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Sexual Precocity in a 16-Month-Old
0 s7 m* G3 m: @# o5 T( a# {Boy Induced by Indirect Topical
$ r! P, y( X/ J0 N# T) FExposure to Testosterone. x* p4 o3 w: g# V* { \. |
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2; b% s0 |' h7 _; M, M
and Kenneth R. Rettig, MD15 z y, B; @# i2 S+ i3 _: H
Clinical Pediatrics6 ?, X' R% b( y$ @4 n
Volume 46 Number 6% j U5 i, q( C; R0 q% `+ `. F
July 2007 540-543. Z& G' M0 Z1 v& _% f5 g
© 2007 Sage Publications; C: i3 ?7 |7 {1 F. |1 v9 m8 l
10.1177/0009922806296651
7 L$ ]- p. u6 N5 Q6 A4 Lhttp://clp.sagepub.com' P3 u8 ~. w' o Y! \- m& w6 v
hosted at
! d' M1 b; E# j6 Z9 A$ ghttp://online.sagepub.com! Z$ n: }6 g; R. y+ _
Precocious puberty in boys, central or peripheral,. M# e5 e4 { a; Q# u# ~+ J. @
is a significant concern for physicians. Central
* x. m, a( `$ y" Aprecocious puberty (CPP), which is mediated
% e! v! S1 T4 Mthrough the hypothalamic pituitary gonadal axis, has
y9 F1 T9 U) I% ~& z* I; ?a higher incidence of organic central nervous system/ z& S0 W4 l0 i; ? E
lesions in boys.1,2 Virilization in boys, as manifested& p3 d# i9 p6 E$ K
by enlargement of the penis, development of pubic
. |( n0 Y K" [; @hair, and facial acne without enlargement of testi-
6 P' v* }: o! h* E& `8 [, j1 b" Scles, suggests peripheral or pseudopuberty.1-3 We6 P8 J3 U) i9 n# x" q
report a 16-month-old boy who presented with the1 P. b$ ?" g( i. M6 `
enlargement of the phallus and pubic hair develop-
* q, F, K7 c+ H4 Y* O4 Wment without testicular enlargement, which was due
% {) z8 E& U/ u9 X* Rto the unintentional exposure to androgen gel used by6 H* @! v" w3 d# T
the father. The family initially concealed this infor-
8 w, X E: i6 }) nmation, resulting in an extensive work-up for this2 m) D# W# g- j+ M
child. Given the widespread and easy availability of/ b4 b3 \# M0 P; i; w( Z
testosterone gel and cream, we believe this is proba-
+ {! S% s3 n& r; X3 {& ^bly more common than the rare case report in the* q: o! d) H+ @2 \, X
literature.4
5 o% k# d, L% k8 h5 C7 G' I' lPatient Report2 w+ I. |+ h, i4 j9 g8 `! Y
A 16-month-old white child was referred to the
- K1 ]* x7 _4 c$ Z, `. e G$ u* jendocrine clinic by his pediatrician with the concern3 N/ a8 [( T9 Q o; i" Y% y' V
of early sexual development. His mother noticed0 P2 X) d% S) J- [
light colored pubic hair development when he was/ g0 C* P/ u, I- W: u6 V
From the 1Division of Pediatric Endocrinology, 2University of
" B+ h' b- q5 ~South Alabama Medical Center, Mobile, Alabama.
9 w- G, L& M( {# \$ j" w3 pAddress correspondence to: Samar K. Bhowmick, MD, FACE,
. T7 n3 o5 K9 ]9 k5 e/ @2 sProfessor of Pediatrics, University of South Alabama, College of
" n+ C* [+ h* r" f1 d1 N5 HMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;( A+ H, P/ G3 y7 f. p( B& z
e-mail: [email protected].; L. R( D+ n6 p" b/ b) Z
about 6 to 7 months old, which progressively became* Y) O! _4 p! Z7 s
darker. She was also concerned about the enlarge-/ M+ k m4 {% ~4 B
ment of his penis and frequent erections. The child
& U* S0 \: ?' [4 E3 [; g% k% Lwas the product of a full-term normal delivery, with
, {5 f, F1 N4 _" F- Ka birth weight of 7 lb 14 oz, and birth length of
" | s( o/ j4 |, |$ j- O20 inches. He was breast-fed throughout the first year
$ H, k# R3 ~3 @# Z# k' ^; {/ ^of life and was still receiving breast milk along with
+ H# z s! |* d; isolid food. He had no hospitalizations or surgery,; R _( X' P9 e) y5 h+ r
