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Sexual Precocity in a 16-Month-Old
5 g D2 m V: Z XBoy Induced by Indirect Topical) w6 q. ~2 }' S" G, ]8 A
Exposure to Testosterone
& P; p+ c; @ w8 T* i7 G4 j, ]Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,29 M/ y N$ N! C$ M- \4 o
and Kenneth R. Rettig, MD1! E& G( X/ u+ ?# r5 r' o0 M
Clinical Pediatrics: [$ k1 f* R$ G5 g. I- S
Volume 46 Number 6
+ K y, g- j Q J, ?- _5 jJuly 2007 540-543
# C* _4 e$ a i/ N6 l5 ~5 Y& Q© 2007 Sage Publications
+ X( B! ]" y' _2 e6 Q! V [' e10.1177/0009922806296651
) r4 N+ X' \- u1 W8 r+ Ehttp://clp.sagepub.com, ]' s) I- O1 _0 y
hosted at H( ~/ }4 y% e0 b3 z0 Y! r) z
http://online.sagepub.com* o3 c0 V7 N8 X- ]- S( o+ p
Precocious puberty in boys, central or peripheral,, h. \- x( j# q/ _, f$ @5 o5 D
is a significant concern for physicians. Central
& h) u# W1 y8 D5 mprecocious puberty (CPP), which is mediated
: t! k! A4 M# I2 s, Lthrough the hypothalamic pituitary gonadal axis, has' I. ?6 o- N# u& z
a higher incidence of organic central nervous system
; z1 {* I4 F) J5 ^9 i! I- L; H, ylesions in boys.1,2 Virilization in boys, as manifested
, V1 t% @" e- F3 p/ M$ Sby enlargement of the penis, development of pubic
; L* H! n9 O* v: r6 mhair, and facial acne without enlargement of testi-+ G7 T+ Q5 m o) {; j, _2 r, g
cles, suggests peripheral or pseudopuberty.1-3 We, d9 c( m" x+ S" Z# V/ _) b
report a 16-month-old boy who presented with the4 R2 Y" x) L' D6 R& ]
enlargement of the phallus and pubic hair develop-! d5 i; {8 C! d. G
ment without testicular enlargement, which was due
. X* J. X" T% Y! C* ~2 U7 N3 R: Yto the unintentional exposure to androgen gel used by" I' x) E$ [( E
the father. The family initially concealed this infor-
; h* t+ k D, Z1 k: Q+ i' B% |mation, resulting in an extensive work-up for this% E+ _# U# ]4 ]9 { i
child. Given the widespread and easy availability of
; |, W% `# d! {: y7 \testosterone gel and cream, we believe this is proba-
s) ~6 r" W. y: ~( E/ mbly more common than the rare case report in the3 q; Q. j: y( O6 v! {' \+ E
literature.4
. n! u& n/ q+ [$ P" Z5 z4 `Patient Report
& E8 a% k5 y+ e: [$ W- aA 16-month-old white child was referred to the" O: I( a$ l: T
endocrine clinic by his pediatrician with the concern6 |+ F, O, L& E; ~) r9 c+ o
of early sexual development. His mother noticed
; v. Y( l) P6 w* Rlight colored pubic hair development when he was
; [; q. M$ O) L: r" B0 P0 _8 ~7 Q* }From the 1Division of Pediatric Endocrinology, 2University of
( u3 E, G/ E$ N0 ?4 TSouth Alabama Medical Center, Mobile, Alabama., t5 T: G! L0 ?
Address correspondence to: Samar K. Bhowmick, MD, FACE,
2 R$ r& r& m/ d# I! j0 Z' RProfessor of Pediatrics, University of South Alabama, College of4 R/ F1 `$ f5 R6 z" U( b
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
/ Y1 ~0 O% _' m2 I7 s, @e-mail: [email protected].: _ x" }- }+ T4 a
about 6 to 7 months old, which progressively became
* z0 I. z( N7 I4 W9 S+ ]5 Hdarker. She was also concerned about the enlarge-; J4 u# f+ J% u# H+ _' S3 v M
ment of his penis and frequent erections. The child Q; O' w3 f6 o: ]( D0 y2 [
was the product of a full-term normal delivery, with8 v* I3 e4 {* S
a birth weight of 7 lb 14 oz, and birth length of4 s( A( O# i K- p) a) D
20 inches. He was breast-fed throughout the first year
/ I7 S2 @5 a8 ~ O& D/ b+ K/ Dof life and was still receiving breast milk along with
2 {1 _2 q6 P7 c8 Y0 A7 Usolid food. He had no hospitalizations or surgery,
: [" p3 c4 V2 l9 |1 p6 f- Rand his psychosocial and psychomotor development
) h. G# {7 t9 r P; fwas age appropriate.
