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Sexual Precocity in a 16-Month-Old% ]1 l, O1 }+ s: c
Boy Induced by Indirect Topical6 \1 P' P. ^' `) X/ u
Exposure to Testosterone# j( x4 ]5 o/ M3 _$ X$ W
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,25 [3 N! l" T9 i
and Kenneth R. Rettig, MD1! ]5 H7 b+ ~7 ?2 x
Clinical Pediatrics U4 E: Z$ G5 }: e
Volume 46 Number 6: X7 r' ~) y- T5 K g
July 2007 540-5435 } S8 c; g' R# k; m* ]- P
© 2007 Sage Publications7 ~$ m( F* _; x
10.1177/0009922806296651( r7 c/ C M* l8 W. R4 Y0 M- i1 G
http://clp.sagepub.com
0 d* ]2 i+ X$ m' a1 u5 Q' m+ O# C* [3 ^hosted at, K Z% K& X- v. x8 A
http://online.sagepub.com0 r; u) Q# A' Z+ l: F9 K* x
Precocious puberty in boys, central or peripheral,+ S/ _* T) i( y9 L# {& |
is a significant concern for physicians. Central$ m8 u$ D+ K+ ^+ Z
precocious puberty (CPP), which is mediated9 ^* m$ W6 ~4 G% |
through the hypothalamic pituitary gonadal axis, has
/ @- |; f, J. ?a higher incidence of organic central nervous system
: w/ ^( X8 ~4 ]7 ^+ Blesions in boys.1,2 Virilization in boys, as manifested
4 _" @6 U2 M$ j( Zby enlargement of the penis, development of pubic4 a8 Y- u& D+ A) A/ t, Y
hair, and facial acne without enlargement of testi-
0 |2 L" Q' D# C5 @2 Z# }cles, suggests peripheral or pseudopuberty.1-3 We
8 K! a6 O+ T6 O5 l5 k. }8 Rreport a 16-month-old boy who presented with the' p2 E- M X* w; x9 a
enlargement of the phallus and pubic hair develop-
' _0 \! V: q0 A, x; qment without testicular enlargement, which was due
- r: y& C! v0 z6 lto the unintentional exposure to androgen gel used by( r) `( D* }; @, Z1 a& x
the father. The family initially concealed this infor-3 G1 p c" I6 X$ L
mation, resulting in an extensive work-up for this2 q8 A( X2 b8 r. S! W
child. Given the widespread and easy availability of* {5 u2 ^) A" p/ s: r1 H$ N4 k" Z
testosterone gel and cream, we believe this is proba-; l, \/ F' Q7 x1 F7 W8 d
bly more common than the rare case report in the% x5 \" S" O* P, h) E5 j
literature.42 x! @. p2 L6 l3 k! D% ?4 j
Patient Report- O# Z' O7 T7 k- x+ h
A 16-month-old white child was referred to the/ ^9 q# V" {5 G
endocrine clinic by his pediatrician with the concern
( i: N- u8 o1 V5 hof early sexual development. His mother noticed
: {/ z( B/ Y! b% Q/ F5 R. Klight colored pubic hair development when he was4 d1 r7 N" M( \! R$ u
From the 1Division of Pediatric Endocrinology, 2University of
4 |8 ?7 b) n, W' pSouth Alabama Medical Center, Mobile, Alabama.
( V6 J2 |1 k5 M. ]8 y: W! Y) e; B0 R/ X( HAddress correspondence to: Samar K. Bhowmick, MD, FACE,8 l% M" o6 F' x" V. [+ P; ?1 [. |
Professor of Pediatrics, University of South Alabama, College of/ w7 a0 m6 M# k3 o d3 c( e3 E' q
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
I& _* m7 V- Y" f7 U& ]e-mail: [email protected]." X2 t/ S& b# F- t( D# F/ g; g
about 6 to 7 months old, which progressively became1 N7 ^! O: z5 ?4 I5 I6 f4 D
darker. She was also concerned about the enlarge-8 x6 V4 |3 n, ^5 U
ment of his penis and frequent erections. The child% d# G/ H' Q) w1 w: r
was the product of a full-term normal delivery, with
# Q3 j; T+ {) z9 ]$ qa birth weight of 7 lb 14 oz, and birth length of
1 u+ |# x8 W# u! I20 inches. He was breast-fed throughout the first year6 ?; ?5 b* Y6 ~8 D1 |' ^* f+ H
of life and was still receiving breast milk along with: [! [2 j2 J2 b, M/ ~! j
solid food. He had no hospitalizations or surgery,3 x& ?4 p# |8 t& h; n
and his psychosocial and psychomotor development
# X5 z9 u: u+ j3 H0 N# Q4 {was age appropriate.) l0 Y" x3 W2 |1 B% J
The family history was remarkable for the father,! j+ o4 c, _6 \9 j l5 H
who was diagnosed with hypothyroidism at age 16, W, ?; k+ {6 c$ w$ J+ R- s3 @
which was treated with thyroxine. The father’s
, [9 k% G& _+ I+ x( iheight was 6 feet, and he went through a somewhat
: J! P3 V3 r# t! }early puberty and had stopped growing by age 14.
