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Sexual Precocity in a 16-Month-Old1 S* C/ c# ~2 r7 [3 U, x
Boy Induced by Indirect Topical' r% \9 G( D+ e; t7 I
Exposure to Testosterone
4 A K4 y4 M9 ?; kSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
, V2 Y( L3 q# P9 v- sand Kenneth R. Rettig, MD1 I) j* G% v/ R# `4 r K
Clinical Pediatrics3 \" Y$ {$ k: \! _6 r' s
Volume 46 Number 6* Y: Z: o9 c* P; U% Y: V6 g( a; |
July 2007 540-543
2 f5 o* @5 E2 B© 2007 Sage Publications
! u. W4 k0 J$ F/ o10.1177/0009922806296651: `9 K Y4 m. j
http://clp.sagepub.com9 _; \4 v7 b$ Y) X. j0 P- `
hosted at
+ m/ y$ _! {, u, Bhttp://online.sagepub.com
+ c' @+ p& L1 v: w5 lPrecocious puberty in boys, central or peripheral,
5 P; o+ D+ [' r" Ois a significant concern for physicians. Central
: S" y1 c' \$ Eprecocious puberty (CPP), which is mediated! T8 @0 x' C- q
through the hypothalamic pituitary gonadal axis, has- d9 b" i; Y8 Z2 W
a higher incidence of organic central nervous system; n3 g4 j ^5 t7 Y# q' L: b; M
lesions in boys.1,2 Virilization in boys, as manifested
1 u6 r; ]+ e1 a4 O# `by enlargement of the penis, development of pubic
) A/ K& u" @2 xhair, and facial acne without enlargement of testi-8 r1 m1 A7 ?* ]; j3 H0 Z( P
cles, suggests peripheral or pseudopuberty.1-3 We& P7 o4 a% G! d* W
report a 16-month-old boy who presented with the
! t- @! R! l/ x* d4 D) i! ^enlargement of the phallus and pubic hair develop-3 K1 e, y6 R# t7 v4 _
ment without testicular enlargement, which was due
% M! c0 h, _! z; Q/ b0 sto the unintentional exposure to androgen gel used by
/ Y9 v6 A/ {1 |( Q6 o" u9 Wthe father. The family initially concealed this infor-3 G6 u) g1 o- P5 ~ c
mation, resulting in an extensive work-up for this! G( h9 I3 C9 P& \7 K0 I' C
child. Given the widespread and easy availability of$ P5 X O' T3 j) l* I
testosterone gel and cream, we believe this is proba-
6 d1 b9 H% S* Vbly more common than the rare case report in the2 n, I' \- _3 r8 Z" I
literature.4# ^" p2 R* q! F! E8 A+ {
Patient Report
" t7 E# h$ @$ \6 yA 16-month-old white child was referred to the
7 P/ S6 F, y) o: Yendocrine clinic by his pediatrician with the concern5 v9 j- r# ?; e2 n
of early sexual development. His mother noticed7 R. p1 Q* P9 E( ]5 O+ j
light colored pubic hair development when he was% h0 T) m* s5 N: a
From the 1Division of Pediatric Endocrinology, 2University of& d% z6 k+ i$ |5 a8 P4 C8 G
South Alabama Medical Center, Mobile, Alabama.
, x3 J( Y' @* |! [ }Address correspondence to: Samar K. Bhowmick, MD, FACE,
" V& y h2 a |: \, J1 G) wProfessor of Pediatrics, University of South Alabama, College of& g6 r7 z. v" R
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
; R& g: |" |6 t* Y6 P- m# Pe-mail: [email protected].
6 S. r0 x0 m7 U: A) qabout 6 to 7 months old, which progressively became
1 \6 U# |3 r$ m ^ f( Fdarker. She was also concerned about the enlarge-4 |0 X% C5 G" J) Z
ment of his penis and frequent erections. The child" s3 ]6 {7 Z' f8 b: u% W
was the product of a full-term normal delivery, with
2 j, }! Z0 s/ ba birth weight of 7 lb 14 oz, and birth length of y c, V9 r S6 m- n. M$ T
20 inches. He was breast-fed throughout the first year8 j" r* S; D3 D" X
of life and was still receiving breast milk along with
2 g1 ? T8 Y; q5 bsolid food. He had no hospitalizations or surgery,- \0 C9 y# n$ N* g
and his psychosocial and psychomotor development- A' I) e+ B5 S: ^7 _ m: R
was age appropriate.
