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Sexual Precocity in a 16-Month-Old
& L+ D+ t( K1 o. E: s1 G8 s9 K6 ]Boy Induced by Indirect Topical
6 z0 g( J# F0 S# `& NExposure to Testosterone5 ?( ^2 h# S& h3 C
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
# N; |) g2 R6 g* B6 O% {and Kenneth R. Rettig, MD13 a; u& ~8 t, ^4 W( {
Clinical Pediatrics
) A: D+ L2 d- G' j, y9 V( g) O! MVolume 46 Number 64 v F; R) P) G9 K
July 2007 540-543
$ r) W, q2 T$ {, w Z© 2007 Sage Publications6 Q5 Q( H# A3 k+ ^
10.1177/0009922806296651, g4 `* p% l" d0 t/ S; J- B2 z
http://clp.sagepub.com
1 O; S" d% J7 F/ Z' I* V# d4 `1 Qhosted at
# G. Y) ^, K& d0 yhttp://online.sagepub.com7 r/ _ s; W8 b1 e
Precocious puberty in boys, central or peripheral,+ s- W3 V4 g) A1 [8 y
is a significant concern for physicians. Central
% V* t- a" \: a u1 Rprecocious puberty (CPP), which is mediated9 z+ W' a. ~* q+ s# u2 G* N4 O
through the hypothalamic pituitary gonadal axis, has
3 k/ v8 D) X/ x) S, n: O+ \' H& ya higher incidence of organic central nervous system1 j0 k2 B4 p8 J/ h* a
lesions in boys.1,2 Virilization in boys, as manifested
, F5 _0 { ?0 }7 sby enlargement of the penis, development of pubic
3 r: w$ D3 q! w3 L2 ]3 Ehair, and facial acne without enlargement of testi-: j8 Z% i' E5 T
cles, suggests peripheral or pseudopuberty.1-3 We
: X1 Y7 E! c4 ~" j+ hreport a 16-month-old boy who presented with the
# G" r3 r3 E/ E0 h6 c# w4 yenlargement of the phallus and pubic hair develop-
# G; D- g$ v( A2 q9 _ment without testicular enlargement, which was due
k! A8 Y' }! Sto the unintentional exposure to androgen gel used by: O4 G. U% K& n! F5 H& B& K4 u
the father. The family initially concealed this infor-
/ e$ a: L: @- N- A' T4 e) }2 L) `mation, resulting in an extensive work-up for this: S' r2 n3 ]8 Y4 Q1 J
child. Given the widespread and easy availability of# _0 d" }& H' u' [) a* ^
testosterone gel and cream, we believe this is proba-; C4 B" D; W3 ^/ b8 a
bly more common than the rare case report in the
5 v$ f; M+ ]' U; p* ?+ b5 bliterature.4
6 O/ J4 W' j+ bPatient Report
" @! u% {4 Q+ ]$ |: XA 16-month-old white child was referred to the
' b! i+ a* \+ E4 Wendocrine clinic by his pediatrician with the concern
3 e0 E: W4 g/ K- v n$ Qof early sexual development. His mother noticed
7 Z3 D% l' E* h' O' L/ ?' z" flight colored pubic hair development when he was5 x5 \/ e' g9 \/ S- b3 h
From the 1Division of Pediatric Endocrinology, 2University of- S0 i- j/ C8 y
South Alabama Medical Center, Mobile, Alabama., A8 |$ c& T: E/ ^
Address correspondence to: Samar K. Bhowmick, MD, FACE,3 j2 B& q" a6 w
Professor of Pediatrics, University of South Alabama, College of8 ]' |9 z) ^# P. t6 E% K _: |' L
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
* ~; x# ?, \2 _/ e: O8 r* ae-mail: [email protected].& D; z" M; @0 z
about 6 to 7 months old, which progressively became$ A5 J. A5 [8 N% V. Y! j) \! w8 j
darker. She was also concerned about the enlarge-
2 Z4 D* U5 E. jment of his penis and frequent erections. The child
1 t/ X( n% O" \% s, d6 j& I% { vwas the product of a full-term normal delivery, with
, r% E9 a! @/ t8 k5 A ca birth weight of 7 lb 14 oz, and birth length of
& ^; u/ J! {. N$ @20 inches. He was breast-fed throughout the first year
d# c E, [! M: v4 u' x4 Qof life and was still receiving breast milk along with
& w7 ]3 r: ^+ ^, T( Nsolid food. He had no hospitalizations or surgery,4 ?) a1 _1 P1 d8 w/ ~ I
and his psychosocial and psychomotor development7 l# f' E( U! R) `( S
was age appropriate.5 s2 E: [9 l% x0 p' M
The family history was remarkable for the father,! u. Q& d$ c8 G# j# W
who was diagnosed with hypothyroidism at age 16,) d# E( Q2 G8 B( O) i* F: N" J4 r
which was treated with thyroxine. The father’s" a6 b/ f' L# w/ {# N% M" h4 G
height was 6 feet, and he went through a somewhat" H4 V5 o* T4 v7 F$ L
early puberty and had stopped growing by age 14.
