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Sexual Precocity in a 16-Month-Old9 s7 f$ X1 [+ E" s! M2 D
Boy Induced by Indirect Topical* j4 f6 W, s5 u
Exposure to Testosterone
O3 {+ L% f6 U! Y3 c+ z, [) zSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
8 X, x) Z9 F9 Z8 Fand Kenneth R. Rettig, MD1
' i, `* f. f: R0 nClinical Pediatrics
* k6 v, C& t* j/ A9 a% hVolume 46 Number 6) `1 S# O) G; H( R" V! \1 d3 D- u) r! V3 P
July 2007 540-5433 ~! g; }7 r4 _5 T
© 2007 Sage Publications
5 q b9 `+ \. `+ ]% V/ j9 I10.1177/0009922806296651
! `/ R6 O. |% l/ W5 Yhttp://clp.sagepub.com6 u, a0 X. {$ |0 r+ ?3 A
hosted at
" Q2 |' ]6 q7 v yhttp://online.sagepub.com
6 A2 M9 Q& c7 X4 ]( c; Z4 {Precocious puberty in boys, central or peripheral,% m! a) T+ s# }0 u
is a significant concern for physicians. Central9 a2 E$ ^$ ~( ]
precocious puberty (CPP), which is mediated# u* M% K, Q) `3 a& D+ q
through the hypothalamic pituitary gonadal axis, has2 R9 }) T9 \% r7 @
a higher incidence of organic central nervous system
- N) x: T3 A' O! |& M% x; Qlesions in boys.1,2 Virilization in boys, as manifested7 e8 n- r, s: b; l" Q7 z
by enlargement of the penis, development of pubic* D; n8 M8 ~! m: |$ _! a
hair, and facial acne without enlargement of testi-" Q3 Y# B( \- W7 T, ]9 ~2 c
cles, suggests peripheral or pseudopuberty.1-3 We
5 Z6 [! y% [ s( V0 g zreport a 16-month-old boy who presented with the( I+ a- e5 ]" K. L
enlargement of the phallus and pubic hair develop-
- D! d+ G+ e6 q, `! F+ dment without testicular enlargement, which was due
% `, V* T$ s& O: pto the unintentional exposure to androgen gel used by4 q1 @5 i/ r2 Q' p- F
the father. The family initially concealed this infor-
& \6 v2 J9 B9 {7 N( m( R+ Gmation, resulting in an extensive work-up for this
" M5 N6 t6 N. E3 N! i; ]child. Given the widespread and easy availability of0 h& {1 r3 x4 {" ^
testosterone gel and cream, we believe this is proba-
' T# y- Q: g5 O0 Y0 {' Dbly more common than the rare case report in the
7 }, b! d- k# Pliterature.4
/ E! r- b5 w1 K( p) O& J8 v% MPatient Report
- v" ]1 `+ l/ I" r) P8 G; h0 |A 16-month-old white child was referred to the
7 ?5 e; [& ^/ k5 ]- m2 c8 aendocrine clinic by his pediatrician with the concern
7 ?3 w. L# D. G2 _" a; H* z, g# pof early sexual development. His mother noticed* O6 _3 f# e6 i( a0 _: M$ |
light colored pubic hair development when he was. J$ J h: ?6 ?* B
From the 1Division of Pediatric Endocrinology, 2University of$ u6 f* D9 D* M4 q0 b8 |- N3 o
South Alabama Medical Center, Mobile, Alabama.
; j: }; v* L: hAddress correspondence to: Samar K. Bhowmick, MD, FACE,
4 F+ u- F5 S' W; |Professor of Pediatrics, University of South Alabama, College of& q; q# |8 a% t
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
- D0 l9 X: A9 i' O# y6 s% ge-mail: [email protected].) N# A9 J- @$ G( E+ Y2 F
about 6 to 7 months old, which progressively became1 |/ g( i) q r3 ^8 C
darker. She was also concerned about the enlarge-, h- o# l3 L+ f7 }: K
ment of his penis and frequent erections. The child$ ]/ c) z5 R: u: i, Z
was the product of a full-term normal delivery, with
! O" n) |* c; s1 e. Va birth weight of 7 lb 14 oz, and birth length of5 @8 ^) l: ]7 i
20 inches. He was breast-fed throughout the first year
; d5 U1 {: ~0 b8 Tof life and was still receiving breast milk along with
# ^, L0 e: S4 |; q7 R$ f I% B1 csolid food. He had no hospitalizations or surgery,
+ r4 ?+ }- Q/ @5 S$ X, yand his psychosocial and psychomotor development
, d0 |0 h# @: d" j7 Jwas age appropriate.