/ ^" L' z+ l$ p) K$ x7 jThe father denied taking any other medication. The
0 K9 k8 K" o o; H$ S3 rchild’s mother was in good health. Her menarche3 _' h- a- ^& S5 D
was at 11 years of age, and her height was at 5 feet( u; }/ e9 t7 v8 O
5 inches. There was no other family history of pre-
4 j/ n1 n7 `2 e# i& ?cocious sexual development in the first-degree rela-& X% ]0 o6 G) A
tives. There were no siblings. x- f# z2 C) W9 s
Physical Examination2 I( x& d' m% Z Z/ B0 @
The physical examination revealed a very active,
( X0 _' e" k5 V: Rplayful, and healthy boy. The vital signs documented
2 e- h4 s: x1 ca blood pressure of 85/50 mm Hg, his length was
3 K* D" N8 r1 b! J90 cm (>97th percentile), and his weight was 14.4 kg
& w% R6 v& j. @(also >97th percentile). The observed yearly growth
$ p; r. n( v. ^' y* Fvelocity was 30 cm (12 inches). The examination of( J. T5 h' p5 B& A. e; Z
the neck revealed no thyroid enlargement." O% _3 H! l8 T1 o$ }5 _( }
The genitourinary examination was remarkable for. K$ s: q8 c0 C$ F2 ~& E
enlargement of the penis, with a stretched length of5 w, n* z/ D8 B! q5 X
8 cm and a width of 2 cm. The glans penis was very well
: _9 C4 o5 G% ~3 V3 e, xdeveloped. The pubic hair was Tanner II, mostly around; w, v- p" w$ f1 {
540! J% }) Y) {+ y m/ D6 m
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
+ T Y5 U9 l4 ^$ uthe base of the phallus and was dark and curled. The
; n/ S t% N. L( a$ {testicular volume was prepubertal at 2 mL each.5 K8 i1 @* e+ W+ j1 E* `$ `
The skin was moist and smooth and somewhat
8 d) I) p1 g% j) Y5 Z5 V1 xoily. No axillary hair was noted. There were no
f3 x- T* ?, Labnormal skin pigmentations or café-au-lait spots.6 f/ Z4 T* |4 ^2 Q7 A9 v: V, N% W: v7 b
Neurologic evaluation showed deep tendon reflex 2+
2 Z2 D$ w* Y7 P3 Pbilateral and symmetrical. There was no suggestion, q+ v9 J) e( }1 Y' Y
of papilledema.
