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Sexual Precocity in a 16-Month-Old
7 }# e, D& b4 h+ v9 b7 j4 y# g/ P) ~Boy Induced by Indirect Topical, `) a( Y: ?/ ~- x0 W" `9 O$ J
Exposure to Testosterone7 P3 }, n0 q' t1 ^
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
% X C% G. j; U- {& Kand Kenneth R. Rettig, MD1
$ M- d7 P, @& M0 d5 N& L8 QClinical Pediatrics0 w" M0 T; V1 ~% O9 j% R$ f. B
Volume 46 Number 6
( P) e# A* Z7 A- tJuly 2007 540-5434 x: k( Z4 O, G5 b$ e
© 2007 Sage Publications6 }* @% j# u7 P8 g D& J# M
10.1177/00099228062966510 }/ h/ a& ^- {
http://clp.sagepub.com+ ~: s, M& J0 S) n! `" s4 T
hosted at
& X; R6 L0 T, Ehttp://online.sagepub.com
+ ` W% j0 ]% F; }, v9 b' s6 R& A0 YPrecocious puberty in boys, central or peripheral,
) d3 E* ?& `9 B% f* x7 ]is a significant concern for physicians. Central
Q! x" T. a# _- w0 ]precocious puberty (CPP), which is mediated
- Y: f8 r1 S% e- wthrough the hypothalamic pituitary gonadal axis, has
& K5 X8 N: V5 J0 B' B [ J+ ~a higher incidence of organic central nervous system/ z: F, e. ?) D; k; w. J, d# N
lesions in boys.1,2 Virilization in boys, as manifested8 r9 J" Q. F+ l+ X( y# T6 P
by enlargement of the penis, development of pubic
8 i _9 }: L3 ^( r' n. b; Khair, and facial acne without enlargement of testi-
/ \! |; ]# Q3 G8 Mcles, suggests peripheral or pseudopuberty.1-3 We
/ _9 w4 @( ^; x' b& Z% sreport a 16-month-old boy who presented with the
+ a6 A1 M% F+ oenlargement of the phallus and pubic hair develop-
: T, ~2 d$ L/ p. N; @: ~% x0 vment without testicular enlargement, which was due% m% B+ w9 R4 A
to the unintentional exposure to androgen gel used by
0 k% N1 M6 \5 L8 othe father. The family initially concealed this infor-
9 k' Q# M4 t6 |" F6 x ]! _3 s. mmation, resulting in an extensive work-up for this
5 e( h# W. E- Pchild. Given the widespread and easy availability of
% i6 Q" s" L& M: ]; Ytestosterone gel and cream, we believe this is proba-
9 {, t0 ^; K$ F$ L2 B, tbly more common than the rare case report in the2 t" i( P5 p' V6 o
literature.46 i4 r* S, M9 k
Patient Report
9 r0 b4 F: ~% m$ g( \+ O4 pA 16-month-old white child was referred to the B9 h. m' f: y
endocrine clinic by his pediatrician with the concern7 ~1 F. ?9 _- x/ |; H' H
of early sexual development. His mother noticed
4 E4 z/ C/ ~9 `4 S! Zlight colored pubic hair development when he was. q1 [0 D8 o' i4 J8 u9 o7 ]
From the 1Division of Pediatric Endocrinology, 2University of
6 [5 ^8 \2 K. o$ S+ C- d6 FSouth Alabama Medical Center, Mobile, Alabama.. u# M8 |# P. P( d9 p G# s
Address correspondence to: Samar K. Bhowmick, MD, FACE,
9 K0 o! s6 h: ]8 b# XProfessor of Pediatrics, University of South Alabama, College of
4 D8 ?, |3 s6 M- [5 ^Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
# r: _: C1 ]( C9 o; }5 Ke-mail: [email protected].
3 s& a8 H3 O$ mabout 6 to 7 months old, which progressively became
0 l# |# C% O+ k2 Ydarker. She was also concerned about the enlarge-- e, F: o |- N) |' W' P
ment of his penis and frequent erections. The child: u( m, ?8 p6 f5 _' T8 K" H
was the product of a full-term normal delivery, with
( P" ~6 X9 m. U. ha birth weight of 7 lb 14 oz, and birth length of
( Z4 m6 S, J% \1 y20 inches. He was breast-fed throughout the first year9 S& ?5 |$ K0 b! K* j7 a
of life and was still receiving breast milk along with
4 G0 v0 _. U, Nsolid food. He had no hospitalizations or surgery,( g& J; A1 e6 p: v" |
and his psychosocial and psychomotor development
. x+ `4 `5 F. B* U5 L) [was age appropriate.
