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Sexual Precocity in a 16-Month-Old# P7 {9 R& ~3 `
Boy Induced by Indirect Topical
! Y, m( i: w& g3 e' pExposure to Testosterone% L n/ y8 F( S% Q, @. G" b
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
3 u6 g5 I5 J& O4 I3 `" t8 \and Kenneth R. Rettig, MD1 @& b9 f. S$ k H' @% ?% ?
Clinical Pediatrics0 I9 Q# \: X* @
Volume 46 Number 6 S. }0 z P- R/ y) d" A3 M
July 2007 540-5436 z6 ^% m0 E+ u* X; C
© 2007 Sage Publications, u, r5 R, b& c, [. ?* B
10.1177/0009922806296651# o: A6 ?7 k/ M6 X8 F
http://clp.sagepub.com+ \. u+ ]! J W& @9 N, K+ r
hosted at
4 |# A, y9 f( C) z* Chttp://online.sagepub.com o+ D" W3 Z( h- n( r- I$ S. e
Precocious puberty in boys, central or peripheral,& w% B: }- n8 x; r; R$ l: y
is a significant concern for physicians. Central
! D2 H( j- v8 Lprecocious puberty (CPP), which is mediated
* Q* u( A7 K8 V, t/ W, ^through the hypothalamic pituitary gonadal axis, has
$ ~% N e+ M1 S# h( sa higher incidence of organic central nervous system
0 `1 W" ^, h; C5 olesions in boys.1,2 Virilization in boys, as manifested
) r @: i! F5 Z% \; {. A* p7 Jby enlargement of the penis, development of pubic
) ~6 }! H) Z+ {7 }hair, and facial acne without enlargement of testi-" ]" w3 C, N" S
cles, suggests peripheral or pseudopuberty.1-3 We6 @, \, z4 l6 j4 J3 O
report a 16-month-old boy who presented with the1 s4 w, f$ ]- t& T
enlargement of the phallus and pubic hair develop-
$ ^4 W& O) n3 g+ s% G0 z: I& pment without testicular enlargement, which was due) t' a! M6 D5 \- j# q; Z2 _
to the unintentional exposure to androgen gel used by8 G/ U5 b: ?# i! T0 o* n
the father. The family initially concealed this infor-9 L" F' S; K- f; N, g
mation, resulting in an extensive work-up for this
& ~0 n& b" W4 T6 p6 Z+ l5 R3 wchild. Given the widespread and easy availability of
' u( u2 I/ V; E2 \, C% J5 ]testosterone gel and cream, we believe this is proba-; w+ `# I7 `) P1 { m2 U6 V+ Z* W
bly more common than the rare case report in the0 v+ Z; f- M y
literature.4
5 P9 ^9 @* h2 ?' t( v0 [Patient Report/ ~- _$ s$ h, D* w
A 16-month-old white child was referred to the' B$ L% g5 {( O+ {
endocrine clinic by his pediatrician with the concern' t* V5 ^6 s' @5 Z O- ?
of early sexual development. His mother noticed
8 {; X5 e* m0 j: k; L4 D% qlight colored pubic hair development when he was
3 l- ^0 r1 g, y; u1 LFrom the 1Division of Pediatric Endocrinology, 2University of
! W& A' U) A j' D2 M, ]& X. }! zSouth Alabama Medical Center, Mobile, Alabama.0 y5 t7 a! _; {5 p4 Q; ~
Address correspondence to: Samar K. Bhowmick, MD, FACE,9 l" M+ S% {4 U
Professor of Pediatrics, University of South Alabama, College of
( u5 m: _- W: K' l4 x- f0 YMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;) j% ?- l1 A. m1 r& \+ w
e-mail: [email protected].! ? J2 [1 u8 j8 P1 I
about 6 to 7 months old, which progressively became
- V# M e+ A; A" M, z; X2 jdarker. She was also concerned about the enlarge-
- e4 c% {2 D, t5 j* h! Iment of his penis and frequent erections. The child
1 i+ f2 p; N, Q H0 L# Jwas the product of a full-term normal delivery, with
6 v) w2 O+ i( U) @9 _5 ]' R( E1 w5 Ra birth weight of 7 lb 14 oz, and birth length of
6 H8 _2 [# O, w z; u. u4 m20 inches. He was breast-fed throughout the first year
* b5 F, L5 R. W$ m$ kof life and was still receiving breast milk along with
2 O. b# p! d" V# Osolid food. He had no hospitalizations or surgery,
- u; v2 \7 ], E4 U) k& kand his psychosocial and psychomotor development
& A# h8 k) y# l9 i, Gwas age appropriate.