; C0 x! c' t# s5 fLaboratory Evaluation0 s2 L( ~3 D: H( Z, R* S
The bone age was consistent with 28 months by
: j* v# J4 d# P" r( ]# B. Y# Musing the standard of Greulich and Pyle at a chrono-
+ S! R7 M \7 V+ b9 Dlogic age of 16 months (advanced).5 Chromosomal, b$ G! j7 x+ E
karyotype was 46XY. The thyroid function test) v9 K& V7 ^! l% ~; ]- J$ B
showed a free T4 of 1.69 ng/dL, and thyroid stimu-: r& L9 O. d! I% |& P
lating hormone level was 1.3 µIU/mL (both normal).* S" N. W& `+ u# m% X, Z
The concentrations of serum electrolytes, blood
& ? d& s# B5 v1 o4 f1 r! d# M) v, {urea nitrogen, creatinine, and calcium all were! ^8 H1 D$ x! D2 U8 Y
within normal range for his age. The concentration" i. X" l- E- t% |0 n
of serum 17-hydroxyprogesterone was 16 ng/dL
4 o5 I# |- Y, ]2 l(normal, 3 to 90 ng/dL), androstenedione was 20
u, B9 A/ m! O) i" y4 n$ Qng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
+ F$ \8 t% j" k! D) @terone was 38 ng/dL (normal, 50 to 760 ng/dL),
. G& U5 {5 V1 W! q* D) S, adesoxycorticosterone was 4.3 ng/dL (normal, 7 to
2 L) _: r! D* t& U4 t$ r49ng/dL), 11-desoxycortisol (specific compound S), R- D8 P9 Y1 ~. l- ^& ^
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-1 L' R, E( |& M% F. S
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
, B9 I- I5 J: g' T, S2 Qtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
( v1 S* @/ h% T8 Tand β-human chorionic gonadotropin was less than
- o9 ^9 n- H$ F5 ?3 w) H( x5 mIU/mL (normal <5 mIU/mL). Serum follicular
" {2 `, C! j& ?1 B2 Nstimulating hormone and leuteinizing hormone) G0 }3 Q* f* I
concentrations were less than 0.05 mIU/mL7 ?- w1 x6 Y) T' i4 J1 c
(prepubertal).6 k( Q( z( [5 m
The parents were notified about the laboratory
0 X& }' c+ S6 F' Z, j" O5 Gresults and were informed that all of the tests were
& {; J* M: n* P- t7 t- u9 rnormal except the testosterone level was high. The
& X* j6 }0 w* @follow-up visit was arranged within a few weeks to) G6 R( }& G0 g- W
obtain testicular and abdominal sonograms; how-
' }" X4 y7 R& x* N. v* Y) H2 Mever, the family did not return for 4 months.
9 M8 k1 |" |6 {7 h* IPhysical examination at this time revealed that the4 ]1 `1 ?) D$ ?1 v; [& C# D+ c9 _! ]
child had grown 2.5 cm in 4 months and had gained
! U; c: G. q5 Q4 R1 Q2 F2 kg of weight. Physical examination remained( t' V7 u6 O: u+ n5 G l
unchanged. Surprisingly, the pubic hair almost com-0 s; ]# |- x! v
pletely disappeared except for a few vellous hairs at1 z* e: v! I" G& `4 L5 W
the base of the phallus. Testicular volume was still 2' C- w) D, F$ i9 \
mL, and the size of the penis remained unchanged.
) g, i3 W( K# R$ EThe mother also said that the boy was no longer hav-: j6 w% F8 n% C6 L$ }, T, H+ _
ing frequent erections.$ f* R5 a5 T) m+ J6 ?+ c8 d
Both parents were again questioned about use of7 M# q/ E! P, }1 Y& m5 m3 |: |
any ointment/creams that they may have applied to
# v7 S: K" v _+ kthe child’s skin. This time the father admitted the# I4 k. _4 a4 ]6 Y4 D
Topical Testosterone Exposure / Bhowmick et al 541
S: o# o8 \* G( Uuse of testosterone gel twice daily that he was apply-
5 \/ s. p( S! ], a# z2 Ting over his own shoulders, chest, and back area for
; X/ y* o* B j7 v, w) I( l8 ?$ ja year. The father also revealed he was embarrassed
?& Z6 u: {' J' Vto disclose that he was using a testosterone gel pre-
, F7 M& V! U- u" f4 \scribed by his family physician for decreased libido
9 k2 U" y. d7 T% U7 h# vsecondary to depression.
6 ?* L: h5 f$ B/ w" gThe child slept in the same bed with parents.( w3 D; l) s$ ?. j8 d; J) Q
The father would hug the baby and hold him on his
, z( u6 b _' L1 U' Lchest for a considerable period of time, causing sig-! D+ ?4 S) E% `$ H* s8 I- b
nificant bare skin contact between baby and father.