$ l% ]$ i% K% [The family history was remarkable for the father,2 x) \7 W# L' w" w0 n6 h$ ^
who was diagnosed with hypothyroidism at age 16,& N" C; i- U g& l8 o2 Q# F8 v
which was treated with thyroxine. The father’s$ L6 ]3 |5 d ~- e6 ?7 i: J, S' ?! i, T
height was 6 feet, and he went through a somewhat
% C/ c) r0 x Q m6 { Aearly puberty and had stopped growing by age 14.
3 m+ o* A* I L) y# IThe father denied taking any other medication. The3 Y2 Z j/ s \) q$ b! i
child’s mother was in good health. Her menarche
, G( k& m8 f* }' i, P [was at 11 years of age, and her height was at 5 feet$ d5 x" C' F4 j" W! I& Q; F
5 inches. There was no other family history of pre-+ v% }8 L0 p+ U- r4 L$ Y
cocious sexual development in the first-degree rela- V/ U) A/ | T2 K I
tives. There were no siblings.
( B+ C( N4 p7 `- M7 @Physical Examination
6 M3 t6 U3 P7 qThe physical examination revealed a very active,7 x* }$ H6 S- O
playful, and healthy boy. The vital signs documented
$ q/ m0 ^8 J$ \5 B/ X/ `a blood pressure of 85/50 mm Hg, his length was
$ ]8 \/ P& C2 s& g$ z% T90 cm (>97th percentile), and his weight was 14.4 kg# J. S; i9 m6 X) _* Z0 S6 ~- P
(also >97th percentile). The observed yearly growth6 V( K, p% H2 F( H: d& j
velocity was 30 cm (12 inches). The examination of% B3 D2 A+ h: |7 x
the neck revealed no thyroid enlargement.& h0 G+ f6 E" [7 _/ p
The genitourinary examination was remarkable for
5 e Z8 w! P/ p- a4 menlargement of the penis, with a stretched length of4 b% S3 r: S. t3 g$ w o
8 cm and a width of 2 cm. The glans penis was very well& r6 _7 A: t) x5 k6 y* ?
developed. The pubic hair was Tanner II, mostly around G" z% |+ P/ J) c
5409 {$ l2 Z# _; [* i( t6 v
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
, p: |' c! q N4 v3 R) ethe base of the phallus and was dark and curled. The; F G7 e% x t+ i
testicular volume was prepubertal at 2 mL each.
1 J1 G) Q2 ?5 J( hThe skin was moist and smooth and somewhat8 |8 G" N, x, Y/ [& e8 a- H2 o' X
oily. No axillary hair was noted. There were no# [+ ]9 K1 @' E2 M' h: F! p
abnormal skin pigmentations or café-au-lait spots.
5 [, Q6 `$ g+ G# {% gNeurologic evaluation showed deep tendon reflex 2+( X0 `; v8 Q$ a" Y# c a' I; g5 c2 i
bilateral and symmetrical. There was no suggestion( |: o, |( A7 |! G8 B8 [- N1 v) F h
of papilledema.