! X# F1 W+ q# R* p( E$ S7 UThe family history was remarkable for the father,
; q; v$ j" X& ^who was diagnosed with hypothyroidism at age 16,$ O. G6 n. @* v* b( g; W4 R: `' _1 q
which was treated with thyroxine. The father’s% \4 n2 x# \) f: [# w4 y8 U% P0 h( s
height was 6 feet, and he went through a somewhat- C/ l8 U5 G: z5 [( j
early puberty and had stopped growing by age 14.
4 w8 V; h" ~5 h8 [( eThe father denied taking any other medication. The0 N8 d8 S0 b, M; J4 a
child’s mother was in good health. Her menarche
% I. P8 W, }; i0 hwas at 11 years of age, and her height was at 5 feet
( Q6 T) ?6 {/ z, j5 inches. There was no other family history of pre-
' s! r7 u) M4 D( dcocious sexual development in the first-degree rela-$ M8 I5 m: T& E8 {
tives. There were no siblings.
, V; O- @" ^. [2 |Physical Examination# h! J, Q1 W9 H
The physical examination revealed a very active, L, t, w6 ^2 ?- u
playful, and healthy boy. The vital signs documented
: B1 m! ?% t9 s& I! Y3 Ha blood pressure of 85/50 mm Hg, his length was
6 D3 |3 w2 s7 S+ f! o3 O, V90 cm (>97th percentile), and his weight was 14.4 kg! g$ |/ C9 F* n5 n! j
(also >97th percentile). The observed yearly growth) u. E; ]$ ~6 T
velocity was 30 cm (12 inches). The examination of
( |$ e& r% v& q/ v9 `, q# Qthe neck revealed no thyroid enlargement.
8 H7 ^/ e# Y4 a4 x- F0 r* a" ]The genitourinary examination was remarkable for
! a) N- W: I- Zenlargement of the penis, with a stretched length of
% l. H ?% Q# }! b' H8 cm and a width of 2 cm. The glans penis was very well5 L c3 V. k3 c z m/ S! Q' i0 W
developed. The pubic hair was Tanner II, mostly around! T3 ?$ o# Q6 |; t8 |% B8 N9 y
5401 C8 v" Q/ d5 V7 ?% V# e: S1 Z
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
* ]0 [! R( r# d1 |the base of the phallus and was dark and curled. The, t1 z3 p& D. V) Y. _
testicular volume was prepubertal at 2 mL each.
7 V; d. t( g0 t8 g; |1 ~: ]" p. O0 d2 MThe skin was moist and smooth and somewhat' `% h) [& M4 K k; W
oily. No axillary hair was noted. There were no
! n& f- \; z; V; ^! u, pabnormal skin pigmentations or café-au-lait spots.
- z" l( {, V" K# R n2 V$ [" |. KNeurologic evaluation showed deep tendon reflex 2+
8 E- R# i; K- Ebilateral and symmetrical. There was no suggestion2 M7 {8 o5 ?2 o2 u A# U. t
of papilledema.