$ B) H6 @- p2 x1 {7 FThe family history was remarkable for the father,
- }6 W9 U0 P% c8 H( M: R, {who was diagnosed with hypothyroidism at age 16,
4 [0 w+ G, h( iwhich was treated with thyroxine. The father’s
5 U2 V/ i, [1 D' V w* xheight was 6 feet, and he went through a somewhat" |9 j' W) M, h* u. e5 g$ J5 }
early puberty and had stopped growing by age 14.. j2 C/ `) L" T3 N8 P( i/ q; `) Z
The father denied taking any other medication. The
6 d. [% q! V; T8 E% S+ k; Zchild’s mother was in good health. Her menarche6 ?% M' x% u& T) j/ S# O
was at 11 years of age, and her height was at 5 feet
' b, E; ^2 S0 k9 g7 v X- B5 inches. There was no other family history of pre-
0 b2 b9 y: a# z+ L, o1 y4 Z) ~cocious sexual development in the first-degree rela-" j+ _! F6 w4 z( w
tives. There were no siblings.
+ p! W9 @: D) h8 iPhysical Examination
1 f; d h: ~9 oThe physical examination revealed a very active,
' F2 b$ q) v9 d1 }( g) g2 B, [playful, and healthy boy. The vital signs documented
0 j; D6 ?6 N7 L- H: \a blood pressure of 85/50 mm Hg, his length was
& P; l$ s1 p1 ~6 }9 D90 cm (>97th percentile), and his weight was 14.4 kg
* p4 W, c1 e, Q/ J& t: o. w(also >97th percentile). The observed yearly growth
. S7 S' f. E! R! j" v8 b( yvelocity was 30 cm (12 inches). The examination of" w' N9 h" W& Z! ?
the neck revealed no thyroid enlargement.3 a3 R: v$ m7 r0 u/ U- E& }. l, A
The genitourinary examination was remarkable for
3 a( W4 {. X' @6 s. q0 u! g9 Ienlargement of the penis, with a stretched length of
) w7 F6 w0 v; b+ ?: U8 cm and a width of 2 cm. The glans penis was very well
0 J3 J) F1 K; [3 |2 ~developed. The pubic hair was Tanner II, mostly around
. L3 |% P- u: Z2 V5406 f4 Q0 p$ i4 V7 X+ Q' }
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
4 w8 {' E9 F! m, A' q( Rthe base of the phallus and was dark and curled. The
; h2 u3 o! H7 Z! q) v0 ~- H& atesticular volume was prepubertal at 2 mL each.
$ G* N ~ S% F% FThe skin was moist and smooth and somewhat
- r1 j" x& k) X1 b- W: [oily. No axillary hair was noted. There were no
& V9 l' V+ e- Q { g) O5 E8 H/ @abnormal skin pigmentations or café-au-lait spots. V* Z1 F U7 G9 |8 y% I$ L2 }: S/ Q
Neurologic evaluation showed deep tendon reflex 2+- ]" A2 v2 ~. M
bilateral and symmetrical. There was no suggestion# x0 p: {8 D$ H
of papilledema.
1 N# v9 Q5 \4 rLaboratory Evaluation8 z' g( D1 B1 e$ G4 Y. i
The bone age was consistent with 28 months by' b e& H9 a' i' Z$ ~6 `
using the standard of Greulich and Pyle at a chrono- \7 v; e/ b2 Q2 b, d
logic age of 16 months (advanced).5 Chromosomal
- s, P9 J8 N9 s; t Ukaryotype was 46XY. The thyroid function test
2 b4 a( o+ H4 [* D0 V! e; Rshowed a free T4 of 1.69 ng/dL, and thyroid stimu-5 s K/ u& r% C, b. H
lating hormone level was 1.3 µIU/mL (both normal).
