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Sexual Precocity in a 16-Month-Old
! y* t+ L! [6 XBoy Induced by Indirect Topical L& r1 f2 [1 I- [. v7 s, z5 _( ^
Exposure to Testosterone
5 O+ y9 G/ K5 J3 b$ PSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
! k/ g p, @+ s, J; Mand Kenneth R. Rettig, MD1
3 i8 G/ m5 ?- I) {Clinical Pediatrics
8 P3 v0 z' Y8 f" E* i! ^Volume 46 Number 6
v5 g! i2 P+ GJuly 2007 540-543) g- M: J! m* f5 ^6 Y$ s% i
© 2007 Sage Publications0 [$ A% I; _8 H8 f! [) E
10.1177/0009922806296651
( T4 Z! @$ i; g2 M9 v- Dhttp://clp.sagepub.com
2 X9 f! \- k+ n- z7 nhosted at g( |+ G3 Q: z& P+ ~! v
http://online.sagepub.com
0 W( h9 N# K/ m z F* m7 gPrecocious puberty in boys, central or peripheral,/ m2 N' p: t4 G" ^
is a significant concern for physicians. Central
+ x0 z6 M+ q; G# U# Q* fprecocious puberty (CPP), which is mediated
& T" m8 w; u7 ythrough the hypothalamic pituitary gonadal axis, has
& l9 t, G, U( d2 ra higher incidence of organic central nervous system. Q; X( ]2 s: g o! p r, T9 u
lesions in boys.1,2 Virilization in boys, as manifested
/ ?- j, P/ h8 H4 S% \/ mby enlargement of the penis, development of pubic
4 E. G. w* E/ I; xhair, and facial acne without enlargement of testi-
8 `! e' |/ }) o1 A, p8 l. Tcles, suggests peripheral or pseudopuberty.1-3 We: @& ~1 X$ k2 g, F: \
report a 16-month-old boy who presented with the5 J% \( C, g6 D! p, b" P; q1 v' M
enlargement of the phallus and pubic hair develop-
+ [2 ?* _4 K/ ^4 D& Tment without testicular enlargement, which was due% R8 a1 t' _. S- u, v# K5 }
to the unintentional exposure to androgen gel used by" U7 z: ^( Y2 C6 ]) I- K9 [ H- z8 _. h
the father. The family initially concealed this infor-
7 }+ q; j! ?8 V8 ]. _& N+ n' u2 Smation, resulting in an extensive work-up for this( I4 D# M! P& U0 g0 ^8 S# O1 } R
child. Given the widespread and easy availability of
5 E& H( ?! S' D% E0 f/ R$ P+ K! e Ktestosterone gel and cream, we believe this is proba-. M7 S( J5 w q0 Y( T: A
bly more common than the rare case report in the
: A. g1 L& I# Y) gliterature.4; B8 L8 l3 G* ~; s# j
Patient Report; b+ n3 ~/ I. C y* i, z9 o$ j
A 16-month-old white child was referred to the- t3 i- c7 K3 z. {
endocrine clinic by his pediatrician with the concern/ ~6 p4 i/ ~7 F+ h- [$ |2 w; R
of early sexual development. His mother noticed
' s6 w& Q1 h: a7 v/ h' f/ T( R' f6 llight colored pubic hair development when he was
, q% r3 W: b; m& o. F7 W; p# t; u# yFrom the 1Division of Pediatric Endocrinology, 2University of
5 M1 K9 ~. B; d# V* w+ jSouth Alabama Medical Center, Mobile, Alabama.6 u" N5 X; A& U7 k
Address correspondence to: Samar K. Bhowmick, MD, FACE,7 U+ `9 s6 T5 w$ J2 b' K2 c, i
Professor of Pediatrics, University of South Alabama, College of
W0 V- n. J" M% NMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
% _5 ^, |/ C3 ]" M6 s i4 @+ s5 ue-mail: [email protected].