: A5 \2 f- K2 W$ `3 W/ sThe father also admitted that after the phone call,; u( O+ L! S. t9 {" X# o
when he learned the testosterone level in the baby, w6 m; T& h* S1 y4 h- t
was high, he then read the product information
! Q! y" @# a5 H3 P0 Hpacket and concluded that it was most likely the rea-9 S5 z, [6 O7 g8 H* B! O7 v2 I3 [
son for the child’s virilization. At that time, they1 C9 Y% ?0 r0 I4 x3 T; Y
decided to put the baby in a separate bed, and the7 ]! R+ ~6 @: _. Z, Y& x
father was not hugging him with bare skin and had. g$ j0 N2 e r' k% z. }9 j, c
been using protective clothing. A repeat testosterone6 U4 P, J2 u3 R: X
test was ordered, but the family did not go to the; Y D6 P& \6 i8 s- J
laboratory to obtain the test.
0 ~0 H0 _) [" X1 o* @Discussion
9 m5 j$ X- h, G. B cPrecocious puberty in boys is defined as secondary3 u# \" p4 q9 \1 {' M: a4 `* @
sexual development before 9 years of age.1,4
/ e& t+ i9 j$ l( s* [) Z0 QPrecocious puberty is termed as central (true) when
2 D4 e4 w3 [$ F fit is caused by the premature activation of hypo-
6 i- q' e$ i N @! \1 X$ R8 {" a A# |thalamic pituitary gonadal axis. CPP is more com-
( x% z x: S P+ T( ~mon in girls than in boys.1,3 Most boys with CPP
$ Z& Q- X1 M& Q% v" f2 cmay have a central nervous system lesion that is6 X, D- B5 n! `" e7 f3 n
responsible for the early activation of the hypothal-
5 n, L: {( f; k7 F! V. Uamic pituitary gonadal axis.1-3 Thus, greater empha-# R+ |/ _1 t! ~/ t, W0 F5 [3 E
sis has been given to neuroradiologic imaging in3 J3 n8 [% `5 @2 ^. v9 S3 T
boys with precocious puberty. In addition to viril-
8 {7 x% X1 e; u1 p8 Q* h) Aization, the clinical hallmark of CPP is the symmet-
; e( B/ m6 ^4 ?7 Lrical testicular growth secondary to stimulation by" O, b3 X/ d6 d# D/ M
gonadotropins.1,3
2 [+ A" }7 l' F* `) KGonadotropin-independent peripheral preco-
}% H" Z$ V" Z) e+ x7 F: tcious puberty in boys also results from inappropriate' r: e) R' [0 Z6 H6 ?$ |: h8 k4 z
androgenic stimulation from either endogenous or
" ^1 [, F5 B: g) z% Sexogenous sources, nonpituitary gonadotropin stim-
5 t# u3 m# w$ U/ M( Uulation, and rare activating mutations.3 Virilizing
/ j5 B G; r E. X( z1 s y# Qcongenital adrenal hyperplasia producing excessive
5 g: G7 b( f: ~+ Vadrenal androgens is a common cause of precocious- g# [. `% n: o$ P- Z
puberty in boys.3,45 J5 [& g# Y' q
The most common form of congenital adrenal
* }, K$ U* E0 j v) T& _hyperplasia is the 21-hydroxylase enzyme deficiency.