; P+ L) R8 J8 X9 O0 yThe concentrations of serum electrolytes, blood
0 J+ a) O |: v* U+ Yurea nitrogen, creatinine, and calcium all were7 ?5 |" X3 d* |, v& k
within normal range for his age. The concentration
' T/ D+ Z, p- q: jof serum 17-hydroxyprogesterone was 16 ng/dL
2 Q8 y* H7 V; M(normal, 3 to 90 ng/dL), androstenedione was 20
# _- `8 R) A5 P2 ]. Sng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
" q! ]6 P. _$ c- gterone was 38 ng/dL (normal, 50 to 760 ng/dL),
; Q7 l* E4 _ Z Q0 u, l0 v y7 idesoxycorticosterone was 4.3 ng/dL (normal, 7 to$ m2 C/ R: u2 K, _2 ^
49ng/dL), 11-desoxycortisol (specific compound S)
$ ~9 K4 q+ ^5 R( Vwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-: N. n; v, h* E/ u9 \# u9 W
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total% Y( v9 f7 T) A5 W, w; [7 ^: J
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),8 f N% K- @% s- @9 M
and β-human chorionic gonadotropin was less than
/ g! e; a+ D: ~9 I4 x5 mIU/mL (normal <5 mIU/mL). Serum follicular
$ E+ F" I U0 M; \0 t7 n* e; vstimulating hormone and leuteinizing hormone! q m1 c$ V$ z* I0 B5 L
concentrations were less than 0.05 mIU/mL' ~6 O( h) N& c( m& a; j# o f
(prepubertal).! {5 i9 [) d6 l: n" x0 _; [3 f
The parents were notified about the laboratory% }* b! Z" Z* Q, @2 v# c7 k
results and were informed that all of the tests were7 Q7 c- y8 i7 o& X0 S5 s
normal except the testosterone level was high. The
6 G. B8 c4 m! B) h1 M( {follow-up visit was arranged within a few weeks to
+ N A8 Q# v2 o) M7 m- ]! ]obtain testicular and abdominal sonograms; how-
9 S8 J, b+ Z& g: U" L* w; a) Wever, the family did not return for 4 months.0 N6 b0 q$ B9 |3 F9 n7 E
Physical examination at this time revealed that the
; \9 e. W# P$ g/ o; }$ qchild had grown 2.5 cm in 4 months and had gained
( g- r( H4 ] S5 l5 D$ e2 kg of weight. Physical examination remained$ \ V* @0 v, e" ~- _
unchanged. Surprisingly, the pubic hair almost com-. {' Y4 G8 L) e
pletely disappeared except for a few vellous hairs at) r$ H0 G6 }0 d/ [& c0 J1 W' R
the base of the phallus. Testicular volume was still 2
_! w4 I$ l4 A% ~9 g* PmL, and the size of the penis remained unchanged.) F$ \* Q. {: f3 o
The mother also said that the boy was no longer hav-
9 n1 s N$ j0 uing frequent erections.9 H4 ~0 @/ D- i( S. x o0 V2 N
Both parents were again questioned about use of. v( g0 }* r# U( o& t
any ointment/creams that they may have applied to2 t" E1 s* s$ W
the child’s skin. This time the father admitted the. y# R: d g) T
Topical Testosterone Exposure / Bhowmick et al 541
" P5 } b; _* F* ~0 x4 F' Xuse of testosterone gel twice daily that he was apply-1 ^7 d# W' j/ t) [
ing over his own shoulders, chest, and back area for* T8 {7 y/ A1 t8 X0 ]
a year. The father also revealed he was embarrassed
! j- S; V0 Z, j: _to disclose that he was using a testosterone gel pre-
+ j1 n2 c* x6 p: F! P" j1 Fscribed by his family physician for decreased libido
5 @1 i. E$ D! _* K( {, \) p- @secondary to depression./ s3 Z, ]( K9 p
The child slept in the same bed with parents.