\' |! x# t1 F& YThe family history was remarkable for the father,
! k% U% n- [% v1 Q' s/ c; ~- j& twho was diagnosed with hypothyroidism at age 16,$ Y& I, u Q7 c, q" [: G
which was treated with thyroxine. The father’s# ], C; b/ |) M; h& D$ t1 d
height was 6 feet, and he went through a somewhat
2 \+ s$ g4 e7 Z/ T" u) Nearly puberty and had stopped growing by age 14.
; f: u$ l8 y) o) `8 PThe father denied taking any other medication. The4 D5 K5 S: g' O" l) z. I7 k: L
child’s mother was in good health. Her menarche
# k/ a; V9 y2 o) H% n: j0 a6 wwas at 11 years of age, and her height was at 5 feet
: j g" d# H* @- C4 C5 inches. There was no other family history of pre-4 }* C0 N7 u* j) u, o r
cocious sexual development in the first-degree rela-' {$ i: |4 D$ ~+ i2 b L- o
tives. There were no siblings.
7 I0 {- j8 S4 YPhysical Examination8 g; ]4 T6 X5 A6 M( D! u
The physical examination revealed a very active,& ]5 D$ h! d! T1 a( p
playful, and healthy boy. The vital signs documented2 h3 H' i" }) n4 _7 O
a blood pressure of 85/50 mm Hg, his length was3 A, s- @9 t; u7 @
90 cm (>97th percentile), and his weight was 14.4 kg- H2 m- Q% N# j) W( `1 ?! @5 ~
(also >97th percentile). The observed yearly growth( y f: b5 n; U& T* m
velocity was 30 cm (12 inches). The examination of: Q' i2 y, @% _1 D- n
the neck revealed no thyroid enlargement.0 v5 R4 q" K; d- n
The genitourinary examination was remarkable for
: R+ V8 N! M4 q5 g+ Lenlargement of the penis, with a stretched length of/ ^, S( D5 F: ]% Q
8 cm and a width of 2 cm. The glans penis was very well
& N9 I% [! n# p+ tdeveloped. The pubic hair was Tanner II, mostly around) \8 B& Y, ]8 q& Q- o- f# y3 i
540
3 p0 Z7 }* q( yat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
1 j4 Z! p! V- P9 u9 ?+ _the base of the phallus and was dark and curled. The. C C, a$ ?- d( K; t
testicular volume was prepubertal at 2 mL each. M( z& M' f- s8 k& H, c. @
The skin was moist and smooth and somewhat; }/ J4 y, r# E+ P& p4 D2 Q
oily. No axillary hair was noted. There were no
7 i; a* f4 Z" P+ T& F) Dabnormal skin pigmentations or café-au-lait spots.# Y. s6 x' k( A; h& R9 q
Neurologic evaluation showed deep tendon reflex 2+
9 y9 ?. d8 b9 Ibilateral and symmetrical. There was no suggestion
' h+ B& d* w! s+ F% u$ ^of papilledema.+ R5 \: ?0 K, @2 \+ ?, h
Laboratory Evaluation
& }3 Z$ D( f! t5 S; `, ]The bone age was consistent with 28 months by1 J9 f/ w. c B& T
