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Sexual Precocity in a 16-Month-Old4 g* J9 w- r' Z2 w
Boy Induced by Indirect Topical- b3 {: @* q+ ?, b) O
Exposure to Testosterone2 {% ?( S6 k! _8 j) ?7 v
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
, S8 |, |8 P8 Y/ x0 C8 X {and Kenneth R. Rettig, MD1' m& Z- g/ b, v! R" l7 M
Clinical Pediatrics. ~4 u* u! t8 N2 E- l2 M( ^/ E
Volume 46 Number 6/ Q2 N) A7 W6 r f
July 2007 540-543: s6 o' U3 j3 B; d! z0 z. g. }
© 2007 Sage Publications
% l- S1 q! z& c: S10.1177/0009922806296651# q5 m3 m/ i7 y4 d
http://clp.sagepub.com5 s8 G& U8 K% d
hosted at
' a) c8 N- x' ?http://online.sagepub.com
6 }% f2 Z: @" r; bPrecocious puberty in boys, central or peripheral,
: Q9 \1 {* A8 l& X; Gis a significant concern for physicians. Central6 c- {$ i; h6 ^5 h% F- }
precocious puberty (CPP), which is mediated! }: r N% Q8 d9 a
through the hypothalamic pituitary gonadal axis, has9 d* M& ^5 n9 k
a higher incidence of organic central nervous system4 C O6 J8 x, W& \
lesions in boys.1,2 Virilization in boys, as manifested( N, ~7 _3 ?' @
by enlargement of the penis, development of pubic0 O! c. x4 R& K% o- j" ]8 w
hair, and facial acne without enlargement of testi-
' z- C3 P7 }' Dcles, suggests peripheral or pseudopuberty.1-3 We% S/ N& G* e4 V. z
report a 16-month-old boy who presented with the
A8 W4 S0 d$ f# V' [enlargement of the phallus and pubic hair develop-
1 ~) m! p4 S) h/ s- a# P9 X" hment without testicular enlargement, which was due
5 d! ?( M# x' U8 Z! X7 qto the unintentional exposure to androgen gel used by I9 I. ^$ [2 x' y9 n
the father. The family initially concealed this infor-- J6 Q( _. [( q0 b) R
mation, resulting in an extensive work-up for this7 L( F0 @' r% O5 H/ \ ?; w' o: R
child. Given the widespread and easy availability of, a4 I Y& X, {( s" o
testosterone gel and cream, we believe this is proba-
/ g3 p7 X+ R8 C R, r6 H0 o& {bly more common than the rare case report in the
3 O, c$ [" I8 B6 a* S. Oliterature.4
4 P, r E; \0 T. P1 `2 cPatient Report* ]9 {$ K+ p+ B
A 16-month-old white child was referred to the- f# x2 J$ t S0 R
endocrine clinic by his pediatrician with the concern
! U$ X+ I% l. `% I* aof early sexual development. His mother noticed
. j! N. C6 D5 j, a6 _light colored pubic hair development when he was
% M4 V. H+ s7 P5 u7 J- u% ]* fFrom the 1Division of Pediatric Endocrinology, 2University of
7 K( g8 H' w# E0 b9 D9 y8 ZSouth Alabama Medical Center, Mobile, Alabama.) b2 a5 ~1 e" I4 O" b4 N
Address correspondence to: Samar K. Bhowmick, MD, FACE,
& }. p3 J6 r1 ~1 ^Professor of Pediatrics, University of South Alabama, College of& O1 V4 j Y+ y ]1 N! S2 S
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
- q- @2 b7 y5 I7 }& Ve-mail: [email protected].+ ?6 e0 W' d; r' L# N
about 6 to 7 months old, which progressively became
4 H) `; `0 Z+ G( @$ y( Vdarker. She was also concerned about the enlarge-- h( c$ I# L. Y7 Z
ment of his penis and frequent erections. The child
9 }* q( D# v. K4 a9 l, |3 l/ {was the product of a full-term normal delivery, with
- c, p- [# ]5 Ia birth weight of 7 lb 14 oz, and birth length of+ L- `) |: ^( u, g" C! S
20 inches. He was breast-fed throughout the first year
! A0 F4 s- I6 F7 O4 `9 R6 \& gof life and was still receiving breast milk along with
/ F# o+ s4 j p4 f( ?9 bsolid food. He had no hospitalizations or surgery,: x+ d! d+ K" `
and his psychosocial and psychomotor development
3 }& V; a. D5 R+ {was age appropriate.2 q* B! d5 S" y- C
The family history was remarkable for the father,+ Y; J. T# y) m; H
who was diagnosed with hypothyroidism at age 16,! r/ K& G& u: w; R5 t' p8 F
which was treated with thyroxine. The father’s& V( |% I1 @: Z7 D$ c6 I7 M* T
height was 6 feet, and he went through a somewhat' `6 }6 U( \6 n7 ]0 n
early puberty and had stopped growing by age 14.- ]3 _. c. m' A" K: S4 H
The father denied taking any other medication. The3 _1 M6 e. M/ Q) |2 ?
