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Sexual Precocity in a 16-Month-Old
: O4 s* A' R9 `! L1 G, LBoy Induced by Indirect Topical+ w1 S n- K* g/ D( v
Exposure to Testosterone
6 ^$ c* ]- ]. XSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
# H4 C5 P9 ?% f0 v1 k1 {; s! aand Kenneth R. Rettig, MD1
2 ~7 k! c; |/ Y8 dClinical Pediatrics
0 R/ H/ |; B) S/ y2 F7 `Volume 46 Number 6
5 L' r2 b* c- l) X! E' |: p6 RJuly 2007 540-543
# L$ ~, x8 M: X© 2007 Sage Publications* e6 C. J; h+ F
10.1177/0009922806296651
! l. g: ?0 V4 [" W( h4 ^+ s" k# \% bhttp://clp.sagepub.com
( ~5 ~- N4 G9 w) Zhosted at
, F ?2 Q, ^- ?5 M# R6 ]http://online.sagepub.com. [" _9 S1 \/ _
Precocious puberty in boys, central or peripheral,* y6 R+ \$ U) q
is a significant concern for physicians. Central7 I! ?. E* s/ N% x7 }+ T1 P
precocious puberty (CPP), which is mediated' u2 l& `% t6 Y2 c/ ^5 A
through the hypothalamic pituitary gonadal axis, has6 @* h; X0 P0 D( C2 Z# ?
a higher incidence of organic central nervous system
# Z0 D$ s1 i6 V! @. V2 Elesions in boys.1,2 Virilization in boys, as manifested
# V+ Z' m9 Y- n# t/ N6 `by enlargement of the penis, development of pubic# n* u! o: A, Y/ X( v
hair, and facial acne without enlargement of testi-
4 e# ^/ n& E' b# f" Ecles, suggests peripheral or pseudopuberty.1-3 We
; @/ z" O) U. e9 kreport a 16-month-old boy who presented with the
$ W8 b' E5 M: K, g/ L# m& Tenlargement of the phallus and pubic hair develop-
5 z7 X c D% ]- o2 cment without testicular enlargement, which was due
; `/ B7 j* y1 p* w- L4 N% Bto the unintentional exposure to androgen gel used by
8 a8 {9 ~4 I- M8 D5 L8 [4 d, cthe father. The family initially concealed this infor-
2 B3 y6 q8 o* P! Qmation, resulting in an extensive work-up for this
_5 B7 t* R# ], n' B* _8 uchild. Given the widespread and easy availability of% `3 X) h2 z, k, M, U; B6 e4 i% u) T
testosterone gel and cream, we believe this is proba-
{' p2 Q# s: E. c+ r, m$ ?bly more common than the rare case report in the& z O2 l) X) Q: l
literature.4
' L2 I6 i4 A8 e2 B8 \" e1 KPatient Report
) T+ a4 K; Q) I" zA 16-month-old white child was referred to the# h0 ?+ Q& [5 A6 K7 M
endocrine clinic by his pediatrician with the concern" b; a- l, c" M; ^
of early sexual development. His mother noticed% J- Q9 V" l& ~: T: [: B2 ]9 M
light colored pubic hair development when he was
1 E' t8 g- k& \From the 1Division of Pediatric Endocrinology, 2University of0 l3 I/ i S6 W2 ^; ~
South Alabama Medical Center, Mobile, Alabama.
, _/ U/ m; R! f M: s3 ^- wAddress correspondence to: Samar K. Bhowmick, MD, FACE,; D6 d) E$ ^! X2 h
Professor of Pediatrics, University of South Alabama, College of8 W" T, ?9 J k4 n
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;& C q# o) r- K. } a
e-mail: [email protected].
( b' D7 D0 s8 |3 ?/ w4 i+ Oabout 6 to 7 months old, which progressively became
' R2 `# b9 b6 R" e1 pdarker. She was also concerned about the enlarge-
4 r+ j) l9 l b2 D& u4 W3 `ment of his penis and frequent erections. The child7 w8 ^9 i d: ?) g' a" S+ Q
was the product of a full-term normal delivery, with
2 n8 N/ Q, W( x0 V) ~a birth weight of 7 lb 14 oz, and birth length of8 i1 p- f1 X6 X3 @; k" L
20 inches. He was breast-fed throughout the first year7 p6 T$ L! i/ Q7 h- y0 U; ?/ h) ?
of life and was still receiving breast milk along with
8 e, b& ~& j8 V$ U) Zsolid food. He had no hospitalizations or surgery,3 |2 T0 e9 s, }. `* g5 p' F
and his psychosocial and psychomotor development. }( L" `& @6 p
was age appropriate.
