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Sexual Precocity in a 16-Month-Old7 l& w5 p7 d- T# R5 @
Boy Induced by Indirect Topical3 \! O: O* ?% i6 y. D
Exposure to Testosterone6 n0 g3 ^1 A3 O$ w" w0 B3 I4 s F1 j
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
5 w; q7 u* a: {6 ~and Kenneth R. Rettig, MD1
9 X4 r) |: D9 w9 {3 U8 u# B) _1 `' |Clinical Pediatrics' i/ Z$ o1 w9 W9 M- y' x, H! u
Volume 46 Number 6
' I) C- Z9 [* b1 \8 V5 x JJuly 2007 540-543
# `. V1 g- F: M- {© 2007 Sage Publications
' h% w, l) g7 A) q3 ]: N3 x+ [10.1177/0009922806296651
6 y% }; t: \ s6 Q; x! M- C1 [http://clp.sagepub.com( w: E8 V/ f" w
hosted at
/ E3 p$ y$ \; t% }# Ehttp://online.sagepub.com3 B& H9 h0 b! R6 A% D: C$ n
Precocious puberty in boys, central or peripheral,
% E9 v& j' s# ?0 C# ?2 R) Lis a significant concern for physicians. Central
/ o( z, y# n+ {3 @2 o- G2 Qprecocious puberty (CPP), which is mediated- ]( l6 }! X- R- v" j
through the hypothalamic pituitary gonadal axis, has
! H9 [' P9 X1 n# D4 ca higher incidence of organic central nervous system
/ q7 A2 @7 j0 g0 Y- d, q6 Alesions in boys.1,2 Virilization in boys, as manifested
) j/ m7 G) O7 }& P6 A% _by enlargement of the penis, development of pubic
" Z' M2 i/ H$ O$ A( @ \hair, and facial acne without enlargement of testi-
! R/ t3 R/ i* dcles, suggests peripheral or pseudopuberty.1-3 We
0 v0 A8 I" Q- t. |5 L1 ireport a 16-month-old boy who presented with the. a8 D, R8 {0 N( t
enlargement of the phallus and pubic hair develop-
7 ?% ]! K' E+ w7 ` h' Ument without testicular enlargement, which was due; x- Q+ W4 r# `7 S+ F
to the unintentional exposure to androgen gel used by
6 D7 N# h, F1 o1 r9 f+ Tthe father. The family initially concealed this infor-
5 f8 q; h# ~' c- z O2 u5 W) ^mation, resulting in an extensive work-up for this9 S( E4 q% B9 \+ p, S' b. }! V* Q
child. Given the widespread and easy availability of
. ]/ f; O) N' _* H3 L+ {4 {testosterone gel and cream, we believe this is proba-# x4 Y7 J2 \: ` l( g8 k- w
bly more common than the rare case report in the
2 W- y6 J" p! ^3 wliterature.40 M) W& g: |: [7 A Z+ i! v8 ~
Patient Report
; _2 \) x/ w2 D8 T7 X" D% b6 U8 AA 16-month-old white child was referred to the& @7 k3 z/ n8 g" c
endocrine clinic by his pediatrician with the concern
' c3 E V4 s- ^of early sexual development. His mother noticed" u" w$ f( N$ y
light colored pubic hair development when he was
/ n# }5 N1 h c7 AFrom the 1Division of Pediatric Endocrinology, 2University of; G3 x& s5 l$ @$ x$ U' l3 l
South Alabama Medical Center, Mobile, Alabama.% p" g) U' L: W, H( c) n" n
Address correspondence to: Samar K. Bhowmick, MD, FACE,
4 L3 O1 x1 O1 o) K; ?& J, g; ^Professor of Pediatrics, University of South Alabama, College of. f, f. m" I! V1 j# x% `, v
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;8 S4 p; @5 r4 @8 x$ _5 a% l z$ g8 I! O
e-mail: [email protected].
x j4 P" R0 u& f0 H; Nabout 6 to 7 months old, which progressively became& J$ s( e- |' Z" ~' H# Y
darker. She was also concerned about the enlarge-/ R, I: [' K8 s; R: x* M
ment of his penis and frequent erections. The child
1 G' [( L) A0 g" Awas the product of a full-term normal delivery, with
. V7 x4 ?3 p& X4 U# F" |$ Ba birth weight of 7 lb 14 oz, and birth length of
' j+ k' l$ P8 u* X3 R5 ^" x4 R20 inches. He was breast-fed throughout the first year- `. s1 R" W4 R' Y7 F5 |
of life and was still receiving breast milk along with2 `2 l. T, H+ k, S6 r. C" g6 Z
solid food. He had no hospitalizations or surgery,2 X: w" T% y1 Y7 V
and his psychosocial and psychomotor development
/ }8 {$ }+ u& S, v8 c7 I9 k" Qwas age appropriate.