: ]' n4 V: e v9 u% |The father denied taking any other medication. The
6 W: h+ m# U% _: Hchild’s mother was in good health. Her menarche
0 h2 e9 ^8 e9 W5 Z1 c* {7 Cwas at 11 years of age, and her height was at 5 feet& U4 P3 @0 h6 k4 [) b! T- {
5 inches. There was no other family history of pre-
6 q2 t: u/ s( L/ M9 W: L% \ ` Vcocious sexual development in the first-degree rela-; J6 p1 E5 B- }6 v% `0 r
tives. There were no siblings.
3 ?9 t0 t9 L$ @: K" VPhysical Examination; e, ^! _, u6 q% |
The physical examination revealed a very active,
" d6 h; A! F' G7 {playful, and healthy boy. The vital signs documented
) L( y) m* I* \( X3 Z# Da blood pressure of 85/50 mm Hg, his length was
, Z* H5 p: A1 E8 ]5 F" F90 cm (>97th percentile), and his weight was 14.4 kg1 Y/ B! i3 {, e- W0 |
(also >97th percentile). The observed yearly growth
8 N6 F4 a7 j8 B9 h% Ivelocity was 30 cm (12 inches). The examination of; Q5 B) R! _+ c9 k o* u
the neck revealed no thyroid enlargement.
& r9 j! X% l' CThe genitourinary examination was remarkable for4 k+ M' u. @6 b7 k6 P% g
enlargement of the penis, with a stretched length of X& s" d# Z6 m9 q9 f
8 cm and a width of 2 cm. The glans penis was very well
! {6 B/ A# l; X6 c3 sdeveloped. The pubic hair was Tanner II, mostly around
! {& U7 s2 M3 G% X/ x ?1 k3 L, R! `540
% V5 M8 q9 I1 s0 k$ yat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from6 u- [0 x5 d6 R, t* S- m
the base of the phallus and was dark and curled. The1 u" n1 I3 ~; k: U% Y
testicular volume was prepubertal at 2 mL each.
# ?0 o! i+ Z7 D; \6 H7 iThe skin was moist and smooth and somewhat# f0 N- j1 E9 b- W: d& }+ ~, o: B
oily. No axillary hair was noted. There were no2 F: w( q9 l% y) q* \1 _
abnormal skin pigmentations or café-au-lait spots.* |5 f+ m8 L8 Z( I
Neurologic evaluation showed deep tendon reflex 2+/ K2 z* v; y6 V! D3 Y+ \
bilateral and symmetrical. There was no suggestion
; W4 a0 y; [# G- [0 u! yof papilledema.
+ t W7 D9 H: T$ I Y# B2 dLaboratory Evaluation
7 h9 g2 b% N& h+ oThe bone age was consistent with 28 months by4 [) e+ `: P. N0 f. _
using the standard of Greulich and Pyle at a chrono-
9 j g- ^& N) P# B0 c: Llogic age of 16 months (advanced).5 Chromosomal( S: \( c E- N8 ~& d! Z
karyotype was 46XY. The thyroid function test8 b5 g$ Q& U8 S) `2 |
showed a free T4 of 1.69 ng/dL, and thyroid stimu-. ]" |; l ~7 C6 j5 U" P
lating hormone level was 1.3 µIU/mL (both normal).