: ` E$ H) C( C, W" _5 r0 b. rabout 6 to 7 months old, which progressively became
' F" R" N! q7 p( d, Cdarker. She was also concerned about the enlarge-4 t: H" p4 {0 f! @& S% i5 f
ment of his penis and frequent erections. The child% N) `# ?6 l5 Z8 g2 X! p N8 A
was the product of a full-term normal delivery, with
1 U" l4 L* m' D' p3 ]$ h# Y9 o) Aa birth weight of 7 lb 14 oz, and birth length of$ L$ A, o% Y; l' ~+ m, H
20 inches. He was breast-fed throughout the first year" C3 E) f# [7 t
of life and was still receiving breast milk along with
) ]- Q8 e) V! N" A D$ X& Asolid food. He had no hospitalizations or surgery,
- b- c8 f4 K6 J$ Dand his psychosocial and psychomotor development6 Q, K; G! z1 D: S
was age appropriate.. k' p7 Z6 _' X- K0 D* {# E
The family history was remarkable for the father,
0 {: y2 b2 e/ e/ `/ Swho was diagnosed with hypothyroidism at age 16,1 _2 I$ B# J3 z) ^7 z1 [
which was treated with thyroxine. The father’s o% U/ u+ U% G/ C
height was 6 feet, and he went through a somewhat, P, [4 w' r3 s1 E) }. O: |
early puberty and had stopped growing by age 14.4 D; h7 L7 j, J" a# _/ Q, j
The father denied taking any other medication. The9 s, w+ q2 U5 l/ n
child’s mother was in good health. Her menarche% }- k2 W8 g( d! u
was at 11 years of age, and her height was at 5 feet) D# e% K: g) ^: ?/ P: o3 o
5 inches. There was no other family history of pre-
( P* {0 z7 A( Qcocious sexual development in the first-degree rela-% n" S/ c9 s4 D+ Z( z
tives. There were no siblings.
1 C+ y$ i7 q, j5 wPhysical Examination/ V, T+ U# C0 Q) J( ]( w* d
The physical examination revealed a very active,
) J2 I7 z, T% f6 vplayful, and healthy boy. The vital signs documented
& O0 Z. ^( Y) ~3 N! }6 v Q* }" Z' Ja blood pressure of 85/50 mm Hg, his length was0 g' c* N" G7 m4 x# J
90 cm (>97th percentile), and his weight was 14.4 kg
5 n. t8 `( p: E: C/ L! M(also >97th percentile). The observed yearly growth
@3 N3 g0 E$ tvelocity was 30 cm (12 inches). The examination of. s* }& s# l- z3 B
the neck revealed no thyroid enlargement.% ]+ K) h7 z" m0 h' b* ?, ^# n
The genitourinary examination was remarkable for) K. n2 o- F4 b5 _: r0 v, L+ ^1 i7 x& f# [
enlargement of the penis, with a stretched length of
/ }; @6 D+ H9 v& J6 i4 b8 cm and a width of 2 cm. The glans penis was very well+ B8 R. P# m: Q
developed. The pubic hair was Tanner II, mostly around( s @: y9 d: M$ f& o8 @+ q- L
540" ]. U: A+ @+ d! Q
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
8 N8 r: w7 _3 O2 D; @the base of the phallus and was dark and curled. The. e* ^1 T/ Y1 W; }* p
testicular volume was prepubertal at 2 mL each.
