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Sexual Precocity in a 16-Month-Old
! d* Q& B0 S6 m) k9 YBoy Induced by Indirect Topical+ ^' V1 |' t% A
Exposure to Testosterone8 S( |5 Z; W5 }8 c# x" A
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
" o9 h. e/ z7 ]7 z2 pand Kenneth R. Rettig, MD17 D+ V& {- m. R5 X0 e' e' `
Clinical Pediatrics) d8 B: A8 n! x1 r0 f' q j
Volume 46 Number 6! D: T6 U% e' {# r% B2 h9 s# [# F
July 2007 540-543
8 r! v9 J4 ]2 C© 2007 Sage Publications
; w9 J6 f2 P1 j- \ s/ K10.1177/00099228062966514 O! m0 ~, M1 l( p
http://clp.sagepub.com
0 m3 d$ l7 o$ `' Z, {hosted at
# z( Z& M% t5 h# Lhttp://online.sagepub.com k f, v( z1 H& ~
Precocious puberty in boys, central or peripheral,
6 K. X5 M/ v' g" f/ _% His a significant concern for physicians. Central
: |4 h V6 j$ }* O6 }8 g3 d9 Vprecocious puberty (CPP), which is mediated9 M- z+ O3 M4 W& x% z
through the hypothalamic pituitary gonadal axis, has
1 n8 T8 R2 B/ r8 Y7 Fa higher incidence of organic central nervous system4 u8 {2 A# V2 A1 l& ?. ^9 G. C
lesions in boys.1,2 Virilization in boys, as manifested
, C3 F9 C+ N, n1 V; A" nby enlargement of the penis, development of pubic. E! h5 T5 Y8 X: S7 e5 q9 C! }
hair, and facial acne without enlargement of testi-
) O5 k2 w) c/ S# i/ jcles, suggests peripheral or pseudopuberty.1-3 We
, D2 W) Y2 @+ S2 g+ Z6 F" wreport a 16-month-old boy who presented with the: C) C( r8 P+ g
enlargement of the phallus and pubic hair develop-
) ~/ t" W m9 cment without testicular enlargement, which was due" ^3 l1 r/ ]2 ~2 Y& S" r3 o5 e$ P
to the unintentional exposure to androgen gel used by
: X. a! r. C" Z+ g8 nthe father. The family initially concealed this infor-
2 A2 V! w+ P9 H; \+ x& n' T' imation, resulting in an extensive work-up for this
; m$ D& x1 W, q! o4 Z; e* x7 Ychild. Given the widespread and easy availability of
$ }4 P2 d+ D6 E- btestosterone gel and cream, we believe this is proba-
( k9 T' e5 E# o9 K% V/ S/ d0 _bly more common than the rare case report in the
1 w T ~! e7 n) w( C( Tliterature.4
( w" L8 i p9 \6 F vPatient Report
5 k& t7 h% F# K$ b$ b. }0 y0 ]( vA 16-month-old white child was referred to the
. h+ @: A/ f" J* d- x9 ^& L H" Uendocrine clinic by his pediatrician with the concern
3 c& P- V! R X$ k1 {4 bof early sexual development. His mother noticed
+ d$ V- i! ?; v$ Y4 Z7 w2 jlight colored pubic hair development when he was& h6 o$ l7 V8 L
From the 1Division of Pediatric Endocrinology, 2University of
2 g( p, F- v- K: Q8 M4 \* WSouth Alabama Medical Center, Mobile, Alabama.
& J. Y) h8 J& M9 aAddress correspondence to: Samar K. Bhowmick, MD, FACE,4 Q# C W/ d% P- {
Professor of Pediatrics, University of South Alabama, College of
/ g# \5 p. v3 sMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;( e& }- c" }4 z6 C: q4 [' Z
e-mail: [email protected].