and his psychosocial and psychomotor development
0 M; Z# }$ I( b! }# x @4 Gwas age appropriate.
! q3 T' o" R) |& @# cThe family history was remarkable for the father,
% Q3 S' R" e6 K! _- ?, Ywho was diagnosed with hypothyroidism at age 16,
5 ?& I- G' \+ S: b& Pwhich was treated with thyroxine. The father’s
& \0 b L: V. t2 t! X0 Mheight was 6 feet, and he went through a somewhat
# M# P9 B2 L5 B. [early puberty and had stopped growing by age 14.0 L9 }/ p% U5 Y8 Z# t- ^$ \
The father denied taking any other medication. The$ a: m" p- |& f, ^: k
child’s mother was in good health. Her menarche x- C. J: Y- Y4 i) ~
was at 11 years of age, and her height was at 5 feet
1 M2 [ B/ ~) R1 w6 ?% F5 inches. There was no other family history of pre-
3 t# a' e1 D) L9 h- p1 o6 d( q/ @0 s4 icocious sexual development in the first-degree rela-& K4 G. F& k) Q( J/ \3 J4 K
tives. There were no siblings.2 n7 j- D8 D. X8 w* x# @0 m
Physical Examination
5 v2 w0 K) P, \: G QThe physical examination revealed a very active,
, x, e: p% ]" zplayful, and healthy boy. The vital signs documented7 H8 f! }6 Z0 t; F% L
a blood pressure of 85/50 mm Hg, his length was% \* ?. x( |/ `, a
90 cm (>97th percentile), and his weight was 14.4 kg
, H3 k3 K5 [0 t+ B. | T4 V(also >97th percentile). The observed yearly growth
: o, m y, B1 a) b8 ]velocity was 30 cm (12 inches). The examination of; [. F5 ?4 }5 I) X- y
the neck revealed no thyroid enlargement. r* k* a6 v% K% { R' l
The genitourinary examination was remarkable for6 u* R0 t/ I2 W4 `/ g
enlargement of the penis, with a stretched length of
( q, R( {7 B4 }6 \) l8 cm and a width of 2 cm. The glans penis was very well a4 f ^) o/ V: K$ s- O( y
developed. The pubic hair was Tanner II, mostly around' D# Z* m' W$ n6 d+ [9 ]$ v9 g
540
+ ?* _* z: G6 zat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from, m5 b* Z L0 w$ a6 o0 T
the base of the phallus and was dark and curled. The4 b. i; y- c" s' i/ K; Y+ ^# B
testicular volume was prepubertal at 2 mL each.$ X$ i; Q4 W, T# o/ j
The skin was moist and smooth and somewhat+ \- ` S$ A# C5 n/ p( p
oily. No axillary hair was noted. There were no' F) x# Q4 ~9 H; u# w; P5 i5 U# f0 _
abnormal skin pigmentations or café-au-lait spots.