: R$ N# e, A6 m% Z7 w. c+ WThe skin was moist and smooth and somewhat. [+ J, K: m1 f2 Y' e
oily. No axillary hair was noted. There were no( h6 s3 t* ]8 M8 p0 f8 m& V3 K7 ]
abnormal skin pigmentations or café-au-lait spots.' s8 q% z% X+ c' g( d
Neurologic evaluation showed deep tendon reflex 2+% s D% ^7 C' D. C# P8 }) A4 R
bilateral and symmetrical. There was no suggestion
4 u) P, Q& W$ M/ s% @0 [of papilledema.2 T) ?" h5 O. N
Laboratory Evaluation1 t7 ?$ N* j/ B) N- t9 R
The bone age was consistent with 28 months by. }" h" M) {0 Q, ?6 b; H+ B
using the standard of Greulich and Pyle at a chrono-, k* h2 a* E o+ Q* [
logic age of 16 months (advanced).5 Chromosomal1 R) a& \2 i; ?. F
karyotype was 46XY. The thyroid function test
0 U' [5 i, d! m6 Jshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
! A4 Y6 g! X4 m, K0 {8 g# wlating hormone level was 1.3 µIU/mL (both normal).1 M1 C q* k8 C8 {
The concentrations of serum electrolytes, blood% W K' Y, n3 l% ^
urea nitrogen, creatinine, and calcium all were$ F! t4 ?! I) S, T2 w4 l, ]
within normal range for his age. The concentration% u: h0 N* m2 y! V
of serum 17-hydroxyprogesterone was 16 ng/dL
, S, n/ A1 `) X. E- P4 m8 ^" ](normal, 3 to 90 ng/dL), androstenedione was 200 m& ~' W9 \* f1 B1 c: }$ \; E
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
) [ \5 u% F+ i$ g1 N. Yterone was 38 ng/dL (normal, 50 to 760 ng/dL),
5 p' h$ o" K, m# c2 S; l2 Ndesoxycorticosterone was 4.3 ng/dL (normal, 7 to
- Z0 S L9 }' a [, [) F2 f0 P49ng/dL), 11-desoxycortisol (specific compound S)
5 }, F. @8 C' Q! Cwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
! o+ h- W. X* }4 e: N/ dtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total" i' c0 x4 F& K1 r, ~
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
" ?4 w. h' T1 E. ]and β-human chorionic gonadotropin was less than
}+ h( e$ j6 \1 l8 Q# d5 mIU/mL (normal <5 mIU/mL). Serum follicular
s$ X: j. ?% mstimulating hormone and leuteinizing hormone% k8 v' C9 V: m& M0 c4 C+ E& h3 `
concentrations were less than 0.05 mIU/mL
9 f5 P, }4 p" i6 I/ O# ?& l6 {(prepubertal).# N# X" K$ Z E, ]8 F* f$ @
The parents were notified about the laboratory
) m, D( e- ^3 p8 H7 wresults and were informed that all of the tests were; ?, A2 L5 w3 w) S
normal except the testosterone level was high. The
; |/ H/ `4 ^( X O, O' \follow-up visit was arranged within a few weeks to
7 p1 B5 d5 \; H' B' u3 lobtain testicular and abdominal sonograms; how-3 D2 w% P! r. ^: ]$ J6 [, _, E
ever, the family did not return for 4 months.
, g! o% ~, y% ~) FPhysical examination at this time revealed that the
6 F! n# g" Y ]( }# V9 wchild had grown 2.5 cm in 4 months and had gained
* |+ t1 [, ^# y2 kg of weight. Physical examination remained Y% |7 \ {4 k" t2 Q
unchanged. Surprisingly, the pubic hair almost com-% u; z+ h9 a1 A6 |
pletely disappeared except for a few vellous hairs at4 Z0 {6 D$ ^6 K, O" [# y
the base of the phallus. Testicular volume was still 2
3 K0 Z9 n: [! _* f! dmL, and the size of the penis remained unchanged.) p! {# `" O: B: o3 b' o+ I
The mother also said that the boy was no longer hav-! m# ^0 u- L2 ]1 m
ing frequent erections." c2 j: _5 ~/ u" S4 S
Both parents were again questioned about use of
. d: n8 h) r. \, N0 h% G" L6 tany ointment/creams that they may have applied to
: p; }4 \% A, S/ v5 ~the child’s skin. This time the father admitted the
* f0 b K. \7 `1 Z; j+ _Topical Testosterone Exposure / Bhowmick et al 541
+ M0 }& G+ ]8 v/ b( z/ Q0 `1 buse of testosterone gel twice daily that he was apply-9 h2 U% g. ]( `0 A) C a( V( A
ing over his own shoulders, chest, and back area for
$ _0 G! P h9 N% [, la year. The father also revealed he was embarrassed
- R; ~/ C U6 o9 x& fto disclose that he was using a testosterone gel pre-2 d: r, ]9 _3 ]# J
scribed by his family physician for decreased libido
0 j; Z; N- h$ L2 U! Q/ L2 Esecondary to depression.
7 t5 O9 ^& Z( i/ f' yThe child slept in the same bed with parents.# X( h1 Y! b' B" h* c$ ~4 }
The father would hug the baby and hold him on his% P- ~8 o5 _; S# @
chest for a considerable period of time, causing sig-! {& O9 q' q9 z1 B7 v
nificant bare skin contact between baby and father.
