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Sexual Precocity in a 16-Month-Old* D" I# C! Q% N+ `3 p- A) |9 |$ O
Boy Induced by Indirect Topical
+ O0 K# i4 p2 L1 f5 i7 jExposure to Testosterone$ c& Y4 g# B% g: j8 f$ ?
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
' a. w/ m2 s3 r1 @8 Y2 E" Dand Kenneth R. Rettig, MD1; u, n \4 u2 r% H f
Clinical Pediatrics6 t% T; b K! b- O U- C
Volume 46 Number 6
1 F9 J7 v2 N8 ^4 ?0 pJuly 2007 540-543
0 x8 k- M- }( I Y- l6 c+ s© 2007 Sage Publications
. u3 @, ~$ g' n9 I! u2 i10.1177/0009922806296651
7 Y% K0 R7 {% Z, D$ E2 @( z" thttp://clp.sagepub.com: J9 o' @5 ?# \: o+ f
hosted at1 d+ X" A5 V4 i _% i8 R& S
http://online.sagepub.com
& ]0 O) T5 C5 E% K, u6 O( ?Precocious puberty in boys, central or peripheral,
' F/ J% N* F+ T( g ~# W K% ]4 iis a significant concern for physicians. Central
5 x; ]: ]7 N0 N& y0 u8 e) jprecocious puberty (CPP), which is mediated6 G& c( p" q4 _8 h f
through the hypothalamic pituitary gonadal axis, has
" Y& r6 l& F% V1 da higher incidence of organic central nervous system- ]3 j, ~* @) N/ C' h \
lesions in boys.1,2 Virilization in boys, as manifested) D$ c4 v6 f& K& \ `
by enlargement of the penis, development of pubic
1 w9 J# u" W! I. h& Dhair, and facial acne without enlargement of testi-
6 c/ J0 u- D, F% ~2 k# ]; u, Xcles, suggests peripheral or pseudopuberty.1-3 We
6 u+ U$ A5 w# P+ S) P# mreport a 16-month-old boy who presented with the
' ~ a2 s1 L* }. V# e0 ]5 G9 f5 renlargement of the phallus and pubic hair develop-
0 Z8 @& ]0 |. r, ]' s" _ment without testicular enlargement, which was due
7 z6 C+ O4 `* p, w8 kto the unintentional exposure to androgen gel used by k4 L1 I, y" j2 ~
the father. The family initially concealed this infor-
* R6 z& B. v& h+ U3 _mation, resulting in an extensive work-up for this
% v' r, V+ Z$ I8 t8 r, Schild. Given the widespread and easy availability of
! n, u7 I. g6 _* otestosterone gel and cream, we believe this is proba-- Q+ |) e. ]2 ^( }
bly more common than the rare case report in the7 G+ S$ ?. V) V, e
literature.4" K, K7 _! x, R8 i) A/ [; t
Patient Report1 I4 y3 I+ q6 I: R, _2 }# T4 X
A 16-month-old white child was referred to the
: K# Y0 s8 {2 r% f3 a/ H! Dendocrine clinic by his pediatrician with the concern
) y/ S; L# b# Y% tof early sexual development. His mother noticed
7 P0 u6 k2 j1 ]( _0 _light colored pubic hair development when he was4 g# n% U) D+ d6 ^
From the 1Division of Pediatric Endocrinology, 2University of
# j/ e- b' s+ b3 W7 ySouth Alabama Medical Center, Mobile, Alabama.
( i; J9 h- `. f/ ^& u* W7 uAddress correspondence to: Samar K. Bhowmick, MD, FACE,
7 I# J9 h0 X* \6 @" O% U. N4 bProfessor of Pediatrics, University of South Alabama, College of
* E2 r7 o$ C5 t+ lMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
' q* H* W3 T* i+ U5 ~* d; @' X: z4 _7 Ae-mail: [email protected].1 ]+ Q `6 W" z: e
about 6 to 7 months old, which progressively became6 r4 ]5 g9 [* j) R" |. |4 v9 s
darker. She was also concerned about the enlarge-
" @1 K- w* d' ?ment of his penis and frequent erections. The child
; r: V4 {& ]8 U+ q2 _9 @0 Z4 Twas the product of a full-term normal delivery, with
1 N/ R, i3 b) d; Ba birth weight of 7 lb 14 oz, and birth length of r6 U" n4 i2 l! {8 t% B
20 inches. He was breast-fed throughout the first year
p" v$ C/ q, |: @: w/ vof life and was still receiving breast milk along with
0 ] h, E3 u) v$ S4 usolid food. He had no hospitalizations or surgery,
3 @9 ^% I1 x' I7 L' m" Wand his psychosocial and psychomotor development
. \ S! b: N- u2 s4 Jwas age appropriate.