- I! o8 Z, Q, E& v \9 oThe family history was remarkable for the father, P6 `$ N( V- A m7 C; b5 \
who was diagnosed with hypothyroidism at age 16,' `4 I% K* C: x' G7 U# D
which was treated with thyroxine. The father’s
- v" k- n6 e# ^; \3 V) S3 Xheight was 6 feet, and he went through a somewhat5 V- y6 ^% [6 p" x4 U
early puberty and had stopped growing by age 14.+ c% j- [- M' V- U4 m# l2 l
The father denied taking any other medication. The: O; r! d: @8 U+ M2 V- L+ P
child’s mother was in good health. Her menarche9 z: y: I& M& _3 J
was at 11 years of age, and her height was at 5 feet; Z [8 ^2 x" S3 ?: W* s$ L
5 inches. There was no other family history of pre-
; C3 G9 ^7 h: E' E8 K1 Pcocious sexual development in the first-degree rela-! |/ w3 z5 A+ C/ D
tives. There were no siblings.
2 @: T7 d( N6 Q; n( N: A. C3 CPhysical Examination
: ^' j: O+ I! A1 {9 d; OThe physical examination revealed a very active,
% A9 U" m9 K& Mplayful, and healthy boy. The vital signs documented) }8 e/ O; _8 Q/ G# e! @" m0 E
a blood pressure of 85/50 mm Hg, his length was
! p. l+ p* J9 z6 c+ }90 cm (>97th percentile), and his weight was 14.4 kg7 J3 B$ ^& K2 B1 ^' [( a/ l
(also >97th percentile). The observed yearly growth
% s& G& ^4 D! z) ?2 U1 Avelocity was 30 cm (12 inches). The examination of8 V4 B; ~* w' w# Q4 E
the neck revealed no thyroid enlargement.7 g8 P- i, J9 ^2 G
The genitourinary examination was remarkable for1 ]# ]5 O) B- Z+ |
enlargement of the penis, with a stretched length of
5 t/ H+ W" o3 |* H9 s1 M8 cm and a width of 2 cm. The glans penis was very well
) k4 ~! q7 L. `! fdeveloped. The pubic hair was Tanner II, mostly around
+ T7 W6 Z( f- t$ t: z540. @1 K6 d; B3 l
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
, f( |% g# v P/ Z- G zthe base of the phallus and was dark and curled. The
# M0 U: j( { Ytesticular volume was prepubertal at 2 mL each." z ]7 }% e: f% T
The skin was moist and smooth and somewhat3 R7 L: B" f. S0 ?/ z" M
oily. No axillary hair was noted. There were no) y( [8 i9 q% r/ j( x& [( j; \1 g
abnormal skin pigmentations or café-au-lait spots.
, U4 Q* K& p5 }, S3 ~$ j/ YNeurologic evaluation showed deep tendon reflex 2+
+ X1 R& e" C0 |3 c/ y. @) Z) J4 tbilateral and symmetrical. There was no suggestion( l# O/ m: s; w- H+ W3 P2 r
of papilledema.