0 I1 a4 D; N' x1 v$ [The concentrations of serum electrolytes, blood* s1 O1 T' K3 ]5 @
urea nitrogen, creatinine, and calcium all were
1 {9 Y7 b) S: E, rwithin normal range for his age. The concentration
1 p1 _/ S, g$ Y4 n, B1 Aof serum 17-hydroxyprogesterone was 16 ng/dL
2 q& ~9 c. `. ~9 u7 w( o4 ^(normal, 3 to 90 ng/dL), androstenedione was 20
0 U2 m' |4 f. [7 v, z! c0 png/dL (normal, 18 to 80 ng/dL), dehydroepiandros-* m, x0 J2 h: Z7 j7 v2 M
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
9 h: Q+ d* p2 R! v0 y4 pdesoxycorticosterone was 4.3 ng/dL (normal, 7 to
3 C8 a$ l0 E! @% \, h49ng/dL), 11-desoxycortisol (specific compound S)
7 G+ \- b4 j$ Awas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
_& m- Q a) L- N [( d( S: btisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
9 N. j* W. W/ `0 D( rtestosterone was 60 ng/dL (normal <3 to 10 ng/dL), Q6 j5 o3 h4 }% |
and β-human chorionic gonadotropin was less than' U1 R7 R7 P0 _! v( u) W, A5 ]
5 mIU/mL (normal <5 mIU/mL). Serum follicular' o2 S; ~0 P# d9 C- \) h
stimulating hormone and leuteinizing hormone( ~5 T+ {& `5 X8 R. C
concentrations were less than 0.05 mIU/mL
' R/ R+ ]9 e9 d/ R4 E(prepubertal).& H7 k5 _# Q, Q/ h. m; s8 d" T, e9 n3 L
The parents were notified about the laboratory
1 V5 ?2 H) r. _6 T2 S8 P! Aresults and were informed that all of the tests were5 j$ ~2 ^+ f9 `# S
normal except the testosterone level was high. The
8 y/ q8 R! o$ b, @- o6 f3 l) ]% \- Nfollow-up visit was arranged within a few weeks to
" ^6 K- [# C4 H7 c/ u/ ^& T. ^% sobtain testicular and abdominal sonograms; how-3 ?7 _! u- i1 x2 E$ l
ever, the family did not return for 4 months.
0 j# f9 G0 N9 r3 R/ w! {Physical examination at this time revealed that the! b- c! p/ F. N" e
child had grown 2.5 cm in 4 months and had gained! V+ i5 q7 g r( [* R
2 kg of weight. Physical examination remained
K, i X9 t ]. @, P3 cunchanged. Surprisingly, the pubic hair almost com-6 X8 N5 k" Y0 E1 E% c. |2 D% g
pletely disappeared except for a few vellous hairs at
; i4 q8 z; o6 K3 O ?the base of the phallus. Testicular volume was still 2
5 d2 ^0 b$ y, c3 O' k! x$ M2 jmL, and the size of the penis remained unchanged." x0 ]7 P. Y3 D, r3 h" H
The mother also said that the boy was no longer hav-; N9 H! _$ y5 e. ^2 M9 e9 p' q3 t
ing frequent erections.
4 v( E+ O8 n& `9 {Both parents were again questioned about use of: `6 U$ g! N% e& Z3 b" E1 G6 R
any ointment/creams that they may have applied to3 b4 H L1 [. H2 |, X f
the child’s skin. This time the father admitted the7 `; }+ X' {8 i+ Y2 ?* |
Topical Testosterone Exposure / Bhowmick et al 541
& t( B* \* x' g/ p4 {use of testosterone gel twice daily that he was apply-" W7 v; y9 T U8 i. C9 J V s9 h
ing over his own shoulders, chest, and back area for
) A3 @2 C$ R9 L I5 p# `- fa year. The father also revealed he was embarrassed M: x( R7 P6 C" F8 H) Z/ ~
to disclose that he was using a testosterone gel pre-" q# g: O3 U$ w
scribed by his family physician for decreased libido
% x# |# Y$ H8 hsecondary to depression.7 Q1 S2 J2 S3 E5 e) y7 F$ Q
The child slept in the same bed with parents. A: H1 a/ a8 \6 Q6 E; G
The father would hug the baby and hold him on his* X* H7 P" l! [# ?3 x" k
chest for a considerable period of time, causing sig-1 H7 |" U1 Q5 j$ d* u) U- S
nificant bare skin contact between baby and father.( C d7 ?- G- P2 E* y5 x! D0 S
The father also admitted that after the phone call,( h' I# J; I5 [& s1 j* t9 L
when he learned the testosterone level in the baby
* P& u1 s, ^! a2 J' cwas high, he then read the product information
2 J B. O- r tpacket and concluded that it was most likely the rea-
& u* v$ m- k! ^1 json for the child’s virilization. At that time, they
4 T/ { B0 [% P' W ~# O& zdecided to put the baby in a separate bed, and the) W% s$ U" w$ p* y+ z; ^0 V
father was not hugging him with bare skin and had" ~! U, m/ ?- y0 D& F% D: B
been using protective clothing. A repeat testosterone
1 o1 G0 L8 j/ E+ Ptest was ordered, but the family did not go to the
|! F$ ? i) f* S7 ^0 M5 vlaboratory to obtain the test.