using the standard of Greulich and Pyle at a chrono- p% v& s1 {- M* f( v7 i
logic age of 16 months (advanced).5 Chromosomal
9 a* ~/ a( S" y- W* e$ nkaryotype was 46XY. The thyroid function test
& M. R$ H5 u. g4 A, zshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
3 I( X/ ^) E& } Alating hormone level was 1.3 µIU/mL (both normal).
! n v% Z& _! \* h6 fThe concentrations of serum electrolytes, blood2 y* H9 _4 ?) Q, `
urea nitrogen, creatinine, and calcium all were
8 _1 q' L$ f$ S$ a% ]6 Zwithin normal range for his age. The concentration
# ]6 h1 x# \: j# oof serum 17-hydroxyprogesterone was 16 ng/dL
& ?: @) F3 M; m1 T4 w(normal, 3 to 90 ng/dL), androstenedione was 20
( V3 Q" ~5 s6 G( L Hng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
" J# a0 n, F4 e0 e" d! k% Iterone was 38 ng/dL (normal, 50 to 760 ng/dL),
o7 p5 k% P7 C* v% F L2 rdesoxycorticosterone was 4.3 ng/dL (normal, 7 to" c: }1 P- s+ f) I. I9 u
49ng/dL), 11-desoxycortisol (specific compound S)
( {4 u/ L( w+ Y1 q; q9 E) }' s( rwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-( r* s/ e" R& \4 t, g, t6 S, ]
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total& X* i! H' J( }( m8 G
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
7 V1 V: ` I( w* {& aand β-human chorionic gonadotropin was less than
U0 f; @7 v9 K) v5 mIU/mL (normal <5 mIU/mL). Serum follicular% C- V4 n5 s* |, k
stimulating hormone and leuteinizing hormone
% b* ~0 k$ a+ c* dconcentrations were less than 0.05 mIU/mL4 P' }* a$ j. Y8 p* U/ ]
(prepubertal).
% c9 c w; N7 I& }4 J- X5 k9 gThe parents were notified about the laboratory5 v3 C+ A1 ?; H0 ^! z: _7 q
results and were informed that all of the tests were7 \5 ]$ K# e( W( s
normal except the testosterone level was high. The
+ }0 ?0 t9 Y+ j3 u' d! e2 G' z$ Pfollow-up visit was arranged within a few weeks to1 ~" w- H, ~" `$ z1 ]: Q
obtain testicular and abdominal sonograms; how-
7 R' g; g& e2 R1 h2 f% N( M) lever, the family did not return for 4 months.( J( ~; s; L6 }2 i
Physical examination at this time revealed that the: a, W9 d9 T' s9 X
child had grown 2.5 cm in 4 months and had gained
$ j- w' @2 N& B* W0 n( g. f2 kg of weight. Physical examination remained+ [! W7 A# a2 S+ N" `$ W( {
unchanged. Surprisingly, the pubic hair almost com-
5 s! k9 W$ a& _; g4 A) N* Opletely disappeared except for a few vellous hairs at; } d( b3 J7 w7 h% a( J8 c
the base of the phallus. Testicular volume was still 2: x( A! b+ J! k% I+ J
mL, and the size of the penis remained unchanged.
8 D: W: w& V* d/ E9 @The mother also said that the boy was no longer hav-
5 y8 P. z; f, n' f; b" Oing frequent erections.3 g4 M' Z8 m# _+ S& r8 v( z& W
Both parents were again questioned about use of g0 h& `; A5 H" z# s5 |
any ointment/creams that they may have applied to
: s1 c" R! x8 P% W" K/ xthe child’s skin. This time the father admitted the0 A! G7 f) N d4 p; D
Topical Testosterone Exposure / Bhowmick et al 541
$ _9 t% _2 u7 Z' R0 fuse of testosterone gel twice daily that he was apply-0 b9 l. ^8 J$ \0 w" P! O4 [& y& L; p
ing over his own shoulders, chest, and back area for
2 `! B0 G; ~. u& F* S2 @6 `a year. The father also revealed he was embarrassed; I- O& ]1 |3 P0 ?* g& P1 T7 Q
to disclose that he was using a testosterone gel pre-
h+ ], d$ t) I+ }# [$ }scribed by his family physician for decreased libido
1 @+ q* k3 H- F) c" Tsecondary to depression.
2 L% I4 ?& o+ Q- i# ~/ JThe child slept in the same bed with parents.
1 M9 I! x" d, B+ t, e) Z5 w4 iThe father would hug the baby and hold him on his! D! O+ s; z1 \
chest for a considerable period of time, causing sig-
% ]3 C C2 j) d2 c+ U1 |nificant bare skin contact between baby and father.