( n' o$ p3 h$ bThe family history was remarkable for the father,* c# M5 H E0 C4 F
who was diagnosed with hypothyroidism at age 16,
% _( n! q7 {0 ], t. |which was treated with thyroxine. The father’s* P- b! o& G! c' H
height was 6 feet, and he went through a somewhat, i8 Y- F3 u) h7 N) U' A, y
early puberty and had stopped growing by age 14.1 U! H+ F }& h; w
The father denied taking any other medication. The& W" L ~! S' m( \( I- I
child’s mother was in good health. Her menarche! f. L- k+ r& ~& }/ v. X# s
was at 11 years of age, and her height was at 5 feet2 y, ^+ x; y' I0 T. g2 B
5 inches. There was no other family history of pre-
% @& [8 j% \( a' m" H3 y; I# f Fcocious sexual development in the first-degree rela-$ I5 k) J* D9 Y
tives. There were no siblings.( T: t3 a7 I2 H
Physical Examination3 Y0 w3 Z* n7 H2 M2 b6 m9 A, i) d( P
The physical examination revealed a very active,
# z- t( ]- o, k; l5 h- Yplayful, and healthy boy. The vital signs documented
% \% q3 u8 x# [5 R" M* \ Pa blood pressure of 85/50 mm Hg, his length was
# c, r+ Y7 v- j90 cm (>97th percentile), and his weight was 14.4 kg
( c, D( D6 Q0 i; n1 D% X(also >97th percentile). The observed yearly growth) Q: V9 {( T5 {+ z* _
velocity was 30 cm (12 inches). The examination of* p, U/ n9 d/ ?- R: Z2 N
the neck revealed no thyroid enlargement.
, V' V e* `% x% zThe genitourinary examination was remarkable for3 L/ T* n- [) ]& O, y2 H' d8 v& E4 T4 i
enlargement of the penis, with a stretched length of
( {" ~: o- I. B# n2 l) ~8 cm and a width of 2 cm. The glans penis was very well
& |; E( D( n. ]' D" U' v7 y; qdeveloped. The pubic hair was Tanner II, mostly around! J5 r+ s( Y, H: p% Y- P
5409 O; ]( i3 v7 C7 V
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from7 |: X7 ], a& Z5 E
the base of the phallus and was dark and curled. The
( R C& {) W/ V* Dtesticular volume was prepubertal at 2 mL each.# ?3 A$ a, m/ Y; \( [
The skin was moist and smooth and somewhat6 R: W# S7 w# {. ], V8 i% I- M
oily. No axillary hair was noted. There were no1 E& J. I6 t. B# A
abnormal skin pigmentations or café-au-lait spots.
4 L1 U9 O: h, ^+ P: I& Z5 gNeurologic evaluation showed deep tendon reflex 2+
3 X+ a4 N+ f" C% n9 X4 O* ?bilateral and symmetrical. There was no suggestion
- l0 \/ |) Z3 q' u7 qof papilledema.
; l0 E. V4 z9 a s& v6 {Laboratory Evaluation
- r9 I& E: p3 N5 `The bone age was consistent with 28 months by
' g, |* [/ M; S: I. m9 X% ]( u1 Cusing the standard of Greulich and Pyle at a chrono-3 d$ \) P5 i! p1 E4 n1 L4 F/ U* V
