {exogenously7; however, we did not measure a dihy-0 ]6 ~: G _* A4 H3 }
drotestosterone level in our patient. In addition to
# ?1 e" ^* t/ K! Svirilization, exposure to exogenous testosterone in+ f& }9 b# U- `( m" v C: w
children results in an increase in growth velocity and
; j2 e3 f+ Z! I( f9 l1 T! madvanced bone age, as seen in our patient.0 {6 p {- f0 \9 L
The long-term effect of androgen exposure during& p, ^9 v; u2 ` N4 s
early childhood on pubertal development and final
1 z7 ^7 O0 b+ n' O2 \, Jadult height are not fully known and always remain: q, N7 G# q0 N2 B" w
a concern. Children treated with short-term testos-8 X) b3 F I5 A( n. |3 W
terone injection or topical androgen may exhibit some2 l: @1 [" g, O2 W
acceleration of the skeletal maturation; however, after
; H+ d: q; f% k4 E2 P5 v6 n. v! Tcessation of treatment, the rate of bone maturation
+ C. r8 F& `, }decelerates and gradually returns to normal.8,9
4 J5 l6 }1 I1 o$ A* Q# L0 {8 c6 S' eThere are conflicting reports and controversy
+ b0 \$ l. @' s2 Z, {over the effect of early androgen exposure on adult
6 e$ D. A1 ?9 gpenile length.10,11 Some reports suggest subnormal% P; X- u( G+ X. e+ r% F
adult penile length, apparently because of downreg-( ?$ c+ u ^5 e. Y
ulation of androgen receptor number.10,12 However,
7 e3 T0 t5 j& _: N% d6 R+ A' }% jSutherland et al13 did not find a correlation between) ?% x. \. S4 T$ T& f. }5 c
childhood testosterone exposure and reduced adult) x! |5 c: o4 E% D! S1 E; ~; q5 Y0 V
penile length in clinical studies.$ ]: q9 h* V: t- A' Q/ m0 `
Nonetheless, we do not believe our patient is
% C# d6 k- D3 r& ^; {/ N3 T. Rgoing to experience any of the untoward effects from
1 b# R* D* W; Y: T& ?2 Ctestosterone exposure as mentioned earlier because \0 T) m& L/ |
the exposure was not for a prolonged period of time.' P) X" K0 [5 H/ c
Although the bone age was advanced at the time of+ I0 H/ ~. j0 o1 H/ ]
diagnosis, the child had a normal growth velocity at2 ]( H6 f6 K. Q* N. h3 e
the follow-up visit. It is hoped that his final adult8 u8 A* d; h; b* G) Z# h
height will not be affected.$ W/ i2 y2 a* Y. k
Although rarely reported, the widespread avail-
! A6 w. B3 [3 u3 I; c2 ?: sability of androgen products in our society may
! [; i8 v7 Y& g6 mindeed cause more virilization in male or female
- n) L+ e; X/ o) Cchildren than one would realize. Exposure to andro-! ?7 t, n5 Q' O% b! \
gen products must be considered and specific ques-
7 e6 m; M: E1 {+ H+ h" utioning about the use of a testosterone product or* p5 q5 s u& ?
gel should be asked of the family members during3 z7 ]+ p" d, s; c, ]+ d' k
the evaluation of any children who present with vir-' p: x( k9 f7 ^; [- v
ilization or peripheral precocious puberty. The diag-# ^, E) m) a Y: L$ y! A: Y# J. U2 v
nosis can be established by just a few tests and by
; t$ C6 a0 n( {* }+ Mappropriate history. The inability to obtain such a
# m. Y% A- L1 F5 U; ]7 s- vhistory, or failure to ask the specific questions, may
j6 N; ~( U! t, H- G$ Iresult in extensive, unnecessary, and expensive% k! T$ u5 i; c# h& K2 Z$ X$ j: k I
investigation. The primary care physician should be
1 k) I% D: B6 K9 s5 ~) {aware of this fact, because most of these children
" i1 k U. G. P3 ^/ f8 B) @may initially present in their practice. The Physicians’$ H0 S/ Y) N. h- W7 m
Desk Reference and package insert should also put a$ G8 [8 q6 k9 y1 s" [# p+ _5 F) r
warning about the virilizing effect on a male or% Z Z( f! w+ s! N
female child who might come in contact with some-7 e1 Z% a6 r% z, J1 y
one using any of these products.
( o; T! y ?4 T, _2 A: w# ?References
( X/ W* L& ]5 b- S2 Y1. Styne DM. The testes: disorder of sexual differentiation
, t" P/ ?: Y6 v) M( hand puberty in the male. In: Sperling MA, ed. Pediatric4 U* M, }1 x" V/ D' j& k
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
0 p% O) x" y3 o2002: 565-628.
) ?# _. b5 A- q3 d$ s1 ?! Y0 H2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
+ z' d) ^+ x, p$ H& vpuberty in children with tumours of the suprasellar pineal |
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