: |2 T( j5 a' Q3 DDiscussion
$ E9 d4 o. \) j- x2 vPrecocious puberty in boys is defined as secondary2 K! }6 g6 }8 r; @" J) J# K) s% [
sexual development before 9 years of age.1,4
+ f: u# x, P- F6 b% x( t& _Precocious puberty is termed as central (true) when% x. d# d8 _8 `5 m9 M# T" s: S
it is caused by the premature activation of hypo-, f1 w0 B9 f4 e. R
thalamic pituitary gonadal axis. CPP is more com-
( i. B2 G! A- u" }. R1 \$ Z5 Imon in girls than in boys.1,3 Most boys with CPP% O4 L% ^! B' } e+ a
may have a central nervous system lesion that is! M4 s7 L4 u% }' g
responsible for the early activation of the hypothal-. o3 ^4 j3 Q3 E% U
amic pituitary gonadal axis.1-3 Thus, greater empha-
( l/ }8 J3 n# @1 Hsis has been given to neuroradiologic imaging in' I7 N' A7 Z% A- i# h9 @* b
boys with precocious puberty. In addition to viril-( s$ X+ Z5 d6 @8 P
ization, the clinical hallmark of CPP is the symmet-6 Q) @! v* K$ b8 t2 _7 h' C* I
rical testicular growth secondary to stimulation by
! e/ I j0 ]) d+ O% ogonadotropins.1,3. V* }. ~" T% z( Y& P6 m+ c
Gonadotropin-independent peripheral preco-
: D& j% R% ]/ T* }cious puberty in boys also results from inappropriate
2 N- f3 ]; h R9 Dandrogenic stimulation from either endogenous or% m& a( a8 D9 s) W1 f
exogenous sources, nonpituitary gonadotropin stim-5 G5 a9 q5 q* Y+ j* v+ o8 q+ }
ulation, and rare activating mutations.3 Virilizing
7 m3 M0 c$ h3 r- A& Z5 gcongenital adrenal hyperplasia producing excessive
4 V ]3 G" A Z$ c) t$ M/ tadrenal androgens is a common cause of precocious
, l& y/ X* s0 p% n- @2 ~puberty in boys.3,4
5 }4 r9 K6 @ y7 `The most common form of congenital adrenal1 i7 @6 j$ y. l ~* y6 D) B1 {% b
hyperplasia is the 21-hydroxylase enzyme deficiency.' t. _( y- T0 h' \2 r% a6 u
The 11-β hydroxylase deficiency may also result in4 A* E/ i7 ^) }, c% X
excessive adrenal androgen production, and rarely,- J, ~. |& h) q
an adrenal tumor may also cause adrenal androgen6 |% c' o, _6 V7 ~+ u0 A8 \
excess.1,3
8 O+ |5 V @$ _/ E. i( W5 e, w, Bat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
2 t& H* N) E1 R5 O0 t1 b542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
6 a& _) j6 l5 B) h/ SA unique entity of male-limited gonadotropin-: q" n, t7 k2 X$ @: ?9 Y
independent precocious puberty, which is also known
# v, e3 b6 o2 s% v" X: J+ M* _' Ias testotoxicosis, may cause precocious puberty at a
: W% r e' ]+ H, |; B3 O, _very young age. The physical findings in these boys; I4 P" [6 P( b+ \
with this disorder are full pubertal development,
( E- U& M% O4 E3 Oincluding bilateral testicular growth, similar to boys- g( S6 ], M4 x" @8 @3 p
with CPP. The gonadotropin levels in this disorder$ c1 O7 i d7 a6 u8 A
are suppressed to prepubertal levels and do not show% v( ]3 C# i( [ x/ L+ |2 m
pubertal response of gonadotropin after gonadotropin-4 y4 ~8 r W M* W
releasing hormone stimulation. This is a sex-linked" _1 U7 D8 I4 k# {& j