logic age of 16 months (advanced).5 Chromosomal! j( K$ S! t; b8 E1 u$ r
karyotype was 46XY. The thyroid function test
0 i! ?8 i$ x; o2 M+ }7 bshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
3 X! Z* g' M% n9 ylating hormone level was 1.3 µIU/mL (both normal).
+ M! z' G0 G$ Z9 o6 [, tThe concentrations of serum electrolytes, blood6 p( v* B8 M' W* e" c6 H- U$ x
urea nitrogen, creatinine, and calcium all were
2 R2 Z9 @: S5 w e! A* e! U6 iwithin normal range for his age. The concentration
# p8 A3 V' b" a* \of serum 17-hydroxyprogesterone was 16 ng/dL5 Q) c8 d$ X# Y# H
(normal, 3 to 90 ng/dL), androstenedione was 208 G1 r% V( R* y+ l" v) Z
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-1 }$ e/ n( z \( r r
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
+ ^1 ? ]" {" `8 D) S# o7 }) r2 Cdesoxycorticosterone was 4.3 ng/dL (normal, 7 to( _ Q& q0 G. |0 r2 B! {
49ng/dL), 11-desoxycortisol (specific compound S)4 D0 M+ [. p% b3 v9 Y5 h) O/ W
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
m* m# m. [! Y4 {" w- stisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
! f$ e& s% v2 A% ltestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
* S6 j3 F2 u9 band β-human chorionic gonadotropin was less than, E0 [! U( O' ]
5 mIU/mL (normal <5 mIU/mL). Serum follicular. I) j* ?* ^4 C* t& Y- H
stimulating hormone and leuteinizing hormone
& C6 r7 _- E& @0 G8 U! qconcentrations were less than 0.05 mIU/mL
: A6 @: ^' N! c2 v$ O(prepubertal).! K+ z; y5 r) ?$ [6 p, a
The parents were notified about the laboratory7 C8 A) {& t: H) |. m
results and were informed that all of the tests were# r9 O( ~- s% w" c j9 _
normal except the testosterone level was high. The
# A' w- {& I5 ]) {" o: mfollow-up visit was arranged within a few weeks to4 S% E! b2 e/ Z- a' z
obtain testicular and abdominal sonograms; how-
1 b1 t- c7 M0 y6 Hever, the family did not return for 4 months.
. D: O; M6 y7 D6 c( ZPhysical examination at this time revealed that the; S% }& K% [; G# V& ~
child had grown 2.5 cm in 4 months and had gained5 W7 z: T5 U! }& |: q& M0 \4 R9 K: Z
2 kg of weight. Physical examination remained* j0 D9 `. t P9 ?) w2 l
unchanged. Surprisingly, the pubic hair almost com-( w8 r+ y; l/ n# a3 @, z5 U
pletely disappeared except for a few vellous hairs at, I* j8 {. E1 Y, h6 b
the base of the phallus. Testicular volume was still 2
4 E# u6 L; _" T# J! Q" lmL, and the size of the penis remained unchanged.5 v$ t- N, r) P y4 F o n0 I9 F
The mother also said that the boy was no longer hav-) X9 I; P A% s8 K! [3 { G2 Y, ?# m
ing frequent erections.
2 g! n5 e5 p- G' FBoth parents were again questioned about use of
/ O6 }( E$ Z3 J! t0 e' n, J9 _1 Xany ointment/creams that they may have applied to3 u/ W( |7 C, p- p
the child’s skin. This time the father admitted the6 A: K3 C. |9 `+ L: I
Topical Testosterone Exposure / Bhowmick et al 5415 Z4 t! V9 i2 t% r7 u( w6 Q: |
use of testosterone gel twice daily that he was apply-/ x. Z: Q$ ]+ }/ E
ing over his own shoulders, chest, and back area for
" ~* J7 S" r7 w2 Oa year. The father also revealed he was embarrassed, _0 S" q% a& T4 F/ K
to disclose that he was using a testosterone gel pre-
& s4 L5 o1 _$ `$ g& Xscribed by his family physician for decreased libido; z1 b: F/ j; J7 g( h( q
