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Sexual Precocity in a 16-Month-Old
! {! S' I- P) P3 p# tBoy Induced by Indirect Topical
$ z/ c! ]9 G( eExposure to Testosterone
1 s. `+ s. M* c: a7 F3 C3 [2 lSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2" m5 U9 T' [6 y
and Kenneth R. Rettig, MD1' d4 O7 C0 c7 {) x0 `
Clinical Pediatrics, T/ k) z' i2 b4 ^ K
Volume 46 Number 6
0 r1 U. c; k" TJuly 2007 540-543 }% M! |& l% h; C5 `
© 2007 Sage Publications- ^) g1 |5 W& P: g+ U5 Q% X
10.1177/0009922806296651
x7 B9 M) q1 Y, V. \$ L% ]) dhttp://clp.sagepub.com- E0 H; f$ L+ R- b; D
hosted at
' z6 v! s* ] {$ |+ Dhttp://online.sagepub.com
$ g! t' {* r( RPrecocious puberty in boys, central or peripheral,
* w0 V& E0 x% O- c- J+ W. dis a significant concern for physicians. Central
- n+ u; C* U# D9 C+ W6 E! iprecocious puberty (CPP), which is mediated
+ f1 C8 O: Z+ [: G8 vthrough the hypothalamic pituitary gonadal axis, has( c9 r# E; m6 S% ?) i( J
a higher incidence of organic central nervous system
' y1 F. D6 R4 Rlesions in boys.1,2 Virilization in boys, as manifested
4 J! g# R) h5 b7 {" ~by enlargement of the penis, development of pubic2 o5 V; G5 x P) A) o. v; y0 F
hair, and facial acne without enlargement of testi-
# M% F$ J" H4 s) Xcles, suggests peripheral or pseudopuberty.1-3 We
C) ^1 G ~' l7 F$ {report a 16-month-old boy who presented with the
: J, R2 M k6 D) N5 R2 benlargement of the phallus and pubic hair develop-# O5 k: V+ |9 h% o2 t' ]% r
ment without testicular enlargement, which was due: k* K) s, b. j# A+ t7 M: M# ]* o
to the unintentional exposure to androgen gel used by* W+ a1 O; X6 z3 x) R) [2 B
the father. The family initially concealed this infor-, c, q+ ~/ y6 o2 P" h7 ?
mation, resulting in an extensive work-up for this. [9 _* L- F9 T1 G' W3 r0 r
child. Given the widespread and easy availability of! G, v$ u( G/ z0 @% `
testosterone gel and cream, we believe this is proba-
& e5 X @2 N8 o3 z; r6 Jbly more common than the rare case report in the N4 }6 e! c* T: ^0 D
literature.42 [# _, O5 I& o1 ]
Patient Report
% j+ H; ] }9 G+ i! R0 bA 16-month-old white child was referred to the
8 O) d" R9 H( H8 {% N( L6 \* bendocrine clinic by his pediatrician with the concern! [9 m+ [" a- F/ b2 J6 Z) |8 O
of early sexual development. His mother noticed. I+ i/ z s8 N, d
light colored pubic hair development when he was
" Z- E, E; g6 I! G! o2 O8 s+ P+ cFrom the 1Division of Pediatric Endocrinology, 2University of
1 [9 d; t9 i, l* |% g; N2 mSouth Alabama Medical Center, Mobile, Alabama.
( S7 x- X, F/ t0 z" m7 O7 nAddress correspondence to: Samar K. Bhowmick, MD, FACE,
2 c( k6 y$ m5 X: n, B. iProfessor of Pediatrics, University of South Alabama, College of7 r6 R- Z# v3 }3 |- n! x. X
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;: p) a) |" \3 k) }! g
e-mail: [email protected].8 l ]* [* R# I. v; ~
about 6 to 7 months old, which progressively became
* e6 |5 r. m1 g2 ]. N6 ^4 i0 p/ M' }darker. She was also concerned about the enlarge-
- f+ ^: @4 l, [$ e% t8 `, p5 Zment of his penis and frequent erections. The child
2 u& z/ b' O! F- A4 y0 gwas the product of a full-term normal delivery, with
5 A' z, {/ Y- U+ r8 J. Ma birth weight of 7 lb 14 oz, and birth length of
. K) x6 i0 u4 E& i% j20 inches. He was breast-fed throughout the first year
& y) r5 Z7 |$ c2 dof life and was still receiving breast milk along with
/ ^: @1 Q* h1 [3 h, dsolid food. He had no hospitalizations or surgery,
& z6 d: ~( D5 w' o5 Aand his psychosocial and psychomotor development
2 z* @8 R" Y4 f# Gwas age appropriate.* ^, `2 v2 z. I+ q
The family history was remarkable for the father,6 y( t$ S, K* I4 S) d
who was diagnosed with hypothyroidism at age 16,% v& F+ _2 k5 ~3 N" B& s1 ~
which was treated with thyroxine. The father’s
: G* l7 S6 a1 o5 m- a' O, K3 Rheight was 6 feet, and he went through a somewhat# o' i/ j' V- ~9 o; F
early puberty and had stopped growing by age 14.
