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Sexual Precocity in a 16-Month-Old) B: k! W& c j( }2 l
Boy Induced by Indirect Topical
+ D& h7 s" a5 }" r* x: |Exposure to Testosterone
. s" c, I3 G) X* d# m7 ~/ V1 C* dSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
1 c8 P/ `/ d- q6 l+ [8 ?+ k8 rand Kenneth R. Rettig, MD1; Y1 p0 o5 z8 w5 l, D& {6 \
Clinical Pediatrics* P& T4 _* j% s
Volume 46 Number 6+ K# i7 l7 b" X+ E5 a( h C4 Q
July 2007 540-543
/ z U6 ]- Y& T# K© 2007 Sage Publications
( N" [. J8 R! T7 X10.1177/0009922806296651. Y/ N' K3 \' Q! u
http://clp.sagepub.com, s) i$ K9 G3 b4 p% R
hosted at
$ S/ \( }6 U/ h2 }, uhttp://online.sagepub.com
9 l% f( I3 T1 a1 {: sPrecocious puberty in boys, central or peripheral,& E7 q9 _0 g$ r3 y
is a significant concern for physicians. Central
, L3 n! Z& b- j8 fprecocious puberty (CPP), which is mediated2 f6 O$ _8 D: ]: e( ]) Y
through the hypothalamic pituitary gonadal axis, has
7 _+ T; H3 u, B8 H1 U" W. Ha higher incidence of organic central nervous system
i' B5 r$ H3 |* M7 @" D) }, \lesions in boys.1,2 Virilization in boys, as manifested
: W( @ }7 X( L& e; |, ?' dby enlargement of the penis, development of pubic
/ ~& t- Y; S7 T) [% _% c3 Y5 bhair, and facial acne without enlargement of testi-
4 b; {. \, a2 A8 K% I0 _. Tcles, suggests peripheral or pseudopuberty.1-3 We" ]7 g: k. O- m: T
report a 16-month-old boy who presented with the8 J* j: P6 `& I6 ]: c! @9 X0 U) V
enlargement of the phallus and pubic hair develop-
2 P- X& X" s, `ment without testicular enlargement, which was due- i0 l/ C: s- [! q5 R6 ^! o
to the unintentional exposure to androgen gel used by
% `% B0 s+ e5 E$ m) v1 ethe father. The family initially concealed this infor-
& S/ J$ E3 _ X$ u0 ]0 `' O$ X) Imation, resulting in an extensive work-up for this2 o/ a4 Q( a& @
child. Given the widespread and easy availability of
8 E4 d* q! J/ v( X- q7 J7 t) y8 [" etestosterone gel and cream, we believe this is proba-' U* }, x- p9 w" d
bly more common than the rare case report in the
8 T4 P/ b; m) A9 Q8 uliterature.4
3 s# G% D% q% }2 `. ^% ]Patient Report7 g. k' P( C% D9 v2 C
A 16-month-old white child was referred to the
8 K' V& e3 d/ dendocrine clinic by his pediatrician with the concern
, `7 n, L1 H/ a8 dof early sexual development. His mother noticed
- ] H4 @2 B6 g! @5 klight colored pubic hair development when he was2 W: d- r* z# i8 g& \3 `
From the 1Division of Pediatric Endocrinology, 2University of; g) [7 l# G' ]
South Alabama Medical Center, Mobile, Alabama.# [$ A8 g0 ~# B* @8 w
Address correspondence to: Samar K. Bhowmick, MD, FACE, K5 i: x. J: A. z0 w2 m' p
Professor of Pediatrics, University of South Alabama, College of
3 L3 B' E% d/ j6 ]Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
/ E: B L: w! Me-mail: [email protected].- R0 O1 a/ N7 T2 d
about 6 to 7 months old, which progressively became
, s% y. f, \4 w- c* k2 I1 `6 adarker. She was also concerned about the enlarge-
/ S2 b* B5 X7 i3 {9 Vment of his penis and frequent erections. The child
5 T$ k7 u7 g: W: L. xwas the product of a full-term normal delivery, with
/ m; B' i$ P- O- h0 s0 Ga birth weight of 7 lb 14 oz, and birth length of! R; R+ z- y/ Q: d- A* I% w: ^
20 inches. He was breast-fed throughout the first year
. b$ Z; Y3 k1 f; i0 bof life and was still receiving breast milk along with7 X& H6 F3 N, ~, ?4 u
solid food. He had no hospitalizations or surgery,
1 W7 p+ P+ ~ ^' B1 [) ]0 wand his psychosocial and psychomotor development
: m1 X, |: b# ~1 Z8 J% Ywas age appropriate.