secondary to depression./ d6 z+ L3 |1 x" b9 g8 E
The child slept in the same bed with parents.& Y# @) v7 `+ `$ L( ^/ k
The father would hug the baby and hold him on his. I- k+ K' W2 R
chest for a considerable period of time, causing sig-
# H0 u G; e1 F7 h& y2 x6 [; f) Knificant bare skin contact between baby and father.
$ o# D @. f* ~# j; F6 XThe father also admitted that after the phone call,
: y* K+ Q. Z' c* n/ H+ }when he learned the testosterone level in the baby
3 b1 Y# |$ x6 O, U5 iwas high, he then read the product information C% ^/ d0 R a4 a
packet and concluded that it was most likely the rea-
! o7 d% M: t& f0 qson for the child’s virilization. At that time, they. m3 F& y+ O* y/ k, ?- X
decided to put the baby in a separate bed, and the2 _& C5 n9 o( {. R! ~+ w
father was not hugging him with bare skin and had
7 P& \ Z1 R* a. n" O; [/ bbeen using protective clothing. A repeat testosterone6 ~( p4 X( D, \% X/ v0 k" ^* z
test was ordered, but the family did not go to the
8 q7 X% I! Y; s& C; hlaboratory to obtain the test., D% u) p' u7 x- D* t( Q9 R
Discussion3 X3 }7 T( v) c# M1 U: j3 p
Precocious puberty in boys is defined as secondary: m, b: I) |% Q3 \. V
sexual development before 9 years of age.1,4: I' Z: |6 D/ u( G& ?, O2 c& H3 M
Precocious puberty is termed as central (true) when; V& V7 f! Y/ ]. G/ J& T
it is caused by the premature activation of hypo-
0 h7 D7 s8 e# {/ l5 Cthalamic pituitary gonadal axis. CPP is more com-
# \$ \, C u; a0 A( ~/ {- L2 Jmon in girls than in boys.1,3 Most boys with CPP' E. ~+ O/ J( S# U" _% i. z
may have a central nervous system lesion that is
( W# T/ t8 f& ^: x3 y' N9 y: `( S' lresponsible for the early activation of the hypothal-
2 d. j! {; _7 m$ m6 q+ J/ Samic pituitary gonadal axis.1-3 Thus, greater empha-1 ^/ ]- U2 U4 E
sis has been given to neuroradiologic imaging in' N1 i" N) P8 d
boys with precocious puberty. In addition to viril-
( l9 e" g0 c" c \7 H( T3 P, jization, the clinical hallmark of CPP is the symmet-1 m: [( _2 o, d: w
rical testicular growth secondary to stimulation by
: W' G+ T. c- B) U. @gonadotropins.1,3
! _, T s \8 H0 r) b8 `: w1 JGonadotropin-independent peripheral preco-; K1 d, p0 \* Q8 c" l
cious puberty in boys also results from inappropriate- ~# F/ @6 {: m1 E4 j, Y3 j
androgenic stimulation from either endogenous or& U! j" Z0 B6 ?+ }3 H/ I
exogenous sources, nonpituitary gonadotropin stim-
+ y' \1 ~" @1 O8 r6 ~- a3 _3 iulation, and rare activating mutations.3 Virilizing
# E2 t. I( U: L/ Y5 A: l0 pcongenital adrenal hyperplasia producing excessive7 A9 }( B D4 e m5 W: @
adrenal androgens is a common cause of precocious
6 S# Z: u6 ?* H! i( j- J; @puberty in boys.3,4" A& z/ _2 Y2 o" M% X4 Y+ J
The most common form of congenital adrenal
+ O X8 B: s7 D2 khyperplasia is the 21-hydroxylase enzyme deficiency.: |( q6 S% U9 t9 J
The 11-β hydroxylase deficiency may also result in
, W2 O0 F" _; ]6 ]excessive adrenal androgen production, and rarely,) k' _5 h% c; E' ~& ?