3 T7 |; v! D' H+ KNeurologic evaluation showed deep tendon reflex 2+
c( x! f4 Y8 {5 q( o7 ]* X0 vbilateral and symmetrical. There was no suggestion1 q* o. S8 G, B `# y; P
of papilledema.- K# Y6 R) F; L1 M* j! {$ Q# v
Laboratory Evaluation; ]1 w, c$ V6 [2 y! B0 D8 j
The bone age was consistent with 28 months by7 w! ~2 M( d+ w4 Q) G
using the standard of Greulich and Pyle at a chrono-
L. c1 A8 r$ S- b" O: f( Alogic age of 16 months (advanced).5 Chromosomal
7 a4 b% t5 M3 ?karyotype was 46XY. The thyroid function test
: p* q2 s6 R4 n6 Nshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
2 r7 }2 _' h1 Q& l I, Blating hormone level was 1.3 µIU/mL (both normal). b4 m$ b& m. x4 H$ _& u
The concentrations of serum electrolytes, blood
# W9 @9 y$ E9 V4 Xurea nitrogen, creatinine, and calcium all were8 O- e7 |" b$ ~/ \/ Z
within normal range for his age. The concentration
" F& q# ]* L! \1 Gof serum 17-hydroxyprogesterone was 16 ng/dL/ L) [+ L* g, `( v- a
(normal, 3 to 90 ng/dL), androstenedione was 20
5 o- {( D2 n) o1 E4 Cng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
, U, Y8 H: @5 [3 Oterone was 38 ng/dL (normal, 50 to 760 ng/dL),
: q7 q9 ~9 j X* ]desoxycorticosterone was 4.3 ng/dL (normal, 7 to
& |3 q& v. \9 j }- r49ng/dL), 11-desoxycortisol (specific compound S)
5 `: G' t% e) J, o6 Mwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
! m5 {& _1 L7 X; D% d" Z4 Z$ xtisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
b% ?- q3 Q. f1 R# [( ^. Ftestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
8 t- O4 N* O7 M5 P3 L0 Tand β-human chorionic gonadotropin was less than
- |0 `- E9 R% M4 r; e5 mIU/mL (normal <5 mIU/mL). Serum follicular
0 b0 |! o/ x/ Jstimulating hormone and leuteinizing hormone
2 k0 Y2 E2 S! {1 j1 e3 Kconcentrations were less than 0.05 mIU/mL
7 c/ b3 \' f1 E2 H" n+ C(prepubertal).
w' l3 k9 p/ b WThe parents were notified about the laboratory
+ e: p; A; a! o0 M5 h) qresults and were informed that all of the tests were
5 V3 @7 {8 l( a. qnormal except the testosterone level was high. The4 i+ `7 _/ s7 t3 d
follow-up visit was arranged within a few weeks to
' z/ H1 W% k5 r# _3 ?$ ^$ F8 Kobtain testicular and abdominal sonograms; how-! {$ K! J" E/ M/ H9 n
ever, the family did not return for 4 months.1 b$ L8 L& r) [
Physical examination at this time revealed that the
/ Z7 Y. d/ ~6 q0 O( L1 mchild had grown 2.5 cm in 4 months and had gained
4 i$ h& t3 _; c3 ~- C$ g( H2 kg of weight. Physical examination remained
& G) i7 o) T* k8 m" a5 s; ?unchanged. Surprisingly, the pubic hair almost com-
% Y' W, e) v% C6 V5 F7 u. Wpletely disappeared except for a few vellous hairs at
: P8 \: _( d8 I) Q9 R7 a0 ethe base of the phallus. Testicular volume was still 2
1 ?! e( r4 }3 m7 `" H$ XmL, and the size of the penis remained unchanged.
. ?. d3 n! M1 SThe mother also said that the boy was no longer hav-" R- H4 O/ C, Q
ing frequent erections.
1 x6 @) J+ O$ Y/ O; o4 z7 W G0 oBoth parents were again questioned about use of
- X5 u8 ?5 z! F7 g/ cany ointment/creams that they may have applied to$ t$ ~9 O9 c: t: O, ~
the child’s skin. This time the father admitted the. N5 E" ?* d; h. G9 Q) F, q4 x# d
Topical Testosterone Exposure / Bhowmick et al 541' a- t x3 @0 d1 S8 x7 D! b# Y
use of testosterone gel twice daily that he was apply-" z7 p9 g1 _+ \) ?, J+ y* H- z
ing over his own shoulders, chest, and back area for+ Z9 b) v1 Q6 |7 Z' i, [2 r0 m
a year. The father also revealed he was embarrassed; t1 C; H/ O7 _1 w' A+ U
to disclose that he was using a testosterone gel pre-
1 |! u& R+ a( b* ~scribed by his family physician for decreased libido
& M5 g$ S0 @6 P5 }3 B; q& \secondary to depression.' ^5 |0 F8 p! q) Z
The child slept in the same bed with parents.
/ [3 f' M- \7 w9 H8 f& vThe father would hug the baby and hold him on his% C8 z7 V! c' n$ S
chest for a considerable period of time, causing sig-* ~( O) Q: Z) d$ W
nificant bare skin contact between baby and father.