: U$ R+ }8 F) U( i* _# ]# HThe father also admitted that after the phone call,' c9 m4 l+ t" N
when he learned the testosterone level in the baby
2 `# y5 q: L; ?6 W5 e" [was high, he then read the product information5 ~* F5 {2 u) m4 ]
packet and concluded that it was most likely the rea-
; u! f9 w. ^ t4 k$ }% l, `, ?' Json for the child’s virilization. At that time, they
" W. }; ~7 ]! q/ fdecided to put the baby in a separate bed, and the
$ j) Y6 C+ T) t/ O1 X6 j) mfather was not hugging him with bare skin and had" B4 {! ?$ e; R. Y5 g/ c
been using protective clothing. A repeat testosterone
! k% H6 {% f: b5 Jtest was ordered, but the family did not go to the
& `- U7 e S+ O+ O* Mlaboratory to obtain the test.$ u7 p) G. O- y2 B# o' {
Discussion; n/ P* }1 @: {8 ^$ E- S9 [" `
Precocious puberty in boys is defined as secondary
& q) _% D9 r6 h- ^6 x- Zsexual development before 9 years of age.1,4
' W+ R3 V- r+ y1 UPrecocious puberty is termed as central (true) when
+ o; u' e. w! k' Qit is caused by the premature activation of hypo-: {& J, s+ r% {* Q# P, W$ | J4 f" d
thalamic pituitary gonadal axis. CPP is more com-
" Z$ z# g. Z0 Z% E) H! q' i' Wmon in girls than in boys.1,3 Most boys with CPP" Z: ?/ |' ]/ F/ R2 z& s
may have a central nervous system lesion that is
$ w+ o0 _4 f% l) t7 {4 ]3 G1 U/ I8 ]responsible for the early activation of the hypothal-
! G- O$ a- c& d2 }8 h% A, c" namic pituitary gonadal axis.1-3 Thus, greater empha-8 D7 T( W9 w4 }0 {# y9 m. T
sis has been given to neuroradiologic imaging in
# q7 o0 o2 V3 M8 `boys with precocious puberty. In addition to viril-
( K i6 Q9 f5 }ization, the clinical hallmark of CPP is the symmet-
- c# D) n ~, [7 D9 b% Mrical testicular growth secondary to stimulation by- a; \/ A! j% i3 y% L2 L1 }
gonadotropins.1,3
$ v2 X/ O8 L: j5 j) G) mGonadotropin-independent peripheral preco-: @ S3 u" T; r5 G
cious puberty in boys also results from inappropriate5 T. L3 ]" Y5 {& n u6 o# O5 ]/ l
androgenic stimulation from either endogenous or: j# L, I& C' s: a1 ?
exogenous sources, nonpituitary gonadotropin stim-
$ @; o7 Q. f- n! i/ Hulation, and rare activating mutations.3 Virilizing
. `# n n: `$ s8 G: D! `congenital adrenal hyperplasia producing excessive
" R: F$ s0 l9 \adrenal androgens is a common cause of precocious
' B* v3 P: N0 F- Zpuberty in boys.3,40 |% Y W5 \, ]7 N- Y' j
The most common form of congenital adrenal5 q! s) h% b" q1 f& D
hyperplasia is the 21-hydroxylase enzyme deficiency.+ B; i$ H% ?8 y0 a- d9 D; ~; a3 w
The 11-β hydroxylase deficiency may also result in
# j. P# t( x1 c1 m. `excessive adrenal androgen production, and rarely,
' V+ z+ ~8 X4 Han adrenal tumor may also cause adrenal androgen. A: Y8 Z* t! J- N3 A. v7 d