8 G& `7 e c; n U- R& hThe family history was remarkable for the father, ^& F4 P/ h% I6 e( R. y$ t
who was diagnosed with hypothyroidism at age 16,
$ D8 f3 A Z! ?) ~which was treated with thyroxine. The father’s" L7 L0 [& @/ O; R3 g' _4 q$ K$ j9 M
height was 6 feet, and he went through a somewhat2 Q$ _0 l) ^5 O$ G
early puberty and had stopped growing by age 14.4 H r& T* h. D+ r' U; A) K* n
The father denied taking any other medication. The
, _ [+ Z" R/ j# Dchild’s mother was in good health. Her menarche! `3 _$ D L% Q$ b, @
was at 11 years of age, and her height was at 5 feet; f) F& ?4 n" l7 s# A, _
5 inches. There was no other family history of pre-' V8 k" O: D7 W+ ]6 ^3 q
cocious sexual development in the first-degree rela-
% V* ~) i: a+ r: q! Htives. There were no siblings.$ J5 g I7 L& ?, l9 c& s
Physical Examination- |1 G( ^7 w; j5 r9 y" ~/ @
The physical examination revealed a very active,
& [+ d* B" @% M, \% Gplayful, and healthy boy. The vital signs documented
$ T" V. h/ ?2 C9 Z7 Ja blood pressure of 85/50 mm Hg, his length was: h" Q, @7 }8 V
90 cm (>97th percentile), and his weight was 14.4 kg
& b3 u) L+ }2 l(also >97th percentile). The observed yearly growth
. z ?% ^: c4 \" uvelocity was 30 cm (12 inches). The examination of- r I- k1 i4 S+ S) j
the neck revealed no thyroid enlargement." F1 T7 ]7 Z" `) D* x/ V* t
The genitourinary examination was remarkable for3 q5 Z, {: ?; R: r% u! G0 n! p
enlargement of the penis, with a stretched length of7 f8 d# E9 B6 S8 J6 C6 x
8 cm and a width of 2 cm. The glans penis was very well
5 |5 h' B# ?( J$ X+ Adeveloped. The pubic hair was Tanner II, mostly around& I+ t! F" b; T" C4 _% E' e
540" V# `/ n, {. r! W6 V) D! F
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
; N* {4 ~) y* ]3 [! uthe base of the phallus and was dark and curled. The
) Y; y) T: b* Y Ntesticular volume was prepubertal at 2 mL each.
. }/ I& x2 s% ]- v* R6 YThe skin was moist and smooth and somewhat
' L7 F7 ^8 |& e% j5 b0 f7 Ioily. No axillary hair was noted. There were no6 T5 M2 l q8 b4 w+ y
abnormal skin pigmentations or café-au-lait spots.) k l+ O3 v: Z$ _2 D, `, Z% p
Neurologic evaluation showed deep tendon reflex 2+0 k# j- }4 I' u0 G6 t
bilateral and symmetrical. There was no suggestion* N, L3 R& q1 E$ Y
of papilledema.