an adrenal tumor may also cause adrenal androgen
+ k _0 l V: O% k$ E( xexcess.1,3
( D5 p6 y$ s% k" M, H' n9 u# gat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
4 ]8 P% l5 G2 U6 e542 Clinical Pediatrics / Vol. 46, No. 6, July 2007; z8 w+ A( d$ Y5 B8 i! r
A unique entity of male-limited gonadotropin-
& H8 q/ m3 i0 K& z9 iindependent precocious puberty, which is also known3 d1 i- Z/ I( I$ ~$ S
as testotoxicosis, may cause precocious puberty at a1 A+ ]7 S* k! V6 `1 q0 `8 a9 B
very young age. The physical findings in these boys
. {8 F! V0 l9 \' C2 kwith this disorder are full pubertal development,& H2 f8 C2 t% ~! o3 D$ D! ] O
including bilateral testicular growth, similar to boys7 V' f# {& t1 h' w
with CPP. The gonadotropin levels in this disorder
. w$ x" ~' u8 t0 _& t T, A( Tare suppressed to prepubertal levels and do not show0 X0 A/ N1 h* e1 [" h" E
pubertal response of gonadotropin after gonadotropin-
9 F. V* @" c: c/ Oreleasing hormone stimulation. This is a sex-linked2 c L/ j" D+ M, ~
autosomal dominant disorder that affects only
* @! ~& o+ M) P, l* ^' o5 Umales; therefore, other male members of the family
9 o3 n& v& d1 v/ C$ C/ }may have similar precocious puberty.3- G0 F: S8 H0 X, V0 C, R5 ~
In our patient, physical examination was incon-
9 q4 K- j- `7 [% Qsistent with true precocious puberty since his testi-
9 p" m5 _$ N# n2 H" f v# A/ dcles were prepubertal in size. However, testotoxicosis
. y5 V2 _/ J, J) {: [% |was in the differential diagnosis because his father; I- p+ s2 X8 Z4 [
started puberty somewhat early, and occasionally,$ I4 U3 `9 s- s
testicular enlargement is not that evident in the
o" L3 `/ Z# w7 g8 M: x) Abeginning of this process.1 In the absence of a neg-
0 m& b D3 A1 K/ B$ dative initial history of androgen exposure, our
8 Y4 t {6 L$ s! ?biggest concern was virilizing adrenal hyperplasia,
/ [0 I& a) j; f% Q' q3 n& Aeither 21-hydroxylase deficiency or 11-β hydroxylase
! O& X. O- z3 l9 ldeficiency. Those diagnoses were excluded by find-. Z6 v$ i+ e) \: y9 G
ing the normal level of adrenal steroids.
% n% W+ A" _/ fThe diagnosis of exogenous androgens was strongly+ A; ~$ x* d, }8 ~- N
suspected in a follow-up visit after 4 months because
, i5 U. g: a6 t m/ Rthe physical examination revealed the complete disap-6 J; x) e* `4 d5 j" E+ e
pearance of pubic hair, normal growth velocity, and! j8 k( m& v2 B) X: {
decreased erections. The father admitted using a testos-
. U1 B, }! O" P1 {0 Q( W( U- {terone gel, which he concealed at first visit. He was
" g6 o. V1 O8 susing it rather frequently, twice a day. The Physicians’& u+ V: l* a% Y, G3 S
Desk Reference, or package insert of this product, gel or2 Z. R7 d* _+ m, T( F Y+ A' S& n
cream, cautions about dermal testosterone transfer to+ G9 A9 F9 t; _7 U7 d
unprotected females through direct skin exposure.
9 Q- x: g0 ]. @3 ?9 @6 RSerum testosterone level was found to be 2 times the8 `- b: a0 X2 Q& X: g+ u. U
baseline value in those females who were exposed to% U8 ~9 q( \' ?; B
even 15 minutes of direct skin contact with their male0 {: }! t% V" |3 @& _' o
partners.6 However, when a shirt covered the applica-( h" S; N2 o2 J' j" N
tion site, this testosterone transfer was prevented.
; m8 _6 T7 g s2 c1 COur patient’s testosterone level was 60 ng/mL,4 Y4 |: @# x: U/ p
which was clearly high. Some studies suggest that& N' s( [0 T' g# ~' _/ U- G
dermal conversion of testosterone to dihydrotestos-
2 @9 _# n9 G6 G- Fterone, which is a more potent metabolite, is more6 _: _' Z% J9 r6 h" G* x( o9 @
active in young children exposed to testosterone
# }( f' K# i7 ~% rexogenously7; however, we did not measure a dihy-) S' f7 y" z1 Y/ ~$ c S4 E! l
drotestosterone level in our patient. In addition to) K3 M) y- X- Y' `
virilization, exposure to exogenous testosterone in5 Q2 ]/ D/ ~2 P8 N( x% o
children results in an increase in growth velocity and; u. \5 Y2 T+ s* h
advanced bone age, as seen in our patient.