( L8 a, ]$ r" q8 d, {( YThe father would hug the baby and hold him on his
; h/ \/ ~) j7 I, mchest for a considerable period of time, causing sig-& {. r7 D! G+ g
nificant bare skin contact between baby and father.' m: }7 a7 @7 T( J% \9 P
The father also admitted that after the phone call,2 T7 J4 G- X6 z( w. N- a* O5 g
when he learned the testosterone level in the baby" w' m2 A5 x% Z/ F- n% Z
was high, he then read the product information% P' x! I5 s+ a# ~/ |2 ]
packet and concluded that it was most likely the rea-
+ o4 a7 S5 |$ V0 @; uson for the child’s virilization. At that time, they' D" E4 v7 o8 R# L% t7 D, y
decided to put the baby in a separate bed, and the, z7 x: u; j V/ X; f
father was not hugging him with bare skin and had+ A" P# j( `: [; w
been using protective clothing. A repeat testosterone: F" p9 M) B1 t
test was ordered, but the family did not go to the
' n# e* A/ H$ @laboratory to obtain the test.
0 `; X L; c4 XDiscussion
K& V& h$ r2 c6 d/ Y* R. lPrecocious puberty in boys is defined as secondary
5 k3 U* b; v# p/ csexual development before 9 years of age.1,4
: q9 {( d$ E. w$ o, ^Precocious puberty is termed as central (true) when2 C; ^0 s9 t; \2 l! e7 C( n
it is caused by the premature activation of hypo-
9 _1 s, @+ y' Z: B; ]thalamic pituitary gonadal axis. CPP is more com-) a& n U; K9 j* W Y. o
mon in girls than in boys.1,3 Most boys with CPP
8 W0 G, p W+ ?9 d( z" a2 hmay have a central nervous system lesion that is4 }: q |6 Z* l, j% g
responsible for the early activation of the hypothal-) o- e( m# x4 [2 g/ U* a. R
amic pituitary gonadal axis.1-3 Thus, greater empha-/ a1 @1 u0 V9 Q" w1 H
sis has been given to neuroradiologic imaging in; i9 F- Q2 C8 q3 a5 e7 M# ?7 k
boys with precocious puberty. In addition to viril-
# J# R! o, N% `: }( yization, the clinical hallmark of CPP is the symmet-5 |! K$ P1 c! c* `
rical testicular growth secondary to stimulation by* ]2 z3 ?4 \3 w, ^/ n* B
gonadotropins.1,34 W+ E2 p# G( _0 N
Gonadotropin-independent peripheral preco-7 s _8 @8 b, i
cious puberty in boys also results from inappropriate1 h2 b0 i; I4 ~4 v! e
androgenic stimulation from either endogenous or
+ F* @$ [# N0 U) }) E3 F" ]$ i# z: yexogenous sources, nonpituitary gonadotropin stim-6 a4 f+ h0 m# g; o1 X3 z; ?
ulation, and rare activating mutations.3 Virilizing4 l9 Q# k7 Y3 Y& L9 v6 m( v
congenital adrenal hyperplasia producing excessive
7 [" s! R! I( } T# L1 I1 a+ qadrenal androgens is a common cause of precocious& ?0 ]4 M, _& x% L( H. H
puberty in boys.3,4; b* T( E7 ?2 t1 O; s# f2 [
The most common form of congenital adrenal! I' i) x2 P5 S. s3 M! Z* s" E
hyperplasia is the 21-hydroxylase enzyme deficiency., Z! c, Z- a* u' w2 I$ j$ ]
The 11-β hydroxylase deficiency may also result in
( P0 H4 R; C- g. ~5 t. Y: S+ kexcessive adrenal androgen production, and rarely,
* U2 F j! ]4 o4 @9 I' B$ L' Lan adrenal tumor may also cause adrenal androgen0 O5 [# a$ y5 L& q
excess.1,31 ^5 w6 Z% a- m4 _- c f( J
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from. O- r' _) C# @; K) S/ u' i6 c
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
1 ^3 m; I8 n& {" l( v9 BA unique entity of male-limited gonadotropin-% k% ~7 a) E: E# V$ ]7 p
independent precocious puberty, which is also known
* G+ p2 t- ^$ S) Z# c5 f* B4 Mas testotoxicosis, may cause precocious puberty at a, N$ N* R5 q& u- |' f
very young age. The physical findings in these boys
2 a) E+ P& A1 t! p! K" Fwith this disorder are full pubertal development,7 U" C" N+ f+ E; U/ {& x6 J