- G+ N ]) I5 n" ~+ k" {about 6 to 7 months old, which progressively became6 w" y0 J* C9 @! u
darker. She was also concerned about the enlarge-
$ P! E2 j+ z2 n& p3 K& `ment of his penis and frequent erections. The child+ q" K5 [) U& x7 ^$ n3 y
was the product of a full-term normal delivery, with' o) }! w: l8 b5 ]* r
a birth weight of 7 lb 14 oz, and birth length of( i0 t4 c C: w0 y4 i+ t9 l7 [
20 inches. He was breast-fed throughout the first year
0 m3 P5 x7 S- Q) A9 Sof life and was still receiving breast milk along with
6 j0 p) O' G/ I7 J4 ssolid food. He had no hospitalizations or surgery,+ g G2 }' M5 X. Z/ C3 i
and his psychosocial and psychomotor development
( o, u' H' s- k+ q \/ ~was age appropriate.* \0 F- V& E* H
The family history was remarkable for the father,
! s0 Y% q/ C0 A1 kwho was diagnosed with hypothyroidism at age 16,0 K( l% V! h: T% Q- O5 ?; O
which was treated with thyroxine. The father’s
/ T! g j* u& ^. N6 Wheight was 6 feet, and he went through a somewhat
1 g- F9 j$ K, W6 {, q- i6 ~early puberty and had stopped growing by age 14.
4 y7 F0 a7 L2 w! vThe father denied taking any other medication. The
4 u* F; f' q* M9 kchild’s mother was in good health. Her menarche
2 B; s9 p+ \6 T8 K8 fwas at 11 years of age, and her height was at 5 feet# V' \4 H1 @9 u# v, |% e2 q
5 inches. There was no other family history of pre-$ i. `' q. M4 J0 C+ G
cocious sexual development in the first-degree rela-9 B/ A* [+ `4 Q2 i _1 i" \
tives. There were no siblings.
+ @9 C- A9 g- g$ g- ]% PPhysical Examination$ J- R% y g' W
The physical examination revealed a very active,& ?9 t6 \ {5 o, \) _
playful, and healthy boy. The vital signs documented
0 d8 X# q- S, P- f+ q& p- T* c* d+ Na blood pressure of 85/50 mm Hg, his length was: b2 O3 `& }6 t# }2 ~
90 cm (>97th percentile), and his weight was 14.4 kg* R1 u) U' Q- t) A9 ]
(also >97th percentile). The observed yearly growth2 X! ? ?! v) C; M- e6 D0 D% T
velocity was 30 cm (12 inches). The examination of* ]; W! \9 W) f2 C: j4 a
the neck revealed no thyroid enlargement." |9 A0 o2 T1 D3 U: w
The genitourinary examination was remarkable for5 g; c: U/ ~3 _
enlargement of the penis, with a stretched length of
9 R2 O! m5 C/ b1 P8 cm and a width of 2 cm. The glans penis was very well4 b0 D* Q9 A1 V7 W
developed. The pubic hair was Tanner II, mostly around% h& S/ x+ A. a7 H# ]- v3 k6 {
540. S1 w7 u/ P9 s0 T* V! ]' P _
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
% h* {% `: y& S# Y% L! d5 o7 [ Pthe base of the phallus and was dark and curled. The
0 b( r, J2 O5 x$ Atesticular volume was prepubertal at 2 mL each.* e3 ]- t c2 W2 _2 w. C6 k8 d1 F
The skin was moist and smooth and somewhat3 v2 B- P4 c; Z! G; Q, b
oily. No axillary hair was noted. There were no
. d: |2 L1 g1 M K0 j3 [1 babnormal skin pigmentations or café-au-lait spots.
4 c4 [% Y8 `% a/ b; I P4 O% {Neurologic evaluation showed deep tendon reflex 2+( Q5 x) C, O& t- a, }7 ]% E) O8 o
bilateral and symmetrical. There was no suggestion
' L* l+ P5 b8 {( Rof papilledema.
% p* W, U; I3 v9 h$ V- zLaboratory Evaluation
9 B7 U7 L# h0 q4 l& _The bone age was consistent with 28 months by
: s) D' t4 Y, H( W+ {using the standard of Greulich and Pyle at a chrono-( N. S8 i+ u, U% ?$ F! Z
logic age of 16 months (advanced).5 Chromosomal
8 K3 O) J3 D" r3 Ukaryotype was 46XY. The thyroid function test0 G, X) |" m! [6 Z) Q$ [
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
. H; j3 Y2 `& ?2 w* {! Q. k4 |9 ulating hormone level was 1.3 µIU/mL (both normal).