4 E! p G' K B. O3 Y' T/ T6 K4 sThe father also admitted that after the phone call,
4 r: ~6 P; A9 ^) J9 ?5 z. N" uwhen he learned the testosterone level in the baby
3 Y* q! z# }7 t X! T/ X) W0 J/ ^was high, he then read the product information! G5 K; N c6 ?" Q9 O. ~/ A' N
packet and concluded that it was most likely the rea-
3 @0 O. E. T4 s, Q$ b. json for the child’s virilization. At that time, they" C [) p( O; N; a
decided to put the baby in a separate bed, and the$ H' ~6 \ A" K- R
father was not hugging him with bare skin and had: V7 \* a! x- b8 d9 _. c
been using protective clothing. A repeat testosterone
8 S7 {7 J1 y% dtest was ordered, but the family did not go to the8 u: b- h- {" w
laboratory to obtain the test.
8 x9 A7 {, j' U( q; v, b5 RDiscussion1 g9 h; E* X6 c' \5 v
Precocious puberty in boys is defined as secondary
, n; ]2 |. ^7 A: |sexual development before 9 years of age.1,4, G* O f0 [. @% a, W; M N
Precocious puberty is termed as central (true) when
( A$ c0 A! m& C1 m! B: Cit is caused by the premature activation of hypo-
+ S6 z6 F2 |! |6 Z1 uthalamic pituitary gonadal axis. CPP is more com-. T* K8 s* P; F: s) n+ ^
mon in girls than in boys.1,3 Most boys with CPP. j- Q u$ }$ Y
may have a central nervous system lesion that is
! U' K$ @5 _: K9 L. ~responsible for the early activation of the hypothal-# M: K1 v5 w, C5 b8 {
amic pituitary gonadal axis.1-3 Thus, greater empha-* q$ o5 B: Y4 a4 s
sis has been given to neuroradiologic imaging in
" C4 k% x9 I: m ?3 h4 aboys with precocious puberty. In addition to viril-
" g- u2 @0 ]1 G- V9 v2 ]4 oization, the clinical hallmark of CPP is the symmet-; B& P% a5 T* f* O- h" v# x- D
rical testicular growth secondary to stimulation by( `6 k! r! T0 g3 G5 l/ ]) y9 ]! o
gonadotropins.1,30 F7 |) |! e4 d9 Z" v; _
Gonadotropin-independent peripheral preco-. Q0 a% n9 f, N
cious puberty in boys also results from inappropriate
: _/ ^, I# Q; {: }) oandrogenic stimulation from either endogenous or$ T3 ~$ R% U7 I. N% J' m$ X# X) f
exogenous sources, nonpituitary gonadotropin stim-: T/ k( O; C: W" p. `1 j: [6 e1 |
ulation, and rare activating mutations.3 Virilizing) k( G; Y6 p( Z+ z' R" X, O
congenital adrenal hyperplasia producing excessive/ q. O! x7 Z% X! G/ f3 [1 R
adrenal androgens is a common cause of precocious
0 E# d8 g8 T6 Z' |. ?, o j/ f; ~puberty in boys.3,4 e' {+ F" N7 d+ H6 { o
The most common form of congenital adrenal) p) `: f7 w+ m9 n8 a! W9 m# h
hyperplasia is the 21-hydroxylase enzyme deficiency.
