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Sexual Precocity in a 16-Month-Old- c6 R/ f6 _1 C5 X& k, q& m
Boy Induced by Indirect Topical
2 R- Z P- j0 L1 rExposure to Testosterone
: Q+ L4 @6 n7 B# iSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2 c- w/ M! |$ I8 ^/ I2 A
and Kenneth R. Rettig, MD10 }, s3 a3 u d# } p
Clinical Pediatrics
3 J- |: d' l% @Volume 46 Number 6* C; H% y* M- F9 ]: [
July 2007 540-543
" u: x( q. `. R4 E7 o© 2007 Sage Publications; E+ R6 C9 C! P D$ |; T% t7 h: H" `
10.1177/0009922806296651, @( H- o8 _$ z, k! S0 H4 M
http://clp.sagepub.com' G3 {; ?" e8 y4 S3 ?# |. q
hosted at
: e( f- K& w0 Uhttp://online.sagepub.com
c; p* s$ y2 F3 ? xPrecocious puberty in boys, central or peripheral,
( e1 F' {3 W6 P. b# q* ^' \is a significant concern for physicians. Central4 m& b9 I4 E9 k/ K/ F7 \
precocious puberty (CPP), which is mediated
# n9 N0 F3 B; T. q2 ?through the hypothalamic pituitary gonadal axis, has2 j5 J) J# G1 K' {
a higher incidence of organic central nervous system
0 p2 _$ D# }% W3 O. Ylesions in boys.1,2 Virilization in boys, as manifested% J U3 @% K4 d5 s
by enlargement of the penis, development of pubic
/ F1 d$ h2 n. r+ chair, and facial acne without enlargement of testi-/ ]7 g8 N! D0 M/ ?" N4 j
cles, suggests peripheral or pseudopuberty.1-3 We
7 @$ V# }' p2 V5 B9 z7 Hreport a 16-month-old boy who presented with the# H, k' g# M* L' {
enlargement of the phallus and pubic hair develop-5 }. |" N3 g& M
ment without testicular enlargement, which was due/ U8 o# e3 q- K& K; T- }
to the unintentional exposure to androgen gel used by
- g7 X5 ~* n' O2 \8 nthe father. The family initially concealed this infor-! M* I: }3 @# k) ~4 T. |2 i
mation, resulting in an extensive work-up for this/ ~' s4 a" {% E Y! V% D0 g; q) q
child. Given the widespread and easy availability of
2 C+ y! W/ v, c+ } P: ~% Btestosterone gel and cream, we believe this is proba-3 y9 ~ D- ^! o j
bly more common than the rare case report in the. w# Q0 j5 D+ p! b$ m1 r
literature.45 {0 {7 `# @+ G( q2 q
Patient Report8 S& V1 m/ V7 K" W' S
A 16-month-old white child was referred to the: U% b# H. K, ]" m6 V4 g
endocrine clinic by his pediatrician with the concern9 I6 i( x% t4 H2 l3 Q. t
of early sexual development. His mother noticed
5 A2 m; Q/ S2 P! V. T# J% elight colored pubic hair development when he was
- @8 s; \2 H" g/ J6 q! x# hFrom the 1Division of Pediatric Endocrinology, 2University of8 j) y* m& w) B: F% p1 ~$ ~+ A
South Alabama Medical Center, Mobile, Alabama.% z& D8 Q7 K4 ~, l; p7 `
Address correspondence to: Samar K. Bhowmick, MD, FACE,
/ e* |- o/ h7 ZProfessor of Pediatrics, University of South Alabama, College of2 b* O% q) v7 ]! }: A6 G
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
. B. {, i) X. j7 U3 Z. e) b5 {! Je-mail: [email protected]./ A# n. d M7 M$ I( \: i! l
about 6 to 7 months old, which progressively became9 \5 x! X6 ]9 e3 S
darker. She was also concerned about the enlarge-
' @. Z0 r4 G0 Z6 ]8 s" f. Bment of his penis and frequent erections. The child/ h/ y) l. x' l8 t: X8 ~7 ^
was the product of a full-term normal delivery, with7 C- P' ?3 _& H" |9 {
a birth weight of 7 lb 14 oz, and birth length of