" X; ^) l8 A- Z3 r4 _4 g0 m& nThe family history was remarkable for the father,* |* }4 z4 L" [9 k/ t
who was diagnosed with hypothyroidism at age 16,0 u, F. e4 t" @. L' t/ E5 ?
which was treated with thyroxine. The father’s9 B0 |* |% f; V3 E& z
height was 6 feet, and he went through a somewhat3 n. s% t& u. A
early puberty and had stopped growing by age 14.5 c6 V' Q" d) z( A
The father denied taking any other medication. The+ A \+ M5 h. @- R9 {- E
child’s mother was in good health. Her menarche7 l4 }$ k9 @3 X
was at 11 years of age, and her height was at 5 feet
5 N4 ~2 U7 k& a1 _5 inches. There was no other family history of pre-
, {+ `& s4 m8 D! l. M) Zcocious sexual development in the first-degree rela-
7 i4 h% r3 f( k% W9 _ G7 rtives. There were no siblings.
]$ O2 |' [6 ^! o) R6 pPhysical Examination
* L& E; e6 R4 u& ^0 g6 u, v E( {The physical examination revealed a very active,$ X4 q+ n8 E" e0 o0 Z$ y* U2 u
playful, and healthy boy. The vital signs documented) a: @: M# F+ J% s
a blood pressure of 85/50 mm Hg, his length was
0 r$ C5 a: J: a" O0 H90 cm (>97th percentile), and his weight was 14.4 kg! F1 `& J y0 N# i, q b& X6 }. i
(also >97th percentile). The observed yearly growth$ a: N" {8 e8 o W9 A
velocity was 30 cm (12 inches). The examination of& w4 p% W/ ]9 F& C3 N8 q6 n8 M
the neck revealed no thyroid enlargement.. j; @5 M& x, U) e; `+ c
The genitourinary examination was remarkable for
$ L/ f5 Q; e+ eenlargement of the penis, with a stretched length of; `6 S7 v& S# f
8 cm and a width of 2 cm. The glans penis was very well8 L% \8 w3 h' H* ]7 w) p& [) e* A
developed. The pubic hair was Tanner II, mostly around
) {8 c9 U) Z& |, H4 ?& B& S540
0 n- g% @7 ] Jat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
6 t' s J$ b/ o6 b' tthe base of the phallus and was dark and curled. The, `9 ~6 U* P8 j- l' m/ g. @' o
testicular volume was prepubertal at 2 mL each./ Q( Z8 u7 ~1 U( }7 M
The skin was moist and smooth and somewhat2 ?0 I* K% Z1 y0 _% X
oily. No axillary hair was noted. There were no4 V: L5 q# R6 f v! {2 V& w7 ^! A" {
abnormal skin pigmentations or café-au-lait spots.
8 d5 x7 X. l3 Q. y% T5 N) [. y1 q' lNeurologic evaluation showed deep tendon reflex 2+
; A# O, K& a% w/ Qbilateral and symmetrical. There was no suggestion% J( K& }( R1 R) r& p
of papilledema.