+ N/ H! i0 i; ^8 F' _The family history was remarkable for the father,
, c6 f: f; H7 i3 Awho was diagnosed with hypothyroidism at age 16,1 J, S0 C& [1 F# f
which was treated with thyroxine. The father’s" D& }$ d$ n: v- n/ x1 A' |! G- T
height was 6 feet, and he went through a somewhat% w5 Z0 p6 N9 H
early puberty and had stopped growing by age 14.
1 }3 f) u& d* P" rThe father denied taking any other medication. The; K" C' l, o' [' N9 u/ |
child’s mother was in good health. Her menarche2 f* o& V7 u0 l/ N! t$ T
was at 11 years of age, and her height was at 5 feet
7 a$ Q5 J$ \2 ~, j: N5 inches. There was no other family history of pre-; v9 Y/ q* a! j' y H. t& t9 ?
cocious sexual development in the first-degree rela-
6 ^! n4 ]& D7 e+ K2 @3 D" {! u# R stives. There were no siblings.
7 R. U3 a1 s3 M; n3 F4 z/ bPhysical Examination
5 Z$ q9 e! c! w9 W( ?The physical examination revealed a very active,
+ d* d! ]7 J1 g, q2 \! Lplayful, and healthy boy. The vital signs documented3 p5 Y- T) t0 e2 d: Y) ?5 R
a blood pressure of 85/50 mm Hg, his length was
2 G; E9 w$ w8 I" N90 cm (>97th percentile), and his weight was 14.4 kg
/ W& w$ N2 e) c6 m1 M1 Y8 ?(also >97th percentile). The observed yearly growth
% E" |2 |! B: p- bvelocity was 30 cm (12 inches). The examination of X4 Y8 o' v' W j
the neck revealed no thyroid enlargement.
& _ [$ S3 M9 dThe genitourinary examination was remarkable for" H% N/ T6 f' V' J6 l& F2 ?' L
enlargement of the penis, with a stretched length of* E2 J. e# s/ I4 f$ j
8 cm and a width of 2 cm. The glans penis was very well
) r1 w6 @8 s. Odeveloped. The pubic hair was Tanner II, mostly around1 {4 u3 w# `) ~( w4 Q7 W
540
, t& F1 [( e, i5 p( f( cat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from& Y1 Y0 }! X2 Q1 s: P# {) ? ]
the base of the phallus and was dark and curled. The+ f3 Z' P, Q% W7 g+ F
testicular volume was prepubertal at 2 mL each.
% m h8 [/ E) f& }, xThe skin was moist and smooth and somewhat7 Z/ b3 [; x G5 ^; \) b$ h
oily. No axillary hair was noted. There were no: `5 G5 \. w* d
abnormal skin pigmentations or café-au-lait spots.