+ q3 P) O7 d+ I1 \# P* N20 inches. He was breast-fed throughout the first year2 e% a. F1 s! T: ^
of life and was still receiving breast milk along with3 ?+ L, c* X1 ?& G( }
solid food. He had no hospitalizations or surgery,
& a" t; e7 X! U! a- ^9 Uand his psychosocial and psychomotor development' F! q$ ~/ C5 I. X) r% T( t
was age appropriate.. w7 I& v- ]2 e; i9 ^% f$ I
The family history was remarkable for the father,' |' a& o4 D4 l# U; m
who was diagnosed with hypothyroidism at age 16,
( w# n" S' V. p- x5 n5 A0 Qwhich was treated with thyroxine. The father’s, a0 O' I; ^: d8 u
height was 6 feet, and he went through a somewhat
- x, P1 I9 x' S1 W$ d1 z4 d! N( B" Q uearly puberty and had stopped growing by age 14.6 q* n9 _1 S( B& @9 y J, ]
The father denied taking any other medication. The
4 ?0 y/ A# n+ n# K0 mchild’s mother was in good health. Her menarche
) \, x1 {8 G$ E. h8 |was at 11 years of age, and her height was at 5 feet
. L! g6 T v2 D# N. A5 inches. There was no other family history of pre-3 ~$ A/ m: N6 Q% V- l
cocious sexual development in the first-degree rela-) q# y+ E. I' ~$ z! h; }0 ^) w
tives. There were no siblings.5 s; \- v9 f+ a$ ~
Physical Examination4 d$ ^ p+ [! J. F
The physical examination revealed a very active,& H+ ~ ]* u, @3 s
playful, and healthy boy. The vital signs documented
' L' g2 N8 Q" P; g6 u3 D' O2 |9 Na blood pressure of 85/50 mm Hg, his length was
/ i2 P p# _: L5 [2 v. u90 cm (>97th percentile), and his weight was 14.4 kg+ W0 m0 Q# Y4 a8 f
(also >97th percentile). The observed yearly growth
" N0 O! y2 G' \ Z+ n9 Wvelocity was 30 cm (12 inches). The examination of
* Y2 L: F( f7 Y, j4 Pthe neck revealed no thyroid enlargement.7 l0 y8 L, E# X$ c, d
The genitourinary examination was remarkable for3 \2 ~' y/ |' ~4 S5 A! s
enlargement of the penis, with a stretched length of7 F1 [# m( |% P7 Z( k1 h
8 cm and a width of 2 cm. The glans penis was very well2 ]. c( v! R# y: R: ?3 P& b$ }
developed. The pubic hair was Tanner II, mostly around% J+ Q; }) y0 B
540
b" x5 U. ?0 `' ^, Q" \. Bat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
5 g& g; d0 g! G; o& z' L$ R, ?the base of the phallus and was dark and curled. The
' V' F/ C4 L1 [7 E% ?5 Qtesticular volume was prepubertal at 2 mL each.$ c% r- j# r& ?% ^! b# P
The skin was moist and smooth and somewhat% M5 E& S0 p s- t. Z# j
oily. No axillary hair was noted. There were no
& \1 G# S( |; W6 y babnormal skin pigmentations or café-au-lait spots.
4 f' R) s8 Z L8 d6 i+ g. Z. S* F4 \Neurologic evaluation showed deep tendon reflex 2+
+ T5 x- M9 C6 v* Bbilateral and symmetrical. There was no suggestion
5 ?, Q* y$ S5 y. zof papilledema./ a2 l6 k: c& `1 J- L" i
Laboratory Evaluation! f0 o( Z" o( H( t
The bone age was consistent with 28 months by1 l7 C4 t4 M2 n: R4 T' q( t* L
using the standard of Greulich and Pyle at a chrono-
$ @3 Z C- o- `# q; x4 s. O6 ^' llogic age of 16 months (advanced).5 Chromosomal1 e4 U, l+ j: A/ f- t
karyotype was 46XY. The thyroid function test# V/ P2 R! o! w* E/ L1 y2 f: L) J
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
$ R1 o6 w8 _2 U/ ulating hormone level was 1.3 µIU/mL (both normal).