: F4 D: f; g7 R- A3 jThe 11-β hydroxylase deficiency may also result in5 U1 o$ | n% R e6 ^; E
excessive adrenal androgen production, and rarely,
% G4 r, B& o$ Y- Kan adrenal tumor may also cause adrenal androgen+ r, ~9 }- B h" @
excess.1,39 c+ P% ~! D H2 E
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from7 ]% T6 k$ b5 C# Q6 r) n/ m* J
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007! T8 D1 j1 ~+ S
A unique entity of male-limited gonadotropin-
9 D1 J4 Z( R. G2 B" [: D6 |independent precocious puberty, which is also known
5 x1 z: y1 x7 _+ `+ las testotoxicosis, may cause precocious puberty at a
) _" c& K2 l# `9 Uvery young age. The physical findings in these boys
* V7 S- J' a6 A+ u9 Pwith this disorder are full pubertal development," }" B" V' ^* F' g
including bilateral testicular growth, similar to boys
# k( a5 G7 d$ V- ?/ R9 n6 n( Rwith CPP. The gonadotropin levels in this disorder
d H7 t/ B1 H3 l# nare suppressed to prepubertal levels and do not show
" C: H! D( O( e3 u; J T9 [pubertal response of gonadotropin after gonadotropin-( X: B6 p( E. p+ w
releasing hormone stimulation. This is a sex-linked* c0 l& F5 E4 _/ ~; D& q' f& F
autosomal dominant disorder that affects only
* H# M7 [6 ?$ @males; therefore, other male members of the family
+ ~7 x, _9 p: h# M0 Zmay have similar precocious puberty.3
! B) ]4 a& A3 ?* g8 G1 C: o) y2 C lIn our patient, physical examination was incon-% ~, V' G4 U& z J$ }- w' l
sistent with true precocious puberty since his testi-
( Q. @7 Z7 v5 ~! V4 l. y- }. `cles were prepubertal in size. However, testotoxicosis& A7 D* l5 w" Y: J7 e
was in the differential diagnosis because his father: I, G/ D3 R8 T, p" [ y' N6 I8 R
started puberty somewhat early, and occasionally,
3 D% h4 f: J4 {1 C" Stesticular enlargement is not that evident in the+ w+ q' r" E( L- ?& O
beginning of this process.1 In the absence of a neg-# g& ?8 m) @& l( b! q0 `
ative initial history of androgen exposure, our
% J- W5 L( i% o: v- z9 \biggest concern was virilizing adrenal hyperplasia,& D$ U5 r4 n3 P- e2 F; ^7 U
either 21-hydroxylase deficiency or 11-β hydroxylase
. L: V+ G% l9 j- e8 o8 Odeficiency. Those diagnoses were excluded by find-6 h. k) C4 @2 K6 a y) u! ]
ing the normal level of adrenal steroids.
' m6 L# f+ v [" l9 x3 O/ ]The diagnosis of exogenous androgens was strongly
* R: F/ \3 G6 t# _4 {! n q9 U: i) jsuspected in a follow-up visit after 4 months because7 m! [& [8 b3 U- l& C6 e7 Z1 O }- h, N
the physical examination revealed the complete disap-
$ Q. s% K2 n g' y, upearance of pubic hair, normal growth velocity, and! c( B0 Z6 Z. V) ^( u% [; {
decreased erections. The father admitted using a testos-
; D( x- @9 A6 Q/ Uterone gel, which he concealed at first visit. He was3 U! U- K" [" C4 X; H
using it rather frequently, twice a day. The Physicians’
" O% D [6 ^1 q) Y3 jDesk Reference, or package insert of this product, gel or
; o- V; ^7 ?- e- T1 g. hcream, cautions about dermal testosterone transfer to
# m& s: w4 I$ ~% V7 [2 _; @unprotected females through direct skin exposure.9 O1 P7 y0 D7 m: X, w( Y4 K2 q8 O
Serum testosterone level was found to be 2 times the \: a7 l& V' Q& K8 ?8 A8 m7 }
baseline value in those females who were exposed to
2 r* @) ?! o& L, Z7 |9 H* neven 15 minutes of direct skin contact with their male e$ h, p' u0 h
partners.6 However, when a shirt covered the applica-8 c" s; ?: G8 P. E
tion site, this testosterone transfer was prevented.
& p. Y e7 @. F- [; w7 W1 D& k$ K! n8 pOur patient’s testosterone level was 60 ng/mL,
- z: ^5 L, k! b1 T& cwhich was clearly high. Some studies suggest that9 A! N. u$ `; `
dermal conversion of testosterone to dihydrotestos-
7 w6 v# w) `( i, r. Eterone, which is a more potent metabolite, is more i0 H4 d8 m! u
active in young children exposed to testosterone
* m) p/ S# `% U) {exogenously7; however, we did not measure a dihy-8 t* N2 c0 I0 ]7 |' \4 c
drotestosterone level in our patient. In addition to* `% t ?- |" i9 f& y/ ?( T) ~
virilization, exposure to exogenous testosterone in% _7 j/ Q q3 M1 j" F* j
children results in an increase in growth velocity and
" Y% R9 q# M* K- T0 Z; xadvanced bone age, as seen in our patient.