+ u# ~* b" ]6 [1 P; p1 _The concentrations of serum electrolytes, blood7 G1 m! H& S0 H) p: `5 U
urea nitrogen, creatinine, and calcium all were
/ K+ O5 l- i8 Z( iwithin normal range for his age. The concentration0 g6 z' b8 ~9 a& H
of serum 17-hydroxyprogesterone was 16 ng/dL
( b/ `' j" m: F8 F/ Q(normal, 3 to 90 ng/dL), androstenedione was 20
8 ^% j O0 J. E2 cng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
, H4 m' e2 p: Y3 I" v$ M2 v# h" cterone was 38 ng/dL (normal, 50 to 760 ng/dL),1 `' }7 k3 a: X9 X! w3 x6 f3 c: @' G
desoxycorticosterone was 4.3 ng/dL (normal, 7 to8 K4 b( k9 f0 Y0 r
49ng/dL), 11-desoxycortisol (specific compound S)- H: V7 n" p0 s# A5 ^5 E
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
, b& |) A8 e; P9 mtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
" m: i+ Z9 |! t ^( Btestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
W! P+ h/ e, Y, k8 Nand β-human chorionic gonadotropin was less than
, ~8 X W& M) x5 mIU/mL (normal <5 mIU/mL). Serum follicular9 @1 r) }. O: M( K3 A. b' `3 l5 Y0 e
stimulating hormone and leuteinizing hormone
) A+ P! r5 Y3 L7 N, n6 A6 c7 @concentrations were less than 0.05 mIU/mL
5 w7 U" X9 W. _* D(prepubertal).
9 Q# h9 Y1 g' B: O9 lThe parents were notified about the laboratory* I( N# s4 T* ? L% J/ Q8 T
results and were informed that all of the tests were
) D& s& E: V$ D# h# J" k* Snormal except the testosterone level was high. The
: [/ D/ {; H- U9 _6 ~follow-up visit was arranged within a few weeks to! p, j8 R' Y4 D
obtain testicular and abdominal sonograms; how-
9 ~% F/ v! a6 K6 b& C! b( Mever, the family did not return for 4 months. H% B1 X- L, K* a
Physical examination at this time revealed that the
3 P$ F, B8 ]. Tchild had grown 2.5 cm in 4 months and had gained
7 v' R' H! ]% |) d- L2 kg of weight. Physical examination remained& T4 ` N& T# l% l1 h; \, E5 B' T
unchanged. Surprisingly, the pubic hair almost com-
7 G1 p Z9 [7 g; ?5 ?/ e* ?7 ppletely disappeared except for a few vellous hairs at
: y! ^, P/ _; K" P, ethe base of the phallus. Testicular volume was still 2
& @! X/ O* U8 w# o1 {4 q, mmL, and the size of the penis remained unchanged.
- u( j! y5 c- N' e# nThe mother also said that the boy was no longer hav-
( Q6 w- L2 x$ A3 q" G: @ing frequent erections.2 K9 }8 C* |7 B8 n+ D/ k* _
Both parents were again questioned about use of
# L, m6 z4 x, |* [3 S1 l$ h3 Rany ointment/creams that they may have applied to
9 T6 q1 G- v3 ^3 Zthe child’s skin. This time the father admitted the( b8 C, o: y2 l8 f2 z" v9 s+ h
Topical Testosterone Exposure / Bhowmick et al 541" X3 l5 T$ _1 r: Z# f
use of testosterone gel twice daily that he was apply-- Z a, K. a) c" j1 |
ing over his own shoulders, chest, and back area for- \$ K7 I! u: Z1 p3 s5 D6 X' F" s
a year. The father also revealed he was embarrassed
/ f, Q" C+ g& L( R! Kto disclose that he was using a testosterone gel pre-
) d- K) l' \# }6 S' }scribed by his family physician for decreased libido" f. x% _3 C) h$ ^
secondary to depression.7 Y3 B! p5 S, k5 }( Q; i L$ }
The child slept in the same bed with parents.
: L; O" J2 R) k( gThe father would hug the baby and hold him on his9 L0 Q) ~* W2 v9 K& N7 K0 w
chest for a considerable period of time, causing sig-# e! }+ z V/ p: W* E7 T
nificant bare skin contact between baby and father.