% V% ^; T- q* \The father denied taking any other medication. The
* N G' v8 z1 p) qchild’s mother was in good health. Her menarche
7 Q! E) j$ J4 c) S0 _" {8 s+ wwas at 11 years of age, and her height was at 5 feet% G' B7 ~* J$ I
5 inches. There was no other family history of pre-
6 s1 l) T1 \: o# m0 H8 ^8 X: s7 J. Lcocious sexual development in the first-degree rela-
0 _7 | C* l0 P# Stives. There were no siblings.
" t6 ]! s0 a% l1 {& tPhysical Examination
$ n3 g6 u$ d- q3 J3 TThe physical examination revealed a very active,
* [9 ?/ j) j# H9 t) J* vplayful, and healthy boy. The vital signs documented: F: C1 i: ^2 T# B; ^
a blood pressure of 85/50 mm Hg, his length was, M) ~7 H0 y# |4 J" {2 g& t
90 cm (>97th percentile), and his weight was 14.4 kg
1 H7 O9 T; \, f; t, i7 n(also >97th percentile). The observed yearly growth
O. l6 _1 b( b8 [velocity was 30 cm (12 inches). The examination of& R& M" W2 T- @: B+ ]6 u' B8 _
the neck revealed no thyroid enlargement.
1 y. B- @1 O0 O7 mThe genitourinary examination was remarkable for1 @0 G7 T1 `+ K9 L" g
enlargement of the penis, with a stretched length of
; \5 C9 @% k4 l! m+ S- U& z" V8 cm and a width of 2 cm. The glans penis was very well7 l( L1 p8 K O' y: t
developed. The pubic hair was Tanner II, mostly around' L! L. W) z( ~! t- a' s B
540/ ?9 S+ q1 g% a; @3 M' i
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from# B8 [1 v9 [* V/ y$ v3 X5 j- O) K
the base of the phallus and was dark and curled. The
: ?8 K- e5 Q1 X% b) L' g# i8 wtesticular volume was prepubertal at 2 mL each.4 h* u2 x# R9 e' k3 I
The skin was moist and smooth and somewhat5 U% m4 N$ G7 m: A* [8 l5 {& `9 A
oily. No axillary hair was noted. There were no
) }) i$ i7 e( m9 t1 Z6 A/ mabnormal skin pigmentations or café-au-lait spots.
_2 [$ s+ M% P6 q0 @Neurologic evaluation showed deep tendon reflex 2+( \! d; Z: v7 B9 `! {. S, S
bilateral and symmetrical. There was no suggestion/ z1 q$ k8 ^9 V; R2 e
of papilledema.
+ G! I7 g" r* |Laboratory Evaluation
: |- o+ q' {. X$ G) b5 }# CThe bone age was consistent with 28 months by0 S, U, C& t6 [2 ?
using the standard of Greulich and Pyle at a chrono-
8 A$ r; r8 ` i) Q0 Plogic age of 16 months (advanced).5 Chromosomal" S, N* \7 A, C/ S/ g+ A' `
karyotype was 46XY. The thyroid function test+ ]4 Z+ V, V6 M0 Y; t4 h6 |8 w$ ^
showed a free T4 of 1.69 ng/dL, and thyroid stimu-/ Z7 C& D5 E3 @4 F. v3 R5 H" m7 S
lating hormone level was 1.3 µIU/mL (both normal).