+ o5 H/ { z4 G$ G- qThe long-term effect of androgen exposure during
6 V0 ?6 `" n0 ^/ p; @early childhood on pubertal development and final
4 s/ D4 b7 g p9 U# _adult height are not fully known and always remain5 Q2 ~: `6 [2 L
a concern. Children treated with short-term testos-' C9 \) z# g; k& L( X
terone injection or topical androgen may exhibit some
?0 v3 `6 F6 M" Sacceleration of the skeletal maturation; however, after
8 p. I, s1 c4 ]2 E1 L: o2 k) A% Acessation of treatment, the rate of bone maturation
+ r2 n/ i0 E4 g% D7 W, wdecelerates and gradually returns to normal.8,97 d0 E, `- b( B D7 c* V% t+ ?7 ]
There are conflicting reports and controversy
: g; _& g: G$ f6 n2 ~# Cover the effect of early androgen exposure on adult( J% C- ]3 l7 X9 X
penile length.10,11 Some reports suggest subnormal
" ~8 G- u1 m" w s! K$ Radult penile length, apparently because of downreg-
5 x& `1 Q. S$ v2 e/ b4 Nulation of androgen receptor number.10,12 However,6 \! \: z) }2 a# x+ | @
Sutherland et al13 did not find a correlation between
6 Q8 B8 u* G, n6 Kchildhood testosterone exposure and reduced adult# P6 G" c" B2 c6 J9 m1 `
penile length in clinical studies.
2 i9 w2 ?" d% e! O* Y8 i6 C- _5 kNonetheless, we do not believe our patient is
5 A v- z N5 ^% }+ u) l" ?going to experience any of the untoward effects from, h$ j! x% C( b$ D
testosterone exposure as mentioned earlier because
% a, _* m5 g! N8 Jthe exposure was not for a prolonged period of time.
% Z, D1 i0 x: Z- DAlthough the bone age was advanced at the time of, b$ Z W. N9 f) g0 Z' ^' _
diagnosis, the child had a normal growth velocity at
- {- j3 W- p: A9 A5 q" I+ ~* I Mthe follow-up visit. It is hoped that his final adult$ p' k8 Z$ p w2 J' t. Q
height will not be affected.
. t& G+ A7 ~& `! a5 n- r0 @$ b' n) ZAlthough rarely reported, the widespread avail-
L9 O' u# f$ o+ n( Sability of androgen products in our society may1 r6 E$ g c7 f2 z
indeed cause more virilization in male or female
$ v5 ~8 ]; f3 p) Bchildren than one would realize. Exposure to andro-7 D& Q1 ^; i3 p& v
gen products must be considered and specific ques-
. D m- Z' T. K! @5 _& Y8 Z% Etioning about the use of a testosterone product or
. {- l% g+ P" o5 y& igel should be asked of the family members during8 c& a( w5 v' b' \" u/ D
the evaluation of any children who present with vir-# x# [$ }- {( s$ u# _( _1 u; r
ilization or peripheral precocious puberty. The diag-2 p1 ?0 O2 t- J
nosis can be established by just a few tests and by
t; g0 X1 ~2 W% Kappropriate history. The inability to obtain such a
# a ]8 p! d r! N$ nhistory, or failure to ask the specific questions, may9 _# o1 [7 ?* z% Q, `2 c
result in extensive, unnecessary, and expensive
4 Z; S1 x- f( D6 O* r6 T' xinvestigation. The primary care physician should be( [+ P! ~1 ~) K& L- W. ?6 H
aware of this fact, because most of these children# a6 b. X* u _
may initially present in their practice. The Physicians’
/ Z+ R: ]0 K* ]Desk Reference and package insert should also put a
. }/ ~5 k6 \. Lwarning about the virilizing effect on a male or
$ v4 ?1 |4 }# O' }: Z$ G2 Sfemale child who might come in contact with some-
; | c6 y O( P3 m x, C0 rone using any of these products.& C7 l! F! P. m; u0 {
References6 F7 p. b1 r3 f
1. Styne DM. The testes: disorder of sexual differentiation2 P7 Q$ b, d) V( Y6 I
and puberty in the male. In: Sperling MA, ed. Pediatric
# h1 v' Z' t" S- R0 jEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
; C8 X! p+ p/ J3 ^% f" k4 V) S2002: 565-628.2 x% G- g1 f0 G8 _' D n0 Z% Q+ Z; q
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
, Y, b( Y+ }3 A6 s' Zpuberty in children with tumours of the suprasellar pineal |
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