9 k9 a5 V! d2 a ?! {2 ]The father also admitted that after the phone call,
/ ~" K1 h! `. Y$ O& ~+ ?when he learned the testosterone level in the baby
) ]- m2 b0 e- F0 twas high, he then read the product information
, Z6 o* |& z& z0 A( Dpacket and concluded that it was most likely the rea-
! {( z- S5 ~ N F) _! Cson for the child’s virilization. At that time, they
1 H5 Q( y9 l1 O5 ]9 Ydecided to put the baby in a separate bed, and the+ \( x% B% A9 p+ u
father was not hugging him with bare skin and had
% P# j) o$ U( L {% {' l/ x4 }been using protective clothing. A repeat testosterone
; A( J! f4 U6 I$ ~test was ordered, but the family did not go to the5 g/ V3 Z" S5 O% P- k/ o5 L
laboratory to obtain the test.
5 ^2 t$ m' e, E8 Z' [Discussion
$ J' B% H* N+ M% _Precocious puberty in boys is defined as secondary T; P7 s+ a7 w
sexual development before 9 years of age.1,4( F% s& I N' d5 {, S1 L9 Y: ^
Precocious puberty is termed as central (true) when X3 {: x& p- n( Q* R
it is caused by the premature activation of hypo-
' H: a- B2 p1 Bthalamic pituitary gonadal axis. CPP is more com-
2 X) Y! Y2 {8 j6 W& Xmon in girls than in boys.1,3 Most boys with CPP
, q# S; y* ?8 V- O& Zmay have a central nervous system lesion that is
8 i ]9 F7 e- ]+ iresponsible for the early activation of the hypothal-. ~6 Y$ ?1 M+ t
amic pituitary gonadal axis.1-3 Thus, greater empha-
' O- l8 B" g3 C& l0 N% C* x& Isis has been given to neuroradiologic imaging in
$ p7 Y& M& u7 `& ?& X7 t7 o* r& bboys with precocious puberty. In addition to viril-* j! h5 m$ S: S$ I/ j( W( v* ^+ i, D
ization, the clinical hallmark of CPP is the symmet-3 K. C$ W% B# a: @
rical testicular growth secondary to stimulation by3 n' Z/ R: c+ C+ Y
gonadotropins.1,3
! d6 X$ Y( o: ~- c8 YGonadotropin-independent peripheral preco-
: g' I. D& w) H( r( n9 Wcious puberty in boys also results from inappropriate7 I; l$ v1 I# v5 K* ]9 Z
androgenic stimulation from either endogenous or
, @9 v7 A9 m- [6 }& `exogenous sources, nonpituitary gonadotropin stim-3 R k ^ T8 S
ulation, and rare activating mutations.3 Virilizing7 u# B9 I9 u0 V* z
congenital adrenal hyperplasia producing excessive
4 k) z; x# M' B4 Aadrenal androgens is a common cause of precocious
$ q3 U) b) T/ }' J& O3 K% M* hpuberty in boys.3,4$ C. L' Z& m \/ h8 |# c
The most common form of congenital adrenal
0 h, }9 j# O0 \. ghyperplasia is the 21-hydroxylase enzyme deficiency.
7 z0 I& t b: ?+ _* ? m D. tThe 11-β hydroxylase deficiency may also result in
$ h1 I( X1 Q# @9 Jexcessive adrenal androgen production, and rarely,
) J" c3 q' ~( Y) |; p. K3 Ean adrenal tumor may also cause adrenal androgen
! @& h9 O, ]3 h4 l% |excess.1,30 u L$ \ {* _" [
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from+ R2 @0 H" E) H/ x) p( L
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
& \& x" _: i, e- u7 N6 mA unique entity of male-limited gonadotropin-6 `; c3 V% j* _) J
independent precocious puberty, which is also known
' E/ S% d: Q L: X6 uas testotoxicosis, may cause precocious puberty at a/ O3 G1 o+ u+ r: b3 ?