/ j* j- P; A9 Q4 Z1 ^- FLaboratory Evaluation6 \# V* [) \! y5 [
The bone age was consistent with 28 months by
1 w6 ?) I( X- X( w/ Kusing the standard of Greulich and Pyle at a chrono-
% D2 e8 u! s* ?: r. Vlogic age of 16 months (advanced).5 Chromosomal$ A" b8 ?! Y5 _& h) O' Y
karyotype was 46XY. The thyroid function test
% q7 c' n2 I% \$ kshowed a free T4 of 1.69 ng/dL, and thyroid stimu-7 i) ^0 g G7 \& t5 }
lating hormone level was 1.3 µIU/mL (both normal).0 |( m. c+ F V8 V9 a
The concentrations of serum electrolytes, blood
+ X5 l3 i. _" b. e, Z3 k9 b& w+ S. yurea nitrogen, creatinine, and calcium all were
4 j! ]) V% Z( o: i4 Nwithin normal range for his age. The concentration, r. V3 i) X# G
of serum 17-hydroxyprogesterone was 16 ng/dL. e3 Q3 l3 B- c& M
(normal, 3 to 90 ng/dL), androstenedione was 20; Y/ r2 U4 ` k" k
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
" v$ M6 B- @* R8 B* dterone was 38 ng/dL (normal, 50 to 760 ng/dL),5 `6 I7 @4 q# s5 V+ v3 A
desoxycorticosterone was 4.3 ng/dL (normal, 7 to2 `! E1 ?6 r$ i8 }1 B
49ng/dL), 11-desoxycortisol (specific compound S)' U: V* X0 o( ~3 R: s
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-! P: q( i+ r; O/ n
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total5 m6 ~ D- l w$ m) |9 ]5 R2 |4 k
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
" k1 H9 L2 a5 q- p4 c7 cand β-human chorionic gonadotropin was less than8 H+ @6 H+ ~- t
5 mIU/mL (normal <5 mIU/mL). Serum follicular6 B0 q2 Q9 m& O4 C6 f
stimulating hormone and leuteinizing hormone7 q+ e% ^' A; f' j8 L8 B& l# K1 ~
concentrations were less than 0.05 mIU/mL
& @3 M% \3 R' A) \- d, V9 a, k(prepubertal).- E4 y* `; ]8 i- f) l% L/ A
The parents were notified about the laboratory
; e% z* r. O$ sresults and were informed that all of the tests were ]6 w: p3 k+ Y
normal except the testosterone level was high. The; o# l# m" v# @; p7 J; o- }: V
follow-up visit was arranged within a few weeks to2 Y: o7 P! Y8 a
obtain testicular and abdominal sonograms; how-, K1 T2 k: F* J% ]8 a8 [: q! f
ever, the family did not return for 4 months.
+ X4 }6 F# U jPhysical examination at this time revealed that the
; H; j( n- c- X5 Qchild had grown 2.5 cm in 4 months and had gained9 x0 ~( _: d8 X; y$ n
2 kg of weight. Physical examination remained6 H5 L P0 m; t8 K4 p' p
unchanged. Surprisingly, the pubic hair almost com-* [8 K' d" R$ u9 e+ y( P
pletely disappeared except for a few vellous hairs at
* f7 ]9 H" C) K$ E( P, ~# N* [the base of the phallus. Testicular volume was still 2
. s# ~" S7 I# c1 R% m* J/ amL, and the size of the penis remained unchanged.0 d! D4 n3 x# W; N9 m5 {9 g
The mother also said that the boy was no longer hav-2 e( g8 {) T3 \. M; v; u
ing frequent erections.
& H8 B( n. y$ `, V6 SBoth parents were again questioned about use of# z* c4 p. s; Q, B5 L
any ointment/creams that they may have applied to
- k- _7 S7 d( }1 zthe child’s skin. This time the father admitted the
: L0 }5 K! D/ l/ eTopical Testosterone Exposure / Bhowmick et al 541" q2 V6 R$ q1 ?7 z F" y
use of testosterone gel twice daily that he was apply-+ b$ ^; Q, c* x
ing over his own shoulders, chest, and back area for
Q$ n2 L) ~/ E/ W8 Ha year. The father also revealed he was embarrassed
# S/ C. \! N: R9 K/ a- s/ P% K% rto disclose that he was using a testosterone gel pre-
0 _& l8 z7 B5 X" G: A3 d+ iscribed by his family physician for decreased libido G: a: P6 @# G2 u) m8 ^
secondary to depression.2 V+ s/ q4 S, F# p; M! z
The child slept in the same bed with parents.