& E, P; E6 w7 D" B O9 I' b8 cThe concentrations of serum electrolytes, blood
) P5 c1 G" b& curea nitrogen, creatinine, and calcium all were
! J) V1 m8 s8 _6 k4 Vwithin normal range for his age. The concentration
2 w! c* g2 s( b3 Tof serum 17-hydroxyprogesterone was 16 ng/dL7 C0 p. S! C$ p6 u
(normal, 3 to 90 ng/dL), androstenedione was 20* c0 j' B |% ~* a: \
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
7 i" W; T7 y' E: Xterone was 38 ng/dL (normal, 50 to 760 ng/dL),3 G( j, w5 O8 K7 b7 q1 W7 j
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
5 P# |( B2 T3 F' A2 v2 P49ng/dL), 11-desoxycortisol (specific compound S). a) h7 s4 K1 u0 Y
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-4 N7 r" U9 y8 C! c$ o" M
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
4 y/ v6 s! j3 vtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),( K! `, n/ s- m1 x2 M
and β-human chorionic gonadotropin was less than, j& Z. X, q1 s+ u
5 mIU/mL (normal <5 mIU/mL). Serum follicular4 I! _6 m, C( z4 H i, f7 |
stimulating hormone and leuteinizing hormone S- C9 B# ^( t( f( k( e4 }% _7 |
concentrations were less than 0.05 mIU/mL6 {& [. }% f# x5 Q; D) A- F+ v& k. l
(prepubertal).4 y6 w" V, h7 m$ D8 i7 I
The parents were notified about the laboratory
1 g/ N# I$ y7 Wresults and were informed that all of the tests were0 u$ B: ]" S* ]6 k9 c
normal except the testosterone level was high. The
7 X/ t+ }+ E& W! T7 ufollow-up visit was arranged within a few weeks to
' I7 |& Y @( I) ^( mobtain testicular and abdominal sonograms; how-% _8 g3 f- S( d8 l1 a- ], |! }
ever, the family did not return for 4 months./ o# T% U3 g# I$ q
Physical examination at this time revealed that the
; B. }$ [ W% S" Uchild had grown 2.5 cm in 4 months and had gained/ N' N- Y: o! a, T/ C1 V- f; D
2 kg of weight. Physical examination remained
6 }6 O i L/ i) `! [- }" h' Tunchanged. Surprisingly, the pubic hair almost com-
- I: Y# @2 o9 K8 O' S/ b4 w0 Opletely disappeared except for a few vellous hairs at
0 z# u$ C: w* M& D! ?! Vthe base of the phallus. Testicular volume was still 2+ V/ N/ Z! ^& r2 v; r( V
mL, and the size of the penis remained unchanged.' D2 j/ M4 n/ S, g
The mother also said that the boy was no longer hav-
: s3 d0 n) T3 ning frequent erections.
" d, n4 S/ R/ H: [" E! H2 |" DBoth parents were again questioned about use of
) q1 }- A/ P0 T- F/ Wany ointment/creams that they may have applied to! N) Z$ ]( N4 O, u
the child’s skin. This time the father admitted the4 H/ V; c/ O/ _: i
Topical Testosterone Exposure / Bhowmick et al 541
* H$ E, K9 f8 e( s huse of testosterone gel twice daily that he was apply-
" y3 l0 B2 z7 q* ~' f0 t8 e1 O- Wing over his own shoulders, chest, and back area for
' \% a; t; w+ q! F- T# C7 oa year. The father also revealed he was embarrassed5 R( e' V7 h5 Z8 M- d ?
to disclose that he was using a testosterone gel pre-
; @' c2 Q4 J9 pscribed by his family physician for decreased libido/ V( J/ W! J% G: }6 E( j
secondary to depression.9 y5 ~1 f3 m- O4 A, w$ n7 u/ G! Q
The child slept in the same bed with parents.
9 ?# N! S# E2 v" Y3 ~" i8 LThe father would hug the baby and hold him on his
3 @) [% J8 z& Mchest for a considerable period of time, causing sig-
4 d2 g5 Y$ z' o! a* x. Anificant bare skin contact between baby and father.