excess.1,31 L1 Z0 e- t: e* }
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
S5 [% L Y* S1 C4 }542 Clinical Pediatrics / Vol. 46, No. 6, July 2007$ P% K$ D3 r9 w& \- @7 g
A unique entity of male-limited gonadotropin-. _6 R- u$ c% J8 q
independent precocious puberty, which is also known# Y; C* i, [0 T h8 ]) B- Q3 F. N7 G
as testotoxicosis, may cause precocious puberty at a
( f- S% f3 r, S1 }. Wvery young age. The physical findings in these boys
% k `+ Z& C: |6 t) Twith this disorder are full pubertal development,
5 @- j; f& v9 p0 G$ Pincluding bilateral testicular growth, similar to boys" c, m& ?+ k; N8 x
with CPP. The gonadotropin levels in this disorder
$ t: r3 ~( k% Vare suppressed to prepubertal levels and do not show5 k3 T7 ~- {0 n2 C* I9 L& L: o
pubertal response of gonadotropin after gonadotropin-
& p* {% a7 ~# G# |" [# `, T9 Nreleasing hormone stimulation. This is a sex-linked* z; I- Z& E1 d( c2 H
autosomal dominant disorder that affects only
" \9 T6 V8 y+ i9 n( {" k, fmales; therefore, other male members of the family
3 b' D) F- x/ ]# K6 O. O1 O* f8 \% imay have similar precocious puberty.3
+ u4 d9 Z/ Y. v% i. C- vIn our patient, physical examination was incon-
" l5 S7 l4 ?* A# F7 Q3 Esistent with true precocious puberty since his testi-
) A ^/ j( I- v6 K" w6 o" @: Dcles were prepubertal in size. However, testotoxicosis
$ { Y/ z- i, h) [was in the differential diagnosis because his father
$ _; h) h) b4 s( Zstarted puberty somewhat early, and occasionally,( w9 l( J% T" [
testicular enlargement is not that evident in the/ y6 v) L* M3 o% `1 _+ w) t3 [( X
beginning of this process.1 In the absence of a neg-
- \( r6 T i1 K" ?' E$ }- Jative initial history of androgen exposure, our
) [+ P" ?# n v Rbiggest concern was virilizing adrenal hyperplasia,
" g& k6 {+ h4 [either 21-hydroxylase deficiency or 11-β hydroxylase
( _' S8 q, s( j8 c/ O- M# Kdeficiency. Those diagnoses were excluded by find-8 m' R* S, {! _7 n4 J
ing the normal level of adrenal steroids.
( T' @; y6 H/ \2 A1 PThe diagnosis of exogenous androgens was strongly2 ^" G0 d) [8 f1 z6 {3 p
suspected in a follow-up visit after 4 months because( x$ I; h% I3 s) E9 j8 s" a
the physical examination revealed the complete disap-
4 \6 G7 N# p! X* M6 S; qpearance of pubic hair, normal growth velocity, and
. D* ]6 m( |/ k' q9 [2 p7 @decreased erections. The father admitted using a testos-
9 c6 g0 {# k) u- Wterone gel, which he concealed at first visit. He was. j9 e; f; d- E8 Y K
using it rather frequently, twice a day. The Physicians’" ~7 p" Q F+ ~2 G$ g T# @9 {