child’s mother was in good health. Her menarche
8 w4 `# a. \2 f! W$ Zwas at 11 years of age, and her height was at 5 feet
# X- i5 K# Q, x( j2 f/ O1 x9 y5 inches. There was no other family history of pre-
( W( R1 r" x* Q L3 S# o6 wcocious sexual development in the first-degree rela-4 Y2 {+ R% U. D# N8 i% \
tives. There were no siblings.
; y6 D4 S! }% P e* bPhysical Examination. c% v L6 P3 K' y* q& S
The physical examination revealed a very active,
$ F8 F* e3 m1 X3 m. gplayful, and healthy boy. The vital signs documented
; B- u3 r' ^) Z6 ]3 t; P$ Ya blood pressure of 85/50 mm Hg, his length was
, W) B- t. N5 o) S9 m90 cm (>97th percentile), and his weight was 14.4 kg
" N: a$ a6 l6 k(also >97th percentile). The observed yearly growth
' D& y9 @+ u W9 B5 S. ^2 Hvelocity was 30 cm (12 inches). The examination of
! m$ U( x% a( h9 R; [, e; Y+ Othe neck revealed no thyroid enlargement.
' X" J. W- n0 {8 ?1 G. Y. j* IThe genitourinary examination was remarkable for
3 N# F g+ t: e3 Y$ B& ^$ Eenlargement of the penis, with a stretched length of+ E, e- _9 u5 {( q0 y
8 cm and a width of 2 cm. The glans penis was very well
1 o! q1 E, ]; y/ r8 Jdeveloped. The pubic hair was Tanner II, mostly around
1 y1 i% M% j# G' ?540
Q% G' F6 O5 i0 Mat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
6 F4 A5 r: Y' `, K( a" B$ b( }& uthe base of the phallus and was dark and curled. The
, Y1 w( n) V2 T3 G9 k3 e: L: Htesticular volume was prepubertal at 2 mL each.
" s; J0 M/ B$ L- V( ?6 FThe skin was moist and smooth and somewhat, y( w% B: ~+ C/ m- e4 g
oily. No axillary hair was noted. There were no
* T) }+ B! _2 l: B9 dabnormal skin pigmentations or café-au-lait spots.) S {* _5 y* r8 K7 W' c. I8 G