/ a+ f* o: j0 d. n( S( D% GLaboratory Evaluation9 [+ Z3 |* ~0 l5 Z x
The bone age was consistent with 28 months by
6 P5 y3 i3 s' h1 ?using the standard of Greulich and Pyle at a chrono-
& `! l5 o ?! ~0 G6 dlogic age of 16 months (advanced).5 Chromosomal
7 _7 z3 p$ b/ h7 a- d) s [karyotype was 46XY. The thyroid function test# n; T3 @5 g) T
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
" R$ m0 t( D. B' i G' i; e1 Y$ Wlating hormone level was 1.3 µIU/mL (both normal).# |- S i9 ]5 h: N3 [
The concentrations of serum electrolytes, blood. {; m" P3 l2 H) @( v
urea nitrogen, creatinine, and calcium all were
, C5 I9 L0 E. }5 [/ A$ hwithin normal range for his age. The concentration
) s. |# k/ b: S6 cof serum 17-hydroxyprogesterone was 16 ng/dL
2 w) q) @% M9 C' s$ z( S(normal, 3 to 90 ng/dL), androstenedione was 207 k- z5 M& o# R# p# J/ Y
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
, G8 W, b# r# J- bterone was 38 ng/dL (normal, 50 to 760 ng/dL),
. t. [; `. w w! n5 Kdesoxycorticosterone was 4.3 ng/dL (normal, 7 to& u) l3 X. @. O. E- @2 h' @+ Y
49ng/dL), 11-desoxycortisol (specific compound S)
; U) I6 W' k" p: A3 U% P. W6 p6 zwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-5 A# R$ Z3 R; N* A' [' n% _5 P
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total2 \% p: y8 y- q# |% u, Y6 o
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
1 {* @; S# z; H+ ], |and β-human chorionic gonadotropin was less than
( @: _9 R% c, i: B" Q* w* {& U; c5 mIU/mL (normal <5 mIU/mL). Serum follicular& N0 c* [9 X5 m! x
stimulating hormone and leuteinizing hormone4 T5 I2 |) K/ T, [
concentrations were less than 0.05 mIU/mL
4 v9 t, t8 E; a5 W(prepubertal).
( v" r' \0 N3 x8 C' b+ |3 oThe parents were notified about the laboratory0 A% v2 |& s' y; ]) U
results and were informed that all of the tests were" ?8 i. c# F* q3 f* o! T0 J
normal except the testosterone level was high. The
: t$ ?! U7 C9 C) h8 Y% z3 Ufollow-up visit was arranged within a few weeks to; N6 d# D6 l0 s. V8 g; E3 b
obtain testicular and abdominal sonograms; how-
2 J& o7 O4 y3 K$ u/ \ever, the family did not return for 4 months.* u. Y/ l: w: a
Physical examination at this time revealed that the- T4 a2 s B2 C' Q0 R
child had grown 2.5 cm in 4 months and had gained
3 e, R0 _# C' }" l$ F5 P3 W2 kg of weight. Physical examination remained _6 i2 [+ {7 ~9 u7 r% K5 T
unchanged. Surprisingly, the pubic hair almost com- k; O3 z) Z" J* z( Y; _1 K8 X
pletely disappeared except for a few vellous hairs at" M& H7 J6 Y5 n W8 t
the base of the phallus. Testicular volume was still 2/ a {) ~9 e/ h" c+ m
mL, and the size of the penis remained unchanged.1 S* L& _; N9 I' g; \9 |
The mother also said that the boy was no longer hav-
. P' e$ ?. U% H% d3 S( v7 Y. King frequent erections.& y8 i& t1 ? H/ s' K
Both parents were again questioned about use of
% M/ X( N0 V3 a; zany ointment/creams that they may have applied to
/ N( j. c7 {( l& ithe child’s skin. This time the father admitted the' _; ]9 I0 w; O+ Q- r' @$ ?
Topical Testosterone Exposure / Bhowmick et al 541* w |' w* O; }& V6 I
use of testosterone gel twice daily that he was apply-
4 b* d$ F4 g, A7 `1 qing over his own shoulders, chest, and back area for) O" ~6 H/ J8 `# T6 L* x
a year. The father also revealed he was embarrassed
: }. b0 ?7 k2 S% p0 W6 M$ kto disclose that he was using a testosterone gel pre-4 R. S3 Y) t6 D0 w( u2 x
scribed by his family physician for decreased libido
! C0 C. C1 d/ O Ysecondary to depression.
, H: ?% X% e4 h" ^The child slept in the same bed with parents.' [: O5 g/ A5 A, H6 y/ R
The father would hug the baby and hold him on his! O, |0 H3 W2 V) q! v
chest for a considerable period of time, causing sig-, z8 \# E; T2 {# r4 L$ e( U) U2 B
nificant bare skin contact between baby and father.