4 X# t$ ]) h, oThe father also admitted that after the phone call,9 s# r# I& C4 L
when he learned the testosterone level in the baby% K" i) P/ o: X0 @5 @) v$ q
was high, he then read the product information
: H5 Q7 M8 F- _! H, p, A1 Tpacket and concluded that it was most likely the rea-
* k6 r4 [- Y3 M& ]8 P ^: t* |$ @son for the child’s virilization. At that time, they
( f5 C+ O& w" I6 ]1 Sdecided to put the baby in a separate bed, and the2 d/ s( Z `, d2 M+ l. D
father was not hugging him with bare skin and had
! r9 ~5 m; S; v2 \been using protective clothing. A repeat testosterone
0 y \/ X- }2 ^; P/ \test was ordered, but the family did not go to the, |+ C2 f; \' O1 {4 p
laboratory to obtain the test.
* T% n$ P" B6 QDiscussion
- S! L6 X- B( M9 N' J7 a3 CPrecocious puberty in boys is defined as secondary
0 h1 K2 d3 Q6 N; O4 B! gsexual development before 9 years of age.1,4
! J* V6 v y1 ~+ n, TPrecocious puberty is termed as central (true) when( _/ @5 K0 F5 E7 F
it is caused by the premature activation of hypo-+ F* R9 r# p: ?
thalamic pituitary gonadal axis. CPP is more com-
- I3 b3 i+ _$ R" gmon in girls than in boys.1,3 Most boys with CPP
0 e+ U4 c7 R, _7 {" j/ Nmay have a central nervous system lesion that is
" R9 z" b y* jresponsible for the early activation of the hypothal-
* S# _+ r8 a, Ramic pituitary gonadal axis.1-3 Thus, greater empha-; G" W) B% n0 T3 d6 ^
sis has been given to neuroradiologic imaging in
* n' |0 N3 ~9 r# X3 H9 Yboys with precocious puberty. In addition to viril-$ D" w* R6 g8 r- Q ?/ N
ization, the clinical hallmark of CPP is the symmet-
0 w; ?. G+ Q+ w* j" Erical testicular growth secondary to stimulation by x4 K( ]( R) a, B( }! @* n# J
gonadotropins.1,3" \7 d; j* N) N \: R0 S+ g1 I/ U
Gonadotropin-independent peripheral preco-& L. d+ N6 `7 {
cious puberty in boys also results from inappropriate
. |7 G7 v6 M$ Uandrogenic stimulation from either endogenous or5 i9 E3 b% X; k: m3 f1 z; _
exogenous sources, nonpituitary gonadotropin stim-
& s/ r* n: ?1 ? g% G- e% Yulation, and rare activating mutations.3 Virilizing7 ~- v0 T! C' g8 \) r2 {
congenital adrenal hyperplasia producing excessive% Z# R5 S6 x- B4 d; m
adrenal androgens is a common cause of precocious
, a% a# B4 z; y+ p. ypuberty in boys.3,4
9 S4 @0 e3 E0 r$ g; q* [7 t$ W' YThe most common form of congenital adrenal$ ^4 a3 k# L# H. D0 F0 W( s
hyperplasia is the 21-hydroxylase enzyme deficiency.