2 q# ^: O i( p( yLaboratory Evaluation
6 ]0 B, i6 ]- b, rThe bone age was consistent with 28 months by
1 V+ ]5 J4 J0 O7 e! A# @using the standard of Greulich and Pyle at a chrono-' k$ ^0 @: J4 r
logic age of 16 months (advanced).5 Chromosomal
- _/ X" k' ]; y$ x' v( ckaryotype was 46XY. The thyroid function test
, o' \# J9 a p0 Y- j' L/ wshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
! {5 U5 ]' U$ ^lating hormone level was 1.3 µIU/mL (both normal).! }& o7 x: L$ F5 L q
The concentrations of serum electrolytes, blood
) O# Y& G( [ {5 L1 wurea nitrogen, creatinine, and calcium all were
- i X9 j2 Q* W' A- t" v z, Cwithin normal range for his age. The concentration, @; a, e3 c9 S: s/ T; @
of serum 17-hydroxyprogesterone was 16 ng/dL
7 g( D, ~3 Z3 W, z; {& O4 p- x(normal, 3 to 90 ng/dL), androstenedione was 203 P- E& m$ l' f4 w
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-/ h9 o6 U. Q6 I0 w
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
. M& s1 W7 x2 i" r) W mdesoxycorticosterone was 4.3 ng/dL (normal, 7 to
* ^/ v8 a5 |# o" I8 {; K49ng/dL), 11-desoxycortisol (specific compound S)
" M- p/ G+ s% {& f* N2 R1 o. Ywas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-) H5 f+ E9 b! a
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total* h- O' h: E. z$ j
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
' `6 _4 d# G! }3 y" y1 H- Dand β-human chorionic gonadotropin was less than& e$ W, x9 k$ j' N
5 mIU/mL (normal <5 mIU/mL). Serum follicular5 y$ g' M- t- \
stimulating hormone and leuteinizing hormone
" j5 w( \; Z7 B; B# E$ D2 dconcentrations were less than 0.05 mIU/mL8 b+ }1 P5 r8 {; @5 k$ A) X
(prepubertal).
" l% F8 E; U/ {1 \+ ^The parents were notified about the laboratory
; a- \" y! ]" i; K' C, |1 Sresults and were informed that all of the tests were# p6 p5 q0 `) k" }% j2 p
normal except the testosterone level was high. The
& B# K, x4 Z3 Z" Rfollow-up visit was arranged within a few weeks to' Q/ {" G' b; T& w( x2 h
obtain testicular and abdominal sonograms; how-
) \/ Q: N- @" N. b- ~% g$ uever, the family did not return for 4 months.
5 ~6 _* \% H8 v+ |: @9 L: ~& ?Physical examination at this time revealed that the/ X$ y1 a* M/ B0 ~, t. |* M
child had grown 2.5 cm in 4 months and had gained
2 H! ^/ h2 ~/ b4 x5 c2 kg of weight. Physical examination remained
1 E; P4 ^4 S; y; E- |5 r6 Eunchanged. Surprisingly, the pubic hair almost com-
! U! C2 Z- A$ d( A, u4 i( mpletely disappeared except for a few vellous hairs at
$ |6 S2 e7 |# ^/ c$ K; zthe base of the phallus. Testicular volume was still 2; x* I `- o/ f( c, F
mL, and the size of the penis remained unchanged. |- e3 a' X S2 x. @& {" n
The mother also said that the boy was no longer hav-# D0 N4 c6 J0 F6 x+ z+ v3 `& f; l
ing frequent erections.
2 r9 i" {5 S9 o& [0 V IBoth parents were again questioned about use of
/ H) \! j' f n5 p' f1 hany ointment/creams that they may have applied to! Z0 d4 ?# ]/ `* S8 ], f0 E
the child’s skin. This time the father admitted the
" ~; v9 X$ B1 o; t9 A0 ^! E) TTopical Testosterone Exposure / Bhowmick et al 541, G: A+ K7 y/ j+ L8 A6 V
use of testosterone gel twice daily that he was apply-
: }9 m2 y b$ z, x7 c: ming over his own shoulders, chest, and back area for9 v9 E: S$ _# i5 D; i
a year. The father also revealed he was embarrassed" E- c2 o' P- e& P) Q2 u
to disclose that he was using a testosterone gel pre-9 C* m2 r0 `$ W; q
scribed by his family physician for decreased libido
6 D+ n; R# Z( D& Y: p4 y- Ssecondary to depression.) p; j3 `" ]) V% X; b1 ]
The child slept in the same bed with parents.
4 ?" g( o' c+ B/ AThe father would hug the baby and hold him on his
_- A4 |1 f, z( jchest for a considerable period of time, causing sig-6 R3 s$ p) i9 B3 W7 _% N9 P" t
nificant bare skin contact between baby and father.