3 W6 h' D o& y% _% c' u5 EThe concentrations of serum electrolytes, blood# r4 A$ w+ Y* H
urea nitrogen, creatinine, and calcium all were
. @* b9 |+ v5 A( @within normal range for his age. The concentration( u) e- b. j3 l
of serum 17-hydroxyprogesterone was 16 ng/dL/ R! B6 w2 b% S0 D) I
(normal, 3 to 90 ng/dL), androstenedione was 20- I. u) n1 V6 Y. ^" L6 H3 |+ {* |% x3 u
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-/ ] S. F# G9 u. u1 p0 m! d
terone was 38 ng/dL (normal, 50 to 760 ng/dL),, ?5 U0 b7 o+ f
desoxycorticosterone was 4.3 ng/dL (normal, 7 to( Z5 r0 n" O* o
49ng/dL), 11-desoxycortisol (specific compound S)
! Q/ n9 Z0 `0 E* G6 }1 ~# Dwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-7 ?- t! ^. C, I/ P
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total% a2 y; ~$ `* o, F- ~8 ~# x
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
6 b! G8 n9 g" ~6 Qand β-human chorionic gonadotropin was less than
% s: t4 I1 v' z: E) r5 mIU/mL (normal <5 mIU/mL). Serum follicular
6 O# A, e* H# {6 r, @stimulating hormone and leuteinizing hormone/ f* l: C: X3 r- Q
concentrations were less than 0.05 mIU/mL
% e) l6 ?5 r. n/ X! T(prepubertal).
7 U: E' V/ E: i4 L' UThe parents were notified about the laboratory. s% T) \5 r5 ^
results and were informed that all of the tests were5 R6 K/ A2 V( p* D- I$ N
normal except the testosterone level was high. The
; e- K8 A, {6 K5 {follow-up visit was arranged within a few weeks to
) T F8 k, j. c1 Y: ?: ~' _' v6 Sobtain testicular and abdominal sonograms; how-) j/ p- S; L9 e/ E) r5 z# ~4 c( ?
ever, the family did not return for 4 months.
, _ H% l. c9 ^9 V# V- F' [+ lPhysical examination at this time revealed that the* c7 s E* }, O6 _
child had grown 2.5 cm in 4 months and had gained$ a3 F& I4 b- {( T4 [
2 kg of weight. Physical examination remained
; ^$ r# p5 v7 \3 ]! L% D. Eunchanged. Surprisingly, the pubic hair almost com-
) f$ E6 [" H- i( |- k) Z, b6 ]pletely disappeared except for a few vellous hairs at
' d# r6 w$ U6 Q, a: F' g! }: S3 xthe base of the phallus. Testicular volume was still 25 ?0 v) c$ F9 K: P3 r! `* p E) |" j
mL, and the size of the penis remained unchanged.
a# r1 N+ K! j LThe mother also said that the boy was no longer hav-
5 r1 ^ P1 t: ?# u4 j: oing frequent erections.$ F4 X8 ~+ N& \" l- \/ {; `
Both parents were again questioned about use of- W; q5 R5 A/ k
any ointment/creams that they may have applied to
% D& p4 U6 B- F7 {the child’s skin. This time the father admitted the
' l1 c; W o) HTopical Testosterone Exposure / Bhowmick et al 541
) y. f& z, x; W! N# E& t* }. uuse of testosterone gel twice daily that he was apply-
% F: |( N) ~+ u# F7 y) Y$ L6 King over his own shoulders, chest, and back area for* O, X+ d/ N# M
a year. The father also revealed he was embarrassed1 n. r6 s/ @8 H) k0 \* B
to disclose that he was using a testosterone gel pre-
/ U, \$ {* E9 ~' Yscribed by his family physician for decreased libido9 w( X& `4 _' X2 z
secondary to depression.