' H L' b% Z* H% t# vThe 11-β hydroxylase deficiency may also result in4 J( w( \! [) q/ x
excessive adrenal androgen production, and rarely,, v: i2 E4 @ @4 \8 U8 e- q7 r+ j
an adrenal tumor may also cause adrenal androgen; R. o* F" t' W* V0 U! ~
excess.1,3* J+ A) H# h3 ]" q; k# ~% D
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
$ I _" A0 D% p0 J, `0 Q. v5 ^542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
) z3 N2 s- m. V8 a% QA unique entity of male-limited gonadotropin-
$ n. I- W; B) H% p" P& E( mindependent precocious puberty, which is also known @) U& a; _3 S
as testotoxicosis, may cause precocious puberty at a
, [1 J$ b3 p/ g7 Q' lvery young age. The physical findings in these boys
! Y: h& L; h& O3 a$ \( u; {with this disorder are full pubertal development,$ v, d+ C. H$ b6 V# ]
including bilateral testicular growth, similar to boys, r& c! n! G; U
with CPP. The gonadotropin levels in this disorder
9 i8 w2 l% A# e. w, qare suppressed to prepubertal levels and do not show5 \" ?& i2 h I) u* q
pubertal response of gonadotropin after gonadotropin-
+ ^' c6 Q3 c4 F1 X8 E; ~$ o# V) qreleasing hormone stimulation. This is a sex-linked
* ~ | z* t& |' n: mautosomal dominant disorder that affects only
; k1 u! Q9 g) X, y A& _males; therefore, other male members of the family
. ]/ W1 }& V/ i% i& gmay have similar precocious puberty.3
; r( I) s3 `3 Y g) Z, lIn our patient, physical examination was incon-
& t0 L- c, L/ H8 h6 F3 Zsistent with true precocious puberty since his testi-
+ b1 j4 w$ h# Tcles were prepubertal in size. However, testotoxicosis3 n U$ A6 p* a& g
was in the differential diagnosis because his father+ [/ [2 j8 l; k, Z* J
started puberty somewhat early, and occasionally,
9 G% o3 g5 G8 u+ Z$ h5 htesticular enlargement is not that evident in the& e# L) A, X6 s
beginning of this process.1 In the absence of a neg-" j" W4 p- m" `' {: D. ~6 n8 |, d1 n
ative initial history of androgen exposure, our
+ i* a5 ^. K7 u9 K2 H ]" S3 ~/ Ebiggest concern was virilizing adrenal hyperplasia,
* @3 n, c; j9 Peither 21-hydroxylase deficiency or 11-β hydroxylase
9 @0 F" m6 b% K, u# Y% Bdeficiency. Those diagnoses were excluded by find-
, c8 X, }7 G/ w% d A; Hing the normal level of adrenal steroids.9 [6 w9 E+ ?$ y1 S/ M* G8 x
The diagnosis of exogenous androgens was strongly: C% T% p+ E0 i9 W% C5 ?
suspected in a follow-up visit after 4 months because) O# j+ J4 l& ~* d4 ~" N c) ], W5 R
the physical examination revealed the complete disap-' \/ S$ W: F# P9 i
pearance of pubic hair, normal growth velocity, and5 ?1 Q' i1 K" R' |8 P: S. z
decreased erections. The father admitted using a testos-
3 q* t4 p* j$ s$ Y" Zterone gel, which he concealed at first visit. He was; J: @( D8 |9 P& n6 q) B
using it rather frequently, twice a day. The Physicians’
2 b7 e7 W4 N# c! V4 cDesk Reference, or package insert of this product, gel or0 R2 E7 E% D9 r. m0 a
cream, cautions about dermal testosterone transfer to
7 ~4 T1 ~, g$ O' y, X" Punprotected females through direct skin exposure.& u' N2 U* x# X- z$ s
Serum testosterone level was found to be 2 times the
9 t/ p5 }% d! b3 i6 k6 l; G7 vbaseline value in those females who were exposed to
5 ^2 y: I. j, ~4 [( h8 T8 Veven 15 minutes of direct skin contact with their male
; B0 G% v7 ?0 hpartners.6 However, when a shirt covered the applica-
! R) a c# F$ d% ction site, this testosterone transfer was prevented.7 Z4 X6 s5 q6 Z+ ?
Our patient’s testosterone level was 60 ng/mL,
0 \3 `) p0 n/ d! x' w% @" Iwhich was clearly high. Some studies suggest that
. p( r5 G5 }- Rdermal conversion of testosterone to dihydrotestos-
4 ^6 P$ K' i. p! E( ?terone, which is a more potent metabolite, is more U$ ]- f7 Q' i1 Q% l8 F% O
active in young children exposed to testosterone: e6 h7 U0 \, C: t
exogenously7; however, we did not measure a dihy-
5 E" s, j7 x q& }( B0 a8 sdrotestosterone level in our patient. In addition to- s. B& W( i# j! w7 N% F1 c( B7 Q
virilization, exposure to exogenous testosterone in. B# e8 i) g# y l, i" Z) D* ?5 R
children results in an increase in growth velocity and+ d- Z6 H! B3 q' F5 d" w6 K" h
advanced bone age, as seen in our patient.