g4 H1 z0 W7 u! wLaboratory Evaluation% o0 Q1 {3 A( `# n! C3 b
The bone age was consistent with 28 months by4 E5 {7 U6 @( V
using the standard of Greulich and Pyle at a chrono-4 r. z2 b3 c& ?$ i w8 `
logic age of 16 months (advanced).5 Chromosomal
+ D6 l" h" t; |& Vkaryotype was 46XY. The thyroid function test
, i; L$ }. Z/ J1 I- i# E ?showed a free T4 of 1.69 ng/dL, and thyroid stimu-; S9 Q, K5 k3 L, h, f' r
lating hormone level was 1.3 µIU/mL (both normal).$ h2 ~3 A* Z, t/ S
The concentrations of serum electrolytes, blood8 s" x o! J7 D6 _& A% t
urea nitrogen, creatinine, and calcium all were
/ D! v7 {; z/ d W5 z- Hwithin normal range for his age. The concentration' S% o% F9 Q' H0 q+ [8 Z
of serum 17-hydroxyprogesterone was 16 ng/dL, p; y+ O8 K7 m" q! v. V) F4 w& x P
(normal, 3 to 90 ng/dL), androstenedione was 20( K7 \: j" e. ]2 k! N _
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
7 T j+ i! {: \ \! _4 x# Kterone was 38 ng/dL (normal, 50 to 760 ng/dL),
3 Y) r, Y# L5 @' udesoxycorticosterone was 4.3 ng/dL (normal, 7 to4 F# U8 ?# J4 p8 u4 ~6 `; y- X
49ng/dL), 11-desoxycortisol (specific compound S)0 h- S& F* \7 V
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-' ?4 C, ]- S4 S
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
: e) c7 b6 A7 K2 L* X: b2 V6 o/ itestosterone was 60 ng/dL (normal <3 to 10 ng/dL),$ e3 g2 G: h6 g+ G' J Q; Z
and β-human chorionic gonadotropin was less than. x7 j( l6 w# k. L) J- J
5 mIU/mL (normal <5 mIU/mL). Serum follicular
7 V9 Y. U8 B) I7 U8 c6 R3 |7 Estimulating hormone and leuteinizing hormone) H# q* i- S4 I, H" X% O
concentrations were less than 0.05 mIU/mL% A& Z- [2 T# l+ E T/ i: A
(prepubertal).
& m: b. ]. B) D& M. n* bThe parents were notified about the laboratory% b8 H) _7 w9 V
results and were informed that all of the tests were( R5 t, z, A( a9 Q) z% u' j
normal except the testosterone level was high. The: @6 u0 S0 I) h J
follow-up visit was arranged within a few weeks to) W/ z! s. V/ u4 I( W1 ?
obtain testicular and abdominal sonograms; how-/ Z+ E! o5 t5 I
ever, the family did not return for 4 months.
' u7 C- L) A, }: YPhysical examination at this time revealed that the
) _$ N$ [ `. U* |% o# Achild had grown 2.5 cm in 4 months and had gained4 G! U) L _1 b- h7 _
2 kg of weight. Physical examination remained+ s. A4 Z, ^# C1 s* q% j" }8 {
unchanged. Surprisingly, the pubic hair almost com-. w7 E0 W+ K$ z: Z$ \$ D
pletely disappeared except for a few vellous hairs at9 U# s: ? }" N9 G* `- U" w
the base of the phallus. Testicular volume was still 25 T3 a( V7 W6 j- \) d' \! q2 @
mL, and the size of the penis remained unchanged.
! y; y- c' W+ ^1 T' n' D( [ ]- ~' TThe mother also said that the boy was no longer hav-
1 K* l0 H1 `* u* b5 Ting frequent erections.
1 p; j) {4 ^8 j0 ^) h: ?6 s xBoth parents were again questioned about use of# [& k: X) Q6 Y: B, Z
any ointment/creams that they may have applied to9 p+ |4 r v C1 k2 b5 a
the child’s skin. This time the father admitted the
6 ]* b5 u, H/ r0 n' z$ F# bTopical Testosterone Exposure / Bhowmick et al 541
" z1 C1 {. I/ H% xuse of testosterone gel twice daily that he was apply-& B/ R8 N$ m% {
ing over his own shoulders, chest, and back area for
7 U+ q/ }) s$ ?; h3 fa year. The father also revealed he was embarrassed
7 R ~1 i+ e: c: f: h; ~ \4 q; yto disclose that he was using a testosterone gel pre-, b+ y v5 G! {; F' F
scribed by his family physician for decreased libido3 w# {, [: J4 R2 z6 o7 U" v2 ^
secondary to depression.- O) A8 D/ m5 o5 e+ l
The child slept in the same bed with parents.