/ n) V: y/ A# u) }4 V2 o+ MThe child slept in the same bed with parents." P; ^$ {5 [$ X+ }. Q; e) P4 ^
The father would hug the baby and hold him on his- r% E, d: u, F4 w. l X* O
chest for a considerable period of time, causing sig-
# f. H, D3 Z$ s. W: }8 D* c" g8 _nificant bare skin contact between baby and father.
/ M! `, i# x/ h6 Y$ W) J# lThe father also admitted that after the phone call,) [: p' A9 w, c# \4 y" j
when he learned the testosterone level in the baby$ d: d& o* Q* }& Y7 M5 y* c
was high, he then read the product information
& s+ L9 T# Q! r. Y8 n" bpacket and concluded that it was most likely the rea-
4 |3 b$ K1 E5 bson for the child’s virilization. At that time, they
8 m4 @ V& U: h5 ^6 D" L+ o9 pdecided to put the baby in a separate bed, and the
( B7 } o# f5 n; B s5 p! dfather was not hugging him with bare skin and had
& q+ W+ V: @4 Sbeen using protective clothing. A repeat testosterone0 d2 E2 W( H {
test was ordered, but the family did not go to the+ g" r: m E$ \# ~+ k5 z2 j* e
laboratory to obtain the test.
6 c, p# M. x9 k* J2 g, nDiscussion9 ^% O6 ?! k$ }* b) D
Precocious puberty in boys is defined as secondary/ Y& g9 |$ U7 I& q4 ~4 H
sexual development before 9 years of age.1,4! t+ v9 q1 J' h; Y3 o& a
Precocious puberty is termed as central (true) when2 T( G2 S! D, L: T
it is caused by the premature activation of hypo-7 q/ Y0 h0 c! n8 I
thalamic pituitary gonadal axis. CPP is more com-* { s+ y5 \6 I( r+ o$ a! V
mon in girls than in boys.1,3 Most boys with CPP2 z! k U7 k3 S4 b4 f7 x
may have a central nervous system lesion that is; ?5 }' _4 F( E1 f7 @! R- h+ H
responsible for the early activation of the hypothal-" T1 ^; U" _' L2 d1 }0 Z
amic pituitary gonadal axis.1-3 Thus, greater empha-
" i, O; `+ ]2 r! v$ g6 |) csis has been given to neuroradiologic imaging in
( n/ W; p' b- ]3 T6 n! N3 l1 `boys with precocious puberty. In addition to viril-! Y$ j8 R- o w* i6 i
ization, the clinical hallmark of CPP is the symmet-
1 Z4 A3 r2 s2 r c/ o. F$ E" irical testicular growth secondary to stimulation by7 G+ g4 U1 D7 |5 ?% ^( W
gonadotropins.1,3
* I1 H2 \0 K' {$ X, k% PGonadotropin-independent peripheral preco-
6 w' c! {. Z* L* Z* Ycious puberty in boys also results from inappropriate$ e. }* X( x1 O2 \- {3 k$ C4 Q
androgenic stimulation from either endogenous or
" w) _( h. S0 z3 J* qexogenous sources, nonpituitary gonadotropin stim-/ J* J/ H/ B# V3 Q, U) W
ulation, and rare activating mutations.3 Virilizing0 z8 x8 D3 s$ ]0 V
congenital adrenal hyperplasia producing excessive
$ y |) p/ M9 C) _) Nadrenal androgens is a common cause of precocious
% B1 t' s7 ]4 d m) c, Bpuberty in boys.3,4
* B) C# ^: J3 o. UThe most common form of congenital adrenal C3 T- Z# _$ C. a
hyperplasia is the 21-hydroxylase enzyme deficiency.