5 j J# h* b% c$ M' @The long-term effect of androgen exposure during7 W! N# e: F4 \5 ?) Z
early childhood on pubertal development and final. D' q6 e: s2 I1 f% ?; u
adult height are not fully known and always remain) `- q U& u7 B$ K
a concern. Children treated with short-term testos-
% M5 V! A F, l& @; A, Y2 Vterone injection or topical androgen may exhibit some9 T) r% B9 S) H+ D
acceleration of the skeletal maturation; however, after X- a' Z% s& v5 |
cessation of treatment, the rate of bone maturation
9 w2 p3 O( o. ^3 _" z% u2 e% ~2 Gdecelerates and gradually returns to normal.8,9
0 b3 k; L v, S0 j" A: J; ?3 r& T# oThere are conflicting reports and controversy& C' f4 t* H4 n
over the effect of early androgen exposure on adult
. T- b$ g; T8 F z1 mpenile length.10,11 Some reports suggest subnormal
B( B! U Q, J$ q# f) I2 ]adult penile length, apparently because of downreg-
6 t7 ~- `0 @+ u; x" A$ E7 S" q, gulation of androgen receptor number.10,12 However,* J( U8 r4 ?6 b
Sutherland et al13 did not find a correlation between
: m, U! V/ |; ?' ~. xchildhood testosterone exposure and reduced adult( c$ |! a# t$ O; \2 `$ W4 d
penile length in clinical studies. [: [. h1 B7 }# m
Nonetheless, we do not believe our patient is
. v: b1 A2 Q: v& O7 |going to experience any of the untoward effects from L5 e" F) ]7 [0 h
testosterone exposure as mentioned earlier because
, b# f1 I: e; h' S! d+ ^3 I" a, Fthe exposure was not for a prolonged period of time.* l- N t! y! k) h# M/ h1 m
Although the bone age was advanced at the time of
2 O6 x8 J) ~/ p3 rdiagnosis, the child had a normal growth velocity at( {2 h% M( i: |1 P1 n4 y
the follow-up visit. It is hoped that his final adult
' g X& W- Z1 }& U% pheight will not be affected.( B# x; J1 O" H8 l7 L* I
Although rarely reported, the widespread avail-/ x& T& e3 k. K2 j0 }1 |! x; w5 ?
ability of androgen products in our society may
2 z. f2 A- z5 ]/ Sindeed cause more virilization in male or female7 b$ |4 s. G$ T1 V/ A$ m- w$ u% @
children than one would realize. Exposure to andro-" j' C: z# X; X
gen products must be considered and specific ques-
/ h* s4 d* i0 \9 M& dtioning about the use of a testosterone product or
7 N8 Y2 A0 `- K; zgel should be asked of the family members during
/ T. ?- ~2 Q# p3 v/ o, Vthe evaluation of any children who present with vir-1 N% {0 t Q1 L& q, u8 `$ H
ilization or peripheral precocious puberty. The diag-
7 J& E' G7 O( z- _nosis can be established by just a few tests and by' R% G4 p ~) O q. O
appropriate history. The inability to obtain such a
) T4 |' [. @ G4 \history, or failure to ask the specific questions, may
. P- n7 _ H4 R, Lresult in extensive, unnecessary, and expensive
( t; ~( n4 z, B& u, o! } \& Ginvestigation. The primary care physician should be5 L9 E7 L8 |: K6 K6 B5 Q, l
aware of this fact, because most of these children6 T5 D1 |! l- N6 S& D
may initially present in their practice. The Physicians’9 e) q2 K0 K) j' m
Desk Reference and package insert should also put a
4 `0 X0 ~: T6 Fwarning about the virilizing effect on a male or
1 f8 e* ~* D; |' o- C/ Mfemale child who might come in contact with some-( J1 P6 M" O( |& H
one using any of these products.
* m' q/ K0 r1 G7 Q+ F3 n: _' YReferences
( ]4 i7 w! F( U" `( y G1. Styne DM. The testes: disorder of sexual differentiation- y% P. i( G/ W+ U
and puberty in the male. In: Sperling MA, ed. Pediatric
! c' K: M' Z+ E5 t; yEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
1 x& U) R* `' Y( L3 a2002: 565-628.
& W. P5 r7 A$ S# }* }2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious0 Y! ^5 `; \" H; B! C& y
puberty in children with tumours of the suprasellar pineal |
|