@1 k4 G3 `' y' D; p$ t" y4 y, F; @The father would hug the baby and hold him on his0 B% F# C; u/ `6 m2 k
chest for a considerable period of time, causing sig-/ j- i7 b& @; C3 A7 c+ A
nificant bare skin contact between baby and father.: W6 }8 h$ |8 e7 ]8 _
The father also admitted that after the phone call,1 o. ]2 W. Y0 Q: j9 k
when he learned the testosterone level in the baby
# n8 W$ f. S2 G, q1 C' ?6 s5 N' S1 ?was high, he then read the product information
% C# u& N; R' Y6 Cpacket and concluded that it was most likely the rea-
R, K8 X. |3 N3 O. F0 i( qson for the child’s virilization. At that time, they2 E7 d) [9 q6 ~: Z
decided to put the baby in a separate bed, and the% G8 x' G0 G& Z4 [1 T
father was not hugging him with bare skin and had
' _' Z3 ?! K6 j8 L3 Obeen using protective clothing. A repeat testosterone
( \: w. h7 w+ }9 r" Dtest was ordered, but the family did not go to the( e" k$ A" p& u- t9 N: x; C% E/ O4 n
laboratory to obtain the test.
u ]5 v' ?! _8 M" @) V8 _% XDiscussion4 |/ c- F% N: F0 A0 u
Precocious puberty in boys is defined as secondary( V4 ^( ~; V" ?' e$ q* c6 V* Y
sexual development before 9 years of age.1,44 S2 B: ?/ o, i* p0 _$ r8 ]
Precocious puberty is termed as central (true) when6 K1 W# {3 |0 {2 j& I
it is caused by the premature activation of hypo-; C% U+ p' o5 c6 P& @: n5 C
thalamic pituitary gonadal axis. CPP is more com-
. j Q( m/ T$ S9 a) p2 mmon in girls than in boys.1,3 Most boys with CPP f+ |- n# Y9 r# }2 t# x
may have a central nervous system lesion that is1 P1 c: a: \' a+ B
responsible for the early activation of the hypothal-8 c) v' T) a J: Y4 s+ F2 S
amic pituitary gonadal axis.1-3 Thus, greater empha-' N1 b9 ^ ~' P
sis has been given to neuroradiologic imaging in8 E$ R0 c# J5 p% z9 c" O
boys with precocious puberty. In addition to viril-) c8 S1 ~3 x) H# O( }. W
ization, the clinical hallmark of CPP is the symmet-
) l+ N6 |5 c9 F% e1 a- ^rical testicular growth secondary to stimulation by8 B# l; B5 R: |/ ^% n
gonadotropins.1,3
2 a6 x L' P( m2 @+ JGonadotropin-independent peripheral preco-
3 E& ?+ T, S Acious puberty in boys also results from inappropriate
' s0 X) z. z3 ]# \6 r: k9 c0 Gandrogenic stimulation from either endogenous or0 ]/ C* U, F& b7 r* g A
exogenous sources, nonpituitary gonadotropin stim-
0 @3 f- G1 ]7 C, U* o4 e0 Lulation, and rare activating mutations.3 Virilizing
! j+ \% ]/ ~( Rcongenital adrenal hyperplasia producing excessive
# ]! I+ P0 a& q$ j% O7 wadrenal androgens is a common cause of precocious
: i# a! s, p4 r- Fpuberty in boys.3,4
5 e/ p/ u& m* |+ h) M" kThe most common form of congenital adrenal
& h( T& H& e$ s" r& E3 Zhyperplasia is the 21-hydroxylase enzyme deficiency.