! u* {* s- z+ ~The father also admitted that after the phone call,
- F, a3 r4 q* W& l; [when he learned the testosterone level in the baby/ v8 g3 w- A# N# g/ E* r4 q5 I; q
was high, he then read the product information$ C; Z3 r( ?$ [8 Y
packet and concluded that it was most likely the rea-8 x1 Y, a$ n% u; Z$ ]
son for the child’s virilization. At that time, they
2 K; m* U0 K1 T4 c2 ~decided to put the baby in a separate bed, and the
" {0 v) l j) `0 W5 U! Ifather was not hugging him with bare skin and had
2 _* n! J/ K- m$ ^: y; N B0 }- ^been using protective clothing. A repeat testosterone0 w! {' K: j9 y; u9 ~6 u# f
test was ordered, but the family did not go to the
! J# O/ c4 n- \* b8 @; [1 jlaboratory to obtain the test.
. C+ h6 F4 k" n1 ~- C; I T9 sDiscussion
# O) b$ J" S6 m. @Precocious puberty in boys is defined as secondary
6 Z4 g; A. Z3 s2 J* K Zsexual development before 9 years of age.1,4
5 b! f0 x' Z; f8 N6 s) bPrecocious puberty is termed as central (true) when
' h* z& ]) H7 i, b) i1 zit is caused by the premature activation of hypo-* ?' a) |4 T* ]/ K2 `$ b
thalamic pituitary gonadal axis. CPP is more com-
* k, [; ]0 r' c( I) }. ^& |mon in girls than in boys.1,3 Most boys with CPP
3 ]4 D* l" G* e1 u$ i) `may have a central nervous system lesion that is
2 [& i, r$ \; tresponsible for the early activation of the hypothal-
5 I/ X4 m' E O# X3 i) M9 ~amic pituitary gonadal axis.1-3 Thus, greater empha-
$ ~9 B+ O$ O/ bsis has been given to neuroradiologic imaging in
( S W! P( I7 p# `- v! ]boys with precocious puberty. In addition to viril-
' g$ d6 ]! u6 b4 S, Jization, the clinical hallmark of CPP is the symmet-" w% O2 m6 n, V* U
rical testicular growth secondary to stimulation by% H- E' ]$ H: S4 T* y7 c
gonadotropins.1,3' J8 ~0 x) Y/ u: w& C
Gonadotropin-independent peripheral preco-
! d. j5 Y7 H a5 K9 D" @& u5 @cious puberty in boys also results from inappropriate
/ l1 t, ~7 j7 w5 K$ _. A8 aandrogenic stimulation from either endogenous or4 m$ y2 i9 \$ ~; H! \9 J. h
exogenous sources, nonpituitary gonadotropin stim-0 } y: J9 Y+ z8 t6 B
ulation, and rare activating mutations.3 Virilizing9 r# R' _4 q' {9 G$ X! w" ^% c, l, z: V
congenital adrenal hyperplasia producing excessive
h; r( h L- H* ^2 ~4 _5 tadrenal androgens is a common cause of precocious/ T+ f" C; B! X1 Q
puberty in boys.3,4
. |2 u) V: b G$ v2 iThe most common form of congenital adrenal0 R# a7 Y+ a' q) B. F8 r3 y' w' o8 [
hyperplasia is the 21-hydroxylase enzyme deficiency.