) w- J9 U: j, W5 EThe 11-β hydroxylase deficiency may also result in
# ^0 t V" U% }# ]/ _excessive adrenal androgen production, and rarely,* f/ `6 p- g I4 C
an adrenal tumor may also cause adrenal androgen
% D/ f* C! B, [. Sexcess.1,3& v# y( r$ d. |+ ]" k4 }
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
5 ?% Q* A* ~- ~542 Clinical Pediatrics / Vol. 46, No. 6, July 2007/ A" i( b8 l2 ~" s
A unique entity of male-limited gonadotropin-
! q' P2 U# G1 ~1 b# t4 |independent precocious puberty, which is also known& j/ \" W' c& P/ O
as testotoxicosis, may cause precocious puberty at a
% }( i; t: A! j( v+ W3 r( T, xvery young age. The physical findings in these boys
/ L6 V. T( h; J$ E6 Qwith this disorder are full pubertal development,9 U# z7 _6 b C9 ~7 `
including bilateral testicular growth, similar to boys
- r0 I& s g+ k1 n) Fwith CPP. The gonadotropin levels in this disorder
6 W, N# U) D; o+ W. @& Y. Aare suppressed to prepubertal levels and do not show) K+ D" j+ N: K O
pubertal response of gonadotropin after gonadotropin-
7 w6 W) w9 K* i# R. d) m. Q% wreleasing hormone stimulation. This is a sex-linked
4 ~3 n* f U+ F9 N1 x. Q( Q2 Gautosomal dominant disorder that affects only
8 Z% ~9 P7 R3 K5 M) Imales; therefore, other male members of the family
4 R% `; r+ T& q! vmay have similar precocious puberty.3
; i [- E- E% \% u% P4 F- RIn our patient, physical examination was incon-
$ R% K- p, ]8 Fsistent with true precocious puberty since his testi-
5 h$ u. O6 }6 z9 x' Ucles were prepubertal in size. However, testotoxicosis
" e. e: _; Z1 a) Bwas in the differential diagnosis because his father
% R2 L, u$ n! i+ [( ^started puberty somewhat early, and occasionally,7 F! N0 _7 A# ]5 O' S0 L: E
testicular enlargement is not that evident in the- ? t8 A$ a8 ?
beginning of this process.1 In the absence of a neg-
4 i$ `) R: a7 p( C3 j5 Tative initial history of androgen exposure, our- Q3 H; e4 U0 j3 b4 r# N
biggest concern was virilizing adrenal hyperplasia,
, c9 r2 W& ]' S# y. teither 21-hydroxylase deficiency or 11-β hydroxylase8 M* Q! D {( y5 p4 V3 ~
deficiency. Those diagnoses were excluded by find-2 B" S: k( _& j, Z
ing the normal level of adrenal steroids.
9 `: `7 _* j( C: t( q" @- ]4 @The diagnosis of exogenous androgens was strongly
: R' R2 B2 s B7 q! Gsuspected in a follow-up visit after 4 months because
' L: Y; y4 [# T) A2 ]5 Vthe physical examination revealed the complete disap-+ D( L) J& @" v* ^6 g
pearance of pubic hair, normal growth velocity, and Y& C8 N) ^. H) J5 V$ `" L/ m
decreased erections. The father admitted using a testos-
7 M" [' X8 F, U$ n$ B% Z3 vterone gel, which he concealed at first visit. He was2 n+ K* C0 Y' |$ D3 a( ] S
using it rather frequently, twice a day. The Physicians’
" q \7 N! J$ h- ?Desk Reference, or package insert of this product, gel or
6 n1 s4 Y" m4 A* m8 p0 acream, cautions about dermal testosterone transfer to2 }! M8 u! s3 S3 H3 G; |* |
unprotected females through direct skin exposure.
$ Y' Y# W6 i5 y) oSerum testosterone level was found to be 2 times the3 ]5 \& u* J! B% |4 J, P
baseline value in those females who were exposed to3 J9 c9 J/ B2 F, B9 x
even 15 minutes of direct skin contact with their male
H/ f/ W! m% q+ Y' l) O/ ]1 q2 Z, wpartners.6 However, when a shirt covered the applica-
T% k: W7 I! _4 p' R( W6 Ltion site, this testosterone transfer was prevented.9 {' m8 A: p& }) y; A
Our patient’s testosterone level was 60 ng/mL,6 S2 s9 T0 E3 g8 X7 y7 `7 k
which was clearly high. Some studies suggest that+ S! C5 x* Y7 k' M6 g, w
dermal conversion of testosterone to dihydrotestos-. O- L( j; |* ~; f: C- J" j: p% c5 n# p: ^
terone, which is a more potent metabolite, is more
. {3 D" {' b9 M0 b' V* Factive in young children exposed to testosterone; o0 h; C( x& j6 `& h
exogenously7; however, we did not measure a dihy-$ \; \! P, S' o8 n
drotestosterone level in our patient. In addition to