" `+ [* S7 R# S* I7 }Neurologic evaluation showed deep tendon reflex 2+
. u6 a8 b7 c4 {: y* Nbilateral and symmetrical. There was no suggestion
7 e. n( S! _9 oof papilledema.0 k2 G6 @* e4 C8 }
Laboratory Evaluation2 \+ p8 n) ?! V" d# X- ?) Z
The bone age was consistent with 28 months by
3 |3 D3 N' B, q9 b4 @ }. Wusing the standard of Greulich and Pyle at a chrono-* \+ Z: o( V) p1 D4 D9 ]3 E
logic age of 16 months (advanced).5 Chromosomal+ z, y$ W/ Y! A; P; D) _ z
karyotype was 46XY. The thyroid function test8 R8 x5 z0 U; I1 U: G
showed a free T4 of 1.69 ng/dL, and thyroid stimu-+ p4 U( i7 v$ v! x; _; @4 {3 o4 F
lating hormone level was 1.3 µIU/mL (both normal).. _7 j4 T1 d9 k
The concentrations of serum electrolytes, blood% ^1 k3 X7 V9 m% I+ c( E
urea nitrogen, creatinine, and calcium all were
* k* y/ n7 y, Wwithin normal range for his age. The concentration+ L0 t5 s7 A; V! L$ |( X6 g$ f
of serum 17-hydroxyprogesterone was 16 ng/dL9 O( W F4 P. `) f" g8 i& ^5 O
(normal, 3 to 90 ng/dL), androstenedione was 204 T2 Y1 `9 J' G4 A8 ^! ^- n
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-3 u+ E' B7 s2 A3 r) L' X3 Y: d& G
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
% L# J8 n4 t% j! adesoxycorticosterone was 4.3 ng/dL (normal, 7 to0 i8 S& O( c9 y8 T
49ng/dL), 11-desoxycortisol (specific compound S)/ i$ @ w: H- @: t7 ~
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
9 Z* T5 B+ Z' H y) g# @tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
$ e J5 r& i( b& P1 |# t. H4 O$ h" gtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
$ Z# w% y& x+ f1 [* J! ?' Jand β-human chorionic gonadotropin was less than* _) y) h2 _! Y9 p
5 mIU/mL (normal <5 mIU/mL). Serum follicular0 X, K) O2 ~, {+ g' H; u" U
stimulating hormone and leuteinizing hormone3 E. t4 ^& z+ o
concentrations were less than 0.05 mIU/mL9 |7 s8 O) q: `! h$ c: Q: x. m
(prepubertal).
0 C! C1 h8 e; ~ mThe parents were notified about the laboratory
' c% _% E! A7 Q) Q, tresults and were informed that all of the tests were
' i2 l1 ?$ O, e3 cnormal except the testosterone level was high. The. h! x1 @5 ^0 s6 j! t- U# o
follow-up visit was arranged within a few weeks to; X/ P. Q' Y7 b- e
obtain testicular and abdominal sonograms; how-$ R; I4 e) s1 Z& [0 y* r
ever, the family did not return for 4 months.
% }/ f1 _+ ], u: M% _Physical examination at this time revealed that the* _( Q" N% O1 c0 b% f: j. q) ?
child had grown 2.5 cm in 4 months and had gained
$ d0 P8 [( N# W4 F" r& ~2 kg of weight. Physical examination remained; h% a. D" w" ]+ w9 J+ ^; g
unchanged. Surprisingly, the pubic hair almost com-# d Z* e: K2 W" d
pletely disappeared except for a few vellous hairs at; u8 X+ m. `0 ^, V* i% B' E# O
the base of the phallus. Testicular volume was still 2* R; c% w( T- {1 s S
mL, and the size of the penis remained unchanged.
, I9 t8 {6 i- M- f4 ~% [5 T2 wThe mother also said that the boy was no longer hav-1 e9 H- W5 h$ X" w: a
ing frequent erections.' c& K, l* N0 Z# V" [
Both parents were again questioned about use of
8 D# U6 h y1 p( N4 {any ointment/creams that they may have applied to
* `* V/ x' K5 {: x% dthe child’s skin. This time the father admitted the
1 b O# ~5 W$ V) _6 ?2 ^ z6 V! _$ w) T2 xTopical Testosterone Exposure / Bhowmick et al 541
% j: O* N. L& ]7 nuse of testosterone gel twice daily that he was apply-
& w; q9 O' N& J$ L E3 }ing over his own shoulders, chest, and back area for1 f6 Q: B5 s# Z2 b