8 e* t5 N! _* ]! QThe father would hug the baby and hold him on his( j, c0 K% L0 I- o9 X( a
chest for a considerable period of time, causing sig-5 S; c1 m, W$ @1 V- m+ B$ e
nificant bare skin contact between baby and father.. ^+ L* N4 `+ h* l
The father also admitted that after the phone call,
$ T' q4 U D$ v# ~when he learned the testosterone level in the baby
9 @" m4 ^' E6 c& k" Rwas high, he then read the product information# a7 f6 W/ U, V0 o* `7 z% }
packet and concluded that it was most likely the rea-
( Q( l' `, I# m4 v9 t( K, Ison for the child’s virilization. At that time, they
?( o9 g- p3 s0 Z* B3 A$ Qdecided to put the baby in a separate bed, and the7 M) s3 |7 e5 S
father was not hugging him with bare skin and had
6 I! x4 b- x' {( Pbeen using protective clothing. A repeat testosterone
4 h) ?& }& h; htest was ordered, but the family did not go to the
& [1 v( o% }/ N: Alaboratory to obtain the test.8 k5 m2 C7 u+ D i t
Discussion5 o3 R4 x1 ~% H8 x; B4 X1 ]% w! p
Precocious puberty in boys is defined as secondary
4 G) X6 e/ M) o9 o, @0 l- L9 Tsexual development before 9 years of age.1,4& l1 x6 F0 L6 v
Precocious puberty is termed as central (true) when8 b8 ~8 z. B" X6 i- J# J
it is caused by the premature activation of hypo-
) t2 B0 O1 }7 Q U& {5 P- Y' mthalamic pituitary gonadal axis. CPP is more com-
3 P2 n0 N8 L. Nmon in girls than in boys.1,3 Most boys with CPP0 S" m. m7 B5 I4 U- ]" Y
may have a central nervous system lesion that is4 r. ~4 M/ |; O
responsible for the early activation of the hypothal-2 Y \4 w/ j3 c8 K5 k0 F
amic pituitary gonadal axis.1-3 Thus, greater empha-0 W3 ^3 O& u& H1 F) Q5 e4 B
sis has been given to neuroradiologic imaging in
) G$ O+ B o, ?) ^5 gboys with precocious puberty. In addition to viril-
% | B, T7 } n) c& \% lization, the clinical hallmark of CPP is the symmet-
7 E* S! [; J7 k* l! R( ^rical testicular growth secondary to stimulation by) y& r0 P% s% h
gonadotropins.1,33 {/ c9 I$ x# N9 R
Gonadotropin-independent peripheral preco-
8 k( k& I% G4 A# Lcious puberty in boys also results from inappropriate- ?+ _6 \/ [" }
androgenic stimulation from either endogenous or; w" q+ N7 ]3 z4 K
exogenous sources, nonpituitary gonadotropin stim-
) }: B! A% d9 f/ Wulation, and rare activating mutations.3 Virilizing8 G1 C U1 e y8 K& m' N
congenital adrenal hyperplasia producing excessive
& g; T+ `. F, O+ k5 O6 c4 u! jadrenal androgens is a common cause of precocious
' C4 u( Q8 B( C( ?puberty in boys.3,46 f( M4 i! _) B* P( N9 g
The most common form of congenital adrenal
$ g# ?( |5 O: mhyperplasia is the 21-hydroxylase enzyme deficiency.