( ]7 }, e) G0 L7 {+ f- O% r( r( sThe father also admitted that after the phone call,
- ^2 c9 D3 @2 v6 `when he learned the testosterone level in the baby/ v. p: X. ?2 B5 k; V4 {1 d
was high, he then read the product information# S% h$ f8 a& ]+ ^& W
packet and concluded that it was most likely the rea-# C2 _: _4 X% n) e3 q0 G) g
son for the child’s virilization. At that time, they4 ]8 q1 @) |* N- E! T( [
decided to put the baby in a separate bed, and the0 f' l# a2 F' G
father was not hugging him with bare skin and had
! G/ ?5 P% S" }1 D# N; Abeen using protective clothing. A repeat testosterone4 Q8 f6 c- {: p6 x/ B% O
test was ordered, but the family did not go to the
. |3 g# E1 I* z9 l0 ?laboratory to obtain the test.
% J( t- |; f& JDiscussion
4 v5 ?; z. Y0 W1 y- B9 Q8 }/ ?# bPrecocious puberty in boys is defined as secondary9 J7 E4 f5 ]) C$ K6 O
sexual development before 9 years of age.1,4/ v7 K- i4 d% u4 F
Precocious puberty is termed as central (true) when
/ w! K2 i# ~4 h" `6 [1 ~ yit is caused by the premature activation of hypo-, d. u+ i1 X% p( q
thalamic pituitary gonadal axis. CPP is more com-
, f; ?! X/ l( o& ^6 h. }0 M! ymon in girls than in boys.1,3 Most boys with CPP) b+ b0 h( W$ B9 g/ v/ h
may have a central nervous system lesion that is0 n! D8 z( C/ W d# y
responsible for the early activation of the hypothal-
" t* E; y: c2 S( |' u' {1 Y* Jamic pituitary gonadal axis.1-3 Thus, greater empha-! l0 q7 J4 ~. l
sis has been given to neuroradiologic imaging in# l% e8 q6 w# o' [# r1 x, y7 Y
boys with precocious puberty. In addition to viril-
9 y6 @' f; b7 q# M$ @6 oization, the clinical hallmark of CPP is the symmet-
) Z0 P6 w* e: D# lrical testicular growth secondary to stimulation by" o' c5 G1 @( r2 J' G
gonadotropins.1,3, p* b9 L1 g3 O
Gonadotropin-independent peripheral preco-( Y0 d" `! w& R( a7 e L
cious puberty in boys also results from inappropriate3 Q. h- o D B
androgenic stimulation from either endogenous or
- x/ |! ]! e; { s9 C( j( S9 P' a. gexogenous sources, nonpituitary gonadotropin stim-
8 w5 Y5 W; `$ gulation, and rare activating mutations.3 Virilizing* F& {2 r. H7 I
congenital adrenal hyperplasia producing excessive- N5 f; m6 U& d
adrenal androgens is a common cause of precocious
. j2 B: C( F" l9 ?0 l3 M7 mpuberty in boys.3,4$ g. x3 ^4 h! ]- W
The most common form of congenital adrenal/ t5 M" ~+ V& ]2 I! {4 q
hyperplasia is the 21-hydroxylase enzyme deficiency.5 }1 k0 Q) ]0 B: n5 i, B* r d
The 11-β hydroxylase deficiency may also result in' x: J0 }& \$ d0 t. S% R
excessive adrenal androgen production, and rarely,$ N( {( f- x4 f ]7 \
an adrenal tumor may also cause adrenal androgen
, G; R) r4 X8 x0 d8 P/ Q& p) ^excess.1,33 v' @1 P; g- q% f* \
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from, W8 m- a& V' G, @0 X
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007% _" f0 o- c0 D2 a4 ]- y
A unique entity of male-limited gonadotropin-; K0 E3 ]; S$ P
independent precocious puberty, which is also known
" Q y3 T: {! kas testotoxicosis, may cause precocious puberty at a
9 f3 z# Y4 L+ n5 ]* C& Rvery young age. The physical findings in these boys
0 y: {6 {0 ~' }0 t, v) x2 owith this disorder are full pubertal development,) Y% R# x) I1 x6 X
including bilateral testicular growth, similar to boys; T# b d1 c0 |
with CPP. The gonadotropin levels in this disorder' `: b( ?0 C7 ~) Q
are suppressed to prepubertal levels and do not show7 Y- m/ H1 [( Z- q5 R1 h3 x- q
pubertal response of gonadotropin after gonadotropin-' `3 \% D& @0 h# k. H; k
releasing hormone stimulation. This is a sex-linked- X% Z2 ?5 @0 {) `# w( A
autosomal dominant disorder that affects only, {4 d+ C+ X4 l4 A" Z% G7 a
males; therefore, other male members of the family