. B0 X" l3 `- r1 p e7 ~1 kLaboratory Evaluation
: F, J/ Z9 {! k# EThe bone age was consistent with 28 months by7 r4 K4 ^0 D6 I" P* a- U
using the standard of Greulich and Pyle at a chrono-
2 d1 f% n. [7 | p- d) ~) mlogic age of 16 months (advanced).5 Chromosomal
5 W7 B1 x( W2 A* ikaryotype was 46XY. The thyroid function test
6 B* I' x; b! X( N* kshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
0 L) X8 |- X: z% Flating hormone level was 1.3 µIU/mL (both normal).' v3 k: x. p/ k; q, x8 \
The concentrations of serum electrolytes, blood
1 A6 K5 X+ W" o; Eurea nitrogen, creatinine, and calcium all were6 c$ J0 G6 R. {7 m
within normal range for his age. The concentration
) b3 O2 h$ O# }6 e6 x( H& Wof serum 17-hydroxyprogesterone was 16 ng/dL
5 t$ i6 e4 w: H- Q! F* D9 u4 P(normal, 3 to 90 ng/dL), androstenedione was 20' z" k$ n$ i- k' W8 C O/ R
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-' r8 }* f& ~! M# } O* e- N! \
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
7 J) b, r* G$ P8 g7 b% fdesoxycorticosterone was 4.3 ng/dL (normal, 7 to
# _) h8 O# I# F, t5 y& n49ng/dL), 11-desoxycortisol (specific compound S)1 V7 F0 Q0 s8 T* v$ y; ]
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
) j* {7 m. I( a ~$ w2 a) Ftisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total) a5 B5 {# ?* g5 N5 W
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),1 `: z) x9 R F
and β-human chorionic gonadotropin was less than- r# g' t8 d; @, {1 i
5 mIU/mL (normal <5 mIU/mL). Serum follicular
1 }( a$ X G4 ?! z& ]5 Hstimulating hormone and leuteinizing hormone5 W1 W. \* i3 a- m1 l
concentrations were less than 0.05 mIU/mL, z; m/ b+ l# f# n3 V: A
(prepubertal).0 r, R# k. r! g" t$ R) d( m
The parents were notified about the laboratory1 h5 g+ b! G+ i% O
results and were informed that all of the tests were
# k; K; r+ E$ Q* Rnormal except the testosterone level was high. The2 P- Z! D& p) Y3 b- R
follow-up visit was arranged within a few weeks to) E# m$ _7 w7 h" B- E
obtain testicular and abdominal sonograms; how-
9 F l' I1 v5 h9 y, oever, the family did not return for 4 months.6 ~+ e1 m. R& A* K D
Physical examination at this time revealed that the
% @: m# x1 i, y9 ychild had grown 2.5 cm in 4 months and had gained
3 m: ^ R4 [8 s( Y F2 kg of weight. Physical examination remained: p( O0 K2 f, {9 \% `3 C! \5 w
unchanged. Surprisingly, the pubic hair almost com-; |6 y% h% O4 B. U V
pletely disappeared except for a few vellous hairs at
* r- E3 A. O# _0 L, g4 Ethe base of the phallus. Testicular volume was still 2( B) c) h. B+ d7 {7 B. f* g
mL, and the size of the penis remained unchanged.* }- j0 {. O4 S2 W; l7 A
The mother also said that the boy was no longer hav-
! p# \6 c4 _1 Cing frequent erections.6 ?/ S/ J7 n" n& v1 e+ H: ^0 G
Both parents were again questioned about use of
f. n" \; K$ n& R' {3 P, e& Lany ointment/creams that they may have applied to
+ O+ \, s# m, `8 Dthe child’s skin. This time the father admitted the/ m0 L* ]. o; B9 w6 W/ Q
Topical Testosterone Exposure / Bhowmick et al 5418 v1 l" N, W" u B: \
use of testosterone gel twice daily that he was apply-
& C+ \; ?( E4 g5 xing over his own shoulders, chest, and back area for
- x% B% o1 j( f2 a g: ^' x( d$ ea year. The father also revealed he was embarrassed2 c- S0 a, I! n* u
to disclose that he was using a testosterone gel pre-" n% ~' h, C# r) T
scribed by his family physician for decreased libido
( T, z9 \8 d/ u Zsecondary to depression.
, L( a; ~4 z+ R2 S5 o* nThe child slept in the same bed with parents.
8 {- b* p; W6 x0 P8 ~ oThe father would hug the baby and hold him on his, X3 U1 D- f$ X' J
chest for a considerable period of time, causing sig-
" k0 ?, C: F5 {nificant bare skin contact between baby and father.