" W$ h* j2 A* M; EThe 11-β hydroxylase deficiency may also result in
S- s1 ~' e# s% m+ w* Eexcessive adrenal androgen production, and rarely,
2 @$ L6 j' O' d4 T/ k$ Gan adrenal tumor may also cause adrenal androgen! @: z- ]+ w# q2 p
excess.1,37 H! h9 N# p0 z4 [
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from7 Z2 E6 G* R% X8 d% h. m: R
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
; Y0 {, n- @9 f& |5 j3 u$ n+ k; hA unique entity of male-limited gonadotropin-
K$ o# }- G" M& _: N$ @# Rindependent precocious puberty, which is also known; }$ M1 o& s4 ^* `
as testotoxicosis, may cause precocious puberty at a. E2 m- _' H6 T) T, ^- H( M7 f
very young age. The physical findings in these boys' U9 i e; N N8 C/ O) ]
with this disorder are full pubertal development,
1 H) I" U3 R, r kincluding bilateral testicular growth, similar to boys
6 G( `0 N: S0 }( J7 \with CPP. The gonadotropin levels in this disorder
) u" c, k, \- B* p0 E5 g5 Dare suppressed to prepubertal levels and do not show7 ~+ S0 U' [6 h; T+ f) \
pubertal response of gonadotropin after gonadotropin-# U9 K0 z) Z$ g! K
releasing hormone stimulation. This is a sex-linked
1 A! D' {3 b6 Z3 Lautosomal dominant disorder that affects only) U1 V) l7 |* I n, Y+ p. K8 S
males; therefore, other male members of the family
: J1 y" M* w3 M1 umay have similar precocious puberty.3
+ N* x: }9 A4 k3 T8 @In our patient, physical examination was incon-- S- o- s! }4 w) W6 M2 n
sistent with true precocious puberty since his testi-+ ~, ]6 O1 i: B1 A1 J2 B6 ]
cles were prepubertal in size. However, testotoxicosis
3 o! a f. t3 A$ Awas in the differential diagnosis because his father8 }4 J* F9 ^+ z3 C
started puberty somewhat early, and occasionally,4 F) O1 m8 e# f& R9 m; D
testicular enlargement is not that evident in the
0 F1 t% @, t$ m5 W8 K% wbeginning of this process.1 In the absence of a neg-$ Y: o. n" W' v; I) |3 N: e4 ]
ative initial history of androgen exposure, our& ]; q: k! a" Z( w* n4 x* D D
biggest concern was virilizing adrenal hyperplasia,: R. z) l$ I1 p9 m4 O$ x
either 21-hydroxylase deficiency or 11-β hydroxylase; Y% f! T' P3 w$ s9 l; b' T* @, P
deficiency. Those diagnoses were excluded by find-& y8 |0 g- S! r1 @. v
ing the normal level of adrenal steroids.
( p- \% |/ u# bThe diagnosis of exogenous androgens was strongly0 E/ c# A, A2 @
suspected in a follow-up visit after 4 months because& \+ z, X; W* k
the physical examination revealed the complete disap-
5 g. A5 s8 B; Y! upearance of pubic hair, normal growth velocity, and
. v h! U4 p4 g2 K- qdecreased erections. The father admitted using a testos-( C) c- B: l; c2 P
terone gel, which he concealed at first visit. He was8 |% O4 K& A n5 o* [. ~) a/ |
using it rather frequently, twice a day. The Physicians’0 K! I! T7 i& S/ C( I! ]
Desk Reference, or package insert of this product, gel or! f: `. R/ ~. ?
cream, cautions about dermal testosterone transfer to
/ v9 A' O' R1 d1 B7 {- Vunprotected females through direct skin exposure.
# \! E8 v- r" F# `6 L! z5 MSerum testosterone level was found to be 2 times the
$ }! e, v& H: O+ Y6 F0 J3 i5 V3 ]baseline value in those females who were exposed to; |, `% J: p+ x, O# o; S; ^
even 15 minutes of direct skin contact with their male
' ]; W1 t8 K {, ~partners.6 However, when a shirt covered the applica-0 p: r& y9 v/ h8 h1 ?7 v7 a
tion site, this testosterone transfer was prevented.3 g8 c1 }( j9 z: n4 S# `# r% N
Our patient’s testosterone level was 60 ng/mL,+ Q- c |9 l4 o9 h8 g# S
which was clearly high. Some studies suggest that
$ S! V+ W+ P+ i5 z. T6 bdermal conversion of testosterone to dihydrotestos-, ]6 H) U* e7 a! P; O
terone, which is a more potent metabolite, is more& _' T- C0 U* J; u
active in young children exposed to testosterone) W; q7 h1 k0 x* a5 o% Y5 ]
exogenously7; however, we did not measure a dihy-6 z3 k: \; n/ e0 u% T$ Z
drotestosterone level in our patient. In addition to. P0 c( t: Z: Y0 E2 u: W" N5 n. N9 K5 I& k
virilization, exposure to exogenous testosterone in
) g- {% Q6 |7 xchildren results in an increase in growth velocity and
' Q- A$ `* J0 B+ R. Radvanced bone age, as seen in our patient.6 Y+ ~8 Q8 }$ k' }! w% e
The long-term effect of androgen exposure during2 _8 C& |$ T b, o) z8 R
early childhood on pubertal development and final
1 Q& N$ S$ a" q4 ^9 N$ G6 Xadult height are not fully known and always remain5 l/ Y7 O6 `) t: B+ n, `& O* e
a concern. Children treated with short-term testos-' n3 K l; V* e- O
terone injection or topical androgen may exhibit some* G- m0 @% N0 r A
acceleration of the skeletal maturation; however, after
5 B; c6 Y2 j' h4 \3 kcessation of treatment, the rate of bone maturation
* W# F0 f) [6 [0 ]# w1 edecelerates and gradually returns to normal.8,98 A s; C3 g: G+ C4 [$ y
There are conflicting reports and controversy- q: |; d# [% D0 A; w/ |5 q
over the effect of early androgen exposure on adult
% L* R6 ~2 x7 }( O) ]penile length.10,11 Some reports suggest subnormal
# U$ W# k4 r9 i3 v0 |8 `adult penile length, apparently because of downreg-
1 ]8 d6 T- x1 g& x& [ulation of androgen receptor number.10,12 However,. S5 g( `# W7 z3 X# ?