including bilateral testicular growth, similar to boys( z4 j. f+ _& P6 V
with CPP. The gonadotropin levels in this disorder2 B- q- j$ _+ U R+ [
are suppressed to prepubertal levels and do not show% Z3 n' R1 _/ N0 k# J/ R
pubertal response of gonadotropin after gonadotropin-
; G& j( I* y1 c0 Jreleasing hormone stimulation. This is a sex-linked4 I2 a$ c+ o. n
autosomal dominant disorder that affects only
" S+ `" k6 S& i2 Qmales; therefore, other male members of the family
5 G/ W/ r& z, a- m1 dmay have similar precocious puberty.30 u8 c/ x% r1 u
In our patient, physical examination was incon-
) x' ]3 n5 _& a5 zsistent with true precocious puberty since his testi-
1 d/ |6 | n5 D' z/ R* a( F3 x, Mcles were prepubertal in size. However, testotoxicosis+ a3 L" b5 W9 K, k$ H2 W% Z# L
was in the differential diagnosis because his father9 p# j# G& t# n4 ?9 y; H
started puberty somewhat early, and occasionally,6 ?1 u- n6 z7 p E" L
testicular enlargement is not that evident in the
8 Q! m) ]$ j9 h3 w5 ~ ybeginning of this process.1 In the absence of a neg-6 B5 p, j( y* Y6 D, B0 M
ative initial history of androgen exposure, our* o; S: ]4 ?9 e# c* a, P$ ?( g9 x, Y
biggest concern was virilizing adrenal hyperplasia,
. c4 V2 E9 x& j. Deither 21-hydroxylase deficiency or 11-β hydroxylase
7 m! ~. }$ l) B Q8 c& Mdeficiency. Those diagnoses were excluded by find-7 Y3 {9 S. S6 Z
ing the normal level of adrenal steroids.
% M4 O) E7 r/ `; F. QThe diagnosis of exogenous androgens was strongly2 C( C- _' r' v' L
suspected in a follow-up visit after 4 months because
7 D! O' j1 q# Q, Ethe physical examination revealed the complete disap-1 c& r9 G) p# I* s- m! B; ], p
pearance of pubic hair, normal growth velocity, and+ A7 X% h9 p$ S: F
decreased erections. The father admitted using a testos-! h# Z2 [. m6 ]; U( \1 s
terone gel, which he concealed at first visit. He was4 v9 L* a) F+ v8 j h4 c
using it rather frequently, twice a day. The Physicians’. @* T* Q+ y# m
Desk Reference, or package insert of this product, gel or( x; X3 F) d9 K# J
cream, cautions about dermal testosterone transfer to
% j( J: Y) ^. H* O8 ~2 \/ _unprotected females through direct skin exposure.
5 x3 R- N( ]+ VSerum testosterone level was found to be 2 times the" [% q/ E6 B. P* m
baseline value in those females who were exposed to3 h7 z1 r; }& t- w' }' B
even 15 minutes of direct skin contact with their male/ w) ^( \( I5 n- u* o
partners.6 However, when a shirt covered the applica-
* _: q, h/ ?) E% ^$ J- U$ otion site, this testosterone transfer was prevented.# N9 ]- u6 W- [2 Z
Our patient’s testosterone level was 60 ng/mL,4 y/ { x: l* L8 ?. y, n) H
which was clearly high. Some studies suggest that* K6 t9 }! t% h
dermal conversion of testosterone to dihydrotestos-
- c. o( c+ p' B7 ?+ pterone, which is a more potent metabolite, is more# e4 j4 c( j& g# K
active in young children exposed to testosterone
* D8 I ]* m2 a' v7 Rexogenously7; however, we did not measure a dihy-, x. a/ d& w; J& g5 J
drotestosterone level in our patient. In addition to
! `3 d+ j0 \/ @ z- wvirilization, exposure to exogenous testosterone in
3 ]! O2 U4 M$ nchildren results in an increase in growth velocity and
/ {9 e, }: k- q$ q9 M- Q# J" W& Gadvanced bone age, as seen in our patient.3 N( R1 w: i' L e& a# Y
The long-term effect of androgen exposure during
' V& s* l- d) c: Oearly childhood on pubertal development and final. s9 @6 V; s5 {8 D8 q; ?