( g$ z% @/ [' I3 @/ o& E& zThe father also admitted that after the phone call,3 V$ a1 s! J* H0 h
when he learned the testosterone level in the baby
+ z5 i% ~3 c4 x4 Iwas high, he then read the product information
+ R% _/ I" L. l) i, z7 Opacket and concluded that it was most likely the rea-, c: }, O. _. t
son for the child’s virilization. At that time, they
; L3 _) L. F( c: W* v8 Y$ R9 Gdecided to put the baby in a separate bed, and the
/ S% i' E4 t3 W, K+ w+ x! B- ^father was not hugging him with bare skin and had
* g" [: }5 u. _8 k/ Z# \been using protective clothing. A repeat testosterone* Y, Z2 r8 p/ Z
test was ordered, but the family did not go to the
/ B5 k+ }7 }% d( ?6 _laboratory to obtain the test.! {& N- \' F2 z7 C3 [" P
Discussion
. ^1 d- a. c. t& YPrecocious puberty in boys is defined as secondary
- _! O- f6 ` s. Y6 R; H' ~% Wsexual development before 9 years of age.1,4. x$ s# }$ f7 v3 p+ \
Precocious puberty is termed as central (true) when6 L d8 j+ T% u
it is caused by the premature activation of hypo-$ g: Z) ~# S4 b% _- H3 j1 E7 z( W
thalamic pituitary gonadal axis. CPP is more com-: V( K: m! h% z; T8 q
mon in girls than in boys.1,3 Most boys with CPP
: ]" r1 v% E- L& g1 L: {/ h8 Pmay have a central nervous system lesion that is
! R: v4 V* o0 C5 \% U/ w" t; lresponsible for the early activation of the hypothal-
! Q& x% A2 c$ ]5 \amic pituitary gonadal axis.1-3 Thus, greater empha-5 s0 q4 u6 I: e% R; ^7 M( b" b, A
sis has been given to neuroradiologic imaging in
% S! a p4 x0 W9 V! ^" n( U" pboys with precocious puberty. In addition to viril-
' T3 b5 {$ K$ {+ {( b- rization, the clinical hallmark of CPP is the symmet-
& s: p2 a4 K1 e2 N- S& t' q7 urical testicular growth secondary to stimulation by, b6 {, A7 h) p% u* r# u! o
gonadotropins.1,3
$ ]8 m! A& L$ o* }) |/ ~Gonadotropin-independent peripheral preco-2 K8 @& ^/ k( h( w b: y i
cious puberty in boys also results from inappropriate
Y8 ]+ J! |4 V- \androgenic stimulation from either endogenous or
5 U" ]& a8 s" \exogenous sources, nonpituitary gonadotropin stim-
$ `) W8 L" u- M" m I2 f$ }& C5 Kulation, and rare activating mutations.3 Virilizing
: r- C( A) z$ e1 D* K# econgenital adrenal hyperplasia producing excessive; Q5 \3 s; ^2 h/ u# ]
adrenal androgens is a common cause of precocious' `% \& Q! Q2 y: ?# U
puberty in boys.3,4) f' y& s" c5 w/ C# h# K: F
The most common form of congenital adrenal
& k* Z& M' c* G8 R! |$ chyperplasia is the 21-hydroxylase enzyme deficiency.) M; d' s& g5 g; w/ ?9 u
The 11-β hydroxylase deficiency may also result in. S `+ d% H( o& ]3 t% _% _
excessive adrenal androgen production, and rarely,
5 m2 \8 b4 e' n6 M4 J- r* s/ Kan adrenal tumor may also cause adrenal androgen
/ x0 p; ^ D0 }) {$ o( Oexcess.1,3
* r B- H- C7 d; B# fat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
& |1 ~( O! F# x: I E542 Clinical Pediatrics / Vol. 46, No. 6, July 2007, r! F* l2 ?9 N p3 L5 b. [1 f
A unique entity of male-limited gonadotropin-
" Z1 k5 m2 O( F. b3 `$ Y) Eindependent precocious puberty, which is also known
% m" Z; e; o. w/ sas testotoxicosis, may cause precocious puberty at a
o" a$ r2 R) e, g8 uvery young age. The physical findings in these boys, N2 p" U3 v% s" i
with this disorder are full pubertal development,7 ` J! x2 u3 K6 r2 T8 I* I
including bilateral testicular growth, similar to boys% Y- ]* K% x# N" P2 R