Desk Reference, or package insert of this product, gel or9 f4 h* ?' P. Z2 P
cream, cautions about dermal testosterone transfer to8 q4 ~5 @; P6 y
unprotected females through direct skin exposure.1 E) s8 e: \2 @# s1 m, K I4 H
Serum testosterone level was found to be 2 times the& V. ^& k$ ^; S9 C# c
baseline value in those females who were exposed to( U3 T; D0 T. Y5 x! Y
even 15 minutes of direct skin contact with their male
7 y0 C+ _# ]3 L: E4 g, a0 |partners.6 However, when a shirt covered the applica-
# s' _; K- T% _( J( }& B9 P0 Ation site, this testosterone transfer was prevented.
) n# W. v5 G6 k7 J6 }9 xOur patient’s testosterone level was 60 ng/mL,6 K5 w; ?- A/ y" a
which was clearly high. Some studies suggest that! t3 B6 e; i D1 z8 j6 `
dermal conversion of testosterone to dihydrotestos-
0 }' G+ _% N! kterone, which is a more potent metabolite, is more8 |. z& b. ?) N2 ^8 m
active in young children exposed to testosterone
2 @9 g8 m/ q! K& H( cexogenously7; however, we did not measure a dihy-
2 h" S0 N4 E) Z$ O: D" i* Hdrotestosterone level in our patient. In addition to q& _2 z- a# h- R+ I4 M [
virilization, exposure to exogenous testosterone in5 j4 V7 J9 f5 X# n* t# M# t
children results in an increase in growth velocity and4 k9 ^7 g$ V/ z" c. A* V1 U% y
advanced bone age, as seen in our patient.( S3 A# c) L) F& \/ m5 H# b6 C1 G
The long-term effect of androgen exposure during# T0 {0 H7 y8 F$ l- m- N) t
early childhood on pubertal development and final
& x& V, x& v( {+ Badult height are not fully known and always remain1 T/ A# ]0 M9 c. P( l+ f# T" J5 e
a concern. Children treated with short-term testos-( N* M8 \+ g K& V% N% m
terone injection or topical androgen may exhibit some
) r4 G* j: M4 ^4 R7 r1 [3 jacceleration of the skeletal maturation; however, after% R& v/ z/ L4 |) A, x# t
cessation of treatment, the rate of bone maturation
* ] |/ G! \* _decelerates and gradually returns to normal.8,9/ m7 b1 K; o/ s0 f
There are conflicting reports and controversy
! R M" N; G2 Q0 U R( Dover the effect of early androgen exposure on adult( ^" f c v; k) N8 _ w' A' _2 G: K
penile length.10,11 Some reports suggest subnormal
0 P5 W' u6 F! qadult penile length, apparently because of downreg-) R# V1 f, q* G) i6 G
ulation of androgen receptor number.10,12 However,
$ o1 ?* f! G8 i2 R6 m, zSutherland et al13 did not find a correlation between1 a0 a+ t* q9 Q7 h% H
childhood testosterone exposure and reduced adult
8 K0 V& t7 r6 b9 f3 g; |6 G" K- tpenile length in clinical studies.
: E5 q# V$ Y5 Y0 ]' P1 v; dNonetheless, we do not believe our patient is; a0 n" k ]3 @
going to experience any of the untoward effects from
0 w: X$ {. G, Utestosterone exposure as mentioned earlier because
; J, n6 c9 P: L! }the exposure was not for a prolonged period of time.
+ X' |2 z% d) P/ _Although the bone age was advanced at the time of9 @* }0 j7 B ~. l* u* T
diagnosis, the child had a normal growth velocity at
! A% y: i- q% ^the follow-up visit. It is hoped that his final adult
* y. p6 d7 e& w2 z& zheight will not be affected.
+ g5 n" ^+ ~# L$ @+ PAlthough rarely reported, the widespread avail-0 B- w, S3 [7 v: B
ability of androgen products in our society may. {9 t/ R. c" i; L0 B# s
indeed cause more virilization in male or female
`, u U' }% echildren than one would realize. Exposure to andro-
: n, _1 u. T, ?9 n, v) \# |- ]gen products must be considered and specific ques-
9 F# f, d# ]% f& f$ Qtioning about the use of a testosterone product or- ^+ a7 I% x4 F( N
gel should be asked of the family members during6 B' a! W9 s% j- D" F9 `
the evaluation of any children who present with vir-
7 I# ~$ u: r$ C8 b" L1 }. Iilization or peripheral precocious puberty. The diag-: t; I% [3 P) o& @) k: G9 B8 O
nosis can be established by just a few tests and by9 i9 @" C; s# g" p7 K5 N/ F- Y
appropriate history. The inability to obtain such a6 x$ F! ?- G) \# j7 S
history, or failure to ask the specific questions, may
: ^- I/ i y# j3 Presult in extensive, unnecessary, and expensive
2 c |1 \- N7 Q' G( r& ^investigation. The primary care physician should be1 _% Y1 {4 T# H) Q" g' Y. F
aware of this fact, because most of these children
J: J+ \0 r3 {9 g3 N4 Dmay initially present in their practice. The Physicians’
: @9 }% D; J: [6 C% @Desk Reference and package insert should also put a y& U: U* A- c+ d- t' {9 f
warning about the virilizing effect on a male or
8 O+ p4 o, E. H! W* @& n" [, cfemale child who might come in contact with some-
$ d& u+ Z2 x- ^( D- Z5 wone using any of these products.
/ ^( ^8 R( Q, i' v5 I, F9 v! sReferences
! q) M# g# J- a* P1 a+ |1. Styne DM. The testes: disorder of sexual differentiation% N5 {, ~; T) \% ~9 G% f
and puberty in the male. In: Sperling MA, ed. Pediatric2 {7 T7 k4 Y" Y% _, u; w/ p! U5 l
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;+ q( F7 k! E' P
2002: 565-628.
& W0 M/ `/ Q. N2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious& C$ R3 ~7 r1 L- [% y/ f
puberty in children with tumours of the suprasellar pineal |
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