Neurologic evaluation showed deep tendon reflex 2+* Q- E* i; w+ @
bilateral and symmetrical. There was no suggestion
; h3 w) a M$ rof papilledema.; D0 O- B! U( e% U( _8 T4 E, }3 N# l# v
Laboratory Evaluation' n2 W7 z4 M1 |
The bone age was consistent with 28 months by
0 b5 z% k" c- b0 D' T2 kusing the standard of Greulich and Pyle at a chrono-
8 D' g8 Q" c, T1 _' Q- \$ alogic age of 16 months (advanced).5 Chromosomal- v' P" o$ w* s
karyotype was 46XY. The thyroid function test$ B8 z* q g' J: D; L! O# O
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
0 H ]2 C( T1 }$ Y; @) Elating hormone level was 1.3 µIU/mL (both normal).
' U' R$ ?! q% F1 ?5 N9 OThe concentrations of serum electrolytes, blood
% L; Y7 h: j4 e: `8 W4 A+ ]urea nitrogen, creatinine, and calcium all were* c, O! ^2 o3 f' W4 F: H3 W8 _
within normal range for his age. The concentration
" U- M' P. ^& k0 V P- ^of serum 17-hydroxyprogesterone was 16 ng/dL+ h( }# g( R _ n3 H1 ^
(normal, 3 to 90 ng/dL), androstenedione was 20
L+ F+ s+ u+ {, Z, A4 P8 z8 @ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-- ^: d+ i! j# T3 Q" L+ B2 h- m. j
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
* l6 G- e- _7 y: W1 ]% G' r. V' Hdesoxycorticosterone was 4.3 ng/dL (normal, 7 to, }1 r( y% n, M% b/ C3 D' L: ^" Q4 g
49ng/dL), 11-desoxycortisol (specific compound S)
`# I- N5 X; z* j& J/ P! {! g* Swas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
9 {8 p! P. E$ A' jtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
: K; T5 y- x& F; y' |testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
: M- f; F+ i' f) T+ O1 o5 d+ Aand β-human chorionic gonadotropin was less than1 N9 s2 K2 F. W% K
5 mIU/mL (normal <5 mIU/mL). Serum follicular
2 ~; E1 W, u0 s$ y% nstimulating hormone and leuteinizing hormone
# B8 }) |3 V2 h+ \ S3 aconcentrations were less than 0.05 mIU/mL' z8 T% h5 U$ U( V1 k
(prepubertal).
. I X8 ~3 `( `+ h) M3 J( lThe parents were notified about the laboratory! h( P% S& V! k- S; Z+ M8 y
results and were informed that all of the tests were6 E3 V1 d4 w0 r
normal except the testosterone level was high. The) R7 [- W$ C W1 t5 @
follow-up visit was arranged within a few weeks to
9 a- H( ^5 a! J) U F. O. ~obtain testicular and abdominal sonograms; how-
! b4 ]5 n, F6 x9 Y' zever, the family did not return for 4 months.# r! z0 `8 L! D% B1 O
Physical examination at this time revealed that the" r4 \+ Q: q7 o; D) P
child had grown 2.5 cm in 4 months and had gained" m) T) D3 u* Z5 p" _/ I3 K( u1 g
2 kg of weight. Physical examination remained w/ ?: _& B% i |# _+ {
unchanged. Surprisingly, the pubic hair almost com-
+ I# c2 a( s+ E& upletely disappeared except for a few vellous hairs at
$ v9 @2 z/ n! |+ o: Ythe base of the phallus. Testicular volume was still 2% k: |3 S0 d) ]+ c5 L: r$ `' M
mL, and the size of the penis remained unchanged.
2 n. C+ t7 H% E9 y' ^# Z: f# I. }The mother also said that the boy was no longer hav-0 H- r& n6 ?# U; q# i. y
ing frequent erections.
8 e4 b8 U( E* xBoth parents were again questioned about use of1 _* B9 H4 ]8 ^/ h- l# n' H
any ointment/creams that they may have applied to' d. C) S. j6 n& ?
the child’s skin. This time the father admitted the7 u6 [! R! G9 h/ h9 X
Topical Testosterone Exposure / Bhowmick et al 541" u: v, w" o6 e! M: b- S4 Q. n( ]0 q
use of testosterone gel twice daily that he was apply-. j g% H. L+ Q( q' J5 E& [
ing over his own shoulders, chest, and back area for
/ _4 G3 B& Z9 Va year. The father also revealed he was embarrassed8 P# V& Y ^ n2 ]! Y5 V c. T
to disclose that he was using a testosterone gel pre-
5 d1 _, ?" F% W: dscribed by his family physician for decreased libido( e) ?2 b9 r$ ?) s1 j) X
secondary to depression.6 r, W2 W$ K( Q8 T& [6 {' A, G# f) P
The child slept in the same bed with parents.2 x% ~3 Y! q/ y' |2 _( n; x) ^5 j