very young age. The physical findings in these boys
. \+ Y/ m# ^ rwith this disorder are full pubertal development,5 C# B- u2 w/ t3 X
including bilateral testicular growth, similar to boys
4 G! A' V9 f- E9 h1 hwith CPP. The gonadotropin levels in this disorder% Z) a/ e4 A2 q4 C) d5 t9 ?
are suppressed to prepubertal levels and do not show1 F2 J1 ^ ]$ O: L; \
pubertal response of gonadotropin after gonadotropin-8 p" A K1 R0 o X G
releasing hormone stimulation. This is a sex-linked5 m. `, F* Y. O6 i2 p+ b" ]* G" y
autosomal dominant disorder that affects only
, g! o. g6 N8 Amales; therefore, other male members of the family( C+ Q/ x/ Y5 h B7 R+ ~
may have similar precocious puberty.3/ U( q, E$ G! F0 t) i1 ~; `
In our patient, physical examination was incon-
+ t! n' }1 T v( {% |% Psistent with true precocious puberty since his testi-
* N6 K7 M) ], d+ Z9 Bcles were prepubertal in size. However, testotoxicosis
W& C1 p* E- s+ ^% O) ?1 o. z8 Cwas in the differential diagnosis because his father# Z( E8 {/ G, u" \( k* o6 L
started puberty somewhat early, and occasionally,
7 M7 m, C( z1 L: E9 Vtesticular enlargement is not that evident in the/ A* D/ G% i( d
beginning of this process.1 In the absence of a neg-
! R% [) X3 l& {2 M+ qative initial history of androgen exposure, our9 P4 k m) n0 V2 @) h
biggest concern was virilizing adrenal hyperplasia,8 X1 ~+ W* A2 J1 P
either 21-hydroxylase deficiency or 11-β hydroxylase
9 w" Y0 j& i7 M5 R5 F5 O$ v( Zdeficiency. Those diagnoses were excluded by find-1 b" p$ {# G( i, {, ]# Y- J" A& ~* N
ing the normal level of adrenal steroids.
% e0 E2 j5 G$ `* k% TThe diagnosis of exogenous androgens was strongly
* J( o' j/ N" g; fsuspected in a follow-up visit after 4 months because
1 M5 z' I8 n, i! q" Ithe physical examination revealed the complete disap-$ E2 x3 |2 Q/ z9 Z
pearance of pubic hair, normal growth velocity, and
- s9 n; H, z+ i: Zdecreased erections. The father admitted using a testos-! s$ c4 x& }1 v( a' t3 J
terone gel, which he concealed at first visit. He was
4 F9 Z y3 C8 U8 s/ C3 }6 busing it rather frequently, twice a day. The Physicians’
2 K# d8 x, u! R5 o: [ m2 u" fDesk Reference, or package insert of this product, gel or
/ d! s; I: h* z0 d, B/ C# X! {cream, cautions about dermal testosterone transfer to' u4 P' k! c9 O
unprotected females through direct skin exposure.
2 z8 i { ]2 R% `& M6 }% P: QSerum testosterone level was found to be 2 times the3 C* [6 v9 x# {
baseline value in those females who were exposed to6 S( i# @' _9 a0 [0 W$ P. S
even 15 minutes of direct skin contact with their male
F- w! o0 e8 p0 S4 i6 v" Upartners.6 However, when a shirt covered the applica-
2 w) V) L1 z' D- G$ [* [ ltion site, this testosterone transfer was prevented.1 h8 E6 O+ w7 K* B2 l+ {3 M* P
Our patient’s testosterone level was 60 ng/mL,5 b/ H: N: O7 n; O
which was clearly high. Some studies suggest that
: E8 ?& S* d) z: f( a9 Kdermal conversion of testosterone to dihydrotestos-
# V4 W& j5 |5 w9 d% B( P+ y! Iterone, which is a more potent metabolite, is more5 q( |/ b. ~6 `2 W! T
active in young children exposed to testosterone h: p+ Y* Q& E4 F4 p4 e
exogenously7; however, we did not measure a dihy-
( U! U, g" d/ H( `6 fdrotestosterone level in our patient. In addition to
6 l/ Y$ J$ j8 A2 Jvirilization, exposure to exogenous testosterone in4 {! {% B7 Y9 t. i& i' j6 N
children results in an increase in growth velocity and
' q, c/ `- f4 `% {" e6 @/ G, Fadvanced bone age, as seen in our patient.