& d8 a0 p* p3 D8 v. W8 H7 cThe father also admitted that after the phone call,$ ?' s% u& a! z1 h$ y
when he learned the testosterone level in the baby- h! [8 a7 v: L x
was high, he then read the product information
$ a; j( W' ^, \7 }" E% H9 |. y% Vpacket and concluded that it was most likely the rea-, ?) D0 J; V- S- b+ r; {2 B! x
son for the child’s virilization. At that time, they
. |6 Z5 a9 ` v p% Cdecided to put the baby in a separate bed, and the
: c! \# c; ` C& C. d; f; dfather was not hugging him with bare skin and had: `% X6 j$ G; k2 b) Q
been using protective clothing. A repeat testosterone0 O& A; A8 a+ B
test was ordered, but the family did not go to the
1 j+ s+ X& _ glaboratory to obtain the test.
; v1 B& R* J/ ^Discussion. h/ U4 X: r+ Q
Precocious puberty in boys is defined as secondary; b) }1 F6 W6 Q& H) @( t. X
sexual development before 9 years of age.1,4
6 I7 L# P! Z6 Z6 E- M5 qPrecocious puberty is termed as central (true) when
/ l" x( f( H4 {2 sit is caused by the premature activation of hypo- V& W, p2 c, f- j
thalamic pituitary gonadal axis. CPP is more com-
( {- D8 ?7 F1 X1 Rmon in girls than in boys.1,3 Most boys with CPP# y7 q3 g- R! f) w
may have a central nervous system lesion that is2 h# _* I1 Z' U: f
responsible for the early activation of the hypothal-: Y" c& v" U* e
amic pituitary gonadal axis.1-3 Thus, greater empha-
5 r& t7 t( q+ |8 J' S7 s: l0 j4 d& z* ?( [4 Msis has been given to neuroradiologic imaging in# y( A# Y% r' }, I
boys with precocious puberty. In addition to viril-* ?. Q' R D+ Z' t
ization, the clinical hallmark of CPP is the symmet-8 `6 O: y/ c5 s
rical testicular growth secondary to stimulation by
+ B" e0 M. t- I0 I. z7 |0 ^gonadotropins.1,3
4 M) O& }* Q. X* y$ m fGonadotropin-independent peripheral preco-5 N: Q/ t8 o- t* n" S0 Z: J. T% z
cious puberty in boys also results from inappropriate, h: j+ c3 I" q2 L
androgenic stimulation from either endogenous or, j7 U( S: Q( x
exogenous sources, nonpituitary gonadotropin stim-
/ K% C) S3 l9 n% xulation, and rare activating mutations.3 Virilizing4 V! t" k8 n( ?3 _$ }1 a
congenital adrenal hyperplasia producing excessive
+ @( m1 Z8 K4 k9 Vadrenal androgens is a common cause of precocious
, ]( d. m- h* l ppuberty in boys.3,41 Z- Y( n4 i6 i! k( S% L& V/ s
The most common form of congenital adrenal
& X* e7 a7 r9 \1 o& ~9 Chyperplasia is the 21-hydroxylase enzyme deficiency., F2 U4 Y& R4 h# G
The 11-β hydroxylase deficiency may also result in
- p3 c: C2 [- t. hexcessive adrenal androgen production, and rarely,3 S' d* E( W0 v! A0 Z9 k
an adrenal tumor may also cause adrenal androgen* d9 d s' @ m
excess.1,3: M) v* j& q9 ~5 z8 Y2 O
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from! {$ q/ h1 B) i( @' ]& \
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
* x& F0 m* @& o! z# T* V" T" sA unique entity of male-limited gonadotropin-
! o' T/ ?+ q$ U* Y: pindependent precocious puberty, which is also known
}8 e; k' U; f! P8 Aas testotoxicosis, may cause precocious puberty at a5 U: S5 x+ L& N8 }' }8 R# x5 P+ }) F
very young age. The physical findings in these boys( t. g5 S; P6 O8 \
with this disorder are full pubertal development,/ K3 V! |6 {0 B# Y! W
including bilateral testicular growth, similar to boys, Y1 C( |7 O Z/ L9 B1 b1 D