% ` H) p1 a4 J, }4 X* E0 sThe 11-β hydroxylase deficiency may also result in5 Y: u6 x2 f& F' U! S9 O
excessive adrenal androgen production, and rarely,
/ V/ K8 D7 T1 f! J4 S* ?$ zan adrenal tumor may also cause adrenal androgen- x6 v. X: g3 A$ W0 P
excess.1,3
0 h! L, X& K% Hat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from+ s' R6 N' }+ Y: \0 U6 p
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007& |# \" j6 b, _! m' k
A unique entity of male-limited gonadotropin-8 E5 G L* E2 p* H; ^$ v
independent precocious puberty, which is also known% H/ c, i( K& u% f( j* V. w
as testotoxicosis, may cause precocious puberty at a5 ]8 O6 u9 t7 U9 l. f/ E
very young age. The physical findings in these boys* e; [( e9 D9 Q. w! H' k
with this disorder are full pubertal development,
* b1 }% \$ ~, I" Q( q- cincluding bilateral testicular growth, similar to boys0 o4 {1 D1 b4 I1 z) W* `$ I
with CPP. The gonadotropin levels in this disorder
* L" V3 g# F' vare suppressed to prepubertal levels and do not show( l; Y+ S P R& v# c8 k' C2 q* M
pubertal response of gonadotropin after gonadotropin-4 Q6 [- w+ x; v$ Y; r" v j* B$ d+ b
releasing hormone stimulation. This is a sex-linked$ G- {4 s, V* l
autosomal dominant disorder that affects only
2 S, Y. G( r0 w- J8 ~males; therefore, other male members of the family
& a2 O& E) R& X+ o. Tmay have similar precocious puberty.3
3 P, p- C5 k* C4 K9 v! K5 K2 d6 jIn our patient, physical examination was incon-
1 f. Q2 _3 F, t/ o6 Y P3 M2 [sistent with true precocious puberty since his testi-
4 c5 c" u& W: h0 _0 [cles were prepubertal in size. However, testotoxicosis
7 d4 ^4 H- d, d0 i# Z3 f& owas in the differential diagnosis because his father
| `) A$ Q# u5 X4 l1 b2 ^" lstarted puberty somewhat early, and occasionally,! Q2 T( l# i1 F+ i
testicular enlargement is not that evident in the, v4 f6 ~9 l2 e* \* f; W
beginning of this process.1 In the absence of a neg-, p5 U: y: \. q% R4 ^9 Q
ative initial history of androgen exposure, our* ]4 F3 P5 A: X+ v8 [' `
biggest concern was virilizing adrenal hyperplasia,$ [; M, o: d$ D6 G
either 21-hydroxylase deficiency or 11-β hydroxylase3 F! o. [7 j9 w& ]6 a
deficiency. Those diagnoses were excluded by find-
6 z' @3 l9 R5 O% N2 ?ing the normal level of adrenal steroids.
' C' n- X, B. X/ Y5 R! S# ZThe diagnosis of exogenous androgens was strongly
* w: @. \9 w: Z i6 w R9 bsuspected in a follow-up visit after 4 months because8 {0 W% G# `, _& V* w; f: m
the physical examination revealed the complete disap-1 x; x; j0 M" L/ W( f. }
pearance of pubic hair, normal growth velocity, and
& \6 {/ K9 l$ c8 Wdecreased erections. The father admitted using a testos-- Y, z! E. {2 ~( t
terone gel, which he concealed at first visit. He was
4 p5 S" V8 G' d; u( M9 V) ausing it rather frequently, twice a day. The Physicians’' `: i# u# M9 a+ @4 l3 m* ~
Desk Reference, or package insert of this product, gel or/ y, V6 h. g4 F5 r( V, v
cream, cautions about dermal testosterone transfer to; J8 C% e; W$ ~. P' Z* @
unprotected females through direct skin exposure.2 ^& Z7 m6 ?' h* t y" G2 u
Serum testosterone level was found to be 2 times the
+ ? `+ E( j8 Obaseline value in those females who were exposed to2 H0 Z' G# [) ?. e
even 15 minutes of direct skin contact with their male* C. B- u& ^/ x! W* O
partners.6 However, when a shirt covered the applica-
+ U9 c0 x, H9 h7 M- _) v& Ytion site, this testosterone transfer was prevented." i6 Y0 G# a3 s$ \ i, H: {* r
Our patient’s testosterone level was 60 ng/mL,
: S4 @% I) T9 [5 P9 [which was clearly high. Some studies suggest that4 G3 I; ^7 M5 C- ^. \' X
dermal conversion of testosterone to dihydrotestos-0 u4 c: ~% t& i( [( H9 G4 C
terone, which is a more potent metabolite, is more
: e8 @5 S; W* q& S- ~active in young children exposed to testosterone3 |9 n+ Q r/ c* s% O) d
exogenously7; however, we did not measure a dihy-
4 I! k! M# l: |" A2 a& edrotestosterone level in our patient. In addition to# w( G# z5 n! ~3 g- H