- I2 c+ ~ Q7 h0 m" a: I8 D+ b# Uvirilization, exposure to exogenous testosterone in
) w- C: f1 F U! o/ t0 echildren results in an increase in growth velocity and
2 l! W1 g9 ?5 r" o+ g) {advanced bone age, as seen in our patient.0 X, A2 `2 K E0 i( w) d
The long-term effect of androgen exposure during
1 l7 |: E# S$ w# [/ rearly childhood on pubertal development and final
. A( b, H8 O* gadult height are not fully known and always remain
- t L& e' u: \a concern. Children treated with short-term testos-& k! c! a0 ^, {0 p9 J6 S
terone injection or topical androgen may exhibit some: q" T) k3 m1 z$ M
acceleration of the skeletal maturation; however, after
1 [( A6 T d& Ucessation of treatment, the rate of bone maturation
/ a- q( r4 }- d) E0 [decelerates and gradually returns to normal.8,9( |: T6 N8 ?' x% t$ [
There are conflicting reports and controversy2 {/ A: V J9 f+ p# F% I7 ~+ ~
over the effect of early androgen exposure on adult* T/ s+ A9 z; G
penile length.10,11 Some reports suggest subnormal% \+ F* S% T4 K; y$ S% L0 |/ g
adult penile length, apparently because of downreg-
( C, a* ~) |; m4 i3 G4 J2 y6 O3 pulation of androgen receptor number.10,12 However,1 Q5 F8 V4 i4 v: M z7 E% m
Sutherland et al13 did not find a correlation between- U5 j" a' E+ w3 p3 c
childhood testosterone exposure and reduced adult+ B, n) h! j* P% H# G
penile length in clinical studies.; w6 h/ t7 L5 o' O
Nonetheless, we do not believe our patient is6 R% ~0 e# ?# l O( g
going to experience any of the untoward effects from( F: g" F$ f/ M
testosterone exposure as mentioned earlier because
! y. ?* p6 x0 q2 x! w5 \0 ]the exposure was not for a prolonged period of time.
7 ^3 F7 u0 h9 V# e" DAlthough the bone age was advanced at the time of4 Q, P; ~0 b7 g# A
diagnosis, the child had a normal growth velocity at
+ F. ]: t* `. r7 d8 fthe follow-up visit. It is hoped that his final adult
8 c8 H. ]! B4 ^" ?7 wheight will not be affected.
; l* j9 L s4 u2 ?Although rarely reported, the widespread avail-
$ J* O- K2 v: q: m- }4 i% c: g# {9 rability of androgen products in our society may
# P9 Z, M! C7 y0 l9 gindeed cause more virilization in male or female
) ]; @5 l* R8 o( V4 Gchildren than one would realize. Exposure to andro-$ x+ u+ K) I/ `+ t- a
gen products must be considered and specific ques-% F7 I# _: j7 k3 z& ]# A
tioning about the use of a testosterone product or
3 r; I5 |, e( e- C. i' kgel should be asked of the family members during6 E* P7 p% p( s
the evaluation of any children who present with vir-* M. ]% }1 N6 }0 {$ ?7 p
ilization or peripheral precocious puberty. The diag-! E/ B" C% E) s! r$ S& O
nosis can be established by just a few tests and by! K9 j7 A* c: p/ g; k" _) z+ O
appropriate history. The inability to obtain such a" k+ q( g! s: C
history, or failure to ask the specific questions, may' @/ Z: H0 A! T& P8 Y
result in extensive, unnecessary, and expensive/ y$ A) k1 O- m3 ^7 o# x3 b, n9 G
investigation. The primary care physician should be) X- w- S; b* Z* ~" ^: R) N
aware of this fact, because most of these children
& M& K; |0 M; K. h7 Q- D0 Amay initially present in their practice. The Physicians’
3 q+ N6 [1 y9 B% W5 b% r4 uDesk Reference and package insert should also put a: n) @5 b: s% p* p) E. a
warning about the virilizing effect on a male or
, c. p7 ~4 o1 u) L- jfemale child who might come in contact with some-3 [% G' v% ?! W! K. M1 L4 T
one using any of these products.
( q& t' e* a. h1 _# U# NReferences% e$ [7 o: y# L2 o/ F! L! G
1. Styne DM. The testes: disorder of sexual differentiation# k2 b) u% @- s; B
and puberty in the male. In: Sperling MA, ed. Pediatric5 r& j# t! I5 ]
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
/ q& _% Q5 _" S. K4 ~# p2002: 565-628.
/ o# f6 I) |$ r8 K+ X* \$ I2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
g# V2 a3 K+ Kpuberty in children with tumours of the suprasellar pineal |
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