with CPP. The gonadotropin levels in this disorder q8 U& y& a5 S! L: Y8 A) a
are suppressed to prepubertal levels and do not show
% o3 l# s' u; M9 v' k V) Mpubertal response of gonadotropin after gonadotropin-
. i$ X+ C& p! ?+ R- @releasing hormone stimulation. This is a sex-linked
3 N$ z( X7 {( Fautosomal dominant disorder that affects only- T6 m# X3 p' Y+ V2 {# P" _
males; therefore, other male members of the family
4 p. s7 N9 o' [; E+ `9 t& Umay have similar precocious puberty.3' a7 R! ~* [; ~. u/ s% I) p
In our patient, physical examination was incon-
# Y& A7 n+ x. x& b3 \sistent with true precocious puberty since his testi-7 E) m6 F6 Q }
cles were prepubertal in size. However, testotoxicosis
. i5 O/ ?- S# Q$ O5 x6 ]" Rwas in the differential diagnosis because his father
/ }$ O8 h O" Y, A* g5 q& _8 ostarted puberty somewhat early, and occasionally,1 j% n# F- d$ h7 B! |& q
testicular enlargement is not that evident in the
% {0 i# \ `/ }& L+ d( nbeginning of this process.1 In the absence of a neg-/ P; M* g n( c: _0 i( I
ative initial history of androgen exposure, our- v" Q$ ?; F, o. N6 V; n( v( g; |
biggest concern was virilizing adrenal hyperplasia,
6 X) c5 i7 k/ c) ~! E3 \% C* M, meither 21-hydroxylase deficiency or 11-β hydroxylase1 I: f5 p' r6 y/ x) ?$ r
deficiency. Those diagnoses were excluded by find-( `4 H8 C3 `4 p) b% h2 I
ing the normal level of adrenal steroids.! \0 W: L* R9 ]$ i! b& R9 c# r
The diagnosis of exogenous androgens was strongly
! @- y. [ M1 t# q- n" s$ k1 Vsuspected in a follow-up visit after 4 months because
$ X) a2 k, X) p5 Nthe physical examination revealed the complete disap-: Q: r$ _. n+ X+ X4 a* ?
pearance of pubic hair, normal growth velocity, and
6 B* {; f. q& k+ b$ I' k5 ~decreased erections. The father admitted using a testos-
+ L; r! G6 k* N/ W8 d# S) Pterone gel, which he concealed at first visit. He was
5 q1 W9 t3 s; s9 vusing it rather frequently, twice a day. The Physicians’
! Q) a( c. Z! u4 w0 ?Desk Reference, or package insert of this product, gel or
5 l$ @; `* d. v4 Mcream, cautions about dermal testosterone transfer to
. u$ R# s7 e# }0 s$ i1 U2 Junprotected females through direct skin exposure.
4 b+ V+ \) a4 \ wSerum testosterone level was found to be 2 times the
& Z! ]! c2 w. [7 [5 W+ Rbaseline value in those females who were exposed to
% O) H/ [. ?, g" z! teven 15 minutes of direct skin contact with their male
: m! \1 Y" C! f. j$ zpartners.6 However, when a shirt covered the applica-
0 X2 g5 r8 G2 ]7 y" E& @tion site, this testosterone transfer was prevented.* y: [; t# J, a6 a" G% F" t
Our patient’s testosterone level was 60 ng/mL,/ L1 z6 A) Z* \ G2 `' J
which was clearly high. Some studies suggest that9 L) W' z# O1 C" Q3 Z
dermal conversion of testosterone to dihydrotestos-; I9 ^9 j* ~; d( @ T9 W1 |# W( u
terone, which is a more potent metabolite, is more- K7 W; S4 v+ M1 l2 }( \$ J
active in young children exposed to testosterone3 X+ O, u2 F! g2 U- f! ~
exogenously7; however, we did not measure a dihy-3 e& D$ V! l, D+ g; b: U9 j
drotestosterone level in our patient. In addition to
4 c! S4 W, X# x5 L! y7 K, Ivirilization, exposure to exogenous testosterone in
8 k2 g4 C* z) r8 Qchildren results in an increase in growth velocity and
* n% _* ~: v. ^advanced bone age, as seen in our patient.