autosomal dominant disorder that affects only8 \: k+ i; J- R' L% T( b- d
males; therefore, other male members of the family+ }3 L: O8 |. W; n: v
may have similar precocious puberty.3" `( k# Y7 Z3 T( F7 K: |- o
In our patient, physical examination was incon-
+ S x! q: L7 Jsistent with true precocious puberty since his testi-
, w4 G& @1 @- T2 O+ S# Hcles were prepubertal in size. However, testotoxicosis
5 U, p! {3 z) s/ j3 Cwas in the differential diagnosis because his father
5 k( v3 M. `, y3 Z& [started puberty somewhat early, and occasionally,! z- N) F- {5 Q9 O4 X' R2 x
testicular enlargement is not that evident in the' f" G: s, l1 ^! w j& @: d& z
beginning of this process.1 In the absence of a neg-6 i1 N( t% a& u! O$ O4 G
ative initial history of androgen exposure, our
, h1 U4 H- W# O4 Qbiggest concern was virilizing adrenal hyperplasia,4 s# q; \' V' L9 U1 e# F
either 21-hydroxylase deficiency or 11-β hydroxylase
: C9 L8 ^2 o* F3 _deficiency. Those diagnoses were excluded by find-
0 F8 J' S: }5 |6 K; w& V% y" F& ling the normal level of adrenal steroids.2 G$ s0 v& A7 Z8 u$ L; j9 h% Y
The diagnosis of exogenous androgens was strongly3 s6 A8 Z2 D2 a V$ _: z
suspected in a follow-up visit after 4 months because
. e+ y2 X1 w9 x$ e% ^; {* [$ sthe physical examination revealed the complete disap-- U- f% E# {+ K J: P! C
pearance of pubic hair, normal growth velocity, and
( @- A' f5 r0 Y1 o, J, r2 M) Cdecreased erections. The father admitted using a testos-
G* z. P+ ?2 n6 m% u# C: B4 oterone gel, which he concealed at first visit. He was
! X9 P5 j: S3 A" rusing it rather frequently, twice a day. The Physicians’
! N( P: k) {0 T, lDesk Reference, or package insert of this product, gel or5 R) f* u& K7 n% N: W$ E& M
cream, cautions about dermal testosterone transfer to- G( X% p6 S# p: H
unprotected females through direct skin exposure.
l6 @5 I4 Y" r$ g4 k8 p: ZSerum testosterone level was found to be 2 times the3 P: n& _4 q o5 f- e$ p
baseline value in those females who were exposed to
) c6 `+ G1 E$ N/ Y# L% W/ Xeven 15 minutes of direct skin contact with their male
. F! F4 g5 P8 ?partners.6 However, when a shirt covered the applica-
8 |' i' Z. c; [1 g& ktion site, this testosterone transfer was prevented.
) S# Y @6 c, NOur patient’s testosterone level was 60 ng/mL,
" t& z i6 s8 Xwhich was clearly high. Some studies suggest that
# m+ J8 @- @9 B% J$ r% w) h. u Udermal conversion of testosterone to dihydrotestos-- I. g* Z" w! W/ e
terone, which is a more potent metabolite, is more
' S* U7 P* U/ q6 L# G# Dactive in young children exposed to testosterone
7 L; L# D6 i. _9 @* X: }7 i( sexogenously7; however, we did not measure a dihy-9 ?8 f, N; z4 G- |7 N" z
drotestosterone level in our patient. In addition to
' b8 b# _: D) R4 k- cvirilization, exposure to exogenous testosterone in" s) G1 U0 l! [) F
children results in an increase in growth velocity and- z. c0 ^/ Q7 [: w
advanced bone age, as seen in our patient.