4 Z/ x7 O- A8 mThe long-term effect of androgen exposure during
6 F, r* x4 W1 Aearly childhood on pubertal development and final
: d% ]/ z: v2 V/ V8 Uadult height are not fully known and always remain
1 b7 i% h& K% xa concern. Children treated with short-term testos-
. w& r m7 a* c8 j* c& \( D- lterone injection or topical androgen may exhibit some
+ Y( V/ }3 E1 `9 z$ }5 Zacceleration of the skeletal maturation; however, after
3 L1 d' U t) x0 |" x# w% A) \$ E/ mcessation of treatment, the rate of bone maturation/ i9 S, L& V5 l5 Y7 l: t0 j
decelerates and gradually returns to normal.8,9* c6 T" } Q- h6 P) F
There are conflicting reports and controversy
9 t, s' c" l" i' [0 [, ?over the effect of early androgen exposure on adult; ]3 }9 I1 ]+ T( b( f
penile length.10,11 Some reports suggest subnormal- C2 @( ]. `6 |+ @9 p; s
adult penile length, apparently because of downreg-; i& H8 ^" n7 N1 U
ulation of androgen receptor number.10,12 However,; p- X2 I# w6 w; b0 J0 {
Sutherland et al13 did not find a correlation between
2 v/ U* i: T+ o* J& \childhood testosterone exposure and reduced adult8 E- `8 P( [5 w) h! L* J
penile length in clinical studies.3 ~; V- J# k2 A; z2 C) D0 G; e8 B
Nonetheless, we do not believe our patient is
* u( Q: B8 V! bgoing to experience any of the untoward effects from( I5 S* {3 L* D7 n0 z9 U+ o) r. K, d
testosterone exposure as mentioned earlier because
9 d" G- t* ^2 Y o8 Gthe exposure was not for a prolonged period of time.4 }/ E" {9 T, S& m) h2 T L v
Although the bone age was advanced at the time of
: ]9 K( A7 k6 H" H6 adiagnosis, the child had a normal growth velocity at
4 }5 @* S: [2 z3 I- u- `2 e5 I3 Rthe follow-up visit. It is hoped that his final adult( V. s8 G0 Z. k5 K9 J
height will not be affected.
% D" `# {$ I* ~Although rarely reported, the widespread avail-" s6 K4 f. j8 D1 Z0 }
ability of androgen products in our society may; r `$ p* |4 |, Y8 \
indeed cause more virilization in male or female
, l) a% v' d7 s, W; T5 Q6 I lchildren than one would realize. Exposure to andro-
: \0 T( h0 U7 H% ~) u) G$ ?gen products must be considered and specific ques-# z+ a; p+ i3 R* `
tioning about the use of a testosterone product or9 y0 J5 I" ^* Q( u& A; V( n7 r% }
gel should be asked of the family members during
. z4 I: I5 n: P8 U) f! m& Jthe evaluation of any children who present with vir-
! L! U0 Y/ k# X* l- Iilization or peripheral precocious puberty. The diag-+ x* s; k: A; h3 T8 ^. I
nosis can be established by just a few tests and by+ G4 u9 z6 }" F6 ~
appropriate history. The inability to obtain such a0 m2 ~$ G% Y( j4 i
history, or failure to ask the specific questions, may2 h2 d" \2 M% [& u/ T3 ?/ s
result in extensive, unnecessary, and expensive2 Z: U4 e, F* Y) J/ s! O0 U. P
investigation. The primary care physician should be, k" H5 r2 I' Q, C0 _, G
aware of this fact, because most of these children$ d# G3 T4 O0 T$ c# L* G3 `3 [
may initially present in their practice. The Physicians’, `) I* c* B. W
Desk Reference and package insert should also put a
; @: B7 P+ p3 t7 M; b2 P5 y+ }warning about the virilizing effect on a male or
2 k: C( s: _5 a* A6 U; G( u4 g" vfemale child who might come in contact with some-
. N% D) x& J+ E c5 g1 m' Aone using any of these products.
) N3 ~7 h2 V a. YReferences
' u3 | S9 @' A4 b5 v1. Styne DM. The testes: disorder of sexual differentiation
$ L% s. h$ L! A* _' O0 k8 Eand puberty in the male. In: Sperling MA, ed. Pediatric- T$ I. }& ^9 ?9 [" ]) c* x
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;/ f1 T1 K8 D% \; @
2002: 565-628.9 | N$ P. j4 `: f
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious- E1 x' C% R* T3 p& {5 B
puberty in children with tumours of the suprasellar pineal |
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