The father would hug the baby and hold him on his
8 A6 o( m* \3 v7 w& O2 A, i$ ]chest for a considerable period of time, causing sig-
" }0 S4 K3 _/ \9 o4 v jnificant bare skin contact between baby and father.; A1 W1 M, O7 ^% K3 E" t9 y
The father also admitted that after the phone call," f) y" N4 `) Q5 z4 Q
when he learned the testosterone level in the baby
$ f* N% O6 E+ Mwas high, he then read the product information) u; Y7 |" C* }0 H
packet and concluded that it was most likely the rea-
1 z. w7 I" u# O. b+ q6 t4 W/ s. b" d* lson for the child’s virilization. At that time, they
) c- h2 @# W# ^3 q5 udecided to put the baby in a separate bed, and the
8 _. e! G' M4 p# _father was not hugging him with bare skin and had
% f! ~& c4 Z8 ~; o# k. S* pbeen using protective clothing. A repeat testosterone
# I8 O4 ]# i; Y# t. `8 F9 h' vtest was ordered, but the family did not go to the
7 D/ F$ Z o! G& Zlaboratory to obtain the test.; k( j; h, v+ X% g; _, Q6 r9 @1 w
Discussion6 h/ w2 P1 e: o, l
Precocious puberty in boys is defined as secondary8 A6 s1 \( f: e2 k* D, ?% ~" j6 P$ a0 i
sexual development before 9 years of age.1,49 H1 P' i8 o, m% c
Precocious puberty is termed as central (true) when
# _0 q+ C3 Z7 \6 T! Sit is caused by the premature activation of hypo-5 l0 d% f8 R* A; H: a% o
thalamic pituitary gonadal axis. CPP is more com-* p! k9 n- e0 y' J5 e( ]
mon in girls than in boys.1,3 Most boys with CPP
3 Q" t- n. q7 L$ l- Omay have a central nervous system lesion that is
( g# k: K( ^' V" L0 e8 B Oresponsible for the early activation of the hypothal-5 p) l6 H5 f, A x. [
amic pituitary gonadal axis.1-3 Thus, greater empha-# Y8 b; [8 ]& P. j4 [
sis has been given to neuroradiologic imaging in
" V* E, t5 e" Hboys with precocious puberty. In addition to viril-! O) W6 T' p* y% h
ization, the clinical hallmark of CPP is the symmet-6 i9 \7 `/ o( K0 ^
rical testicular growth secondary to stimulation by* U# x4 g _; [
gonadotropins.1,3# E# x* B' m/ ~7 o+ Z
Gonadotropin-independent peripheral preco-
- l: |+ t* Y' E% P6 tcious puberty in boys also results from inappropriate
3 X) i9 x8 j: R9 Yandrogenic stimulation from either endogenous or! h+ @. j9 @4 c, g7 N
exogenous sources, nonpituitary gonadotropin stim-
" [" p# U$ N/ g7 O! }6 V) Lulation, and rare activating mutations.3 Virilizing: \5 W! K) j, C9 a8 V2 p7 X0 ?; j5 i
congenital adrenal hyperplasia producing excessive$ {( [; z) ~# Y' H% k* B$ c4 d
adrenal androgens is a common cause of precocious7 K6 s; U; ^3 R
puberty in boys.3,4' k& g9 n/ Z: f r7 s7 Q. A' `
The most common form of congenital adrenal8 y& B8 V" p/ E
hyperplasia is the 21-hydroxylase enzyme deficiency.
0 M9 z7 ]* t& NThe 11-β hydroxylase deficiency may also result in
6 J- y N2 g' nexcessive adrenal androgen production, and rarely,$ R1 h4 n* P" a8 P
an adrenal tumor may also cause adrenal androgen
3 I6 L- T6 I5 z" fexcess.1,3
' }+ Z {& v E1 U' Eat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
2 S. f2 Z' R* c542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
: `2 @$ s7 O, l. X }1 ~5 aA unique entity of male-limited gonadotropin-: X M' v7 ^2 q, ^
independent precocious puberty, which is also known2 l8 t1 H7 Q. k, K! m) n, {5 ^
as testotoxicosis, may cause precocious puberty at a7 W5 g3 p2 u" @/ Q! M- u/ n4 C: c4 T
very young age. The physical findings in these boys, f9 e, U' r/ f3 |
with this disorder are full pubertal development,( T% T' J$ B5 E' R( X$ w
including bilateral testicular growth, similar to boys
$ I' b8 z6 y) E" j1 x% g5 Jwith CPP. The gonadotropin levels in this disorder
) u% Y) G8 s4 care suppressed to prepubertal levels and do not show
6 \5 c* j; {- \' m' L, C6 Gpubertal response of gonadotropin after gonadotropin-
, a- W! Z' l) e( a; dreleasing hormone stimulation. This is a sex-linked- S: O, Q' i" e