2 q+ c# K n+ ~; VThe 11-β hydroxylase deficiency may also result in. x% Y9 t1 `/ k( u+ M
excessive adrenal androgen production, and rarely,3 F' L; T3 W, g( A2 c7 w) l
an adrenal tumor may also cause adrenal androgen
) R6 G6 a1 t1 iexcess.1,3/ m% u2 ?9 _2 r1 x& @
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from4 D: C5 T" H+ S$ j* [0 T
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007* Z* ~" z- Q: ~; X
A unique entity of male-limited gonadotropin-3 u7 X* ^! G2 u* D7 \, w* Z
independent precocious puberty, which is also known% \; S9 _4 {, p4 ?- u4 M; E
as testotoxicosis, may cause precocious puberty at a
; Z! U6 N& `* i$ ]very young age. The physical findings in these boys
0 n6 Y. i. R' ywith this disorder are full pubertal development,# h7 H/ g, |: a/ u% X
including bilateral testicular growth, similar to boys
2 x/ _. M: e* S' N1 q2 l. T( jwith CPP. The gonadotropin levels in this disorder9 \+ l& F4 V" x6 n+ V6 p
are suppressed to prepubertal levels and do not show1 E8 K( L& o0 J6 K. s7 J! ^
pubertal response of gonadotropin after gonadotropin-& ~* q( q' B* R
releasing hormone stimulation. This is a sex-linked$ ^. L5 j5 }3 @; n$ ]
autosomal dominant disorder that affects only
8 O% J Q* O A" U& M0 Omales; therefore, other male members of the family+ U s) \# o: G" x! V" |
may have similar precocious puberty.3, ^( |4 o6 u! T6 V
In our patient, physical examination was incon-( `* x8 d& ?7 H# z
sistent with true precocious puberty since his testi-* M; z8 ]8 A( q
cles were prepubertal in size. However, testotoxicosis
% `8 ^9 J0 s' |was in the differential diagnosis because his father0 v7 u$ ~! a+ r. ~7 }* K
started puberty somewhat early, and occasionally,! K0 q* W0 a9 D. ~
testicular enlargement is not that evident in the
' n/ r. H0 S- E, \% p4 E: C; Tbeginning of this process.1 In the absence of a neg-
: p+ k6 a- ^2 G( }( h$ V. R% lative initial history of androgen exposure, our
2 a; P! P& a8 f0 N3 hbiggest concern was virilizing adrenal hyperplasia," M5 p _. C- K( F% i' _
either 21-hydroxylase deficiency or 11-β hydroxylase
6 p& n" A$ t9 K( rdeficiency. Those diagnoses were excluded by find-
1 \9 @0 R2 y0 @; @/ ?ing the normal level of adrenal steroids.1 k6 k/ v6 e+ O8 u$ v
The diagnosis of exogenous androgens was strongly% g+ d/ m/ } N. E: U* @0 d) O
suspected in a follow-up visit after 4 months because% J5 M1 W8 V$ Q: ?7 C; K9 _
the physical examination revealed the complete disap-4 x8 u& P8 i" h7 p. {/ p
pearance of pubic hair, normal growth velocity, and
1 V+ m( ]: J+ E) g' Y. Rdecreased erections. The father admitted using a testos-2 B6 C2 s7 U' A( Z5 q) G
terone gel, which he concealed at first visit. He was
9 ?" a J h/ x; w, d8 \using it rather frequently, twice a day. The Physicians’
8 D0 I; T& k4 g! V; D3 eDesk Reference, or package insert of this product, gel or& ~, K: X% P, e1 e- _' h
cream, cautions about dermal testosterone transfer to. J' w) }5 V; U8 \7 S7 I
unprotected females through direct skin exposure.+ k9 Z+ ~( e4 L: Y% N
Serum testosterone level was found to be 2 times the
1 w+ S: Z0 ^2 ~: G. Mbaseline value in those females who were exposed to& M* |% y# m: Z& T( h
even 15 minutes of direct skin contact with their male
# t& d4 i J. ]2 \partners.6 However, when a shirt covered the applica-
' f- E" k" Y0 d, N. D0 Wtion site, this testosterone transfer was prevented., S; Z! @2 H; l* G) R- c- j
Our patient’s testosterone level was 60 ng/mL,
; Y- d/ b& ?# Y& I' Twhich was clearly high. Some studies suggest that
+ V5 t" o; I) n! u7 o( O% sdermal conversion of testosterone to dihydrotestos-
2 @) S9 K3 ~6 M# s0 d& iterone, which is a more potent metabolite, is more
+ w& O. @- T9 Pactive in young children exposed to testosterone \! _+ W7 `# a8 w' x. q
exogenously7; however, we did not measure a dihy-) G* e8 }- j' R+ ?
drotestosterone level in our patient. In addition to: J3 A( q' U2 a% a ^" ~) w
virilization, exposure to exogenous testosterone in8 `6 u; O7 Y8 h- T3 U+ @+ J
children results in an increase in growth velocity and5 a( j, D* L& K/ A$ K/ D
advanced bone age, as seen in our patient.