with CPP. The gonadotropin levels in this disorder( }2 ?3 P& ^* T& r* t
are suppressed to prepubertal levels and do not show
% u2 [& ] q) v3 X- Q* opubertal response of gonadotropin after gonadotropin-, E/ D' {+ N* K6 \ _. @
releasing hormone stimulation. This is a sex-linked
! w7 c9 _! o! j, c, Q1 d7 Yautosomal dominant disorder that affects only# a- c0 }$ R; Z0 X$ J0 F. O5 F" R, c6 w
males; therefore, other male members of the family6 x' l' M2 x, o$ b2 ^% ]9 O/ W
may have similar precocious puberty.3
! J3 G2 l+ P7 d. n) i8 rIn our patient, physical examination was incon-
+ l! a/ t- C: g8 \sistent with true precocious puberty since his testi-: R u) E6 \/ }/ q* W9 U1 X
cles were prepubertal in size. However, testotoxicosis4 a3 ~3 T7 M- z* f
was in the differential diagnosis because his father
) ~$ {7 ]! I, P+ {) ystarted puberty somewhat early, and occasionally,
+ o, N7 a& x* o3 X" x H% y1 Rtesticular enlargement is not that evident in the
# q) k+ s* L5 `+ ~( S5 p9 {$ q8 ^beginning of this process.1 In the absence of a neg-
! H. F* @8 o/ D4 q5 J4 {, i9 m: Pative initial history of androgen exposure, our
2 T: @ |4 p2 L$ i N8 t kbiggest concern was virilizing adrenal hyperplasia,, u* u. }5 p! ]% s- v4 R
either 21-hydroxylase deficiency or 11-β hydroxylase
1 I( h1 H8 l G5 w3 W8 udeficiency. Those diagnoses were excluded by find-
) q% ?; Y8 E$ D) ^- Ming the normal level of adrenal steroids.5 r- p+ q# y3 T/ y) w
The diagnosis of exogenous androgens was strongly
6 ]$ q0 X& ]! w& s ^2 \suspected in a follow-up visit after 4 months because5 W$ [& N; w7 ?7 D2 I4 A9 T; {1 G
the physical examination revealed the complete disap-
0 `7 \$ P7 ?5 T4 {) B2 q- xpearance of pubic hair, normal growth velocity, and3 b' n) P. i9 r! }" }* X3 C
decreased erections. The father admitted using a testos-
5 ?+ L3 G. ~& _ J7 Y6 Vterone gel, which he concealed at first visit. He was
; W% G/ i$ ?, [" @3 m3 C4 ]using it rather frequently, twice a day. The Physicians’& z" ~# V4 l# a7 G+ Z
Desk Reference, or package insert of this product, gel or2 J1 h. |! S: f `( u
cream, cautions about dermal testosterone transfer to2 Q) S, `3 C. B3 M
unprotected females through direct skin exposure.
+ N/ I/ V1 V% L% |Serum testosterone level was found to be 2 times the
+ o& Q6 ? d5 A6 ~- T- tbaseline value in those females who were exposed to
% r0 T7 i( P' ]) [* c5 V8 weven 15 minutes of direct skin contact with their male
4 l" A8 F) E( }5 }. Jpartners.6 However, when a shirt covered the applica-
+ k H/ B9 g( g2 ttion site, this testosterone transfer was prevented.2 N5 \- f' p" s' J5 Q
Our patient’s testosterone level was 60 ng/mL,$ Z/ _+ a. N" y* z# t) _2 K8 g
which was clearly high. Some studies suggest that: C' D' S5 w6 Y' S
dermal conversion of testosterone to dihydrotestos-
+ E% q+ ?6 ? q3 n8 ~. P- L: Vterone, which is a more potent metabolite, is more3 ~% L" v! N% H" F3 U9 d2 R
active in young children exposed to testosterone# I+ u2 Y5 l9 b K8 ]! g5 R2 P' S
exogenously7; however, we did not measure a dihy-! D9 i+ a* E# q: t9 C
drotestosterone level in our patient. In addition to
* B9 Y8 m- x+ t1 h' Bvirilization, exposure to exogenous testosterone in
1 H: o* z7 y! J1 M1 b- @children results in an increase in growth velocity and
% V. J; T- W( Oadvanced bone age, as seen in our patient.