a year. The father also revealed he was embarrassed" X% }3 \, t& D
to disclose that he was using a testosterone gel pre-5 n/ p6 C" l& s; C7 u- w
scribed by his family physician for decreased libido
2 L6 I; Y; _" r& Esecondary to depression.
- a" j; ^) j0 r& @1 c+ [/ h. ~/ H dThe child slept in the same bed with parents.* j6 v) E' J) `8 [/ w8 l3 ]
The father would hug the baby and hold him on his
, p0 g5 T( r' U. N# Lchest for a considerable period of time, causing sig-
# A l# K& ~' a% fnificant bare skin contact between baby and father.: O( @" p# Z _0 t( q" M) v* d# N
The father also admitted that after the phone call,
% k( l6 D3 e; Q7 i4 fwhen he learned the testosterone level in the baby
. w# X) X$ w) P Awas high, he then read the product information
2 R" F7 \! ~! U) N( d) npacket and concluded that it was most likely the rea-4 l! Y. ?5 r+ y4 F" O
son for the child’s virilization. At that time, they
1 R' t5 S3 u+ cdecided to put the baby in a separate bed, and the
* X! s+ M3 C/ F4 A' r, b4 pfather was not hugging him with bare skin and had* G: J- B9 E9 u' w: j9 q; Y/ O# [3 d
been using protective clothing. A repeat testosterone* _9 H7 W% n9 g
test was ordered, but the family did not go to the/ r& u6 p% ]- P" t' s# j0 |
laboratory to obtain the test.
6 L; x9 Y% k- X% YDiscussion7 r8 \4 E3 U [$ A" I
Precocious puberty in boys is defined as secondary; N8 ~) O" {, x& F3 E
sexual development before 9 years of age.1,4
^! D: x" r( W6 m3 A n) s' MPrecocious puberty is termed as central (true) when; }0 Z+ b9 r/ ^9 b
it is caused by the premature activation of hypo-. H* F; h7 J" z( O
thalamic pituitary gonadal axis. CPP is more com-- x+ Z( m% d, @' Y
mon in girls than in boys.1,3 Most boys with CPP: w. N1 P2 H; ^# T& c
may have a central nervous system lesion that is
' i+ `" @* V$ @' a Zresponsible for the early activation of the hypothal-8 A3 c9 x+ Z ?, V @7 {1 K
amic pituitary gonadal axis.1-3 Thus, greater empha-* ]$ ^' e' n8 f
sis has been given to neuroradiologic imaging in
@( r8 E' q, ^' Xboys with precocious puberty. In addition to viril-
2 [2 p: M, m! A, c3 D, Rization, the clinical hallmark of CPP is the symmet-/ P' S# n3 S( e4 v1 @0 _
rical testicular growth secondary to stimulation by
8 r! Z o+ X$ o* h5 {( X/ v3 Hgonadotropins.1,3
1 m! d: R# i/ m" R* yGonadotropin-independent peripheral preco-1 c K6 P# k! v# p/ `8 ]7 j
cious puberty in boys also results from inappropriate3 Y! f8 R9 H* k
androgenic stimulation from either endogenous or
( d [. R5 p; `- q+ pexogenous sources, nonpituitary gonadotropin stim-
; k( q5 R5 @; [/ bulation, and rare activating mutations.3 Virilizing
D% ^6 ~2 {7 A) N2 Hcongenital adrenal hyperplasia producing excessive% K }3 P& I( D
adrenal androgens is a common cause of precocious
) q5 V- }& e- X+ B& u# Hpuberty in boys.3,4
8 V% O! I0 [ r' L B( M7 v+ SThe most common form of congenital adrenal
' x0 i) T5 a' r( i) m N# v* @3 p# B. khyperplasia is the 21-hydroxylase enzyme deficiency.