9 w7 {; Q6 b1 |* a1 T3 fThe long-term effect of androgen exposure during& v+ k" M, \1 d6 S$ z3 V
early childhood on pubertal development and final4 H" A- E6 N `0 S; L" n! \
adult height are not fully known and always remain5 R% J2 e0 o; Q! H5 w
a concern. Children treated with short-term testos-& ^) f' @3 A* a
terone injection or topical androgen may exhibit some- y: \& ^( I$ U8 F) `: F
acceleration of the skeletal maturation; however, after
" u- ~% G) @( Bcessation of treatment, the rate of bone maturation* W7 t& c0 _4 Z7 h: P
decelerates and gradually returns to normal.8,9
/ M, e( E& i4 h$ K+ a9 xThere are conflicting reports and controversy
6 M$ }( B$ ?; E" I4 Iover the effect of early androgen exposure on adult: k) t R9 W0 @; ~! S
penile length.10,11 Some reports suggest subnormal
6 e; S8 L3 a! F& A; o) Cadult penile length, apparently because of downreg-
$ I3 i! t7 U, W4 N+ |1 U6 z2 culation of androgen receptor number.10,12 However,0 h- P' u6 Z4 f6 F
Sutherland et al13 did not find a correlation between# X2 g Z3 ? w/ E& d2 l* U
childhood testosterone exposure and reduced adult
# h* ], e. a" Y% J. Ppenile length in clinical studies.0 g% [5 H( B( T9 C
Nonetheless, we do not believe our patient is
+ p- s# W' [6 y! e$ \going to experience any of the untoward effects from
$ l+ }, s) t9 Jtestosterone exposure as mentioned earlier because
. h" T; S( _% B6 K) @: |7 dthe exposure was not for a prolonged period of time.% m( r9 N" z, B4 K; A' z: O
Although the bone age was advanced at the time of$ G" z& {- [. ?1 {2 P
diagnosis, the child had a normal growth velocity at1 G3 D) x( z5 }1 ^, ~
the follow-up visit. It is hoped that his final adult
, t" c8 v0 \! E7 `height will not be affected.( M0 J4 X, A7 z c7 j+ ~% F
Although rarely reported, the widespread avail-$ W. {1 J% j, |' e
ability of androgen products in our society may4 ?3 ?8 g9 u9 Q# e; t: Z$ r
indeed cause more virilization in male or female( d% n. o/ W( ?- W [! L# |
children than one would realize. Exposure to andro-
! E% C1 t5 y0 Z* N0 Kgen products must be considered and specific ques-* Z# w! N! _/ t+ V
tioning about the use of a testosterone product or# t7 U. P" s/ V+ C9 C. A
gel should be asked of the family members during% m: k, i; J3 p) u; u" d
the evaluation of any children who present with vir-8 g# G; t) Z* v. @5 f* P1 a/ l. c
ilization or peripheral precocious puberty. The diag-3 q( o) ^5 M$ w" L7 J
nosis can be established by just a few tests and by+ M6 b: [* }2 v% I3 X' G6 [: ?4 R
appropriate history. The inability to obtain such a! t! H5 t; f9 c. h1 [* B# q
history, or failure to ask the specific questions, may+ _$ K/ i/ D7 j
result in extensive, unnecessary, and expensive. @* T3 n% L( x, c2 f0 O
investigation. The primary care physician should be j' v, a0 A. W6 E8 ]
aware of this fact, because most of these children
. M( y8 |7 [$ t6 k% C6 u" B: zmay initially present in their practice. The Physicians’1 s5 Z, N" r; e
Desk Reference and package insert should also put a
1 O2 v9 z9 ]4 [8 [8 L5 b1 T( Qwarning about the virilizing effect on a male or+ C# a) D, O4 V- [, ~1 X$ \; ~
female child who might come in contact with some-% H5 \1 ~ B2 n7 U0 f- }% E+ t- r
one using any of these products.3 J: _: a# A+ ?( e4 ^% F
References2 z2 H' Q8 D( X! Q0 [% Y) O/ E
1. Styne DM. The testes: disorder of sexual differentiation; j9 l- S, p# M$ I4 d# i& _
and puberty in the male. In: Sperling MA, ed. Pediatric
- V0 D6 O- S2 {( d# B9 ~5 @Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
0 K" J3 T0 a J- N! \ I, E2002: 565-628.
: ?* Y( [9 y" L2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
/ }$ D7 `5 M& epuberty in children with tumours of the suprasellar pineal |
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