( ~% d! I/ o; R, pThe long-term effect of androgen exposure during2 P: y" Y: b7 Y* k5 J% J5 ~0 K
early childhood on pubertal development and final9 k) G4 [1 `5 D" V5 b7 b
adult height are not fully known and always remain+ p$ U4 W) Q. i# |: M
a concern. Children treated with short-term testos-( z3 e8 {. ?! `7 r
terone injection or topical androgen may exhibit some$ T4 }; Z- w3 E. t, [8 x- l
acceleration of the skeletal maturation; however, after
- |( L6 ?+ D+ }cessation of treatment, the rate of bone maturation
6 w6 a' e' j. n3 `decelerates and gradually returns to normal.8,9
: l7 m3 O- c+ ?1 dThere are conflicting reports and controversy* o4 g! t/ F, M5 ^
over the effect of early androgen exposure on adult
0 @2 o6 _$ u' Q0 }+ _! ^6 Epenile length.10,11 Some reports suggest subnormal4 K# L$ e" B& B( D1 i! n
adult penile length, apparently because of downreg-+ E: ~5 r$ ]8 |0 u
ulation of androgen receptor number.10,12 However,6 @3 |: l: E/ q: G j1 P0 H
Sutherland et al13 did not find a correlation between; O. U6 z7 q; \& U Y* a9 F
childhood testosterone exposure and reduced adult
3 l0 a5 k+ A9 c. g( Fpenile length in clinical studies.& ?& [ O& ~7 ]8 N+ S' [4 e
Nonetheless, we do not believe our patient is9 c: Y) C0 ~6 s7 b. c* W
going to experience any of the untoward effects from1 [" O4 }* I1 Z
testosterone exposure as mentioned earlier because( W! U% z ~$ d) u; {
the exposure was not for a prolonged period of time.
# b% g% @1 b: l9 d& r; [' e5 ?Although the bone age was advanced at the time of, ?$ n- R0 Y7 V+ v# T
diagnosis, the child had a normal growth velocity at' J) h8 D& y' ^: ]% {
the follow-up visit. It is hoped that his final adult1 r, x* g- f. V
height will not be affected.
$ Y4 o( l) O) C: ^4 dAlthough rarely reported, the widespread avail-" ~) u @+ v$ M2 S! Q
ability of androgen products in our society may; X! `5 C$ n% ]6 R3 y
indeed cause more virilization in male or female' [& C+ g" q D o6 X: D4 u
children than one would realize. Exposure to andro-
) K0 n" H) b& q2 Wgen products must be considered and specific ques-
# I: P# x9 A% y- wtioning about the use of a testosterone product or
( t4 P/ b+ C1 C' _gel should be asked of the family members during# r. O S& l$ B4 ^/ N; q. {; ~
the evaluation of any children who present with vir- x0 C- k) n4 l" p6 C8 T p
ilization or peripheral precocious puberty. The diag-' t k# K/ }7 H0 H7 Z: u
nosis can be established by just a few tests and by
# v! Q o4 `/ n$ Y& k# F! Z$ wappropriate history. The inability to obtain such a) r6 i' O0 w1 K) j- D# ?" R0 t- [# {
history, or failure to ask the specific questions, may, P i) x3 Y1 ^( l4 x9 T8 P
result in extensive, unnecessary, and expensive
: F* _- J9 g- e9 d; L0 ^4 l4 finvestigation. The primary care physician should be
2 T0 X0 r3 X5 aaware of this fact, because most of these children1 u/ w( D; d1 D' _
may initially present in their practice. The Physicians’* t3 p; V# d& ^0 Q+ G7 {3 u
Desk Reference and package insert should also put a
& ]( J+ \ m8 w2 N: H( R- hwarning about the virilizing effect on a male or( `( z/ }. x6 W
female child who might come in contact with some-
* r- v; S% a% O" J) Lone using any of these products.
& b, T1 w6 @$ ?# R6 o0 JReferences$ R7 g4 R! F% u7 ^
1. Styne DM. The testes: disorder of sexual differentiation
9 C+ y/ s6 }; w, p( t. iand puberty in the male. In: Sperling MA, ed. Pediatric
8 j0 K8 h, f: X }Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
3 A' u0 Z. a5 `* a% _4 W2002: 565-628.$ E R) `; z, M
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious$ E( s( X0 G0 `8 S3 k
puberty in children with tumours of the suprasellar pineal |
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