6 B+ N' d; n6 |+ o$ LThe 11-β hydroxylase deficiency may also result in
% W5 \" ]1 u& Hexcessive adrenal androgen production, and rarely,
4 x) p' X0 ^0 A/ S7 {6 X. T, ^# kan adrenal tumor may also cause adrenal androgen1 _* a l( w z, l1 z7 I; r
excess.1,3
4 f$ S4 I) L. m) M fat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
i% I3 u' m+ l4 |, R- f+ D542 Clinical Pediatrics / Vol. 46, No. 6, July 20070 I6 c' |0 A" u1 N/ D
A unique entity of male-limited gonadotropin-
7 K, E! s/ L+ s- w# @6 V. Oindependent precocious puberty, which is also known
6 N8 b7 O/ g) [4 c" v9 m" K& vas testotoxicosis, may cause precocious puberty at a" J9 u: b$ h( P
very young age. The physical findings in these boys' k, C% ~7 a8 h- E" z) m6 z
with this disorder are full pubertal development,, q. j' Q& ^: H
including bilateral testicular growth, similar to boys
1 x+ O: b( B: Z6 f, Lwith CPP. The gonadotropin levels in this disorder: U) s2 v1 j6 L6 w
are suppressed to prepubertal levels and do not show
- q, D8 H( p6 s! mpubertal response of gonadotropin after gonadotropin-/ Q. f) W) b( }2 h3 M/ [/ ~5 a
releasing hormone stimulation. This is a sex-linked
1 H; A, E3 m( D% l2 ]/ y! Eautosomal dominant disorder that affects only
4 Y2 f& `1 k0 Tmales; therefore, other male members of the family
F; c o$ c, F$ kmay have similar precocious puberty.38 ?: `1 l( X0 _
In our patient, physical examination was incon-, m/ A0 [0 ~9 R
sistent with true precocious puberty since his testi-
, x# X$ K% a$ i n" Acles were prepubertal in size. However, testotoxicosis
$ k* R( D3 F5 y z+ ]8 T# L) Lwas in the differential diagnosis because his father6 N; A; B1 T- A1 N
started puberty somewhat early, and occasionally,
5 }5 a' H' t2 x0 @- A& F% Xtesticular enlargement is not that evident in the
* h7 A: E2 s H6 T% Rbeginning of this process.1 In the absence of a neg-
4 B8 s! p# \# ~( E; Y! a" hative initial history of androgen exposure, our
; k( c9 i+ a+ l% [biggest concern was virilizing adrenal hyperplasia,, d1 q( T2 m; ]' R
either 21-hydroxylase deficiency or 11-β hydroxylase" @5 ^5 ]4 }1 t5 N
deficiency. Those diagnoses were excluded by find-
3 b2 f! p# h& ~& t3 y' king the normal level of adrenal steroids.
8 n! Y. J* |6 iThe diagnosis of exogenous androgens was strongly
6 Z; {* F" j) `8 asuspected in a follow-up visit after 4 months because
& d' v/ l: f8 J1 S/ gthe physical examination revealed the complete disap-
* m K$ o) s9 S- Z' @! r, e8 g% Hpearance of pubic hair, normal growth velocity, and) T$ [) x8 P, ]
decreased erections. The father admitted using a testos-7 d$ o4 Q- M, K$ W: U1 `
terone gel, which he concealed at first visit. He was
1 R- i9 ?0 O, Iusing it rather frequently, twice a day. The Physicians’: R# G. g! t6 ~
Desk Reference, or package insert of this product, gel or i% _' s9 v* @! U
cream, cautions about dermal testosterone transfer to
. }& @3 v4 z. punprotected females through direct skin exposure.* y8 J9 @7 Z9 \$ Z5 p
Serum testosterone level was found to be 2 times the) R/ v0 a7 A8 L* \$ {9 L
baseline value in those females who were exposed to: _& i1 | _4 t" y- {* |2 J9 G
even 15 minutes of direct skin contact with their male
, a% y6 G' K2 Q! @partners.6 However, when a shirt covered the applica-* [ M! h; C" l- T
tion site, this testosterone transfer was prevented." w9 o0 e- Z; B/ j1 ]
Our patient’s testosterone level was 60 ng/mL,8 S" Q; |3 ~: G) Y1 n
which was clearly high. Some studies suggest that
$ B; {% G7 x, R* u/ j# Mdermal conversion of testosterone to dihydrotestos-
& O f n' t" tterone, which is a more potent metabolite, is more
7 K I% I. P Z2 s! i3 lactive in young children exposed to testosterone
6 C5 l0 @3 D1 T% |$ P) kexogenously7; however, we did not measure a dihy-. b# j) {7 S0 j; ?* T" B5 ~0 z7 F' U
drotestosterone level in our patient. In addition to, Y9 ?5 r/ F. p: g+ B
virilization, exposure to exogenous testosterone in+ ]* `% R8 h! x# r4 c
children results in an increase in growth velocity and$ g; x% F1 e6 t) a
advanced bone age, as seen in our patient.