1 q5 e6 K/ n, _9 Q5 n9 PThe 11-β hydroxylase deficiency may also result in/ @" k' U9 q/ f4 z
excessive adrenal androgen production, and rarely,
8 m$ V3 Q6 [1 v5 l" p# pan adrenal tumor may also cause adrenal androgen
8 q# n" r( p3 S! P: Q! sexcess.1,34 c! f# ^& g% i/ I' o" [9 N
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
: M; h, A |# D1 @! V( ]542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
* ]/ ]( O9 o- SA unique entity of male-limited gonadotropin-
3 h" s! K( @" y, A( L" E( ~5 R4 Rindependent precocious puberty, which is also known# M' D, y/ N% }8 w1 {: G
as testotoxicosis, may cause precocious puberty at a
4 f/ Q( e0 Q9 @) b% v5 D/ Kvery young age. The physical findings in these boys
' ^) t9 N; E2 }) o: J6 zwith this disorder are full pubertal development,: r; C" {/ T- h5 ~3 D
including bilateral testicular growth, similar to boys
, Z8 h; T" x$ P" twith CPP. The gonadotropin levels in this disorder
( l# p7 Q- M" [1 J# Z7 Qare suppressed to prepubertal levels and do not show
% E' q7 i$ m. d# E' j6 V! k# Xpubertal response of gonadotropin after gonadotropin-2 }5 B! D1 S, Z0 W/ H
releasing hormone stimulation. This is a sex-linked* m( T1 P# z" u: [5 `2 ~
autosomal dominant disorder that affects only$ w8 ~* `% g; d0 [5 j
males; therefore, other male members of the family
0 ~8 o& `- W3 ^8 k: _+ O) tmay have similar precocious puberty.3
6 D K4 l: y& K% t8 E6 ~In our patient, physical examination was incon-1 S/ U ]5 Q3 U
sistent with true precocious puberty since his testi-; Y* v3 P0 i' h9 p
cles were prepubertal in size. However, testotoxicosis
; S+ q+ n; `: Z2 bwas in the differential diagnosis because his father
' \# M5 v a% Bstarted puberty somewhat early, and occasionally,
" @9 p# B0 C1 l5 O+ i ~5 [testicular enlargement is not that evident in the
# K# r5 j, x! Z# Sbeginning of this process.1 In the absence of a neg-
! Q* l4 N; D9 w" z8 K+ e7 ~ative initial history of androgen exposure, our+ ]$ M% R$ I/ x7 K W; {1 j/ C
biggest concern was virilizing adrenal hyperplasia,; G5 C! l) x/ H2 m2 H* K
either 21-hydroxylase deficiency or 11-β hydroxylase; i% i+ R3 I& ^
deficiency. Those diagnoses were excluded by find-
" ]" D1 z; i% h" Ting the normal level of adrenal steroids.
6 N3 o# E5 J! [# \2 I7 ZThe diagnosis of exogenous androgens was strongly
) b; T. ^* F4 J4 u3 d, ksuspected in a follow-up visit after 4 months because4 `9 F( V9 \. O, \) n
the physical examination revealed the complete disap-
; n$ p' r3 F& s" n+ `( v6 m+ rpearance of pubic hair, normal growth velocity, and
( n& z ~- i, k8 _* Cdecreased erections. The father admitted using a testos- }% ^2 j6 L6 g
terone gel, which he concealed at first visit. He was
/ c2 G# B+ q" S) V" ^using it rather frequently, twice a day. The Physicians’
8 e6 e& u" F* ]4 A$ j, XDesk Reference, or package insert of this product, gel or
& k9 s3 f4 }1 M( c4 C4 Y& e# Pcream, cautions about dermal testosterone transfer to
+ E z' d& _1 U4 Hunprotected females through direct skin exposure.
$ [6 H! X9 c$ jSerum testosterone level was found to be 2 times the
6 u# J/ ?3 \: Bbaseline value in those females who were exposed to1 @$ o' y+ z: I1 g, m. B9 J
even 15 minutes of direct skin contact with their male; H6 J, J$ Z) I" y2 v% A
partners.6 However, when a shirt covered the applica-: d% c0 b% y4 g" J2 E! Y
tion site, this testosterone transfer was prevented.
4 G3 V3 Y! G) r TOur patient’s testosterone level was 60 ng/mL,
3 _2 }% M- U3 P# g, swhich was clearly high. Some studies suggest that
" o& f+ |! C0 |! v! ^; Cdermal conversion of testosterone to dihydrotestos-
: i- v' s: R5 i6 U8 x: K- C0 Wterone, which is a more potent metabolite, is more
9 @" u- d5 _1 a3 m# x* ractive in young children exposed to testosterone u. Q6 f- e8 s+ P$ ^: |( o' }
exogenously7; however, we did not measure a dihy-6 n; N8 \! v, r9 r2 u& |4 Y, B) x