virilization, exposure to exogenous testosterone in
1 U3 `& _' c2 N' G; fchildren results in an increase in growth velocity and
7 k$ L# ~" E9 k0 @5 ^: jadvanced bone age, as seen in our patient.' E2 C% F' H( N, V9 ]; @
The long-term effect of androgen exposure during
' S h$ j, m$ C4 g$ X% z- uearly childhood on pubertal development and final
$ p! z0 p( J" h: c; jadult height are not fully known and always remain
0 C/ G+ ^+ E$ F: ja concern. Children treated with short-term testos-9 d2 ~' C* d0 f8 b- f- Z- p
terone injection or topical androgen may exhibit some0 o: _: \5 |3 e* p
acceleration of the skeletal maturation; however, after
1 C$ C$ [- T+ N; Ccessation of treatment, the rate of bone maturation0 V- b! z/ d4 T8 ~$ o! a& ?& K R/ B
decelerates and gradually returns to normal.8,9; a( {: H& q( D
There are conflicting reports and controversy
, g, y* w1 J3 i; [over the effect of early androgen exposure on adult1 B0 m8 ]( A0 H: ]( y9 p
penile length.10,11 Some reports suggest subnormal0 J& S q. I- X- q" j( p
adult penile length, apparently because of downreg-
5 P. C5 k, w( a* m. E* Aulation of androgen receptor number.10,12 However,: |* f' \- b% N( o" o1 D
Sutherland et al13 did not find a correlation between
0 K3 M0 a, {+ k$ u' Ochildhood testosterone exposure and reduced adult) h7 o8 f& ~ i+ @
penile length in clinical studies.. B# ]+ @& r+ b* O7 x9 K
Nonetheless, we do not believe our patient is
4 }8 Z, v5 b. |" r7 }going to experience any of the untoward effects from
; |! Y# e: r5 S/ q: a$ _, |( ktestosterone exposure as mentioned earlier because- c; V# B T7 ?: H
the exposure was not for a prolonged period of time.
* h* L4 T! I* n+ c1 gAlthough the bone age was advanced at the time of
) N2 p: F1 f! ]& s3 [- L3 M- W$ h0 e& Qdiagnosis, the child had a normal growth velocity at
$ F1 H7 C9 ^! Hthe follow-up visit. It is hoped that his final adult
% B9 u6 B: ]; ~1 ?, jheight will not be affected.4 s, c0 m2 ^+ I7 q j$ v+ ]
Although rarely reported, the widespread avail-' R* m" a" b4 [! z9 @& @9 x- K
ability of androgen products in our society may$ { b2 c4 l& {2 O3 L6 p
indeed cause more virilization in male or female" j, i# p) E, J& G# P3 f# z
children than one would realize. Exposure to andro-* I# {! }- O- ^* ^
gen products must be considered and specific ques-
0 M; N2 Z4 B2 ^: Rtioning about the use of a testosterone product or/ N! t; _& w, I. c7 \& Z
gel should be asked of the family members during
+ S9 I& O" m* S. }$ Hthe evaluation of any children who present with vir-, C2 ~% o' g: `) t; M
ilization or peripheral precocious puberty. The diag-
* y7 \& a( G- w, p1 _1 w Bnosis can be established by just a few tests and by& u! B2 [: B% ]9 i( j) q
appropriate history. The inability to obtain such a
( F R* k! ], H5 P8 w' |% W( y& Whistory, or failure to ask the specific questions, may
8 Z( U) y9 y8 J/ X& Iresult in extensive, unnecessary, and expensive9 f# F# A' w5 [( x5 d+ q# z
investigation. The primary care physician should be
) B6 |1 ^' t- V5 v) w( B$ K2 i" h( Saware of this fact, because most of these children
0 Z) o' J& R$ J+ r, pmay initially present in their practice. The Physicians’
; h3 X4 V& n# ^5 W% y }Desk Reference and package insert should also put a8 m9 d1 J% _% z8 ]8 O* W
warning about the virilizing effect on a male or' z7 |) W) f4 R1 Q1 I8 k
female child who might come in contact with some-
! q' s1 F, ~( v6 w6 q1 rone using any of these products.9 k) k6 E3 E [* t
References) [% a" f3 m5 X% V6 \, e" _' s
1. Styne DM. The testes: disorder of sexual differentiation
( L- Y& l) L0 D. aand puberty in the male. In: Sperling MA, ed. Pediatric1 e3 ?0 X4 \% ]) X. Q
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
" X! U; r9 a. Q' c% g; T2002: 565-628.- N+ L. S: K) |
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious4 N! c2 B# C: w
puberty in children with tumours of the suprasellar pineal |
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