autosomal dominant disorder that affects only
) h' L4 l! I% I3 smales; therefore, other male members of the family
6 N3 O4 I/ |0 Z1 {may have similar precocious puberty.3$ g% J2 {* V/ R! \+ E. v2 ?
In our patient, physical examination was incon-
4 }8 w8 T9 ~# g& k. {! ^4 Asistent with true precocious puberty since his testi-
+ F; z* t; ]7 ~0 x3 t, ?6 ^+ gcles were prepubertal in size. However, testotoxicosis
1 F7 X" f2 T7 n' ]- Gwas in the differential diagnosis because his father
{6 q$ g. F) |# Nstarted puberty somewhat early, and occasionally,
7 p. v7 Q; V0 m8 A1 o8 Htesticular enlargement is not that evident in the7 E2 Y' A9 {2 w) [9 O4 a7 q
beginning of this process.1 In the absence of a neg-1 a- a& g9 ?1 ]* b
ative initial history of androgen exposure, our
& M. X$ e+ y0 ?; F. Z- |biggest concern was virilizing adrenal hyperplasia,
; U4 W' u; d4 U: R6 e" teither 21-hydroxylase deficiency or 11-β hydroxylase6 N; i- S' k1 T, F5 m: ]/ ^* {
deficiency. Those diagnoses were excluded by find-
4 |+ v" g+ v8 v# @) Xing the normal level of adrenal steroids.
: d- i" g* v% kThe diagnosis of exogenous androgens was strongly
7 k5 d; J3 H" ~6 Y5 T2 Q( Fsuspected in a follow-up visit after 4 months because
5 r# Y, v5 t/ F4 _' y! a# n* ythe physical examination revealed the complete disap-% w7 P/ N) T; W. ^
pearance of pubic hair, normal growth velocity, and
# b/ J/ Y% m. O8 i, O5 }decreased erections. The father admitted using a testos-
" y/ ^- b+ m# p7 Qterone gel, which he concealed at first visit. He was
1 F" N3 Y5 g0 Z% r; Fusing it rather frequently, twice a day. The Physicians’; w" F4 r* D. r2 s4 k; h
Desk Reference, or package insert of this product, gel or) p2 \( u/ U, P9 P( k( K
cream, cautions about dermal testosterone transfer to
( b! t* @' x* X1 gunprotected females through direct skin exposure.& |: `8 v+ p, H, _$ u; N
Serum testosterone level was found to be 2 times the& k! `' j9 L* H0 s: c* r9 L
baseline value in those females who were exposed to3 b0 ^6 d; m7 t8 l2 g, E. U
even 15 minutes of direct skin contact with their male. ^' E. o" O- z2 E% ?# B& Q* J2 q
partners.6 However, when a shirt covered the applica-! ?% g5 W: p5 G9 T0 m! e
tion site, this testosterone transfer was prevented.3 K# Z# J2 k1 T/ }8 @4 C4 M
Our patient’s testosterone level was 60 ng/mL,1 F/ a, K( n+ ]* B x7 m' a+ m
which was clearly high. Some studies suggest that
0 s0 m1 f6 O- L x2 Sdermal conversion of testosterone to dihydrotestos-" s+ ?* i s' r6 j& a6 _+ }
terone, which is a more potent metabolite, is more$ q% r3 [' q. R' y
active in young children exposed to testosterone
v" M! w" O( Aexogenously7; however, we did not measure a dihy-$ d% u% O& S; P
drotestosterone level in our patient. In addition to) W" c7 f9 a$ D1 m |; b
virilization, exposure to exogenous testosterone in
2 {. U8 X' |! {- g; tchildren results in an increase in growth velocity and
9 c5 _% ~, A( I4 E/ aadvanced bone age, as seen in our patient.