Sutherland et al13 did not find a correlation between- u, U) [ j3 {- }1 ~6 p
childhood testosterone exposure and reduced adult3 g# v# V3 m. y7 _! W% g) p
penile length in clinical studies.6 m2 b) |" w0 \, R
Nonetheless, we do not believe our patient is( y, Y7 Y4 f" L% R) s/ f' i
going to experience any of the untoward effects from
& M4 R8 A& k. D! X+ Atestosterone exposure as mentioned earlier because0 J8 c6 P, _- n7 a+ O/ k! [9 R9 f- B
the exposure was not for a prolonged period of time.2 V! L2 ^, c4 Q1 s
Although the bone age was advanced at the time of
4 o/ g# r. B) vdiagnosis, the child had a normal growth velocity at
- |9 Q, m4 W1 ] Fthe follow-up visit. It is hoped that his final adult
: L& g9 z" a' j2 Z* ]5 j4 vheight will not be affected.# u9 X- r) H% t0 D- H0 d3 Y
Although rarely reported, the widespread avail-; m4 ?! |$ h# j6 B4 w/ |7 x) E* x
ability of androgen products in our society may" @! z4 B) s0 A& \
indeed cause more virilization in male or female7 f, [9 [" m! i
children than one would realize. Exposure to andro-" X! c7 G x0 R" h) b" ?
gen products must be considered and specific ques-. [+ p) a# _, q' K8 n" B
tioning about the use of a testosterone product or
+ K* y1 h1 L, S, r9 S* Tgel should be asked of the family members during. [* S( P Z! e6 n
the evaluation of any children who present with vir-
1 X6 Q' ?* M f& Ailization or peripheral precocious puberty. The diag-
6 u! [. U6 J8 w; F2 ]' ^2 T' Xnosis can be established by just a few tests and by7 E+ t v3 B! |$ ]0 D
appropriate history. The inability to obtain such a+ x `, t0 ~1 s
history, or failure to ask the specific questions, may
5 E9 @7 X% p0 ^! u. N5 }- dresult in extensive, unnecessary, and expensive
( N+ B/ S, T2 L' U1 z/ v2 Vinvestigation. The primary care physician should be; |- u0 s f- s8 Y1 I& B
aware of this fact, because most of these children1 l2 x* U6 z( u4 ]' d
may initially present in their practice. The Physicians’9 @ g9 o. Z0 Y
Desk Reference and package insert should also put a
5 E8 F; p# @+ j0 lwarning about the virilizing effect on a male or/ v# }+ k. ]2 ?1 O% x
female child who might come in contact with some-: t) }) p" B0 _7 A, u
one using any of these products. \* Z, \3 F- A$ @
References
. L0 I' N- t& f, c0 d. R. t1. Styne DM. The testes: disorder of sexual differentiation; j3 C6 Q! s8 `. _7 {
and puberty in the male. In: Sperling MA, ed. Pediatric: }( p1 ?% J: V& C( n7 Q' J
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
* p( o6 n3 _: W* c4 W. L2002: 565-628.
4 A" r' e) ~+ c1 j. E1 i' b. L2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious* l% s6 ~1 q& w0 c" q8 P1 Y. ]
puberty in children with tumours of the suprasellar pineal |
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