2 P$ d. a3 Y. n0 R$ z6 umay have similar precocious puberty.3
% V, S' f7 Z5 G* ^' {; Q7 i- cIn our patient, physical examination was incon-
% y2 \4 p4 x- }. @7 zsistent with true precocious puberty since his testi-
1 g% g6 i; I: i- kcles were prepubertal in size. However, testotoxicosis
2 r; o" k4 h3 l# i) S1 l' Ewas in the differential diagnosis because his father
/ I/ N* I' w" V2 Istarted puberty somewhat early, and occasionally,% F2 {. k7 p3 `) }+ a
testicular enlargement is not that evident in the8 G n$ k( T" F% X' c. d
beginning of this process.1 In the absence of a neg-
; m2 j7 v2 M1 L9 i) `$ native initial history of androgen exposure, our% e- J4 c- u6 R: W# l) O
biggest concern was virilizing adrenal hyperplasia,/ s6 j: P" Q, }5 I6 O( e" M2 J
either 21-hydroxylase deficiency or 11-β hydroxylase
* i. \! ~7 Z/ P, j; G. E6 Bdeficiency. Those diagnoses were excluded by find-
* b- {1 H$ V0 ^4 Cing the normal level of adrenal steroids.1 t% ?# b2 j! H7 p2 C
The diagnosis of exogenous androgens was strongly
' g1 N7 h2 m' D( n' Jsuspected in a follow-up visit after 4 months because3 s( O7 `2 d1 }& t+ ^. _3 }
the physical examination revealed the complete disap-* O$ B% o* Q1 o0 j6 {; t& ^9 R+ R
pearance of pubic hair, normal growth velocity, and
. k+ _( n( w, L" ?! V: x1 }decreased erections. The father admitted using a testos-
" s1 R2 M: e! E9 @/ oterone gel, which he concealed at first visit. He was
' i* V6 A7 T4 g( O ausing it rather frequently, twice a day. The Physicians’
7 {- J, `6 c$ A; ~& T+ N2 ^% ^Desk Reference, or package insert of this product, gel or) \8 `" _, |" Y, v& L+ |+ m
cream, cautions about dermal testosterone transfer to
6 d3 b5 }* n: G; p( E- vunprotected females through direct skin exposure., o6 v% N7 W! O2 Y& E- F5 {# k
Serum testosterone level was found to be 2 times the
! H7 g0 G9 ^4 F! [baseline value in those females who were exposed to
L$ ~- |& R! P+ r+ A2 A% `even 15 minutes of direct skin contact with their male M- L; ]5 _5 g- Y' t, y4 j
partners.6 However, when a shirt covered the applica-) |1 D6 A+ p3 S; }: J
tion site, this testosterone transfer was prevented.4 {9 }8 x4 @) v/ }! m% I
Our patient’s testosterone level was 60 ng/mL,6 [- ^; Z2 ?/ X
which was clearly high. Some studies suggest that4 d7 A. h$ g% q% Z+ L: A5 V y
dermal conversion of testosterone to dihydrotestos-
. S: A2 B6 K. T, |terone, which is a more potent metabolite, is more
" }: u! j# \; b+ D4 Eactive in young children exposed to testosterone5 {" x u( Q6 T8 G
exogenously7; however, we did not measure a dihy-0 E; q* R: L7 A3 e+ P) h- Z
drotestosterone level in our patient. In addition to
; \" x* k8 g, ~; R& e; Q7 \virilization, exposure to exogenous testosterone in% T1 q7 @8 m( k$ [5 x- n9 ~
children results in an increase in growth velocity and, g) `( q9 L9 r8 }9 W0 p
advanced bone age, as seen in our patient.% k0 j9 Y2 V, V7 c+ t* P
The long-term effect of androgen exposure during; ]9 j. R( W! [! j: g4 {5 ~
early childhood on pubertal development and final
3 [2 J5 t; k2 H& ^adult height are not fully known and always remain5 i7 |2 C5 [6 k! C
a concern. Children treated with short-term testos-
2 h5 t. C9 _5 ~% R$ T$ Oterone injection or topical androgen may exhibit some7 }: ?+ Z. [7 J3 h0 [& Y4 ]
acceleration of the skeletal maturation; however, after
7 ~; j) T; H& d- H4 k$ [cessation of treatment, the rate of bone maturation; V) n3 r8 ~, q7 y: W* _
decelerates and gradually returns to normal.8,9
. x( g% ?: z! W3 j& l+ FThere are conflicting reports and controversy& B3 w/ _$ h/ j q1 U" f
over the effect of early androgen exposure on adult
( Z. Y2 |; K$ j8 c5 Npenile length.10,11 Some reports suggest subnormal* g" t+ o7 ^( e- t, |7 B6 s