% J( U& S( h1 e& X* Z7 PThe long-term effect of androgen exposure during
6 s- w. F A$ b* q8 `early childhood on pubertal development and final- Q \% `" h: e
adult height are not fully known and always remain
) F( h: W6 k6 n' o5 u$ L( Q4 F% ua concern. Children treated with short-term testos-
' D E. |7 F! s7 `& @7 Kterone injection or topical androgen may exhibit some$ Z2 v+ b2 E* M1 J/ ^
acceleration of the skeletal maturation; however, after& o; J* k- a* Q5 M8 h; s; l' G% L
cessation of treatment, the rate of bone maturation
; O# \" v* R& b6 _) Adecelerates and gradually returns to normal.8,9/ T0 O- y9 y% ~6 |" y; d
There are conflicting reports and controversy$ g0 K! ]+ P* r- K
over the effect of early androgen exposure on adult
/ H% `) ` p# V6 j+ R- a; S; jpenile length.10,11 Some reports suggest subnormal
7 d) M% _: a+ [/ v1 X3 b0 uadult penile length, apparently because of downreg-
. P5 t/ ?4 `5 a, z# Z& |ulation of androgen receptor number.10,12 However,+ H& H6 U7 \4 J x5 J2 p2 P' Q
Sutherland et al13 did not find a correlation between2 E8 _, u; O5 f9 {
childhood testosterone exposure and reduced adult, T& U# U4 T. M+ U
penile length in clinical studies.3 v: G1 o* N! n+ O
Nonetheless, we do not believe our patient is
/ Z- i) V. b5 \' `1 r! agoing to experience any of the untoward effects from
; n; A) i$ s2 q) ltestosterone exposure as mentioned earlier because
6 p$ R3 X' P: Y7 [1 {, Rthe exposure was not for a prolonged period of time.+ w: K- T+ t H2 Y% `7 o* N; A9 a
Although the bone age was advanced at the time of
: T1 L, I2 L% P/ X0 Q- Fdiagnosis, the child had a normal growth velocity at& X8 g) x# w1 D
the follow-up visit. It is hoped that his final adult) n! Z9 k# Z: M& m" P6 n
height will not be affected.
8 l+ ]5 n9 ` W! nAlthough rarely reported, the widespread avail-; a2 V j. g- ^ _4 w( P8 x; a
ability of androgen products in our society may4 v [, b0 w9 @7 m9 S& M
indeed cause more virilization in male or female+ A) M! w' V; T6 d
children than one would realize. Exposure to andro-7 U t v/ u7 u
gen products must be considered and specific ques-) Z F1 n0 q7 y# J M7 K
tioning about the use of a testosterone product or) X# W9 i3 j, _
gel should be asked of the family members during# A% V7 ^6 i1 i. O, z; M
the evaluation of any children who present with vir-
( A0 _6 P- g- d, o+ |5 ]/ u# tilization or peripheral precocious puberty. The diag-
8 b) m- ]7 F2 g& Jnosis can be established by just a few tests and by
$ J" d/ X+ Y" b, J3 }! Jappropriate history. The inability to obtain such a
! T/ x# A. n8 P- V3 fhistory, or failure to ask the specific questions, may. @, u [7 W1 e9 ]7 J6 `0 p
result in extensive, unnecessary, and expensive/ N7 Y7 ~8 q- ~6 d! v
investigation. The primary care physician should be
3 R; y3 \, `' xaware of this fact, because most of these children6 D' a9 B' t- p( Z$ [
may initially present in their practice. The Physicians’
1 \: V6 ^! @4 t# o9 `$ J1 g3 EDesk Reference and package insert should also put a
* z7 B8 } G- R6 O9 ]warning about the virilizing effect on a male or
4 B1 f$ M: F, @/ _6 M( tfemale child who might come in contact with some-
2 L# n$ Q$ \# Z6 E7 i1 l/ Qone using any of these products.
% [) ?, C. Z1 g8 _References
0 x5 e4 S9 h/ S7 x1. Styne DM. The testes: disorder of sexual differentiation- G, K0 M+ W; K. z) K
and puberty in the male. In: Sperling MA, ed. Pediatric
, y F) y$ R/ ~$ q" T' O( v oEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
" W) C" B. S! F. q# f, p# V9 `( z2002: 565-628.
3 X! o# a% Y8 b# `* t5 A" v" o2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious2 j1 R2 N2 m8 R' h! g H0 G3 r; f
puberty in children with tumours of the suprasellar pineal |
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