" m, e/ m" A4 y. V+ GThe long-term effect of androgen exposure during
% h q+ K/ h& _early childhood on pubertal development and final
% m& ]' K( j/ q4 Y. \. P8 z9 oadult height are not fully known and always remain
) B; Z$ B5 J$ m/ ~% }; n: ea concern. Children treated with short-term testos-
4 p# ^' t/ q5 Z4 e. | J7 `2 \& Hterone injection or topical androgen may exhibit some1 O+ O. a, Y% X( j4 n2 \: @( r
acceleration of the skeletal maturation; however, after
J4 @* e) @! @1 |cessation of treatment, the rate of bone maturation' T: I( g6 o0 G+ S5 v6 @& v
decelerates and gradually returns to normal.8,9
4 f5 b; K* l" S8 }: k jThere are conflicting reports and controversy" g/ R# t5 I; G& s, `/ `
over the effect of early androgen exposure on adult
+ r9 B% Q* ?7 h( Dpenile length.10,11 Some reports suggest subnormal0 C% |3 K# ^, z
adult penile length, apparently because of downreg-. T. \, |" U6 W5 j% z
ulation of androgen receptor number.10,12 However,
1 k: v- b+ q; `Sutherland et al13 did not find a correlation between
2 _* P+ v7 _* ]4 W. pchildhood testosterone exposure and reduced adult
( R, B B7 p0 H/ N0 Epenile length in clinical studies.% h# E- X8 V/ E% D3 [
Nonetheless, we do not believe our patient is
; C4 T! X+ w; y6 O4 b Q2 Fgoing to experience any of the untoward effects from
2 t. s0 q- L- itestosterone exposure as mentioned earlier because
, `- `% W, M+ u" |2 c0 K! lthe exposure was not for a prolonged period of time.6 H3 S+ ~9 {4 R4 }* S2 O8 u) K6 k( j6 t3 F
Although the bone age was advanced at the time of
! `1 Q# k7 Y& _diagnosis, the child had a normal growth velocity at
3 @0 Z5 g M# I/ S' b" F1 q: z& h$ `the follow-up visit. It is hoped that his final adult
/ V1 E& J5 i" ]6 s( a) L8 uheight will not be affected.
. X$ F& N2 a' B4 E5 w8 JAlthough rarely reported, the widespread avail-
. {; H* n9 z; h7 T5 Kability of androgen products in our society may
( v1 Z) V, b6 q' w8 o; J7 e9 i( Zindeed cause more virilization in male or female) F; Z I; M" }- F
children than one would realize. Exposure to andro-) @" z6 ^( ]" @; ]
gen products must be considered and specific ques-
$ Q8 [' O- b% f& E" A5 ~tioning about the use of a testosterone product or5 c. [+ {8 y% q7 ~+ i
gel should be asked of the family members during" T$ Z7 N' v7 ^( u- _
the evaluation of any children who present with vir-
; l6 _- ]& _- D9 g; Gilization or peripheral precocious puberty. The diag-
6 k. p/ s, P9 {& w) F* rnosis can be established by just a few tests and by3 c) B8 S d3 g6 b
appropriate history. The inability to obtain such a
6 O5 ?8 S3 h8 `, [7 c/ {: X- Lhistory, or failure to ask the specific questions, may" w, f, ?, f' ^) i! R4 z- ^
result in extensive, unnecessary, and expensive+ [9 t! L/ k. b& j
investigation. The primary care physician should be5 B& r4 Z/ y* e
aware of this fact, because most of these children% t" |3 L: S/ @
may initially present in their practice. The Physicians’
1 X6 Q& D$ q3 ^3 ^Desk Reference and package insert should also put a
$ p; ~' o( y) J5 ~, ^3 Awarning about the virilizing effect on a male or
- y% z; o- n4 Z/ H# b& [female child who might come in contact with some-
5 L, r6 z, h0 |4 r4 [& H2 c2 z) Q# u: kone using any of these products.% K: V4 @; o( N7 S3 E2 J% z, g4 @5 w$ R
References1 r- ~- X* }2 _1 C+ o
1. Styne DM. The testes: disorder of sexual differentiation
; O* ?) g# I5 @& U# R2 Pand puberty in the male. In: Sperling MA, ed. Pediatric
7 g- h) S6 r& N: l6 Z. rEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
% {8 M& C* Q' `8 U0 Y/ k/ @4 A4 d2002: 565-628.# D4 D% z8 { V
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious x& i0 K4 g( ~' J" A
puberty in children with tumours of the suprasellar pineal |
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