$ i: p8 y' z: I* S( {( ]The long-term effect of androgen exposure during
8 B$ j* M" h' G1 A, rearly childhood on pubertal development and final; s; ]# l& p1 J6 y4 g3 B
adult height are not fully known and always remain* P/ h4 o$ R- _. I# F0 q
a concern. Children treated with short-term testos-3 n/ A( H7 `. H1 o7 Z8 R; V) t
terone injection or topical androgen may exhibit some$ U& N) q; j9 O% P7 U! w6 C- j4 w( ]
acceleration of the skeletal maturation; however, after
$ i: M: Q, Z/ Rcessation of treatment, the rate of bone maturation4 U6 [& U8 I; q/ @. Z" ]: A
decelerates and gradually returns to normal.8,9
* X& e8 z _ b4 ]: a( tThere are conflicting reports and controversy
4 N1 E! n7 B4 ]2 F, Z# nover the effect of early androgen exposure on adult3 u& J! g" A0 Y) m: x. ~* k
penile length.10,11 Some reports suggest subnormal
. `. O0 M/ H+ T* Y2 ]adult penile length, apparently because of downreg-/ a( F7 L0 A+ j3 ?+ _! ~3 q4 T
ulation of androgen receptor number.10,12 However,
8 \- J8 o! E$ T3 L* B% x, oSutherland et al13 did not find a correlation between
: Z2 e; h1 g; r' \. xchildhood testosterone exposure and reduced adult/ O# c6 f3 A7 V. D
penile length in clinical studies.& u6 u2 R. y( ?' z
Nonetheless, we do not believe our patient is
- p' P. F8 i& l6 m3 m! Pgoing to experience any of the untoward effects from
8 o/ q, B* W# l. f v$ ]testosterone exposure as mentioned earlier because
" |: @% X9 {/ y' X% Hthe exposure was not for a prolonged period of time.. P" G& F) X% e/ Y0 D# S
Although the bone age was advanced at the time of/ U0 r. k+ \- o
diagnosis, the child had a normal growth velocity at
0 ]4 M! }8 G% H6 W* Y9 _the follow-up visit. It is hoped that his final adult( @, W [# @' w) x
height will not be affected.( h1 S- {. }3 |' v( C" Z
Although rarely reported, the widespread avail-
* Z" E$ ~+ _" s2 o4 yability of androgen products in our society may
! q) t! e/ _5 T) @indeed cause more virilization in male or female& _# [9 w! C s' h# m& L! G
children than one would realize. Exposure to andro-
8 t( B# E9 ]0 B$ r5 i+ Bgen products must be considered and specific ques-
' g: D. \1 b/ ^ I) B' }- Ytioning about the use of a testosterone product or/ ?: H2 D$ M* S' }: G: D8 u9 b( M
gel should be asked of the family members during
8 b4 {; K1 r8 s, \2 ethe evaluation of any children who present with vir-( W8 {9 B- G+ N; h/ c/ a
ilization or peripheral precocious puberty. The diag-
- K( c1 p. U% P6 D: Bnosis can be established by just a few tests and by
6 N8 U, d3 H6 g$ X% Mappropriate history. The inability to obtain such a
) V4 ]8 P5 I4 ]2 B$ F9 o) M Mhistory, or failure to ask the specific questions, may2 u! f* `; j6 i/ l+ Q% I1 @% v
result in extensive, unnecessary, and expensive
7 d/ h3 @2 z3 Q& W" o4 P5 g; sinvestigation. The primary care physician should be ?, f2 q% V# l' \
aware of this fact, because most of these children) P0 O J% j* V% l, U1 k
may initially present in their practice. The Physicians’$ d* C' p7 r1 X% o" \# b# `* U6 \( l& E
Desk Reference and package insert should also put a
2 t# z# f% f2 g8 ?) N1 q0 b# b" Jwarning about the virilizing effect on a male or' U; U0 r9 ~# ^7 E
female child who might come in contact with some-+ B1 v) h. l$ b0 n3 R: }4 _2 ?
one using any of these products.$ Y& }( O) u0 o) z: l
References2 T& f- c+ u9 t3 q
1. Styne DM. The testes: disorder of sexual differentiation: r. S+ L, g, j, X' V* ]. ]
and puberty in the male. In: Sperling MA, ed. Pediatric
3 F Y) h* S" U3 Q2 `! SEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;. `9 R3 ], H% U) m
2002: 565-628.
Q7 J5 O- X8 \7 ?4 J( Y2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious# l3 A2 k6 B) A% G7 t" Y! S' D
puberty in children with tumours of the suprasellar pineal |
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