( \4 X: j* w- M( ~7 u2 E* [The long-term effect of androgen exposure during- \& H. Z7 `+ c) [4 M2 d) l
early childhood on pubertal development and final
: o# W: N& d9 L5 U1 P+ I9 _" f3 Kadult height are not fully known and always remain
. B8 v/ J( G; G' h6 wa concern. Children treated with short-term testos-
/ s7 O. K) ^& M+ U" P' _terone injection or topical androgen may exhibit some
, B2 \5 V, e4 V0 z; O3 H; b @acceleration of the skeletal maturation; however, after$ i# u! F8 U; F8 |; H
cessation of treatment, the rate of bone maturation
3 V. o/ I8 i- ^1 k( g6 ?decelerates and gradually returns to normal.8,9: K& J+ j0 Z* M9 L- b2 y
There are conflicting reports and controversy7 d5 \5 P9 ~/ \2 R
over the effect of early androgen exposure on adult) }2 O: {% {# B* ]# e) j; Q( U( S
penile length.10,11 Some reports suggest subnormal. \3 `) a4 t& D7 ?7 Y
adult penile length, apparently because of downreg-' d- d4 X; r. f" M
ulation of androgen receptor number.10,12 However,
\ O9 [9 Y8 FSutherland et al13 did not find a correlation between, J) v$ j# \7 Q1 T8 _. l6 K) E5 Y
childhood testosterone exposure and reduced adult
6 `, W9 ~& z4 Q: |penile length in clinical studies.: B3 w3 Q, g5 n
Nonetheless, we do not believe our patient is* {7 R7 M# y- n& o d, C
going to experience any of the untoward effects from1 X& S1 m( j/ a$ s
testosterone exposure as mentioned earlier because% L! l" W: } w) _
the exposure was not for a prolonged period of time.
6 m" m9 h K$ X$ c! S5 R5 qAlthough the bone age was advanced at the time of
^0 u+ U% H! ^/ L, Mdiagnosis, the child had a normal growth velocity at! u6 s& o7 l; B5 s/ F9 G
the follow-up visit. It is hoped that his final adult
. m5 q8 N. l- _" k8 J* hheight will not be affected.
: {& s7 i% g* b' ?2 ^5 i5 vAlthough rarely reported, the widespread avail-. @! Z: F$ t4 d$ F* L6 E; ?
ability of androgen products in our society may
, s& f/ C! B/ e0 T$ c6 ~$ rindeed cause more virilization in male or female# g/ p7 A: T! b Y) C+ h* ]
children than one would realize. Exposure to andro-; \5 b7 G* I- c6 y
gen products must be considered and specific ques-
, H0 c4 k/ ^- Ytioning about the use of a testosterone product or) v! o. v$ F, b- g j* @7 O2 Y, ^
gel should be asked of the family members during* y* k+ w- G$ g. S2 T/ Y. {
the evaluation of any children who present with vir-
% {6 o5 { `3 T* `9 F8 zilization or peripheral precocious puberty. The diag-
7 a* V/ I1 K! d) nnosis can be established by just a few tests and by [$ m! a: J- W7 t2 f
appropriate history. The inability to obtain such a& S9 Z7 } I8 F
history, or failure to ask the specific questions, may( s! U# Z8 v8 T% I
result in extensive, unnecessary, and expensive3 x/ |. ]) v$ }8 Z6 e6 K5 }
investigation. The primary care physician should be
3 ]' J: H3 J5 caware of this fact, because most of these children
& A1 ^; H- y' K* ^may initially present in their practice. The Physicians’) P5 A8 A% \* z, \' A% P7 ]4 V
Desk Reference and package insert should also put a
, ]3 Y% [0 j8 I- mwarning about the virilizing effect on a male or
t" N4 R! {: Ufemale child who might come in contact with some-
& E* O! c$ d% j h* mone using any of these products.5 U+ u9 R+ B7 d$ i" V5 o
References
* Z- {/ k5 x: v8 v8 Z9 |4 \1. Styne DM. The testes: disorder of sexual differentiation5 F# E* N2 c" {5 e4 G
and puberty in the male. In: Sperling MA, ed. Pediatric! V0 ?7 I' p! f3 d4 W# c+ N6 _8 i
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;! i( v+ I7 I4 T: P8 W
2002: 565-628.9 L" \# x3 \' i1 D2 O
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious$ k# f/ D5 b" X2 @4 A* {
puberty in children with tumours of the suprasellar pineal |
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