; m9 g' ^# X9 n5 {The long-term effect of androgen exposure during
- a V# Z& ]. I2 k% b6 x2 s$ g' y6 Uearly childhood on pubertal development and final
! G; u) }9 e! y# jadult height are not fully known and always remain+ N7 F$ S1 T: r4 c* A0 u! L
a concern. Children treated with short-term testos-
5 Q6 v4 a) H7 Q; K) k3 kterone injection or topical androgen may exhibit some
" F& t- K! c: ?) h4 j2 ~4 {acceleration of the skeletal maturation; however, after: ?8 G, ^. `+ P# u0 \% _0 ~
cessation of treatment, the rate of bone maturation
& F# y* a l8 E+ J6 D! \, {decelerates and gradually returns to normal.8,97 [+ j* Z0 k6 q
There are conflicting reports and controversy- K# p8 p, X* H ], S( @ J
over the effect of early androgen exposure on adult+ W2 e3 E6 H$ Q( \8 ^$ M4 y
penile length.10,11 Some reports suggest subnormal" F p1 M3 Y: q9 r
adult penile length, apparently because of downreg-
$ t$ ^8 K0 e* ^ D" Nulation of androgen receptor number.10,12 However,; P6 C% H& K+ L( e, p
Sutherland et al13 did not find a correlation between, y! J9 ~- H9 K2 |! @$ _) ~. |8 \% L
childhood testosterone exposure and reduced adult6 S9 V6 I1 m: T% a7 e" p
penile length in clinical studies.$ H+ X7 Z& x4 Y5 Y. T; o% ~$ x& W; u
Nonetheless, we do not believe our patient is+ x, i9 a- W/ z" k
going to experience any of the untoward effects from
% [4 f( u# |- S: C% qtestosterone exposure as mentioned earlier because& M: j2 W# w# S( _
the exposure was not for a prolonged period of time.
6 L; q2 C) U( I, k& wAlthough the bone age was advanced at the time of8 h" L$ B$ k5 x; z
diagnosis, the child had a normal growth velocity at
" K2 Q8 @1 a( `# Wthe follow-up visit. It is hoped that his final adult% v& t0 _8 s, g3 U6 ^, c
height will not be affected.
' `( J# J. |0 E O) e G. A% V5 MAlthough rarely reported, the widespread avail-% V& \' T$ {" i- M
ability of androgen products in our society may9 W, |. ]! W1 s3 A; T3 B( y
indeed cause more virilization in male or female
% z- s z; U: {3 E8 d% G3 \2 xchildren than one would realize. Exposure to andro-) |$ C% ?2 ^8 {4 m
gen products must be considered and specific ques-
+ ^! O4 ?& r$ d1 z" B5 Ytioning about the use of a testosterone product or& U+ R1 f1 } @' ?, \& C
gel should be asked of the family members during" L$ `8 m; N, `6 f# C
the evaluation of any children who present with vir-$ B' {9 N% C) t3 }
ilization or peripheral precocious puberty. The diag-# s& K w& Z5 h# {: m; Q' v6 u$ f
nosis can be established by just a few tests and by9 x0 O+ z; G3 `! b
appropriate history. The inability to obtain such a7 ]8 c; H7 K% i `8 e; S b4 _
history, or failure to ask the specific questions, may4 J" \2 O6 U* p
result in extensive, unnecessary, and expensive
( @, K0 g- o1 L2 Finvestigation. The primary care physician should be& r( j! y% t; z
aware of this fact, because most of these children
. X2 C5 M1 h. T& u' S" Xmay initially present in their practice. The Physicians’
6 ]1 [6 n; z1 QDesk Reference and package insert should also put a
% D( R& v9 h1 Hwarning about the virilizing effect on a male or$ z* h8 o; d6 u7 j/ V6 f1 n" t
female child who might come in contact with some-
* _+ e: g* ^2 g+ b2 W$ {one using any of these products.
2 v3 C( l" `$ K6 X# K4 NReferences
1 T# o6 y6 {, Y1 c. F+ T1. Styne DM. The testes: disorder of sexual differentiation
' L) R4 _+ k2 \* ^and puberty in the male. In: Sperling MA, ed. Pediatric% P3 R8 y4 j6 e, q9 G) H- k1 \
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;: F2 A6 F% J8 D$ a+ h# p% j
2002: 565-628.
1 i/ w7 ]8 w7 p/ n; d2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
$ ? b' [ |& O) a5 G O3 ?! Vpuberty in children with tumours of the suprasellar pineal |
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