adult height are not fully known and always remain
1 h& U% A( B7 `( L: ^5 a5 S! o8 wa concern. Children treated with short-term testos-
' E! n8 ?8 t. J; Xterone injection or topical androgen may exhibit some) U5 w: J! H, x+ `: N
acceleration of the skeletal maturation; however, after
. {2 T6 @5 Q: L: k* P- }cessation of treatment, the rate of bone maturation3 K+ ~ i5 B: X! S. ~3 V3 a: k
decelerates and gradually returns to normal.8,9+ g+ _3 A& e% p; J; z6 ^
There are conflicting reports and controversy* {+ ^1 C9 H* U5 k3 z
over the effect of early androgen exposure on adult
$ S3 z, X* S5 N: N! R; Lpenile length.10,11 Some reports suggest subnormal
7 ]* m5 ?/ i, wadult penile length, apparently because of downreg-
8 x. X) |3 E0 \ E9 S: [4 M$ ?ulation of androgen receptor number.10,12 However,
4 ~9 |4 Y* f# B- N/ e1 j6 K6 nSutherland et al13 did not find a correlation between
# O# F" } J! l% schildhood testosterone exposure and reduced adult0 G5 x) Z! _7 P
penile length in clinical studies.
( u X* B$ z8 `; `# n6 }! t% m8 {Nonetheless, we do not believe our patient is- u! \ K$ _: ]9 B. c4 \. u
going to experience any of the untoward effects from
& y9 \$ w7 q6 z) Itestosterone exposure as mentioned earlier because
) j. C3 N8 O8 W* G: J+ U% o zthe exposure was not for a prolonged period of time.* q) J6 `4 r1 \/ F6 o: H n
Although the bone age was advanced at the time of
% k) n6 Y+ Q q$ |2 }& R* Ndiagnosis, the child had a normal growth velocity at* H7 ~' d9 b$ G( Q# i) o
the follow-up visit. It is hoped that his final adult
. F" G9 ^1 g2 P: C# \- z/ H/ Fheight will not be affected.8 I. N; I$ q% H) h' @) Q
Although rarely reported, the widespread avail-5 n' }1 i; p) f' D# ~5 o
ability of androgen products in our society may5 d5 ~$ { h$ y0 A( g
indeed cause more virilization in male or female
3 Q% L2 l: @* Ychildren than one would realize. Exposure to andro-! r7 X, S$ I& H9 Y# Q6 ]* e. n
gen products must be considered and specific ques-+ B6 Z/ m( S1 ` D( d0 x" Z
tioning about the use of a testosterone product or
$ d' d+ K: p' }gel should be asked of the family members during0 T. [# c2 g6 i. s6 I
the evaluation of any children who present with vir-
7 g* k: m4 _! K6 n+ y: wilization or peripheral precocious puberty. The diag-( T1 K0 u. R! R7 m% T$ x: c
nosis can be established by just a few tests and by; n# g. h" Q' N3 U6 X
appropriate history. The inability to obtain such a9 C5 N$ L; ?8 {7 _
history, or failure to ask the specific questions, may
8 Y. `( J1 ~, T7 Q4 m6 O) tresult in extensive, unnecessary, and expensive
P" t+ c& H! y, N% P3 p6 [+ X. k! A7 _9 |investigation. The primary care physician should be
5 K. h% ~+ a6 r g( f0 v# W* `( _aware of this fact, because most of these children
1 g. l( T+ x; w0 _4 pmay initially present in their practice. The Physicians’
* R' i e" l4 h7 [Desk Reference and package insert should also put a
( U1 W: {( {' _6 xwarning about the virilizing effect on a male or; g% q7 A, r) Y a2 U. f
female child who might come in contact with some-, ^2 \* F! M4 }3 u
one using any of these products.
1 F4 r/ S3 {0 j- b$ O2 [2 eReferences
Z4 u, Y! B' t, H: ]1. Styne DM. The testes: disorder of sexual differentiation
: A/ _% S; R; E0 p: q8 F0 dand puberty in the male. In: Sperling MA, ed. Pediatric* |4 a. R% y, r
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
& \( Y; m* t0 R0 ^8 u/ G2002: 565-628.
6 N# G' N' E8 s8 \7 Q4 D2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
, [7 r8 |9 O* ipuberty in children with tumours of the suprasellar pineal |
|