drotestosterone level in our patient. In addition to3 }8 M5 p7 H5 B( E/ ~5 \1 k
virilization, exposure to exogenous testosterone in
3 D7 {+ V4 y3 ], Cchildren results in an increase in growth velocity and/ x3 D8 ^( B9 h" E0 C) l1 n+ ?
advanced bone age, as seen in our patient.; j) c- b: `7 r
The long-term effect of androgen exposure during
( G7 i3 a% O5 ]4 Tearly childhood on pubertal development and final
& c) S' P& K9 A7 _* @+ w2 wadult height are not fully known and always remain& R6 G: W1 ?' o3 g4 B9 u
a concern. Children treated with short-term testos-6 e! U2 S, a" u
terone injection or topical androgen may exhibit some
. P- i& g: ~0 N2 ]) \% {3 R: `* |) lacceleration of the skeletal maturation; however, after
8 G7 ]5 n. R I% k \: @cessation of treatment, the rate of bone maturation( ^; ]& g& }: S( C9 L
decelerates and gradually returns to normal.8,9
+ c+ a" a; ?- t. J3 b, h0 {; GThere are conflicting reports and controversy
- K `; o# z% @. T/ W+ u/ X+ kover the effect of early androgen exposure on adult
$ Y. W( J6 @' W- t! X, rpenile length.10,11 Some reports suggest subnormal
8 \% k3 I! m8 A6 A, e5 u) Z* @adult penile length, apparently because of downreg-* a0 \9 ]: D# B8 c8 N
ulation of androgen receptor number.10,12 However,
" f/ q" A$ @7 DSutherland et al13 did not find a correlation between& |( N b/ y, Y; P3 O7 p
childhood testosterone exposure and reduced adult) R3 v* c, O! a
penile length in clinical studies.
5 z- f: f0 X: P W. `1 O: _Nonetheless, we do not believe our patient is5 W+ O" T5 P; v+ g0 g
going to experience any of the untoward effects from4 ^9 n$ _8 g) |5 }. Y
testosterone exposure as mentioned earlier because
$ h! F4 b4 R/ R Zthe exposure was not for a prolonged period of time.6 p. |4 u, g' m
Although the bone age was advanced at the time of
2 O S) s6 m5 ddiagnosis, the child had a normal growth velocity at$ d S: S5 Q" b/ ^
the follow-up visit. It is hoped that his final adult
% [, q5 `& a) c! C) n0 q% E7 y! ?height will not be affected./ h: v* p' ^, {: s9 Y
Although rarely reported, the widespread avail-$ B, Y9 v' ]. T: C# [. {1 r7 m
ability of androgen products in our society may% F+ D V3 T1 |0 G5 a5 \4 d$ \
indeed cause more virilization in male or female" M' T u8 P$ o( o* P0 n
children than one would realize. Exposure to andro-
0 _) G; E+ q0 \- `* kgen products must be considered and specific ques-
' W+ E G* U2 l, X" htioning about the use of a testosterone product or* C9 [6 e$ p% |2 W% a& c+ y
gel should be asked of the family members during8 j* s( u8 S3 Z
the evaluation of any children who present with vir-9 F& y7 p1 P: e: U+ Q' }
ilization or peripheral precocious puberty. The diag-
2 y; f$ v2 `- ?# a6 h Cnosis can be established by just a few tests and by6 b9 o6 F6 w0 M
appropriate history. The inability to obtain such a6 \' k) w: l% ]! ~5 I9 B8 B
history, or failure to ask the specific questions, may6 \; w% [, ~9 w1 T1 r9 ]
result in extensive, unnecessary, and expensive
/ } @, c6 E5 d* T1 Sinvestigation. The primary care physician should be
/ r. n4 Z! L6 x: U2 ?; z+ t: g5 jaware of this fact, because most of these children
* h6 p, C+ b! K( W3 M5 |- d- smay initially present in their practice. The Physicians’
9 l- Y! q! A0 \8 w) h0 b. c# o) bDesk Reference and package insert should also put a
7 T: O: |' o) V9 q0 r# u5 A0 Mwarning about the virilizing effect on a male or1 V9 v- F' z$ [8 ~1 {# L
female child who might come in contact with some-) c4 d! r1 i9 m) C% v, x m
one using any of these products.' R& P5 @8 }4 a
References( q' e/ S0 g* \! C2 Q1 R( D
1. Styne DM. The testes: disorder of sexual differentiation! t: A; z. \# h2 p; l" ^) `( f
and puberty in the male. In: Sperling MA, ed. Pediatric& I2 P( s0 f) U. D/ G, l2 W/ Z
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;% S6 ~) R. Q2 O5 P* v3 r
2002: 565-628.
9 [5 L7 |$ S/ y" C0 N9 ]2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
& x, {( W* ~" Xpuberty in children with tumours of the suprasellar pineal |
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