adult penile length, apparently because of downreg-+ j5 v; t) g" [ v) S
ulation of androgen receptor number.10,12 However,' d7 s4 E3 L6 g, P" U
Sutherland et al13 did not find a correlation between
4 a3 z9 s6 C! O9 C) ?& }5 c( Bchildhood testosterone exposure and reduced adult
# p% H c1 L! J' b, k( jpenile length in clinical studies.
; r/ H! ?) }* K" lNonetheless, we do not believe our patient is
4 J$ `6 ~* l( L" jgoing to experience any of the untoward effects from; g4 M* ^ {) i, @
testosterone exposure as mentioned earlier because; x9 X, M ^, W, l. z- {
the exposure was not for a prolonged period of time.
. V$ D0 n$ o3 s8 T% f# |6 E8 JAlthough the bone age was advanced at the time of
% ~5 N! ?7 N; p* V. I" I) Odiagnosis, the child had a normal growth velocity at) u [' w" K+ J# C1 @4 k1 p, E
the follow-up visit. It is hoped that his final adult: H' e8 C+ \2 u; p
height will not be affected.( d; z# o" h3 `) W! P
Although rarely reported, the widespread avail-8 S4 ~7 P, B8 q7 x: X
ability of androgen products in our society may! o7 I% s) Z; _- Y4 n0 j8 f
indeed cause more virilization in male or female" g: @% ~; c$ ?7 s
children than one would realize. Exposure to andro-! v" X3 @: Q: _( `! E. I
gen products must be considered and specific ques-
7 I7 }2 P: P' U3 d! y: e8 H& Ztioning about the use of a testosterone product or! S# u' `: |; T5 n7 }$ m
gel should be asked of the family members during# L) O, d1 L) U
the evaluation of any children who present with vir-
# y% N) {4 K& O9 D9 rilization or peripheral precocious puberty. The diag-
- z+ A* `8 x! enosis can be established by just a few tests and by* k2 G' p! ?8 ^/ b
appropriate history. The inability to obtain such a
$ G4 Q# b5 Y F7 r u; v% {history, or failure to ask the specific questions, may5 N: X" q$ D3 ]% v) {, s* A: B% ?
result in extensive, unnecessary, and expensive
: C" A* v4 r! @, Ainvestigation. The primary care physician should be- ?+ c' V- g, C
aware of this fact, because most of these children
# i( p" V0 l( R* R N+ Kmay initially present in their practice. The Physicians’8 M1 A. c( h- M8 ~
Desk Reference and package insert should also put a: } Y1 l$ m' B2 {" c. [
warning about the virilizing effect on a male or9 l) b8 D5 E. l: t+ t$ j0 C8 v
female child who might come in contact with some-& E2 m0 N1 W+ |- k. q' ^5 p+ P
one using any of these products.: `8 Z$ ?) n7 ]- f+ D) N
References
! [9 y" K$ }! N! f6 k2 Z1. Styne DM. The testes: disorder of sexual differentiation
. N( [( a3 i6 K# l: Iand puberty in the male. In: Sperling MA, ed. Pediatric
, ~$ @! R& R. m2 |9 r" h- x( @Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;+ \: l1 c: ~2 I9 W! g, h" B2 Y" _
2002: 565-628.
5 |4 ^ i* R# \9 @& h9 R5 I' g2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
- X* @: N6 \+ H& M2 K3 G7 h, [puberty in children with tumours of the suprasellar pineal |
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